TDMS Study 92013-06 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst 4-METHYLIMIDAZOLE DATE: 01/12/04 EXPERIMENT: 92013 TEST: 06 TIME: 14:42:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92013B PATHOLOGIST: HEATH, JAMES CAS: 822-36-6 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst 4-METHYLIMIDAZOLE DATE: 01/12/04 EXPERIMENT: 92013 TEST: 06 TIME: 14:42:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92013B PATHOLOGIST: HEATH, JAMES CAS: 822-36-6 Mice(B6C3F1) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Bone Marrow Brain Heart Islets, Pancreatic Kidney Liver Lung Ovary Pituitary Gland Prostate Spleen Testes Thyroid Gland NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Southern Research Inst 4-METHYLIMIDAZOLE DATE: 01/12/04 EXPERIMENT: 92013 TEST: 06 TIME: 14:42:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92013B PATHOLOGIST: HEATH, JAMES CAS: 822-36-6 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF 4-METHYLIMIDAZOLE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Adenoma Lung Alveolar/Bronchiolar Carcinoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Stomach, Forestomach Squamous Cell Papilloma All Organs Malignant Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Ovary Granulosa Cell Tumor Benign All Organs Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 1 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 4/48.24 1/47.90 1/45.68 0/47.85 |0/46.61 1/47.80 0/48.01 0/46.05 | |POLY-3 PERCENT (g) | 8.3% 2.1% 2.2% 0.0% |0.0% 2.1% 0.0% 0.0% | |TERMINAL (d) | 4/45 (9%) 1/44 (2%) 1/42 (2%) 0/46 (0%) |0/43 (0%) 1/40 (3%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.035N* P=0.187N P=0.201N P=0.061N |P=0.574N P=0.486 (e) (e) | |POLY 3 | P=0.034N* P=0.181N P=0.196N P=0.062N |P=0.562N P=0.505 (e) (e) | |POLY 1.5 | P=0.034N* P=0.181N P=0.190N P=0.061N |P=0.563N P=0.505 (e) (e) | |POLY 6 | P=0.034N* P=0.182N P=0.203N P=0.062N |P=0.563N P=0.504 (e) (e) | |LOGISTIC REGRESSION| P=0.035N* P=0.187N P=0.201N (e) |(e) P=0.486 (e) (e) | |COCH-ARM / FISHERS | P=0.034N* P=0.181N P=0.181N P=0.059N |P=0.567N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.012N* (e) (e) (e) |P=0.388N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 9/50 (18%) 4/50 (8%) 7/50 (14%) |6/50 (12%) 1/50 (2%) 5/50 (10%) 6/50 (12%) | |POLY-3 RATE (b) | 4/48.24 9/48.10 4/45.68 7/47.85 |6/47.07 1/47.80 5/48.04 6/46.22 | |POLY-3 PERCENT (g) | 8.3% 18.7% 8.8% 14.6% |12.8% 2.1% 10.4% 13.0% | |TERMINAL (d) | 4/45 (9%) 8/44 (18%) 4/42 (10%) 7/46 (15%) |5/43 (12%) 1/40 (3%) 4/43 (9%) 5/40 (13%) | |FIRST INCIDENCE | 729 (T) 676 729 (T) 729 (T) |593 729 (T) 720 685 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.401 P=0.111 P=0.605 P=0.274 |P=0.310 P=0.069N P=0.496N P=0.574 | |POLY 3 | P=0.373 P=0.115 P=0.613 P=0.257 |P=0.323 P=0.054N P=0.486N P=0.608 | |POLY 1.5 | P=0.376 P=0.115 P=0.624 P=0.258 |P=0.329 P=0.054N P=0.486N P=0.617 | |POLY 6 | P=0.369 P=0.115 P=0.601 P=0.256 |P=0.317 P=0.055N P=0.488N P=0.596 | |LOGISTIC REGRESSION| P=0.374 P=0.114 P=0.605 P=0.274 |P=0.329 P=0.057N P=0.489N P=0.618 | |COCH-ARM / FISHERS | P=0.385 P=0.117 P=0.643N P=0.262 |P=0.338 P=0.056N P=0.500N P=0.620N | |ORDER RESTRICTED | P=0.275 (e) (e) (e) |P=0.284 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 2 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/48.29 1/47.90 0/45.68 1/47.85 |1/46.61 1/47.80 0/48.01 2/46.12 | |POLY-3 PERCENT (g) | 2.1% 2.1% 0.0% 2.1% |2.2% 2.1% 0.0% 4.3% | |TERMINAL (d) | 0/45 (0%) 1/44 (2%) 0/42 (0%) 1/46 (2%) |1/43 (2%) 1/40 (3%) 0/43 (0%) 1/40 (3%) | |FIRST INCIDENCE | 715 729 (T) --- 729 (T) |729 (T) 729 (T) --- 711 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.611N P=0.758 P=0.518N P=0.758N |P=0.353 P=0.746 P=0.500N P=0.478 | |POLY 3 | P=0.620N P=0.759 P=0.511N P=0.758 |P=0.364 P=0.755N P=0.494N P=0.496 | |POLY 1.5 | P=0.618N P=0.759 P=0.507N P=0.759 |P=0.366 P=0.755N P=0.495N P=0.500 | |POLY 6 | P=0.621N P=0.758 P=0.515N P=0.758 |P=0.362 P=0.756N P=0.494N P=0.492 | |LOGISTIC REGRESSION| P=0.618N P=0.761 P=0.506N P=0.761 |P=0.356 P=0.746 (e) P=0.491 | |COCH-ARM / FISHERS | P=0.616N P=0.753N P=0.500N P=0.753N |P=0.366 P=0.753N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.542N (e) (e) (e) |P=0.265 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 10/50 (20%) 4/50 (8%) 8/50 (16%) |7/50 (14%) 2/50 (4%) 5/50 (10%) 8/50 (16%) | |POLY-3 RATE (b) | 5/48.29 10/48.10 4/45.68 8/47.85 |7/47.07 2/47.80 5/48.04 8/46.29 | |POLY-3 PERCENT (g) | 10.4% 20.8% 8.8% 16.7% |14.9% 4.2% 10.4% 17.3% | |TERMINAL (d) | 4/45 (9%) 9/44 (21%) 4/42 (10%) 8/46 (17%) |6/43 (14%) 2/40 (5%) 4/43 (9%) 6/40 (15%) | |FIRST INCIDENCE | 715 676 729 (T) 729 (T) |593 729 (T) 720 685 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.421 P=0.127 P=0.544N P=0.291 |P=0.221 P=0.097N P=0.377N P=0.448 | |POLY 3 | P=0.390 P=0.128 P=0.535N P=0.270 |P=0.233 P=0.076N P=0.365N P=0.486 | |POLY 1.5 | P=0.394 P=0.129 P=0.522N P=0.272 |P=0.238 P=0.075N P=0.366N P=0.496 | |POLY 6 | P=0.385 P=0.128 P=0.548N P=0.269 |P=0.228 P=0.078N P=0.367N P=0.473 | |LOGISTIC REGRESSION| P=0.392 P=0.127 P=0.555N P=0.269 |P=0.235 P=0.078N P=0.366N P=0.494 | |COCH-ARM / FISHERS | P=0.404 P=0.131 P=0.500N P=0.277 |P=0.246 P=0.080N P=0.380N P=0.500 | |ORDER RESTRICTED | P=0.292 (e) (e) (e) |P=0.188 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 3 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Intestine Small: Duodenum | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.24 2/47.90 0/45.68 0/47.85 |0/46.61 0/47.80 2/48.01 0/46.05 | |POLY-3 PERCENT (g) | 0.0% 4.2% 0.0% 0.0% |0.0% 0.0% 4.2% 0.0% | |TERMINAL (d) | 0/45 (0%) 2/44 (5%) 0/42 (0%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 2/43 (5%) 0/40 (0%) | |FIRST INCIDENCE | --- 729 (T) --- --- |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.401N P=0.234 (e) (e) |P=0.585 (e) P=0.238 (e) | |POLY 3 | P=0.410N P=0.236 (e) (e) |P=0.582 (e) P=0.244 (e) | |POLY 1.5 | P=0.408N P=0.236 (e) (e) |P=0.589 (e) P=0.243 (e) | |POLY 6 | P=0.412N P=0.235 (e) (e) |P=0.574 (e) P=0.244 (e) | |LOGISTIC REGRESSION| (e) P=0.234 (e) (e) |(e) (e) P=0.238 (e) | |COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) |P=0.595 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.247N (e) (e) (e) |P=0.254 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Intestine Small: Site Unspecified | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.24 3/47.90 0/45.68 0/47.85 |0/46.61 0/47.80 2/48.01 0/46.05 | |POLY-3 PERCENT (g) | 0.0% 6.3% 0.0% 0.0% |0.0% 0.0% 4.2% 0.0% | |TERMINAL (d) | 0/45 (0%) 3/44 (7%) 0/42 (0%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 2/43 (5%) 0/40 (0%) | |FIRST INCIDENCE | --- 729 (T) --- --- |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.308N P=0.117 (e) (e) |P=0.585 (e) P=0.238 (e) | |POLY 3 | P=0.315N P=0.118 (e) (e) |P=0.582 (e) P=0.244 (e) | |POLY 1.5 | P=0.313N P=0.118 (e) (e) |P=0.589 (e) P=0.243 (e) | |POLY 6 | P=0.317N P=0.117 (e) (e) |P=0.574 (e) P=0.244 (e) | |LOGISTIC REGRESSION| (e) P=0.117 (e) (e) |(e) (e) P=0.238 (e) | |COCH-ARM / FISHERS | P=0.311N P=0.121 (e) (e) |P=0.595 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.163N (e) (e) (e) |P=0.254 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 4 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/49 (2%) 0/50 (0%) 1/50 (2%) |0/49 (0%) 3/48 (6%) 0/47 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/47.37 1/47.79 0/45.68 1/47.85 |0/46.61 3/46.38 0/45.13 0/45.05 | |POLY-3 PERCENT (g) | 0.0% 2.1% 0.0% 2.1% |0.0% 6.5% 0.0% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 1/46 (2%) |0/43 (0%) 2/40 (5%) 0/42 (0%) 0/39 (0%) | |FIRST INCIDENCE | --- 613 --- 729 (T) |--- 668 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.408 P=0.500 (e) P=0.504 |P=0.326N P=0.116 (e) (e) | |POLY 3 | P=0.406 P=0.502 (e) P=0.502 |P=0.314N P=0.118 (e) (e) | |POLY 1.5 | P=0.408 P=0.501 (e) P=0.503 |P=0.312N P=0.117 (e) (e) | |POLY 6 | P=0.405 P=0.503 (e) P=0.501 |P=0.316N P=0.118 (e) (e) | |LOGISTIC REGRESSION| P=0.420 P=0.543 (e) P=0.504 |P=0.306N P=0.113 (e) (e) | |COCH-ARM / FISHERS | P=0.410 P=0.500 (e) P=0.505 |P=0.312N P=0.117 (e) (e) | |ORDER RESTRICTED | P=0.254 (e) (e) (e) |P=0.168N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/49 (2%) 0/50 (0%) 1/50 (2%) |0/49 (0%) 4/48 (8%) 1/47 (2%) 0/49 (0%) | |POLY-3 RATE (b) | 0/47.37 1/47.79 0/45.68 1/47.85 |0/46.61 4/46.38 1/45.13 0/45.05 | |POLY-3 PERCENT (g) | 0.0% 2.1% 0.0% 2.1% |0.0% 8.6% 2.2% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 1/46 (2%) |0/43 (0%) 3/40 (8%) 1/42 (2%) 0/39 (0%) | |FIRST INCIDENCE | --- 613 --- 729 (T) |--- 668 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.408 P=0.500 (e) P=0.504 |P=0.316N P=0.059 P=0.495 (e) | |POLY 3 | P=0.406 P=0.502 (e) P=0.502 |P=0.304N P=0.060 P=0.494 (e) | |POLY 1.5 | P=0.408 P=0.501 (e) P=0.503 |P=0.300N P=0.059 P=0.493 (e) | |POLY 6 | P=0.405 P=0.503 (e) P=0.501 |P=0.310N P=0.060 P=0.494 (e) | |LOGISTIC REGRESSION| P=0.420 P=0.543 (e) P=0.504 |P=0.300N P=0.059 P=0.495 (e) | |COCH-ARM / FISHERS | P=0.410 P=0.500 (e) P=0.505 |P=0.296N P=0.056 P=0.490 (e) | |ORDER RESTRICTED | P=0.254 (e) (e) (e) |P=0.155N (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 5 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 2/45.68 0/47.85 |0/46.61 0/47.80 0/48.01 0/46.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.4% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 2/42 (5%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.598 (e) P=0.223 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.596 (e) P=0.225 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.595 (e) P=0.230 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.597 (e) P=0.221 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.223 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.595 (e) P=0.247 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.237 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 3/45.68 0/47.85 |0/46.61 0/47.80 0/48.01 0/46.