TDMS Study 99022-02 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst AZT TRANSPLACENTAL CARCINOGENESIS STUDY DATE: 09/09/04 EXPERIMENT: 99022 TEST: 02 TIME: 14:02:01 TEST TYPE: PERINATAL EXPOS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-15328 ROUTE: IN-UTERO NTP C#: C99022 PATHOLOGIST: HEATH, JAMES E. CAS: 30516-87-1 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #2; REVISION #1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: MERGE 001 001,011 0 MG/KG/DY MERGE 002 002,012 50 MG/KG/DY MERGE 003 003,013 100 MG/KG/DY MERGE 004 004,014 200 MG/KG/DY MERGE 005 005,015 300 MG/KG/DY MERGE 006 006,016 0 MG/KG/DY MERGE 007 007,017 50 MG/KG/DY MERGE 008 008,018 100 MG/KG/DY MERGE 009 009,019 200 MG/KG/DY MERGE 010 010,020 300 MG/KG/DY NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst AZT TRANSPLACENTAL CARCINOGENESIS STUDY DATE: 09/09/04 EXPERIMENT: 99022 TEST: 02 TIME: 14:02:01 TEST TYPE: PERINATAL EXPOS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-15328 ROUTE: IN-UTERO NTP C#: C99022 PATHOLOGIST: HEATH, JAMES E. CAS: 30516-87-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF AZT TRANSPLACENTAL CARCINOGENESIS =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Bone: Femur Osteopetrosis Heart Cardiomyopathy Intestine Large, Cecum Edema Kidney Amyloid Deposition Cyst Hydronephrosis Infiltration Cellular Mixed Cell Inflammation Nephropathy Kidney: Renal Tubule Dilatation Liver Infiltration Cellular Mixed Cell Liver: Hepatocyte Hypertrophy Lung Edema Infiltration Cellular Histiocyte Lung: Alveolar Epithelium Hyperplasia Lymph Node Hyperplasia Lymph Node, Mandibular Hematopoietic Cell Proliferation Hyperplasia Lymph Node, Mesenteric Ectasia Hematopoietic Cell Proliferation Hemorrhage Mesentery: Fat Necrosis Penis Inflammation Chronic Preputial Gland Inflammation Chronic Salivary Glands Hyperplasia Lymphoid Infiltration Cellular Lymphoid Seminal Vesicle Dilatation Skin Edema Spleen: Lymphoid Follicle Hyperplasia Stomach, Glandular: Glands Hyperplasia Cystic Thymus Hyperplasia Lymphoid Urethra Angiectasis Inflammation Chronic Urinary Bladder Edema Hemorrhage Inflammation Chronic =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Bone Fibrous Osteodystrophy Bone Marrow Hyperplasia Clitoral Gland Cyst Heart Inflammation Chronic Intestine Large, Cecum Edema Intestine Small, Duodenum: Epithelium Hyperplasia NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst AZT TRANSPLACENTAL CARCINOGENESIS STUDY DATE: 09/09/04 EXPERIMENT: 99022 TEST: 02 TIME: 14:02:01 TEST TYPE: PERINATAL EXPOS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-15328 ROUTE: IN-UTERO NTP C#: C99022 PATHOLOGIST: HEATH, JAMES E. CAS: 30516-87-1 Islets, Pancreatic Hyperplasia Kidney Cyst Infiltration Cellular Mixed Cell Inflammation Chronic Nephropathy Liver: Hepatocyte Hypertrophy Lung Foreign Body Infiltration Cellular Histiocyte Lung: Alveolar Epithelium Hyperplasia Lymph Node Hyperplasia Lymph Node, Mandibular Hyperplasia Infiltration Cellular Plasma Cell Lymph Node: Inguinal Hyperplasia Mesentery: Fat Necrosis Nose Foreign Body Inflammation Chronic Ovary Angiectasis Pancreas: Acinus Cytoplasmic Alteration Pituitary Gland: Pars Distalis Angiectasis Skin Cyst Epithelial Inclusion Edema Ulcer Spleen Hematopoietic Cell Proliferation Pigmentation Stomach, Forestomach Erosion Thyroid Gland Degeneration Cystic Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 9/50 (18%) 7/50 (14%) 6/37 (16%) 6/32 (19%) | |POLY-3 RATE (b) | 8/35.78 9/33.66 7/31.13 6/24.16 6/20.28 | |POLY-3 PERCENT (g) | 22.4% 26.7% 22.5% 24.8% 29.6% | |TERMINAL (d) | 5/19 (26%) 5/21 (24%) 3/13 (23%) 1/7 (14%) 1/8 (13%) | |FIRST INCIDENCE | 322 147 320 157 563 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.212 P=0.524 P=0.504 P=0.358 P=0.327 | |POLY 3 | P=0.351 P=0.442 P=0.612 P=0.536 P=0.391 | |POLY 1.5 | P=0.373 P=0.448 P=0.579N P=0.557 P=0.404 | |POLY 6 | P=0.339 P=0.461 P=0.576 P=0.517 P=0.398 | |LOGISTIC REGRESSION| P=0.432 P=0.514 P=0.526N P=0.592N P=0.448 | |COCH-ARM / FISHERS | P=0.448 P=0.500 P=0.500N P=0.601 P=0.485 | |ORDER RESTRICTED | P=0.502 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 8/49 (16%) 11/50 (22%) 7/38 (18%) 6/42 (14%) | |POLY-3 RATE (b) | 10/37.67 8/34.35 11/38.86 7/30.93 6/30.78 | |POLY-3 PERCENT (g) | 26.6% 23.3% 28.3% 22.6% 19.5% | |TERMINAL (d) | 4/20 (20%) 1/17 (6%) 5/24 (21%) 5/18 (28%) 3/19 (16%) | |FIRST INCIDENCE | 287 219 460 359 43 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.210N P=0.534N P=0.569N P=0.394N P=0.322N | |POLY 3 | P=0.269N P=0.481N P=0.533 P=0.463N P=0.344N | |POLY 1.5 | P=0.276N P=0.442N P=0.518 P=0.468N P=0.334N | |POLY 6 | P=0.273N P=0.528N P=0.563 P=0.479N P=0.357N | |LOGISTIC REGRESSION| P=0.301N P=0.401N P=0.519 P=0.493N P=0.328N | |COCH-ARM / FISHERS | P=0.303N P=0.416N P=0.500 P=0.538N P=0.331N | |ORDER RESTRICTED | P=0.435N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/49 (4%) 0/50 (0%) 0/38 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 2/31.07 0/36.65 0/29.97 1/29.68 | |POLY-3 PERCENT (g) | 0.0% 6.4% 0.0% 0.0% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 0/24 (0%) 0/18 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 500 --- --- 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.535 P=0.205 (e) (e) P=0.466 | |POLY 3 | P=0.544 P=0.210 (e) (e) P=0.467 | |POLY 1.5 | P=0.545 P=0.221 (e) (e) P=0.466 | |POLY 6 | P=0.539 P=0.201 (e) (e) P=0.469 | |LOGISTIC REGRESSION| P=0.523 P=0.238 (e) (e) P=0.508 | |COCH-ARM / FISHERS | P=0.527 P=0.242 (e) (e) P=0.457 | |ORDER RESTRICTED | P=0.273 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 5/50 (10%) 3/50 (6%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 2/33.95 5/31.08 3/29.72 2/21.52 0/19.14 | |POLY-3 PERCENT (g) | 5.9% 16.1% 10.1% 9.3% 0.0% | |TERMINAL (d) | 1/19 (5%) 3/21 (14%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 373 523 536 580 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.275N P=0.229 P=0.388 P=0.470 P=0.405N | |POLY 3 | P=0.207N P=0.176 P=0.439 P=0.522 P=0.372N | |POLY 1.5 | P=0.194N P=0.181 P=0.462 P=0.541 P=0.366N | |POLY 6 | P=0.225N P=0.184 P=0.412 P=0.501 P=0.380N | |LOGISTIC REGRESSION| P=0.185N P=0.188 P=0.471 P=0.567 P=0.334N | |COCH-ARM / FISHERS | P=0.158N P=0.218 P=0.500 P=0.571 P=0.369N | |ORDER RESTRICTED | P=0.185N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/50 (0%) 0/38 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/30.04 0/36.65 0/29.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 0/24 (0%) 0/18 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 5/50 (10%) 4/50 (8%) 4/37 (11%) 4/32 (13%) | |POLY-3 RATE (b) | 6/33.13 5/30.37 4/30.01 4/21.27 4/19.52 | |POLY-3 PERCENT (g) | 18.1% 16.5% 13.3% 18.8% 20.5% | |TERMINAL (d) | 6/19 (32%) 5/21 (24%) 2/13 (15%) 2/7 (29%) 3/8 (38%) | |FIRST INCIDENCE | 668 (T) 668 (T) 490 625 569 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.155 P=0.424N P=0.587N P=0.294 P=0.357 | |POLY 3 | P=0.423 P=0.563N P=0.430N P=0.615 P=0.560 | |POLY 1.5 | P=0.436 P=0.556N P=0.408N P=0.630N P=0.563 | |POLY 6 | P=0.404 P=0.552N P=0.458N P=0.581 P=0.559 | |LOGISTIC REGRESSION| P=0.332 P=0.424N P=0.512N P=0.414 P=0.500 | |COCH-ARM / FISHERS | P=0.477 P=0.500N P=0.370N P=0.571N P=0.602 | |ORDER RESTRICTED | P=0.599 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/50 (0%) 0/38 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 0/30.04 0/36.65 0/29.97 1/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 3.5% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 0/24 (0%) 0/18 (0%) 1/19 (5%) | |FIRST INCIDENCE | --- --- --- --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.125 (e) (e) (e) P=0.490 | |POLY 3 | P=0.136 (e) (e) (e) P=0.461 | |POLY 1.5 | P=0.130 (e) (e) (e) P=0.462 | |POLY 6 | P=0.141 (e) (e) (e) P=0.461 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.490 | |COCH-ARM / FISHERS | P=0.111 (e) (e) (e) P=0.457 | |ORDER RESTRICTED | P=0.062 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex: Capsule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 1/50 (2%) 3/37 (8%) 2/32 (6%) | |POLY-3 RATE (b) | 2/33.13 2/30.37 1/29.15 3/21.18 2/20.07 | |POLY-3 PERCENT (g) | 6.0% 6.6% 3.4% 14.2% 10.0% | |TERMINAL (d) | 2/19 (11%) 2/21 (10%) 1/13 (8%) 2/7 (29%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) 668 (T) 668 (T) 608 404 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.094 P=0.662N P=0.634N P=0.136 P=0.430 | |POLY 3 | P=0.219 P=0.664 P=0.545N P=0.301 P=0.504 | |POLY 1.5 | P=0.217 P=0.667 P=0.527N P=0.322 P=0.502 | |POLY 6 | P=0.219 P=0.672 P=0.569N P=0.275 P=0.506 | |LOGISTIC REGRESSION| P=0.182 P=0.662N P=0.634N P=0.201 P=0.496 | |COCH-ARM / FISHERS | P=0.230 P=0.691N P=0.500N P=0.359 P=0.510 | |ORDER RESTRICTED | P=0.343 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex: Capsule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 0/50 (0%) 2/38 (5%) 2/42 (5%) | |POLY-3 RATE (b) | 1/34.96 1/30.57 0/36.65 2/29.97 2/29.11 | |POLY-3 PERCENT (g) | 2.9% 3.3% 0.0% 6.7% 6.9% | |TERMINAL (d) | 1/20 (5%) 0/17 (0%) 0/24 (0%) 2/18 (11%) 1/19 (5%) | |FIRST INCIDENCE | 668 (T) 521 --- 668 (T) 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.176 P=0.726 P=0.464N P=0.463 P=0.462 | |POLY 3 | P=0.153 P=0.731 P=0.491N P=0.446 P=0.436 | |POLY 1.5 | P=0.149 P=0.744 P=0.494N P=0.437 P=0.435 | |POLY 6 | P=0.156 P=0.718 P=0.483N P=0.450 P=0.438 | |LOGISTIC REGRESSION| P=0.154 P=0.743 (e) P=0.463 P=0.432 | |COCH-ARM / FISHERS | P=0.142 P=0.747 P=0.500N P=0.397 P=0.434 | |ORDER RESTRICTED | P=0.263 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/49 (2%) 0/37 (0%) 1/32 (3%) | |POLY-3 RATE (b) | 2/33.72 0/30.37 1/28.71 0/20.93 1/19.75 | |POLY-3 PERCENT (g) | 5.9% 0.0% 3.5% 0.0% 5.1% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 567 --- 668 (T) --- 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.563N P=0.253N P=0.598N P=0.363N P=0.670N | |POLY 3 | P=0.527N P=0.260N P=0.556N P=0.350N P=0.682N | |POLY 1.5 | P=0.512N P=0.256N P=0.537N P=0.333N P=0.678N | |POLY 6 | P=0.554N P=0.259N P=0.583N P=0.373N P=0.688N | |LOGISTIC REGRESSION| P=0.524N P=0.251N P=0.554N P=0.331N P=0.666N | |COCH-ARM / FISHERS | P=0.505N P=0.247N P=0.508N P=0.327N P=0.779 | |ORDER RESTRICTED | P=0.391N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/49 (6%) 1/50 (2%) 0/38 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 1/34.96 3/30.04 1/36.65 0/29.97 0/28.81 | |POLY-3 PERCENT (g) | 2.9% 10.0% 2.7% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 3/17 (18%) 1/24 (4%) 0/18 (0%) 0/19 (0%) | |FIRST INCIDENCE | 668 (T) 668 (T) 668 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.072N P=0.244 P=0.722N P=0.521N P=0.510N | |POLY 3 | P=0.098N P=0.251 P=0.751N P=0.531N P=0.539N | |POLY 1.5 | P=0.097N P=0.273 P=0.755N P=0.536N P=0.538N | |POLY 6 | P=0.101N P=0.227 P=0.743N P=0.528N P=0.539N | |LOGISTIC REGRESSION| P=0.072N P=0.244 P=0.722N (e) (e) | |COCH-ARM / FISHERS | P=0.098N P=0.301 P=0.753N P=0.568N P=0.543N | |ORDER RESTRICTED | P=0.131N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 1/29.53 1/21.43 1/19.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 3.4% 4.7% 5.2% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 570 531 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.106 (e) P=0.469 P=0.428 P=0.415 | |POLY 3 | P=0.100 (e) P=0.477 P=0.414 P=0.393 | |POLY 1.5 | P=0.101 (e) P=0.486 P=0.422 P=0.395 | |POLY 6 | P=0.098 (e) P=0.466 P=0.403 P=0.391 | |LOGISTIC REGRESSION| P=0.102 (e) P=0.490 P=0.440 P=0.388 | |COCH-ARM / FISHERS | P=0.109 (e) P=0.500 P=0.425 P=0.390 | |ORDER RESTRICTED | P=0.219 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 7/50 (14%) 9/50 (18%) 6/40 (15%) 4/42 (10%) | |POLY-3 RATE (b) | 2/35.72 7/35.55 9/41.01 6/34.10 4/31.68 | |POLY-3 PERCENT (g) | 5.6% 19.7% 22.0% 17.6% 12.6% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 443 326 328 359 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.417 P=0.070 P=0.048 * P=0.134 P=0.267 | |POLY 3 | P=0.434 P=0.073 P=0.041 * P=0.113 P=0.280 | |POLY 1.5 | P=0.401 P=0.077 P=0.034 * P=0.100 P=0.271 | |POLY 6 | P=0.465 P=0.071 P=0.054 P=0.125 P=0.291 | |LOGISTIC REGRESSION| P=0.314 P=0.088 P=0.024 * P=0.049 * P=0.281 | |COCH-ARM / FISHERS | P=0.346 P=0.080 P=0.026 * P=0.074 P=0.259 | |ORDER RESTRICTED | P=0.132 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 43/50 (86%) 29/50 (58%) 35/50 (70%) 27/37 (73%) 24/32 (75%) | |POLY-3 RATE (b) | 43/48.79 29/41.81 35/43.29 27/33.80 24/27.74 | |POLY-3 PERCENT (g) | 88.1% 69.4% 80.9% 79.9% 86.5% | |TERMINAL (d) | 15/19 (79%) 11/21 (52%) 10/13 (77%) 3/7 (43%) 5/8 (63%) | |FIRST INCIDENCE | 104 147 147 157 192 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.149 P=0.050N P=0.530 P=0.313 P=0.466 | |POLY 3 | P=0.460 P=0.020N* P=0.231N P=0.228N P=0.562N | |POLY 1.5 | P=0.471 P=0.009N** P=0.130N P=0.172N P=0.501N | |POLY 6 | P=0.452 P=0.037N* P=0.422N P=0.301N P=0.593N | |LOGISTIC REGRESSION| P=0.459N P=0.002N** P=0.041N* P=0.068N P=0.193N | |COCH-ARM / FISHERS | P=0.455N P=0.002N** P=0.045N* P=0.108N P=0.167N | |ORDER RESTRICTED | P=0.262N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/50 (66%) 24/50 (48%) 30/50 (60%) 22/40 (55%) 26/42 (62%) | |POLY-3 RATE (b) | 33/47.13 24/40.22 30/43.46 22/36.73 26/38.16 | |POLY-3 PERCENT (g) | 70.0% 59.7% 69.0% 59.9% 68.1% | |TERMINAL (d) | 11/20 (55%) 6/18 (33%) 13/24 (54%) 8/20 (40%) 10/19 (53%) | |FIRST INCIDENCE | 105 207 182 414 43 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.314N P=0.283N P=0.220N P=0.105N P=0.404N | |POLY 3 | P=0.451N P=0.208N P=0.551N P=0.225N P=0.520N | |POLY 1.5 | P=0.482N P=0.134N P=0.501N P=0.211N P=0.495N | |POLY 6 | P=0.424N P=0.271N P=0.551N P=0.232N P=0.523N | |LOGISTIC REGRESSION| P=0.489 P=0.043N* P=0.345N P=0.303N P=0.404N | |COCH-ARM / FISHERS | P=0.501 P=0.053N P=0.339N P=0.199N P=0.424N | |ORDER RESTRICTED | P=0.478N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone: Femur | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/37 (0%) 2/32 (6%) | |POLY-3 RATE (b) | 0/33.13 1/30.76 0/29.15 0/20.93 2/19.14 | |POLY-3 PERCENT (g) | 0.0% 3.3% 0.0% 0.0% 10.5% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 2/8 (25%) | |FIRST INCIDENCE | --- 567 --- --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.033 * P=0.493 (e) (e) P=0.076 | |POLY 3 | P=0.054 P=0.485 (e) (e) P=0.126 | |POLY 1.5 | P=0.057 P=0.486 (e) (e) P=0.129 | |POLY 6 | P=0.050 P=0.491 (e) (e) P=0.122 | |LOGISTIC REGRESSION| P=0.054 P=0.492 (e) (e) P=0.076 | |COCH-ARM / FISHERS | P=0.064 P=0.500 (e) (e) P=0.149 | |ORDER RESTRICTED | P=0.015 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone: Femur | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.65 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/50 (44%) 18/50 (36%) 25/50 (50%) 14/40 (35%) 12/42 (29%) | |POLY-3 RATE (b) | 22/39.10 18/34.48 25/42.10 14/34.07 12/29.74 | |POLY-3 PERCENT (g) | 56.3% 52.2% 59.4% 41.1% 40.4% | |TERMINAL (d) | 10/20 (50%) 10/18 (56%) 12/24 (50%) 7/20 (35%) 10/19 (53%) | |FIRST INCIDENCE | 443 412 332 497 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.025N* P=0.521N P=0.557N P=0.116N P=0.078N | |POLY 3 | P=0.044N* P=0.452N P=0.476 P=0.136N P=0.134N | |POLY 1.5 | P=0.047N* P=0.347N P=0.424 P=0.152N P=0.111N | |POLY 6 | P=0.053N P=0.586N P=0.543 P=0.138N P=0.187N | |LOGISTIC REGRESSION| P=0.033N* P=0.425N P=0.382 P=0.134N P=0.093N | |COCH-ARM / FISHERS | P=0.068N P=0.270N P=0.344 P=0.258N P=0.095N | |ORDER RESTRICTED | P=0.154N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/50 (46%) 19/50 (38%) 17/50 (34%) 14/40 (35%) 16/42 (38%) | |POLY-3 RATE (b) | 23/39.22 19/34.35 17/39.14 14/33.17 16/32.10 | |POLY-3 PERCENT (g) | 58.7% 55.3% 43.4% 42.2% 49.8% | |TERMINAL (d) | 11/20 (55%) 11/18 (61%) 9/24 (38%) 8/20 (40%) 10/19 (53%) | |FIRST INCIDENCE | 443 500 332 539 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.120N P=0.550N P=0.084N P=0.081N P=0.256N | |POLY 3 | P=0.167N P=0.478N P=0.123N P=0.113N P=0.300N | |POLY 1.5 | P=0.197N P=0.362N P=0.126N P=0.119N P=0.295N | |POLY 6 | P=0.165N P=0.593 P=0.121N P=0.129N P=0.328N | |LOGISTIC REGRESSION| P=0.173N P=0.453N P=0.113N P=0.081N P=0.305N | |COCH-ARM / FISHERS | P=0.270N P=0.272N P=0.154N P=0.201N P=0.291N | |ORDER RESTRICTED | P=0.198N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Epididymis | | Atypia Cellular | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 3/50 (6%) 3/37 (8%) 3/32 (9%) | |POLY-3 RATE (b) | 1/33.13 3/31.36 3/30.69 3/21.41 3/19.67 | |POLY-3 PERCENT (g) | 3.0% 9.6% 9.8% 14.0% 15.3% | |TERMINAL (d) | 1/19 (5%) 2/21 (10%) 0/13 (0%) 1/7 (14%) 1/8 (13%) | |FIRST INCIDENCE | 668 (T) 157 147 607 563 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051 P=0.332 P=0.246 P=0.090 P=0.102 | |POLY 3 | P=0.079 P=0.283 P=0.276 P=0.163 P=0.139 | |POLY 1.5 | P=0.083 P=0.285 P=0.288 P=0.176 P=0.141 | |POLY 6 | P=0.075 P=0.290 P=0.261 P=0.149 P=0.138 | |LOGISTIC REGRESSION| P=0.094 P=0.301 P=0.318 P=0.132 P=0.129 | |COCH-ARM / FISHERS | P=0.104 P=0.309 P=0.309 P=0.204 P=0.162 | |ORDER RESTRICTED | P=0.141 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Epididymis | | Atypia Cellular | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Epididymis | | Spermatocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/37 (0%) 1/32 (3%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 2/29.77 0/20.93 1/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 0.0% 5.2% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | --- --- 544 --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.204 (e) P=0.193 (e) P=0.328 | |POLY 3 | P=0.224 (e) P=0.213 (e) P=0.391 | |POLY 1.5 | P=0.233 (e) P=0.221 (e) P=0.394 | |POLY 6 | P=0.210 (e) P=0.202 (e) P=0.387 | |LOGISTIC REGRESSION| P=0.235 (e) P=0.219 (e) P=0.328 | |COCH-ARM / FISHERS | P=0.256 (e) P=0.247 (e) P=0.390 | |ORDER RESTRICTED | P=0.216 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Epididymis | | Spermatocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/49 (2%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 2/33.40 0/30.37 1/28.48 1/21.68 1/19.32 | |POLY-3 PERCENT (g) | 6.0% 0.0% 3.5% 4.6% 5.2% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 601 --- 651 419 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.428 P=0.250N P=0.617N P=0.715N P=0.712N | |POLY 3 | P=0.507 P=0.258N P=0.556N P=0.648N P=0.686N | |POLY 1.5 | P=0.510 P=0.255N P=0.537N P=0.633N P=0.680N | |POLY 6 | P=0.498 P=0.255N P=0.580N P=0.668N P=0.692N | |LOGISTIC REGRESSION| P=0.492 P=0.253N P=0.581N P=0.624N P=0.693N | |COCH-ARM / FISHERS | P=0.517 P=0.247N P=0.508N P=0.613N P=0.779 | |ORDER RESTRICTED | P=0.530N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/49 (0%) 1/50 (2%) 2/40 (5%) 1/41 (2%) | |POLY-3 RATE (b) | 0/34.94 0/30.96 1/36.65 2/31.97 1/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.7% 6.3% 3.5% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 1/24 (4%) 2/20 (10%) 1/19 (5%) | |FIRST INCIDENCE | --- --- 668 (T) 668 (T) 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.129 (e) P=0.536 P=0.237 P=0.490 | |POLY 3 | P=0.111 (e) P=0.510 P=0.216 P=0.461 | |POLY 1.5 | P=0.107 (e) P=0.506 P=0.210 P=0.462 | |POLY 6 | P=0.116 (e) P=0.517 P=0.220 P=0.461 | |LOGISTIC REGRESSION| (e) (e) P=0.536 P=0.237 P=0.490 | |COCH-ARM / FISHERS | P=0.102 (e) P=0.505 P=0.199 P=0.456 | |ORDER RESTRICTED | P=0.177 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 7/50 (14%) 19/50 (38%) 13/37 (35%) 7/32 (22%) | |POLY-3 RATE (b) | 12/35.85 7/30.49 19/35.38 13/25.36 7/20.85 | |POLY-3 PERCENT (g) | 33.5% 23.0% 53.7% 51.3% 33.6% | |TERMINAL (d) | 6/19 (32%) 6/21 (29%) 3/13 (23%) 3/7 (43%) 1/8 (13%) | |FIRST INCIDENCE | 322 640 147 298 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.077 P=0.134N P=0.032 * P=0.029 * P=0.469 | |POLY 3 | P=0.205 P=0.248N P=0.060 P=0.120 P=0.612 | |POLY 1.5 | P=0.213 P=0.222N P=0.068 P=0.136 P=0.602N | |POLY 6 | P=0.193 P=0.262N P=0.063 P=0.104 P=0.606 | |LOGISTIC REGRESSION| P=0.198 P=0.195N P=0.065 P=0.128 P=0.592N | |COCH-ARM / FISHERS | P=0.267 P=0.154N P=0.097 P=0.185 P=0.523N | |ORDER RESTRICTED | P=0.138 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 2/49 (4%) 6/50 (12%) 1/40 (3%) 2/42 (5%) | |POLY-3 RATE (b) | 3/36.19 2/31.43 6/37.61 1/31.97 2/29.97 | |POLY-3 PERCENT (g) | 8.3% 6.4% 16.0% 3.1% 6.7% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 2/24 (8%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 255 560 514 668 (T) 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.292N P=0.571N P=0.316 P=0.328N P=0.577N | |POLY 3 | P=0.296N P=0.565N P=0.257 P=0.349N P=0.586N | |POLY 1.5 | P=0.317N P=0.538N P=0.249 P=0.357N P=0.588N | |POLY 6 | P=0.278N P=0.592N P=0.278 P=0.345N P=0.583N | |LOGISTIC REGRESSION| P=0.342N P=0.507N P=0.247 P=0.433N P=0.567N | |COCH-ARM / FISHERS | P=0.348N P=0.510N P=0.243 P=0.397N P=0.583N | |ORDER RESTRICTED | P=0.362N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 3/50 (6%) 2/37 (5%) 1/32 (3%) | |POLY-3 RATE (b) | 1/33.13 5/31.97 3/29.40 2/21.67 1/19.75 | |POLY-3 PERCENT (g) | 3.0% 15.6% 10.2% 9.2% 5.1% | |TERMINAL (d) | 1/19 (5%) 2/21 (10%) 2/13 (15%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) 157 608 501 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.518 P=0.110 P=0.185 P=0.275 P=0.608 | |POLY 3 | P=0.507N P=0.089 P=0.261 P=0.354 P=0.641 | |POLY 1.5 | P=0.497N P=0.089 P=0.278 P=0.367 P=0.641 | |POLY 6 | P=0.520N P=0.096 P=0.240 P=0.339 P=0.642 | |LOGISTIC REGRESSION| P=0.479N P=0.096 P=0.210 P=0.351 P=0.647 | |COCH-ARM / FISHERS | P=0.450N P=0.102 P=0.309 P=0.387 P=0.631 | |ORDER RESTRICTED | P=0.325 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 1/49 (2%) 2/50 (4%) 2/40 (5%) 2/42 (5%) | |POLY-3 RATE (b) | 7/37.15 1/31.02 2/36.65 2/32.23 2/29.43 | |POLY-3 PERCENT (g) | 18.8% 3.2% 5.5% 6.2% 6.8% | |TERMINAL (d) | 3/20 (15%) 0/18 (0%) 2/24 (8%) 1/20 (5%) 1/19 (5%) | |FIRST INCIDENCE | 255 655 668 (T) 603 482 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.113N P=0.061N P=0.063N P=0.104N P=0.133N | |POLY 3 | P=0.113N P=0.051N P=0.078N P=0.111N P=0.141N | |POLY 1.5 | P=0.127N P=0.041N* P=0.078N P=0.117N P=0.138N | |POLY 6 | P=0.102N P=0.066N P=0.075N P=0.109N P=0.147N | |LOGISTIC REGRESSION| P=0.139N P=0.036N* P=0.078N P=0.146N P=0.129N | |COCH-ARM / FISHERS | P=0.149N P=0.032N* P=0.080N P=0.144N P=0.128N | |ORDER RESTRICTED | P=0.035N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 1/37 (3%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 2/31.49 1/29.88 1/21.92 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 6.4% 3.4% 4.6% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 432 434 157 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.524N P=0.224 P=0.490 P=0.448 (e) | |POLY 3 | P=0.548N P=0.225 P=0.479 P=0.418 (e) | |POLY 1.5 | P=0.540N P=0.223 P=0.487 P=0.426 (e) | |POLY 6 | P=0.561N