TDMS Study 88050-06 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus METHACRYLONITRILE DATE: 10/25/99 EXPERIMENT: 88050 TEST: 06 TIME: 08:33:40 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-55388 ROUTE: GAVAGE NTP C#: 88050B PATHOLOGIST: TOFT, JOHN CAS: 126-98-7 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#1, CORE STUDY MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus METHACRYLONITRILE DATE: 10/25/99 EXPERIMENT: 88050 TEST: 06 TIME: 08:33:40 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-55388 ROUTE: GAVAGE NTP C#: 88050B PATHOLOGIST: TOFT, JOHN CAS: 126-98-7 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF METHACRYLONITRILE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Hypertrophy Adrenal Cortex: Capsule Hyperplasia Epididymis Infiltration Cellular Mononuclear Cell Islets, Pancreatic Hyperplasia Kidney Infiltration Cellular Mononuclear Cell Mineralization Nephropathy Kidney: Renal Tubule Hyperplasia Liver Basophilic Focus Eosinophilic Focus Mixed Cell Focus Necrosis Liver: Hepatocyte Vacuolization Cytoplasmic Nose: Nasolacrimal Duct Inflammation Oral Mucosa: Gingival Inflammation Acute Inflammation Chronic Preputial Gland Infiltration Cellular Mononuclear Cell Inflammation Chronic Prostate Infiltration Cellular Mononuclear Cell Salivary Glands Infiltration Cellular Mononuclear Cell Spleen Hematopoietic Cell Proliferation Stomach, Glandular: Glands Ectasia =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Adrenal Cortex: Capsule Hyperplasia Clitoral Gland: Duct Cyst Intestine Small, Jejunum: Peyer's Patch Hyperplasia Lymphoid Kidney Accumulation, Hyaline Droplet Infiltration Cellular Mononuclear Cell Liver Basophilic Focus Infiltration Cellular Mononuclear Cell Inflammation Chronic Pigmentation Liver: Hepatocyte Vacuolization Cytoplasmic Lymph Node, Mandibular Pigmentation Mammary Gland Hyperplasia Cystic Mesentery Mineralization Ovary Pigmentation Pancreas Infiltration Cellular Mononuclear Cell Spleen Hematopoietic Cell Proliferation Stomach, Glandular: Glands Ectasia Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 5.7% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 0/43 (0%) 0/22 (0%) |0/34 (0%) 0/35 (0%) 0/43 (0%) 2/25 (8%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.024 * (e) (e) P=0.173 | |POLY 3 | (e) (e) (e) (e) |P=0.040 * (e) (e) P=0.189 | |POLY 1.5 | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.206 | |POLY 6 | (e) (e) (e) (e) |P=0.040 * (e) (e) P=0.176 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.173 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.253 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 14/49 (29%) 12/50 (24%) 16/50 (32%) 7/50 (14%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 30.9% 25.0% 33.3% 22.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 13/35 (37%) 11/43 (26%) 14/43 (33%) 6/22 (27%) |0/34 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 600 629 429 481 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.417N P=0.209N P=0.516N P=0.358N |(e) (e) (e) (e) | |POLY 3 | P=0.362N P=0.346N P=0.488 P=0.279N |(e) (e) (e) (e) | |POLY 1.5 | P=0.233N P=0.364N P=0.464 P=0.170N |(e) (e) (e) (e) | |POLY 6 | P=0.477N P=0.320N P=0.530 P=0.402N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.351N P=0.325N P=0.447 P=0.394N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.071N P=0.387N P=0.440 P=0.063N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 26/49 (53%) 34/50 (68%) 28/50 (56%) 15/50 (30%) |1/49 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 56.0% 70.9% 59.7% 44.2% |2.2% 0.0% 2.1% 0.0% | |TERMINAL (d) | 21/35 (60%) 32/43 (74%) 27/43 (63%) 11/22 (50%) |0/34 (0%) 0/35 (0%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | 501 644 703 481 |625 --- 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.253N P=0.396 P=0.331N P=0.396N |P=0.462N P=0.514N P=0.732N P=0.574N | |POLY 3 | P=0.120N P=0.092 P=0.441 P=0.204N |P=0.426N P=0.507N P=0.746N P=0.548N | |POLY 1.5 | P=0.034N* P=0.092 P=0.442 P=0.088N |P=0.419N P=0.504N P=0.750N P=0.530N | |POLY 6 | P=0.262N P=0.095 P=0.463 P=0.373N |P=0.431N P=0.507N P=0.740N P=0.563N | |LOGISTIC REGRESSION| P=0.236N P=0.143 P=0.530 P=0.257N |P=0.397N P=0.457N P=0.741 P=0.453N | |COCH-ARM / FISHERS | P=0.002N** P=0.094 P=0.463 P=0.017N* |P=0.402N P=0.495N P=0.747N P=0.495N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex: Capsule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 41/49 (84%) 41/50 (82%) 40/50 (80%) 45/50 (90%) |48/49 (98%) 48/50 (96%) 50/50 (100%) 50/50 (100%) | |POLY-3 ADJUSTED (b)| 83.8% 82.5% 81.5% 96.8% |98.0% 99.3% 100.0% 100.0% | |TERMINAL (d) | 28/35 (80%) 35/43 (81%) 35/43 (81%) 22/22 (100%)|34/34 (100%) 35/35 (100%) 43/43 (100%) 25/25 (100%) | |FIRST INCIDENCE | 501 563 429 481 |362 374 533 212 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.136N P=0.101N P<0.001 ** |P=0.003 ** P=0.540N P=0.072N P=0.010 * | |POLY 3 | P=0.033 * P=0.538N P=0.486N P=0.029 * |P=0.254 P=0.637 P=0.501 P=0.501 | |POLY 1.5 | P=0.060 P=0.529N P=0.462N P=0.064 |P=0.216 P=0.752 P=0.498 P=0.498 | |POLY 6 | P=0.018 * P=0.551N P=0.505N P=0.012 * |P=0.292 P=0.547 P=0.506 P=0.506 | |LOGISTIC REGRESSION| P=0.097 P=0.583N P=0.420N P=0.084 |P=0.052 P=0.744N P=0.468 P=0.565 | |COCH-ARM / FISHERS | P=0.206 P=0.518N P=0.416N P=0.264 |P=0.185 P=0.508N P=0.495 P=0.495 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 4/50 (8%) 0/50 (0%) |2/50 (4%) 2/50 (4%) 4/50 (8%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 8.3% 0.0% |4.4% 4.7% 8.2% 2.8% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 2/43 (5%) 0/22 (0%) |1/35 (3%) 2/35 (6%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 439 --- |607 730 (T) 589 641 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.385 (e) P=0.080 (e) |P=0.577N P=0.683 P=0.374 P=0.626N | |POLY 3 | P=0.205 (e) P=0.070 (e) |P=0.558N P=0.673 P=0.371 P=0.589N | |POLY 1.5 | P=0.310 (e) P=0.067 (e) |P=0.516N P=0.678 P=0.357 P=0.558N | |POLY 6 | P=0.139 (e) P=0.076 (e) |P=0.549 P=0.673 P=0.390 P=0.612N | |LOGISTIC REGRESSION| P=0.529N (e) P=0.077 (e) |P=0.375N P=0.688 P=0.193 P=0.500N | |COCH-ARM / FISHERS | P=0.505 (e) P=0.061 (e) |P=0.431N P=0.691N P=0.339 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Bone Marrow | | Myelofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 3/50 (6%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 7.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 0/43 (0%) 0/22 (0%) |1/35 (3%) 3/35 (9%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |727 730 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.092N P=0.497 P=0.199N P=0.320N | |POLY 3 | (e) (e) (e) (e) |P=0.084N P=0.478 P=0.226N P=0.299N | |POLY 1.5 | (e) (e) (e) (e) |P=0.081N P=0.483 P=0.230N P=0.276N | |POLY 6 | (e) (e) (e) (e) |P=0.084N P=0.480 P=0.219N P=0.319N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.092N P=0.504 P=0.203N P=0.316N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.073N P=0.500 P=0.247N P=0.247N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Brain | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 0/43 (0%) 0/22 (0%) |2/35 (6%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.124N P=0.238N P=0.194N P=0.315N | |POLY 3 | (e) (e) (e) (e) |P=0.094N P=0.248N P=0.226N P=0.299N | |POLY 1.5 | (e) (e) (e) (e) |P=0.102N P=0.246N P=0.230N P=0.276N | |POLY 6 | (e) (e) (e) (e) |P=0.086N P=0.247N P=0.219N P=0.319N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.124N (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.115N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |4/50 (8%) 2/50 (4%) 3/50 (6%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| |8.8% 4.7% 6.3% 2.9% | |TERMINAL (d) | |3/35 (9%) 2/35 (6%) 1/43 (2%) 1/25 (4%) | |FIRST INCIDENCE | |593 730 (T) 653 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.246N P=0.348N P=0.421N P=0.302N | |POLY 3 | |P=0.232N P=0.364N P=0.473N P=0.282N | |POLY 1.5 | |P=0.210N P=0.357N P=0.484N P=0.244N | |POLY 6 | |P=0.247N P=0.365N P=0.456N P=0.314N | |LOGISTIC REGRESSION| |P=0.218N P=0.353N P=0.532N P=0.269N | |COCH-ARM / FISHERS | |P=0.167N P=0.339N P=0.500N P=0.187N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 1/50 (2%) 0/50 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| |4.4% 2.3% 0.0% 2.9% | |TERMINAL (d) | |2/35 (6%) 1/35 (3%) 0/43 (0%) 1/25 (4%) | |FIRST INCIDENCE | |730 (T) 730 (T) --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.440N P=0.500N P=0.194N P=0.617N | |POLY 3 | |P=0.359N P=0.517N P=0.226N P=0.597N | |POLY 1.5 | |P=0.368N P=0.513N P=0.230N P=0.566N | |POLY 6 | |P=0.345N P=0.515N P=0.219N P=0.622N | |LOGISTIC REGRESSION| |P=0.440N P=0.500N (e) P=0.617N | |COCH-ARM / FISHERS | |P=0.372N P=0.500N P=0.247N P=0.508N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 0/50 (0%) 2/50 (4%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| |0.0% 0.0% 4.2% 5.9% | |TERMINAL (d) | |0/35 (0%) 0/35 (0%) 2/43 (5%) 2/25 (8%) | |FIRST INCIDENCE | |--- --- 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.043 * (e) P=0.285 P=0.167 | |POLY 3 | |P=0.048 * (e) P=0.249 P=0.180 | |POLY 1.5 | |P=0.058 (e) P=0.244 P=0.197 | |POLY 6 | |P=0.041 * (e) P=0.256 P=0.167 | |LOGISTIC REGRESSION| |(e) (e) P=0.285 P=0.167 | |COCH-ARM / FISHERS | |P=0.083 (e) P=0.247 P=0.242 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Epididymis | | Granuloma Sperm | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 4.4% 0.0% 2.1% 0.0% | | |TERMINAL (d) | 1/35 (3%) 0/43 (0%) 1/43 (2%) 0/22 (0%) | | |FIRST INCIDENCE | 663 --- 729 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.252N P=0.215N P=0.447N P=0.365N | | |POLY 3 | P=0.212N P=0.226N P=0.487N P=0.329N | | |POLY 1.5 | P=0.206N P=0.229N P=0.491N P=0.291N | | |POLY 6 | P=0.226N P=0.222N P=0.479N P=0.366N | | |LOGISTIC REGRESSION| P=0.223N P=0.246N P=0.493N P=0.313N | | |COCH-ARM / FISHERS | P=0.185N P=0.242N P=0.492N P=0.242N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Epididymis | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 15/49 (31%) 26/50 (52%) 30/50 (60%) 21/50 (42%) | | |POLY-3 ADJUSTED (b)| 32.7% 54.6% 62.8% 57.0% | | |TERMINAL (d) | 10/35 (29%) 25/43 (58%) 28/43 (65%) 12/22 (55%) | | |FIRST INCIDENCE | 600 714 502 481 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.115 P=0.028 * P=0.012 * | | |POLY 3 | P=0.014 * P=0.024 * P=0.002 ** P=0.020 * | | |POLY 1.5 | P=0.044 * P=0.024 * P=0.002 ** P=0.048 * | | |POLY 6 | P=0.004 ** P=0.024 * P=0.003 ** P=0.008 ** | | |LOGISTIC REGRESSION| P=0.013 * P=0.040 * P=0.003 ** P=0.046 * | | |COCH-ARM / FISHERS | P=0.244 P=0.025 * P=0.003 ** P=0.166 | | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Epididymis | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 4.4% 0.0% 2.1% 0.0% | | |TERMINAL (d) | 1/35 (3%) 0/43 (0%) 1/43 (2%) 0/22 (0%) | | |FIRST INCIDENCE | 650 --- 729 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.253N P=0.217N P=0.447N P=0.368N | | |POLY 3 | P=0.212N P=0.226N P=0.488N P=0.329N | | |POLY 1.5 | P=0.206N P=0.229N P=0.491N P=0.291N | | |POLY 6 | P=0.226N P=0.222N P=0.479N P=0.367N | | |LOGISTIC REGRESSION| P=0.212N P=0.252N P=0.494N P=0.298N | | |COCH-ARM / FISHERS | P=0.185N P=0.242N P=0.492N P=0.242N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Heart | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.5% 2.1% 0.0% 3.