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.6% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 3/42 (7%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.544 (e) P=0.109 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.540 (e) P=0.109 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.539 (e) P=0.113 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.541 (e) P=0.106 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.109 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.539 (e) P=0.121 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.153 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 6 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 2/46.46 1/47.85 |0/46.61 0/47.80 0/48.01 0/46.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.3% 2.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 1/42 (2%) 1/46 (2%) |0/43 (0%) 0/40 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 441 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.251 (e) P=0.230 P=0.504 |(e) (e) (e) (e) | |POLY 3 | P=0.244 (e) P=0.229 P=0.498 |(e) (e) (e) (e) | |POLY 1.5 | P=0.244 (e) P=0.232 P=0.499 |(e) (e) (e) (e) | |POLY 6 | P=0.244 (e) P=0.226 P=0.498 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.257 (e) P=0.342 P=0.504 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.246 (e) P=0.247 P=0.500 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.161 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 9/50 (18%) 11/50 (22%) 11/50 (22%) |4/50 (8%) 5/50 (10%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 17/48.29 9/47.90 11/45.68 11/48.73 |4/46.61 5/47.80 0/48.01 1/46.05 | |POLY-3 PERCENT (g) | 35.2% 18.8% 24.1% 22.6% |8.6% 10.5% 0.0% 2.2% | |TERMINAL (d) | 16/45 (36%) 9/44 (21%) 11/42 (26%) 10/46 (22%) |4/43 (9%) 5/40 (13%) 0/43 (0%) 1/40 (3%) | |FIRST INCIDENCE | 715 729 (T) 729 (T) 355 |729 (T) 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.171N P=0.062N P=0.183N P=0.123N |P=0.055N P=0.455 P=0.063N P=0.202N | |POLY 3 | P=0.179N P=0.055N P=0.170N P=0.125N |P=0.048N* P=0.516 P=0.057N P=0.183N | |POLY 1.5 | P=0.180N P=0.055N P=0.155N P=0.127N |P=0.048N* P=0.514 P=0.057N P=0.179N | |POLY 6 | P=0.178N P=0.056N P=0.187N P=0.124N |P=0.049N* P=0.513 P=0.057N P=0.187N | |LOGISTIC REGRESSION| P=0.194N P=0.058N P=0.195N P=0.132N |P=0.055N P=0.455 (e) P=0.202N | |COCH-ARM / FISHERS | P=0.185N P=0.055N P=0.133N P=0.133N |P=0.050N P=0.500 P=0.059N P=0.181N | |ORDER RESTRICTED | P=0.093N (e) (e) (e) |P=0.049N* (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 7 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 13/50 (26%) 11/50 (22%) 10/50 (20%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 10/49.18 13/49.04 11/46.97 10/48.52 |1/46.61 2/48.07 0/48.01 1/46.05 | |POLY-3 PERCENT (g) | 20.3% 26.5% 23.4% 20.6% |2.2% 4.2% 0.0% 2.2% | |TERMINAL (d) | 7/45 (16%) 9/44 (21%) 8/42 (19%) 8/46 (17%) |1/43 (2%) 1/40 (3%) 0/43 (0%) 1/40 (3%) | |FIRST INCIDENCE | 459 586 535 628 |729 (T) 656 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.444N P=0.312 P=0.434 P=0.582N |P=0.513N P=0.488 P=0.500N P=0.746 | |POLY 3 | P=0.475N P=0.315 P=0.453 P=0.585 |P=0.499N P=0.511 P=0.494N P=0.758 | |POLY 1.5 | P=0.469N P=0.314 P=0.469 P=0.588 |P=0.498N P=0.509 P=0.495N P=0.760 | |POLY 6 | P=0.478N P=0.320 P=0.440 P=0.585 |P=0.501N P=0.511 P=0.494N P=0.755 | |LOGISTIC REGRESSION| P=0.441N P=0.330 P=0.557 P=0.585N |P=0.500N P=0.495 (e) P=0.746 | |COCH-ARM / FISHERS | P=0.454N P=0.318 P=0.500 P=0.598N |P=0.500N P=0.500 P=0.500N P=0.753N | |ORDER RESTRICTED | P=0.554 (e) (e) (e) |P=0.388N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 18/50 (36%) 18/50 (36%) 20/50 (40%) |5/50 (10%) 6/50 (12%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 23/49.18 18/49.04 18/46.97 20/49.40 |5/46.61 6/48.07 0/48.01 2/46.05 | |POLY-3 PERCENT (g) | 46.8% 36.7% 38.3% 40.5% |10.7% 12.5% 0.0% 4.3% | |TERMINAL (d) | 20/45 (44%) 14/44 (32%) 15/42 (36%) 17/46 (37%) |5/43 (12%) 5/40 (13%) 0/43 (0%) 2/40 (5%) | |FIRST INCIDENCE | 459 586 535 355 |729 (T) 656 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.359N P=0.249N P=0.309N P=0.327N |P=0.074N P=0.457 P=0.033N* P=0.246N | |POLY 3 | P=0.375N P=0.211N P=0.264N P=0.336N |P=0.065N P=0.521 P=0.028N* P=0.221N | |POLY 1.5 | P=0.374N P=0.213N P=0.245N P=0.339N |P=0.064N P=0.518 P=0.029N* P=0.217N | |POLY 6 | P=0.376N P=0.204N P=0.282N P=0.332N |P=0.066N P=0.521 P=0.028N* P=0.227N | |LOGISTIC REGRESSION| P=0.371N P=0.205N P=0.221N P=0.330N |P=0.069N P=0.516 (e) P=0.246N | |COCH-ARM / FISHERS | P=0.375N P=0.208N P=0.208N P=0.343N |P=0.066N P=0.500 P=0.028N* P=0.218N | |ORDER RESTRICTED | P=0.319N (e) (e) (e) |P=0.050N (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 