P=0.233 P=0.469 P=0.406 (e) | |LOGISTIC REGRESSION| P=0.458N P=0.246 P=0.521 P=0.441 (e) | |COCH-ARM / FISHERS | P=0.505N P=0.247 P=0.500 P=0.425 (e) | |ORDER RESTRICTED | P=0.403 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 3/49 (6%) 2/50 (4%) 1/40 (3%) 2/42 (5%) | |POLY-3 RATE (b) | 2/35.82 3/32.81 2/38.05 1/32.44 2/30.54 | |POLY-3 PERCENT (g) | 5.6% 9.1% 5.3% 3.1% 6.6% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 352 417 322 541 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.459N P=0.463 P=0.674N P=0.531N P=0.641 | |POLY 3 | P=0.452N P=0.460 P=0.673N P=0.535N P=0.637 | |POLY 1.5 | P=0.461N P=0.476 P=0.682N P=0.545N P=0.634 | |POLY 6 | P=0.446N P=0.445 P=0.658N P=0.526N P=0.641 | |LOGISTIC REGRESSION| P=0.487N P=0.498 P=0.677 P=0.664N P=0.674 | |COCH-ARM / FISHERS | P=0.483N P=0.490 P=0.691N P=0.584N P=0.623 | |ORDER RESTRICTED | P=0.577N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 5/50 (10%) 3/37 (8%) 3/32 (9%) | |POLY-3 RATE (b) | 2/34.18 4/32.17 5/30.52 3/21.52 3/19.44 | |POLY-3 PERCENT (g) | 5.9% 12.4% 16.4% 13.9% 15.4% | |TERMINAL (d) | 0/19 (0%) 2/21 (10%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 104 236 544 563 635 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.165 P=0.340 P=0.140 P=0.230 P=0.232 | |POLY 3 | P=0.192 P=0.306 P=0.167 P=0.295 P=0.254 | |POLY 1.5 | P=0.209 P=0.306 P=0.181 P=0.315 P=0.261 | |POLY 6 | P=0.174 P=0.316 P=0.155 P=0.273 P=0.248 | |LOGISTIC REGRESSION| P=0.249 P=0.393 P=0.215 P=0.371 P=0.299 | |COCH-ARM / FISHERS | P=0.268 P=0.339 P=0.218 P=0.359 P=0.296 | |ORDER RESTRICTED | P=0.296 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 3/50 (6%) 0/40 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 0/30.96 3/39.34 0/31.97 1/29.09 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.6% 0.0% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- 181 --- 598 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.388 (e) P=0.128 (e) P=0.445 | |POLY 3 | P=0.449 (e) P=0.140 (e) P=0.463 | |POLY 1.5 | P=0.424 (e) P=0.133 (e) P=0.463 | |POLY 6 | P=0.475 (e) P=0.150 (e) P=0.465 | |LOGISTIC REGRESSION| P=0.424 (e) P=0.063 (e) P=0.462 | |COCH-ARM / FISHERS | P=0.380 (e) P=0.121 (e) P=0.457 | |ORDER RESTRICTED | P=0.265 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Large, Cecum | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/49 (27%) 11/49 (22%) 8/48 (17%) 14/35 (40%) 2/30 (7%) | |POLY-3 RATE (b) | 13/35.52 11/32.02 8/31.58 14/24.03 2/19.56 | |POLY-3 PERCENT (g) | 36.6% 34.4% 25.3% 58.3% 10.2% | |TERMINAL (d) | 8/19 (42%) 8/21 (38%) 2/13 (15%) 4/7 (57%) 1/8 (13%) | |FIRST INCIDENCE | 392 385 147 341 495 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.503N P=0.372N P=0.372N P=0.019 * P=0.073N | |POLY 3 | P=0.254N P=0.525N P=0.228N P=0.073 P=0.033N* | |POLY 1.5 | P=0.234N P=0.503N P=0.200N P=0.092 P=0.032N* | |POLY 6 | P=0.298N P=0.528N P=0.266N P=0.060 P=0.037N* | |LOGISTIC REGRESSION| P=0.246N P=0.490N P=0.209N P=0.073 P=0.033N* | |COCH-ARM / FISHERS | P=0.213N P=0.407N P=0.176N P=0.143 P=0.025N* | |ORDER RESTRICTED | P=0.039N* (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Large, Cecum | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/47 (6%) 3/48 (6%) 4/45 (9%) 4/38 (11%) 8/40 (20%) | |POLY-3 RATE (b) | 3/34.13 3/31.75 4/36.01 4/32.38 8/31.32 | |POLY-3 PERCENT (g) | 8.8% 9.5% 11.1% 12.4% 25.5% | |TERMINAL (d) | 1/20 (5%) 1/18 (6%) 1/24 (4%) 1/20 (5%) 2/19 (11%) | |FIRST INCIDENCE | 588 500 362 530 467 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.027 * P=0.546 P=0.539 P=0.457 P=0.065 | |POLY 3 | P=0.026 * P=0.631 P=0.530 P=0.471 P=0.066 | |POLY 1.5 | P=0.021 * P=0.653 P=0.509 P=0.448 P=0.060 | |POLY 6 | P=0.031 * P=0.603 P=0.556 P=0.490 P=0.074 | |LOGISTIC REGRESSION| P=0.014 * P=0.648 P=0.470 P=0.410 P=0.057 | |COCH-ARM / FISHERS | P=0.015 * P=0.651N P=0.475 P=0.381 P=0.057 | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Large, Colon | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/50 (0%) 2/49 (4%) 1/37 (3%) 0/32 (0%) | |POLY-3 RATE (b) | 0/31.88 0/30.37 2/28.73 1/21.28 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.0% 4.7% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 605 580 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.445 (e) P=0.194 P=0.423 (e) | |POLY 3 | P=0.439 (e) P=0.213 P=0.420 (e) | |POLY 1.5 | P=0.445 (e) P=0.224 P=0.429 (e) | |POLY 6 | P=0.430 (e) P=0.202 P=0.409 (e) | |LOGISTIC REGRESSION| P=0.454 (e) P=0.212 P=0.430 (e) | |COCH-ARM / FISHERS | P=0.475 (e) P=0.253 P=0.435 (e) | |ORDER RESTRICTED | P=0.302 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Large, Colon | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/49 (2%) 1/49 (2%) 0/39 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 1/31.54 1/37.21 0/31.44 1/29.45 | |POLY-3 PERCENT (g) | 0.0% 3.2% 2.7% 0.0% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 500 460 --- 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.438 P=0.478 P=0.505 (e) P=0.467 | |POLY 3 | P=0.464 P=0.479 P=0.512 (e) P=0.466 | |POLY 1.5 | P=0.452 P=0.488 P=0.506 (e) P=0.464 | |POLY 6 | P=0.474 P=0.470 P=0.522 (e) P=0.468 | |LOGISTIC REGRESSION| P=0.421 P=0.499 P=0.478 (e) P=0.475 | |COCH-ARM / FISHERS | P=0.421 P=0.495 P=0.495 (e) P=0.457 | |ORDER RESTRICTED | P=0.276 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/36 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/32.39 0/30.37 0/28.72 0/19.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/48 (0%) 0/40 (0%) 2/42 (5%) | |POLY-3 RATE (b) | 1/34.96 1/31.04 0/36.41 0/31.97 2/29.78 | |POLY-3 PERCENT (g) | 2.9% 3.2% 0.0% 0.0% 6.7% | |TERMINAL (d) | 1/20 (5%) 1/18 (6%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 668 (T) 668 (T) --- --- 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.323 P=0.740 P=0.464N P=0.500N P=0.437 | |POLY 3 | P=0.330 P=0.735 P=0.492N P=0.518N P=0.444 | |POLY 1.5 | P=0.322 P=0.748 P=0.498N P=0.524N P=0.439 | |POLY 6 | P=0.333 P=0.720 P=0.484N P=0.513N P=0.452 | |LOGISTIC REGRESSION| P=0.300 P=0.740 (e) (e) P=0.436 | |COCH-ARM / FISHERS | P=0.293 P=0.753N P=0.510N P=0.556N P=0.434 | |ORDER RESTRICTED | P=0.145 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/36 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/32.39 0/30.37 0/28.72 0/19.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/48 (4%) 0/40 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 2/36.97 0/31.97 1/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.4% 0.0% 3.5% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | --- --- 537 --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.345 (e) P=0.262 (e) P=0.490 | |POLY 3 | P=0.379 (e) P=0.249 (e) P=0.461 | |POLY 1.5 | P=0.358 (e) P=0.241 (e) P=0.462 | |POLY 6 | P=0.400 (e) P=0.261 (e) P=0.461 | |LOGISTIC REGRESSION| P=0.330 (e) P=0.233 (e) P=0.490 | |COCH-ARM / FISHERS | P=0.319 (e) P=0.237 (e) P=0.457 | |ORDER RESTRICTED | P=0.269 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Duodenum: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/49 (6%) 4/50 (8%) 4/49 (8%) 1/36 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 3/32.98 4/31.97 4/28.72 1/20.16 1/19.44 | |POLY-3 PERCENT (g) | 9.1% 12.5% 13.9% 5.0% 5.1% | |TERMINAL (d) | 2/19 (11%) 1/21 (5%) 4/13 (31%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 497 467 668 (T) 612 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.356N P=0.497 P=0.317 P=0.611N P=0.574N | |POLY 3 | P=0.252N P=0.483 P=0.423 P=0.493N P=0.507N | |POLY 1.5 | P=0.232N P=0.479 P=0.454 P=0.466N P=0.500N | |POLY 6 | P=0.283N P=0.502 P=0.381 P=0.527N P=0.515N | |LOGISTIC REGRESSION| P=0.232N P=0.484 P=0.386 P=0.489N P=0.501N | |COCH-ARM / FISHERS | P=0.194N P=0.511 P=0.500 P=0.432N P=0.482N | |ORDER RESTRICTED | P=0.404N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Duodenum: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 7/50 (14%) 12/48 (25%) 4/40 (10%) 9/42 (21%) | |POLY-3 RATE (b) | 12/37.69 7/34.28 12/36.78 4/31.97 9/29.70 | |POLY-3 PERCENT (g) | 31.8% 20.4% 32.6% 12.5% 30.3% | |TERMINAL (d) | 7/20 (35%) 2/18 (11%) 8/24 (33%) 4/20 (20%) 7/19 (37%) | |FIRST INCIDENCE | 372 341 631 668 (T) 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.220N P=0.247N P=0.430N P=0.032N* P=0.419N | |POLY 3 | P=0.308N P=0.200N P=0.570 P=0.047N* P=0.552N | |POLY 1.5 | P=0.321N P=0.172N P=0.565 P=0.050N P=0.529N | |POLY 6 | P=0.306N P=0.232N P=0.584 P=0.048N* P=0.576N | |LOGISTIC REGRESSION| P=0.299N P=0.164N P=0.557N P=0.047N* P=0.501N | |COCH-ARM / FISHERS | P=0.354N P=0.154N P=0.547 P=0.072N P=0.484N | |ORDER RESTRICTED | P=0.270N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Jejunum: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/49 (8%) 2/50 (4%) 0/46 (0%) 1/36 (3%) 1/29 (3%) | |POLY-3 RATE (b) | 4/33.56 2/31.21 0/28.05 1/20.92 1/18.70 | |POLY-3 PERCENT (g) | 11.9% 6.4% 0.0% 4.8% 5.4% | |TERMINAL (d) | 1/19 (5%) 1/21 (5%) 0/13 (0%) 1/7 (14%) 0/8 (0%) | |FIRST INCIDENCE | 413 363 --- 668 (T) 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.281N P=0.354N P=0.106N P=0.453N P=0.391N | |POLY 3 | P=0.221N P=0.369N P=0.083N P=0.345N P=0.389N | |POLY 1.5 | P=0.213N P=0.363N P=0.076N P=0.318N P=0.385N | |POLY 6 | P=0.237N P=0.368N P=0.095N P=0.387N P=0.397N | |LOGISTIC REGRESSION| P=0.214N P=0.341N P=0.075N P=0.317N P=0.372N | |COCH-ARM / FISHERS | P=0.208N P=0.329N P=0.067N P=0.291N P=0.381N | |ORDER RESTRICTED | P=0.191N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Intestine Small, Jejunum: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/46 (0%) 1/49 (2%) 1/46 (2%) 0/40 (0%) 1/40 (3%) | |POLY-3 RATE (b) | 0/32.73 1/31.06 1/35.55 0/31.97 1/29.37 | |POLY-3 PERCENT (g) | 0.0% 3.2% 2.8% 0.0% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 1/24 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 644 668 (T) --- 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.449 P=0.464 P=0.536 (e) P=0.466 | |POLY 3 | P=0.467 P=0.490 P=0.516 (e) P=0.478 | |POLY 1.5 | P=0.457 P=0.500 P=0.510 (e) P=0.476 | |POLY 6 | P=0.473 P=0.477 P=0.525 (e) P=0.480 | |LOGISTIC REGRESSION| P=0.421 P=0.475 P=0.536 (e) P=0.516 | |COCH-ARM / FISHERS | P=0.428 P=0.516 P=0.500 (e) P=0.465 | |ORDER RESTRICTED | P=0.287 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/50 (30%) 13/50 (26%) 12/50 (24%) 6/36 (17%) 6/31 (19%) | |POLY-3 RATE (b) | 15/38.90 13/34.71 12/33.74 6/22.28 6/20.45 | |POLY-3 PERCENT (g) | 38.6% 37.5% 35.6% 26.9% 29.3% | |TERMINAL (d) | 4/19 (21%) 6/21 (29%) 1/13 (8%) 1/6 (17%) 1/8 (13%) | |FIRST INCIDENCE | 322 236 320 341 473 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263N P=0.448N P=0.567N P=0.359N P=0.348N | |POLY 3 | P=0.177N P=0.557N P=0.492N P=0.262N P=0.338N | |POLY 1.5 | P=0.141N P=0.529N P=0.429N P=0.202N P=0.305N | |POLY 6 | P=0.237N P=0.563N P=0.558N P=0.348N P=0.381N | |LOGISTIC REGRESSION| P=0.104N P=0.438N P=0.343N P=0.132N P=0.230N | |COCH-ARM / FISHERS | P=0.089N P=0.412N P=0.326N P=0.121N P=0.213N | |ORDER RESTRICTED | P=0.399N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 5/49 (10%) 6/49 (12%) 7/40 (18%) 10/41 (24%) | |POLY-3 RATE (b) | 2/35.26 5/31.54 6/38.30 7/32.22 10/31.73 | |POLY-3 PERCENT (g) | 5.7% 15.9% 15.7% 21.7% 31.5% | |TERMINAL (d) | 1/20 (5%) 4/18 (22%) 3/24 (13%) 6/20 (30%) 4/19 (21%) | |FIRST INCIDENCE | 593 500 425 608 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.005 ** P=0.162 P=0.176 P=0.075 P=0.010 * | |POLY 3 | P=0.003 ** P=0.168 P=0.158 P=0.053 P=0.005 ** | |POLY 1.5 | P=0.002 ** P=0.189 P=0.145 P=0.049 * P=0.004 ** | |POLY 6 | P=0.004 ** P=0.146 P=0.177 P=0.055 P=0.007 ** | |LOGISTIC REGRESSION| P=0.002 ** P=0.153 P=0.133 P=0.063 P=0.005 ** | |COCH-ARM / FISHERS | P=0.002 ** P=0.210 P=0.128 P=0.038 * P=0.005 ** | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Amyloid Deposition | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 3/35.36 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 8.5% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 373 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.057N P=0.148N P=0.134N P=0.210N P=0.240N | |POLY 3 | P=0.044N* P=0.146N P=0.155N P=0.231N P=0.250N | |POLY 1.5 | P=0.043N* P=0.140N P=0.140N P=0.210N P=0.239N | |POLY 6 | P=0.048N* P=0.148N P=0.177N P=0.258N P=0.263N | |LOGISTIC REGRESSION| P=0.043N* P=0.087N P=0.098N P=0.140N P=0.159N | |COCH-ARM / FISHERS | P=0.050N P=0.121N P=0.121N P=0.185N P=0.221N | |ORDER RESTRICTED | P=0.042N* (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Amyloid Deposition | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/40 (0%) 2/42 (5%) | |POLY-3 RATE (b) | 2/34.96 0/31.04 1/37.53 0/31.97 2/30.57 | |POLY-3 PERCENT (g) | 5.7% 0.0% 2.7% 0.0% 6.5% | |TERMINAL (d) | 2/20 (10%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 668 (T) --- 328 --- 43 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.459 P=0.260N P=0.455N P=0.237N P=0.656 | |POLY 3 | P=0.491 P=0.263N P=0.475N P=0.255N P=0.647 | |POLY 1.5 | P=0.469 P=0.250N P=0.485N P=0.263N P=0.642 | |POLY 6 | P=0.509 P=0.279N P=0.461N P=0.250N P=0.653 | |LOGISTIC REGRESSION| P=0.429 (e) P=0.503N (e) P=0.659 | |COCH-ARM / FISHERS | P=0.425 P=0.247N P=0.500N P=0.306N P=0.623 | |ORDER RESTRICTED | P=0.267 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 27/50 (54%) 23/50 (46%) 26/50 (52%) 24/37 (65%) 17/32 (53%) | |POLY-3 RATE (b) | 27/38.88 23/33.16 26/35.47 24/26.73 17/23.92 | |POLY-3 PERCENT (g) | 69.5% 69.4% 73.3% 89.8% 71.1% | |TERMINAL (d) | 15/19 (79%) 17/21 (81%) 9/13 (69%) 7/7 (100%) 4/8 (50%) | |FIRST INCIDENCE | 322 432 229 301 229 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * P=0.229N P=0.185 P=0.006 ** P=0.255 | |POLY 3 | P=0.171 P=0.607N P=0.451 P=0.028 * P=0.563 | |POLY 1.5 | P=0.165 P=0.512N P=0.524 P=0.057 P=0.537 | |POLY 6 | P=0.225 P=0.596 P=0.424 P=0.022 * P=0.628N | |LOGISTIC REGRESSION| P=0.096 P=0.430N P=0.475 P=0.050 P=0.480 | |COCH-ARM / FISHERS | P=0.247 P=0.274N P=0.500N P=0.213 P=0.559N | |ORDER RESTRICTED | P=0.238 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 7/50 (14%) 5/50 (10%) 7/40 (18%) 5/42 (12%) | |POLY-3 RATE (b) | 2/35.79 7/35.16 5/37.71 7/32.90 5/31.34 | |POLY-3 PERCENT (g) | 5.6% 19.9% 13.3% 21.3% 16.0% | |TERMINAL (d) | 1/20 (5%) 2/18 (11%) 3/24 (13%) 4/20 (20%) 1/19 (5%) | |FIRST INCIDENCE | 372 219 432 497 43 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.207 P=0.078 P=0.266 P=0.080 P=0.168 | |POLY 3 | P=0.170 P=0.069 P=0.235 P=0.055 P=0.160 | |POLY 1.5 | P=0.158 P=0.076 P=0.226 P=0.050 P=0.156 | |POLY 6 | P=0.187 P=0.062 P=0.252 P=0.060 P=0.168 | |LOGISTIC REGRESSION| P=0.130 P=0.086 P=0.219 P=0.047 * P=0.164 | |COCH-ARM / FISHERS | P=0.139 P=0.080 P=0.218 P=0.038 * P=0.152 | |ORDER RESTRICTED | P=0.109 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Hydronephrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 30/50 (60%) 20/50 (40%) 17/50 (34%) 16/37 (43%) 14/32 (44%) | |POLY-3 RATE (b) | 30/42.16 20/37.16 17/36.51 16/25.32 14/24.87 | |POLY-3 PERCENT (g) | 71.2% 53.8% 46.6% 63.2% 56.3% | |TERMINAL (d) | 12/19 (63%) 10/21 (48%) 2/13 (15%) 4/7 (57%) 4/8 (50%) | |FIRST INCIDENCE | 104 168 315 329 41 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.426 P=0.075N P=0.154N P=0.482 P=0.433N | |POLY 3 | P=0.230N P=0.074N P=0.016N* P=0.333N P=0.152N | |POLY 1.5 | P=0.209N P=0.066N P=0.013N* P=0.239N P=0.145N | |POLY 6 | P=0.265N P=0.075N P=0.020N* P=0.425N P=0.169N | |LOGISTIC REGRESSION| P=0.205N P=0.045N* P=0.010N* P=0.142N P=0.121N | |COCH-ARM / FISHERS | P=0.173N P=0.036N* P=0.008N** P=0.092N P=0.113N | |ORDER RESTRICTED | P=0.137N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Hydronephrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 7/50 (14%) 5/50 (10%) 5/40 (13%) 3/42 (7%) | |POLY-3 RATE (b) | 2/34.96 7/33.14 5/39.05 5/32.78 3/30.44 | |POLY-3 PERCENT (g) | 5.7% 21.1% 12.8% 15.3% 9.9% | |TERMINAL (d) | 2/20 (10%) 3/18 (17%) 0/24 (0%) 2/20 (10%) 0/19 (0%) | |FIRST INCIDENCE | 668 (T) 326 432 541 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.528N P=0.053 P=0.266 P=0.213 P=0.449 | |POLY 3 | P=0.531 P=0.061 P=0.261 P=0.185 P=0.436 | |POLY 1.5 | P=0.508 P=0.070 P=0.241 P=0.171 P=0.428 | |POLY 6 | P=0.549N P=0.055 P=0.292 P=0.201 P=0.447 | |LOGISTIC REGRESSION| P=0.472 P=0.065 P=0.216 P=0.181 P=0.421 | |COCH-ARM / FISHERS | P=0.470 P=0.080 P=0.218 P=0.136 P=0.417 | |ORDER RESTRICTED | P=0.241 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 1/33.13 0/30.37 0/29.15 1/21.51 1/19.44 | |POLY-3 PERCENT (g) | 3.0% 0.0% 0.0% 4.7% 5.1% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) --- --- 501 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.210 P=0.480N P=0.576N P=0.613 P=0.595 | |POLY 3 | P=0.256 P=0.517N P=0.526N P=0.661 P=0.637 | |POLY 1.5 | P=0.254 P=0.516N P=0.515N P=0.671 P=0.639 | |POLY 6 | P=0.256 P=0.514N P=0.539N P=0.648 P=0.636 | |LOGISTIC REGRESSION| P=0.242 (e) (e) P=0.673 P=0.633 | |COCH-ARM / FISHERS | P=0.256 P=0.500N P=0.500N P=0.673 P=0.631 | |ORDER RESTRICTED | P=0.325 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 2/40 (5%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 1/31.04 3/37.71 2/32.58 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 3.2% 8.0% 6.1% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/18 (6%) 1/24 (4%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | --- 668 (T) 514 488 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.571N P=0.479 P=0.137 P=0.237 (e) | |POLY 3 | P=0.567 P=0.476 P=0.131 P=0.220 (e) | |POLY 1.5 | P=0.554 P=0.488 P=0.126 P=0.211 (e) | |POLY 6 | P=0.581 P=0.464 P=0.142 P=0.227 (e) | |LOGISTIC REGRESSION| P=0.549 P=0.479 P=0.120 P=0.181 (e) | |COCH-ARM / FISHERS | P=0.542 P=0.500 P=0.121 P=0.195 (e) | |ORDER RESTRICTED | P=0.251 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 11/50 (22%) 17/50 (34%) 9/37 (24%) 12/32 (38%) | |POLY-3 RATE (b) | 9/35.03 11/30.84 17/31.57 9/22.37 12/23.36 | |POLY-3 PERCENT (g) | 25.7% 35.7% 53.9% 40.2% 51.4% | |TERMINAL (d) | 5/19 (26%) 9/21 (43%) 9/13 (69%) 4/7 (57%) 3/8 (38%) | |FIRST INCIDENCE | 322 580 538 531 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.445 P=0.007 ** P=0.062 P=0.017 * | |POLY 3 | P=0.031 * P=0.267 P=0.013 * P=0.190 P=0.035 * | |POLY 1.5 | P=0.030 * P=0.295 P=0.022 * P=0.231 P=0.031 * | |POLY 6 | P=0.032 * P=0.261 P=0.007 ** P=0.154 P=0.041 * | |LOGISTIC REGRESSION| P=0.017 * P=0.317 P=0.015 * P=0.198 P=0.030 * | |COCH-ARM / FISHERS | P=0.046 * P=0.402 P=0.055 P=0.324 P=0.044 * | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 20/50 (40%) 15/50 (30%) 14/40 (35%) 15/42 (36%) | |POLY-3 RATE (b) | 10/37.52 20/39.54 15/38.49 14/35.56 15/33.38 | |POLY-3 PERCENT (g) | 26.7% 50.6% 39.0% 39.4% 44.9% | |TERMINAL (d) | 4/20 (20%) 5/18 (28%) 9/24 (38%) 7/20 (35%) 7/19 (37%) | |FIRST INCIDENCE | 372 326 425 359 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.309 P=0.021 * P=0.314 P=0.223 P=0.110 | |POLY 3 | P=0.230 P=0.022 * P=0.180 P=0.177 P=0.081 | |POLY 1.5 | P=0.192 P=0.023 * P=0.177 P=0.149 P=0.072 | |POLY 6 | P=0.270 P=0.024 * P=0.194 P=0.201 P=0.094 | |LOGISTIC REGRESSION| P=0.156 P=0.025 * P=0.197 P=0.091 P=0.069 | |COCH-ARM / FISHERS | P=0.148 P=0.024 * P=0.178 P=0.087 P=0.073 | |ORDER RESTRICTED | P=0.088 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 4/35.28 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 11.3% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 104 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032N* P=0.078N P=0.091N P=0.154N P=0.161N | |POLY 3 | P=0.019N* P=0.080N P=0.086N P=0.149N P=0.166N | |POLY 1.5 | P=0.018N* P=0.076N P=0.076N P=0.132N P=0.158N | |POLY 6 | P=0.021N* P=0.080N P=0.103N P=0.173N P=0.177N | |LOGISTIC REGRESSION| P=0.020N* P=0.044N* P=0.049N* P=0.080N P=0.097N | |COCH-ARM / FISHERS | P=0.024N* P=0.059N P=0.059N P=0.103N P=0.132N | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.65 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 1/50 (2%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 1/34.03 2/32.27 1/30.05 2/22.75 0/19.14 | |POLY-3 PERCENT (g) | 2.9% 6.2% 3.3% 8.8% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 308 147 308 298 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.482N P=0.474 P=0.747 P=0.372 P=0.607N | |POLY 3 | P=0.518N P=0.481 P=0.734 P=0.361 P=0.613N | |POLY 1.5 | P=0.507N P=0.482 P=0.744 P=0.373 P=0.608N | |POLY 6 | P=0.530N P=0.489 P=0.719 P=0.343 P=0.618N | |LOGISTIC REGRESSION| P=0.332N P=0.677 P=0.738N P=0.498 P=0.499N | |COCH-ARM / FISHERS | P=0.465N P=0.500 P=0.753N P=0.387 P=0.610N | |ORDER RESTRICTED | P=0.378N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 3/35.88 0/31.04 0/36.65 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 8.4% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/20 (10%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 287 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.035N* P=0.132N P=0.100N P=0.130N P=0.138N | |POLY 3 | P=0.033N* P=0.145N P=0.113N P=0.137N P=0.159N | |POLY 1.5 | P=0.036N* P=0.132N P=0.116N P=0.143N P=0.158N | |POLY 6 | P=0.030N* P=0.159N P=0.108N P=0.133N P=0.160N | |LOGISTIC REGRESSION| P=0.045N* P=0.118N P=0.123N P=0.183N P=0.151N | |COCH-ARM / FISHERS | P=0.043N* P=0.121N P=0.121N P=0.167N P=0.156N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 1/33.13 1/30.37 1/29.53 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 3.0% 3.3% 3.4% 0.0% 0.0% | |TERMINAL (d) | 1/19 (5%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) 668 (T) 570 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.298N P=0.741N P=0.700 P=0.699N P=0.672N | |POLY 3 | P=0.246N P=0.742 P=0.736 P=0.590N P=0.608N | |POLY 1.5 | P=0.235N P=0.744 P=0.745 P=0.580N P=0.605N | |POLY 6 | P=0.263N P=0.747 P=0.723 P=0.604N P=0.612N | |LOGISTIC REGRESSION| P=0.246N P=0.741N P=0.732 (e) (e) | |COCH-ARM / FISHERS | P=0.218N P=0.753N P=0.753N P=0.575N P=0.610N | |ORDER RESTRICTED | P=0.424N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/40 (0%) 2/42 (5%) | |POLY-3 RATE (b) | 1/35.25 0/31.04 0/36.65 0/31.97 2/28.91 | |POLY-3 PERCENT (g) | 2.8% 0.0% 0.0% 0.0% 6.9% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | 598 --- --- --- 645 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174 P=0.564N P=0.480N P=0.514N P=0.446 | |POLY 3 | P=0.191 P=0.525N P=0.492N P=0.520N P=0.430 | |POLY 1.5 | P=0.179 P=0.513N P=0.495N P=0.525N P=0.432 | |POLY 6 | P=0.200 P=0.539N P=0.487N P=0.517N P=0.428 | |LOGISTIC REGRESSION| P=0.163 P=0.514N P=0.496N P=0.536N P=0.432 | |COCH-ARM / FISHERS | P=0.153 P=0.500N P=0.500N P=0.556N P=0.434 | |ORDER RESTRICTED | P=0.052 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 40/50 (80%) 40/50 (80%) 42/50 (84%) 30/37 (81%) 23/32 (72%) | |POLY-3 RATE (b) | 40/44.84 40/42.51 42/43.51 30/31.20 23/24.60 | |POLY-3 PERCENT (g) | 89.2% 94.1% 96.5% 96.2% 93.5% | |TERMINAL (d) | 17/19 (90%) 20/21 (95%) 13/13 (100%) 7/7 (100%) 7/8 (88%) | |FIRST INCIDENCE | 111 157 147 301 404 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.120 P=0.551 P=0.076 P=0.047 * P=0.361 | |POLY 3 | P=0.208 P=0.311 P=0.142 P=0.226 P=0.432 | |POLY 1.5 | P=0.338 P=0.367 P=0.201 P=0.275 P=0.536 | |POLY 6 | P=0.194 P=0.297 P=0.127 P=0.232 P=0.425 | |LOGISTIC REGRESSION| P=0.400N P=0.396 P=0.248 P=0.339 P=0.497N | |COCH-ARM / FISHERS | P=0.238N P=0.598N P=0.398 P=0.562 P=0.278N | |ORDER RESTRICTED | P=0.222 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/50 (58%) 31/50 (62%) 41/50 (82%) 26/40 (65%) 33/42 (79%) | |POLY-3 RATE (b) | 29/43.26 31/45.61 41/47.70 26/38.11 33/40.07 | |POLY-3 PERCENT (g) | 67.0% 68.0% 86.0% 68.2% 82.4% | |TERMINAL (d) | 12/20 (60%) 7/18 (39%) 20/24 (83%) 11/20 (55%) 14/19 (74%) | |FIRST INCIDENCE | 248 207 237 359 43 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.310 P=0.244 P=0.152 P=0.458N P=0.134 | |POLY 3 | P=0.111 P=0.555 P=0.022 * P=0.551 P=0.077 | |POLY 1.5 | P=0.080 P=0.525 P=0.012 * P=0.486 P=0.056 | |POLY 6 | P=0.156 P=0.595 P=0.046 * P=0.590N P=0.116 | |LOGISTIC REGRESSION| P=0.033 * P=0.459 P=0.009 ** P=0.321 P=0.031 * | |COCH-ARM / FISHERS | P=0.038 * P=0.419 P=0.008 ** P=0.324 P=0.030 * | |ORDER RESTRICTED | P=0.074 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 35 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 2/50 (4%) 3/40 (8%) 3/42 (7%) | |POLY-3 RATE (b) | 1/35.38 2/31.50 2/37.65 3/32.64 3/29.94 | |POLY-3 PERCENT (g) | 2.8% 6.4% 5.3% 9.2% 10.