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 1/43 (2%) 0/43 (0%) 1/22 (5%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 650 729 (T) --- 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.499N P=0.452N P=0.213N P=0.678N |(e) (e) (e) (e) | |POLY 3 | P=0.347N P=0.475N P=0.225N P=0.618N |(e) (e) (e) (e) | |POLY 1.5 | P=0.361N P=0.479N P=0.227N P=0.570N |(e) (e) (e) (e) | |POLY 6 | P=0.336N P=0.469N P=0.220N P=0.661N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.456N P=0.498N P=0.228N P=0.642N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.357N P=0.485N P=0.237N P=0.485N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.5% 0.0% 2.1% 3.2% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 1/43 (2%) 1/22 (5%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 650 --- 729 (T) 729 (T) |623 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.647 P=0.229N P=0.458N P=0.687N |P=0.343N P=0.518N P=0.500N P=0.579N | |POLY 3 | P=0.517N P=0.222N P=0.481N P=0.619N |P=0.258N P=0.511N P=0.491N P=0.553N | |POLY 1.5 | P=0.517N P=0.225N P=0.485N P=0.570N |P=0.278N P=0.508N P=0.495N P=0.534N | |POLY 6 | P=0.523N P=0.219N P=0.474N P=0.662N |P=0.240N P=0.511N P=0.486N P=0.568N | |LOGISTIC REGRESSION| P=0.574N P=0.268N P=0.486N P=0.613N |P=0.257N P=0.459N P=0.591N P=0.453N | |COCH-ARM / FISHERS | P=0.490N P=0.237N P=0.485N P=0.485N |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 3/49 (6%) 1/50 (2%) 1/50 (2%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 6.4% 2.1% 3.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 3/43 (7%) 1/43 (2%) 1/22 (5%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.442 P=0.160 P=0.541 P=0.407 |(e) (e) (e) (e) | |POLY 3 | P=0.422 P=0.127 P=0.508 P=0.429 |(e) (e) (e) (e) | |POLY 1.5 | P=0.485 P=0.123 P=0.506 P=0.456 |(e) (e) (e) (e) | |POLY 6 | P=0.388 P=0.132 P=0.514 P=0.405 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.160 P=0.541 P=0.407 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.598 P=0.121 P=0.505 P=0.505 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Intestine Small, Jejunum: Peyer's Patch | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.1% 3.2% |0.0% 0.0% 0.0% 5.6% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 1/43 (2%) 1/22 (5%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 1/25 (4%) | |FIRST INCIDENCE | --- --- 729 (T) 729 (T) |--- --- --- 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.140 (e) P=0.541 P=0.407 |P=0.034 * (e) (e) P=0.199 | |POLY 3 | P=0.142 (e) P=0.508 P=0.429 |P=0.040 * (e) (e) P=0.188 | |POLY 1.5 | P=0.174 (e) P=0.506 P=0.456 |P=0.041 * (e) (e) P=0.204 | |POLY 6 | P=0.129 (e) P=0.514 P=0.405 |P=0.040 * (e) (e) P=0.177 | |LOGISTIC REGRESSION| (e) (e) P=0.541 P=0.407 |P=0.076 (e) (e) P=0.292 | |COCH-ARM / FISHERS | P=0.238 (e) P=0.505 P=0.505 |P=0.046 * (e) (e) P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 47/49 (96%) 43/50 (86%) 48/50 (96%) 46/50 (92%) |41/50 (82%) 37/50 (74%) 40/50 (80%) 33/49 (67%) | |POLY-3 ADJUSTED (b)| 96.6% 86.1% 96.0% 96.7% |85.2% 80.8% 81.5% 73.8% | |TERMINAL (d) | 35/35 (100%) 37/43 (86%) 41/43 (95%) 21/22 (96%) |31/35 (89%) 29/35 (83%) 37/43 (86%) 15/25 (60%) | |FIRST INCIDENCE | 501 563 429 481 |492 405 533 212 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.012N* P=0.081N P=0.004 ** |P=0.327 P=0.302N P=0.057N P=0.394 | |POLY 3 | P=0.276 P=0.062N P=0.648N P=0.730 |P=0.106N P=0.382N P=0.411N P=0.126N | |POLY 1.5 | P=0.336 P=0.072N P=0.675N P=0.654N |P=0.097N P=0.332N P=0.438N P=0.106N | |POLY 6 | P=0.245 P=0.047N* P=0.594N P=0.729 |P=0.105N P=0.407N P=0.390N P=0.133N | |LOGISTIC REGRESSION| P=0.345 P=0.094N P=0.688 P=0.588 |P=0.233N P=0.381N P=0.390N P=0.122N | |COCH-ARM / FISHERS | P=0.528N P=0.085N P=0.684 P=0.349N |P=0.079N P=0.235N P=0.500N P=0.074N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 1/50 (2%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 0/43 (0%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |623 422 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.120N P=0.524N P=0.232N P=0.330N | |POLY 3 | (e) (e) (e) (e) |P=0.098N P=0.515N P=0.231N P=0.303N | |POLY 1.5 | (e) (e) (e) (e) |P=0.101N P=0.511N P=0.236N P=0.278N | |POLY 6 | (e) (e) (e) (e) |P=0.093N P=0.516N P=0.226N P=0.325N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.040N* P=0.355N P=0.317N P=0.191N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.101N P=0.500N P=0.253N P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.5% 4.2% 2.1% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/35 (6%) 2/43 (5%) 1/43 (2%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |593 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.181N P=0.619N P=0.428N P=0.345N |P=0.348N P=0.527N P=0.508N P=0.587N | |POLY 3 | P=0.173N P=0.673N P=0.485N P=0.328N |P=0.258N P=0.512N P=0.494N P=0.553N | |POLY 1.5 | P=0.157N P=0.679N P=0.490N P=0.290N |P=0.278N P=0.509N P=0.498N P=0.534N | |POLY 6 | P=0.192N P=0.664N P=0.475N P=0.364N |P=0.239N P=0.512N P=0.488N P=0.568N | |LOGISTIC REGRESSION| P=0.181N P=0.619N P=0.428N (e) |P=0.237N P=0.437N P=0.643N P=0.415N | |COCH-ARM / FISHERS | P=0.122N P=0.684N P=0.492N P=0.242N |P=0.306N P=0.500N P=0.505N P=0.500N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 26/49 (53%) 37/50 (74%) 39/50 (78%) 22/50 (44%) |35/50 (70%) 42/50 (84%) 44/49 (90%) 35/50 (70%) | |POLY-3 ADJUSTED (b)| 57.3% 77.3% 82.8% 58.7% |75.9% 89.5% 92.5% 81.8% | |TERMINAL (d) | 23/35 (66%) 36/43 (84%) 38/43 (88%) 13/22 (59%) |31/35 (89%) 32/35 (91%) 42/43 (98%) 23/25 (92%) | |FIRST INCIDENCE | 650 644 655 481 |607 374 589 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.075 P=0.188 P=0.091 P=0.205 |P=0.018 * P=0.083 P=0.465 P=0.020 * | |POLY 3 | P=0.468 P=0.026 * P=0.004 ** P=0.538 |P=0.316 P=0.057 P=0.017 * P=0.323 | |POLY 1.5 | P=0.375N P=0.025 * P=0.004 ** P=0.491N |P=0.426 P=0.054 P=0.014 * P=0.401 | |POLY 6 | P=0.287 P=0.030 * P=0.005 ** P=0.411 |P=0.243 P=0.085 P=0.022 * P=0.278 | |LOGISTIC REGRESSION| P=0.144 P=0.050 P=0.017 * P=0.437 |P=0.108 P=0.019 * P=0.051 P=0.117 | |COCH-ARM / FISHERS | P=0.082N P=0.025 * P=0.008 ** P=0.242N |P=0.417N P=0.077 P=0.013 * P=0.586N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.4% 2.1% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 1/43 (2%) 0/43 (0%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 670 729 (T) --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.131N P=0.447N P=0.210N P=0.363N |(e) (e) (e) (e) | |POLY 3 | P=0.096N P=0.482N P=0.229N P=0.329N |(e) (e) (e) (e) | |POLY 1.5 | P=0.100N P=0.486N P=0.232N P=0.290N |(e) (e) (e) (e) | |POLY 6 | P=0.096N P=0.475N P=0.224N P=0.366N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.118N P=0.494N P=0.234N P=0.321N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.099N P=0.492N P=0.242N P=0.242N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 43/49 (88%) 49/50 (98%) 47/50 (94%) 36/50 (72%) |5/50 (10%) 5/50 (10%) 5/49 (10%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 89.6% 98.7% 95.5% 87.5% |11.0% 11.5% 10.6% 16.4% | |TERMINAL (d) | 33/35 (94%) 43/43 (100%) 41/43 (95%) 20/22 (91%) |4/35 (11%) 3/35 (9%) 4/43 (9%) 3/25 (12%) | |FIRST INCIDENCE | 501 563 439 481 |671 638 653 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.019 * P=0.373N P=0.242N P=0.066 |P=0.246 P=0.623 P=0.511N P=0.314 | |POLY 3 | P=0.279N P=0.050 P=0.220 P=0.511N |P=0.303 P=0.602 P=0.604N P=0.351 | |POLY 1.5 | P=0.062N P=0.051 P=0.211 P=0.244N |P=0.340 P=0.608 P=0.619N P=0.403 | |POLY 6 | P=0.562 P=0.052 P=0.268 P=0.546 |P=0.279 P=0.607 P=0.581N P=0.312 | |LOGISTIC REGRESSION| P=0.557N P=0.079 P=0.215 P=0.579 |P=0.376 P=0.603 P=0.615N P=0.478 | |COCH-ARM / FISHERS | P=0.002N** P=0.053 P=0.233 P=0.044N* |P=0.421 P=0.630N P=0.617 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 43/49 (88%) 48/50 (96%) 47/50 (94%) 39/50 (78%) |15/50 (30%) 19/50 (38%) 22/49 (45%) 9/50 (18%) | |POLY-3 ADJUSTED (b)| 90.9% 96.7% 94.3% 91.7% |33.1% 43.8% 46.4% 25.1% | |TERMINAL (d) | 34/35 (97%) 43/43 (100%) 41/43 (95%) 22/22 (100%)|14/35 (40%) 17/35 (49%) 21/43 (49%) 7/25 (28%) | |FIRST INCIDENCE | 513 563 429 481 |662 638 589 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.269N P=0.226N P=0.015 * |P=0.316N P=0.252 P=0.304 P=0.391N | |POLY 3 | P=0.532N P=0.198 P=0.400 P=0.620 |P=0.304N P=0.204 P=0.134 P=0.297N | |POLY 1.5 | P=0.255N P=0.162 P=0.318 P=0.466N |P=0.207N P=0.217 P=0.115 P=0.224N | |POLY 6 | P=0.353 P=0.264 P=0.529 P=0.358 |P=0.382N P=0.209 P=0.165 P=0.361N | |LOGISTIC REGRESSION| P=0.313 P=0.216 P=0.217 P=0.195 |P=0.340N P=0.220 P=0.174 P=0.381N | |COCH-ARM / FISHERS | P=0.030N* P=0.128 P=0.233 P=0.154N |P=0.082N P=0.263 P=0.093 P=0.121N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney: Cortex | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 11/49 (22%) 12/50 (24%) 8/50 (16%) 9/50 (18%) |2/50 (4%) 3/50 (6%) 1/49 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 24.5% 25.0% 17.0% 26.8% |4.4% 7.0% 2.1% 2.9% | |TERMINAL (d) | 11/35 (31%) 11/43 (26%) 7/43 (16%) 5/22 (23%) |2/35 (6%) 3/35 (9%) 1/43 (2%) 1/25 (4%) | |FIRST INCIDENCE | 729 (T) 605 694 481 |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.406 P=0.471N P=0.156N P=0.405 |P=0.365N P=0.500 P=0.428N P=0.617N | |POLY 3 | P=0.502N P=0.573 P=0.266N P=0.512 |P=0.334N P=0.478 P=0.486N P=0.589N | |POLY 1.5 | P=0.424N P=0.551 P=0.279N P=0.579N |P=0.319N P=0.483 P=0.494N P=0.558N | |POLY 6 | P=0.522 P=0.586N P=0.240N P=0.419 |P=0.339N P=0.480 P=0.474N P=0.613N | |LOGISTIC REGRESSION| P=0.548 P=0.586N P=0.188N P=0.513 |P=0.365N P=0.500 P=0.428N P=0.617N | |COCH-ARM / FISHERS | P=0.261N P=0.522 P=0.288N P=0.382N |P=0.280N P=0.500 P=0.508N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/49 (18%) 8/50 (16%) 9/50 (18%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 20.0% 16.8% 19.2% 6.