TDMS Study 92012-06 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst 2-METHYLIMIDAZOLE DATE: 02/24/03 EXPERIMENT: 92012 TEST: 06 TIME: 15:04:05 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: HEATH, JAMES E. CAS: 693-98-1 ------------------------------------------------------------------------------------------------------------------------------------ 27 WEEK SSAC/FINAL#1 MICE 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: 06 TIME: 15:04:05 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: HEATH, JAMES E. CAS: 693-98-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF 2-METHYLIMIDAZOLE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Bone Marrow Hyperplasia Kidney: Renal Tubule Pigmentation Liver Infiltration Cellular Mixed Cell Liver: Hepatocyte Karyomegaly Vacuolization Cytoplasmic Spleen Hematopoietic Cell Proliferation Pigmentation Spleen: Lymphoid Follicle Atrophy Thyroid Gland: Follicular Cell Hypertrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Liver: Hepatocyte Vacuolization Cytoplasmic Spleen Hematopoietic Cell Proliferation Pigmentation Spleen: Lymphoid Follicle Atrophy Thyroid Gland: Follicular Cell Hypertrophy =============================================================== Date: 02/24/03 EXPERIMENT: 92012 TEST: 06 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 0/10 (0%) 1/10 (10%) |2/10 (20%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 2/2.05 0/0.06 0/0.06 1/1.06 |2/2.05 0/0.06 0/0.06 1/1.06 | |POLY-3 PERCENT (g) | 97.6% 0.0% 0.0% 94.8% |97.6% 0.0% 0.0% 94.8% | |INT SACRIFICE 1 (c)| 2/10 (20%) 0/10 (0%) 0/10 (0%) 1/10 (10%) |2/10 (20%) 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) |183 (I) --- --- 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.460N P=0.234N P=0.234N P=0.500N |P=0.460N P=0.234N P=0.234N P=0.500N | |POLY 3 | P=0.330N P=0.067N P=0.067N P=0.300N |P=0.330N P=0.067N P=0.067N P=0.300N | |POLY 1.5 | P=0.336N P=0.076N P=0.076N P=0.315N |P=0.336N P=0.076N P=0.076N P=0.315N | |POLY 6 | P=0.329N P=0.067N P=0.067N P=0.299N |P=0.329N P=0.067N P=0.067N P=0.299N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.460N P=0.237N P=0.237N P=0.500N |P=0.460N P=0.237N P=0.237N P=0.500N | |ORDER RESTRICTED | P=0.041N* (e) (e) (e) |P=0.041N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 2/10 (20%) 5/10 (50%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 1/1.06 0/0.06 2/2.05 5/5.03 |0/0.06 0/0.06 0/0.06 0/0.06 | |POLY-3 PERCENT (g) | 94.8% 0.0% 97.6% 99.4% |0.0% 0.0% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 2/10 (20%) 5/10 (50%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 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=0.009 ** P=0.500N P=0.500 P=0.077 |(e) (e) (e) (e) | |POLY 3 | P=0.003 ** P=0.160N P=0.300 P=0.023 * |(e) (e) (e) (e) | |POLY 1.5 | P=0.003 ** P=0.183N P=0.315 P=0.025 * |(e) (e) (e) (e) | |POLY 6 | P=0.003 ** P=0.159N P=0.299 P=0.023 * |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.008 ** P=0.500N P=0.500 P=0.070 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 06 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 1/10 (10%) 2/10 (20%) |1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 1/1.06 0/0.06 1/1.06 2/2.05 |1/1.06 1/1.06 0/0.06 0/0.06 | |POLY-3 PERCENT (g) | 94.8% 0.0% 94.8% 97.6% |94.8% 94.8% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 1/10 (10%) 2/10 (20%) |1/10 (10%) 1/10 (10%) 0/10 (0%) 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) 183 (I) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.241 P=0.500N P=0.766 P=0.500 |P=0.234N P=0.766 P=0.500N P=0.500N | |POLY 3 | P=0.161 P=0.160N P=0.530 P=0.300 |P=0.121N P=0.530 P=0.160N P=0.160N | |POLY 1.5 | P=0.168 P=0.183N P=0.548 P=0.315 |P=0.124N P=0.548 P=0.183N P=0.183N | |POLY 6 | P=0.161 P=0.159N P=0.528 P=0.299 |P=0.121N P=0.528 P=0.159N P=0.159N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.238 P=0.500N P=0.763N P=0.500 |P=0.231N P=0.763N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.140 (e) (e) (e) |P=0.362N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 1/10 (10%) 10/10 (100%)|0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 1/1.06 10/10.00 |0/0.06 0/0.06 0/0.06 0/0.