TDMS Study 92012-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst 2-METHYLIMIDAZOLE DATE: 02/24/03 EXPERIMENT: 92012 TEST: 05 TIME: 14:13:53 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: FARNELL, DANIEL R. CAS: 693-98-1 ------------------------------------------------------------------------------------------------------------------------------------ 27 WEEK SSAC REASONS FOR REMOVAL: 25017 Scheduled Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst 2-METHYLIMIDAZOLE DATE: 02/24/03 EXPERIMENT: 92012 TEST: 05 TIME: 14:13:53 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: FARNELL, DANIEL R. CAS: 693-98-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF 2-METHYLIMIDAZOLE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Pituitary Gland: Pars Intermedia Cyst Thyroid Gland: Follicle Mineralization Focal Thyroid Gland: Follicular Cell Hyperplasia =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Harderian Gland Inflammation Focal Granulomatous Lymph Node: Pancreatic Hyperplasia Lymphoid Thyroid Gland: Follicle Mineralization Focal Thyroid Gland: Follicular Cell Hyperplasia =============================================================== Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 0/0.06 2/2.05 |0/0.06 0/0.06 0/0.06 1/1.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 97.6% |0.0% 0.0% 0.0% 94.8% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 183 (I) |--- --- --- 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.040 * (e) (e) P=0.234 |P=0.194 (e) (e) P=0.500 | |POLY 3 | P=0.007 ** (e) (e) P=0.067 |P=0.064 (e) (e) P=0.160 | |POLY 1.5 | P=0.008 ** (e) (e) P=0.076 |P=0.075 (e) (e) P=0.183 | |POLY 6 | P=0.007 ** (e) (e) P=0.067 |P=0.063 (e) (e) P=0.159 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.038 * (e) (e) P=0.237 |P=0.191 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.328 (e) (e) (e) |P=0.442 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Inflammation Focal Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 1/10 (10%) 5/10 (50%) | |POLY-3 RATE (b) | 1/1.06 0/0.06 0/0.06 0/0.06 |0/0.06 0/0.06 1/1.06 5/5.03 | |POLY-3 PERCENT (g) | 94.8% 0.0% 0.0% 0.0% |0.0% 0.0% 94.8% 99.4% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 1/10 (10%) 5/10 (50%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 183 (I) --- --- --- |--- --- 183 (I) 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.474N P=0.500N P=0.500N P=0.500N |P<0.001 ** (e) P=0.500 P=0.022 * | |POLY 3 | P=0.180N P=0.160N P=0.160N P=0.160N |P<0.001 ** (e) P=0.160 P<0.001 ** | |POLY 1.5 | P=0.197N P=0.183N P=0.183N P=0.183N |P<0.001 ** (e) P=0.183 P=0.002 ** | |POLY 6 | P=0.179N P=0.159N P=0.159N P=0.159N |P<0.001 ** (e) P=0.159 P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.474N P=0.500N P=0.500N P=0.500N |P<0.001 ** (e) P=0.500 P=0.016 * | |ORDER RESTRICTED | P=0.442N (e) (e) (e) |P=0.085 (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) |1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 2/2.05 0/0.06 1/1.06 0/0.06 |1/1.06 0/0.06 1/1.06 0/0.06 | |POLY-3 PERCENT (g) | 97.6% 0.0% 94.8% 0.0% |94.8% 0.0% 94.8% 0.0% | |INT SACRIFICE 1 (c)| 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) |1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 183 (I) --- 183 (I) --- |183 (I) --- 183 (I) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.267N P=0.234N P=0.500N P=0.234N |P=0.425N P=0.500N P=0.766 P=0.500N | |POLY 3 | P=0.131N P=0.067N P=0.300N P=0.067N |P=0.264N P=0.160N P=0.530 P=0.160N | |POLY 1.5 | P=0.132N P=0.076N P=0.315N P=0.076N |P=0.269N P=0.183N P=0.548 P=0.183N | |POLY 6 | P=0.131N P=0.067N P=0.299N P=0.067N |P=0.263N P=0.159N P=0.528 P=0.159N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.265N P=0.237N P=0.500N P=0.237N |P=0.424N P=0.500N P=0.763N P=0.500N | |ORDER RESTRICTED | P=0.274N (e) (e) (e) |P=0.362N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/10 (90%) 7/10 (70%) 10/10 (100%) 10/10 (100%)|10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 9/9.01 7/7.02 10/10.00 10/10.00 |10/10.00 10/10.00 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 99.9% 99.7% 100.0% 100.0% |100.0% 100.0% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 9/10 (90%) 7/10 (70%) 10/10 (100%) 10/10 (100%)|10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 