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 8/35 (23%) 8/43 (19%) 9/43 (21%) 2/22 (9%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 694 729 (T) 729 (T) 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.114N P=0.324N P=0.416N P=0.124N |(e) (e) (e) (e) | |POLY 3 | P=0.131N P=0.451N P=0.567N P=0.099N |(e) (e) (e) (e) | |POLY 1.5 | P=0.078N P=0.464N P=0.578N P=0.059N |(e) (e) (e) (e) | |POLY 6 | P=0.190N P=0.432N P=0.544N P=0.149N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.129N P=0.375N P=0.471N P=0.139N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.025N* P=0.482N P=0.584N P=0.023N* |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 4/50 (8%) 6/50 (12%) 2/50 (4%) |1/50 (2%) 7/50 (14%) 2/49 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 8.3% 12.8% 6.3% |2.2% 16.3% 4.3% 5.7% | |TERMINAL (d) | 0/35 (0%) 3/43 (7%) 6/43 (14%) 1/22 (5%) |1/35 (3%) 7/35 (20%) 2/43 (5%) 2/25 (8%) | |FIRST INCIDENCE | --- 563 729 (T) 481 |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.147 P=0.089 P=0.031 * P=0.189 |P=0.569N P=0.031 * P=0.572 P=0.383 | |POLY 3 | P=0.114 P=0.070 P=0.018 * P=0.171 |P=0.549N P=0.025 * P=0.514 P=0.411 | |POLY 1.5 | P=0.182 P=0.067 P=0.017 * P=0.194 |P=0.510N P=0.026 * P=0.506 P=0.442 | |POLY 6 | P=0.074 P=0.074 P=0.019 * P=0.152 |P=0.551 P=0.025 * P=0.526 P=0.386 | |LOGISTIC REGRESSION| P=0.243 P=0.048 * P=0.031 * P=0.281 |P=0.569N P=0.031 * P=0.572 P=0.383 | |COCH-ARM / FISHERS | P=0.351 P=0.061 P=0.014 * P=0.253 |P=0.422N P=0.030 * P=0.492 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/49 (14%) 10/50 (20%) 10/50 (20%) 4/50 (8%) |3/50 (6%) 6/50 (12%) 6/49 (12%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 15.6% 21.0% 21.4% 12.6% |6.6% 13.7% 12.8% 2.9% | |TERMINAL (d) | 7/35 (20%) 10/43 (23%) 10/43 (23%) 3/22 (14%) |3/35 (9%) 4/35 (11%) 6/43 (14%) 1/25 (4%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 481 |730 (T) 521 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.483N P=0.472 P=0.472 P=0.537N |P=0.311N P=0.244 P=0.352 P=0.431N | |POLY 3 | P=0.458N P=0.343 P=0.330 P=0.485N |P=0.348N P=0.226 P=0.263 P=0.403N | |POLY 1.5 | P=0.341N P=0.331 P=0.320 P=0.392N |P=0.289N P=0.228 P=0.250 P=0.368N | |POLY 6 | P=0.522 P=0.362 P=0.353 P=0.569N |P=0.394N P=0.232 P=0.280 P=0.433N | |LOGISTIC REGRESSION| P=0.534N P=0.472 P=0.472 P=0.558N |P=0.301N P=0.226 P=0.352 P=0.431N | |COCH-ARM / FISHERS | P=0.160N P=0.314 P=0.314 P=0.251N |P=0.191N P=0.243 P=0.233 P=0.309N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 16/49 (33%) 10/50 (20%) 12/50 (24%) 3/50 (6%) |9/50 (18%) 3/50 (6%) 11/49 (22%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 34.7% 21.0% 25.6% 9.6% |19.9% 7.0% 23.2% 8.4% | |TERMINAL (d) | 12/35 (34%) 10/43 (23%) 12/43 (28%) 2/22 (9%) |8/35 (23%) 3/35 (9%) 10/43 (23%) 2/25 (8%) | |FIRST INCIDENCE | 583 729 (T) 729 (T) 710 |687 730 (T) 589 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020N* P=0.048N* P=0.110N P=0.027N* |P=0.281N P=0.061N P=0.592 P=0.162N | |POLY 3 | P=0.021N* P=0.105N P=0.234N P=0.013N* |P=0.279N P=0.071N P=0.447 P=0.133N | |POLY 1.5 | P=0.009N** P=0.109N P=0.237N P=0.004N** |P=0.226N P=0.068N P=0.420 P=0.102N | |POLY 6 | P=0.042N* P=0.101N P=0.224N P=0.033N* |P=0.324N P=0.069N P=0.484 P=0.163N | |LOGISTIC REGRESSION| P=0.023N* P=0.098N P=0.213N P=0.017N* |P=0.268N P=0.061N P=0.458 P=0.141N | |COCH-ARM / FISHERS | P<0.001N** P=0.115N P=0.232N P<0.001N** |P=0.145N P=0.061N P=0.382 P=0.061N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 3/50 (6%) 1/50 (2%) |2/50 (4%) 2/50 (4%) 6/49 (12%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 6.3% 3.2% |4.4% 4.7% 12.6% 5.7% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 2/43 (5%) 1/22 (5%) |2/35 (6%) 2/35 (6%) 5/43 (12%) 0/25 (0%) | |FIRST INCIDENCE | --- --- 439 729 (T) |730 (T) 730 (T) 589 641 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.155 (e) P=0.148 P=0.407 |P=0.345 P=0.695 P=0.202 P=0.569 | |POLY 3 | P=0.097 (e) P=0.130 P=0.429 |P=0.319 P=0.677 P=0.150 P=0.602 | |POLY 1.5 | P=0.144 (e) P=0.126 P=0.456 |P=0.379 P=0.680 P=0.140 P=0.634 | |POLY 6 | P=0.072 (e) P=0.136 P=0.405 |P=0.279 P=0.679 P=0.164 P=0.577 | |LOGISTIC REGRESSION| P=0.297 (e) P=0.138 P=0.407 |P=0.388 P=0.695 P=0.132 P=0.611 | |COCH-ARM / FISHERS | P=0.251 (e) P=0.125 P=0.505 |P=0.499 P=0.691N P=0.128 P=0.691N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/49 (18%) 11/50 (22%) 7/50 (14%) 6/50 (12%) |30/50 (60%) 36/50 (72%) 40/49 (82%) 30/50 (60%) | |POLY-3 ADJUSTED (b)| 19.6% 23.1% 14.9% 18.9% |65.2% 80.2% 84.1% 70.0% | |TERMINAL (d) | 6/35 (17%) 11/43 (26%) 7/43 (16%) 5/22 (23%) |26/35 (74%) 30/35 (86%) 38/43 (88%) 18/25 (72%) | |FIRST INCIDENCE | 513 729 (T) 729 (T) 481 |607 422 589 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.492N P=0.582 P=0.258N P=0.569 |P=0.045 * P=0.134 P=0.302 P=0.073 | |POLY 3 | P=0.384N P=0.436 P=0.376N P=0.582N |P=0.405 P=0.073 P=0.024 * P=0.397 | |POLY 1.5 | P=0.297N P=0.430 P=0.379N P=0.461N |P=0.458 P=0.088 P=0.019 * P=0.445 | |POLY 6 | P=0.451N P=0.446 P=0.362N P=0.531 |P=0.392 P=0.075 P=0.034 * P=0.384 | |LOGISTIC REGRESSION| P=0.444N P=0.439 P=0.372N P=0.558N |P=0.149 P=0.052 P=0.055 P=0.287 | |COCH-ARM / FISHERS | P=0.150N P=0.421 P=0.376N P=0.274N |P=0.466N P=0.146 P=0.016 * P=0.581N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 22/49 (45%) 21/50 (42%) 19/50 (38%) 21/50 (42%) |32/50 (64%) 36/50 (72%) 41/49 (84%) 38/50 (76%) | |POLY-3 ADJUSTED (b)| 47.2% 43.8% 40.0% 53.5% |70.3% 80.4% 86.2% 87.0% | |TERMINAL (d) | 17/35 (49%) 20/43 (47%) 17/43 (40%) 9/22 (41%) |31/35 (89%) 32/35 (91%) 39/43 (91%) 23/25 (92%) | |FIRST INCIDENCE | 501 625 612 481 |607 521 589 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.076 P=0.217N P=0.134N P=0.145 |P<0.001 ** P=0.174 P=0.409 P<0.001 ** | |POLY 3 | P=0.341 P=0.451N P=0.310N P=0.357 |P=0.023 * P=0.176 P=0.041 * P=0.033 * | |POLY 1.5 | P=0.435 P=0.457N P=0.317N P=0.470 |P=0.032 * P=0.186 P=0.031 * P=0.050 | |POLY 6 | P=0.282 P=0.441N P=0.286N P=0.274 |P=0.023 * P=0.211 P=0.068 P=0.031 * | |LOGISTIC REGRESSION| P=0.540 P=0.424N P=0.301N P=0.517N |P<0.001 ** P=0.107 P=0.107 P=0.005 ** | |COCH-ARM / FISHERS | P=0.424N P=0.465N P=0.311N P=0.465N |P=0.097 P=0.260 P=0.022 * P=0.138 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 11/50 (22%) 11/50 (22%) 2/50 (4%) |3/50 (6%) 1/50 (2%) 3/49 (6%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 23.1% 23.2% 6.4% |6.6% 2.3% 6.4% 0.0% | |TERMINAL (d) | 0/35 (0%) 11/43 (26%) 10/43 (23%) 2/22 (9%) |3/35 (9%) 1/35 (3%) 3/43 (7%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) 502 729 (T) |730 (T) 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.265 P=0.002 ** P=0.002 ** P=0.143 |P=0.180N P=0.305N P=0.565N P=0.186N | |POLY 3 | P=0.168 P<0.001 ** P<0.001 ** P=0.167 |P=0.194N P=0.323N P=0.643N P=0.172N | |POLY 1.5 | P=0.315 P<0.001 ** P<0.001 ** P=0.192 |P=0.173N P=0.319N P=0.655N P=0.152N | |POLY 6 | P=0.089 P<0.001 ** P<0.001 ** P=0.147 |P=0.212N P=0.320N P=0.627N P=0.191N | |LOGISTIC REGRESSION| P=0.258 P=0.002 ** P<0.001 ** P=0.143 |P=0.180N P=0.305N P=0.565N (e) | |COCH-ARM / FISHERS | P=0.488N P<0.001 ** P<0.001 ** P=0.253 |P=0.136N P=0.309N P=0.651 P=0.121N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/49 (12%) 5/50 (10%) 1/50 (2%) 0/50 (0%) |3/50 (6%) 2/50 (4%) 2/49 (4%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 12.8% 10.3% 2.1% 0.0% |6.6% 4.7% 4.2% 2.8% | |TERMINAL (d) | 1/35 (3%) 2/43 (5%) 0/43 (0%) 0/22 (0%) |2/35 (6%) 2/35 (6%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | 501 625 655 --- |623 730 (T) 701 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.015N* P=0.432N P=0.054N P=0.082N |P=0.312N P=0.508N P=0.430N P=0.409N | |POLY 3 | P=0.009N** P=0.476N P=0.055N P=0.055N |P=0.288N P=0.526N P=0.484N P=0.397N | |POLY 1.5 | P=0.007N** P=0.480N P=0.055N P=0.034N* |P=0.270N P=0.519N P=0.494N P=0.363N | |POLY 6 | P=0.012N* P=0.468N P=0.053N P=0.084N |P=0.299N P=0.526N P=0.470N P=0.426N | |LOGISTIC REGRESSION| P<0.001N** P=0.613 P=0.037N* P=0.006N** |P=0.196N P=0.518N P=0.524N P=0.179N | |COCH-ARM / FISHERS | P=0.004N** P=0.486N P=0.053N P=0.012N* |P=0.233N P=0.500N P=0.510N P=0.309N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 0/50 (0%) 2/50 (4%) 3/50 (6%) |18/50 (36%) 12/50 (24%) 17/49 (35%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 6.7% 0.0% 4.2% 9.4% |39.8% 27.9% 36.2% 20.1% | |TERMINAL (d) | 3/35 (9%) 0/43 (0%) 1/43 (2%) 2/22 (9%) |17/35 (49%) 12/35 (34%) 17/43 (40%) 7/25 (28%) | |FIRST INCIDENCE | 729 (T) --- 612 481 |704 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.233 P=0.087N P=0.422N P=0.476 |P=0.073N P=0.120N P=0.214N P=0.068N | |POLY 3 | P=0.305 P=0.109N P=0.477N