8 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 18/50 (36%) 18/50 (36%) 20/50 (40%) |5/50 (10%) 6/50 (12%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 23/49.18 18/49.04 18/46.97 20/49.40 |5/46.61 6/48.07 0/48.01 2/46.05 | |POLY-3 PERCENT (g) | 46.8% 36.7% 38.3% 40.5% |10.7% 12.5% 0.0% 4.3% | |TERMINAL (d) | 20/45 (44%) 14/44 (32%) 15/42 (36%) 17/46 (37%) |5/43 (12%) 5/40 (13%) 0/43 (0%) 2/40 (5%) | |FIRST INCIDENCE | 459 586 535 355 |729 (T) 656 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.359N P=0.249N P=0.309N P=0.327N |P=0.074N P=0.457 P=0.033N* P=0.246N | |POLY 3 | P=0.375N P=0.211N P=0.264N P=0.336N |P=0.065N P=0.521 P=0.028N* P=0.221N | |POLY 1.5 | P=0.374N P=0.213N P=0.245N P=0.339N |P=0.064N P=0.518 P=0.029N* P=0.217N | |POLY 6 | P=0.376N P=0.204N P=0.282N P=0.332N |P=0.066N P=0.521 P=0.028N* P=0.227N | |LOGISTIC REGRESSION| P=0.371N P=0.205N P=0.221N P=0.330N |P=0.069N P=0.516 (e) P=0.246N | |COCH-ARM / FISHERS | P=0.375N P=0.208N P=0.208N P=0.343N |P=0.066N P=0.500 P=0.028N* P=0.218N | |ORDER RESTRICTED | P=0.319N (e) (e) (e) |P=0.050N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 11/50 (22%) 13/50 (26%) 15/50 (30%) |0/50 (0%) 8/50 (16%) 16/50 (32%) 8/50 (16%) | |POLY-3 RATE (b) | 8/48.24 11/47.95 13/45.68 15/47.85 |0/46.61 8/48.15 16/48.18 8/46.05 | |POLY-3 PERCENT (g) | 16.6% 22.9% 28.5% 31.4% |0.0% 16.6% 33.2% 17.4% | |TERMINAL (d) | 8/45 (18%) 10/44 (23%) 13/42 (31%) 15/46 (33%) |0/43 (0%) 7/40 (18%) 15/43 (35%) 8/40 (20%) | |FIRST INCIDENCE | 729 (T) 716 729 (T) 729 (T) |--- 632 684 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.070 P=0.288 P=0.120 P=0.084 |P=0.019 * P=0.004 ** P<0.001 ** P=0.004 ** | |POLY 3 | P=0.055 P=0.300 P=0.128 P=0.071 |P=0.017 * P=0.004 ** P<0.001 ** P=0.003 ** | |POLY 1.5 | P=0.056 P=0.301 P=0.140 P=0.072 |P=0.019 * P=0.004 ** P<0.001 ** P=0.004 ** | |POLY 6 | P=0.053 P=0.298 P=0.116 P=0.070 |P=0.015 * P=0.004 ** P<0.001 ** P=0.003 ** | |LOGISTIC REGRESSION| P=0.059 P=0.291 P=0.120 P=0.084 |P=0.019 * P=0.005 ** P<0.001 ** P=0.004 ** | |COCH-ARM / FISHERS | P=0.061 P=0.306 P=0.163 P=0.077 |P=0.025 * P=0.003 ** P<0.001 ** P=0.003 ** | |ORDER RESTRICTED | P=0.067 (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 9 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 4/50 (8%) 8/50 (16%) |3/50 (6%) 0/50 (0%) 2/50 (4%) 7/50 (14%) | |POLY-3 RATE (b) | 2/48.89 4/48.31 4/45.68 8/47.85 |3/46.61 0/47.80 2/48.01 7/46.21 | |POLY-3 PERCENT (g) | 4.1% 8.3% 8.8% 16.7% |6.4% 0.0% 4.2% 15.2% | |TERMINAL (d) | 1/45 (2%) 3/44 (7%) 4/42 (10%) 8/46 (17%) |3/43 (7%) 0/40 (0%) 2/43 (5%) 6/40 (15%) | |FIRST INCIDENCE | 513 613 729 (T) 729 (T) |729 (T) --- 729 (T) 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.032 * P=0.333 P=0.311 P=0.053 |P=0.018 * P=0.134N P=0.500N P=0.133 | |POLY 3 | P=0.024 * P=0.332 P=0.307 P=0.042 * |P=0.019 * P=0.114N P=0.487N P=0.154 | |POLY 1.5 | P=0.025 * P=0.334 P=0.318 P=0.043 * |P=0.020 * P=0.115N P=0.489N P=0.158 | |POLY 6 | P=0.023 * P=0.331 P=0.296 P=0.041 * |P=0.019 * P=0.115N P=0.486N P=0.149 | |LOGISTIC REGRESSION| P=0.027 * P=0.362 P=0.364 P=0.049 * |P=0.018 * (e) P=0.500N P=0.144 | |COCH-ARM / FISHERS | P=0.027 * P=0.339 P=0.339 P=0.046 * |P=0.022 * P=0.121N P=0.500N P=0.159 | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) |P=0.011 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 13/50 (26%) 16/50 (32%) 22/50 (44%) |3/50 (6%) 8/50 (16%) 17/50 (34%) 14/50 (28%) | |POLY-3 RATE (b) | 9/48.89 13/48.36 16/45.68 22/47.85 |3/46.61 8/48.15 17/48.18 14/46.21 | |POLY-3 PERCENT (g) | 18.4% 26.9% 35.0% 46.0% |6.4% 16.6% 35.3% 30.3% | |TERMINAL (d) | 8/45 (18%) 11/44 (25%) 16/42 (38%) 22/46 (48%) |3/43 (7%) 7/40 (18%) 16/43 (37%) 13/40 (33%) | |FIRST INCIDENCE | 513 613 729 (T) 729 (T) |729 (T) 632 684 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.003 ** P=0.225 P=0.056 P=0.006 ** |P=0.002 ** P=0.084 P<0.001 ** P=0.002 ** | |POLY 3 | P<0.001 ** P=0.226 P=0.053 P=0.003 ** |P=0.002 ** P=0.109 P<0.001 ** P=0.002 ** | |POLY 1.5 | P=0.002 ** P=0.228 P=0.063 P=0.003 ** |P=0.002 ** P=0.108 P<0.001 ** P=0.003 ** | |POLY 6 | P<0.001 ** P=0.224 P=0.045 * P=0.002 ** |P<0.001 ** P=0.109 P<0.001 ** P=0.002 ** | |LOGISTIC REGRESSION| P=0.002 ** P=0.237 P=0.061 P=0.004 ** |P=0.002 ** P=0.107 P<0.001 ** P=0.003 ** | |COCH-ARM / FISHERS | P=0.002 ** P=0.235 P=0.083 P=0.004 ** |P=0.003 ** P=0.100 P<0.001 ** P=0.003 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 10 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 0/45.68 0/47.85 |1/46.61 1/47.92 0/48.01 2/46.