TDMS Study 96007-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02 EXPERIMENT: 96007 TEST: 03 TIME: 12:14:20 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6 ------------------------------------------------------------------------------------------------------------------------------------ 53 WEEK SSAC REASONS FOR REMOVAL: 25017 Scheduled Sacrifice REMOVAL DATE RANGE: 060399 060499 TREATMENT GROUPS: INCLUDE 001 0 NG/KG INCLUDE 002 3 NG/KG INCLUDE 003 10 NG/KG INCLUDE 004 22 NG/KG INCLUDE 005 46 NG/KG INCLUDE 006 100 NG/KG NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02 EXPERIMENT: 96007 TEST: 03 TIME: 12:14:20 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Hyperplasia Liver Basophilic Focus Fatty Change Diffuse Mixed Cell Focus Pigmentation Toxic Hepatopathy Liver: Bile Duct Fibrosis Hyperplasia Liver: Hepatocyte Hypertrophy Multinucleated Mammary Gland Cyst Pancreas Inflammation Chronic Pancreas: Acinus Atrophy Vacuolization Cytoplasmic Thymus Atrophy Thyroid Gland: Follicular Cell Hypertrophy Uterus Metaplasia =============================================================== Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/8 (13%) 1/8 (13%) 1/8 (13%) 2/8 (25%) 0/8 (0%) 1/8 (13%) | |POLY-3 RATE (b) | 1/1.35 1/1.35 1/1.35 2/2.30 0/0.40 1/1.35 | |POLY-3 PERCENT (g) | 74.1% 74.1% 74.1% 87.0% 0.0% 74.1% | |INT SACRIFICE 1 (c)| 1/8 (12.5%) 1/8 (12.5%) 1/8 (12.5%) 2/8 (25%) 0/8 (0%) 1/8 (12.5%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) 368 (I) 368 (I) 368 (I) --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.515N P=0.768 P=0.768 P=0.500 P=0.500N P=0.768 | |POLY 3 | P=0.413N P=0.548 P=0.548 P=0.314 P=0.174N P=0.548 | |POLY 1.5 | P=0.431N P=0.590 P=0.590 P=0.348 P=0.229N P=0.590 | |POLY 6 | P=0.409N P=0.536 P=0.536 P=0.304 P=0.159N P=0.536 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.515N P=0.767N P=0.767N P=0.500 P=0.500N P=0.767N | |ORDER RESTRICTED | P=0.435N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/8 (13%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 3/8 (38%) 2/8 (25%) | |POLY-3 RATE (b) | 1/1.35 0/0.40 0/0.40 0/0.40 3/3.25 2/2.30 | |POLY-3 PERCENT (g) | 74.1% 0.0% 0.0% 0.0% 92.3% 87.0% | |INT SACRIFICE 1 (c)| 1/8 (12.5%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 3/8 (37.5%) 2/8 (25%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- --- 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.053 P=0.500N P=0.500N P=0.500N P=0.288 P=0.500 | |POLY 3 | P=0.026 * P=0.174N P=0.174N P=0.174N P=0.156 P=0.314 | |POLY 1.5 | P=0.029 * P=0.229N P=0.229N P=0.229N P=0.180 P=0.348 | |POLY 6 | P=0.026 * P=0.159N P=0.159N P=0.159N P=0.149 P=0.304 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.051 P=0.500N P=0.500N P=0.500N P=0.285 P=0.500 | |ORDER RESTRICTED | P=0.017 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/8 (63%) 3/8 (38%) 4/8 (50%) 4/8 (50%) 5/8 (63%) 7/8 (88%) | |POLY-3 RATE (b) | 5/5.15 3/3.25 4/4.20 4/4.20 5/5.15 7/7.05 | |POLY-3 PERCENT (g) | 97.1% 92.3% 95.2% 95.2% 97.1% 99.3% | |INT SACRIFICE 1 (c)| 5/8 (62.5%) 3/8 (37.5%) 4/8 (50%) 4/8 (50%) 5/8 (62.5%) 7/8 (87.5%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.052 P=0.314N P=0.500N P=0.500N P=0.691 P=0.288 | |POLY 3 | P=0.050 P=0.231N P=0.420N P=0.420N P=0.623 P=0.237 | |POLY 1.5 | P=0.051 P=0.247N P=0.435N P=0.435N P=0.635 P=0.247 | |POLY 6 | P=0.050 P=0.227N P=0.417N P=0.417N P=0.621 P=0.235 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.050 P=0.310N P=0.500N P=0.500N P=0.696N P=0.285 | |ORDER RESTRICTED | P=0.123 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 1/8 (13%) 1/8 (13%) 0/8 (0%) 0/8 (0%) 3/8 (38%) | |POLY-3 RATE (b) | 0/0.40 1/1.35 1/1.35 0/0.40 0/0.40 3/3.25 | |POLY-3 PERCENT (g) | 0.0% 74.1% 74.1% 0.0% 0.0% 92.3% | |INT SACRIFICE 1 (c)| 0/8 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/8 (0%) 0/8 (0%) 3/8 (37.5%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 368 (I) 368 (I) --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.035 * P=0.500 P=0.500 (e) (e) P=0.107 | |POLY 3 | P=0.014 * P=0.174 P=0.174 (e) (e) P=0.022 * | |POLY 1.5 | P=0.018 * P=0.229 P=0.229 (e) (e) P=0.031 * | |POLY 6 | P=0.013 * P=0.159 P=0.159 (e) (e) P=0.020 * | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.033 * P=0.500 P=0.500 (e) (e) P=0.100 | |ORDER RESTRICTED | P=0.160 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/8 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) | |POLY-3 RATE (b) | 2/2.30 0/0.40 0/0.40 0/0.40 0/0.40 0/0.40 | |POLY-3 PERCENT (g) | 87.