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 94.8% 100.0% |0.0% 0.0% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 1/10 (10%) 10/10 (100%)|0/10 (0%) 0/10 (0%) 0/10 (0%) 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<0.001 ** (e) P=0.500 P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P<0.001 ** (e) P=0.160 P<0.001 ** |(e) (e) (e) (e) | |POLY 1.5 | P<0.001 ** (e) P=0.183 P<0.001 ** |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** (e) P=0.159 P<0.001 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.500 P<0.001 ** |(e) (e) (e) (e) | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 06 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 3/10 (30%) 6/10 (60%) 2/10 (20%) |6/10 (60%) 7/10 (70%) 3/10 (30%) 5/10 (50%) | |POLY-3 RATE (b) | 2/2.05 3/3.04 6/6.03 2/2.05 |6/6.03 7/7.02 3/3.04 5/5.03 | |POLY-3 PERCENT (g) | 97.6% 98.6% 99.6% 97.6% |99.6% 99.7% 98.6% 99.4% | |INT SACRIFICE 1 (c)| 2/10 (20%) 3/10 (30%) 6/10 (60%) 2/10 (20%) |6/10 (60%) 7/10 (70%) 3/10 (30%) 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) 183 (I) |183 (I) 183 (I) 183 (I) 183 (I) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.567 P=0.500 P=0.091 P=0.707 |P=0.281N P=0.500 P=0.190N P=0.500N | |POLY 3 | P=0.493 P=0.353 P=0.037 * P=0.543 |P=0.249N P=0.437 P=0.119N P=0.423N | |POLY 1.5 | P=0.498 P=0.364 P=0.040 * P=0.555 |P=0.251N P=0.442 P=0.124N P=0.428N | |POLY 6 | P=0.493 P=0.352 P=0.037 * P=0.542 |P=0.249N P=0.436 P=0.119N P=0.422N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.278N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.568 P=0.500 P=0.085 P=0.709N |P=0.278N P=0.500 P=0.185N P=0.500N | |ORDER RESTRICTED | P=0.341 (e) (e) (e) |P=0.172N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Karyomegaly | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 0/0.06 5/5.03 |0/0.06 0/0.06 0/0.06 0/0.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 99.4% |0.0% 0.0% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 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) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P=0.022 * |(e) (e) (e) (e) | |POLY 3 | P<0.001 ** (e) (e) P<0.001 ** |(e) (e) (e) (e) | |POLY 1.5 | P<0.001 ** (e) (e) P=0.002 ** |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** (e) (e) P<0.001 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.016 * |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.091 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 06 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 4/10 (40%) |0/10 (0%) 1/10 (10%) 2/10 (20%) 4/10 (40%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 0/0.06 4/4.04 |0/0.06 1/1.06 2/2.05 4/4.04 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 99.1% |0.0% 94.8% 97.6% 99.1% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 4/10 (40%) |0/10 (0%) 1/10 (10%) 2/10 (20%) 4/10 (40%) | |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=0.002 ** (e) (e) P=0.051 |P=0.016 * P=0.500 P=0.234 P=0.051 | |POLY 3 | P<0.001 ** (e) (e) P=0.007 ** |P=0.007 ** P=0.160 P=0.067 P=0.007 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.008 ** |P=0.007 ** P=0.183 P=0.076 P=0.008 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.007 ** |P=0.007 ** P=0.159 P=0.067 P=0.007 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.002 ** (e) (e) P=0.043 * |P=0.015 * P=0.500 P=0.237 P=0.043 * | |ORDER RESTRICTED | P=0.154 (e) (e) (e) |P=0.095 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) |2/10 (20%) 1/10 (10%) 0/10 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 0/0.06 0/0.06 |2/2.05 1/1.06 0/0.06 2/2.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |97.6% 94.8% 0.0% 97.6% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) |2/10 (20%) 1/10 (10%) 0/10 (0%) 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) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.595 P=0.500N P=0.234N P=0.707 | |POLY 3 | (e) (e) (e) (e) |P=0.496 P=0.300N P=0.067N P=0.543 | |POLY 1.5 | (e) (e) (e) (e) |P=0.504 P=0.315N P=0.076N P=0.555 | |POLY 6 | (e) (e) (e) (e) |P=0.495 P=0.299N P=0.067N P=0.542 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.596 P=0.500N P=0.237N P=0.709N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.328 (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 06 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 5/10 (50%) 10/10 (100%) 10/10 (100%)|2/10 (20%) 5/10 (50%) 6/10 (60%) 10/10 (100%) | |POLY-3 RATE (b) | 0/0.06 5/5.03 10/10.00 10/10.00 |2/2.05 5/5.03 6/6.03 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 99.4% 100.0% 100.0% |97.6% 99.4% 99.6% 100.