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 558 577 524 510 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.138 P=0.402 P=0.497 P=0.288 P=0.225 | |POLY 3 | P=0.133 P=0.459 P=0.522 P=0.274 P=0.245 | |POLY 1.5 | P=0.124 P=0.479 P=0.513 P=0.263 P=0.242 | |POLY 6 | P=0.141 P=0.439 P=0.537 P=0.283 P=0.251 | |LOGISTIC REGRESSION| P=0.113 P=0.478 P=0.494 P=0.236 P=0.243 | |COCH-ARM / FISHERS | P=0.112 P=0.500 P=0.500 P=0.229 P=0.245 | |ORDER RESTRICTED | P=0.212 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 36 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 5/50 (10%) 2/37 (5%) 1/32 (3%) | |POLY-3 RATE (b) | 0/33.13 1/31.13 5/32.45 2/21.97 1/19.62 | |POLY-3 PERCENT (g) | 0.0% 3.2% 15.4% 9.1% 5.1% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 418 376 434 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.244 P=0.480 P=0.033 * P=0.150 P=0.402 | |POLY 3 | P=0.215 P=0.488 P=0.027 * P=0.151 P=0.396 | |POLY 1.5 | P=0.221 P=0.487 P=0.028 * P=0.157 P=0.397 | |POLY 6 | P=0.206 P=0.493 P=0.025 * P=0.144 P=0.395 | |LOGISTIC REGRESSION| P=0.278 P=0.536 P=0.039 * P=0.179 P=0.409 | |COCH-ARM / FISHERS | P=0.258 P=0.500 P=0.028 * P=0.178 P=0.390 | |ORDER RESTRICTED | P=0.124 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 0/50 (0%) 1/40 (3%) 0/42 (0%) | |POLY-3 RATE (b) | 1/34.96 3/32.90 0/36.65 1/32.58 0/28.81 | |POLY-3 PERCENT (g) | 2.9% 9.1% 0.0% 3.1% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 668 (T) 417 --- 488 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.273 P=0.464N P=0.757 P=0.510N | |POLY 3 | P=0.199N P=0.282 P=0.491N P=0.746 P=0.539N | |POLY 1.5 | P=0.196N P=0.294 P=0.494N P=0.737 P=0.538N | |POLY 6 | P=0.203N P=0.272 P=0.483N P=0.754 P=0.539N | |LOGISTIC REGRESSION| P=0.198N P=0.312 (e) P=0.712 (e) | |COCH-ARM / FISHERS | P=0.190N P=0.309 P=0.500N P=0.694 P=0.543N | |ORDER RESTRICTED | P=0.146N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 37 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 1/37 (3%) 0/32 (0%) | |POLY-3 RATE (b) | 3/34.31 0/30.37 0/29.15 1/21.09 0/19.14 | |POLY-3 PERCENT (g) | 8.7% 0.0% 0.0% 4.7% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 392 --- --- 631 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.209N P=0.148N P=0.169N P=0.558N P=0.263N | |POLY 3 | P=0.155N P=0.140N P=0.148N P=0.491N P=0.242N | |POLY 1.5 | P=0.154N P=0.136N P=0.136N P=0.464N P=0.234N | |POLY 6 | P=0.160N P=0.140N P=0.168N P=0.525N P=0.253N | |LOGISTIC REGRESSION| P=0.171N P=0.122N P=0.122N P=0.440N P=0.211N | |COCH-ARM / FISHERS | P=0.162N P=0.121N P=0.121N P=0.429N P=0.221N | |ORDER RESTRICTED | P=0.070N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/40 (3%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 1/36.85 1/32.73 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.7% 3.1% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- 619 414 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.503 (e) P=0.551 P=0.485 (e) | |POLY 3 | P=0.502 (e) P=0.511 P=0.487 (e) | |POLY 1.5 | P=0.491 (e) P=0.506 P=0.479 (e) | |POLY 6 | P=0.516 (e) P=0.519 P=0.493 (e) | |LOGISTIC REGRESSION| P=0.474 (e) P=0.507 P=0.293 (e) | |COCH-ARM / FISHERS | P=0.479 (e) P=0.500 P=0.444 (e) | |ORDER RESTRICTED | P=0.413 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 38 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 1/30.37 2/29.86 2/21.81 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 3.3% 6.7% 9.2% 0.0% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 668 (T) 544 434 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.366 P=0.520 P=0.202 P=0.124 (e) | |POLY 3 | P=0.383 P=0.483 P=0.213 P=0.150 (e) | |POLY 1.5 | P=0.390 P=0.484 P=0.222 P=0.157 (e) | |POLY 6 | P=0.372 P=0.486 P=0.204 P=0.142 (e) | |LOGISTIC REGRESSION| P=0.409 P=0.520 P=0.224 P=0.172 (e) | |COCH-ARM / FISHERS | P=0.428 P=0.500 P=0.247 P=0.178 (e) | |ORDER RESTRICTED | P=0.290 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 2/40 (5%) 2/42 (5%) | |POLY-3 RATE (b) | 1/35.26 1/31.40 1/37.13 2/32.61 2/29.41 | |POLY-3 PERCENT (g) | 2.8% 3.2% 2.7% 6.1% 6.8% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 593 577 537 565 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.207 P=0.675 P=0.753N P=0.466 P=0.422 | |POLY 3 | P=0.205 P=0.735 P=0.750N P=0.472 P=0.436 | |POLY 1.5 | P=0.196 P=0.748 P=0.754N P=0.460 P=0.435 | |POLY 6 | P=0.215 P=0.721 P=0.742N P=0.484 P=0.440 | |LOGISTIC REGRESSION| P=0.183 P=0.753 P=0.762 P=0.426 P=0.435 | |COCH-ARM / FISHERS | P=0.180 P=0.753N P=0.753N P=0.416 P=0.434 | |ORDER RESTRICTED | P=0.386 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 39 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 2/50 (4%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 2/33.13 4/30.37 2/29.39 2/21.55 0/19.14 | |POLY-3 PERCENT (g) | 6.0% 13.2% 6.8% 9.3% 0.0% | |TERMINAL (d) | 2/19 (11%) 4/21 (19%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) 668 (T) 633 580 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.363N P=0.380 P=0.557 P=0.423 P=0.442N | |POLY 3 | P=0.231N P=0.294 P=0.652 P=0.532 P=0.366N | |POLY 1.5 | P=0.223N P=0.299 P=0.668 P=0.548 P=0.362N | |POLY 6 | P=0.242N P=0.300 P=0.631 P=0.515 P=0.371N | |LOGISTIC REGRESSION| P=0.257N P=0.380 P=0.595 P=0.503 (e) | |COCH-ARM / FISHERS | P=0.195N P=0.339 P=0.691N P=0.571 P=0.369N | |ORDER RESTRICTED | P=0.208N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/40 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 1/36.66 0/31.97 1/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.7% 0.0% 3.5% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | --- --- 666 --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.267 (e) P=0.545 (e) P=0.490 | |POLY 3 | P=0.281 (e) P=0.509 (e) P=0.461 | |POLY 1.5 | P=0.266 (e) P=0.506 (e) P=0.462 | |POLY 6 | P=0.295 (e) P=0.517 (e) P=0.461 | |LOGISTIC REGRESSION| P=0.260 (e) P=0.537 (e) P=0.490 | |COCH-ARM / FISHERS | P=0.235 (e) P=0.500 (e) P=0.457 | |ORDER RESTRICTED | P=0.183 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 40 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/37 (3%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 2/29.85 1/21.38 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 4.7% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 510 549 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.442 (e) P=0.194 P=0.422 (e) | |POLY 3 | P=0.432 (e) P=0.213 P=0.413 (e) | |POLY 1.5 | P=0.437 (e) P=0.222 P=0.422 (e) | |POLY 6 | P=0.423 (e) P=0.203 P=0.403 (e) | |LOGISTIC REGRESSION| P=0.456 (e) P=0.225 P=0.434 (e) | |COCH-ARM / FISHERS | P=0.467 (e) P=0.247 P=0.425 (e) | |ORDER RESTRICTED | P=0.306 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 1/40 (3%) 0/42 (0%) | |POLY-3 RATE (b) | 2/35.19 0/31.04 1/36.65 1/31.97 0/28.81 | |POLY-3 PERCENT (g) | 5.7% 0.0% 2.7% 3.1% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 1/24 (4%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 612 --- 668 (T) 668 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.218N P=0.276N P=0.429N P=0.500N P=0.265N | |POLY 3 | P=0.248N P=0.265N P=0.486N P=0.534N P=0.282N | |POLY 1.5 | P=0.258N P=0.251N P=0.491N P=0.543N P=0.281N | |POLY 6 | P=0.240N P=0.282N P=0.476N P=0.528N P=0.283N | |LOGISTIC REGRESSION| P=0.230N P=0.275N P=0.468N P=0.521N P=0.280N | |COCH-ARM / FISHERS | P=0.261N P=0.247N P=0.500N P=0.584N P=0.293N | |ORDER RESTRICTED | P=0.122N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 41 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 2/50 (4%) 1/37 (3%) 2/32 (6%) | |POLY-3 RATE (b) | 3/34.22 2/30.37 2/29.84 1/21.09 2/19.44 | |POLY-3 PERCENT (g) | 8.8% 6.6% 6.7% 4.7% 10.3% | |TERMINAL (d) | 1/19 (5%) 2/21 (10%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 446 668 (T) 490 631 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.444 P=0.494N P=0.589N P=0.557N P=0.593 | |POLY 3 | P=0.543 P=0.555N P=0.563N P=0.490N P=0.617 | |POLY 1.5 | P=0.557 P=0.544N P=0.538N P=0.463N P=0.626 | |POLY 6 | P=0.521 P=0.557N P=0.595N P=0.523N P=0.608 | |LOGISTIC REGRESSION| P=0.545 P=0.532N P=0.518N P=0.448N P=0.638 | |COCH-ARM / FISHERS | P=0.540N P=0.500N P=0.500N P=0.429N P=0.652 | |ORDER RESTRICTED | P=0.583 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 1/40 (3%) 3/42 (7%) | |POLY-3 RATE (b) | 1/34.96 2/31.46 3/37.39 1/32.58 3/29.89 | |POLY-3 PERCENT (g) | 2.9% 6.4% 8.0% 3.1% 10.0% | |TERMINAL (d) | 1/20 (5%) 1/18 (6%) 1/24 (4%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | 668 (T) 559 514 488 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283 P=0.446 P=0.363 P=0.757 P=0.267 | |POLY 3 | P=0.288 P=0.463 P=0.328 P=0.746 P=0.248 | |POLY 1.5 | P=0.269 P=0.481 P=0.318 P=0.737 P=0.244 | |POLY 6 | P=0.306 P=0.445 P=0.347 P=0.754 P=0.254 | |LOGISTIC REGRESSION| P=0.239 P=0.446 P=0.317 P=0.712 P=0.241 | |COCH-ARM / FISHERS | P=0.233 P=0.500 P=0.309 P=0.694 P=0.245 | |ORDER RESTRICTED | P=0.196 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 42 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 7/50 (14%) 12/50 (24%) 6/37 (16%) 5/32 (16%) | |POLY-3 RATE (b) | 9/37.84 7/35.33 12/35.05 6/24.88 5/21.68 | |POLY-3 PERCENT (g) | 23.8% 19.8% 34.2% 24.1% 23.1% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 2/13 (15%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 111 157 229 298 192 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.470 P=0.459N P=0.199 P=0.537 P=0.587N | |POLY 3 | P=0.508 P=0.449N P=0.230 P=0.607 P=0.599N | |POLY 1.5 | P=0.531N P=0.443N P=0.263 P=0.594N P=0.581N | |POLY 6 | P=0.454 P=0.447N P=0.183 P=0.553 P=0.625N | |LOGISTIC REGRESSION| P=0.375N P=0.274N P=0.375 P=0.417N P=0.434N | |COCH-ARM / FISHERS | P=0.456N P=0.393N P=0.312 P=0.531N P=0.515N | |ORDER RESTRICTED | P=0.534 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 5/50 (10%) 5/50 (10%) 5/40 (13%) 8/42 (19%) | |POLY-3 RATE (b) | 8/38.10 5/34.04 5/38.64 5/33.23 8/31.44 | |POLY-3 PERCENT (g) | 21.0% 14.7% 12.9% 15.0% 25.4% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 1/24 (4%) 2/20 (10%) 3/19 (16%) | |FIRST INCIDENCE | 179 207 182 414 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.355 P=0.379N P=0.226N P=0.324N P=0.474 | |POLY 3 | P=0.317 P=0.348N P=0.261N P=0.365N P=0.439 | |POLY 1.5 | P=0.295 P=0.312N P=0.266N P=0.378N P=0.437 | |POLY 6 | P=0.332 P=0.387N P=0.253N P=0.363N P=0.445 | |LOGISTIC REGRESSION| P=0.250 P=0.252N P=0.291N P=0.510N P=0.459 | |COCH-ARM / FISHERS | P=0.265 P=0.277N P=0.277N P=0.437N P=0.455 | |ORDER RESTRICTED | P=0.262 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 43 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 1/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 3.4% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 668 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.663 (e) P=0.424 (e) (e) | |POLY 3 | P=0.680N (e) P=0.474 (e) (e) | |POLY 1.5 | P=0.665N (e) P=0.485 (e) (e) | |POLY 6 | P=0.700N (e) P=0.461 (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.424 (e) (e) | |COCH-ARM / FISHERS | P=0.647N (e) P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.512 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 3/40 (8%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.65 3/32.44 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 9.3% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 2/20 (10%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- 541 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174 (e) (e) P=0.113 (e) | |POLY 3 | P=0.133 (e) (e) P=0.103 (e) | |POLY 1.5 | P=0.134 (e) (e) P=0.097 (e) | |POLY 6 | P=0.133 (e) (e) P=0.108 (e) | |LOGISTIC REGRESSION| P=0.161 (e) (e) P=0.101 (e) | |COCH-ARM / FISHERS | P=0.153 (e) (e) P=0.084 (e) | |ORDER RESTRICTED | P=0.119 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 44 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 7/50 (14%) 2/50 (4%) 5/37 (14%) 2/32 (6%) | |POLY-3 RATE (b) | 10/35.49 7/30.89 2/29.65 5/21.36 2/19.75 | |POLY-3 PERCENT (g) | 28.2% 22.7% 6.8% 23.4% 10.1% | |TERMINAL (d) | 6/19 (32%) 6/21 (29%) 0/13 (0%) 3/7 (43%) 1/8 (13%) | |FIRST INCIDENCE | 308 523 606 608 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.243N P=0.264N P=0.052N P=0.527 P=0.180N | |POLY 3 | P=0.086N P=0.407N P=0.026N* P=0.467N P=0.111N | |POLY 1.5 | P=0.080N P=0.384N P=0.020N* P=0.407N P=0.105N | |POLY 6 | P=0.095N P=0.408N P=0.034N* P=0.539N P=0.118N | |LOGISTIC REGRESSION| P=0.099N P=0.356N P=0.021N* P=0.412N P=0.097N | |COCH-ARM / FISHERS | P=0.072N P=0.298N P=0.014N* P=0.310N P=0.077N | |ORDER RESTRICTED | P=0.093N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 6/50 (12%) 6/50 (12%) 9/40 (23%) 9/42 (21%) | |POLY-3 RATE (b) | 7/35.41 6/33.58 6/37.69 9/33.46 9/29.89 | |POLY-3 PERCENT (g) | 19.8% 17.9% 15.9% 26.9% 30.1% | |TERMINAL (d) | 4/20 (20%) 1/18 (6%) 4/24 (17%) 4/20 (20%) 5/19 (26%) | |FIRST INCIDENCE | 588 369 460 530 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.142 P=0.605N P=0.392N P=0.385 P=0.305 | |POLY 3 | P=0.088 P=0.543N P=0.451N P=0.338 P=0.245 | |POLY 1.5 | P=0.079 P=0.518N P=0.471N P=0.302 P=0.243 | |POLY 6 | P=0.099 P=0.566N P=0.419N P=0.375 P=0.253 | |LOGISTIC REGRESSION| P=0.086 P=0.555N P=0.455N P=0.317 P=0.229 | |COCH-ARM / FISHERS | P=0.071 P=0.500N P=0.500N P=0.220 P=0.254 | |ORDER RESTRICTED | P=0.198 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 45 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 9/50 (18%) 7/50 (14%) 4/37 (11%) 3/32 (9%) | |POLY-3 RATE (b) | 8/34.88 9/33.08 7/31.07 4/22.82 3/19.74 | |POLY-3 PERCENT (g) | 22.9% 27.2% 22.5% 17.5% 15.2% | |TERMINAL (d) | 3/19 (16%) 3/21 (14%) 2/13 (15%) 1/7 (14%) 1/8 (13%) | |FIRST INCIDENCE | 463 254 243 157 538 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.325N P=0.487 P=0.496 P=0.582N P=0.434N | |POLY 3 | P=0.190N P=0.449 P=0.601N P=0.436N P=0.370N | |POLY 1.5 | P=0.172N P=0.450 P=0.558N P=0.401N P=0.355N | |POLY 6 | P=0.225N P=0.468 P=0.575 P=0.485N P=0.392N | |LOGISTIC REGRESSION| P=0.163N P=0.446 P=0.571N P=0.390N P=0.352N | |COCH-ARM / FISHERS | P=0.138N P=0.500 P=0.500N P=0.357N P=0.305N | |ORDER RESTRICTED | P=0.382N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 8/50 (16%) 5/50 (10%) 4/40 (10%) 6/42 (14%) | |POLY-3 RATE (b) | 6/36.84 8/34.89 5/37.43 4/33.22 6/29.23 | |POLY-3 PERCENT (g) | 16.3% 22.9% 13.4% 12.0% 20.5% | |TERMINAL (d) | 3/20 (15%) 1/18 (6%) 2/24 (8%) 1/20 (5%) 4/19 (21%) | |FIRST INCIDENCE | 255 369 524 414 585 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.431N P=0.292 P=0.416N P=0.418N P=0.530 | |POLY 3 | P=0.504N P=0.339 P=0.489N P=0.434N P=0.451 | |POLY 1.5 | P=0.512N P=0.360 P=0.496N P=0.453N P=0.463 | |POLY 6 | P=0.502N P=0.330 P=0.468N P=0.419N P=0.442 | |LOGISTIC REGRESSION| P=0.517N P=0.396 P=0.491N P=0.562N P=0.484 | |COCH-ARM / FISHERS | P=0.528N P=0.387 P=0.500N P=0.519N P=0.492 | |ORDER RESTRICTED | P=0.550N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 46 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 2/33.99 0/30.37 1/29.77 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 5.9% 0.0% 3.4% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 475 --- 482 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.159N P=0.266N P=0.548N P=0.364N P=0.363N | |POLY 3 | P=0.151N P=0.262N P=0.546N P=0.352N P=0.373N | |POLY 1.5 | P=0.145N P=0.257N P=0.528N P=0.335N P=0.365N | |POLY 6 | P=0.164N P=0.262N P=0.571N P=0.376N P=0.383N | |LOGISTIC REGRESSION| P=0.143N P=0.240N P=0.495N P=0.309N P=0.343N | |COCH-ARM / FISHERS | P=0.143N P=0.247N P=0.500N P=0.327N P=0.369N | |ORDER RESTRICTED | P=0.163N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.65 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 47 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/50 (30%) 15/50 (30%) 9/50 (18%) 6/37 (16%) 15/32 (47%) | |POLY-3 RATE (b) | 15/35.89 15/33.83 9/33.41 6/22.46 15/23.78 | |POLY-3 PERCENT (g) | 41.8% 44.3% 26.9% 26.7% 63.1% | |TERMINAL (d) | 8/19 (42%) 10/21 (48%) 1/13 (8%) 0/7 (0%) 6/8 (75%) | |FIRST INCIDENCE | 322 254 229 563 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.038 * P=0.561N P=0.336N P=0.417N P=0.027 * | |POLY 3 | P=0.118 P=0.511 P=0.140N P=0.184N P=0.076 | |POLY 1.5 | P=0.130 P=0.516 P=0.128N P=0.155N P=0.070 | |POLY 6 | P=0.106 P=0.521 P=0.166N P=0.217N P=0.081 | |LOGISTIC REGRESSION| P=0.140 P=0.493 P=0.146N P=0.179N P=0.054 | |COCH-ARM / FISHERS | P=0.190 P=0.586N P=0.121N P=0.108N P=0.095 | |ORDER RESTRICTED | P=0.023 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 6/50 (12%) 3/50 (6%) 2/40 (5%) 2/42 (5%) | |POLY-3 RATE (b) | 1/35.32 6/35.10 3/37.76 2/32.44 2/29.28 | |POLY-3 PERCENT (g) | 2.8% 17.1% 7.9% 6.2% 6.8% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | 577 326 362 608 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.413N P=0.047 * P=0.347 P=0.478 P=0.435 | |POLY 3 | P=0.434N P=0.051 P=0.328 P=0.470 P=0.434 | |POLY 1.5 | P=0.440N P=0.055 P=0.319 P=0.458 P=0.434 | |POLY 6 | P=0.430N P=0.048 * P=0.343 P=0.480 P=0.435 | |LOGISTIC REGRESSION| P=0.468N P=0.060 P=0.302 P=0.438 P=0.435 | |COCH-ARM / FISHERS | P=0.453N P=0.056 P=0.309 P=0.416 P=0.434 | |ORDER RESTRICTED | P=0.286 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 48 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 0/37 (0%) 1/32 (3%) | |POLY-3 RATE (b) | 1/33.32 1/30.37 2/30.05 0/20.93 1/19.79 | |POLY-3 PERCENT (g) | 3.0% 3.3% 6.7% 0.0% 5.1% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 621 668 (T) 315 --- 473 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.519 P=0.754N P=0.416 P=0.622N P=0.652 | |POLY 3 | P=0.571 P=0.741 P=0.464 P=0.591N P=0.640 | |POLY 1.5 | P=0.580 P=0.743 P=0.479 P=0.580N P=0.641 | |POLY 6 | P=0.556 P=0.744 P=0.442 P=0.606N P=0.639 | |LOGISTIC REGRESSION| P=0.581N P=0.749 P=0.500 P=0.597N P=0.656 | |COCH-ARM / FISHERS | P=0.572N P=0.753N P=0.500 P=0.575N P=0.631 | |ORDER RESTRICTED | P=0.616 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 0/40 (0%) 2/42 (5%) | |POLY-3 RATE (b) | 0/34.96 1/31.32 3/37.67 0/31.97 2/29.97 | |POLY-3 PERCENT (g) | 0.0% 3.2% 8.0% 0.0% 6.7% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 1/24 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 600 514 --- 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.275 P=0.457 P=0.137 (e) P=0.192 | |POLY 3 | P=0.305 P=0.478 P=0.131 (e) P=0.202 | |POLY 1.5 | P=0.287 P=0.489 P=0.126 (e) P=0.200 | |POLY 6 | P=0.322 P=0.467 P=0.141 (e) P=0.205 | |LOGISTIC REGRESSION| P=0.245 P=0.485 P=0.121 (e) P=0.210 | |COCH-ARM / FISHERS | P=0.249 P=0.500 P=0.121 (e) P=0.206 | |ORDER RESTRICTED | P=0.126 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 49 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Kupffer Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 2/33.47 0/30.37 0/29.15 1/20.96 1/19.28 | |POLY-3 PERCENT (g) | 6.0% 0.0% 0.0% 4.8% 5.2% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 619 --- --- 662 635 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.406 P=0.254N P=0.326N P=0.701 P=0.687N | |POLY 3 | P=0.498 P=0.258N P=0.268N P=0.659N P=0.687N | |POLY 1.5 | P=0.497 P=0.255N P=0.255N P=0.639N P=0.681N | |POLY 6 | P=0.495 P=0.256N P=0.287N P=0.685N P=0.695N | |LOGISTIC REGRESSION| P=0.451 P=0.254N P=0.273N P=0.690N P=0.692N | |COCH-ARM / FISHERS | P=0.495 P=0.247N P=0.247N P=0.613N P=0.779 | |ORDER RESTRICTED | P=0.394N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Kupffer Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 1/40 (3%) 2/42 (5%) | |POLY-3 RATE (b) | 1/34.96 0/31.04 1/36.65 1/32.49 2/30.40 | |POLY-3 PERCENT (g) | 2.9% 0.0% 2.7% 3.1% 6.6% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 1/24 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 668 (T) --- 668 (T) 523 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.170 P=0.521N P=0.722N P=0.751 P=0.447 | |POLY 3 | P=0.187 P=0.524N P=0.751N P=0.746 P=0.451 | |POLY 1.5 | P=0.173 P=0.512N P=0.755N P=0.737 P=0.446 | |POLY 6 | P=0.201 P=0.536N P=0.743N P=0.754 P=0.457 | |LOGISTIC REGRESSION| P=0.146 (e) P=0.722N P=0.723 P=0.461 | |COCH-ARM / FISHERS | P=0.148 P=0.500N P=0.753N P=0.694 P=0.434 | |ORDER RESTRICTED | P=0.200 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 50 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Kupffer Cell | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 0/50 (0%) 2/37 (5%) 3/32 (9%) | |POLY-3 RATE (b) | 2/33.19 3/30.37 0/29.15 2/22.07 3/19.89 | |POLY-3 PERCENT (g) | 6.0% 9.9% 0.0% 9.1% 15.1% | |TERMINAL (d) | 1/19 (5%) 3/21 (14%) 0/13 (0%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | 654 668 (T) --- 157 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.087 P=0.537 P=0.338N P=0.416 P=0.211 | |POLY 3 | P=0.166 P=0.459 P=0.266N P=0.541 P=0.273 | |POLY 1.5 | P=0.170 P=0.464 P=0.254N P=0.557 P=0.274 | |POLY 6 | P=0.162 P=0.466 P=0.282N P=0.519 P=0.273 | |LOGISTIC REGRESSION| P=0.162 P=0.500 P=0.309N P=0.587 P=0.258 | |COCH-ARM / FISHERS | P=0.184 P=0.500 P=0.247N P=0.571 P=0.296 | |ORDER RESTRICTED | P=0.184 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Kupffer Cell | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) 2/50 (4%) 6/40 (15%) 6/42 (14%) | |POLY-3 RATE (b) | 4/36.27 4/32.56 2/37.00 6/33.02 6/30.88 | |POLY-3 PERCENT (g) | 11.0% 12.3% 5.4% 18.2% 19.4% | |TERMINAL (d) | 1/20 (5%) 1/18 (6%) 0/24 (0%) 3/20 (15%) 3/19 (16%) | |FIRST INCIDENCE | 248 500 621 523 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.116 P=0.550 P=0.285N P=0.349 P=0.289 | |POLY 3 | P=0.091 P=0.584 P=0.326N P=0.306 P=0.266 | |POLY 1.5 | P=0.084 P=0.611 P=0.332N P=0.288 P=0.263 | |POLY 6 | P=0.097 P=0.561 P=0.311N P=0.323 P=0.271 | |LOGISTIC REGRESSION| P=0.074 P=0.644N P=0.336N P=0.242 P=0.269 | |COCH-ARM / FISHERS | P=0.073 P=0.643N P=0.339N P=0.237 P=0.264 | |ORDER RESTRICTED | P=0.189 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 51 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 4/37 (11%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 1/30.37 2/29.55 4/21.96 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 3.3% 6.8% 18.2% 0.0% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 668 (T) 606 580 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.166 P=0.520 P=0.179 P=0.020 * (e) | |POLY 3 | P=0.166 P=0.483 P=0.211 P=0.019 * (e) | |POLY 1.5 | P=0.172 P=0.484 P=0.221 P=0.022 * (e) | |POLY 6 | P=0.155 P=0.486 P=0.200 P=0.018 * (e) | |LOGISTIC REGRESSION| P=0.176 P=0.520 P=0.204 P=0.020 * (e) | |COCH-ARM / FISHERS | P=0.205 P=0.500 P=0.247 P=0.030 * (e) | |ORDER RESTRICTED | P=0.125 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/49 (6%) 4/50 (8%) 1/40 (3%) 3/42 (7%) | |POLY-3 RATE (b) | 1/35.82 3/32.64 4/37.37 1/32.81 3/31.17 | |POLY-3 PERCENT (g) | 2.8% 9.2% 10.7% 3.1% 9.6% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 352 417 585 359 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.389 P=0.282 P=0.229 P=0.737 P=0.249 | |POLY 3 | P=0.409 P=0.271 P=0.189 P=0.743 P=0.254 | |POLY 1.5 | P=0.389 P=0.285 P=0.184 P=0.735 P=0.250 | |POLY 6 | P=0.425 P=0.258 P=0.204 P=0.748 P=0.260 | |LOGISTIC REGRESSION| P=0.335 P=0.296 P=0.179 P=0.453 P=0.284 | |COCH-ARM / FISHERS | P=0.345 P=0.301 P=0.181 P=0.694 P=0.245 | |ORDER RESTRICTED | P=0.238 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 52 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 1/33.19 0/30.37 1/29.79 1/21.33 1/20.14 | |POLY-3 PERCENT (g) | 3.0% 0.0% 3.4% 4.7% 5.