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 2.1% 0.0% 4.3% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |1/43 (2%) 0/40 (0%) 0/43 (0%) 2/40 (5%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 697 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.349 P=0.752 P=0.500N P=0.475 | |POLY 3 | (e) (e) (e) (e) |P=0.363 P=0.754N P=0.494N P=0.496 | |POLY 1.5 | (e) (e) (e) (e) |P=0.366 P=0.755N P=0.495N P=0.499 | |POLY 6 | (e) (e) (e) (e) |P=0.361 P=0.755N P=0.494N P=0.491 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.360 P=0.761N (e) P=0.475 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.366 P=0.753N P=0.500N P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.264 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 0/45.68 0/47.85 |1/46.61 1/47.92 0/48.01 2/46.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 2.1% 0.0% 4.3% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |1/43 (2%) 0/40 (0%) 0/43 (0%) 2/40 (5%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 697 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.349 P=0.752 P=0.500N P=0.475 | |POLY 3 | (e) (e) (e) (e) |P=0.363 P=0.754N P=0.494N P=0.496 | |POLY 1.5 | (e) (e) (e) (e) |P=0.366 P=0.755N P=0.495N P=0.499 | |POLY 6 | (e) (e) (e) (e) |P=0.361 P=0.755N P=0.494N P=0.491 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.360 P=0.761N (e) P=0.475 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.366 P=0.753N P=0.500N P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.264 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 11 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |2/48 (4%) 0/49 (0%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | |2/44.61 0/46.80 1/47.01 1/46.05 | |POLY-3 PERCENT (g) | |4.5% 0.0% 2.1% 2.2% | |TERMINAL (d) | |2/41 (5%) 0/39 (0%) 1/42 (2%) 1/40 (3%) | |FIRST INCIDENCE | |729 (T) --- 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.502N P=0.249N P=0.492N P=0.509N | |POLY 3 | |P=0.495N P=0.227N P=0.482N P=0.489N | |POLY 1.5 | |P=0.493N P=0.227N P=0.484N P=0.486N | |POLY 6 | |P=0.495N P=0.228N P=0.481N P=0.494N | |LOGISTIC REGRESSION| |P=0.502N (e) P=0.492N P=0.509N | |COCH-ARM / FISHERS | |P=0.489N P=0.242N P=0.492N P=0.485N | |ORDER RESTRICTED | |P=0.257N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Granulosa Cell Tumor Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |2/48 (4%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | |2/44.61 0/46.80 0/47.01 0/46.05 | |POLY-3 PERCENT (g) | |4.5% 0.0% 0.0% 0.0% | |TERMINAL (d) | |2/41 (5%) 0/39 (0%) 0/42 (0%) 0/40 (0%) | |FIRST INCIDENCE | |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.115N P=0.249N P=0.233N P=0.244N | |POLY 3 | |P=0.111N P=0.227N P=0.226N P=0.230N | |POLY 1.5 | |P=0.112N P=0.227N P=0.227N P=0.228N | |POLY 6 | |P=0.110N P=0.228N P=0.225N P=0.233N | |LOGISTIC REGRESSION| |P=0.115N (e) (e) (e) | |COCH-ARM / FISHERS | |P=0.112N P=0.242N P=0.242N P=0.237N | |ORDER RESTRICTED | |P=0.027N* (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 12 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Luteoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |0/48 (0%) 1/49 (2%) 2/49 (4%) 2/50 (4%) | |POLY-3 RATE (b) | |0/44.61 1/46.89 2/47.01 2/46.21 | |POLY-3 PERCENT (g) | |0.0% 2.1% 4.3% 4.3% | |TERMINAL (d) | |0/41 (0%) 0/39 (0%) 2/42 (5%) 1/40 (3%) | |FIRST INCIDENCE | |--- 705 729 (T) 687 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.154 P=0.491 P=0.244 P=0.230 | |POLY 3 | |P=0.165 P=0.510 P=0.249 P=0.245 | |POLY 1.5 | |P=0.168 P=0.509 P=0.248 P=0.247 | |POLY 6 | |P=0.162 P=0.509 P=0.249 P=0.243 | |LOGISTIC REGRESSION| |P=0.166 P=0.502 P=0.244 P=0.247 | |COCH-ARM / FISHERS | |P=0.168 P=0.505 P=0.253 P=0.258 | |ORDER RESTRICTED | |P=0.162 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/48 (2%) 0/49 (0%) 0/50 (0%) |5/49 (10%) 4/46 (9%) 3/49 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 0/47.37 1/46.38 0/44.68 0/47.85 |5/45.61 4/44.25 3/47.04 2/46.05 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |11.0% 9.0% 6.4% 4.3% | |TERMINAL (d) | 0/45 (0%) 1/43 (2%) 0/41 (0%) 0/46 (0%) |5/42 (12%) 4/38 (11%) 3/43 (7%) 2/40 (5%) | |FIRST INCIDENCE | --- 729 (T) --- --- |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.561N P=0.491 (e) (e) |P=0.154N P=0.563N P=0.343N P=0.236N | |POLY 3 | P=0.567N P=0.496 (e) (e) |P=0.145N P=0.519N P=0.340N P=0.212N | |POLY 1.5 | P=0.565N P=0.496 (e) (e) |P=0.142N P=0.522N P=0.343N P=0.209N | |POLY 6 | P=0.568N P=0.496 (e) (e) |P=0.149N P=0.518N P=0.338N P=0.218N | |LOGISTIC REGRESSION| (e) P=0.491 (e) (e) |P=0.154N P=0.563N P=0.343N P=0.236N | |COCH-ARM / FISHERS | P=0.563N P=0.495 (e) (e) |P=0.139N P=0.541N P=0.357N P=0.210N | |ORDER RESTRICTED | P=0.375N (e) (e) (e) |P=0.182N (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 13 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 0/45.68 0/47.85 |2/47.26 0/47.80 0/48.01 1/46.22 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.2% 0.0% 0.0% 2.2% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |555 --- --- 685 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.470N P=0.240N P=0.235N P=0.513N | |POLY 3 | (e) (e) (e) (e) |P=0.461N P=0.235N P=0.234N P=0.508N | |POLY 1.5 | (e) (e) (e) (e) |P=0.462N