TDMS Study 97013-89 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (DICHLOROACETIC ACID) DATE: 12/05/03 EXPERIMENT: 97013 TEST: 89 TIME: 09:29:20 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: SKIN APPLICATION NTP C#: 97013D PATHOLOGIST: MISSING CAS: 79-43-6 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (DICHLOROACETIC ACID) DATE: 12/05/03 EXPERIMENT: 97013 TEST: 89 TIME: 09:29:20 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: SKIN APPLICATION NTP C#: 97013D PATHOLOGIST: MISSING CAS: 79-43-6 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF WATER DISINFECTION MODEL (DICHLOROACET =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Kidney Mineralization Nephropathy Liver: Hepatocyte Necrosis Vacuolization Cytoplasmic Skin Inflammation Chronic Skin: Epidermis Hyperplasia Focal Skin: Site of Application - Epidermis Hyperkeratosis Hyperplasia Testes Cyst Testes: Germinal Epithelium Degeneration Thymus Atrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Mineralization Liver: Hepatocyte Necrosis Vacuolization Cytoplasmic Lung Inflammation Chronic Skin: Site of Application - Epidermis Hyperkeratosis Hyperplasia Thyroid Gland: Follicle Degeneration =============================================================== Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHL OROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) |3/10 (30%) 0/10 (0%) 2/10 (20%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.46 0/7.30 0/9.02 1/8.95 |3/9.08 0/7.11 2/8.71 0/8.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 11.2% |33.0% 0.0% 23.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/7 (0%) |2/8 (25%) 0/5 (0%) 2/6 (33%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- 225 |146 --- 274 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.244 (e) (e) P=0.500 |P=0.152N P=0.185N P=0.612N P=0.119N | |POLY 3 | P=0.236 (e) (e) P=0.489 |P=0.130N P=0.142N P=0.521N P=0.099N | |POLY 1.5 | P=0.234 (e) (e) P=0.493 |P=0.141N P=0.128N P=0.517N P=0.100N | |POLY 6 | P=0.237 (e) (e) P=0.485 |P=0.120N P=0.164N P=0.533N P=0.102N | |LOGISTIC REGRESSION| P=0.204 (e) (e) P=0.646 |P=0.174N P=0.100N P=0.500N P=0.105N | |COCH-ARM / FISHERS | P=0.225 (e) (e) P=0.500 |P=0.179N P=0.105N P=0.500N P=0.105N | |ORDER RESTRICTED | P=0.110 (e) (e) (e) |P=0.026N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/10 (80%) 8/10 (80%) 6/10 (60%) 7/10 (70%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 8/9.46 8/8.75 6/9.02 7/8.51 |0/8.23 0/7.11 0/8.71 0/8.73 | |POLY-3 PERCENT (g) | 84.5% 91.4% 66.5% 82.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 8/9 (89%) 6/6 (100%) 6/8 (75%) 7/7 (100%) |0/8 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 274 (T) 121 274 (T) 274 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.630N P=0.133 P=0.457N P=0.550 |(e) (e) (e) (e) | |POLY 3 | P=0.586N P=0.618 P=0.354N P=0.711N |(e) (e) (e) (e) | |POLY 1.5 | P=0.518N P=0.654 P=0.334N P=0.613N |(e) (e) (e) (e) | |POLY 6 | P=0.689 P=0.577 P=0.393N P=0.750 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.436N P=0.454 P=0.457N P=0.550 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.450N P=0.709N P=0.314N P=0.500N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.328N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |3/10 (30%) 1/10 (10%) 2/10 (20%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.46 0/7.30 0/9.02 0/8.51 |3/8.23 1/7.11 2/8.71 0/8.