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 654 --- 474 563 41 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.272 P=0.500N P=0.708 P=0.605 P=0.624 | |POLY 3 | P=0.306 P=0.518N P=0.737 P=0.658 P=0.646 | |POLY 1.5 | P=0.307 P=0.516N P=0.746 P=0.670 P=0.648 | |POLY 6 | P=0.300 P=0.515N P=0.725 P=0.644 P=0.643 | |LOGISTIC REGRESSION| P=0.333 P=0.510N P=0.755 P=0.661 P=0.753 | |COCH-ARM / FISHERS | P=0.305 P=0.500N P=0.753N P=0.673 P=0.631 | |ORDER RESTRICTED | P=0.443 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/49 (0%) 0/50 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 3/35.75 0/30.96 0/36.65 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 8.4% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 577 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.039N* P=0.191N P=0.113N P=0.153N P=0.171N | |POLY 3 | P=0.034N* P=0.145N P=0.113N P=0.137N P=0.158N | |POLY 1.5 | P=0.037N* P=0.132N P=0.115N P=0.141N P=0.156N | |POLY 6 | P=0.031N* P=0.162N P=0.109N P=0.135N P=0.162N | |LOGISTIC REGRESSION| P=0.040N* P=0.134N P=0.116N P=0.148N P=0.155N | |COCH-ARM / FISHERS | P=0.042N* P=0.125N P=0.121N P=0.167N P=0.156N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 53 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) 7/50 (14%) 5/37 (14%) 2/32 (6%) | |POLY-3 RATE (b) | 5/34.44 3/32.15 7/32.61 5/22.33 2/20.67 | |POLY-3 PERCENT (g) | 14.5% 9.3% 21.5% 22.4% 9.7% | |TERMINAL (d) | 2/19 (11%) 1/21 (5%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 475 322 147 501 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.445 P=0.372N P=0.263 P=0.256 P=0.501N | |POLY 3 | P=0.513 P=0.392N P=0.335 P=0.344 P=0.459N | |POLY 1.5 | P=0.519 P=0.389N P=0.355 P=0.372 P=0.456N | |POLY 6 | P=0.495 P=0.388N P=0.309 P=0.318 P=0.467N | |LOGISTIC REGRESSION| P=0.532N P=0.357N P=0.385 P=0.358 P=0.428N | |COCH-ARM / FISHERS | P=0.534N P=0.357N P=0.380 P=0.429 P=0.436N | |ORDER RESTRICTED | P=0.460N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 6/49 (12%) 6/50 (12%) 2/40 (5%) 8/42 (19%) | |POLY-3 RATE (b) | 7/37.57 6/33.99 6/37.25 2/32.44 8/32.68 | |POLY-3 PERCENT (g) | 18.6% 17.7% 16.1% 6.2% 24.5% | |TERMINAL (d) | 2/20 (10%) 1/18 (6%) 3/24 (13%) 1/20 (5%) 3/19 (16%) | |FIRST INCIDENCE | 372 207 585 539 49 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.491 P=0.606N P=0.415N P=0.107N P=0.385 | |POLY 3 | P=0.481 P=0.579N P=0.507N P=0.113N P=0.379 | |POLY 1.5 | P=0.462 P=0.543N P=0.505N P=0.117N P=0.377 | |POLY 6 | P=0.492 P=0.616N P=0.495N P=0.111N P=0.381 | |LOGISTIC REGRESSION| P=0.390 P=0.501N P=0.489N P=0.165N P=0.375 | |COCH-ARM / FISHERS | P=0.405 P=0.516N P=0.500N P=0.144N P=0.355 | |ORDER RESTRICTED | P=0.233 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 54 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 1/33.13 0/30.37 0/29.15 1/21.09 1/19.54 | |POLY-3 PERCENT (g) | 3.0% 0.0% 0.0% 4.7% 5.1% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) --- --- 631 563 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.206 P=0.480N P=0.576N P=0.557 P=0.602 | |POLY 3 | P=0.259 P=0.517N P=0.526N P=0.656 P=0.639 | |POLY 1.5 | P=0.256 P=0.516N P=0.515N P=0.668 P=0.640 | |POLY 6 | P=0.260 P=0.514N P=0.539N P=0.640 P=0.638 | |LOGISTIC REGRESSION| P=0.233 (e) (e) P=0.622 P=0.637 | |COCH-ARM / FISHERS | P=0.256 P=0.500N P=0.500N P=0.673 P=0.631 | |ORDER RESTRICTED | P=0.326 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 3/50 (6%) 4/40 (10%) 1/42 (2%) | |POLY-3 RATE (b) | 1/34.96 1/31.54 3/37.40 4/32.19 1/28.81 | |POLY-3 PERCENT (g) | 2.9% 3.2% 8.0% 12.4% 3.5% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 1/24 (4%) 3/20 (15%) 1/19 (5%) | |FIRST INCIDENCE | 668 (T) 500 460 614 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.348 P=0.736 P=0.361 P=0.180 P=0.752 | |POLY 3 | P=0.294 P=0.738 P=0.329 P=0.150 P=0.718 | |POLY 1.5 | P=0.286 P=0.748 P=0.319 P=0.142 P=0.718 | |POLY 6 | P=0.303 P=0.728 P=0.346 P=0.157 P=0.718 | |LOGISTIC REGRESSION| P=0.307 P=0.751 P=0.315 P=0.163 P=0.752 | |COCH-ARM / FISHERS | P=0.286 P=0.747 P=0.309 P=0.119 P=0.707 | |ORDER RESTRICTED | P=0.334 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 55 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 16/50 (32%) 13/50 (26%) 16/37 (43%) 14/32 (44%) | |POLY-3 RATE (b) | 12/36.08 16/35.72 13/32.37 16/25.52 14/22.06 | |POLY-3 PERCENT (g) | 33.3% 44.8% 40.2% 62.7% 63.5% | |TERMINAL (d) | 3/19 (16%) 6/21 (29%) 6/13 (46%) 4/7 (57%) 4/8 (50%) | |FIRST INCIDENCE | 446 322 376 341 376 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.258 P=0.245 P=0.008 ** P=0.024 * | |POLY 3 | P=0.003 ** P=0.219 P=0.364 P=0.016 * P=0.018 * | |POLY 1.5 | P=0.005 ** P=0.206 P=0.417 P=0.021 * P=0.022 * | |POLY 6 | P=0.002 ** P=0.251 P=0.294 P=0.013 * P=0.017 * | |LOGISTIC REGRESSION| P=0.006 ** P=0.198 P=0.389 P=0.018 * P=0.023 * | |COCH-ARM / FISHERS | P=0.016 * P=0.252 P=0.500 P=0.048 * P=0.052 | |ORDER RESTRICTED | P=0.020 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 11/49 (22%) 21/50 (42%) 12/40 (30%) 10/42 (24%) | |POLY-3 RATE (b) | 12/37.09 11/35.32 21/43.08 12/33.52 10/30.37 | |POLY-3 PERCENT (g) | 32.4% 31.1% 48.8% 35.8% 32.9% | |TERMINAL (d) | 4/20 (20%) 2/18 (11%) 9/24 (38%) 7/20 (35%) 7/19 (37%) | |FIRST INCIDENCE | 497 369 181 539 412 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.387N P=0.494 P=0.129 P=0.540 P=0.548N | |POLY 3 | P=0.519N P=0.557N P=0.099 P=0.478 P=0.585 | |POLY 1.5 | P=0.530N P=0.530N P=0.076 P=0.450 P=0.592 | |POLY 6 | P=0.532N P=0.588N P=0.130 P=0.490 P=0.565 | |LOGISTIC REGRESSION| P=0.520N P=0.562N P=0.046 * P=0.480 P=0.588 | |COCH-ARM / FISHERS | P=0.508 P=0.522N P=0.044 * P=0.344 P=0.590N | |ORDER RESTRICTED | P=0.419 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 56 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/49 (0%) 0/50 (0%) 1/40 (3%) 1/42 (2%) | |POLY-3 RATE (b) | 2/35.32 0/30.96 0/36.65 1/31.97 1/28.81 | |POLY-3 PERCENT (g) | 5.7% 0.0% 0.0% 3.1% 3.5% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 1/19 (5%) | |FIRST INCIDENCE | 577 --- --- 668 (T) 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.577N P=0.295N P=0.220N P=0.527N P=0.543N | |POLY 3 | P=0.604 P=0.266N P=0.228N P=0.535N P=0.571N | |POLY 1.5 | P=0.589 P=0.253N P=0.232N P=0.544N P=0.568N | |POLY 6 | P=0.599N P=0.283N P=0.222N P=0.530N P=0.575N | |LOGISTIC REGRESSION| P=0.595 P=0.265N P=0.228N P=0.529N P=0.568N | |COCH-ARM / FISHERS | P=0.567 P=0.253N P=0.247N P=0.584N P=0.566N | |ORDER RESTRICTED | P=0.257N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 57 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 5/50 (10%) 2/37 (5%) 1/32 (3%) | |POLY-3 RATE (b) | 2/33.19 1/30.37 5/31.01 2/22.71 1/19.26 | |POLY-3 PERCENT (g) | 6.0% 3.3% 16.1% 8.8% 5.2% | |TERMINAL (d) | 1/19 (5%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 654 668 (T) 474 298 640 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.421 P=0.477N P=0.135 P=0.439 P=0.713 | |POLY 3 | P=0.496 P=0.531N P=0.183 P=0.552 P=0.685N | |POLY 1.5 | P=0.507 P=0.528N P=0.194 P=0.562 P=0.680N | |POLY 6 | P=0.474 P=0.526N P=0.174 P=0.534 P=0.691N | |LOGISTIC REGRESSION| P=0.521 P=0.506N P=0.180 P=0.610 P=0.709N | |COCH-ARM / FISHERS | P=0.537 P=0.500N P=0.218 P=0.571 P=0.779 | |ORDER RESTRICTED | P=0.403 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 0/50 (0%) 2/40 (5%) 2/42 (5%) | |POLY-3 RATE (b) | 1/35.01 0/30.96 0/36.65 2/33.37 2/29.44 | |POLY-3 PERCENT (g) | 2.9% 0.0% 0.0% 6.0% 6.8% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | 658 --- --- 359 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.085 P=0.531N P=0.465N P=0.488 P=0.460 | |POLY 3 | P=0.084 P=0.525N P=0.491N P=0.483 P=0.439 | |POLY 1.5 | P=0.078 P=0.514N P=0.495N P=0.467 P=0.437 | |POLY 6 | P=0.090 P=0.537N P=0.484N P=0.497 P=0.442 | |LOGISTIC REGRESSION| P=0.071 P=0.540N P=0.474N P=0.320 P=0.434 | |COCH-ARM / FISHERS | P=0.072 P=0.505N P=0.500N P=0.416 P=0.434 | |ORDER RESTRICTED | P=0.147 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 58 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 3/50 (6%) 0/50 (0%) 1/37 (3%) 4/32 (13%) | |POLY-3 RATE (b) | 6/34.31 3/31.86 0/29.15 1/21.41 4/19.78 | |POLY-3 PERCENT (g) | 17.5% 9.4% 0.0% 4.7% 20.2% | |TERMINAL (d) | 2/19 (11%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 2/8 (25%) | |FIRST INCIDENCE | 538 418 --- 539 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.402 P=0.260N P=0.043N* P=0.236N P=0.452 | |POLY 3 | P=0.538 P=0.274N P=0.024N* P=0.164N P=0.545 | |POLY 1.5 | P=0.555 P=0.273N P=0.020N* P=0.146N P=0.557 | |POLY 6 | P=0.508 P=0.268N P=0.031N* P=0.192N P=0.525 | |LOGISTIC REGRESSION| P=0.533 P=0.268N P=0.025N* P=0.154N P=0.548 | |COCH-ARM / FISHERS | P=0.537N P=0.243N P=0.013N* P=0.118N P=0.602 | |ORDER RESTRICTED | P=0.163 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 2/49 (4%) 10/50 (20%) 3/40 (8%) 2/42 (5%) | |POLY-3 RATE (b) | 2/35.32 2/30.96 10/37.79 3/32.09 2/29.68 | |POLY-3 PERCENT (g) | 5.7% 6.5% 26.5% 9.4% 6.7% | |TERMINAL (d) | 1/20 (5%) 2/18 (11%) 8/24 (33%) 2/20 (10%) 1/19 (5%) | |FIRST INCIDENCE | 577 668 (T) 181 641 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.434N P=0.631 P=0.029 * P=0.479 P=0.644 | |POLY 3 | P=0.462N P=0.647 P=0.016 * P=0.456 P=0.632 | |POLY 1.5 | P=0.495N P=0.669 P=0.015 * P=0.443 P=0.630 | |POLY 6 | P=0.434N P=0.621 P=0.018 * P=0.464 P=0.632 | |LOGISTIC REGRESSION| P=0.506N P=0.628 P=0.017 * P=0.467 P=0.631 | |COCH-ARM / FISHERS | P=0.539N P=0.684 P=0.014 * P=0.394 P=0.623 | |ORDER RESTRICTED | P=0.194 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 59 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/12 (25%) 2/10 (20%) 1/15 (7%) 0/6 (0%) 0/2 (0%) | |POLY-3 RATE (b) | 3/6.80 2/6.23 1/9.95 0/2.81 0/0.97 | |POLY-3 PERCENT (g) | 44.1% 32.1% 10.1% 0.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 308 322 243 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.558N P=0.335N P=0.206N P=0.237N | |POLY 3 | P=0.067N P=0.551N P=0.148N P=0.283N P=0.603N | |POLY 1.5 | P=0.073N P=0.540N P=0.168N P=0.262N P=0.576N | |POLY 6 | P=0.060N P=0.619N P=0.140N P=0.314N P=0.637N | |LOGISTIC REGRESSION| P=0.099N P=0.651 P=0.327N P=0.284N P=0.601N | |COCH-ARM / FISHERS | P=0.075N P=0.594N P=0.216N P=0.270N P=0.604N | |ORDER RESTRICTED | P=0.560N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 1/23 (4%) 2/16 (13%) 0/12 (0%) 0/16 (0%) | |POLY-3 RATE (b) | 1/6.20 1/12.90 2/10.85 0/9.59 0/11.87 | |POLY-3 PERCENT (g) | 16.1% 7.8% 18.4% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 460 475 654 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.098N P=0.749 P=0.734N P=0.510N P=0.538N | |POLY 3 | P=0.097N P=0.590N P=0.694 P=0.416N P=0.376N | |POLY 1.5 | P=0.123N P=0.610N P=0.637 P=0.459N P=0.411N | |POLY 6 | P=0.070N P=0.567N P=0.710N P=0.364N P=0.337N | |LOGISTIC REGRESSION| P=0.133N P=0.673N P=0.762N P=0.644N P=0.576N | |COCH-ARM / FISHERS | P=0.178N P=0.620N P=0.552 P=0.538N P=0.467N | |ORDER RESTRICTED | P=0.256N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 60 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/12 (25%) 0/10 (0%) 0/15 (0%) 0/6 (0%) 2/2 (100%) | |POLY-3 RATE (b) | 3/6.80 0/4.46 0/9.00 0/2.81 2/2.00 | |POLY-3 PERCENT (g) | 44.1% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 308 --- --- --- 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.474 P=0.148N P=0.140N P=0.206N P=0.609 | |POLY 3 | P=0.040 * P=0.161N P=0.045N* P=0.283N P=0.213 | |POLY 1.5 | P=0.054 P=0.134N P=0.051N P=0.262N P=0.142 | |POLY 6 | P=0.045 * P=0.238N P=0.042N* P=0.314N P=0.317 | |LOGISTIC REGRESSION| P=0.191 P=0.192N P=0.112N P=0.284N P=0.092 | |COCH-ARM / FISHERS | P=0.219 P=0.143N P=0.075N P=0.270N P=0.110 | |ORDER RESTRICTED | P=0.028 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/14 (14%) 0/23 (0%) 0/16 (0%) 0/12 (0%) 1/16 (6%) | |POLY-3 RATE (b) | 2/6.48 0/12.26 0/10.79 0/9.59 1/12.56 | |POLY-3 PERCENT (g) | 30.9% 0.0% 0.0% 0.0% 8.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 460 --- --- --- 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.444N P=0.274N P=0.214N P=0.250N P=0.557N | |POLY 3 | P=0.493N P=0.095N P=0.123N P=0.145N P=0.277N | |POLY 1.5 | P=0.481N P=0.105N P=0.149N P=0.185N P=0.337N | |POLY 6 | P=0.506N P=0.088N P=0.097N P=0.109N P=0.220N | |LOGISTIC REGRESSION| P=0.527N P=0.103N P=0.163N P=0.220N P=0.510N | |COCH-ARM / FISHERS | P=0.459N P=0.137N P=0.209N P=0.280N P=0.448N | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 61 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/12 (8%) 3/10 (30%) 2/15 (13%) 2/6 (33%) 0/2 (0%) | |POLY-3 RATE (b) | 1/5.02 3/6.89 2/10.84 2/4.57 0/0.97 | |POLY-3 PERCENT (g) | 19.9% 43.6% 18.5% 43.8% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 453 322 243 329 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.396N P=0.269 P=0.479 P=0.357 P=0.600N | |POLY 3 | P=0.612 P=0.409 P=0.710N P=0.460 P=0.844N | |POLY 1.5 | P=0.558 P=0.344 P=0.695 P=0.373 P=0.841N | |POLY 6 | P=0.656 P=0.445 P=0.675N P=0.532 P=0.851N | |LOGISTIC REGRESSION| P=0.364 P=0.152 P=0.460 P=0.203 P=0.850N | |COCH-ARM / FISHERS | P=0.451 P=0.226 P=0.586 P=0.245 P=0.857N | |ORDER RESTRICTED | P=0.644N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 3/23 (13%) 0/16 (0%) 1/12 (8%) 0/16 (0%) | |POLY-3 RATE (b) | 1/6.11 3/14.27 0/10.79 1/10.20 0/11.87 | |POLY-3 PERCENT (g) | 16.4% 21.0% 0.0% 9.8% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 497 219 --- 488 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.183N P=0.263 P=0.505N P=0.749 P=0.559N | |POLY 3 | P=0.108N P=0.634 P=0.390N P=0.637N P=0.374N | |POLY 1.5 | P=0.128N P=0.583 P=0.422N P=0.704N P=0.409N | |POLY 6 | P=0.089N P=0.697 P=0.352N P=0.551N P=0.335N | |LOGISTIC REGRESSION| P=0.317N P=0.422 P=0.485N P=0.710 P=0.517N | |COCH-ARM / FISHERS | P=0.176N P=0.509 P=0.467N P=0.720 P=0.467N | |ORDER RESTRICTED | P=0.215N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 62 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/49 (2%) 3/37 (8%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 1/29.14 3/23.31 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 3.4% 12.9% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/12 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 147 157 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.156 (e) P=0.508 P=0.072 (e) | |POLY 3 | P=0.128 (e) P=0.474 P=0.061 (e) | |POLY 1.5 | P=0.133 (e) P=0.484 P=0.064 (e) | |POLY 6 | P=0.121 (e) P=0.461 P=0.057 (e) | |LOGISTIC REGRESSION| P=0.228 (e) P=0.371 P=0.104 (e) | |COCH-ARM / FISHERS | P=0.157 (e) P=0.495 P=0.073 (e) | |ORDER RESTRICTED | P=0.144 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 2/47 (4%) 1/49 (2%) 0/40 (0%) 4/42 (10%) | |POLY-3 RATE (b) | 2/35.09 2/30.36 1/36.48 0/31.97 4/30.87 | |POLY-3 PERCENT (g) | 5.7% 6.6% 2.7% 0.0% 13.0% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 443 536 490 --- 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.229 P=0.611 P=0.496N P=0.270N P=0.263 | |POLY 3 | P=0.253 P=0.642 P=0.486N P=0.256N P=0.276 | |POLY 1.5 | P=0.245 P=0.661 P=0.492N P=0.261N P=0.272 | |POLY 6 | P=0.255 P=0.622 P=0.476N P=0.255N P=0.281 | |LOGISTIC REGRESSION| P=0.209 P=0.686 P=0.512N P=0.333N P=0.277 | |COCH-ARM / FISHERS | P=0.216 P=0.676 P=0.500N P=0.300N P=0.268 | |ORDER RESTRICTED | P=0.075 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 63 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/49 (2%) 1/37 (3%) 2/32 (6%) | |POLY-3 RATE (b) | 2/34.92 0/30.37 1/28.76 1/21.09 2/20.90 | |POLY-3 PERCENT (g) | 5.7% 0.0% 3.5% 4.7% 9.6% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/12 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 308 --- 490 631 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.224 P=0.267N P=0.524N P=0.675N P=0.499 | |POLY 3 | P=0.232 P=0.268N P=0.568N P=0.670N P=0.499 | |POLY 1.5 | P=0.233 P=0.263N P=0.545N P=0.648N P=0.501 | |POLY 6 | P=0.225 P=0.268N P=0.594N P=0.694N P=0.496 | |LOGISTIC REGRESSION| P=0.277 P=0.153N P=0.452N P=0.548N P=0.695 | |COCH-ARM / FISHERS | P=0.233 P=0.247N P=0.508N P=0.613N P=0.510 | |ORDER RESTRICTED | P=0.232 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 1/47 (2%) 0/49 (0%) 3/40 (8%) 2/42 (5%) | |POLY-3 RATE (b) | 2/34.50 1/30.07 0/35.88 3/32.00 2/30.15 | |POLY-3 PERCENT (g) | 5.8% 3.3% 0.0% 9.4% 6.6% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 0/24 (0%) 2/20 (10%) 0/19 (0%) | |FIRST INCIDENCE | 577 475 --- 662 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.266 P=0.568N P=0.221N P=0.488 P=0.632 | |POLY 3 | P=0.252 P=0.548N P=0.227N P=0.465 P=0.647 | |POLY 1.5 | P=0.242 P=0.530N P=0.231N P=0.453 P=0.641 | |POLY 6 | P=0.261 P=0.569N P=0.221N P=0.471 P=0.652 | |LOGISTIC REGRESSION| P=0.232 P=0.520N P=0.229N P=0.480 P=0.642 | |COCH-ARM / FISHERS | P=0.230 P=0.516N P=0.247N P=0.404 P=0.631 | |ORDER RESTRICTED | P=0.302 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 64 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 0/50 (0%) 6/49 (12%) 4/37 (11%) 5/32 (16%) | |POLY-3 RATE (b) | 7/36.88 0/30.37 6/31.19 4/23.16 5/21.09 | |POLY-3 PERCENT (g) | 19.0% 0.0% 19.2% 17.3% 23.7% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 1/12 (8%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | 308 --- 229 298 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.136 P=0.015N* P=0.587 P=0.582N P=0.451 | |POLY 3 | P=0.178 P=0.015N* P=0.611 P=0.569N P=0.464 | |POLY 1.5 | P=0.185 P=0.012N* P=0.582N P=0.527N P=0.481 | |POLY 6 | P=0.162 P=0.016N* P=0.547 P=0.623N P=0.444 | |LOGISTIC REGRESSION| P=0.214 P=0.007N** P=0.458N P=0.390N P=0.578 | |COCH-ARM / FISHERS | P=0.195 P=0.006N** P=0.516N P=0.459N P=0.540 | |ORDER RESTRICTED | P=0.162 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/49 (14%) 3/47 (6%) 2/49 (4%) 4/40 (10%) 6/42 (14%) | |POLY-3 RATE (b) | 7/36.00 3/31.46 2/35.94 4/32.49 6/30.97 | |POLY-3 PERCENT (g) | 19.4% 9.5% 5.6% 12.3% 19.4% | |TERMINAL (d) | 3/20 (15%) 0/17 (0%) 1/24 (4%) 3/20 (15%) 3/19 (16%) | |FIRST INCIDENCE | 460 207 654 523 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.402 P=0.249N P=0.064N P=0.297N P=0.605N | |POLY 3 | P=0.394 P=0.211N P=0.075N P=0.317N P=0.619N | |POLY 1.5 | P=0.372 P=0.187N P=0.076N P=0.328N P=0.619N | |POLY 6 | P=0.408 P=0.242N P=0.072N P=0.317N P=0.622 | |LOGISTIC REGRESSION| P=0.336 P=0.170N P=0.074N P=0.340N P=0.615 | |COCH-ARM / FISHERS | P=0.336 P=0.176N P=0.080N P=0.391N P=0.616 | |ORDER RESTRICTED | P=0.286N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 65 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/49 (6%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 3/30.02 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 10.