183 (I) 183 (I) 183 (I) 183 (I) |183 (I) 183 (I) 183 (I) 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.143 P=0.293N P=0.500 P=0.500 |(e) (e) (e) (e) | |POLY 3 | P=0.130 P=0.251N P=0.478 P=0.478 |(e) (e) (e) (e) | |POLY 1.5 | P=0.130 P=0.255N P=0.480 P=0.480 |(e) (e) (e) (e) | |POLY 6 | P=0.130 P=0.251N P=0.478 P=0.478 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.140 P=0.291N P=0.500 P=0.500 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.074 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 1/1 (100%) 0/1 (0%) 1/1 (100%) |1/3 (33%) 1/4 (25%) 0/1 (0%) 2/3 (67%) | |POLY-3 RATE (b) | 0/0.00 1/1.00 0/0.01 1/1.00 |1/1.01 1/1.02 0/0.01 2/2.01 | |POLY-3 PERCENT (g) | 0.0% 100.0% 0.0% 100.0% |98.8% 98.2% 0.0% 99.7% | |INT SACRIFICE 1 (c)| 0/0 (0%) 1/1 (100%) 0/1 (0%) 1/1 (100%) |1/3 (33.3%) 1/4 (25%) 0/1 (0%) 2/3 (66.7%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 183 (I) --- 183 (I) |183 (I) 183 (I) --- 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.690 (e) (e) (e) |P=0.280 P=0.712N P=0.718N P=0.500 | |POLY 3 | (e) (e) (e) (e) |P=0.225 P=0.501N P=0.311N P=0.337 | |POLY 1.5 | (e) (e) (e) (e) |P=0.236 P=0.517N P=0.338N P=0.351 | |POLY 6 | (e) (e) (e) (e) |P=0.224 P=0.500N P=0.309N P=0.336 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.728 (e) (e) (e) |P=0.271 P=0.714N P=0.750N P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.276 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) |0/3 (0%) 2/4 (50%) 0/1 (0%) 1/3 (33%) | |POLY-3 RATE (b) | 0/0.00 0/0.01 1/1.00 0/0.01 |0/0.02 2/2.01 0/0.01 1/1.01 | |POLY-3 PERCENT (g) | 0.0% 0.0% 100.0% 0.0% |0.0% 99.4% 0.0% 98.8% | |INT SACRIFICE 1 (c)| 0/0 (0%) 0/1 (0%) 1/1 (100%) 0/1 (0%) |0/3 (0%) 2/4 (50%) 0/1 (0%) 1/3 (33.3%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 183 (I) --- |--- 183 (I) --- 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.690N (e) (e) (e) |P=0.515 P=0.288 (e) P=0.500 | |POLY 3 | (e) (e) (e) (e) |P=0.422 P=0.072 (e) P=0.160 | |POLY 1.5 | (e) (e) (e) (e) |P=0.427 P=0.082 (e) P=0.182 | |POLY 6 | (e) (e) (e) (e) |P=0.421 P=0.072 (e) P=0.159 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.728N (e) (e) (e) |P=0.515 P=0.286 (e) P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.225 (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) |2/3 (67%) 1/4 (25%) 1/1 (100%) 0/3 (0%) | |POLY-3 RATE (b) | 0/0.00 0/0.01 0/0.01 0/0.01 |2/2.01 1/1.02 1/1.00 0/0.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |99.7% 98.2% 100.0% 0.0% | |INT SACRIFICE 1 (c)| 0/0 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%) |2/3 (66.7%) 1/4 (25%) 1/1 (100%) 0/3 (0%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- |183 (I) 183 (I) 183 (I) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.177N P=0.380N P=0.718 P=0.215N | |POLY 3 | (e) (e) (e) (e) |P=0.112N P=0.214N P=0.640 P=0.023N* | |POLY 1.5 | (e) (e) (e) (e) |P=0.113N P=0.228N P=0.646 P=0.028N* | |POLY 6 | (e) (e) (e) (e) |P=0.112N P=0.212N P=0.640 P=0.023N* | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.166N P=0.371N P=0.750 P=0.200N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.128N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 2/10 (20%) 0/10 (0%) 1/10 (10%) |1/10 (10%) 2/10 (20%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 1/1.06 2/2.05 0/0.06 1/1.06 |1/1.06 2/2.05 0/0.06 1/1.06 | |POLY-3 PERCENT (g) | 94.8% 97.6% 0.0% 94.8% |94.8% 97.6% 0.0% 94.8% | |INT SACRIFICE 1 (c)| 1/10 (10%) 2/10 (20%) 0/10 (0%) 1/10 (10%) |1/10 (10%) 2/10 (20%) 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 183 (I) 183 (I) --- 183 (I) |183 (I) 183 (I) --- 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.553N P=0.500 P=0.500N P=0.766 |P=0.472N P=0.500 P=0.500N P=0.766 | |POLY 3 | P=0.399N P=0.300 P=0.160N P=0.530 |P=0.359N P=0.300 P=0.160N P=0.530 | |POLY 1.5 | P=0.409N P=0.315 P=0.183N P=0.548 |P=0.366N P=0.315 P=0.183N P=0.548 | |POLY 6 | P=0.398N P=0.299 P=0.159N P=0.528 |P=0.359N P=0.299 P=0.159N P=0.528 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.554N P=0.500 P=0.500N P=0.763N |P=0.472N P=0.500 P=0.500N P=0.763N | |ORDER RESTRICTED | P=0.278N (e) (e) (e) |P=0.278N (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Mitotic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) |1/10 (10%) 