P=0.496 |P=0.080N P=0.167N P=0.443N P=0.049N* | |POLY 1.5 | P=0.335 P=0.112N P=0.485N P=0.563 |P=0.050N P=0.161N P=0.478N P=0.027N* | |POLY 6 | P=0.298 P=0.105N P=0.461N P=0.436 |P=0.110N P=0.161N P=0.393N P=0.075N | |LOGISTIC REGRESSION| P=0.378 (e) P=0.491N P=0.520 |P=0.083N P=0.112N P=0.252N P=0.070N | |COCH-ARM / FISHERS | P=0.410 P=0.117N P=0.490N P=0.651N |P=0.018N* P=0.138N P=0.530N P=0.010N* | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Tension Lipidosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 3/50 (6%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.2% 0.0% 2.1% 0.0% |4.4% 6.9% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/43 (0%) 1/43 (2%) 0/22 (0%) |1/35 (3%) 2/35 (6%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) --- 729 (T) --- |727 556 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.492N P=0.459N P=0.715N P=0.593N |P=0.096N P=0.490 P=0.199N P=0.320N | |POLY 3 | P=0.447N P=0.488N P=0.751N P=0.571N |P=0.085N P=0.484 P=0.228N P=0.299N | |POLY 1.5 | P=0.435N P=0.492N P=0.754N P=0.543N |P=0.082N P=0.486 P=0.234N P=0.276N | |POLY 6 | P=0.476N P=0.484N P=0.745N P=0.595N |P=0.084N P=0.489 P=0.221N P=0.319N | |LOGISTIC REGRESSION| P=0.492N (e) P=0.715N (e) |P=0.077N P=0.494 P=0.203N P=0.316N | |COCH-ARM / FISHERS | P=0.402N P=0.495N P=0.747N P=0.495N |P=0.074N P=0.500 P=0.253N P=0.247N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/49 (12%) 10/50 (20%) 9/50 (18%) 16/50 (32%) |7/50 (14%) 9/50 (18%) 3/49 (6%) 18/50 (36%) | |POLY-3 ADJUSTED (b)| 13.2% 21.0% 19.2% 40.4% |14.9% 20.1% 6.4% 42.4% | |TERMINAL (d) | 5/35 (14%) 10/43 (23%) 9/43 (21%) 4/22 (18%) |2/35 (6%) 5/35 (14%) 3/43 (7%) 8/25 (32%) | |FIRST INCIDENCE | 501 729 (T) 729 (T) 481 |492 374 730 (T) 212 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.344 P=0.436 P=0.004 ** |P<0.001 ** P=0.372 P=0.123N P=0.003 ** | |POLY 3 | P=0.003 ** P=0.233 P=0.307 P=0.003 ** |P=0.002 ** P=0.350 P=0.158N P=0.003 ** | |POLY 1.5 | P=0.005 ** P=0.227 P=0.302 P=0.005 ** |P=0.002 ** P=0.362 P=0.161N P=0.004 ** | |POLY 6 | P=0.002 ** P=0.244 P=0.323 P=0.002 ** |P=0.002 ** P=0.348 P=0.152N P=0.002 ** | |LOGISTIC REGRESSION| P=0.064 P=0.234 P=0.311 P=0.142 |P=0.047 * P=0.466 P=0.245N P=0.100 | |COCH-ARM / FISHERS | P=0.013 * P=0.220 P=0.303 P=0.016 * |P=0.004 ** P=0.393 P=0.167N P=0.010 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 3/50 (6%) 0/50 (0%) 4/50 (8%) |2/50 (4%) 1/50 (2%) 3/50 (6%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.4% 6.2% 0.0% 12.7% |4.4% 2.3% 6.3% 2.9% | |TERMINAL (d) | 0/35 (0%) 2/43 (5%) 0/43 (0%) 3/22 (14%) |1/35 (3%) 0/35 (0%) 2/43 (5%) 0/25 (0%) | |FIRST INCIDENCE | 501 563 --- 623 |645 422 701 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.115 P=0.546 P=0.237N P=0.131 |P=0.579N P=0.516N P=0.574 P=0.625N | |POLY 3 | P=0.239 P=0.522 P=0.232N P=0.188 |P=0.572N P=0.513N P=0.522 P=0.590N | |POLY 1.5 | P=0.253 P=0.516 P=0.234N P=0.240 |P=0.539N P=0.510N P=0.513 P=0.559N | |POLY 6 | P=0.248 P=0.531 P=0.228N P=0.149 |P=0.558 P=0.511N P=0.534 P=0.615N | |LOGISTIC REGRESSION| P=0.358 P=0.320 P=0.146N P=0.274 |P=0.438N P=0.398N P=0.499 P=0.572N | |COCH-ARM / FISHERS | P=0.308 P=0.510 P=0.242N P=0.349 |P=0.474N P=0.500N P=0.500 P=0.500N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |5/50 (10%) 1/50 (2%) 2/50 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 6.6% 2.1% 0.0% 6.4% |11.0% 2.3% 4.2% 5.6% | |TERMINAL (d) | 2/35 (6%) 1/43 (2%) 0/43 (0%) 2/22 (9%) |3/35 (9%) 1/35 (3%) 2/43 (5%) 1/25 (4%) | |FIRST INCIDENCE | 650 729 (T) --- 729 (T) |662 730 (T) 730 (T) 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.621N P=0.254N P=0.097N P=0.643 |P=0.309N P=0.110N P=0.157N P=0.353N | |POLY 3 | P=0.424N P=0.287N P=0.112N P=0.662N |P=0.251N P=0.115N P=0.200N P=0.329N | |POLY 1.5 | P=0.443N P=0.292N P=0.114N P=0.600N |P=0.243N P=0.112N P=0.206N P=0.287N | |POLY 6 | P=0.402N P=0.281N P=0.108N P=0.628 |P=0.255N P=0.116N P=0.191N P=0.367N | |LOGISTIC REGRESSION| P=0.606N P=0.297N P=0.117N P=0.649 |P=0.248N P=0.112N P=0.206N P=0.248N | |COCH-ARM / FISHERS | P=0.438N P=0.301N P=0.117N P=0.490N |P=0.221N P=0.102N P=0.218N P=0.218N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.5% 4.2% 2.1% 3.2% |0.0% 2.3% 2.1% 0.0% | |TERMINAL (d) | 0/35 (0%) 1/43 (2%) 1/43 (2%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 583 605 729 (T) 623 |--- 374 533 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.352N P=0.465N P=0.285N P=0.546N |P=0.638N P=0.500 P=0.508 (e) | |POLY 3 | P=0.251N P=0.482N P=0.300N P=0.452N |P=0.651 P=0.494 P=0.513 (e) | |POLY 1.5 | P=0.236N P=0.486N P=0.301N P=0.392N |P=0.634N P=0.495 P=0.508 (e) | |POLY 6 | P=0.264N P=0.477N P=0.296N P=0.506N |P=0.613 P=0.496 P=0.520 (e) | |LOGISTIC REGRESSION| P=0.085N P=0.690N P=0.258N P=0.190N |P=0.310N P=0.769 P=0.280 (e) | |COCH-ARM / FISHERS | P=0.194N P=0.490N P=0.301N P=0.301N |P=0.595N P=0.500 P=0.500 (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 6/50 (12%) 5/50 (10%) 4/50 (8%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.6% 12.6% 10.7% 12.6% |2.2% 2.3% 2.1% 0.0% | |TERMINAL (d) | 2/35 (6%) 6/43 (14%) 5/43 (12%) 2/22 (9%) |1/35 (3%) 0/35 (0%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | 663 729 (T) 729 (T) 481 |730 (T) 644 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.253 P=0.342 P=0.462 P=0.286 |P=0.373N P=0.752 P=0.715N P=0.567N | |POLY 3 | P=0.291 P=0.269 P=0.377 P=0.319 |P=0.355N P=0.752 P=0.749N P=0.551N | |POLY 1.5 | P=0.372 P=0.262 P=0.371 P=0.387 |P=0.342N P=0.753 P=0.753N P=0.533N | |POLY 6 | P=0.240 P=0.278 P=0.390 P=0.263 |P=0.363N P=0.754 P=0.742N P=0.565N | |LOGISTIC REGRESSION| P=0.286 P=0.284 P=0.391 P=0.356 |P=0.341N P=0.763N P=0.715N (e) | |COCH-ARM / FISHERS | P=0.544 P=0.254 P=0.369 P=0.511 |P=0.311N P=0.753N P=0.753N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 8/50 (16%) 3/50 (6%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 8.9% 16.6% 6.3% 9.4% |2.2% 0.0% 0.0% 5.7% | |TERMINAL (d) | 3/35 (9%) 6/43 (14%) 1/43 (2%) 2/22 (9%) |1/35 (3%) 0/35 (0%) 0/43 (0%) 1/25 (4%) | |FIRST INCIDENCE | 663 563 612 481 |730 (T) --- --- 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478N P=0.281 P=0.426N P=0.588 |P=0.175 P=0.500N P=0.459N P=0.388 | |POLY 3 | P=0.382N P=0.210 P=0.472N P=0.619 |P=0.233 P=0.510N P=0.490N P=0.412 | |POLY 1.5 | P=0.327N P=0.201 P=0.482N P=0.613N |P=0.235 P=0.507N P=0.494N P=0.443 | |POLY 6 | P=0.420N P=0.223 P=0.454N P=0.553 |P=0.234 P=0.509N P=0.484N P=0.389 | |LOGISTIC REGRESSION| P=0.269N P=0.183 P=0.489N P=0.656N |P=0.179 (e) (e) P=0.383 | |COCH-ARM / FISHERS | P=0.218N P=0.188 P=0.489N P=0.489N |P=0.246 P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/46 (2%) 1/48 (2%) 0/50 (0%) 0/47 (0%) |5/48 (10%) 4/49 (8%) 3/46 (7%) 1/47 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 2.2% 0.0% 0.0% |11.4% 9.3% 6.9% 3.1% | |TERMINAL (d) | 1/33 (3%) 1/42 (2%) 0/43 (0%) 0/22 (0%) |5/35 (14%) 4/35 (11%) 3/39 (8%) 1/24 (4%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.275N P=0.707N P=0.447N P=0.581N |P=0.123N P=0.500N P=0.297N P=0.207N | |POLY 3 | P=0.223N P=0.740N P=0.479N P=0.568N |P=0.120N P=0.515N P=0.360N P=0.185N | |POLY 1.5 | P=0.231N P=0.745N P=0.482N P=0.542N |P=0.103N P=0.508N P=0.368N P=0.153N | |POLY 6 | P=0.223N P=0.734N P=0.473N P=0.591N |P=0.133N P=0.515N P=0.350N P=0.215N | |LOGISTIC REGRESSION| P=0.275N P=0.707N (e) (e) |P=0.123N P=0.500N P=0.297N P=0.207N | |COCH-ARM / FISHERS | P=0.230N P=0.742N P=0.479N P=0.495N |P=0.072N P=0.487N P=0.381N P=0.107N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/46 (0%) 0/48 (0%) 0/50 (0%) 0/47 (0%) |3/48 (6%) 16/49 (33%) 9/46 (20%) 4/47 (9%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |6.8% 36.7% 20.6% 12.2% | |TERMINAL (d) | 0/33 (0%) 0/42 (0%) 0/43 (0%) 0/22 (0%) |2/35 (6%) 13/35 (37%) 8/39 (21%) 4/24 (17%) | |FIRST INCIDENCE | --- --- --- --- |671 476 716 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.527N P<0.001 ** P=0.095 P=0.305 | |POLY 3 | (e) (e) (e) (e) |P=0.509 P<0.001 ** P=0.056 P=0.342 | |POLY 1.5 | (e) (e) (e) (e) |P=0.471N P<0.001 ** P=0.054 P=0.393 | |POLY 6 | (e) (e) (e) (e) |P=0.415 P<0.001 ** P=0.058 P=0.300 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.543N P<0.001 ** P=0.063 P=0.291 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.282N P<0.001 ** P=0.051 P=0.488 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.2% 0.0% 4.2% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 0/43 (0%) 0/22 (0%) |1/35 (3%) 0/35 (0%) 2/43 (5%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) --- 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.533N P=0.500N P=0.572 P=0.567N | |POLY 3 | (e) (e) (e) (e) |P=0.533N P=0.510N P=0.518 P=0.551N | |POLY 1.5 | (e) (e) (e) (e) |P=0.508N P=0.507N P=0.511 P=0.533N | |POLY 6 | (e) (e) (e) (e) |P=0.554N P=0.509N P=0.529 P=0.565N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.533N (e) P=0.572 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.461N P=0.500N P=0.500 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/46 (0%) 0/43 (0%) 0/49 (0%) 0/47 (0%) |2/47 (4%) 0/48 (0%) 0/47 (0%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/42 (0%) 0/22 (0%) |2/34 (6%) 0/35 (0%) 0/40 (0%) 0/24 (0%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.128N P=0.232N P=0.203N P=0.318N | |POLY 3 | (e) (e) (e) (e) |P=0.095N P=0.246N P=0.229N P=0.305N | |POLY 1.5 | (e) (e) (e) (e) |P=0.103N P=0.243N P=0.233N P=0.281N | |POLY 6 | (e) (e) (e) (e) |P=0.088N P=0.245N P=0.225N P=0.324N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.128N (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.116N P=0.242N P=0.247N P=0.253N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/46 (2%) 0/43 (0%) 0/49 (0%) 0/47 (0%) |2/47 (4%) 1/48 (2%) 0/47 (0%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 0.0% 0.0% |4.6% 2.4% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/38 (0%) 0/42 (0%) 0/22 (0%) |2/34 (6%) 1/35 (3%) 0/40 (0%) 0/24 