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 1/12 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 187 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.588N (e) P=0.093 (e) (e) | |POLY 3 | P=0.589N (e) P=0.099 (e) (e) | |POLY 1.5 | P=0.568N (e) P=0.106 (e) (e) | |POLY 6 | P=0.619N (e) P=0.090 (e) (e) | |LOGISTIC REGRESSION| P=0.490N (e) P=0.139 (e) (e) | |COCH-ARM / FISHERS | P=0.532N (e) P=0.117 (e) (e) | |ORDER RESTRICTED | P=0.297 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/49 (6%) 4/47 (9%) 5/49 (10%) 5/40 (13%) 7/42 (17%) | |POLY-3 RATE (b) | 3/34.07 4/30.41 5/37.31 5/32.32 7/30.42 | |POLY-3 PERCENT (g) | 8.8% 13.2% 13.4% 15.5% 23.0% | |TERMINAL (d) | 3/20 (15%) 2/17 (12%) 0/24 (0%) 2/20 (10%) 4/19 (21%) | |FIRST INCIDENCE | 668 (T) 500 460 608 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083 P=0.399 P=0.446 P=0.361 P=0.124 | |POLY 3 | P=0.071 P=0.437 P=0.406 P=0.323 P=0.106 | |POLY 1.5 | P=0.063 P=0.459 P=0.384 P=0.304 P=0.102 | |POLY 6 | P=0.078 P=0.417 P=0.442 P=0.341 P=0.111 | |LOGISTIC REGRESSION| P=0.059 P=0.404 P=0.375 P=0.344 P=0.097 | |COCH-ARM / FISHERS | P=0.051 P=0.476 P=0.357 P=0.250 P=0.103 | |ORDER RESTRICTED | P=0.084 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 66 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/50 (22%) 9/50 (18%) 6/49 (12%) 3/37 (8%) 4/32 (13%) | |POLY-3 RATE (b) | 11/40.21 9/34.75 6/31.16 3/22.91 4/22.76 | |POLY-3 PERCENT (g) | 27.4% 25.9% 19.3% 13.1% 17.6% | |TERMINAL (d) | 0/19 (0%) 3/21 (14%) 0/12 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 308 147 229 298 192 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.133N P=0.476N P=0.242N P=0.138N P=0.276N | |POLY 3 | P=0.111N P=0.548N P=0.303N P=0.165N P=0.287N | |POLY 1.5 | P=0.091N P=0.508N P=0.236N P=0.123N P=0.263N | |POLY 6 | P=0.149N P=0.576N P=0.390N P=0.229N P=0.327N | |LOGISTIC REGRESSION| P=0.041N* P=0.300N P=0.102N P=0.034N* P=0.093N | |COCH-ARM / FISHERS | P=0.070N P=0.402N P=0.154N P=0.071N P=0.216N | |ORDER RESTRICTED | P=0.244N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/49 (10%) 0/47 (0%) 0/49 (0%) 0/40 (0%) 3/42 (7%) | |POLY-3 RATE (b) | 5/35.69 0/29.43 0/35.88 0/31.97 3/30.15 | |POLY-3 PERCENT (g) | 14.0% 0.0% 0.0% 0.0% 10.0% | |TERMINAL (d) | 1/20 (5%) 0/17 (0%) 0/24 (0%) 0/20 (0%) 1/19 (5%) | |FIRST INCIDENCE | 460 --- --- --- 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.423N P=0.053N P=0.029N* P=0.040N* P=0.445N | |POLY 3 | P=0.386N P=0.048N* P=0.029N* P=0.038N* P=0.451N | |POLY 1.5 | P=0.412N P=0.040N* P=0.029N* P=0.040N* P=0.450N | |POLY 6 | P=0.365N P=0.059N P=0.027N* P=0.038N* P=0.455N | |LOGISTIC REGRESSION| P=0.461N P=0.038N* P=0.033N* P=0.052N P=0.443N | |COCH-ARM / FISHERS | P=0.458N P=0.031N* P=0.028N* P=0.046N* P=0.447N | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 67 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/50 (22%) 7/50 (14%) 9/49 (18%) 6/37 (16%) 9/32 (28%) | |POLY-3 RATE (b) | 11/36.87 7/32.62 9/31.66 6/24.31 9/22.72 | |POLY-3 PERCENT (g) | 29.8% 21.5% 28.4% 24.7% 39.6% | |TERMINAL (d) | 4/19 (21%) 4/21 (19%) 4/12 (33%) 1/7 (14%) 2/8 (25%) | |FIRST INCIDENCE | 111 322 243 167 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.096 P=0.233N P=0.523 P=0.574 P=0.223 | |POLY 3 | P=0.220 P=0.299N P=0.556N P=0.441N P=0.308 | |POLY 1.5 | P=0.223 P=0.289N P=0.504N P=0.408N P=0.298 | |POLY 6 | P=0.211 P=0.294N P=0.590 P=0.489N P=0.325 | |LOGISTIC REGRESSION| P=0.251 P=0.223N P=0.408N P=0.298N P=0.359 | |COCH-ARM / FISHERS | P=0.250 P=0.218N P=0.421N P=0.348N P=0.354 | |ORDER RESTRICTED | P=0.226 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/49 (18%) 10/47 (21%) 17/49 (35%) 10/40 (25%) 4/42 (10%) | |POLY-3 RATE (b) | 9/36.43 10/33.94 17/38.21 10/33.69 4/30.17 | |POLY-3 PERCENT (g) | 24.7% 29.5% 44.5% 29.7% 13.3% | |TERMINAL (d) | 5/20 (25%) 2/17 (12%) 11/24 (46%) 7/20 (35%) 1/19 (5%) | |FIRST INCIDENCE | 179 207 425 488 455 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.100N P=0.392 P=0.125 P=0.460 P=0.187N | |POLY 3 | P=0.127N P=0.427 P=0.055 P=0.420 P=0.192N | |POLY 1.5 | P=0.146N P=0.449 P=0.049 * P=0.386 P=0.196N | |POLY 6 | P=0.107N P=0.409 P=0.072 P=0.452 P=0.183N | |LOGISTIC REGRESSION| P=0.141N P=0.477 P=0.061 P=0.322 P=0.184N | |COCH-ARM / FISHERS | P=0.152N P=0.459 P=0.054 P=0.308 P=0.184N | |ORDER RESTRICTED | P=0.054N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 68 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/28.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/12 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 0/47 (0%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 2/34.14 0/29.43 0/35.88 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 5.9% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/17 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 651 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083N P=0.274N P=0.202N P=0.240N P=0.262N | |POLY 3 | P=0.088N P=0.270N P=0.225N P=0.250N P=0.275N | |POLY 1.5 | P=0.092N P=0.257N P=0.230N P=0.258N P=0.275N | |POLY 6 | P=0.085N P=0.286N P=0.217N P=0.245N P=0.275N | |LOGISTIC REGRESSION| P=0.082N P=0.286N P=0.203N P=0.236N P=0.267N | |COCH-ARM / FISHERS | P=0.096N P=0.258N P=0.247N P=0.300N P=0.287N | |ORDER RESTRICTED | P=0.026N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 69 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/49 (2%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 1/30.37 1/28.53 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 3.3% 3.5% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 0/12 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 668 (T) 570 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.504N P=0.520 P=0.469 (e) (e) | |POLY 3 | P=0.481N P=0.483 P=0.470 (e) (e) | |POLY 1.5 | P=0.465N P=0.484 P=0.480 (e) (e) | |POLY 6 | P=0.502N P=0.486 P=0.458 (e) (e) | |LOGISTIC REGRESSION| P=0.457N P=0.520 P=0.484 (e) (e) | |COCH-ARM / FISHERS | P=0.434N P=0.500 P=0.495 (e) (e) | |ORDER RESTRICTED | P=0.492N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/49 (10%) 4/47 (9%) 2/49 (4%) 4/40 (10%) 6/42 (14%) | |POLY-3 RATE (b) | 5/34.72 4/30.01 2/35.94 4/32.31 6/28.81 | |POLY-3 PERCENT (g) | 14.4% 13.3% 5.6% 12.4% 20.8% | |TERMINAL (d) | 3/20 (15%) 1/17 (6%) 1/24 (4%) 2/20 (10%) 6/19 (32%) | |FIRST INCIDENCE | 573 559 654 608 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.284 P=0.626N P=0.165N P=0.523N P=0.432 | |POLY 3 | P=0.243 P=0.593N P=0.198N P=0.546N P=0.366 | |POLY 1.5 | P=0.232 P=0.558N P=0.205N P=0.564N P=0.375 | |POLY 6 | P=0.247 P=0.631N P=0.187N P=0.535N P=0.352 | |LOGISTIC REGRESSION| P=0.257 P=0.617N P=0.183N P=0.533N P=0.384 | |COCH-ARM / FISHERS | P=0.211 P=0.527N P=0.218N P=0.646 P=0.391 | |ORDER RESTRICTED | P=0.208 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 70 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 2/49 (4%) 3/36 (8%) 0/32 (0%) | |POLY-3 RATE (b) | 1/33.27 0/30.28 2/30.60 3/22.31 0/19.14 | |POLY-3 PERCENT (g) | 3.0% 0.0% 6.5% 13.5% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 635 --- 147 157 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.354 P=0.509N P=0.456 P=0.158 P=0.614N | |POLY 3 | P=0.332 P=0.519N P=0.471 P=0.172 P=0.609N | |POLY 1.5 | P=0.341 P=0.518N P=0.481 P=0.181 P=0.605N | |POLY 6 | P=0.316 P=0.516N P=0.455 P=0.159 P=0.614N | |LOGISTIC REGRESSION| P=0.447 P=0.515N P=0.531 P=0.253 P=0.614N | |COCH-ARM / FISHERS | P=0.374 P=0.505N P=0.492 P=0.196 P=0.610N | |ORDER RESTRICTED | P=0.327 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 4/48 (8%) 2/46 (4%) 1/40 (3%) 5/42 (12%) | |POLY-3 RATE (b) | 2/35.99 4/32.87 2/35.54 1/32.56 5/31.91 | |POLY-3 PERCENT (g) | 5.6% 12.2% 5.6% 3.1% 15.7% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/22 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 443 417 328 497 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.206 P=0.266 P=0.687N P=0.537N P=0.157 | |POLY 3 | P=0.229 P=0.293 P=0.691 P=0.535N P=0.165 | |POLY 1.5 | P=0.219 P=0.307 P=0.681 P=0.544N P=0.159 | |POLY 6 | P=0.234 P=0.281 P=0.688N P=0.530N P=0.171 | |LOGISTIC REGRESSION| P=0.182 P=0.325 P=0.642 P=0.680N P=0.165 | |COCH-ARM / FISHERS | P=0.190 P=0.319 P=0.659 P=0.584N P=0.152 | |ORDER RESTRICTED | P=0.101 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 71 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 7/49 (14%) 3/49 (6%) 6/36 (17%) 2/32 (6%) | |POLY-3 RATE (b) | 2/33.83 7/31.16 3/31.13 6/22.60 2/19.93 | |POLY-3 PERCENT (g) | 5.9% 22.5% 9.6% 26.6% 10.0% | |TERMINAL (d) | 1/19 (5%) 6/21 (29%) 0/13 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 446 329 229 329 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.200 P=0.088 P=0.426 P=0.025 * P=0.476 | |POLY 3 | P=0.288 P=0.055 P=0.462 P=0.034 * P=0.493 | |POLY 1.5 | P=0.296 P=0.057 P=0.475 P=0.038 * P=0.495 | |POLY 6 | P=0.282 P=0.056 P=0.440 P=0.029 * P=0.492 | |LOGISTIC REGRESSION| P=0.342 P=0.062 P=0.535 P=0.052 P=0.513 | |COCH-ARM / FISHERS | P=0.353 P=0.075 P=0.490 P=0.053 P=0.510 | |ORDER RESTRICTED | P=0.185 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 3/48 (6%) 2/46 (4%) 3/40 (8%) 1/42 (2%) | |POLY-3 RATE (b) | 2/35.30 3/30.60 2/34.41 3/31.97 1/28.81 | |POLY-3 PERCENT (g) | 5.7% 9.8% 5.8% 9.4% 3.5% | |TERMINAL (d) | 0/20 (0%) 3/18 (17%) 0/22 (0%) 3/20 (15%) 1/19 (5%) | |FIRST INCIDENCE | 612 668 (T) 621 668 (T) 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.374N P=0.435 P=0.621N P=0.496 P=0.547N | |POLY 3 | P=0.453N P=0.434 P=0.686 P=0.454 P=0.571N | |POLY 1.5 | P=0.454N P=0.460 P=0.677 P=0.443 P=0.568N | |POLY 6 | P=0.456N P=0.404 P=0.692N P=0.460 P=0.575N | |LOGISTIC REGRESSION| P=0.400N P=0.407 P=0.686 P=0.475 P=0.568N | |COCH-ARM / FISHERS | P=0.450N P=0.480 P=0.659 P=0.394 P=0.566N | |ORDER RESTRICTED | P=0.454N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 72 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 3/49 (6%) 8/49 (16%) 3/36 (8%) 4/32 (13%) | |POLY-3 RATE (b) | 12/40.25 3/31.56 8/33.78 3/21.09 4/21.42 | |POLY-3 PERCENT (g) | 29.8% 9.5% 23.7% 14.2% 18.7% | |TERMINAL (d) | 1/19 (5%) 1/21 (5%) 1/13 (8%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 308 322 229 298 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.227N P=0.028N* P=0.349N P=0.129N P=0.229N | |POLY 3 | P=0.203N P=0.034N* P=0.370N P=0.157N P=0.263N | |POLY 1.5 | P=0.174N P=0.025N* P=0.317N P=0.108N P=0.234N | |POLY 6 | P=0.248N P=0.041N* P=0.442N P=0.233N P=0.296N | |LOGISTIC REGRESSION| P=0.112N P=0.008N** P=0.172N P=0.033N* P=0.105N | |COCH-ARM / FISHERS | P=0.142N P=0.013N* P=0.242N P=0.052N P=0.160N | |ORDER RESTRICTED | P=0.200N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 6/48 (13%) 2/46 (4%) 3/40 (8%) 8/42 (19%) | |POLY-3 RATE (b) | 6/35.74 6/32.04 2/34.11 3/32.19 8/31.07 | |POLY-3 PERCENT (g) | 16.8% 18.7% 5.9% 9.3% 25.8% | |TERMINAL (d) | 4/20 (20%) 3/18 (17%) 1/22 (5%) 2/20 (10%) 3/19 (16%) | |FIRST INCIDENCE | 460 207 654 614 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.302 P=0.541 P=0.106N P=0.246N P=0.302 | |POLY 3 | P=0.264 P=0.544 P=0.143N P=0.291N P=0.273 | |POLY 1.5 | P=0.247 P=0.575 P=0.150N P=0.306N P=0.261 | |POLY 6 | P=0.280 P=0.509 P=0.132N P=0.279N P=0.297 | |LOGISTIC REGRESSION| P=0.233 P=0.554 P=0.135N P=0.282N P=0.247 | |COCH-ARM / FISHERS | P=0.216 P=0.591 P=0.163N P=0.367N P=0.259 | |ORDER RESTRICTED | P=0.103 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 73 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 14/49 (29%) 17/49 (35%) 8/36 (22%) 9/32 (28%) | |POLY-3 RATE (b) | 7/34.41 14/32.00 17/33.70 8/21.62 9/20.50 | |POLY-3 PERCENT (g) | 20.4% 43.7% 50.5% 37.0% 43.9% | |TERMINAL (d) | 3/19 (16%) 10/21 (48%) 5/13 (39%) 2/6 (33%) 2/8 (25%) | |FIRST INCIDENCE | 463 418 481 483 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.045 * P=0.081 P=0.005 ** P=0.059 P=0.045 * | |POLY 3 | P=0.103 P=0.032 * P=0.006 ** P=0.142 P=0.056 | |POLY 1.5 | P=0.126 P=0.035 * P=0.007 ** P=0.171 P=0.061 | |POLY 6 | P=0.087 P=0.034 * P=0.006 ** P=0.117 P=0.054 | |LOGISTIC REGRESSION| P=0.118 P=0.037 * P=0.006 ** P=0.127 P=0.055 | |COCH-ARM / FISHERS | P=0.221 P=0.063 P=0.015 * P=0.240 P=0.100 | |ORDER RESTRICTED | P=0.060 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 10/48 (21%) 9/46 (20%) 9/40 (23%) 11/42 (26%) | |POLY-3 RATE (b) | 12/36.87 10/32.31 9/34.98 9/33.36 11/31.98 | |POLY-3 PERCENT (g) | 32.5% 31.0% 25.7% 27.0% 34.4% | |TERMINAL (d) | 7/20 (35%) 5/18 (28%) 4/22 (18%) 4/20 (20%) 5/19 (26%) | |FIRST INCIDENCE | 372 500 514 510 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.517 P=0.545N P=0.225N P=0.335N P=0.551 | |POLY 3 | P=0.491 P=0.547N P=0.352N P=0.401N P=0.538 | |POLY 1.5 | P=0.442 P=0.496N P=0.369N P=0.433N P=0.514 | |POLY 6 | P=0.528N P=0.592N P=0.318N P=0.369N P=0.576 | |LOGISTIC REGRESSION| P=0.420 P=0.546N P=0.336N P=0.419N P=0.485 | |COCH-ARM / FISHERS | P=0.371 P=0.447N P=0.391N P=0.535N P=0.499 | |ORDER RESTRICTED | P=0.541 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 74 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/50 (30%) 16/49 (33%) 9/49 (18%) 10/36 (28%) 6/32 (19%) | |POLY-3 RATE (b) | 15/38.25 16/35.08 9/32.05 10/24.29 6/22.30 | |POLY-3 PERCENT (g) | 39.2% 45.6% 28.1% 41.2% 26.9% | |TERMINAL (d) | 6/19 (32%) 8/21 (38%) 3/13 (23%) 2/6 (33%) 1/8 (13%) | |FIRST INCIDENCE | 329 157 308 298 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.421N P=0.493 P=0.317N P=0.315 P=0.348N | |POLY 3 | P=0.180N P=0.373 P=0.229N P=0.545 P=0.243N | |POLY 1.5 | P=0.169N P=0.387 P=0.185N P=0.594 P=0.235N | |POLY 6 | P=0.210N P=0.381 P=0.295N P=0.477 P=0.260N | |LOGISTIC REGRESSION| P=0.154N P=0.438 P=0.146N P=0.528N P=0.190N | |COCH-ARM / FISHERS | P=0.139N P=0.473 P=0.132N P=0.509N P=0.190N | |ORDER RESTRICTED | P=0.210N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 7/48 (15%) 9/46 (20%) 10/40 (25%) 7/42 (17%) | |POLY-3 RATE (b) | 6/35.39 7/32.39 9/35.76 10/32.80 7/30.78 | |POLY-3 PERCENT (g) | 17.0% 21.6% 25.2% 30.5% 22.7% | |TERMINAL (d) | 4/20 (20%) 3/18 (17%) 6/22 (27%) 8/20 (40%) 4/19 (21%) | |FIRST INCIDENCE | 577 341 332 488 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300 P=0.411 P=0.354 P=0.191 P=0.424 | |POLY 3 | P=0.242 P=0.429 P=0.287 P=0.146 P=0.389 | |POLY 1.5 | P=0.215 P=0.455 P=0.264 P=0.132 P=0.375 | |POLY 6 | P=0.269 P=0.397 P=0.320 P=0.157 P=0.404 | |LOGISTIC REGRESSION| P=0.213 P=0.409 P=0.257 P=0.154 P=0.353 | |COCH-ARM / FISHERS | P=0.189 P=0.468 P=0.230 P=0.093 P=0.366 | |ORDER RESTRICTED | P=0.297 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 75 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 3/49 (6%) 0/36 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 1/33.13 1/31.27 3/30.44 0/19.93 0/19.14 | |POLY-3 PERCENT (g) | 3.0% 3.2% 9.9% 0.0% 0.0% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 1/13 (8%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) 157 308 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.309N P=0.749N P=0.235 P=0.729N P=0.672N | |POLY 3 | P=0.294N P=0.749 P=0.273 P=0.599N P=0.608N | |POLY 1.5 | P=0.275N P=0.747 P=0.282 P=0.587N P=0.605N | |POLY 6 | P=0.324N P=0.755 P=0.259 P=0.615N P=0.612N | |LOGISTIC REGRESSION| P=0.219N P=0.732N P=0.297 (e) (e) | |COCH-ARM / FISHERS | P=0.240N P=0.747 P=0.301 P=0.581N P=0.610N | |ORDER RESTRICTED | P=0.322N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/48 (0%) 0/46 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/30.60 0/34.05 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/22 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 76 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 1/49 (2%) 0/36 (0%) 1/32 (3%) | |POLY-3 RATE (b) | 1/33.92 1/30.28 1/28.97 0/19.93 1/19.62 | |POLY-3 PERCENT (g) | 3.0% 3.3% 3.5% 0.0% 5.1% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 1/13 (8%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 392 668 (T) 668 (T) --- 538 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.495 P=0.755 P=0.707 P=0.593N P=0.639 | |POLY 3 | P=0.557 P=0.736 P=0.726 P=0.604N P=0.633 | |POLY 1.5 | P=0.567 P=0.738 P=0.738 P=0.590N P=0.637 | |POLY 6 | P=0.543 P=0.739 P=0.708 P=0.621N P=0.631 | |LOGISTIC REGRESSION| P=0.578 P=0.760 P=0.761 P=0.523N P=0.690 | |COCH-ARM / FISHERS | P=0.593 P=0.747 P=0.747 P=0.581N P=0.631 | |ORDER RESTRICTED | P=0.552 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 7/48 (15%) 3/46 (7%) 2/40 (5%) 4/42 (10%) | |POLY-3 RATE (b) | 2/34.96 7/32.05 3/34.05 2/31.97 4/29.20 | |POLY-3 PERCENT (g) | 5.7% 21.8% 8.8% 6.3% 13.7% | |TERMINAL (d) | 2/20 (10%) 5/18 (28%) 3/22 (14%) 2/20 (10%) 3/19 (16%) | |FIRST INCIDENCE | 668 (T) 341 668 (T) 668 (T) 565 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.493N P=0.058 P=0.545 P=0.699 P=0.295 | |POLY 3 | P=0.544 P=0.054 P=0.488 P=0.664 P=0.253 | |POLY 1.5 | P=0.531 P=0.062 P=0.477 P=0.651 P=0.253 | |POLY 6 | P=0.553 P=0.046 * P=0.505 P=0.673 P=0.256 | |LOGISTIC REGRESSION| P=0.543 P=0.054 P=0.545 P=0.699 P=0.250 | |COCH-ARM / FISHERS | P=0.498 P=0.070 P=0.460 P=0.603 P=0.259 | |ORDER RESTRICTED | P=0.268 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 77 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Iliac | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/12 (0%) 0/10 (0%) 1/15 (7%) 1/6 (17%) 0/2 (0%) | |POLY-3 RATE (b) | 0/4.33 0/4.46 1/9.00 1/2.90 0/0.97 | |POLY-3 PERCENT (g) | 0.0% 0.0% 11.1% 34.5% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 1/3 (33%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 668 (T) 647 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.219 (e) P=0.718 P=0.331 (e) | |POLY 3 | P=0.291 (e) P=0.636 P=0.409 (e) | |POLY 1.5 | P=0.263 (e) P=0.599 P=0.384 (e) | |POLY 6 | P=0.338 (e) P=0.667 P=0.445 (e) | |LOGISTIC REGRESSION| P=0.163 (e) P=0.718 P=0.387 (e) | |COCH-ARM / FISHERS | P=0.226 (e) P=0.556 P=0.333 (e) | |ORDER RESTRICTED | P=0.589 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Iliac | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 2/23 (9%) 2/16 (13%) 0/12 (0%) 0/16 (0%) | |POLY-3 RATE (b) | 0/5.53 2/13.28 2/11.79 0/9.59 0/11.87 | |POLY-3 PERCENT (g) | 0.0% 15.1% 17.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 207 460 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.238N P=0.239 P=0.253 (e) (e) | |POLY 3 | P=0.099N P=0.447 P=0.421 (e) (e) | |POLY 1.5 | P=0.145N P=0.410 P=0.351 (e) (e) | |POLY 6 | P=0.062N P=0.501 P=0.515 (e) (e) | |LOGISTIC REGRESSION| P=0.345N P=0.299 P=0.262 (e) (e) | |COCH-ARM / FISHERS | P=0.248N P=0.380 P=0.276 (e) (e) | |ORDER RESTRICTED | P=0.387N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 78 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Inguinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/12 (17%) 0/10 (0%) 0/15 (0%) 0/6 (0%) 0/2 (0%) | |POLY-3 RATE (b) | 2/6.22 0/4.46 0/9.00 0/2.81 0/0.97 | |POLY-3 PERCENT (g) | 32.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 111 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.116N P=0.252N P=0.250N P=0.319N P=0.356N | |POLY 3 | P=0.111N P=0.294N P=0.139N P=0.417N P=0.704N | |POLY 1.5 | P=0.122N P=0.277N P=0.159N P=0.413N P=0.692N | |POLY 6 | P=0.095N P=0.350N P=0.125N P=0.427N P=0.720N | |LOGISTIC REGRESSION| P=0.172N P=0.591N P=0.221N P=0.540N P=0.853N | |COCH-ARM / FISHERS | P=0.135N P=0.286N P=0.188N P=0.431N P=0.725N | |ORDER RESTRICTED | P=0.516N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Inguinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 0/23 (0%) 0/16 (0%) 0/12 (0%) 0/16 (0%) | |POLY-3 RATE (b) | 1/6.08 0/12.26 0/10.79 0/9.59 0/11.87 | |POLY-3 PERCENT (g) | 16.5% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 510 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.244N P=0.541N P=0.505N P=0.522N P=0.554N | |POLY 3 | P=0.308N P=0.360N P=0.389N P=0.412N P=0.373N | |POLY 1.5 | P=0.281N P=0.373N P=0.421N P=0.457N P=0.409N | |POLY 6 | P=0.351N P=0.347N P=0.351N P=0.361N P=0.334N | |LOGISTIC REGRESSION| P=0.255N P=0.384N P=0.471N P=0.560N P=0.495N | |COCH-ARM / FISHERS | P=0.245N P=0.378N P=0.467N P=0.538N P=0.467N | |ORDER RESTRICTED | P=0.029N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 79 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Inguinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/12 (17%) 1/10 (10%) 6/15 (40%) 1/6 (17%) 0/2 (0%) | |POLY-3 RATE (b) | 2/6.02 1/4.46 6/11.42 1/3.72 0/0.97 | |POLY-3 PERCENT (g) | 33.2% 22.4% 52.6% 26.9% 0.0% | |TERMINAL (d) | 0/1 (0%) 1/1 (100%) 1/3 (33%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 111 668 (T) 243 298 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.356N P=0.513N P=0.139 P=0.622N P=0.354N | |POLY 3 | P=0.502N P=0.622N P=0.399 P=0.695N P=0.699N | |POLY 1.5 | P=0.558N P=0.582N P=0.294 P=0.715N P=0.687N | |POLY 6 | P=0.450N P=0.725N P=0.492 P=0.690N P=0.717N | |LOGISTIC REGRESSION| P=0.567 P=0.619N P=0.151 P=0.693 P=0.780N | |COCH-ARM / FISHERS | P=0.581 P=0.571N P=0.186 P=0.730 P=0.725N | |ORDER RESTRICTED | P=0.607N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Inguinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/14 (14%) 4/23 (17%) 2/16 (13%) 1/12 (8%) 2/16 (13%) | |POLY-3 RATE (b) | 2/7.16 4/14.28 2/12.19 1/9.59 2/13.18 | |POLY-3 PERCENT (g) | 28.0% 28.0% 16.4% 10.4% 15.2% | |TERMINAL (d) | 0/0 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 287 207 432 667 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300N P=0.468 P=0.689N P=0.519N P=0.629 | |POLY 3 | P=0.224N P=0.692 P=0.491N P=0.393N P=0.460N | |POLY 1.5 | P=0.277N P=0.653 P=0.557N P=0.456N P=0.533N | |POLY 6 | P=0.172N P=0.669N P=0.408N P=0.313N P=0.372N | |LOGISTIC REGRESSION| P=0.487 P=0.498 P=0.584 P=0.733N P=0.446 | |COCH-ARM / FISHERS | P=0.379N P=0.593 P=0.648N P=0.560N P=0.648N | |ORDER RESTRICTED | P=0.419N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 80 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/12 (8%) 0/10 (0%) 0/15 (0%) 0/6 (0%) 0/2 (0%) | |POLY-3 RATE (b) | 1/4.61 0/4.46 0/9.00 0/2.81 0/0.97 | |POLY-3 PERCENT (g) | 21.7% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 601 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.288N P=0.532N P=0.541N P=0.604N P=0.617N | |POLY 3 | P=0.372N P=0.507N P=0.370N P=0.607N P=0.838N | |POLY 1.5 | P=0.358N P=0.508N P=0.403N P=0.618N P=0.838N | |POLY 6 | P=0.375N P=0.540N P=0.349N P=0.604N P=0.842N | |LOGISTIC REGRESSION| P=0.275N P=0.510N P=0.340N P=0.577N P=0.799N | |COCH-ARM / FISHERS | P=0.328N P=0.545N P=0.444N P=0.667N P=0.857N | |ORDER RESTRICTED | P=0.548N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 1/23 (4%) 2/16 (13%) 0/12 (0%) 1/16 (6%) | |POLY-3 RATE (b) | 1/6.47 1/12.74 2/11.14 0/9.59 1/11.87 | |POLY-3 PERCENT (g) | 15.5% 7.9% 18.0% 0.0% 8.4% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/8 (13%) | |FIRST INCIDENCE | 248 536 612 --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.353N P=0.746 P=0.543 P=0.532N P=0.537N | |POLY 3 | P=0.338N P=0.605N P=0.688 P=0.423N P=0.616N | |POLY 1.5 | P=0.389N P=0.622N P=0.628 P=0.467N P=0.665N | |POLY 6 | P=0.282N P=0.577N P=0.698N P=0.368N P=0.548N | |LOGISTIC REGRESSION| P=0.475N P=0.730N P=0.532 P=0.983N P=0.719 | |COCH-ARM / FISHERS | P=0.475N P=0.620N P=0.552 P=0.538N P=0.724N | |ORDER RESTRICTED | P=0.452N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 81 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/12 (0%) 0/10 (0%) 3/15 (20%) 0/6 (0%) 0/2 (0%) | |POLY-3 RATE (b) | 0/4.33 0/4.46 3/9.49 0/2.81 0/0.97 | |POLY-3 PERCENT (g) | 0.0% 0.0% 31.6% 0.