P=0.234N P=0.234N P=0.503N | |POLY 6 | (e) (e) (e) (e) |P=0.459N P=0.237N P=0.235N P=0.514N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.493N P=0.283N P=0.283N P=0.525N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.461N P=0.247N P=0.247N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.135N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 0/45.68 0/47.85 |2/47.26 0/47.80 0/48.01 1/46.22 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.2% 0.0% 0.0% 2.2% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |555 --- --- 685 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.470N P=0.240N P=0.235N P=0.513N | |POLY 3 | (e) (e) (e) (e) |P=0.461N P=0.235N P=0.234N P=0.508N | |POLY 1.5 | (e) (e) (e) (e) |P=0.462N P=0.234N P=0.234N P=0.503N | |POLY 6 | (e) (e) (e) (e) |P=0.459N P=0.237N P=0.235N P=0.514N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.493N P=0.283N P=0.283N P=0.525N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.461N P=0.247N P=0.247N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.135N (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 14 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Skin | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 0/45.68 0/47.85 |2/46.61 0/47.80 0/48.01 1/46.29 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.3% 0.0% 0.0% 2.2% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |2/43 (5%) 0/40 (0%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) --- --- 665 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.472N P=0.254N P=0.238N P=0.519N | |POLY 3 | (e) (e) (e) (e) |P=0.463N P=0.232N P=0.231N P=0.502N | |POLY 1.5 | (e) (e) (e) (e) |P=0.463N P=0.232N P=0.232N P=0.500N | |POLY 6 | (e) (e) (e) (e) |P=0.461N P=0.233N P=0.230N P=0.506N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.461N (e) (e) P=0.500N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.461N P=0.247N P=0.247N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.131N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/49 (2%) 0/50 (0%) 1/50 (2%) |2/49 (4%) 2/49 (4%) 0/49 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/47.24 1/47.38 0/45.68 1/47.85 |2/46.70 2/47.15 0/47.04 0/45.35 | |POLY-3 PERCENT (g) | 0.0% 2.1% 0.0% 2.1% |4.3% 4.2% 0.0% 0.0% | |TERMINAL (d) | 0/44 (0%) 1/44 (2%) 0/42 (0%) 1/46 (2%) |1/43 (2%) 2/40 (5%) 0/43 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |706 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.415 P=0.500 (e) P=0.509 |P=0.092N P=0.667 P=0.240N P=0.258N | |POLY 3 | P=0.407 P=0.501 (e) P=0.503 |P=0.087N P=0.690N P=0.236N P=0.244N | |POLY 1.5 | P=0.408 P=0.500 (e) P=0.503 |P=0.087N P=0.691N P=0.236N P=0.242N | |POLY 6 | P=0.407 P=0.501 (e) P=0.502 |P=0.088N P=0.691N P=0.236N P=0.247N | |LOGISTIC REGRESSION| (e) P=0.500 (e) P=0.509 |P=0.088N P=0.691N P=0.237N P=0.242N | |COCH-ARM / FISHERS | P=0.410 P=0.500 (e) P=0.505 |P=0.086N P=0.691N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.254 (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 15 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/48.24 0/47.90 0/45.68 0/47.85 |0/46.61 0/47.80 2/48.01 0/46.05 | |POLY-3 PERCENT (g) | 2.1% 0.0% 0.0% 0.0% |0.0% 0.0% 4.2% 0.0% | |TERMINAL (d) | 1/45 (2%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |0/43 (0%) 0/40 (0%) 2/43 (5%) 0/40 (0%) | |FIRST INCIDENCE | 729 (T) --- --- --- |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.306N P=0.504N P=0.514N P=0.496N |P=0.585 (e) P=0.238 (e) | |POLY 3 | P=0.308N P=0.501N P=0.511N P=0.502N |P=0.582 (e) P=0.244 (e) | |POLY 1.5 | P=0.307N P=0.501N P=0.507N P=0.501N |P=0.589 (e) P=0.243 (e) | |POLY 6 | P=0.309N P=0.502N P=0.515N P=0.502N |P=0.574 (e) P=0.244 (e) | |LOGISTIC REGRESSION| P=0.306N (e) (e) (e) |(e) (e) P=0.238 (e) | |COCH-ARM / FISHERS | P=0.306N P=0.500N P=0.500N P=0.500N |P=0.595 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.122N (e) (e) (e) |P=0.254 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 3/50 (6%) |2/50 (4%) 0/50 (0%) 3/50 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 1/48.24 2/47.90 0/45.68 3/47.85 |2/46.61 0/47.80 3/48.01 2/46.05 | |POLY-3 PERCENT (g) | 2.1% 4.2% 0.0% 6.3% |4.3% 0.0% 6.3% 4.3% | |TERMINAL (d) | 1/45 (2%) 2/44 (5%) 0/42 (0%) 3/46 (7%) |2/43 (5%) 0/40 (0%) 3/43 (7%) 2/40 (5%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- 729 (T) |729 (T) --- 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.252 P=0.492 P=0.514N P=0.313 |P=0.403 P=0.254N P=0.500 P=0.669 | |POLY 3 | P=0.237 P=0.498 P=0.511N P=0.303 |P=0.410 P=0.232N P=0.513 P=0.689 | |POLY 1.5 | P=0.239 P=0.498 P=0.507N P=0.303 |P=0.416 P=0.232N P=0.511 P=0.693 | |POLY 6 | P=0.236 P=0.497 P=0.515N P=0.302 |P=0.404 P=0.233N P=0.514 P=0.684 | |LOGISTIC REGRESSION| P=0.252 P=0.492 (e) P=0.313 |P=0.403 (e) P=0.500 P=0.669 | |COCH-ARM / FISHERS | P=0.242 P=0.500 P=0.500N P=0.309 |P=0.422 P=0.247N P=0.500 P=0.691N | |ORDER