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |730 (T) 730 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.342N P=0.484N P=0.464N P=0.593N |P=0.118N P=0.490N P=0.203N P=0.318N | |POLY 3 | P=0.243N P=0.505N P=0.485N P=0.568N |P=0.099N P=0.513N P=0.229N P=0.305N | |POLY 1.5 | P=0.269N P=0.509N P=0.486N P=0.542N |P=0.101N P=0.508N P=0.233N P=0.281N | |POLY 6 | P=0.230N P=0.500N P=0.480N P=0.590N |P=0.095N P=0.512N P=0.225N P=0.324N | |LOGISTIC REGRESSION| P=0.342N (e) (e) (e) |P=0.118N P=0.490N (e) (e) | |COCH-ARM / FISHERS | P=0.299N P=0.517N P=0.484N P=0.495N |P=0.103N P=0.492N P=0.247N P=0.253N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/46 (2%) 1/43 (2%) 1/49 (2%) 0/47 (0%) |2/47 (4%) 0/48 (0%) 1/47 (2%) 1/46 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 2.4% 2.2% 0.0% |4.6% 0.0% 2.2% 3.1% | |TERMINAL (d) | 1/35 (3%) 1/38 (3%) 1/42 (2%) 0/22 (0%) |2/34 (6%) 0/35 (0%) 1/40 (3%) 1/24 (4%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |730 (T) --- 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.395N P=0.743N P=0.721N P=0.593N |P=0.596N P=0.232N P=0.443N P=0.621N | |POLY 3 | P=0.367N P=0.755 P=0.743N P=0.568N |P=0.518N P=0.246N P=0.488N P=0.596N | |POLY 1.5 | P=0.346N P=0.751 P=0.745N P=0.542N |P=0.517N P=0.243N P=0.493N P=0.565N | |POLY 6 | P=0.391N P=0.760 P=0.739N P=0.590N |P=0.516N P=0.245N P=0.481N P=0.621N | |LOGISTIC REGRESSION| P=0.395N P=0.743N P=0.721N (e) |P=0.596N (e) P=0.443N P=0.621N | |COCH-ARM / FISHERS | P=0.300N P=0.736 P=0.737N P=0.495N |P=0.509N P=0.242N P=0.500N P=0.508N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) |3/49 (6%) 1/50 (2%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |6.8% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |3/35 (9%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) 711 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.051N P=0.302N P=0.087N P=0.186N | |POLY 3 | (e) (e) (e) (e) |P=0.040N* P=0.316N P=0.109N P=0.170N | |POLY 1.5 | (e) (e) (e) (e) |P=0.042N* P=0.312N P=0.113N P=0.150N | |POLY 6 | (e) (e) (e) (e) |P=0.038N* P=0.314N P=0.103N P=0.188N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.054N P=0.309N (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.044N* P=0.301N P=0.121N P=0.121N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/3 (33%) 1/6 (17%) 0/6 (0%) 0/1 (0%) |8/16 (50%) 7/11 (64%) 10/15 (67%) 2/4 (50%) | |POLY-3 ADJUSTED (b)| 36.0% 20.4% 0.0% 0.0% |54.5% 69.6% 71.1% 52.9% | |TERMINAL (d) | 1/2 (50%) 0/2 (0%) 0/5 (0%) 0/0 (0%) |6/10 (60%) 6/9 (67%) 10/11 (91%) 2/3 (67%) | |FIRST INCIDENCE | 729 (T) 563 --- --- |709 638 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.302N P=0.749N P=0.318N P=1.000 |P=0.500N P=0.596N P=0.490 P=0.439N | |POLY 3 | P=0.183N P=0.639N P=0.348N P=0.786N |P=0.485 P=0.369 P=0.292 P=0.697N | |POLY 1.5 | P=0.187N P=0.621N P=0.350N P=0.753N |P=0.471 P=0.349 P=0.288 P=0.699N | |POLY 6 | P=0.174N P=0.667N P=0.343N P=0.815N |P=0.500 P=0.431 P=0.301 P=0.696N | |LOGISTIC REGRESSION| P=0.191N P=0.492N (e) (e) |P=0.555 P=0.395 P=0.388 P=0.694N | |COCH-ARM / FISHERS | P=0.284N P=0.583N P=0.333N P=0.750N |P=0.445 P=0.381 P=0.283 P=0.709N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/3 (33%) 1/6 (17%) 1/6 (17%) 1/1 (100%) |5/16 (31%) 6/11 (55%) 8/15 (53%) 0/4 (0%) | |POLY-3 ADJUSTED (b)| 36.0% 23.0% 17.9% 100.0% |34.1% 59.6% 55.3% 0.0% | |TERMINAL (d) | 1/2 (50%) 1/2 (50%) 1/5 (20%) 0/0 (0%) |4/10 (40%) 5/9 (56%) 6/11 (55%) 0/3 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 481 |709 638 653 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.381 P=0.807 P=0.549N P=0.382 |P=0.256N P=0.425 P=0.328 P=0.174N | |POLY 3 | P=0.426 P=0.674N P=0.601N P=0.525 |P=0.398N P=0.198 P=0.217 P=0.244N | |POLY 1.5 | P=0.408 P=0.639N P=0.601N P=0.513 |P=0.417N P=0.188 P=0.203 P=0.252N | |POLY 6 | P=0.457 P=0.729N P=0.596N P=0.548 |P=0.374N P=0.231 P=0.243 P=0.235N | |LOGISTIC REGRESSION| P=0.406 P=0.807 P=0.549N (e) |P=0.403N P=0.197 P=0.221 P=0.229N | |COCH-ARM / FISHERS | P=0.386 P=0.583N P=0.583N P=0.500 |P=0.445N P=0.208 P=0.189 P=0.282N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/3 (0%) 0/6 (0%) 2/6 (33%) 0/1 (0%) |0/16 (0%) 0/11 (0%) 0/15 (0%) 0/4 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 35.8% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/2 (0%) 0/2 (0%) 2/5 (40%) 0/0 (0%) |0/10 (0%) 0/9 (0%) 0/11 (0%) 0/3 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.379 (e) P=0.451 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.167 (e) P=0.393 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.198 (e) P=0.393 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.166 (e) P=0.398 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.451 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.424 (e) P=0.417 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/3 (0%) 1/6 (17%) 1/6 (17%) 0/1 (0%) |5/16 (31%) 7/11 (64%) 12/15 (80%) 1/4 (25%) | |POLY-3 ADJUSTED (b)| 0.0% 23.0% 17.9% 0.0% |34.3% 69.6% 80.9% 26.4% | |TERMINAL (d) | 0/2 (0%) 1/2 (50%) 1/5 (20%) 0/0 (0%) |4/10 (40%) 6/9 (67%) 10/11 (91%) 1/3 (33%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |727 638 589 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.731 P=0.500 P=0.682 (e) |P=0.468 P=0.277 P=0.032 * P=0.472N | |POLY 3 | P=0.497 P=0.593 P=0.636 (e) |P=0.257 P=0.085 P=0.007 ** P=0.625N | |POLY 1.5 | P=0.516 P=0.613 P=0.635 (e) |P=0.235 P=0.080 P=0.005 ** P=0.630N | |POLY 6 | P=0.498 P=0.558 P=0.640 (e) |P=0.288 P=0.107 P=0.010 * P=0.618N | |LOGISTIC REGRESSION| (e) P=0.500 P=0.682 (e) |P=0.260 P=0.096 P=0.010 * P=0.611N | |COCH-ARM / FISHERS | P=0.716 P=0.667 P=0.667 (e) |P=0.225 P=0.102 P=0.008 ** P=0.657N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/3 (33%) 2/6 (33%) 1/6 (17%) 0/1 (0%) |8/16 (50%) 7/11 (64%) 11/15 (73%) 3/4 (75%) | |POLY-3 ADJUSTED (b)| 36.0% 37.6% 17.9% 0.0% |54.5% 69.6% 75.6% 79.3% | |TERMINAL (d) | 1/2 (50%) 0/2 (0%) 1/5 (20%) 0/0 (0%) |6/10 (60%) 6/9 (67%) 10/11 (91%) 3/3 (100%) | |FIRST INCIDENCE | 729 (T) 563 729 (T) --- |709 638 589 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.391N P=0.522 P=0.549N P=1.000N |P=0.388 P=0.596N P=0.344 P=0.651 | |POLY 3 | P=0.392N P=0.744 P=0.601N P=0.786N |P=0.170 P=0.369 P=0.201 P=0.384 | |POLY 1.5 | P=0.367N P=0.745 P=0.601N P=0.753N |P=0.162 P=0.349 P=0.185 P=0.379 | |POLY 6 | P=0.394N P=0.745 P=0.596N P=0.815N |P=0.176 P=0.431 P=0.229 P=0.389 | |LOGISTIC REGRESSION| P=0.294N P=0.559N P=0.549N (e) |P=0.189 P=0.395 P=0.209 P=0.399 | |COCH-ARM / FISHERS | P=0.386N P=0.762N P=0.583N P=0.750N |P=0.147 P=0.381 P=0.168 P=0.375 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 3/50 (6%) 4/50 (8%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.6% 6.3% 8.5% 3.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 2/43 (5%) 3/43 (7%) 1/22 (5%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 638 714 694 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.448N P=0.587N P=0.582 P=0.510N |(e) (e) (e) (e) | |POLY 3 | P=0.430N P=0.640N P=0.519 P=0.450N |(e) (e) (e) (e) | |POLY 1.5 | P=0.361N P=0.645N P=0.513 P=0.390N |(e) (e) (e) (e) | |POLY 6 | P=0.496N P=0.632N P=0.531 P=0.505N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.412N P=0.664 P=0.511 P=0.445N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.241N P=0.651N P=0.511 P=0.301N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Nose | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.4% 0.0% 6.4% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/43 (0%) 2/43 (5%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 638 --- 694 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.434N P=0.217N P=0.568 P=0.371N |(e) (e) (e) (e) | |POLY 3 | P=0.438N P=0.226N P=0.517 P=0.329N |(e) (e) (e) (e) | |POLY 1.5 | P=0.384N P=0.229N P=0.512 P=0.291N |(e) (e) (e) (e) | |POLY 6 | P=0.501N P=0.222N P=0.529 P=0.367N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.367N P=0.259N P=0.509 P=0.285N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.291N P=0.242N P=0.510 P=0.242N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 8.8% 0.0% 2.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/35 (6%) 0/43 (0%) 1/43 (2%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 501 --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060N P=0.050N P=0.143N P=0.155N |(e) (e) (e) (e) | |POLY 3 | P=0.042N* P=0.055N P=0.171N P=0.128N |(e) (e) (e) (e) | |POLY 1.5 | P=0.042N* P=0.057N P=0.174N P=0.096N |(e) (e) (e) (e) | |POLY 6 | P=0.044N* P=0.053N P=0.165N P=0.164N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.022N* P=0.086N P=0.166N P=0.057N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.038N* P=0.056N P=0.175N P=0.056N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 27/31 (87%) 29/30 (97%) 26/27 (96%) 10/10 (100%)|2/3 (67%) 5/5 (100%) 1/2 (50%) 0/1 (0%) | |POLY-3 ADJUSTED (b)| 87.1% 96.7% 96.3% 100.0% |72.3% 100.0% 50.0% 0.0% | |TERMINAL (d) | 19/23 (83%) 24/25 (96%) 20/21 (95%) 6/6 (100%) |2/2 (100%) 5/5 (100%) 1/2 (50%) 0/0 (0%) | |FIRST INCIDENCE | 513 605 429 481 |730 (T) 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.375 P=0.574N P=0.568 P=0.503 |P=0.500N P=1.000 P=0.500N P=1.000 | |POLY 3 | P=0.104 P=0.186 P=0.220 P=0.281 |P=0.132N P=0.507 P=0.649N P=0.511N | |POLY 1.5 | P=0.104 P=0.186 P=0.220 P=0.281 |P=0.149N P=0.445 P=0.660N P=0.504N | |POLY 6 | P=0.104 P=0.186 P=0.220 P=0.281 |P=0.105N P=0.655 P=0.628N P=0.530N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.500N P=1.000 P=0.500N (e) | |COCH-ARM / FISHERS | P=0.104 P=0.187 P=0.222 P=0.311 |P=0.188N P=0.375 P=0.700N P=0.500N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Inflammation Acute | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/31 (29%) 3/30 (10%) 10/27 (37%) 6/10 (60%) |0/3 (0%) 0/5 (0%) 0/2 (0%) 0/1 (0%) | |POLY-3 ADJUSTED (b)| 29.9% 10.4% 38.7% 64.