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 1/3 (33%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 607 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.597 (e) P=0.148 (e) (e) | |POLY 3 | P=0.648 (e) P=0.284 (e) (e) | |POLY 1.5 | P=0.580 (e) P=0.216 (e) (e) | |POLY 6 | P=0.652N (e) P=0.360 (e) (e) | |LOGISTIC REGRESSION| P=0.626 (e) P=0.301 (e) (e) | |COCH-ARM / FISHERS | P=0.510 (e) P=0.156 (e) (e) | |ORDER RESTRICTED | P=0.642 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 2/23 (9%) 0/16 (0%) 1/12 (8%) 0/16 (0%) | |POLY-3 RATE (b) | 1/6.51 2/13.39 0/10.79 1/9.59 0/11.87 | |POLY-3 PERCENT (g) | 15.4% 14.9% 0.0% 10.4% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 1/6 (17%) 0/8 (0%) | |FIRST INCIDENCE | 179 472 --- 668 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.158N P=0.482 P=0.500N P=0.540N P=0.540N | |POLY 3 | P=0.187N P=0.731N P=0.401N P=0.670N P=0.384N | |POLY 1.5 | P=0.208N P=0.712 P=0.433N P=0.728N P=0.420N | |POLY 6 | P=0.169N P=0.693N P=0.359N P=0.584N P=0.340N | |LOGISTIC REGRESSION| P=0.368N P=0.577 (e) P=0.570 (e) | |COCH-ARM / FISHERS | P=0.248N P=0.772N P=0.467N P=0.720 P=0.467N | |ORDER RESTRICTED | P=0.262N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 82 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Renal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/12 (0%) 0/10 (0%) 0/15 (0%) 0/6 (0%) 0/2 (0%) | |POLY-3 RATE (b) | 0/4.33 0/4.46 0/9.00 0/2.81 0/0.97 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Renal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 2/23 (9%) 1/16 (6%) 0/12 (0%) 0/16 (0%) | |POLY-3 RATE (b) | 0/5.53 2/13.10 1/10.87 0/9.59 0/11.87 | |POLY-3 PERCENT (g) | 0.0% 15.3% 9.2% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 549 650 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.253N P=0.177 P=0.550 (e) (e) | |POLY 3 | P=0.130N P=0.443 P=0.626 (e) (e) | |POLY 1.5 | P=0.170N P=0.404 P=0.586 (e) (e) | |POLY 6 | P=0.094N P=0.506 P=0.675 (e) (e) | |LOGISTIC REGRESSION| P=0.173N P=0.410 P=0.895 (e) (e) | |COCH-ARM / FISHERS | P=0.256N P=0.380 P=0.533 (e) (e) | |ORDER RESTRICTED | P=0.411N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 83 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Renal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/12 (8%) 0/10 (0%) 0/15 (0%) 1/6 (17%) 0/2 (0%) | |POLY-3 RATE (b) | 1/4.61 0/4.46 0/9.00 1/2.90 0/0.97 | |POLY-3 PERCENT (g) | 21.7% 0.0% 0.0% 34.5% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 601 --- --- 647 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.626N P=0.532N P=0.541N P=0.602 P=0.617N | |POLY 3 | P=0.596 P=0.507N P=0.370N P=0.681 P=0.838N | |POLY 1.5 | P=0.586 P=0.508N P=0.403N P=0.646 P=0.838N | |POLY 6 | P=0.614 P=0.540N P=0.349N P=0.714 P=0.842N | |LOGISTIC REGRESSION| P=0.660 P=0.510N P=0.340N P=0.728 P=0.799N | |COCH-ARM / FISHERS | P=0.569 P=0.545N P=0.444N P=0.569 P=0.857N | |ORDER RESTRICTED | P=0.620N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Renal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 3/23 (13%) 2/16 (13%) 0/12 (0%) 0/16 (0%) | |POLY-3 RATE (b) | 0/5.53 3/14.15 2/11.54 0/9.59 0/11.87 | |POLY-3 PERCENT (g) | 0.0% 21.2% 17.3% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 207 460 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.171N P=0.123 P=0.270 (e) (e) | |POLY 3 | P=0.055N P=0.329 P=0.415 (e) (e) | |POLY 1.5 | P=0.088N P=0.283 P=0.348 (e) (e) | |POLY 6 | P=0.030N* P=0.398 P=0.507 (e) (e) | |LOGISTIC REGRESSION| P=0.289N P=0.144 P=0.310 (e) (e) | |COCH-ARM / FISHERS | P=0.176N P=0.228 P=0.276 (e) (e) | |ORDER RESTRICTED | P=0.338N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 84 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 9/50 (18%) 8/49 (16%) 6/40 (15%) 7/42 (17%) | |POLY-3 RATE (b) | 9/37.83 9/34.73 8/39.31 6/32.95 7/31.10 | |POLY-3 PERCENT (g) | 23.8% 25.9% 20.4% 18.2% 22.5% | |TERMINAL (d) | 2/20 (10%) 1/18 (6%) 1/24 (4%) 2/20 (10%) 2/19 (11%) | |FIRST INCIDENCE | 391 369 425 488 482 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.326N P=0.466 P=0.425N P=0.321N P=0.544N | |POLY 3 | P=0.376N P=0.525 P=0.464N P=0.389N P=0.564N | |POLY 1.5 | P=0.391N P=0.565 P=0.485N P=0.399N P=0.562N | |POLY 6 | P=0.367N P=0.488 P=0.433N P=0.389N P=0.560N | |LOGISTIC REGRESSION| P=0.412N P=0.598 P=0.519N P=0.438N P=0.549N | |COCH-ARM / FISHERS | P=0.417N P=0.602N P=0.518N P=0.465N P=0.545N | |ORDER RESTRICTED | P=0.567N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 85 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/1 (0%) 1/2 (50%) 0/0 (0%) 3/3 (100%) 0/1 (0%) | |POLY-3 RATE (b) | 0/1.00 1/2.00 0/0.00 3/3.00 0/1.00 | |POLY-3 PERCENT (g) | 0.0% 50.0% 0.0% 100.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- 363 --- 434 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.185 P=0.479 (e) P=0.039 * (e) | |POLY 3 | (e) P=0.614 (e) P=0.250N (e) | |POLY 1.5 | (e) P=0.614 (e) P=0.250N (e) | |POLY 6 | (e) P=0.614 (e) P=0.250N (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.415 P=0.667 (e) P=0.250 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/4 (0%) 5/8 (63%) 4/7 (57%) 2/3 (67%) 3/5 (60%) | |POLY-3 RATE (b) | 0/2.87 5/6.55 4/6.33 2/2.74 3/5.00 | |POLY-3 PERCENT (g) | 0.0% 76.4% 63.2% 73.1% 60.0% | |TERMINAL (d) | 0/0 (0%) 3/3 (100%) 2/3 (67%) 1/1 (100%) 2/4 (50%) | |FIRST INCIDENCE | --- 500 362 488 412 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.389N P=0.184 P=0.251 P=0.495 P=0.475 | |POLY 3 | P=0.397 P=0.030 * P=0.121 P=0.116 P=0.172 | |POLY 1.5 | P=0.277 P=0.034 * P=0.099 P=0.101 P=0.126 | |POLY 6 | P=0.613N P=0.047 * P=0.187 P=0.158 P=0.276 | |LOGISTIC REGRESSION| P=0.176 P=0.057 P=0.113 P=0.145 P=0.102 | |COCH-ARM / FISHERS | P=0.182 P=0.071 P=0.106 P=0.143 P=0.119 | |ORDER RESTRICTED | P=0.070 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 86 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 0/36 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 1/33.19 1/30.56 1/29.79 0/20.80 0/19.14 | |POLY-3 PERCENT (g) | 3.0% 3.3% 3.4% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 654 624 474 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.259N P=0.760 P=0.708 P=0.692N P=0.648N | |POLY 3 | P=0.245N P=0.743 P=0.737 P=0.592N P=0.609N | |POLY 1.5 | P=0.235N P=0.744 P=0.746 P=0.583N P=0.605N | |POLY 6 | P=0.261N P=0.749 P=0.725 P=0.605N P=0.613N | |LOGISTIC REGRESSION| P=0.232N P=0.748 P=0.755 P=0.635N P=0.622N | |COCH-ARM / FISHERS | P=0.220N P=0.753N P=0.753N P=0.581N P=0.610N | |ORDER RESTRICTED | P=0.426N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 2/35.04 0/31.04 0/36.65 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 5.7% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 651 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083N P=0.268N P=0.202N P=0.240N P=0.262N | |POLY 3 | P=0.089N P=0.264N P=0.226N P=0.256N P=0.281N | |POLY 1.5 | P=0.093N P=0.250N P=0.231N P=0.263N P=0.280N | |POLY 6 | P=0.086N P=0.280N P=0.219N P=0.251N P=0.281N | |LOGISTIC REGRESSION| P=0.084N P=0.280N P=0.205N P=0.242N P=0.272N | |COCH-ARM / FISHERS | P=0.099N P=0.247N P=0.247N P=0.306N P=0.293N | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 87 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 5/50 (10%) 5/50 (10%) 3/36 (8%) 4/32 (13%) | |POLY-3 RATE (b) | 5/33.58 5/30.56 5/30.25 3/21.07 4/19.49 | |POLY-3 PERCENT (g) | 14.9% 16.4% 16.5% 14.2% 20.5% | |TERMINAL (d) | 3/19 (16%) 4/21 (19%) 3/13 (23%) 1/7 (14%) 1/8 (13%) | |FIRST INCIDENCE | 565 624 474 607 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.195 P=0.591N P=0.430 P=0.474 P=0.340 | |POLY 3 | P=0.391 P=0.572 P=0.566 P=0.626N P=0.442 | |POLY 1.5 | P=0.410 P=0.579 P=0.591 P=0.598N P=0.451 | |POLY 6 | P=0.362 P=0.581 P=0.531 P=0.641 P=0.433 | |LOGISTIC REGRESSION| P=0.356 P=0.597 P=0.531 P=0.622 P=0.420 | |COCH-ARM / FISHERS | P=0.458 P=0.630N P=0.630N P=0.552N P=0.495 | |ORDER RESTRICTED | P=0.535 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/50 (22%) 2/50 (4%) 7/50 (14%) 2/40 (5%) 4/42 (10%) | |POLY-3 RATE (b) | 11/35.72 2/31.69 7/38.60 2/32.58 4/29.55 | |POLY-3 PERCENT (g) | 30.8% 6.3% 18.1% 6.1% 13.5% | |TERMINAL (d) | 7/20 (35%) 1/18 (6%) 2/24 (8%) 1/20 (5%) 2/19 (11%) | |FIRST INCIDENCE | 577 472 182 488 565 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.018N* P=0.137N P=0.010N* P=0.077N | |POLY 3 | P=0.044N* P=0.010N* P=0.155N P=0.008N** P=0.083N | |POLY 1.5 | P=0.057N P=0.008N** P=0.175N P=0.011N* P=0.087N | |POLY 6 | P=0.035N* P=0.013N* P=0.129N P=0.007N** P=0.078N | |LOGISTIC REGRESSION| P=0.069N P=0.016N* P=0.193N P=0.011N* P=0.090N | |COCH-ARM / FISHERS | P=0.085N P=0.007N** P=0.218N P=0.021N* P=0.090N | |ORDER RESTRICTED | P=0.013N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 88 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 4/49 (8%) 3/40 (8%) 4/42 (10%) | |POLY-3 RATE (b) | 1/34.96 1/31.44 4/36.89 3/32.69 4/29.41 | |POLY-3 PERCENT (g) | 2.9% 3.2% 10.8% 9.2% 13.6% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 2/24 (8%) 1/20 (5%) 2/19 (11%) | |FIRST INCIDENCE | 668 (T) 565 612 539 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.071 P=0.706 P=0.243 P=0.297 P=0.146 | |POLY 3 | P=0.063 P=0.738 P=0.193 P=0.279 P=0.126 | |POLY 1.5 | P=0.056 P=0.749 P=0.185 P=0.265 P=0.125 | |POLY 6 | P=0.072 P=0.726 P=0.208 P=0.293 P=0.129 | |LOGISTIC REGRESSION| P=0.053 P=0.739 P=0.206 P=0.262 P=0.123 | |COCH-ARM / FISHERS | P=0.047 * P=0.753N P=0.175 P=0.229 P=0.131 | |ORDER RESTRICTED | P=0.090 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 89 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 38/50 (76%) 35/50 (70%) 37/49 (76%) 29/40 (73%) 29/42 (69%) | |POLY-3 RATE (b) | 38/43.53 35/44.59 37/45.21 29/36.51 29/34.65 | |POLY-3 PERCENT (g) | 87.3% 78.5% 81.9% 79.4% 83.7% | |TERMINAL (d) | 18/20 (90%) 10/18 (56%) 20/24 (83%) 16/20 (80%) 16/19 (84%) | |FIRST INCIDENCE | 179 326 181 497 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.127N P=0.421 P=0.239N P=0.140N P=0.276N | |POLY 3 | P=0.434N P=0.193N P=0.329N P=0.240N P=0.444N | |POLY 1.5 | P=0.386N P=0.226N P=0.399N P=0.268N P=0.399N | |POLY 6 | P=0.521N P=0.158N P=0.269N P=0.243N P=0.516N | |LOGISTIC REGRESSION| P=0.237N P=0.380N P=0.510N P=0.186N P=0.320N | |COCH-ARM / FISHERS | P=0.306N P=0.326N P=0.570N P=0.445N P=0.304N | |ORDER RESTRICTED | P=0.385N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 90 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 7/49 (14%) 5/40 (13%) 4/42 (10%) | |POLY-3 RATE (b) | 2/35.30 2/32.42 7/38.54 5/32.69 4/28.81 | |POLY-3 PERCENT (g) | 5.7% 6.2% 18.2% 15.3% 13.9% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 3/24 (13%) 3/20 (15%) 4/19 (21%) | |FIRST INCIDENCE | 581 395 432 539 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.182 P=0.634 P=0.118 P=0.202 P=0.294 | |POLY 3 | P=0.142 P=0.665 P=0.098 P=0.180 P=0.244 | |POLY 1.5 | P=0.133 P=0.680 P=0.088 P=0.169 P=0.249 | |POLY 6 | P=0.149 P=0.647 P=0.113 P=0.191 P=0.238 | |LOGISTIC REGRESSION| P=0.133 P=0.690N P=0.080 P=0.175 P=0.251 | |COCH-ARM / FISHERS | P=0.123 P=0.691N P=0.075 P=0.136 P=0.259 | |ORDER RESTRICTED | P=0.178 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 91 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/49 (4%) 1/40 (3%) 1/42 (2%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 2/36.54 1/31.97 1/29.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.5% 3.1% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 2/24 (8%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- 668 (T) 667 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.257 (e) P=0.278 P=0.510 P=0.455 | |POLY 3 | P=0.252 (e) P=0.246 P=0.482 P=0.463 | |POLY 1.5 | P=0.238 (e) P=0.241 P=0.476 P=0.463 | |POLY 6 | P=0.268 (e) P=0.255 P=0.487 P=0.465 | |LOGISTIC REGRESSION| P=0.235 (e) P=0.278 P=0.506 P=0.463 | |COCH-ARM / FISHERS | P=0.216 (e) P=0.242 P=0.444 P=0.457 | |ORDER RESTRICTED | P=0.257 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 92 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pancreas | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 2/37 (5%) 0/31 (0%) | |POLY-3 RATE (b) | 1/33.77 0/30.37 2/29.55 2/21.66 0/18.96 | |POLY-3 PERCENT (g) | 3.0% 0.0% 6.8% 9.2% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 475 --- 607 531 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.484 P=0.523N P=0.425 P=0.345 P=0.604N | |POLY 3 | P=0.489 P=0.521N P=0.453 P=0.348 P=0.614N | |POLY 1.5 | P=0.490 P=0.518N P=0.471 P=0.363 P=0.611N | |POLY 6 | P=0.480 P=0.520N P=0.431 P=0.330 P=0.618N | |LOGISTIC REGRESSION| P=0.495 P=0.483N P=0.482 P=0.391 P=0.578N | |COCH-ARM / FISHERS | P=0.509 P=0.500N P=0.500 P=0.387 P=0.617N | |ORDER RESTRICTED | P=0.405N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pancreas | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/49 (4%) 1/49 (2%) 0/40 (0%) 1/41 (2%) | |POLY-3 RATE (b) | 0/34.96 2/32.33 1/37.21 0/31.97 1/29.32 | |POLY-3 PERCENT (g) | 0.0% 6.2% 2.7% 0.0% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 326 460 --- 482 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.581 P=0.228 P=0.505 (e) P=0.454 | |POLY 3 | P=0.599 P=0.219 P=0.512 (e) P=0.465 | |POLY 1.5 | P=0.591 P=0.227 P=0.506 (e) P=0.462 | |POLY 6 | P=0.603 P=0.210 P=0.522 (e) P=0.468 | |LOGISTIC REGRESSION| P=0.556 P=0.223 P=0.478 (e) P=0.466 | |COCH-ARM / FISHERS | P=0.562 P=0.242 P=0.495 (e) P=0.451 | |ORDER RESTRICTED | P=0.335 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 93 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pancreas: Acinus | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 1/50 (2%) 1/37 (3%) 1/31 (3%) | |POLY-3 RATE (b) | 1/33.40 2/31.54 1/29.31 1/21.21 1/19.14 | |POLY-3 PERCENT (g) | 3.0% 6.3% 3.4% 4.7% 5.2% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 601 168 631 599 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.495 P=0.475 P=0.699 P=0.638 P=0.639 | |POLY 3 | P=0.494 P=0.480 P=0.732 P=0.655 P=0.632 | |POLY 1.5 | P=0.499 P=0.481 P=0.744 P=0.668 P=0.633 | |POLY 6 | P=0.485 P=0.487 P=0.716 P=0.638 P=0.629 | |LOGISTIC REGRESSION| P=0.520 P=0.535 P=0.734 P=0.665 P=0.635 | |COCH-ARM / FISHERS | P=0.526 P=0.500 P=0.753N P=0.673 P=0.622 | |ORDER RESTRICTED | P=0.622 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pancreas: Acinus | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 4/49 (8%) 0/49 (0%) 2/40 (5%) 4/41 (10%) | |POLY-3 RATE (b) | 0/34.96 4/33.58 0/36.54 2/33.10 4/31.19 | |POLY-3 PERCENT (g) | 0.0% 11.9% 0.0% 6.0% 12.8% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 326 --- 488 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.060 P=0.062 (e) P=0.228 P=0.043 * | |POLY 3 | P=0.061 P=0.053 (e) P=0.223 P=0.044 * | |POLY 1.5 | P=0.057 P=0.057 (e) P=0.213 P=0.041 * | |POLY 6 | P=0.064 P=0.049 * (e) P=0.233 P=0.048 * | |LOGISTIC REGRESSION| P=0.045 * P=0.053 (e) P=0.119 P=0.043 * | |COCH-ARM / FISHERS | P=0.049 * P=0.056 (e) P=0.195 P=0.038 * | |ORDER RESTRICTED | P=0.019 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 94 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Penis | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 2/2 (100%) 1/1 (100%) 1/3 (33%) 0/1 (0%) | |POLY-3 RATE (b) | 0/0.00 2/2.00 1/1.00 1/1.64 0/0.70 | |POLY-3 PERCENT (g) | 0.0% 100.0% 100.0% 61.2% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 479 631 599 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.554N (e) (e) P=0.370 (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.040N* (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.057N (e) (e) P=1.000 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Penis | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 95 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/49 (0%) 0/49 (0%) 0/36 (0%) 0/31 (0%) | |POLY-3 RATE (b) | 0/32.18 0/30.26 0/28.40 0/20.80 0/18.74 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 1/50 (2%) 1/40 (3%) 2/42 (5%) | |POLY-3 RATE (b) | 0/34.96 0/31.01 1/36.73 1/31.97 2/29.20 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.7% 3.1% 6.9% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 1/19 (5%) | |FIRST INCIDENCE | --- --- 650 668 (T) 565 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051 (e) P=0.541 P=0.500 P=0.206 | |POLY 3 | P=0.052 (e) P=0.510 P=0.482 P=0.196 | |POLY 1.5 | P=0.048 * (e) P=0.506 P=0.476 P=0.196 | |POLY 6 | P=0.055 (e) P=0.517 P=0.487 P=0.198 | |LOGISTIC REGRESSION| P=0.045 * (e) P=0.519 P=0.500 P=0.196 | |COCH-ARM / FISHERS | P=0.042 * (e) P=0.500 P=0.444 P=0.206 | |ORDER RESTRICTED | P=0.061 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 96 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 2/49 (4%) 3/49 (6%) 2/36 (6%) 1/31 (3%) | |POLY-3 RATE (b) | 1/32.66 2/30.78 3/29.02 2/21.38 1/19.04 | |POLY-3 PERCENT (g) | 3.1% 6.5% 10.3% 9.4% 5.3% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 2/13 (15%) 1/7 (14%) 0/8 (0%) | |FIRST INCIDENCE | 538 523 482 501 593 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.326 P=0.489 P=0.229 P=0.313 P=0.642 | |POLY 3 | P=0.391 P=0.479 P=0.261 P=0.354 P=0.635 | |POLY 1.5 | P=0.398 P=0.479 P=0.279 P=0.368 P=0.637 | |POLY 6 | P=0.382 P=0.487 P=0.241 P=0.335 P=0.635 | |LOGISTIC REGRESSION| P=0.412 P=0.490 P=0.277 P=0.379 P=0.652 | |COCH-ARM / FISHERS | P=0.443 P=0.508 P=0.316 P=0.392 P=0.634 | |ORDER RESTRICTED | P=0.416 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/49 (0%) 0/50 (0%) 3/40 (8%) 0/42 (0%) | |POLY-3 RATE (b) | 3/35.88 0/31.01 0/36.65 3/31.97 0/28.81 | |POLY-3 PERCENT (g) | 8.4% 0.0% 0.0% 9.4% 0.0% | |TERMINAL (d) | 2/20 (10%) 0/18 (0%) 0/24 (0%) 2/20 (10%) 0/19 (0%) | |FIRST INCIDENCE | 287 --- --- 667 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.325N P=0.132N P=0.100N P=0.656 P=0.138N | |POLY 3 | P=0.387N P=0.145N P=0.113N P=0.610 P=0.159N | |POLY 1.5 | P=0.394N P=0.133N P=0.116N P=0.598 P=0.158N | |POLY 6 | P=0.381N P=0.159N P=0.108N P=0.619 P=0.160N | |LOGISTIC REGRESSION| P=0.367N P=0.122N P=0.123N P=0.588 P=0.151N | |COCH-ARM / FISHERS | P=0.380N P=0.125N P=0.121N P=0.550 P=0.156N | |ORDER RESTRICTED | P=0.057N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 97 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/49 (0%) 0/49 (0%) 0/36 (0%) 0/31 (0%) | |POLY-3 RATE (b) | 0/32.18 0/30.26 0/28.40 0/20.80 0/18.74 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 4/49 (8%) 1/50 (2%) 2/40 (5%) 4/42 (10%) | |POLY-3 RATE (b) | 3/35.30 4/31.12 1/36.65 2/32.22 4/29.43 | |POLY-3 PERCENT (g) | 8.5% 12.9% 2.7% 6.2% 13.6% | |TERMINAL (d) | 1/20 (5%) 3/18 (17%) 1/24 (4%) 1/20 (5%) 3/19 (16%) | |FIRST INCIDENCE | 612 644 668 (T) 608 482 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.433 P=0.422 P=0.245N P=0.504N P=0.439 | |POLY 3 | P=0.390 P=0.430 P=0.290N P=0.542N P=0.399 | |POLY 1.5 | P=0.377 P=0.463 P=0.296N P=0.556N P=0.399 | |POLY 6 | P=0.396 P=0.392 P=0.281N P=0.533N P=0.399 | |LOGISTIC REGRESSION| P=0.391 P=0.388 P=0.272N P=0.536N P=0.394 | |COCH-ARM / FISHERS | P=0.348 P=0.489 P=0.309N P=0.606N P=0.402 | |ORDER RESTRICTED | P=0.330 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 98 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Preputial Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 7/50 (14%) 6/50 (12%) 6/37 (16%) 2/32 (6%) | |POLY-3 RATE (b) | 6/34.00 7/32.33 6/31.18 6/22.31 2/19.37 | |POLY-3 PERCENT (g) | 17.7% 21.7% 19.2% 26.9% 10.3% | |TERMINAL (d) | 3/19 (16%) 4/21 (19%) 1/13 (8%) 2/7 (29%) 0/8 (0%) | |FIRST INCIDENCE | 497 329 481 382 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.520 P=0.510 P=0.433 P=0.133 P=0.447N | |POLY 3 | P=0.413N P=0.459 P=0.561 P=0.310 P=0.375N | |POLY 1.5 | P=0.389N P=0.456 P=0.582 P=0.340 P=0.364N | |POLY 6 | P=0.449N P=0.479 P=0.538 P=0.275 P=0.389N | |LOGISTIC REGRESSION| P=0.384N P=0.446 P=0.548 P=0.291 P=0.372N | |COCH-ARM / FISHERS | P=0.327N P=0.500 P=0.620N P=0.398 P=0.326N | |ORDER RESTRICTED | P=0.338N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Preputial Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 99 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/50 (22%) 11/50 (22%) 18/50 (36%) 8/37 (22%) 9/32 (28%) | |POLY-3 RATE (b) | 11/34.90 11/32.88 18/35.14 8/23.90 9/21.47 | |POLY-3 PERCENT (g) | 31.5% 33.5% 51.2% 33.5% 41.9% | |TERMINAL (d) | 5/19 (26%) 5/21 (24%) 6/13 (46%) 2/7 (29%) 2/8 (25%) | |FIRST INCIDENCE | 308 329 147 382 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.126 P=0.584N P=0.024 * P=0.260 P=0.193 | |POLY 3 | P=0.295 P=0.536 P=0.066 P=0.551 P=0.303 | |POLY 1.5 | P=0.303 P=0.530 P=0.074 P=0.565 P=0.299 | |POLY 6 | P=0.281 P=0.572 P=0.060 P=0.535 P=0.314 | |LOGISTIC REGRESSION| P=0.295 P=0.517 P=0.062 P=0.522 P=0.274 | |COCH-ARM / FISHERS | P=0.367 P=0.595N P=0.093 P=0.590N P=0.354 | |ORDER RESTRICTED | P=0.339 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 100 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 3/50 (6%) 12/50 (24%) 6/37 (16%) 5/32 (16%) | |POLY-3 RATE (b) | 8/36.18 3/31.26 12/33.45 6/22.27 5/20.74 | |POLY-3 PERCENT (g) | 22.1% 9.6% 35.9% 26.9% 24.1% | |TERMINAL (d) | 1/19 (5%) 2/21 (10%) 4/13 (31%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | 104 322 413 580 376 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.204 P=0.123N P=0.125 P=0.381 P=0.526 | |POLY 3 | P=0.275 P=0.144N P=0.153 P=0.459 P=0.561 | |POLY 1.5 | P=0.292 P=0.134N P=0.171 P=0.504 P=0.571 | |POLY 6 | P=0.253 P=0.150N P=0.134 P=0.416 P=0.550 | |LOGISTIC REGRESSION| P=0.322 P=0.099N P=0.214 P=0.568 P=0.612N | |COCH-ARM / FISHERS | P=0.359 P=0.100N P=0.227 P=0.601 P=0.633 | |ORDER RESTRICTED | P=0.222 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 101 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 1/32 (3%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/29.15 0/20.93 1/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.2% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | --- --- --- --- 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.048 * (e) (e) (e) P=0.328 | |POLY 3 | P=0.082 (e) (e) (e) P=0.391 | |POLY 1.5 | P=0.083 (e) (e) (e) P=0.394 | |POLY 6 | P=0.081 (e) (e) (e) P=0.387 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.328 | |COCH-ARM / FISHERS | P=0.086 (e) (e) (e) P=0.390 | |ORDER RESTRICTED | P=0.037 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 6/49 (12%) 3/49 (6%) 1/40 (3%) 4/42 (10%) | |POLY-3 RATE (b) | 2/35.24 6/33.81 3/36.00 1/31.97 4/30.13 | |POLY-3 PERCENT (g) | 5.7% 17.7% 8.3% 3.1% 13.3% | |TERMINAL (d) | 1/20 (5%) 1/18 (6%) 2/24 (8%) 1/20 (5%) 1/19 (5%) | |FIRST INCIDENCE | 599 369 640 668 (T) 482 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.534N P=0.109 P=0.578 P=0.500N P=0.264 | |POLY 3 | P=0.550 P=0.114 P=0.510 P=0.534N P=0.263 | |POLY 1.5 | P=0.535 P=0.122 P=0.502 P=0.544N P=0.259 | |POLY 6 | P=0.550N P=0.106 P=0.526 P=0.529N P=0.272 | |LOGISTIC REGRESSION| P=0.502 P=0.130 P=0.532 P=0.524N P=0.254 | |COCH-ARM / FISHERS | P=0.494 P=0.128 P=0.490 P=0.584N P=0.259 | |ORDER RESTRICTED | P=0.259 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 102 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 5/32 (16%) | |POLY-3 RATE (b) | 1/33.13 0/30.37 0/29.15 0/20.93 5/20.04 | |POLY-3 PERCENT (g) | 3.0% 0.0% 0.0% 0.0% 25.0% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 3/8 (38%) | |FIRST INCIDENCE | 668 (T) --- --- --- 495 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.480N P=0.576N P=0.699N P=0.010 * | |POLY 3 | P<0.001 ** P=0.517N P=0.526N P=0.590N P=0.020 * | |POLY 1.5 | P<0.001 ** P=0.516N P=0.515N P=0.580N P=0.020 * | |POLY 6 | P<0.001 ** P=0.514N P=0.539N P=0.604N P=0.019 * | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.019 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.500N P=0.575N P=0.031 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/30.96 0/35.88 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 103 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 1/33.13 0/30.37 1/29.15 2/21.09 0/19.14 | |POLY-3 PERCENT (g) | 3.0% 0.0% 3.4% 9.5% 0.0% | |TERMINAL (d) | 1/19 (5%) 0/21 (0%) 1/13 (8%) 1/7 (14%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) --- 668 (T) 631 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.354 P=0.480N P=0.676 P=0.204 P=0.672N | |POLY 3 | P=0.482 P=0.517N P=0.733 P=0.345 P=0.608N | |POLY 1.5 | P=0.480 P=0.516N P=0.744 P=0.362 P=0.605N | |POLY 6 | P=0.481 P=0.514N P=0.717 P=0.324 P=0.612N | |LOGISTIC REGRESSION| P=0.413 (e) P=0.676 P=0.264 (e) | |COCH-ARM / FISHERS | P=0.495 P=0.500N P=0.753N P=0.387 P=0.610N | |ORDER