2/10 (20%) 2/10 (20%) 2/10 (20%) | |POLY-3 RATE (b) | 0/0.06 1/1.06 1/1.06 0/0.06 |1/1.06 2/2.05 2/2.05 2/2.05 | |POLY-3 PERCENT (g) | 0.0% 94.8% 94.8% 0.0% |94.8% 97.6% 97.6% 97.6% | |INT SACRIFICE 1 (c)| 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) |1/10 (10%) 2/10 (20%) 2/10 (20%) 2/10 (20%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 183 (I) 183 (I) --- |183 (I) 183 (I) 183 (I) 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.537N P=0.500 P=0.500 (e) |P=0.424 P=0.500 P=0.500 P=0.500 | |POLY 3 | P=0.311N P=0.160 P=0.160 (e) |P=0.347 P=0.300 P=0.300 P=0.300 | |POLY 1.5 | P=0.318N P=0.183 P=0.183 (e) |P=0.352 P=0.315 P=0.315 P=0.315 | |POLY 6 | P=0.311N P=0.159 P=0.159 (e) |P=0.346 P=0.299 P=0.299 P=0.299 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.537N P=0.500 P=0.500 (e) |P=0.423 P=0.500 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.478 (e) (e) (e) |P=0.423 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 0/0.06 2/2.05 |0/0.06 1/1.06 1/1.06 0/0.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 97.6% |0.0% 94.8% 94.8% 0.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 183 (I) |--- 183 (I) 183 (I) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.040 * (e) (e) P=0.234 |P=0.575N P=0.500 P=0.500 (e) | |POLY 3 | P=0.007 ** (e) (e) P=0.067 |P=0.401N P=0.160 P=0.160 (e) | |POLY 1.5 | P=0.008 ** (e) (e) P=0.076 |P=0.408N P=0.183 P=0.183 (e) | |POLY 6 | P=0.007 ** (e) (e) P=0.067 |P=0.400N P=0.159 P=0.159 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.038 * (e) (e) P=0.237 |P=0.576N P=0.500 P=0.500 (e) | |ORDER RESTRICTED | P=0.328 (e) (e) (e) |P=0.478 (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 0/0.06 2/2.05 0/0.06 0/0.06 |0/0.06 0/0.06 1/1.06 0/0.06 | |POLY-3 PERCENT (g) | 0.0% 97.6% 0.0% 0.0% |0.0% 0.0% 94.8% 0.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 183 (I) --- --- |--- --- 183 (I) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.368N P=0.234 (e) (e) |P=0.679 (e) P=0.500 (e) | |POLY 3 | P=0.161N P=0.067 (e) (e) |P=0.423 (e) P=0.160 (e) | |POLY 1.5 | P=0.173N P=0.076 (e) (e) |P=0.440 (e) P=0.183 (e) | |POLY 6 | P=0.160N P=0.067 (e) (e) |P=0.421 (e) P=0.159 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.366N P=0.237 (e) (e) |P=0.681 (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.454N (e) (e) (e) |P=0.545 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 4/10 (40%) 9/10 (90%) 9/10 (90%) |1/10 (10%) 6/10 (60%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 1/1.06 4/4.04 9/9.01 9/9.01 |1/1.06 6/6.03 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 94.8% 99.1% 99.9% 99.9% |94.8% 99.6% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 1/10 (10%) 4/10 (40%) 9/10 (90%) 9/10 (90%) |1/10 (10%) 6/10 (60%) 10/10 (100%) 10/10 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 183 (I) 183 (I) 183 (I) 183 (I) |183 (I) 183 (I) 183 (I) 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.157 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.034 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.067 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.072 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.006 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.066 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.152 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.029 * P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 05 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 7/10 (70%) 10/10 (100%) 10/10 (100%)|0/10 (0%) 5/10 (50%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 0/0.06 7/7.02 10/10.00 10/10.00 |0/0.06 5/5.03 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 99.7% 100.0% 100.0% |0.0% 99.4% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 7/10 (70%) 10/10 (100%) 10/10 (100%)|0/10 (0%) 5/10 (50%) 10/10 (100%) 10/10 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 183 (I) 183 (I) 183 (I) |--- 183 (I) 183 (I) 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.022 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001N** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001N** |P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001N** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (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).