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 5/23 (22%) 2/25 (8%) 8/21 (38%) 3/6 (50%) |0/2 (0%) 0/5 (0%) 0/2 (0%) 0/0 (0%) | |FIRST INCIDENCE | 513 625 429 481 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060 P=0.052N P=0.452 P=0.209 |(e) (e) (e) (e) | |POLY 3 | P=0.016 * P=0.060N P=0.341 P=0.062 |(e) (e) (e) (e) | |POLY 1.5 | P=0.017 * P=0.059N P=0.347 P=0.067 |(e) (e) (e) (e) | |POLY 6 | P=0.016 * P=0.060N P=0.337 P=0.060 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.114 P=0.081N P=0.387 P=0.302 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.024 * P=0.060N P=0.356 P=0.084 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 19/31 (61%) 27/30 (90%) 16/27 (59%) 2/10 (20%) |2/3 (67%) 5/5 (100%) 2/2 (100%) 0/1 (0%) | |POLY-3 ADJUSTED (b)| 64.5% 91.1% 62.0% 28.0% |72.3% 100.0% 100.0% 0.0% | |TERMINAL (d) | 15/23 (65%) 23/25 (92%) 12/21 (57%) 2/6 (33%) |2/2 (100%) 5/5 (100%) 2/2 (100%) 0/0 (0%) | |FIRST INCIDENCE | 638 605 502 729 (T) |730 (T) 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.022N* P=0.101 P=0.393N P=0.046N* |P=1.000N P=1.000N P=1.000N P=1.000 | |POLY 3 | P=0.059N P=0.010 * P=0.536N P=0.098N |P=0.248N P=0.507 P=0.666 P=0.511N | |POLY 1.5 | P=0.030N* P=0.009 ** P=0.545N P=0.059N |P=0.268N P=0.445 P=0.619 P=0.504N | |POLY 6 | P=0.088N P=0.013 * P=0.512N P=0.144N |P=0.211N P=0.655 P=0.769 P=0.530N | |LOGISTIC REGRESSION| P=0.055N P=0.014 * P=0.570N P=0.105N |P=1.000N P=1.000N P=1.000N (e) | |COCH-ARM / FISHERS | P=0.011N* P=0.010 * P=0.544N P=0.027N* |P=0.328N P=0.375 P=0.600 P=0.500N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |17/50 (34%) 14/50 (28%) 18/50 (36%) 10/49 (20%) | |POLY-3 ADJUSTED (b)| |37.0% 31.9% 37.8% 28.0% | |TERMINAL (d) | |13/35 (37%) 13/35 (37%) 17/43 (40%) 8/25 (32%) | |FIRST INCIDENCE | |625 405 701 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.330N P=0.337N P=0.388N P=0.344N | |POLY 3 | |P=0.298N P=0.390N P=0.553 P=0.268N | |POLY 1.5 | |P=0.221N P=0.374N P=0.533 P=0.192N | |POLY 6 | |P=0.366N P=0.397N P=0.578 P=0.345N | |LOGISTIC REGRESSION| |P=0.294N P=0.388N P=0.549N P=0.262N | |COCH-ARM / FISHERS | |P=0.111N P=0.333N P=0.500 P=0.098N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 1/50 (2%) 4/50 (8%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| |0.0% 2.3% 8.4% 2.9% | |TERMINAL (d) | |0/35 (0%) 0/35 (0%) 3/43 (7%) 0/25 (0%) | |FIRST INCIDENCE | |--- 405 716 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.264 P=0.496 P=0.094 P=0.492 | |POLY 3 | |P=0.193 P=0.494 P=0.068 P=0.450 | |POLY 1.5 | |P=0.237 P=0.495 P=0.065 P=0.466 | |POLY 6 | |P=0.161 P=0.496 P=0.072 P=0.438 | |LOGISTIC REGRESSION| |P=0.496 P=0.733 P=0.078 P=0.894 | |COCH-ARM / FISHERS | |P=0.330 P=0.500 P=0.059 P=0.495 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 3/50 (6%) 2/50 (4%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| |4.4% 6.8% 4.2% 2.9% | |TERMINAL (d) | |2/35 (6%) 2/35 (6%) 2/43 (5%) 1/25 (4%) | |FIRST INCIDENCE | |730 (T) 405 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.402N P=0.498 P=0.619N P=0.617N | |POLY 3 | |P=0.403N P=0.487 P=0.675N P=0.595N | |POLY 1.5 | |P=0.378N P=0.489 P=0.682N P=0.565N | |POLY 6 | |P=0.419N P=0.491 P=0.664N P=0.618N | |LOGISTIC REGRESSION| |P=0.343N P=0.531 P=0.619N P=0.617N | |COCH-ARM / FISHERS | |P=0.320N P=0.500 P=0.691N P=0.508N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |7/50 (14%) 16/50 (32%) 11/50 (22%) 6/49 (12%) | |POLY-3 ADJUSTED (b)| |15.1% 36.1% 22.8% 17.3% | |TERMINAL (d) | |5/35 (14%) 12/35 (34%) 9/43 (21%) 2/25 (8%) | |FIRST INCIDENCE | |362 405 602 641 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.447N P=0.032 * P=0.348 P=0.491 | |POLY 3 | |P=0.475N P=0.017 * P=0.244 P=0.516 | |POLY 1.5 | |P=0.385N P=0.019 * P=0.232 P=0.584 | |POLY 6 | |P=0.527N P=0.018 * P=0.266 P=0.469 | |LOGISTIC REGRESSION| |P=0.318N P=0.028 * P=0.164 P=0.610N | |COCH-ARM / FISHERS | |P=0.216N P=0.028 * P=0.218 P=0.516N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 1/50 (2%) 3/50 (6%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| |0.0% 2.3% 6.3% 0.0% | |TERMINAL (d) | |0/35 (0%) 0/35 (0%) 2/43 (5%) 0/25 (0%) | |FIRST INCIDENCE | |--- 405 716 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.575 P=0.496 P=0.162 (e) | |POLY 3 | |P=0.445 P=0.494 P=0.129 (e) | |POLY 1.5 | |P=0.513 P=0.495 P=0.125 (e) | |POLY 6 | |P=0.391 P=0.496 P=0.135 (e) | |LOGISTIC REGRESSION| |P=0.576N P=0.733 P=0.139 (e) | |COCH-ARM / FISHERS | |P=0.628 P=0.500 P=0.121 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/48 (4%) | |POLY-3 ADJUSTED (b)| 2.2% 2.1% 0.0% 3.2% |0.0% 0.0% 0.0% 5.6% | |TERMINAL (d) | 1/35 (3%) 1/43 (2%) 0/43 (0%) 1/22 (5%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- 729 (T) |--- --- --- 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.598 P=0.715N P=0.459N P=0.655 |P=0.046 * (e) (e) P=0.229 | |POLY 3 | P=0.598N P=0.748N P=0.492N P=0.671 |P=0.038 * (e) (e) P=0.189 | |POLY 1.5 | P=0.613N P=0.751N P=0.494N P=0.709 |P=0.039 * (e) (e) P=0.201 | |POLY 6 | P=0.589N P=0.742N P=0.486N P=0.636 |P=0.038 * (e) (e) P=0.179 | |LOGISTIC REGRESSION| P=0.598 P=0.715N (e) P=0.655 |P=0.139 (e) (e) P=0.472 | |COCH-ARM / FISHERS | P=0.612N P=0.747N P=0.495N P=0.747N |P=0.043 * (e) (e) P=0.237 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Parathyroid Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/42 (2%) 2/35 (6%) 1/39 (3%) 1/38 (3%) |0/39 (0%) 0/39 (0%) 0/34 (0%) 0/40 (0%) | |POLY-3 ADJUSTED (b)| 2.5% 6.1% 2.8% 3.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/33 (3%) 2/30 (7%) 1/32 (3%) 0/21 (0%) |0/29 (0%) 0/28 (0%) 0/30 (0%) 0/19 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 481 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.599 P=0.467 P=0.755 P=0.686 |(e) (e) (e) (e) | |POLY 3 | P=0.587 P=0.434 P=0.737 P=0.676 |(e) (e) (e) (e) | |POLY 1.5 | P=0.591N P=0.435 P=0.739 P=0.701 |(e) (e) (e) (e) | |POLY 6 | P=0.556 P=0.435 P=0.738 P=0.655 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.502N P=0.467 P=0.755 P=0.654N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.548N P=0.431 P=0.734 P=0.728 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/49 (0%) 0/49 (0%) 0/46 (0%) |2/49 (4%) 3/49 (6%) 6/49 (12%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 7.0% 12.8% 5.8% | |TERMINAL (d) | 0/35 (0%) 0/42 (0%) 0/42 (0%) 0/22 (0%) |0/35 (0%) 3/35 (9%) 6/43 (14%) 2/25 (8%) | |FIRST INCIDENCE | --- --- --- --- |625 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.399 P=0.494 P=0.201 P=0.564 | |POLY 3 | (e) (e) (e) (e) |P=0.351 P=0.475 P=0.147 P=0.591 | |POLY 1.5 | (e) (e) (e) (e) |P=0.422 P=0.481 P=0.142 P=0.629 | |POLY 6 | (e) (e) (e) (e) |P=0.296 P=0.473 P=0.154 P=0.558 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.405 P=0.492 P=0.135 P=0.628 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.558 P=0.500 P=0.134 P=0.691N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 35 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 2/49 (4%) 5/49 (10%) 3/46 (7%) |1/49 (2%) 0/49 (0%) 2/49 (4%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 2.3% 4.3% 10.9% 10.1% |2.2% 0.0% 4.3% 5.8% | |TERMINAL (d) | 1/35 (3%) 2/42 (5%) 4/42 (10%) 3/22 (14%) |1/35 (3%) 0/35 (0%) 2/43 (5%) 1/25 (4%) | |FIRST INCIDENCE | 729 (T) 729 (T) 694 729 (T) |730 (T) --- 730 (T) 641 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.065 P=0.564 P=0.149 P=0.156 |P=0.159 P=0.500N P=0.572 P=0.383 | |POLY 3 | P=0.070 P=0.519 P=0.111 P=0.182 |P=0.179 P=0.509N P=0.519 P=0.414 | |POLY 1.5 | P=0.103 P=0.514 P=0.108 P=0.217 |P=0.200 P=0.507N P=0.511 P=0.443 | |POLY 6 | P=0.052 P=0.526 P=0.118 P=0.155 |P=0.165 P=0.508N P=0.529 P=0.392 | |LOGISTIC REGRESSION| P=0.057 P=0.564 P=0.118 P=0.156 |P=0.175 (e) P=0.572 P=0.415 | |COCH-ARM / FISHERS | P=0.196 P=0.508 P=0.107 P=0.292 |P=0.245 P=0.500N P=0.500 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 2/49 (4%) 0/49 (0%) 0/46 (0%) |9/49 (18%) 12/49 (24%) 10/49 (20%) 11/49 (22%) | |POLY-3 ADJUSTED (b)| 4.5% 4.3% 0.0% 0.0% |20.0% 27.8% 21.3% 31.9% | |TERMINAL (d) | 2/35 (6%) 2/42 (5%) 0/42 (0%) 0/22 (0%) |6/35 (17%) 11/35 (31%) 10/43 (23%) 9/25 (36%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |625 568 730 (T) 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.116N P=0.628N P=0.199N P=0.345N |P=0.156 P=0.305 P=0.519N P=0.138 | |POLY 3 | P=0.098N P=0.674N P=0.229N P=0.335N |P=0.207 P=0.269 P=0.540 P=0.171 | |POLY 1.5 | P=0.098N P=0.679N P=0.231N P=0.301N |P=0.272 P=0.279 P=0.525 P=0.243 | |POLY 6 | P=0.098N P=0.667N P=0.223N P=0.365N |P=0.167 P=0.270 P=0.560 P=0.123 | |LOGISTIC REGRESSION| P=0.116N P=0.628N (e) (e) |P=0.148 P=0.273 P=0.572 P=0.121 | |COCH-ARM / FISHERS | P=0.089N P=0.684N P=0.242N P=0.258N |P=0.430 P=0.312 P=0.500 P=0.401 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 36 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Preputial Gland | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 20/49 (41%) 25/50 (50%) 27/50 (54%) 26/49 (53%) | | |POLY-3 ADJUSTED (b)| 43.1% 52.1% 54.9% 65.4% | | |TERMINAL (d) | 15/35 (43%) 24/43 (56%) 23/43 (54%) 12/22 (55%) | | |FIRST INCIDENCE | 513 605 429 481 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.521 P=0.366 P=0.010 * | | |POLY 3 | P=0.026 * P=0.249 P=0.169 P=0.028 * | | |POLY 1.5 | P=0.047 * P=0.244 P=0.152 P=0.052 | | |POLY 6 | P=0.017 * P=0.259 P=0.195 P=0.017 * | | |LOGISTIC REGRESSION| P=0.102 P=0.279 P=0.128 P=0.119 | | |COCH-ARM / FISHERS | P=0.150 P=0.237 P=0.133 P=0.156 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/49 (27%) 6/50 (12%) 7/50 (14%) 3/49 (6%) | | |POLY-3 ADJUSTED (b)| 28.1% 12.6% 14.9% 9.4% | | |TERMINAL (d) | 9/35 (26%) 6/43 (14%) 7/43 (16%) 1/22 (5%) | | |FIRST INCIDENCE | 501 729 (T) 729 (T) 481 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.044N* P=0.027N* P=0.049N* P=0.065N | | |POLY 3 | P=0.032N* P=0.051N P=0.096N P=0.044N* | | |POLY 1.5 | P=0.021N* P=0.053N P=0.098N P=0.022N* | | |POLY 6 | P=0.043N* P=0.049N* P=0.090N P=0.077N | | |LOGISTIC REGRESSION| P=0.015N* P=0.059N P=0.095N P=0.012N* | | |COCH-ARM / FISHERS | P=0.008N** P=0.056N