RESTRICTED | P=0.442N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/30.96 0/35.88 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 104 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Seminal Vesicle | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 3/32 (9%) | |POLY-3 RATE (b) | 2/33.72 0/30.37 0/29.15 0/20.93 3/19.32 | |POLY-3 PERCENT (g) | 5.9% 0.0% 0.0% 0.0% 15.5% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 2/8 (25%) | |FIRST INCIDENCE | 538 --- --- --- 627 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.056 P=0.256N P=0.298N P=0.384N P=0.218 | |POLY 3 | P=0.087 P=0.260N P=0.270N P=0.350N P=0.256 | |POLY 1.5 | P=0.092 P=0.256N P=0.256N P=0.333N P=0.266 | |POLY 6 | P=0.079 P=0.259N P=0.290N P=0.373N P=0.245 | |LOGISTIC REGRESSION| P=0.080 P=0.251N P=0.255N P=0.329N P=0.255 | |COCH-ARM / FISHERS | P=0.097 P=0.247N P=0.247N P=0.327N P=0.296 | |ORDER RESTRICTED | P=0.012 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Seminal Vesicle | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 105 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Seminal Vesicle | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 0/50 (0%) 3/37 (8%) 0/32 (0%) | |POLY-3 RATE (b) | 2/34.47 3/30.49 0/29.15 3/21.21 0/19.14 | |POLY-3 PERCENT (g) | 5.8% 9.8% 0.0% 14.2% 0.0% | |TERMINAL (d) | 0/19 (0%) 2/21 (10%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 418 640 --- 631 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.512N P=0.498 P=0.255N P=0.234 P=0.368N | |POLY 3 | P=0.412N P=0.444 P=0.275N P=0.286 P=0.376N | |POLY 1.5 | P=0.400N P=0.455 P=0.259N P=0.314 P=0.368N | |POLY 6 | P=0.429N P=0.443 P=0.297N P=0.256 P=0.387N | |LOGISTIC REGRESSION| P=0.403N P=0.476 P=0.218N P=0.334 P=0.306N | |COCH-ARM / FISHERS | P=0.368N P=0.500 P=0.247N P=0.359 P=0.369N | |ORDER RESTRICTED | P=0.247N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Seminal Vesicle | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 106 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin | | Cyst Epithelial Inclusion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/37 (3%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 2/31.03 0/29.15 1/21.11 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 6.5% 0.0% 4.7% 0.0% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 467 --- 625 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.590N P=0.241 (e) P=0.370 (e) | |POLY 3 | P=0.570N P=0.221 (e) P=0.411 (e) | |POLY 1.5 | P=0.562N P=0.222 (e) P=0.421 (e) | |POLY 6 | P=0.578N P=0.227 (e) P=0.399 (e) | |LOGISTIC REGRESSION| P=0.550N P=0.228 (e) P=0.400 (e) | |COCH-ARM / FISHERS | P=0.533N P=0.247 (e) P=0.425 (e) | |ORDER RESTRICTED | P=0.433N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin | | Cyst Epithelial Inclusion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 1/40 (3%) 2/42 (5%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.54 1/32.58 2/29.92 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 3.1% 6.7% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- 488 412 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.019 * (e) (e) P=0.495 P=0.201 | |POLY 3 | P=0.021 * (e) (e) P=0.486 P=0.201 | |POLY 1.5 | P=0.020 * (e) (e) P=0.478 P=0.199 | |POLY 6 | P=0.023 * (e) (e) P=0.493 P=0.205 | |LOGISTIC REGRESSION| P=0.018 * (e) (e) P=0.374 P=0.206 | |COCH-ARM / FISHERS | P=0.017 * (e) (e) P=0.444 P=0.206 | |ORDER RESTRICTED | P=0.032 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 107 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 2/50 (4%) 7/50 (14%) 7/37 (19%) 1/32 (3%) | |POLY-3 RATE (b) | 10/38.55 2/31.55 7/30.92 7/22.84 1/19.92 | |POLY-3 PERCENT (g) | 25.9% 6.3% 22.6% 30.7% 5.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 322 322 536 531 404 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.264N P=0.032N* P=0.463N P=0.465 P=0.059N | |POLY 3 | P=0.225N P=0.030N* P=0.485N P=0.459 P=0.058N | |POLY 1.5 | P=0.201N P=0.024N* P=0.409N P=0.527 P=0.048N* | |POLY 6 | P=0.270N P=0.035N* P=0.566N P=0.400 P=0.074N | |LOGISTIC REGRESSION| P=0.181N P=0.011N* P=0.301N P=0.566N P=0.022N* | |COCH-ARM / FISHERS | P=0.170N P=0.014N* P=0.298N P=0.562N P=0.026N* | |ORDER RESTRICTED | P=0.051N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 7/50 (14%) 7/49 (14%) 6/40 (15%) 5/42 (12%) | |POLY-3 RATE (b) | 3/37.45 7/35.64 7/40.09 6/34.17 5/32.19 | |POLY-3 PERCENT (g) | 8.0% 19.6% 17.5% 17.6% 15.5% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 248 290 362 414 43 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.337 P=0.140 P=0.186 P=0.209 P=0.271 | |POLY 3 | P=0.331 P=0.132 P=0.183 P=0.193 P=0.272 | |POLY 1.5 | P=0.319 P=0.144 P=0.167 P=0.179 P=0.273 | |POLY 6 | P=0.347 P=0.124 P=0.210 P=0.209 P=0.277 | |LOGISTIC REGRESSION| P=0.229 P=0.157 P=0.112 P=0.040 * P=0.303 | |COCH-ARM / FISHERS | P=0.280 P=0.159 P=0.151 P=0.145 P=0.264 | |ORDER RESTRICTED | P=0.236 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 108 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/50 (28%) 14/50 (28%) 13/50 (26%) 7/37 (19%) 6/32 (19%) | |POLY-3 RATE (b) | 14/41.05 14/37.73 13/36.82 7/26.13 6/22.90 | |POLY-3 PERCENT (g) | 34.1% 37.1% 35.3% 26.8% 26.2% | |TERMINAL (d) | 3/19 (16%) 4/21 (19%) 1/13 (8%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | 111 147 229 167 192 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.251N P=0.523 P=0.506 P=0.410N P=0.370N | |POLY 3 | P=0.187N P=0.483 P=0.552 P=0.359N P=0.355N | |POLY 1.5 | P=0.157N P=0.499 P=0.589N P=0.310N P=0.326N | |POLY 6 | P=0.243N P=0.482 P=0.496 P=0.430N P=0.399N | |LOGISTIC REGRESSION| P=0.057N P=0.462N P=0.371N P=0.101N P=0.136N | |COCH-ARM / FISHERS | P=0.110N P=0.588N P=0.500N P=0.235N P=0.248N | |ORDER RESTRICTED | P=0.417N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 5/50 (10%) 1/49 (2%) 5/40 (13%) 3/42 (7%) | |POLY-3 RATE (b) | 8/37.53 5/33.53 1/36.54 5/33.47 3/30.15 | |POLY-3 PERCENT (g) | 21.3% 14.9% 2.7% 14.9% 10.0% | |TERMINAL (d) | 3/20 (15%) 0/18 (0%) 1/24 (4%) 2/20 (10%) 1/19 (5%) | |FIRST INCIDENCE | 255 207 668 (T) 488 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.371N P=0.014N* P=0.319N P=0.160N | |POLY 3 | P=0.196N P=0.348N P=0.016N* P=0.349N P=0.175N | |POLY 1.5 | P=0.207N P=0.311N P=0.016N* P=0.368N P=0.173N | |POLY 6 | P=0.187N P=0.386N P=0.015N* P=0.333N P=0.177N | |LOGISTIC REGRESSION| P=0.227N P=0.264N P=0.019N* P=0.472N P=0.162N | |COCH-ARM / FISHERS | P=0.219N P=0.277N P=0.017N* P=0.437N P=0.164N | |ORDER RESTRICTED | P=0.104N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 109 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/50 (26%) 12/50 (24%) 12/50 (24%) 8/37 (22%) 5/32 (16%) | |POLY-3 RATE (b) | 13/40.05 12/35.83 12/36.82 8/26.31 5/22.76 | |POLY-3 PERCENT (g) | 32.5% 33.5% 32.6% 30.4% 22.0% | |TERMINAL (d) | 3/19 (16%) 4/21 (19%) 0/13 (0%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | 308 254 229 167 192 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.297N P=0.553N P=0.520 P=0.578 P=0.318N | |POLY 3 | P=0.211N P=0.560 P=0.593 P=0.537N P=0.277N | |POLY 1.5 | P=0.185N P=0.583 P=0.559N P=0.486N P=0.254N | |POLY 6 | P=0.264N P=0.554 P=0.545 P=0.604N P=0.317N | |LOGISTIC REGRESSION| P=0.097N P=0.437N P=0.388N P=0.278N P=0.118N | |COCH-ARM / FISHERS | P=0.153N P=0.500N P=0.500N P=0.416N P=0.204N | |ORDER RESTRICTED | P=0.348N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 5/50 (10%) 3/49 (6%) 4/40 (10%) 3/42 (7%) | |POLY-3 RATE (b) | 7/36.86 5/33.53 3/37.13 4/32.61 3/30.15 | |POLY-3 PERCENT (g) | 19.0% 14.9% 8.1% 12.3% 10.0% | |TERMINAL (d) | 2/20 (10%) 0/18 (0%) 2/24 (8%) 2/20 (10%) 1/19 (5%) | |FIRST INCIDENCE | 460 207 495 488 453 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.169N P=0.493N P=0.127N P=0.279N P=0.238N | |POLY 3 | P=0.194N P=0.445N P=0.149N P=0.330N P=0.245N | |POLY 1.5 | P=0.205N P=0.408N P=0.154N P=0.342N P=0.243N | |POLY 6 | P=0.190N P=0.487N P=0.143N P=0.330N P=0.250N | |LOGISTIC REGRESSION| P=0.219N P=0.377N P=0.156N P=0.361N P=0.240N | |COCH-ARM / FISHERS | P=0.219N P=0.380N P=0.167N P=0.405N P=0.239N | |ORDER RESTRICTED | P=0.236N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 110 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 31/49 (63%) 29/50 (58%) 27/50 (54%) 18/37 (49%) 20/32 (63%) | |POLY-3 RATE (b) | 31/47.16 29/41.27 27/41.65 18/29.69 20/26.79 | |POLY-3 PERCENT (g) | 65.7% 70.3% 64.8% 60.6% 74.7% | |TERMINAL (d) | 7/18 (39%) 12/21 (57%) 5/13 (39%) 0/7 (0%) 6/8 (75%) | |FIRST INCIDENCE | 104 147 147 167 41 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.266 P=0.474N P=0.508 P=0.549N P=0.324 | |POLY 3 | P=0.390 P=0.409 P=0.554N P=0.416N P=0.293 | |POLY 1.5 | P=0.498 P=0.504 P=0.430N P=0.310N P=0.387 | |POLY 6 | P=0.265 P=0.351 P=0.498 P=0.522N P=0.198 | |LOGISTIC REGRESSION| P=0.330N P=0.313N P=0.142N P=0.064N P=0.482N | |COCH-ARM / FISHERS | P=0.368N P=0.371N P=0.232N P=0.128N P=0.564N | |ORDER RESTRICTED | P=0.391 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 31/50 (62%) 21/50 (42%) 32/49 (65%) 26/40 (65%) 29/42 (69%) | |POLY-3 RATE (b) | 31/43.75 21/38.39 32/43.18 26/37.62 29/36.68 | |POLY-3 PERCENT (g) | 70.9% 54.7% 74.1% 69.1% 79.1% | |TERMINAL (d) | 13/20 (65%) 7/18 (39%) 17/24 (71%) 11/20 (55%) 14/19 (74%) | |FIRST INCIDENCE | 179 207 182 359 49 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.305 P=0.204N P=0.388N P=0.337N P=0.429 | |POLY 3 | P=0.110 P=0.087N P=0.459 P=0.530N P=0.271 | |POLY 1.5 | P=0.078 P=0.054N P=0.452 P=0.564N P=0.267 | |POLY 6 | P=0.153 P=0.137N P=0.491 P=0.509N P=0.291 | |LOGISTIC REGRESSION| P=0.065 P=0.041N* P=0.484 P=0.505 P=0.294 | |COCH-ARM / FISHERS | P=0.056 P=0.036N* P=0.447 P=0.472 P=0.314 | |ORDER RESTRICTED | P=0.083 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 111 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 3/50 (6%) 4/50 (8%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 2/32.24 3/30.89 4/30.90 2/22.05 0/19.14 | |POLY-3 PERCENT (g) | 6.2% 9.7% 12.9% 9.1% 0.0% | |TERMINAL (d) | 1/18 (6%) 2/21 (10%) 2/13 (15%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 641 523 147 320 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.377N P=0.529 P=0.239 P=0.426 P=0.427N | |POLY 3 | P=0.275N P=0.480 P=0.314 P=0.552 P=0.359N | |POLY 1.5 | P=0.267N P=0.479 P=0.329 P=0.564 P=0.356N | |POLY 6 | P=0.293N P=0.494 P=0.292 P=0.534 P=0.364N | |LOGISTIC REGRESSION| P=0.243N P=0.481 P=0.346 P=0.573 P=0.368N | |COCH-ARM / FISHERS | P=0.235N P=0.510 P=0.349 P=0.579 P=0.363N | |ORDER RESTRICTED | P=0.224N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/50 (26%) 24/50 (48%) 12/49 (24%) 10/40 (25%) 12/42 (29%) | |POLY-3 RATE (b) | 13/38.73 24/39.56 12/40.21 10/33.81 12/32.91 | |POLY-3 PERCENT (g) | 33.6% 60.7% 29.9% 29.6% 36.5% | |TERMINAL (d) | 7/20 (35%) 11/18 (61%) 5/24 (21%) 6/20 (30%) 5/19 (26%) | |FIRST INCIDENCE | 248 290 328 488 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.135N P=0.014 * P=0.380N P=0.362N P=0.541 | |POLY 3 | P=0.170N P=0.010 * P=0.454N P=0.455N P=0.497 | |POLY 1.5 | P=0.190N P=0.013 * P=0.487N P=0.480N P=0.482 | |POLY 6 | P=0.147N P=0.009 ** P=0.401N P=0.425N P=0.526 | |LOGISTIC REGRESSION| P=0.231N P=0.019 * P=0.530N P=0.552N P=0.486 | |COCH-ARM / FISHERS | P=0.227N P=0.019 * P=0.523N P=0.555N P=0.482 | |ORDER RESTRICTED | P=0.138N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 112 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/49 (8%) 5/50 (10%) 5/50 (10%) 7/37 (19%) 2/32 (6%) | |POLY-3 RATE (b) | 4/34.81 5/34.01 5/31.51 7/25.40 2/19.67 | |POLY-3 PERCENT (g) | 11.5% 14.7% 15.9% 27.6% 10.2% | |TERMINAL (d) | 0/18 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 104 45 474 157 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.336 P=0.462 P=0.420 P=0.081 P=0.624N | |POLY 3 | P=0.298 P=0.485 P=0.436 P=0.101 P=0.615N | |POLY 1.5 | P=0.319 P=0.484 P=0.458 P=0.108 P=0.603N | |POLY 6 | P=0.274 P=0.505 P=0.418 P=0.094 P=0.625N | |LOGISTIC REGRESSION| P=0.477 P=0.598N P=0.559 P=0.197 P=0.481N | |COCH-ARM / FISHERS | P=0.401 P=0.513 P=0.513 P=0.125 P=0.555N | |ORDER RESTRICTED | P=0.398 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 6/50 (12%) 5/49 (10%) 6/40 (15%) 4/42 (10%) | |POLY-3 RATE (b) | 4/37.45 6/34.60 5/40.25 6/33.38 4/31.30 | |POLY-3 PERCENT (g) | 10.7% 17.3% 12.4% 18.0% 12.8% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 248 412 237 488 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.466 P=0.322 P=0.512 P=0.354 P=0.557 | |POLY 3 | P=0.434 P=0.317 P=0.546 P=0.294 P=0.543 | |POLY 1.5 | P=0.423 P=0.338 P=0.523 P=0.280 P=0.541 | |POLY 6 | P=0.444 P=0.305 P=0.577 P=0.310 P=0.548 | |LOGISTIC REGRESSION| P=0.371 P=0.393 P=0.410 P=0.147 P=0.590 | |COCH-ARM / FISHERS | P=0.406 P=0.370 P=0.487 P=0.237 P=0.541 | |ORDER RESTRICTED | P=0.503 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 113 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 6/50 (12%) 5/50 (10%) 2/37 (5%) 1/32 (3%) | |POLY-3 RATE (b) | 0/32.13 6/30.37 5/29.30 2/21.09 1/19.14 | |POLY-3 PERCENT (g) | 0.0% 19.8% 17.1% 9.5% 5.2% | |TERMINAL (d) | 0/18 (0%) 6/21 (29%) 4/13 (31%) 1/7 (14%) 1/8 (13%) | |FIRST INCIDENCE | --- 668 (T) 633 631 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.340 P=0.023 * P=0.011 * P=0.083 P=0.338 | |POLY 3 | P=0.552 P=0.011 * P=0.021 * P=0.150 P=0.397 | |POLY 1.5 | P=0.542N P=0.012 * P=0.025 * P=0.158 P=0.400 | |POLY 6 | P=0.530 P=0.011 * P=0.017 * P=0.139 P=0.394 | |LOGISTIC REGRESSION| P=0.452 P=0.023 * P=0.012 * P=0.117 P=0.338 | |COCH-ARM / FISHERS | P=0.475N P=0.014 * P=0.030 * P=0.182 P=0.395 | |ORDER RESTRICTED | P=0.108 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 3/50 (6%) 7/49 (14%) 6/40 (15%) 7/42 (17%) | |POLY-3 RATE (b) | 7/36.24 3/32.79 7/37.23 6/32.44 7/30.09 | |POLY-3 PERCENT (g) | 19.3% 9.2% 18.8% 18.5% 23.3% | |TERMINAL (d) | 3/20 (15%) 1/18 (6%) 5/24 (21%) 5/20 (25%) 5/19 (26%) | |FIRST INCIDENCE | 510 326 574 541 467 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.293 P=0.230N P=0.511N P=0.532N P=0.513 | |POLY 3 | P=0.244 P=0.194N P=0.595N P=0.588N P=0.464 | |POLY 1.5 | P=0.223 P=0.172N P=0.607N P=0.603N P=0.465 | |POLY 6 | P=0.260 P=0.228N P=0.577N P=0.587N P=0.458 | |LOGISTIC REGRESSION| P=0.221 P=0.165N P=0.580N P=0.573N P=0.460 | |COCH-ARM / FISHERS | P=0.196 P=0.159N P=0.597 P=0.563 P=0.472 | |ORDER RESTRICTED | P=0.307 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 114 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 2/50 (4%) 1/37 (3%) 0/32 (0%) | |POLY-3 RATE (b) | 1/32.92 0/30.37 2/30.24 1/21.18 0/19.14 | |POLY-3 PERCENT (g) | 3.0% 0.0% 6.6% 4.7% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 392 --- 490 607 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.520N P=0.530N P=0.474 P=0.651 P=0.616N | |POLY 3 | P=0.533N P=0.516N P=0.470 P=0.658 P=0.607N | |POLY 1.5 | P=0.522N P=0.513N P=0.483 P=0.672 P=0.602N | |POLY 6 | P=0.552N P=0.514N P=0.455 P=0.642 P=0.612N | |LOGISTIC REGRESSION| P=0.496N P=0.453N P=0.530 P=0.712 P=0.537N | |COCH-ARM / FISHERS | P=0.501N P=0.495N P=0.508 P=0.678 P=0.605N | |ORDER RESTRICTED | P=0.446N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 3/49 (6%) 2/40 (5%) 4/42 (10%) | |POLY-3 RATE (b) | 1/35.79 5/33.87 3/36.77 2/32.44 4/28.92 | |POLY-3 PERCENT (g) | 2.8% 14.8% 8.2% 6.2% 13.8% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 2/24 (8%) 1/20 (5%) 3/19 (16%) | |FIRST INCIDENCE | 372 395 612 541 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.296 P=0.088 P=0.361 P=0.469 P=0.155 | |POLY 3 | P=0.260 P=0.086 P=0.314 P=0.465 P=0.116 | |POLY 1.5 | P=0.255 P=0.093 P=0.307 P=0.455 P=0.120 | |POLY 6 | P=0.264 P=0.081 P=0.326 P=0.474 P=0.113 | |LOGISTIC REGRESSION| P=0.243 P=0.109 P=0.300 P=0.346 P=0.126 | |COCH-ARM / FISHERS | P=0.239 P=0.102 P=0.301 P=0.416 P=0.131 | |ORDER RESTRICTED | P=0.103 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 115 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/32.13 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/40 (0%) 2/42 (5%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.54 0/31.97 2/29.77 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 6.7% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.022 * (e) (e) (e) P=0.192 | |POLY 3 | P=0.025 * (e) (e) (e) P=0.200 | |POLY 1.5 | P=0.024 * (e) (e) (e) P=0.198 | |POLY 6 | P=0.026 * (e) (e) (e) P=0.204 | |LOGISTIC REGRESSION| P=0.020 * (e) (e) (e) P=0.202 | |COCH-ARM / FISHERS | P=0.020 * (e) (e) (e) P=0.206 | |ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 116 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 1/50 (2%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 2/32.13 0/30.37 1/29.41 1/21.82 1/19.52 | |POLY-3 PERCENT (g) | 6.2% 0.0% 3.4% 4.6% 5.1% | |TERMINAL (d) | 2/18 (11%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) --- 605 320 569 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.433 P=0.203N P=0.595N P=0.721 P=0.731 | |POLY 3 | P=0.517 P=0.248N P=0.531N P=0.634N P=0.671N | |POLY 1.5 | P=0.517 P=0.248N P=0.517N P=0.621N P=0.669N | |POLY 6 | P=0.512 P=0.242N P=0.549N P=0.651N P=0.671N | |LOGISTIC REGRESSION| P=0.507 (e) P=0.570N P=0.610N P=0.683N | |COCH-ARM / FISHERS | P=0.521 P=0.242N P=0.492N P=0.605N P=0.657N | |ORDER RESTRICTED | P=0.504N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 0/49 (0%) 2/40 (5%) 4/42 (10%) | |POLY-3 RATE (b) | 4/36.11 3/32.31 0/36.54 2/32.34 4/31.57 | |POLY-3 PERCENT (g) | 11.1% 9.3% 0.0% 6.2% 12.7% | |TERMINAL (d) | 2/20 (10%) 0/18 (0%) 0/24 (0%) 1/20 (5%) 0/19 (0%) | |FIRST INCIDENCE | 372 500 --- 572 207 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.415 P=0.593N P=0.054N P=0.379N P=0.544 | |POLY 3 | P=0.419 P=0.561N P=0.057N P=0.387N P=0.569 | |POLY 1.5 | P=0.404 P=0.533N P=0.059N P=0.399N P=0.560 | |POLY 6 | P=0.428 P=0.587N P=0.054N P=0.378N P=0.580 | |LOGISTIC REGRESSION| P=0.357 P=0.508N P=0.065N P=0.434N P=0.567 | |COCH-ARM / FISHERS | P=0.369 P=0.500N P=0.061N P=0.450N P=0.541 | |ORDER RESTRICTED | P=0.296 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 117 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/32.88 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 2/31.52 0/36.54 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 6.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/18 (6%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 536 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.248N P=0.212 (e) (e) (e) | |POLY 3 | P=0.290N P=0.214 (e) (e) (e) | |POLY 1.5 | P=0.279N P=0.225 (e) (e) (e) | |POLY 6 | P=0.304N P=0.203 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.261N P=0.219 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.268N P=0.247 (e) (e) (e) | |ORDER RESTRICTED | P=0.240N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 118 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 2/50 (4%) 2/37 (5%) 0/32 (0%) | |POLY-3 RATE (b) | 0/32.88 1/30.37 2/29.86 2/21.27 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 3.3% 6.7% 9.4% 0.0% | |TERMINAL (d) | 0/19 (0%) 1/21 (5%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 668 (T) 544 625 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.368 P=0.520 P=0.197 P=0.106 (e) | |POLY 3 | P=0.385 P=0.484 P=0.215 P=0.147 (e) | |POLY 1.5 | P=0.393 P=0.487 P=0.225 P=0.157 (e) | |POLY 6 | P=0.374 P=0.487 P=0.204 P=0.137 (e) | |LOGISTIC REGRESSION| P=0.396 P=0.520 P=0.227 P=0.134 (e) | |COCH-ARM / FISHERS | P=0.432 P=0.505 P=0.253 P=0.182 (e) | |ORDER RESTRICTED | P=0.288 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/49 (2%) 0/40 (0%) 2/42 (5%) | |POLY-3 RATE (b) | 0/34.96 2/32.51 1/37.21 0/31.97 2/29.57 | |POLY-3 PERCENT (g) | 0.0% 6.2% 2.7% 0.0% 6.8% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- 326 460 --- 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.292 P=0.232 P=0.505 (e) P=0.207 | |POLY 3 | P=0.305 P=0.220 P=0.512 (e) P=0.199 | |POLY 1.5 | P=0.297 P=0.229 P=0.506 (e) P=0.198 | |POLY 6 | P=0.308 P=0.211 P=0.522 (e) P=0.201 | |LOGISTIC REGRESSION| P=0.268 P=0.231 P=0.478 (e) P=0.200 | |COCH-ARM / FISHERS | P=0.270 P=0.247 P=0.495 (e) P=0.206 | |ORDER RESTRICTED | P=0.093 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 119 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 1/50 (2%) 0/37 (0%) 1/32 (3%) | |POLY-3 RATE (b) | 2/34.35 2/31.41 1/29.91 0/20.93 1/19.62 | |POLY-3 PERCENT (g) | 5.8% 6.4% 3.3% 0.0% 5.1% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 392 432 413 --- 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.339N P=0.648 P=0.523N P=0.341N P=0.677N | |POLY 3 | P=0.357N P=0.663 P=0.548N P=0.355N P=0.689N | |POLY 1.5 | P=0.335N P=0.668 P=0.526N P=0.335N P=0.680N | |POLY 6 | P=0.389N P=0.668 P=0.576N P=0.381N P=0.697N | |LOGISTIC REGRESSION| P=0.285N P=0.655N P=0.450N P=0.260N P=0.608N | |COCH-ARM / FISHERS | P=0.305N P=0.684N P=0.492N P=0.322N P=0.657N | |ORDER RESTRICTED | P=0.491N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 1/49 (2%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 1/35.91 2/31.10 1/37.49 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 2.8% 6.4% 2.7% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/18 (6%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 255 655 237 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.119N P=0.479 P=0.760 P=0.532N P=0.537N | |POLY 3 | P=0.135N P=0.450 P=0.752N P=0.523N P=0.544N | |POLY 1.5 | P=0.134N P=0.473 P=0.757N P=0.528N P=0.542N | |POLY 6 | P=0.138N P=0.426 P=0.744N P=0.520N P=0.545N | |LOGISTIC REGRESSION| P=0.140N P=0.508 P=0.706 P=0.931N P=0.461N | |COCH-ARM / FISHERS | P=0.132N P=0.500 P=0.747 P=0.556N P=0.543N | |ORDER RESTRICTED | P=0.215N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 120 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular: Glands | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/49 (18%) 13/50 (26%) 10/50 (20%) 15/37 (41%) 6/32 (19%) | |POLY-3 RATE (b) | 9/33.42 13/32.85 10/30.42 15/25.57 6/20.17 | |POLY-3 PERCENT (g) | 26.9% 39.6% 32.9% 58.7% 29.8% | |TERMINAL (d) | 6/19 (32%) 9/21 (43%) 7/13 (54%) 5/7 (71%) 2/8 (25%) | |FIRST INCIDENCE | 601 147 510 320 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026 * P=0.270 P=0.197 P<0.001 ** P=0.348 | |POLY 3 | P=0.160 P=0.196 P=0.401 P=0.009 ** P=0.537 | |POLY 1.5 | P=0.171 P=0.200 P=0.448 P=0.011 * P=0.539 | |POLY 6 | P=0.150 P=0.210 P=0.343 P=0.007 ** P=0.541 | |LOGISTIC REGRESSION| P=0.153 P=0.170 P=0.290 P=0.006 ** P=0.485 | |COCH-ARM / FISHERS | P=0.244 P=0.251 P=0.520 P=0.022 * P=0.593 | |ORDER RESTRICTED | P=0.148 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular: Glands | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 12/50 (24%) 8/49 (16%) 10/40 (25%) 6/42 (14%) | |POLY-3 RATE (b) | 6/36.78 12/34.62 8/38.19 10/34.09 6/30.06 | |POLY-3 PERCENT (g) | 16.3% 34.7% 21.0% 29.3% 20.0% | |TERMINAL (d) | 0/20 (0%) 6/18 (33%) 4/24 (17%) 5/20 (25%) 4/19 (21%) | |FIRST