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 Cy