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 2/8 (25%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.247N P=0.232N P=0.232N P=0.232N P=0.232N P=0.232N | |POLY 3 | P=0.097N P=0.069N P=0.069N P=0.069N P=0.069N P=0.069N | |POLY 1.5 | P=0.116N P=0.093N P=0.093N P=0.093N P=0.093N P=0.093N | |POLY 6 | P=0.092N P=0.064N P=0.064N P=0.064N P=0.064N P=0.064N | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.244N P=0.233N P=0.233N P=0.233N P=0.233N P=0.233N | |ORDER RESTRICTED | P=0.217N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) 6/8 (75%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 0/0.40 0/0.40 2/2.30 6/6.10 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 87.0% 98.4% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) 6/8 (75%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.232 P=0.006 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.069 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.093 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.064 P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.233 P=0.003 ** | |ORDER RESTRICTED | P=0.020 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/8 (100%) 8/8 (100%) 8/8 (100%) 8/8 (100%) 8/8 (100%) 8/8 (100%) | |POLY-3 RATE (b) | 8/8.00 8/8.00 8/8.00 8/8.00 8/8.00 8/8.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 8/8 (100%) 8/8 (100%) 8/8 (100%) 8/8 (100%) 8/8 (100%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/8 (25%) 5/8 (63%) 0/8 (0%) 6/8 (75%) 7/8 (88%) 8/8 (100%) | |POLY-3 RATE (b) | 2/2.30 5/5.15 0/0.40 6/6.10 7/7.05 8/8.00 | |POLY-3 PERCENT (g) | 87.0% 97.1% 0.0% 98.4% 99.3% 100.0% | |INT SACRIFICE 1 (c)| 2/8 (25%) 5/8 (62.5%) 0/8 (0%) 6/8 (75%) 7/8 (87.5%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) 368 (I) --- 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.165 P=0.232N P=0.073 P=0.025 * P=0.006 ** | |POLY 3 | P<0.001 ** P=0.089 P=0.069N P=0.024 * P=0.002 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.101 P=0.093N P=0.029 * P=0.003 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.085 P=0.064N P=0.023 * P=0.002 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.157 P=0.233N P=0.066 P=0.020 * P=0.003 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 5/8 (63%) 8/8 (100%) 8/8 (100%) 8/8 (100%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 5/5.15 8/8.00 8/8.00 8/8.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 97.1% 100.0% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 5/8 (62.5%) 8/8 (100%) 8/8 (100%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.018 * P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) P<0.001 ** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001 ** (e) P<0.001 ** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001 ** (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.013 * P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Toxic Hepatopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 1/8 (13%) 0/8 (0%) 6/8 (75%) 8/8 (100%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 1/1.35 0/0.40 6/6.10 8/8.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 74.1% 0.0% 98.4% 100.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 0/8 (0%) 6/8 (75%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 368 (I) --- 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.500 (e) P=0.006 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.174 (e) P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.229 (e) P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.159 (e) P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.500 (e) P=0.003 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/8 (13%) 2/8 (25%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 0/0.40 0/0.40 1/1.35 2/2.30 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 74.1% 87.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 2/8 (25%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * (e) (e) (e) P=0.500 P=0.232 | |POLY 3 | P=0.004 ** (e) (e) (e) P=0.174 P=0.069 | |POLY 1.5 | P=0.006 ** (e) (e) (e) P=0.229 P=0.093 | |POLY 6 | P=0.004 ** (e) (e) (e) P=0.159 P=0.064 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.014 * (e) (e) (e) P=0.500 P=0.233 | |ORDER RESTRICTED | P=0.232 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 1/8 (13%) 2/8 (25%) 3/8 (38%) 8/8 (100%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 1/1.35 2/2.30 3/3.25 8/8.