P=0.096N P=0.006N** | | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 37 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Preputial Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 18/49 (37%) 20/50 (40%) 18/50 (36%) 16/49 (33%) | | |POLY-3 ADJUSTED (b)| 39.2% 41.1% 38.1% 48.1% | | |TERMINAL (d) | 13/35 (37%) 17/43 (40%) 16/43 (37%) 12/22 (55%) | | |FIRST INCIDENCE | 638 605 655 481 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.153 P=0.475N P=0.325N P=0.190 | | |POLY 3 | P=0.303 P=0.510 P=0.540N P=0.290 | | |POLY 1.5 | P=0.453 P=0.485 P=0.551N P=0.460 | | |POLY 6 | P=0.208 P=0.542 P=0.515N P=0.166 | | |LOGISTIC REGRESSION| P=0.262 P=0.482 P=0.513N P=0.237 | | |COCH-ARM / FISHERS | P=0.314N P=0.449 P=0.553N P=0.416N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Prostate | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 24/49 (49%) 31/50 (62%) 34/50 (68%) 32/50 (64%) | | |POLY-3 ADJUSTED (b)| 52.1% 64.3% 70.2% 75.2% | | |TERMINAL (d) | 21/35 (60%) 29/43 (67%) 31/43 (72%) 15/22 (68%) | | |FIRST INCIDENCE | 501 625 439 481 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.435 P=0.231 P<0.001 ** | | |POLY 3 | P=0.014 * P=0.157 P=0.050 P=0.016 * | | |POLY 1.5 | P=0.026 * P=0.146 P=0.045 * P=0.029 * | | |POLY 6 | P=0.009 ** P=0.179 P=0.064 P=0.010 * | | |LOGISTIC REGRESSION| P=0.017 * P=0.190 P=0.045 * P=0.047 * | | |COCH-ARM / FISHERS | P=0.098 P=0.135 P=0.043 * P=0.096 | | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 38 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 22/49 (45%) 35/50 (70%) 36/50 (72%) 29/50 (58%) |27/48 (56%) 29/50 (58%) 32/50 (64%) 27/49 (55%) | |POLY-3 ADJUSTED (b)| 46.2% 71.4% 72.5% 74.5% |60.3% 65.8% 65.1% 65.1% | |TERMINAL (d) | 16/35 (46%) 31/43 (72%) 31/43 (72%) 18/22 (82%) |22/35 (63%) 25/35 (71%) 28/43 (65%) 16/25 (64%) | |FIRST INCIDENCE | 501 605 429 481 |623 521 533 212 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.097 P=0.071 P=0.002 ** |P=0.072 P=0.413 P=0.536N P=0.104 | |POLY 3 | P=0.005 ** P=0.008 ** P=0.006 ** P=0.005 ** |P=0.387 P=0.374 P=0.397 P=0.404 | |POLY 1.5 | P=0.026 * P=0.008 ** P=0.005 ** P=0.021 * |P=0.449 P=0.414 P=0.352 P=0.481 | |POLY 6 | P<0.001 ** P=0.009 ** P=0.007 ** P<0.001 ** |P=0.350 P=0.355 P=0.452 P=0.353 | |LOGISTIC REGRESSION| P=0.052 P=0.008 ** P=0.004 ** P=0.038 * |P=0.259 P=0.341 P=0.348 P=0.422 | |COCH-ARM / FISHERS | P=0.232 P=0.010 * P=0.005 ** P=0.135 |P=0.501N P=0.512 P=0.282 P=0.536N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Salivary Glands | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/48 (0%) 0/50 (0%) 2/50 (4%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 2.2% 0.0% 2.1% 0.0% |0.0% 0.0% 4.2% 2.9% | |TERMINAL (d) | 1/35 (3%) 0/43 (0%) 0/43 (0%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 2/43 (5%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) --- 439 --- |--- --- 730 (T) 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.446N P=0.459N P=0.738N P=0.593N |P=0.173 (e) P=0.285 P=0.432 | |POLY 3 | P=0.446N P=0.488N P=0.747N P=0.571N |P=0.155 (e) P=0.256 P=0.450 | |POLY 1.5 | P=0.435N P=0.492N P=0.752N P=0.543N |P=0.185 (e) P=0.252 P=0.469 | |POLY 6 | P=0.477N P=0.484N P=0.740N P=0.595N |P=0.132 (e) P=0.260 P=0.435 | |LOGISTIC REGRESSION| P=0.203N (e) P=0.700N (e) |P=0.173 (e) P=0.285 P=0.449 | |COCH-ARM / FISHERS | P=0.402N P=0.495N P=0.747N P=0.495N |P=0.247 (e) P=0.258 P=0.505 | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 39 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Seminal Vesicle | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 0.0% 4.2% 4.3% 0.0% | | |TERMINAL (d) | 0/35 (0%) 1/43 (2%) 2/43 (5%) 0/22 (0%) | | |FIRST INCIDENCE | --- 644 729 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.651N P=0.265 P=0.285 (e) | | |POLY 3 | P=0.534 P=0.252 P=0.247 (e) | | |POLY 1.5 | P=0.601N P=0.248 P=0.244 (e) | | |POLY 6 | P=0.466 P=0.258 P=0.253 (e) | | |LOGISTIC REGRESSION| P=0.607N P=0.211 P=0.285 (e) | | |COCH-ARM / FISHERS | P=0.495N P=0.253 P=0.253 (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/50 (4%) 3/50 (6%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.2% 6.3% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/43 (5%) 2/43 (5%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) 439 --- |607 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.609 P=0.285 P=0.148 (e) |P=0.345N P=0.522N P=0.504N P=0.583N | |POLY 3 | P=0.437 P=0.250 P=0.130 (e) |P=0.258N P=0.511N P=0.491N P=0.553N | |POLY 1.5 | P=0.545 P=0.247 P=0.126 (e) |P=0.278N P=0.508N P=0.495N P=0.534N | |POLY 6 | P=0.358 P=0.256 P=0.136 (e) |P=0.239N P=0.512N P=0.487N P=0.568N | |LOGISTIC REGRESSION| P=0.492N P=0.285 P=0.138 (e) |P=0.246N P=0.447N P=0.611N P=0.433N | |COCH-ARM / FISHERS | P=0.525N P=0.253 P=0.125 (e) |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 40 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.2% 4.3% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/43 (5%) 2/43 (5%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.642N P=0.285 P=0.285 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.534 P=0.250 P=0.247 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.601N P=0.247 P=0.244 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.466 P=0.256 P=0.253 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.285 P=0.285 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.495N P=0.253 P=0.253 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin: Epidermis | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.2% 4.2% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/43 (5%) 1/43 (2%) 0/22 (0%) |0/35 (0%) 0/35 (0%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) 439 --- |607 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.604N P=0.285 P=0.262 (e) |P=0.345N P=0.522N P=0.504N P=0.583N | |POLY 3 | P=0.534 P=0.250 P=0.251 (e) |P=0.258N P=0.511N P=0.491N P=0.553N | |POLY 1.5 | P=0.600N P=0.247 P=0.246 (e) |P=0.278N P=0.508N P=0.495N P=0.534N | |POLY 6 | P=0.469 P=0.256 P=0.258 (e) |P=0.239N P=0.512N P=0.487N P=0.568N | |LOGISTIC REGRESSION| P=0.410N P=0.285 P=0.300 (e) |P=0.246N P=0.447N P=0.611N P=0.433N | |COCH-ARM / FISHERS | P=0.495N P=0.253 P=0.253 (e) |P=0.306N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 41 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 12/49 (24%) 13/50 (26%) 14/50 (28%) 4/50 (8%) |18/50 (36%) 22/50 (44%) 15/49 (31%) 10/49 (20%) | |POLY-3 ADJUSTED (b)| 25.7% 26.2% 28.1% 12.8% |39.0% 47.9% 31.1% 28.0% | |TERMINAL (d) | 7/35 (20%) 7/43 (16%) 8/43 (19%) 3/22 (14%) |14/35 (40%) 16/35 (46%) 12/43 (28%) 5/25 (20%) | |FIRST INCIDENCE | 513 563 429 710 |607 405 589 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.201N P=0.519N P=0.563 P=0.207N |P=0.122N P=0.273 P=0.161N P=0.299N | |POLY 3 | P=0.197N P=0.569 P=0.488 P=0.146N |P=0.088N P=0.256 P=0.278N P=0.210N | |POLY 1.5 | P=0.102N P=0.549 P=0.464 P=0.078N |P=0.057N P=0.254 P=0.310N P=0.144N | |POLY 6 | P=0.307N P=0.585N P=0.522 P=0.238N |P=0.112N P=0.273 P=0.238N P=0.272N | |LOGISTIC REGRESSION| P=0.010N* P=0.387 P=0.363 P=0.106N |P=0.045N* P=0.242 P=0.342N P=0.216N | |COCH-ARM / FISHERS | P=0.020N* P=0.523 P=0.433 P=0.024N* |P=0.021N* P=0.270 P=0.361N P=0.066N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 4/50 (8%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 3/50 (6%) 1/49 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 2.2% 8.4% 2.1% 0.0% |2.2% 7.0% 2.1% 0.0% | |TERMINAL (d) | 1/35 (3%) 4/43 (9%) 1/43 (2%) 0/22 (0%) |0/35 (0%) 3/35 (9%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |645 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.249N P=0.246 P=0.715N P=0.593N |P=0.257N P=0.298 P=0.733N P=0.583N | |POLY 3 | P=0.251N P=0.197 P=0.751N P=0.571N |P=0.264N P=0.286 P=0.753N P=0.555N | |POLY 1.5 | P=0.217N P=0.192 P=0.754N P=0.543N |P=0.245N P=0.291 P=0.758N P=0.537N | |POLY 6 | P=0.286N P=0.204 P=0.745N P=0.595N |P=0.276N P=0.285 P=0.746N P=0.569N | |LOGISTIC REGRESSION| P=0.249N P=0.246 P=0.715N (e) |P=0.250N P=0.291 P=0.738 P=0.485N | |COCH-ARM / FISHERS | P=0.159N P=0.187 P=0.747N P=0.495N |P=0.205N P=0.309 P=0.747 P=0.505N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 42 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 3/50 (6%) 1/50 (2%) 1/50 (2%) |3/50 (6%) 2/50 (4%) 1/50 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.4% 6.3% 2.1% 3.2% |6.6% 4.7% 2.1% 2.9% | |TERMINAL (d) | 0/35 (0%) 2/43 (5%) 1/43 (2%) 0/22 (0%) |2/35 (6%) 2/35 (6%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | 513 644 729 (T) 710 |625 730 (T) 730 (T) 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.448N P=0.551 P=0.465N P=0.685N |P=0.270N P=0.506N P=0.252N P=0.433N | |POLY 3 | P=0.363N P=0.521 P=0.491N P=0.628N |P=0.230N P=0.526N P=0.290N P=0.405N | |POLY 1.5 | P=0.337N P=0.516 P=0.494N P=0.579N |P=0.222N P=0.519N P=0.296N P=0.369N | |POLY 6 | P=0.387N P=0.530 P=0.485N P=0.669N |P=0.233N P=0.526N P=0.281N P=0.435N | |LOGISTIC REGRESSION| P=0.247N P=0.388 P=0.461N P=0.469N |P=0.252N P=0.518N P=0.309N P=0.380N | |COCH-ARM / FISHERS | P=0.274N P=0.510 P=0.492N P=0.492N |P=0.199N P=0.500N P=0.309N P=0.309N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 2/50 (4%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.3% 2.1% 4.3% 0.0% |2.2% 4.6% 4.2% 2.9% | |TERMINAL (d) | 0/35 (0%) 0/43 (0%) 2/43 (5%) 0/22 (0%) |0/35 (0%) 1/35 (3%) 1/43 (2%) 0/25 (0%) | |FIRST INCIDENCE | 501 625 729 (T) --- |625 722 589 694 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.322N P=0.486N P=0.659N P=0.394N |P=0.562 P=0.492 P=0.529 P=0.683 | |POLY 3 | P=0.298N P=0.487N P=0.689N P=0.335N |P=0.540 P=0.481 P=0.519 P=0.698 | |POLY 1.5 | P=0.261N P=0.490N P=0.690N P=0.294N |P=0.583 P=0.486 P=0.511 P=0.721 | |POLY 6 | P=0.342N P=0.481N P=0.683N P=0.374N |P=0.506 P=0.481 P=0.529 P=0.679 | |LOGISTIC REGRESSION| P=0.061N P=0.682 P=0.639N P=0.051N |P=0.566N P=0.498 P=0.395 P=0.777 | |COCH-ARM / FISHERS | P=0.196N P=0.492N P=0.684N