RESTRICTED | P=0.184 (e) (e) (e) |P=0.333 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 16 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 3/50 (6%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.24 2/47.90 0/45.68 3/47.85 |2/46.61 0/47.80 1/48.01 2/46.05 | |POLY-3 PERCENT (g) | 0.0% 4.2% 0.0% 6.3% |4.3% 0.0% 2.1% 4.3% | |TERMINAL (d) | 0/45 (0%) 2/44 (5%) 0/42 (0%) 3/46 (7%) |2/43 (5%) 0/40 (0%) 1/43 (2%) 2/40 (5%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |729 (T) --- 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.103 P=0.234 (e) P=0.125 |P=0.453 P=0.254N P=0.500N P=0.669 | |POLY 3 | P=0.093 P=0.236 (e) P=0.118 |P=0.461 P=0.232N P=0.490N P=0.689 | |POLY 1.5 | P=0.094 P=0.236 (e) P=0.118 |P=0.464 P=0.232N P=0.491N P=0.693 | |POLY 6 | P=0.092 P=0.235 (e) P=0.117 |P=0.458 P=0.233N P=0.489N P=0.684 | |LOGISTIC REGRESSION| (e) P=0.234 (e) P=0.125 |P=0.453 (e) P=0.500N P=0.669 | |COCH-ARM / FISHERS | P=0.097 P=0.247 (e) P=0.121 |P=0.469 P=0.247N P=0.500N P=0.691N | |ORDER RESTRICTED | P=0.036 * (e) (e) (e) |P=0.402 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Testes | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | | |POLY-3 RATE (b) | 0/48.24 2/47.90 0/45.68 0/47.85 | | |POLY-3 PERCENT (g) | 0.0% 4.2% 0.0% 0.0% | | |TERMINAL (d) | 0/45 (0%) 2/44 (5%) 0/42 (0%) 0/46 (0%) | | |FIRST INCIDENCE | --- 729 (T) --- --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.401N P=0.234 (e) (e) | | |POLY 3 | P=0.410N P=0.236 (e) (e) | | |POLY 1.5 | P=0.408N P=0.236 (e) (e) | | |POLY 6 | P=0.412N P=0.235 (e) (e) | | |LOGISTIC REGRESSION| (e) P=0.234 (e) (e) | | |COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) | | |ORDER RESTRICTED | P=0.247N (e) (e) (e) | | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 17 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |0/50 (0%) 2/50 (4%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | |0/46.61 2/47.80 0/48.01 2/46.05 | |POLY-3 PERCENT (g) | |0.0% 4.2% 0.0% 4.3% | |TERMINAL (d) | |0/43 (0%) 2/40 (5%) 0/43 (0%) 2/40 (5%) | |FIRST INCIDENCE | |--- 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.235 P=0.223 (e) P=0.223 | |POLY 3 | |P=0.246 P=0.243 (e) P=0.235 | |POLY 1.5 | |P=0.248 P=0.243 (e) P=0.237 | |POLY 6 | |P=0.242 P=0.242 (e) P=0.231 | |LOGISTIC REGRESSION| |(e) P=0.223 (e) P=0.223 | |COCH-ARM / FISHERS | |P=0.248 P=0.247 (e) P=0.247 | |ORDER RESTRICTED | |P=0.114 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |0/50 (0%) 2/50 (4%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | |0/46.61 2/47.80 1/48.01 2/46.05 | |POLY-3 PERCENT (g) | |0.0% 4.2% 2.1% 4.3% | |TERMINAL (d) | |0/43 (0%) 2/40 (5%) 1/43 (2%) 2/40 (5%) | |FIRST INCIDENCE | |--- 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.232 P=0.223 P=0.500 P=0.223 | |POLY 3 | |P=0.242 P=0.243 P=0.506 P=0.235 | |POLY 1.5 | |P=0.246 P=0.243 P=0.505 P=0.237 | |POLY 6 | |P=0.238 P=0.242 P=0.506 P=0.231 | |LOGISTIC REGRESSION| |(e) P=0.223 P=0.500 P=0.223 | |COCH-ARM / FISHERS | |P=0.246 P=0.247 P=0.500 P=0.247 | |ORDER RESTRICTED | |P=0.153 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 18 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 3/50 (6%) |3/50 (6%) 4/50 (8%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/48.24 2/47.90 3/46.46 3/47.85 |3/46.70 4/47.83 0/48.01 2/46.29 | |POLY-3 PERCENT (g) | 2.1% 4.2% 6.5% 6.3% |6.4% 8.4% 0.0% 4.3% | |TERMINAL (d) | 1/45 (2%) 2/44 (5%) 2/42 (5%) 3/46 (7%) |2/43 (5%) 3/40 (8%) 0/43 (0%) 1/40 (3%) | |FIRST INCIDENCE | 729 (T) 729 (T) 441 729 (T) |706 721 --- 665 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.237 P=0.492 P=0.287 P=0.313 |P=0.283N P=0.465 P=0.123N P=0.530N | |POLY 3 | P=0.224 P=0.498 P=0.292 P=0.303 |P=0.263N P=0.513 P=0.114N P=0.504N | |POLY 1.5 | P=0.226 P=0.498 P=0.297 P=0.303 |P=0.261N P=0.512 P=0.115N P=0.500N | |POLY 6 | P=0.224 P=0.497 P=0.287 P=0.302 |P=0.265N P=0.510 P=0.114N P=0.510N | |LOGISTIC REGRESSION| P=0.231 P=0.492 P=0.376 P=0.313 |P=0.266N P=0.509 P=0.116N P=0.501N | |COCH-ARM / FISHERS | P=0.227 P=0.500 P=0.309 P=0.309 |P=0.263N P=0.500 P=0.121N P=0.500N | |ORDER RESTRICTED | P=0.255 (e) (e) (e) |P=0.182N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 3/50 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 0/48.24 0/47.90 0/45.68 0/47.85 |1/46.61 1/48.42 3/48.01 2/46.35 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 2.1% 6.3% 4.3% | |TERMINAL (d) | 0/45 (0%) 0/44 (0%) 0/42 (0%) 0/46 (0%) |1/43 (2%) 0/40 (0%) 3/43 (7%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 525 729 (T) 647 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.311 P=0.755 P=0.305 P=0.483 | |POLY 3 | (e) (e) (e) (e) |P=0.316 P=0.752N P=0.316 P=0.498 | |POLY 1.5 | (e) (e) (e) (e) |P=0.321 P=0.753N P=0.315 P=0.501 | |POLY 6 | (e) (e) (e) (e) |P=0.311 P=0.752N P=0.317 P=0.495 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.319 P=0.714 P=0.305 P=0.500 