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 74.1% 87.0% 92.3% 100.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 1/8 (12.5%) 2/8 (25%) 3/8 (37.5%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.500 P=0.232 P=0.107 P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.174 P=0.069 P=0.022 * P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.229 P=0.093 P=0.031 * P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.159 P=0.064 P=0.020 * P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.500 P=0.233 P=0.100 P<0.001 ** | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 4/8 (50%) 7/8 (88%) 8/8 (100%) 8/8 (100%) 8/8 (100%) | |POLY-3 RATE (b) | 0/0.40 4/4.20 7/7.05 8/8.00 8/8.00 8/8.00 | |POLY-3 PERCENT (g) | 0.0% 95.2% 99.3% 100.0% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 4/8 (50%) 7/8 (87.5%) 8/8 (100%) 8/8 (100%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.047 * P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.007 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.038 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Multinucleated | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) 8/8 (100%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 0/0.40 0/0.40 2/2.30 8/8.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 87.0% 100.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.232 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.069 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.093 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.064 P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.233 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/8 (38%) 1/8 (13%) 2/8 (25%) 1/8 (13%) 4/8 (50%) 3/8 (38%) | |POLY-3 RATE (b) | 3/3.25 1/1.35 2/2.30 1/1.35 4/4.20 3/3.25 | |POLY-3 PERCENT (g) | 92.3% 74.1% 87.0% 74.1% 95.2% 92.3% | |INT SACRIFICE 1 (c)| 3/8 (37.5%) 1/8 (12.5%) 2/8 (25%) 1/8 (12.5%) 4/8 (50%) 3/8 (37.5%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.236 P=0.288N P=0.500N P=0.288N P=0.500 P=0.691 | |POLY 3 | P=0.195 P=0.156N P=0.366N P=0.156N P=0.398 P=0.578 | |POLY 1.5 | P=0.202 P=0.180N P=0.391N P=0.180N P=0.417 P=0.599 | |POLY 6 | P=0.193 P=0.149N P=0.360N P=0.149N P=0.393 P=0.573 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.233 P=0.285N P=0.500N P=0.285N P=0.500 P=0.696N | |ORDER RESTRICTED | P=0.262 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/8 (38%) 0/2 (0%) 0/2 (0%) 0/0 (0%) 0/0 (0%) 0/8 (0%) | |POLY-3 RATE (b) | 3/3.25 0/0.10 0/0.10 0/0.00 0/0.00 0/0.40 | |POLY-3 PERCENT (g) | 92.3% 0.0% 0.0% 0.0% 0.0% 0.0% | |INT SACRIFICE 1 (c)| 3/8 (37.5%) 0/2 (0%) 0/2 (0%) 0/0 (0%) 0/0 (0%) 0/8 (0%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.109N P=0.435N P=0.435N P=1.000N P=1.000N P=0.107N | |POLY 3 | (e) P=0.174N P=0.174N (e) (e) P=0.022N* | |POLY 1.5 | (e) P=0.216N P=0.216N (e) (e) P=0.031N* | |POLY 6 | (e) P=0.164N P=0.164N (e) (e) P=0.020N* | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.103N P=0.467N P=0.467N P=1.000 P=1.000 P=0.100N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/8 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 5/7 (71%) | |POLY-3 RATE (b) | 8/8.00 0/0.00 0/0.00 0/0.00 0/0.00 5/5.10 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 98.0% | |INT SACRIFICE 1 (c)| 8/8 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 5/7 (71.4%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.121N (e) (e) (e) (e) P=0.202N | |POLY 3 | (e) (e) (e) (e) (e) P=0.153N | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.160N | |POLY 6 | (e) (e) (e) (e) (e) P=0.152N | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.113N (e) (e) (e) (e) P=0.200N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 0/0.40 0/0.40 0/0.40 2/2.30 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 87.