INCIDENCE | 443 326 362 488 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.468N P=0.061 P=0.481 P=0.191 P=0.507 | |POLY 3 | P=0.488 P=0.060 P=0.413 P=0.149 P=0.474 | |POLY 1.5 | P=0.477 P=0.076 P=0.400 P=0.133 P=0.480 | |POLY 6 | P=0.487 P=0.047 * P=0.429 P=0.159 P=0.462 | |LOGISTIC REGRESSION| P=0.488 P=0.082 P=0.387 P=0.108 P=0.486 | |COCH-ARM / FISHERS | P=0.462 P=0.096 P=0.371 P=0.093 P=0.492 | |ORDER RESTRICTED | P=0.301 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 121 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 7/50 (14%) 5/50 (10%) 3/37 (8%) 4/32 (13%) | |POLY-3 RATE (b) | 4/33.45 7/31.35 5/30.77 3/21.68 4/19.54 | |POLY-3 PERCENT (g) | 12.0% 22.3% 16.3% 13.8% 20.5% | |TERMINAL (d) | 2/19 (11%) 4/21 (19%) 2/13 (15%) 1/7 (14%) 3/8 (38%) | |FIRST INCIDENCE | 619 562 147 531 563 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.237 P=0.287 P=0.330 P=0.412 P=0.222 | |POLY 3 | P=0.396 P=0.216 P=0.446 P=0.582 P=0.332 | |POLY 1.5 | P=0.417 P=0.218 P=0.470 P=0.603 P=0.341 | |POLY 6 | P=0.365 P=0.231 P=0.414 P=0.555 P=0.322 | |LOGISTIC REGRESSION| P=0.405 P=0.213 P=0.455 P=0.547 P=0.309 | |COCH-ARM / FISHERS | P=0.477 P=0.262 P=0.500 P=0.641 P=0.379 | |ORDER RESTRICTED | P=0.400 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 122 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/48 (31%) 12/45 (27%) 15/47 (32%) 13/33 (39%) 7/32 (22%) | |POLY-3 RATE (b) | 15/37.70 12/35.05 15/34.91 13/25.81 7/21.66 | |POLY-3 PERCENT (g) | 39.8% 34.2% 43.0% 50.4% 32.3% | |TERMINAL (d) | 3/19 (16%) 2/18 (11%) 2/12 (17%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 104 45 243 157 376 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.421 P=0.434N P=0.372 P=0.195 P=0.437N | |POLY 3 | P=0.474 P=0.401N P=0.485 P=0.278 P=0.385N | |POLY 1.5 | P=0.507 P=0.394N P=0.512 P=0.285 P=0.355N | |POLY 6 | P=0.434 P=0.419N P=0.442 P=0.263 P=0.423N | |LOGISTIC REGRESSION| P=0.359N P=0.244N P=0.582 P=0.353 P=0.253N | |COCH-ARM / FISHERS | P=0.411N P=0.399N P=0.560 P=0.301 P=0.255N | |ORDER RESTRICTED | P=0.462N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/49 (14%) 3/44 (7%) 5/46 (11%) 2/36 (6%) 4/42 (10%) | |POLY-3 RATE (b) | 7/38.61 3/30.14 5/38.16 2/29.78 4/32.18 | |POLY-3 PERCENT (g) | 18.1% 10.0% 13.1% 6.7% 12.4% | |TERMINAL (d) | 1/20 (5%) 0/17 (0%) 0/23 (0%) 0/19 (0%) 0/19 (0%) | |FIRST INCIDENCE | 105 412 237 641 49 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.257N P=0.207N P=0.347N P=0.109N P=0.366N | |POLY 3 | P=0.243N P=0.272N P=0.385N P=0.150N P=0.371N | |POLY 1.5 | P=0.258N P=0.242N P=0.406N P=0.158N P=0.369N | |POLY 6 | P=0.230N P=0.302N P=0.355N P=0.142N P=0.368N | |LOGISTIC REGRESSION| P=0.248N P=0.215N P=0.462N P=0.346N P=0.247N | |COCH-ARM / FISHERS | P=0.280N P=0.206N P=0.425N P=0.176N P=0.358N | |ORDER RESTRICTED | P=0.231N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 123 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/48 (4%) 1/45 (2%) 2/47 (4%) 1/33 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 2/31.51 1/26.53 2/28.17 1/19.03 1/19.52 | |POLY-3 PERCENT (g) | 6.4% 3.8% 7.1% 5.3% 5.1% | |TERMINAL (d) | 1/19 (5%) 1/18 (6%) 1/12 (8%) 1/7 (14%) 0/8 (0%) | |FIRST INCIDENCE | 641 668 (T) 567 668 (T) 569 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.473 P=0.518N P=0.558 P=0.667 P=0.726 | |POLY 3 | P=0.538N P=0.560N P=0.655 P=0.672N P=0.664N | |POLY 1.5 | P=0.530N P=0.555N P=0.669 P=0.657N P=0.662N | |POLY 6 | P=0.554N P=0.558N P=0.634 P=0.693N P=0.667N | |LOGISTIC REGRESSION| P=0.557N P=0.548N P=0.628 P=0.734 P=0.673N | |COCH-ARM / FISHERS | P=0.514N P=0.524N P=0.684 P=0.639N P=0.650N | |ORDER RESTRICTED | P=0.712N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/44 (0%) 0/46 (0%) 0/36 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.91 0/28.79 0/34.75 0/29.65 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 0/23 (0%) 0/19 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 124 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 0/45 (0%) 0/47 (0%) 0/33 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/31.39 0/26.53 0/27.78 0/19.03 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/18 (0%) 0/12 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/49 (2%) 4/44 (9%) 2/46 (4%) 0/36 (0%) 3/42 (7%) | |POLY-3 RATE (b) | 1/35.01 4/30.86 2/35.35 0/29.65 3/30.42 | |POLY-3 PERCENT (g) | 2.9% 13.0% 5.7% 0.0% 9.9% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 1/23 (4%) 0/19 (0%) 0/19 (0%) | |FIRST INCIDENCE | 644 417 490 --- 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.491 P=0.130 P=0.533 P=0.508N P=0.248 | |POLY 3 | P=0.523 P=0.138 P=0.503 P=0.533N P=0.254 | |POLY 1.5 | P=0.508 P=0.145 P=0.492 P=0.541N P=0.250 | |POLY 6 | P=0.536 P=0.134 P=0.521 P=0.526N P=0.259 | |LOGISTIC REGRESSION| P=0.473 P=0.149 P=0.485 P=0.527N P=0.260 | |COCH-ARM / FISHERS | P=0.471 P=0.149 P=0.476 P=0.576N P=0.252 | |ORDER RESTRICTED | P=0.198 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 125 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/48 (2%) 1/45 (2%) 6/47 (13%) 1/33 (3%) 6/32 (19%) | |POLY-3 RATE (b) | 1/31.59 1/26.53 6/28.99 1/19.89 6/20.45 | |POLY-3 PERCENT (g) | 3.2% 3.8% 20.7% 5.0% 29.3% | |TERMINAL (d) | 0/19 (0%) 1/18 (6%) 2/12 (17%) 0/7 (0%) 3/8 (38%) | |FIRST INCIDENCE | 621 668 (T) 546 341 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.750 P=0.025 * P=0.642 P=0.005 ** | |POLY 3 | P=0.006 ** P=0.722 P=0.038 * P=0.654 P=0.008 ** | |POLY 1.5 | P=0.006 ** P=0.725 P=0.043 * P=0.661 P=0.009 ** | |POLY 6 | P=0.004 ** P=0.724 P=0.033 * P=0.642 P=0.008 ** | |LOGISTIC REGRESSION| P=0.007 ** P=0.730 P=0.036 * P=0.695 P=0.010 * | |COCH-ARM / FISHERS | P=0.009 ** P=0.736 P=0.052 P=0.652 P=0.015 * | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/49 (14%) 3/44 (7%) 3/46 (7%) 7/36 (19%) 2/42 (5%) | |POLY-3 RATE (b) | 7/36.44 3/28.89 3/35.06 7/30.00 2/29.50 | |POLY-3 PERCENT (g) | 19.2% 10.4% 8.6% 23.3% 6.8% | |TERMINAL (d) | 3/20 (15%) 2/17 (12%) 2/23 (9%) 5/19 (26%) 0/19 (0%) | |FIRST INCIDENCE | 497 644 590 608 565 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.270N P=0.251N P=0.134N P=0.563 P=0.142N | |POLY 3 | P=0.344N P=0.262N P=0.168N P=0.457 P=0.134N | |POLY 1.5 | P=0.354N P=0.227N P=0.175N P=0.436 P=0.131N | |POLY 6 | P=0.333N P=0.308N P=0.156N P=0.471 P=0.136N | |LOGISTIC REGRESSION| P=0.307N P=0.246N P=0.166N P=0.477 P=0.129N | |COCH-ARM / FISHERS | P=0.341N P=0.206N P=0.185N P=0.365 P=0.121N | |ORDER RESTRICTED | P=0.110N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 126 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thyroid Gland | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/50 (58%) 23/50 (46%) 33/50 (66%) 15/37 (41%) 15/32 (47%) | |POLY-3 RATE (b) | 29/43.08 23/36.66 33/40.94 15/25.47 15/23.95 | |POLY-3 PERCENT (g) | 67.3% 62.7% 80.6% 58.9% 62.6% | |TERMINAL (d) | 10/19 (53%) 13/21 (62%) 10/13 (77%) 5/7 (71%) 3/8 (38%) | |FIRST INCIDENCE | 308 322 308 329 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.423 P=0.233N P=0.080 P=0.565N P=0.534N | |POLY 3 | P=0.314N P=0.421N P=0.113 P=0.325N P=0.452N | |POLY 1.5 | P=0.235N P=0.341N P=0.151 P=0.208N P=0.396N | |POLY 6 | P=0.409N P=0.483N P=0.082 P=0.483N P=0.496N | |LOGISTIC REGRESSION| P=0.171N P=0.214N P=0.212 P=0.117N P=0.277N | |COCH-ARM / FISHERS | P=0.124N P=0.158N P=0.268 P=0.082N P=0.224N | |ORDER RESTRICTED | P=0.369N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thyroid Gland | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 26/50 (52%) 18/49 (37%) 39/50 (78%) 24/40 (60%) 29/42 (69%) | |POLY-3 RATE (b) | 26/39.66 18/39.25 39/43.95 24/35.26 29/35.45 | |POLY-3 PERCENT (g) | 65.6% 45.9% 88.7% 68.1% 81.8% | |TERMINAL (d) | 11/20 (55%) 3/18 (17%) 21/24 (88%) 14/20 (70%) 16/19 (84%) | |FIRST INCIDENCE | 443 207 181 488 325 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.153 P=0.300N P=0.119 P=0.486N P=0.171 | |POLY 3 | P=0.015 * P=0.053N P=0.006 ** P=0.507 P=0.077 | |POLY 1.5 | P=0.011 * P=0.054N P=0.004 ** P=0.467 P=0.065 | |POLY 6 | P=0.019 * P=0.061N P=0.010 * P=0.501 P=0.084 | |LOGISTIC REGRESSION| P=0.018 * P=0.107N P=0.004 ** P=0.536 P=0.046 * | |COCH-ARM / FISHERS | P=0.014 * P=0.092N P=0.006 ** P=0.293 P=0.073 | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 127 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 2/50 (4%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 3/33.13 0/30.37 2/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 9.1% 0.0% 6.9% 0.0% 0.0% | |TERMINAL (d) | 3/19 (16%) 0/21 (0%) 2/13 (15%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 668 (T) --- 668 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.166N P=0.101N P=0.676N P=0.338N P=0.304N | |POLY 3 | P=0.090N P=0.133N P=0.559N P=0.213N P=0.232N | |POLY 1.5 | P=0.085N P=0.132N P=0.536N P=0.200N P=0.229N | |POLY 6 | P=0.100N P=0.128N P=0.590N P=0.231N P=0.236N | |LOGISTIC REGRESSION| P=0.166N (e) P=0.676N (e) (e) | |COCH-ARM / FISHERS | P=0.083N P=0.121N P=0.500N P=0.185N P=0.221N | |ORDER RESTRICTED | P=0.095N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 2/49 (4%) 5/50 (10%) 4/40 (10%) 1/42 (2%) | |POLY-3 RATE (b) | 4/35.25 2/30.91 5/36.80 4/32.23 1/28.81 | |POLY-3 PERCENT (g) | 11.4% 6.5% 13.6% 12.4% 3.5% | |TERMINAL (d) | 2/20 (10%) 2/18 (11%) 4/24 (17%) 3/20 (15%) 1/19 (5%) | |FIRST INCIDENCE | 609 668 (T) 631 603 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.227N P=0.403N P=0.614 P=0.640N P=0.211N | |POLY 3 | P=0.292N P=0.398N P=0.528 P=0.596 P=0.242N | |POLY 1.5 | P=0.307N P=0.370N P=0.516 P=0.577 P=0.240N | |POLY 6 | P=0.279N P=0.432N P=0.548 P=0.610 P=0.244N | |LOGISTIC REGRESSION| P=0.252N P=0.431N P=0.576 P=0.615 P=0.233N | |COCH-ARM / FISHERS | P=0.319N P=0.349N P=0.500 P=0.512 P=0.240N | |ORDER RESTRICTED | P=0.256N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 128 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ureter | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 2/3 (67%) 1/1 (100%) 1/1 (100%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 2/3.00 1/1.00 1/1.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 66.7% 100.0% 100.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 2/3 (67%) 1/1 (100%) 1/1 (100%) 0/0 (0%) | |FIRST INCIDENCE | --- 668 (T) 668 (T) 668 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.568 P=1.000 (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=1.000 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.576 P=1.000 (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ureter | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 129 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urethra | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/4 (0%) 3/5 (60%) 1/3 (33%) 1/3 (33%) | |POLY-3 RATE (b) | 1/1.00 0/2.87 3/4.11 1/2.68 1/2.97 | |POLY-3 PERCENT (g) | 100.0% 0.0% 73.0% 37.4% 33.7% | |TERMINAL (d) | 0/0 (0%) 0/2 (0%) 0/1 (0%) 0/0 (0%) 1/2 (50%) | |FIRST INCIDENCE | 641 --- 376 589 668 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407 P=0.509N P=0.250 P=0.593 P=0.657N | |POLY 3 | P=0.387N P=0.002N** P=0.762N P=0.538N P=0.503N | |POLY 1.5 | P=0.452N P<0.001N** P=0.729N P=0.518N P=0.502N | |POLY 6 | P=0.330N P=0.048N* P=0.773N P=0.580N P=0.506N | |LOGISTIC REGRESSION| P=0.571 P=0.245N P=0.702N P=0.365N P=0.657N | |COCH-ARM / FISHERS | P=0.553N P=0.200N P=0.667N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.371N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urethra | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 130 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urethra | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 1/4 (25%) 3/5 (60%) 1/3 (33%) 0/3 (0%) | |POLY-3 RATE (b) | 1/1.00 1/2.87 3/4.11 1/2.46 0/2.97 | |POLY-3 PERCENT (g) | 100.0% 34.9% 73.0% 40.7% 0.0% | |TERMINAL (d) | 0/0 (0%) 1/2 (50%) 0/1 (0%) 0/0 (0%) 0/2 (0%) | |FIRST INCIDENCE | 641 668 (T) 376 647 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.379N P=0.509N P=0.250 P=0.562 P=0.657N | |POLY 3 | P=0.040N* P=0.518N P=0.762N P=0.574N P<0.001N** | |POLY 1.5 | P=0.061N P=0.467N P=0.729N P=0.534N P<0.001N** | |POLY 6 | P=0.025N* P=0.587N P=0.773N P=0.668N P<0.001N** | |LOGISTIC REGRESSION| P=0.124N P=0.513N P=0.702N (e) (e) | |COCH-ARM / FISHERS | P=0.113N P=0.400N P=0.667N P=0.500N P=0.250N | |ORDER RESTRICTED | P=0.185N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urethra | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 131 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urethra: Bulbourethral Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/1 (0%) 1/4 (25%) 2/5 (40%) 1/3 (33%) 2/3 (67%) | |POLY-3 RATE (b) | 0/0.88 1/2.87 2/3.10 1/2.59 2/3.00 | |POLY-3 PERCENT (g) | 0.0% 34.9% 64.6% 38.6% 66.7% | |TERMINAL (d) | 0/0 (0%) 1/2 (50%) 1/1 (100%) 0/0 (0%) 1/2 (50%) | |FIRST INCIDENCE | --- 668 (T) 322 612 661 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.162 P=1.000N P=0.495 P=0.343 P=0.351 | |POLY 3 | P=0.287 P=0.740 P=0.564 P=0.699 P=0.536 | |POLY 1.5 | P=0.246 P=0.743 P=0.596 P=0.695 P=0.518 | |POLY 6 | P=0.361 P=0.744 P=0.531 P=0.710 P=0.569 | |LOGISTIC REGRESSION| P=0.232 P=1.000N P=0.702 P=0.888 (e) | |COCH-ARM / FISHERS | P=0.173 P=0.800 P=0.667 P=0.750 P=0.500 | |ORDER RESTRICTED | P=0.419 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urethra: Bulbourethral Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 132 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/37 (0%) 2/32 (6%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 1/29.88 0/20.93 2/20.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 3.4% 0.0% 9.8% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 434 --- 376 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.035 * (e) P=0.490 (e) P=0.137 | |POLY 3 | P=0.030 * (e) P=0.479 (e) P=0.135 | |POLY 1.5 | P=0.031 * (e) P=0.487 (e) P=0.135 | |POLY 6 | P=0.028 * (e) P=0.469 (e) P=0.137 | |LOGISTIC REGRESSION| P=0.040 * (e) P=0.521 (e) P=0.166 | |COCH-ARM / FISHERS | P=0.035 * (e) P=0.500 (e) P=0.149 | |ORDER RESTRICTED | P=0.017 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.54 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 133 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 2/37 (5%) 2/32 (6%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 3/30.84 2/21.43 2/19.62 | |POLY-3 PERCENT (g) | 0.0% 0.0% 9.7% 9.3% 10.2% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 1/8 (13%) | |FIRST INCIDENCE | --- --- 481 589 539 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032 * (e) P=0.114 P=0.137 P=0.108 | |POLY 3 | P=0.030 * (e) P=0.104 P=0.147 P=0.129 | |POLY 1.5 | P=0.031 * (e) P=0.109 P=0.155 P=0.131 | |POLY 6 | P=0.028 * (e) P=0.099 P=0.139 P=0.128 | |LOGISTIC REGRESSION| P=0.035 * (e) P=0.126 P=0.144 P=0.129 | |COCH-ARM / FISHERS | P=0.038 * (e) P=0.121 P=0.178 P=0.149 | |ORDER RESTRICTED | P=0.103 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.54 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 134 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/37 (0%) 0/32 (0%) | |POLY-3 RATE (b) | 0/33.13 0/30.37 0/29.15 0/20.93 0/19.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 0/13 (0%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 3/49 (6%) 2/40 (5%) 3/42 (7%) | |POLY-3 RATE (b) | 1/35.52 1/31.45 3/36.69 2/32.58 3/30.37 | |POLY-3 PERCENT (g) | 2.8% 3.2% 8.2% 6.1% 9.9% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 2/24 (8%) 1/20 (5%) 1/19 (5%) | |FIRST INCIDENCE | 510 560 631 488 332 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.151 P=0.708 P=0.357 P=0.491 P=0.255 | |POLY 3 | P=0.154 P=0.734 P=0.316 P=0.470 P=0.248 | |POLY 1.5 | P=0.141 P=0.747 P=0.309 P=0.459 P=0.246 | |POLY 6 | P=0.165 P=0.720 P=0.327 P=0.478 P=0.250 | |LOGISTIC REGRESSION| P=0.118 P=0.759N P=0.314 P=0.385 P=0.255 | |COCH-ARM / FISHERS | P=0.119 P=0.753N P=0.301 P=0.416 P=0.245 | |ORDER RESTRICTED | P=0.196 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 135 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 0/50 (0%) 2/50 (4%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 4/35.61 0/30.37 2/29.76 1/21.24 1/19.96 | |POLY-3 PERCENT (g) | 11.2% 0.0% 6.7% 4.7% 5.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 104 --- 489 589 376 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.363N P=0.077N P=0.413N P=0.353N P=0.378N | |POLY 3 | P=0.317N P=0.081N P=0.422N P=0.364N P=0.388N | |POLY 1.5 | P=0.308N P=0.077N P=0.390N P=0.335N P=0.379N | |POLY 6 | P=0.336N P=0.082N P=0.463N P=0.401N P=0.402N | |LOGISTIC REGRESSION| P=0.281N P=0.038N* P=0.300N P=0.229N P=0.241N | |COCH-ARM / FISHERS | P=0.303N P=0.059N P=0.339N P=0.288N P=0.348N | |ORDER RESTRICTED | P=0.255N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 1/35.05 1/31.10 0/36.54 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 2.9% 3.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 648 655 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.150N P=0.728 P=0.468N P=0.509N P=0.538N | |POLY 3 | P=0.176N P=0.734 P=0.492N P=0.518N P=0.539N | |POLY 1.5 | P=0.174N P=0.748 P=0.496N P=0.524N P=0.538N | |POLY 6 | P=0.179N P=0.719 P=0.485N P=0.514N P=0.540N | |LOGISTIC REGRESSION| P=0.153N P=0.720 P=0.483N P=0.513N P=0.538N | |COCH-ARM / FISHERS | P=0.170N P=0.753N P=0.505N P=0.556N P=0.543N | |ORDER RESTRICTED | P=0.243N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 136 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 3/50 (6%) 1/37 (3%) 1/32 (3%) | |POLY-3 RATE (b) | 4/35.54 1/31.26 3/30.64 1/21.82 1/19.92 | |POLY-3 PERCENT (g) | 11.3% 3.2% 9.8% 4.6% 5.0% | |TERMINAL (d) | 0/19 (0%) 0/21 (0%) 1/13 (8%) 0/7 (0%) 0/8 (0%) | |FIRST INCIDENCE | 104 322 413 320 404 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300N P=0.213N P=0.578N P=0.350N P=0.376N | |POLY 3 | P=0.274N P=0.217N P=0.582N P=0.352N P=0.388N | |POLY 1.5 | P=0.261N P=0.211N P=0.553N P=0.327N P=0.379N | |POLY 6 | P=0.299N P=0.218N P=0.621N P=0.389N P=0.402N | |LOGISTIC REGRESSION| P=0.198N P=0.116N P=0.452N P=0.204N P=0.251N | |COCH-ARM / FISHERS | P=0.242N P=0.181N P=0.500N P=0.288N P=0.348N | |ORDER RESTRICTED | P=0.355N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/40 (0%) 0/42 (0%) | |POLY-3 RATE (b) | 0/34.96 0/31.04 0/36.54 0/31.97 0/28.81 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 0/24 (0%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 137 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 4/49 (8%) 0/40 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 1/35.45 0/31.04 4/37.34 0/31.97 1/29.43 | |POLY-3 PERCENT (g) | 2.8% 0.0% 10.7% 0.0% 3.4% | |TERMINAL (d) | 0/20 (0%) 0/18 (0%) 1/24 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 535 --- 524 --- 482 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.499N P=0.535N P=0.224 P=0.529N P=0.703 | |POLY 3 | P=0.475N P=0.526N P=0.192 P=0.521N P=0.720 | |POLY 1.5 | P=0.499N P=0.513N P=0.184 P=0.526N P=0.719 | |POLY 6 | P=0.452N P=0.541N P=0.206 P=0.518N P=0.720 | |LOGISTIC REGRESSION| P=0.532N P=0.497N P=0.180 P=0.583N P=0.730 | |COCH-ARM / FISHERS | P=0.535N P=0.500N P=0.175 P=0.556N P=0.707 | |ORDER RESTRICTED | P=0.392 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 138 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 3/49 (6%) 0/40 (0%) 1/42 (2%) | |POLY-3 RATE (b) | 2/35.52 0/31.04 3/37.26 0/31.97 1/29.44 | |POLY-3 PERCENT (g) | 5.6% 0.0% 8.1% 0.0% 3.4% | |TERMINAL (d) | 1/20 (5%) 0/18 (0%) 1/24 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 510 --- 524 --- 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.340N P=0.271N P=0.555 P=0.246N P=0.560N | |POLY 3 | P=0.327N P=0.267N P=0.522 P=0.259N P=0.566N | |POLY 1.5 | P=0.348N P=0.252N P=0.510 P=0.265N P=0.565N | |POLY 6 | P=0.308N P=0.285N P=0.542 P=0.256N P=0.566N | |LOGISTIC REGRESSION| P=0.378N P=0.248N P=0.502 P=0.281N P=0.560N | |COCH-ARM / FISHERS | P=0.382N P=0.247N P=0.490 P=0.306N P=0.566N | |ORDER RESTRICTED | P=0.344N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 139 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/50 (44%) 27/50 (54%) 29/49 (59%) 24/40 (60%) 22/42 (52%) | |POLY-3 RATE (b) | 22/38.24 27/36.01 29/38.68 24/35.15 22/31.91 | |POLY-3 PERCENT (g) | 57.5% 75.0% 75.0% 68.3% 69.0% | |TERMINAL (d) | 11/20 (55%) 16/18 (89%) 21/24 (88%) 15/20 (75%) 13/19 (68%) | |FIRST INCIDENCE | 497 472 514 497 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.474N P=0.068 P=0.335 P=0.370 P=0.361 | |POLY 3 | P=0.337 P=0.071 P=0.069 P=0.226 P=0.217 | |POLY 1.5 | P=0.288 P=0.125 P=0.077 P=0.191 P=0.229 | |POLY 6 | P=0.375 P=0.036 * P=0.064 P=0.242 P=0.210 | |LOGISTIC REGRESSION| P=0.367 P=0.045 * P=0.126 P=0.231 P=0.210 | |COCH-ARM / FISHERS | P=0.239 P=0.212 P=0.095 P=0.097 P=0.277 | |ORDER RESTRICTED | P=0.133 (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 140 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Vagina | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Vagina | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 0/49 (0%) 1/47 (2%) 0/40 (0%) 0/41 (0%) | |POLY-3 RATE (b) | 2/36.32 0/30.04 1/35.49 0/31.97 0/28.15 | |POLY-3 PERCENT (g) | 5.5% 0.0% 2.8% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 1/23 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 248 --- 668 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.112N P=0.271N P=0.490N P=0.281N P=0.296N | |POLY 3 | P=0.104N P=0.281N P=0.508N P=0.265N P=0.295N | |POLY 1.5 | P=0.111N P=0.262N P=0.512N P=0.269N P=0.292N | |POLY 6 | P=0.097N P=0.303N P=0.501N P=0.262N P=0.298N | |LOGISTIC REGRESSION| P=0.123N P=0.204N P=0.531N P=0.484N P=0.213N | |COCH-ARM / FISHERS | P=0.120N P=0.247N P=0.516N P=0.300N P=0.294N | |ORDER RESTRICTED | P=0.085N (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/09/04 EXPERIMENT: 99022 TEST: 02 Page 141 Statistical Analysis of Non-neoplastic Lesions in Mice(SWISS) - AZT TRANSPLACENTAL CARCINOGENESIS Terminal Sacrifice at 96 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Vagina: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 50 100 200 300 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Vagina: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/49 (2%) 1/49 (2%) 2/47 (4%) 0/40 (0%) 0/41 (0%) | |POLY-3 RATE (b) | 1/35.51 1/30.40 2/35.80 0/31.97 0/28.15 | |POLY-3 PERCENT (g) | 2.8% 3.3% 5.6% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/17 (0%) 1/23 (4%) 0/20 (0%) 0/19 (0%) | |FIRST INCIDENCE | 510 577 590 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.171N P=0.697 P=0.527 P=0.511N P=0.554N | |POLY 3 | P=0.180N P=0.726 P=0.503 P=0.521N P=0.546N | |POLY 1.5 | P=0.185N P=0.741 P=0.495 P=0.525N P=0.544N | |POLY 6 | P=0.176N P=0.709 P=0.515 P=0.519N P=0.548N | |LOGISTIC REGRESSION| P=0.186N P=0.759N P=0.489 P=0.605N P=0.524N | |COCH-ARM / FISHERS | P=0.189N P=0.753N P=0.484 P=0.551N P=0.544N | |ORDER RESTRICTED | P=0.281N (e) (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).