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 5/10 (50%) 10/10 (100%) 10/10 (100%)|2/10 (20%) 5/10 (50%) 6/10 (60%) 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) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.022 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.180 P=0.091 P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.099 P=0.037 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.104 P=0.040 * P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.098 P=0.037 * P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.175 P=0.085 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 1/10 (10%) 10/10 (100%) 10/10 (100%)|1/10 (10%) 3/10 (30%) 7/10 (70%) 10/10 (100%) | |POLY-3 RATE (b) | 0/0.06 1/1.06 10/10.00 10/10.00 |1/1.06 3/3.04 7/7.02 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 94.8% 100.0% 100.0% |94.8% 98.6% 99.7% 100.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 1/10 (10%) 10/10 (100%) 10/10 (100%)|1/10 (10%) 3/10 (30%) 7/10 (70%) 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) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.293 P=0.013 * P<0.001 ** | |POLY 3 | P<0.001 ** P=0.160 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.152 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.183 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.163 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.159 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.152 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.291 P=0.010 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 02/24/03 EXPERIMENT: 92012 TEST: 06 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 5/10 (50%) 10/10 (100%)|0/10 (0%) 0/10 (0%) 0/10 (0%) 4/10 (40%) | |POLY-3 RATE (b) | 0/0.06 0/0.06 5/5.03 10/10.00 |0/0.06 0/0.06 0/0.06 4/4.04 | |POLY-3 PERCENT (g) | 0.0% 0.0% 99.4% 100.0% |0.0% 0.0% 0.0% 99.1% | |INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 5/10 (50%) 10/10 (100%)|0/10 (0%) 0/10 (0%) 0/10 (0%) 4/10 (40%) | |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<0.001 ** (e) P=0.022 * P<0.001 ** |P=0.002 ** (e) (e) P=0.051 | |POLY 3 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) (e) P=0.007 ** | |POLY 1.5 | P<0.001 ** (e) P=0.002 ** P<0.001 ** |P<0.001 ** (e) (e) P=0.008 ** | |POLY 6 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) (e) P=0.007 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.016 * P<0.001 ** |P=0.002 ** (e) (e) P=0.043 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.154 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 5/10 (50%) 9/10 (90%) 10/10 (100%)|0/8 (0%) 8/10 (80%) 10/10 (100%) 10/10 (100%) | |POLY-3 RATE (b) | 0/0.06 5/5.03 9/9.01 10/10.00 |0/0.05 8/8.01 10/10.00 10/10.00 | |POLY-3 PERCENT (g) | 0.0% 99.4% 99.9% 100.0% |0.0% 99.9% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 0/10 (0%) 5/10 (50%) 9/10 (90%) 10/10 (100%)|0/8 (0%) 8/10 (80%) 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=0.022 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |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=0.016 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** 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: 06 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 625 PPM 1250 PPM 2500 PPM |0PPM 625 PPM 1250 PPM 2500 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/10 (30%) 1/10 (10%) 4/10 (40%) 1/10 (10%) | |POLY-3 RATE (b) | |3/3.04 1/1.06 4/4.04 1/1.06 | |POLY-3 PERCENT (g) | |98.6% 94.8% 99.1% 94.8% | |INT SACRIFICE 1 (c)| |3/10 (30%) 1/10 (10%) 4/10 (40%) 1/10 (10%) | |TERMINAL (d) | |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=0.329N P=0.293N P=0.500 P=0.293N | |POLY 3 | |P=0.256N P=0.152N P=0.384 P=0.152N | |POLY 1.5 | |P=0.259N P=0.163N P=0.393 P=0.163N | |POLY 6 | |P=0.256N P=0.152N P=0.383 P=0.152N | |LOGISTIC REGRESSION| |P=0.327N (e) (e) (e) | |COCH-ARM / FISHERS | |P=0.327N P=0.291N P=0.500 P=0.291N | |ORDER RESTRICTED | |P=0.221N (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).