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010 * (e) (e) (e) (e) P=0.232 | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P=0.069 | |POLY 1.5 | P=0.002 ** (e) (e) (e) (e) P=0.093 | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P=0.064 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.010 * (e) (e) (e) (e) P=0.233 | |ORDER RESTRICTED | P=0.217 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 0/0.40 0/0.40 0/0.40 2/2.30 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 87.0% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 2/8 (25%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010 * (e) (e) (e) (e) P=0.232 | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P=0.069 | |POLY 1.5 | P=0.002 ** (e) (e) (e) (e) P=0.093 | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P=0.064 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.010 * (e) (e) (e) (e) P=0.233 | |ORDER RESTRICTED | P=0.217 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 7/8 (88%) | |POLY-3 RATE (b) | 0/0.40 0/0.40 0/0.40 0/0.40 0/0.40 7/7.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 99.3% | |INT SACRIFICE 1 (c)| 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 0/8 (0%) 7/8 (87.5%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.002 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/8 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/8 (100%) | |POLY-3 RATE (b) | 8/8.00 0/0.00 0/0.00 0/0.00 0/0.00 8/8.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |INT SACRIFICE 1 (c)| 8/8 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/8 (50%) 2/8 (25%) 3/7 (43%) 7/8 (88%) 8/8 (100%) 8/8 (100%) | |POLY-3 RATE (b) | 4/4.20 2/2.30 3/3.20 7/7.05 8/8.00 8/8.00 | |POLY-3 PERCENT (g) | 95.2% 87.0% 93.8% 99.3% 100.0% 100.0% | |INT SACRIFICE 1 (c)| 4/8 (50%) 2/8 (25%) 3/7 (42.9%) 7/8 (87.5%) 8/8 (100%) 8/8 (100%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.309N P=0.592N P=0.148 P=0.047 * P=0.047 * | |POLY 3 | P<0.001 ** P=0.204N P=0.491N P=0.095 P=0.013 * P=0.013 * | |POLY 1.5 | P<0.001 ** P=0.224N P=0.509N P=0.103 P=0.015 * P=0.015 * | |POLY 6 | P<0.001 ** P=0.199N P=0.487N P=0.093 P=0.013 * P=0.013 * | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.304N P=0.595N P=0.141 P=0.038 * P=0.038 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/8 (0%) 1/8 (13%) 2/8 (25%) 2/8 (25%) 3/8 (38%) 5/8 (63%) | |POLY-3 RATE (b) | 0/0.40 1/1.35 2/2.30 2/2.30 3/3.25 5/5.15 | |POLY-3 PERCENT (g) | 0.0% 74.1% 87.0% 87.0% 92.3% 97.1% | |INT SACRIFICE 1 (c)| 0/8 (0%) 1/8 (12.5%) 2/8 (25%) 2/8 (25%) 3/8 (37.5%) 5/8 (62.5%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 368 (I) 368 (I) 368 (I) 368 (I) 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** P=0.500 P=0.232 P=0.232 P=0.107 P=0.018 * | |POLY 3 | P=0.002 ** P=0.174 P=0.069 P=0.069 P=0.022 * P<0.001 ** | |POLY 1.5 | P=0.002 ** P=0.229 P=0.093 P=0.093 P=0.031 * P<0.001 ** | |POLY 6 | P=0.002 ** P=0.159 P=0.064 P=0.064 P=0.020 * P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.004 ** P=0.500 P=0.233 P=0.233 P=0.100 P=0.013 * | |ORDER RESTRICTED | P=0.035 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/8 (88%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) 4/8 (50%) | |POLY-3 RATE (b) | 7/7.05 0/0.00 0/0.00 0/0.05 0/0.00 4/4.20 | |POLY-3 PERCENT (g) | 99.3% 0.0% 0.0% 0.0% 0.0% 95.2% | |INT SACRIFICE 1 (c)| 7/8 (87.5%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) 4/8 (50%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- --- --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.146N P=1.000N P=1.000N P=0.252N P=1.000 P=0.148N | |POLY 3 | (e) (e) (e) P=0.012N* (e) P=0.095N | |POLY 1.5 | (e) (e) (e) P=0.023N* (e) P=0.103N | |POLY 6 | (e) (e) (e) P=0.010N* (e) P=0.093N | |LOGISTIC REGRESSION| P=0.138N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.138N P=1.000 P=1.000 P=0.222N P=1.000 P=0.141N | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 143 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/8 (63%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) 2/8 (25%) | |POLY-3 RATE (b) | 5/5.15 0/0.00 0/0.00 1/1.00 0/0.00 2/2.30 | |POLY-3 PERCENT (g) | 97.1% 0.0% 0.0% 100.0% 0.0% 87.0% | |INT SACRIFICE 1 (c)| 5/8 (62.5%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) 2/8 (25%) | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 368 (I) --- --- 368 (I) --- 368 (I) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.092N P=1.000 P=1.000 P=0.638 P=1.000N P=0.165N | |POLY 3 | (e) (e) (e) P=0.603 (e) P=0.089N | |POLY 1.5 | (e) (e) (e) P=0.612 (e) P=0.101N | |POLY 6 | (e) (e) (e) P=0.602 (e) P=0.085N | |LOGISTIC REGRESSION| P=0.086N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.086N P=1.000 P=1.000 P=0.667 P=1.000 P=0.157N | |ORDER RESTRICTED | (e) (e) (e) (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).