P=0.242N |P=0.556N P=0.500 P=0.500 P=0.753N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 43 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 2.1% 0.0% 6.3% |2.2% 2.3% 0.0% 2.8% | |TERMINAL (d) | 0/35 (0%) 1/43 (2%) 0/43 (0%) 1/22 (5%) |1/35 (3%) 1/35 (3%) 0/43 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 729 (T) --- 481 |730 (T) 730 (T) --- 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.085 P=0.541 (e) P=0.189 |P=0.651 P=0.762 P=0.459N P=0.719 | |POLY 3 | P=0.108 P=0.512 (e) P=0.171 |P=0.607N P=0.750 P=0.490N P=0.706 | |POLY 1.5 | P=0.116 P=0.508 (e) P=0.194 |P=0.614N P=0.752 P=0.494N P=0.726 | |POLY 6 | P=0.111 P=0.516 (e) P=0.152 |P=0.596N P=0.751 P=0.484N P=0.688 | |LOGISTIC REGRESSION| P=0.177 P=0.541 (e) P=0.281 |P=0.485N P=0.762 (e) P=0.608N | |COCH-ARM / FISHERS | P=0.142 P=0.505 (e) P=0.253 |P=0.616N P=0.753N P=0.500N P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Glandular: Glands | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 17/49 (35%) 10/50 (20%) 20/50 (40%) 5/50 (10%) |16/50 (32%) 9/50 (18%) 10/50 (20%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 37.8% 21.0% 42.6% 16.1% |34.3% 20.9% 21.0% 8.3% | |TERMINAL (d) | 16/35 (46%) 10/43 (23%) 19/43 (44%) 5/22 (23%) |13/35 (37%) 8/35 (23%) 10/43 (23%) 1/25 (4%) | |FIRST INCIDENCE | 712 729 (T) 694 729 (T) |362 709 730 (T) 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.150N P=0.020N* P=0.523N P=0.054N |P=0.006N** P=0.085N P=0.045N* P=0.010N* | |POLY 3 | P=0.172N P=0.058N P=0.399 P=0.037N* |P=0.005N** P=0.117N P=0.111N P=0.005N** | |POLY 1.5 | P=0.077N P=0.066N P=0.379 P=0.014N* |P=0.003N** P=0.107N P=0.118N P=0.002N** | |POLY 6 | P=0.290N P=0.049N* P=0.444 P=0.079N |P=0.007N** P=0.118N P=0.100N P=0.008N** | |LOGISTIC REGRESSION| P=0.174N P=0.023N* P=0.573 P=0.055N |P=0.003N** P=0.099N P=0.119N P<0.001N** | |COCH-ARM / FISHERS | P=0.013N* P=0.078N P=0.368 P=0.003N** |P<0.001N** P=0.083N P=0.127N P<0.001N** | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 44 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Testes | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 4.5% 4.2% 2.1% 0.0% | | |TERMINAL (d) | 2/35 (6%) 2/43 (5%) 1/43 (2%) 0/22 (0%) | | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.181N P=0.619N P=0.428N P=0.345N | | |POLY 3 | P=0.173N P=0.673N P=0.485N P=0.328N | | |POLY 1.5 | P=0.157N P=0.679N P=0.490N P=0.290N | | |POLY 6 | P=0.192N P=0.664N P=0.475N P=0.364N | | |LOGISTIC REGRESSION| P=0.181N P=0.619N P=0.428N (e) | | |COCH-ARM / FISHERS | P=0.122N P=0.684N P=0.492N P=0.242N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 2.2% 4.2% 4.3% 0.0% | | |TERMINAL (d) | 1/35 (3%) 2/43 (5%) 2/43 (5%) 0/22 (0%) | | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.418N P=0.572 P=0.572 P=0.593N | | |POLY 3 | P=0.431N P=0.520 P=0.515 P=0.571N | | |POLY 1.5 | P=0.381N P=0.515 P=0.510 P=0.543N | | |POLY 6 | P=0.486N P=0.528 P=0.525 P=0.595N | | |LOGISTIC REGRESSION| P=0.418N P=0.572 P=0.572 (e) | | |COCH-ARM / FISHERS | P=0.291N P=0.508 P=0.508 P=0.495N | | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 45 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 16/40 (40%) 19/48 (40%) 18/46 (39%) 17/49 (35%) |20/47 (43%) 17/43 (40%) 23/46 (50%) 19/48 (40%) | |POLY-3 ADJUSTED (b)| 41.0% 40.9% 40.9% 47.0% |44.6% 42.4% 52.2% 52.5% | |TERMINAL (d) | 11/31 (36%) 17/42 (41%) 15/39 (39%) 9/22 (41%) |16/34 (47%) 14/32 (44%) 23/41 (56%) 16/25 (64%) | |FIRST INCIDENCE | 501 605 502 481 |362 374 730 (T) 212 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.088 P=0.460N P=0.482N P=0.163 |P=0.146 P=0.426N P=0.523N P=0.225 | |POLY 3 | P=0.337 P=0.585N P=0.585N P=0.383 |P=0.207 P=0.506N P=0.308 P=0.314 | |POLY 1.5 | P=0.477 P=0.579N P=0.578N P=0.532 |P=0.333 P=0.501N P=0.304 P=0.459 | |POLY 6 | P=0.238 P=0.584 P=0.583N P=0.260 |P=0.127 P=0.495N P=0.322 P=0.202 | |LOGISTIC REGRESSION| P=0.408N P=0.566 P=0.554N P=0.448N |P=0.348 P=0.458N P=0.341 P=0.437 | |COCH-ARM / FISHERS | P=0.321N P=0.570N P=0.555N P=0.383N |P=0.484N P=0.470N P=0.304 P=0.466N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Ectopic Parathyroid Gland | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/40 (8%) 1/48 (2%) 3/46 (7%) 1/49 (2%) |1/47 (2%) 1/43 (2%) 1/46 (2%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 8.1% 2.2% 7.0% 3.3% |2.3% 2.6% 2.3% 0.0% | |TERMINAL (d) | 2/31 (7%) 1/42 (2%) 3/39 (8%) 1/22 (5%) |1/34 (3%) 1/32 (3%) 1/41 (2%) 0/25 (0%) | |FIRST INCIDENCE | 694 729 (T) 729 (T) 729 (T) |730 (T) 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.460N P=0.220N P=0.560N P=0.452N |P=0.357N P=0.748 P=0.720N P=0.561N | |POLY 3 | P=0.390N P=0.235N P=0.596N P=0.380N |P=0.350N P=0.733 P=0.755N P=0.548N | |POLY 1.5 | P=0.343N P=0.237N P=0.597N P=0.321N |P=0.335N P=0.734 P=0.759N P=0.529N | |POLY 6 | P=0.434N P=0.232N P=0.591N P=0.439N |P=0.360N P=0.734 P=0.749N P=0.563N | |LOGISTIC REGRESSION| P=0.461N P=0.231N P=0.588N P=0.441N |P=0.357N P=0.748 P=0.720N (e) | |COCH-ARM / FISHERS | P=0.255N P=0.243N P=0.593N P=0.236N |P=0.303N P=0.730 P=0.747 P=0.495N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 46 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/40 (0%) 0/48 (0%) 0/46 (0%) 0/49 (0%) |0/47 (0%) 0/43 (0%) 2/46 (4%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 4.5% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/42 (0%) 0/39 (0%) 0/22 (0%) |0/34 (0%) 0/32 (0%) 2/41 (5%) 0/25 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.550 (e) P=0.280 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.440 (e) P=0.242 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.503 (e) P=0.238 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.384 (e) P=0.249 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) P=0.280 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.604 (e) P=0.242 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |5/49 (10%) 3/50 (6%) 3/50 (6%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 4.5% 4.2% 4.3% 0.0% |11.3% 7.0% 6.3% 11.5% | |TERMINAL (d) | 2/35 (6%) 2/43 (5%) 2/43 (5%) 0/22 (0%) |5/35 (14%) 2/35 (6%) 3/43 (7%) 4/25 (16%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |730 (T) 709 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.249N P=0.619N P=0.619N P=0.345N |P=0.500 P=0.353N P=0.249N P=0.572 | |POLY 3 | P=0.258N P=0.673N P=0.679N P=0.328N |P=0.553N P=0.373N P=0.320N P=0.624 | |POLY 1.5 | P=0.222N P=0.679N P=0.683N P=0.290N |P=0.530N P=0.367N P=0.330N P=0.593N | |POLY 6 | P=0.298N P=0.664N P=0.668N P=0.364N |P=0.543 P=0.371N P=0.306N P=0.577 | |LOGISTIC REGRESSION| P=0.249N P=0.619N P=0.619N (e) |P=0.488 P=0.356N P=0.249N P=0.572 | |COCH-ARM / FISHERS | P=0.159N P=0.684N P=0.684N P=0.242N |P=0.472N P=0.346N P=0.346N P=0.487N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 47 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Tooth | | Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/6 (100%) 0/0 (0%) 1/1 (100%) 2/2 (100%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 ADJUSTED (b)| 100.0% 0.0% 100.0% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 4/4 (100%) 0/0 (0%) 1/1 (100%) 2/2 (100%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 663 --- 729 (T) 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Urinary Bladder | | Infiltration Cellular Mononuclear Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 12/49 (24%) 17/50 (34%) 9/50 (18%) 10/50 (20%) |28/50 (56%) 31/50 (62%) 29/50 (58%) 22/50 (44%) | |POLY-3 ADJUSTED (b)| 26.2% 35.2% 18.4% 29.8% |60.0% 66.8% 60.4% 55.1% | |TERMINAL (d) | 9/35 (26%) 15/43 (35%) 6/43 (14%) 6/22 (27%) |24/35 (69%) 23/35 (66%) 28/43 (65%) 12/25 (48%) | |FIRST INCIDENCE | 583 625 429 481 |362 374 589 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478 P=0.384 P=0.194N P=0.351 |P=0.533N P=0.338 P=0.230N P=0.474 | |POLY 3 | P=0.423N P=0.235 P=0.254N P=0.463 |P=0.283N P=0.318 P=0.567 P=0.403N | |POLY 1.5 | P=0.336N P=0.223 P=0.271N P=0.590 |P=0.206N P=0.309 P=0.536 P=0.314N | |POLY 6 | P=0.477N P=0.255 P=0.230N P=0.353 |P=0.330N P=0.365 P=0.557N P=0.452N | |LOGISTIC REGRESSION| P=0.232N P=0.225 P=0.296N P=0.548 |P=0.252N P=0.281 P=0.549N P=0.392N | |COCH-ARM / FISHERS | P=0.172N P=0.207 P=0.294N P=0.384N |P=0.082N P=0.342 P=0.500 P=0.159N | |=================================================================================================================================| Date: 10/25/99 EXPERIMENT: 88050 TEST: 06 Page 48 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHACRYLONITRILE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |23/50 (46%) 28/50 (56%) 31/50 (62%) 20/50 (40%) | |POLY-3 ADJUSTED (b)| |49.6% 60.7% 62.4% 49.0% | |TERMINAL (d) | |18/35 (51%) 21/35 (60%) 26/43 (61%) 10/25 (40%) | |FIRST INCIDENCE | |607 405 533 480 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.325 P=0.219 P=0.344 P=0.337 | |POLY 3 | |P=0.483N P=0.188 P=0.141 P=0.564N | |POLY 1.5 | |P=0.405N P=0.189 P=0.114 P=0.494N | |POLY 6 | |P=0.526N P=0.202 P=0.181 P=0.569 | |LOGISTIC REGRESSION| |P=0.381N P=0.166 P=0.095 P=0.492N | |COCH-ARM / FISHERS | |P=0.237N P=0.212 P=0.080 P=0.343N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 1.5 3 MG/KG 6 MG/KG |0 MG/KG 1.5 3 MG/KG 6 MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |27/50 (54%) 24/50 (48%) 24/50 (48%) 32/50 (64%) | |POLY-3 ADJUSTED (b)| |57.7% 54.4% 50.0% 74.0% | |TERMINAL (d) | |20/35 (57%) 20/35 (57%) 23/43 (54%) 18/25 (72%) | |FIRST INCIDENCE | |593 405 589 343 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.007 ** P=0.365N P=0.099N P=0.017 * | |POLY 3 | |P=0.063 P=0.458N P=0.291N P=0.072 | |POLY 1.5 | |P=0.079 P=0.421N P=0.309N P=0.105 | |POLY 6 | |P=0.053 P=0.482N P=0.273N P=0.054 | |LOGISTIC REGRESSION| |P=0.039 * P=0.440N P=0.250N P=0.092 | |COCH-ARM / FISHERS | |P=0.130 P=0.345N P=0.345N P=0.208 | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Poly-3 adjusted lifetime tumor incidence. (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).