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.324 P=0.753N P=0.309 P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.333 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 19 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 4/50 (8%) 2/50 (4%) |7/50 (14%) 10/50 (20%) 12/50 (24%) 13/50 (26%) | |POLY-3 RATE (b) | 3/48.24 3/47.95 4/46.05 2/47.85 |7/46.61 10/48.51 12/49.23 13/48.13 | |POLY-3 PERCENT (g) | 6.2% 6.3% 8.7% 4.2% |15.0% 20.6% 24.4% 27.0% | |TERMINAL (d) | 3/45 (7%) 2/44 (5%) 3/42 (7%) 2/46 (4%) |7/43 (16%) 6/40 (15%) 7/43 (16%) 9/40 (23%) | |FIRST INCIDENCE | 729 (T) 716 623 729 (T) |729 (T) 629 541 409 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.412N P=0.653 P=0.463 P=0.490N |P=0.081 P=0.264 P=0.170 P=0.088 | |POLY 3 | P=0.426N P=0.659 P=0.475 P=0.504N |P=0.100 P=0.329 P=0.187 P=0.119 | |POLY 1.5 | P=0.425N P=0.660 P=0.484 P=0.503N |P=0.099 P=0.322 P=0.177 P=0.117 | |POLY 6 | P=0.428N P=0.659 P=0.467 P=0.504N |P=0.100 P=0.334 P=0.198 P=0.119 | |LOGISTIC REGRESSION| P=0.425N P=0.658 P=0.488 P=0.490N |P=0.089 P=0.312 P=0.154 P=0.103 | |COCH-ARM / FISHERS | P=0.420N P=0.661N P=0.500 P=0.500N |P=0.089 P=0.298 P=0.154 P=0.105 | |ORDER RESTRICTED | P=0.448N (e) (e) (e) |P=0.124 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 26/50 (52%) 29/50 (58%) 23/50 (46%) 27/50 (54%) |18/50 (36%) 23/50 (46%) 23/50 (46%) 21/50 (42%) | |POLY-3 RATE (b) | 26/48.29 29/48.56 23/45.68 27/48.73 |18/47.07 23/48.47 23/48.22 21/46.68 | |POLY-3 PERCENT (g) | 53.8% 59.7% 50.4% 55.4% |38.2% 47.5% 47.7% 45.0% | |TERMINAL (d) | 25/45 (56%) 26/44 (59%) 23/42 (55%) 26/46 (57%) |17/43 (40%) 20/40 (50%) 21/43 (49%) 18/40 (45%) | |FIRST INCIDENCE | 715 613 729 (T) 355 |593 632 684 647 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.462N P=0.306 P=0.475N P=0.545 |P=0.299 P=0.144 P=0.212 P=0.251 | |POLY 3 | P=0.508N P=0.352 P=0.448N P=0.519 |P=0.347 P=0.241 P=0.234 P=0.325 | |POLY 1.5 | P=0.505N P=0.345 P=0.408N P=0.514 |P=0.366 P=0.237 P=0.232 P=0.339 | |POLY 6 | P=0.519N P=0.364 P=0.491N P=0.519 |P=0.330 P=0.240 P=0.232 P=0.311 | |LOGISTIC REGRESSION| P=0.538 P=0.325 P=0.509N P=0.487 |P=0.332 P=0.237 P=0.244 P=0.314 | |COCH-ARM / FISHERS | P=0.509N P=0.344 P=0.345N P=0.500 |P=0.377 P=0.208 P=0.208 P=0.341 | |ORDER RESTRICTED | P=0.550N (e) (e) (e) |P=0.326 (e) (e) (e) | |=================================================================================================================================| Date: 01/12/04 EXPERIMENT: 92013 TEST: 06 Page 20 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - 4-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 15/50 (30%) 25/50 (50%) 21/50 (42%) 22/50 (44%) |20/50 (40%) 20/50 (40%) 23/50 (46%) 29/50 (58%) | |POLY-3 RATE (b) | 15/49.83 25/49.10 21/48.76 22/48.52 |20/47.95 20/49.64 23/49.83 29/50.00 | |POLY-3 PERCENT (g) | 30.1% 50.9% 43.1% 45.4% |41.7% 40.3% 46.2% 58.0% | |TERMINAL (d) | 11/45 (24%) 20/44 (46%) 15/42 (36%) 20/46 (44%) |16/43 (37%) 12/40 (30%) 17/43 (40%) 19/40 (48%) | |FIRST INCIDENCE | 459 586 441 628 |539 525 539 409 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.242 P=0.042 * P=0.124 P=0.135 |P=0.033 * P=0.499 P=0.367 P=0.055 | |POLY 3 | P=0.163 P=0.027 * P=0.130 P=0.087 |P=0.038 * P=0.525N P=0.406 P=0.078 | |POLY 1.5 | P=0.173 P=0.028 * P=0.135 P=0.093 |P=0.035 * P=0.536N P=0.392 P=0.072 | |POLY 6 | P=0.157 P=0.027 * P=0.126 P=0.085 |P=0.042 * P=0.516N P=0.419 P=0.086 | |LOGISTIC REGRESSION| P=0.207 P=0.034 * P=0.233 P=0.111 |P=0.030 * P=0.565 P=0.330 P=0.054 | |COCH-ARM / FISHERS | P=0.198 P=0.033 * P=0.149 P=0.107 |P=0.028 * P=0.581N P=0.343 P=0.055 | |ORDER RESTRICTED | P=0.074 (e) (e) (e) |P=0.068 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 312 PPM 625 PPM 1250 PPM |0 PPM 312 PPM 625 PPM 1250 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 34/50 (68%) 38/50 (76%) 36/50 (72%) 39/50 (78%) |29/50 (58%) 36/50 (72%) 37/50 (74%) 40/50 (80%) | |POLY-3 RATE (b) | 34/49.83 38/49.10 36/48.76 39/49.40 |29/48.41 36/49.99 37/50.00 40/50.00 | |POLY-3 PERCENT (g) | 68.2% 77.4% 73.8% 79.0% |59.9% 72.0% 74.0% 80.0% | |TERMINAL (d) | 30/45 (67%) 33/44 (75%) 30/42 (71%) 36/46 (78%) |24/43 (56%) 27/40 (68%) 30/43 (70%) 30/40 (75%) | |FIRST INCIDENCE | 459 586 441 355 |539 525 539 409 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.285 P=0.239 P=0.268 P=0.256 |P=0.024 * P=0.091 P=0.115 P=0.019 * | |POLY 3 | P=0.179 P=0.213 P=0.348 P=0.162 |P=0.025 * P=0.146 P=0.101 P=0.023 * | |POLY 1.5 | P=0.188 P=0.220 P=0.367 P=0.170 |P=0.023 * P=0.137 P=0.094 P=0.021 * | |POLY 6 | P=0.172 P=0.215 P=0.337 P=0.157 |P=0.027 * P=0.153 P=0.107 P=0.025 * | |LOGISTIC REGRESSION| P=0.197 P=0.249 P=0.430 P=0.187 |P=0.016 * P=0.109 P=0.074 P=0.015 * | |COCH-ARM / FISHERS | P=0.201 P=0.252 P=0.414 P=0.184 |P=0.015 * P=0.104 P=0.069 P=0.015 * | |ORDER RESTRICTED | P=0.169 (e) (e) (e) |P=0.018 * (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).