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |36.5% 14.1% 23.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/7 (0%) |3/8 (38%) 1/5 (20%) 2/6 (33%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- |274 (T) 274 (T) 274 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.091N P=0.482N P=0.651N P=0.107N | |POLY 3 | (e) (e) (e) (e) |P=0.092N P=0.343N P=0.471N P=0.080N | |POLY 1.5 | (e) (e) (e) (e) |P=0.102N P=0.331N P=0.483N P=0.086N | |POLY 6 | (e) (e) (e) (e) |P=0.084N P=0.372N P=0.474N P=0.079N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.091N P=0.482N P=0.651N (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.126N P=0.291N P=0.500N P=0.105N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.032N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 1/10 (10%) 1/10 (10%) 1/10 (10%) |7/10 (70%) 6/10 (60%) 8/10 (80%) 5/10 (50%) | |POLY-3 RATE (b) | 0/9.46 1/7.30 1/9.46 1/8.95 |7/8.23 6/7.53 8/9.02 5/9.01 | |POLY-3 PERCENT (g) | 0.0% 13.7% 10.6% 11.2% |85.0% 79.6% 88.7% 55.5% | |TERMINAL (d) | 0/9 (0%) 1/6 (17%) 0/8 (0%) 0/7 (0%) |7/8 (88%) 4/5 (80%) 5/6 (83%) 4/8 (50%) | |FIRST INCIDENCE | --- 274 (T) 225 225 |274 (T) 246 260 246 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.536 P=0.419 P=0.500 P=0.500 |P=0.121N P=0.349 P=0.221 P=0.312N | |POLY 3 | P=0.521 P=0.448 P=0.500 P=0.489 |P=0.088N P=0.653N P=0.686 P=0.208N | |POLY 1.5 | P=0.525 P=0.466 P=0.500 P=0.493 |P=0.130N P=0.635N P=0.602 P=0.256N | |POLY 6 | P=0.516 P=0.433 P=0.500 P=0.485 |P=0.066N P=0.689N P=0.729 P=0.185N | |LOGISTIC REGRESSION| P=0.518 P=0.419 P=0.577 P=0.646 |P=0.090N P=0.769 P=0.698 P=0.224N | |COCH-ARM / FISHERS | P=0.528 P=0.500 P=0.500 P=0.500 |P=0.258N P=0.500N P=0.500 P=0.325N | |ORDER RESTRICTED | P=0.297 (e) (e) (e) |P=0.101N (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Epididymis | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/10 (30%) 2/10 (20%) 1/10 (10%) 1/10 (10%) | | |POLY-3 RATE (b) | 3/10.00 2/8.22 1/9.02 1/8.51 | | |POLY-3 PERCENT (g) | 30.0% 24.3% 11.1% 11.8% | | |TERMINAL (d) | 2/9 (22%) 1/6 (17%) 1/8 (13%) 1/7 (14%) | | |FIRST INCIDENCE | 212 121 274 (T) 274 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.319N P=0.632N P=0.332N P=0.381N | | |POLY 3 | P=0.306N P=0.597N P=0.332N P=0.355N | | |POLY 1.5 | P=0.297N P=0.559N P=0.314N P=0.328N | | |POLY 6 | P=0.319N P=0.636N P=0.355N P=0.388N | | |LOGISTIC REGRESSION| P=0.291N P=0.298N P=0.255N P=0.261N | | |COCH-ARM / FISHERS | P=0.284N P=0.500N P=0.291N P=0.291N | | |ORDER RESTRICTED | P=0.255N (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/9.46 0/7.30 1/9.02 0/8.51 |0/8.23 0/7.11 0/8.71 0/8.73 | |POLY-3 PERCENT (g) | 21.1% 0.0% 11.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/9 (22%) 0/6 (0%) 1/8 (13%) 0/7 (0%) |0/8 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 274 (T) --- 274 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.316N P=0.327N P=0.543N P=0.290N |(e) (e) (e) (e) | |POLY 3 | P=0.263N P=0.290N P=0.518N P=0.251N |(e) (e) (e) (e) | |POLY 1.5 | P=0.271N P=0.267N P=0.510N P=0.241N |(e) (e) (e) (e) | |POLY 6 | P=0.261N P=0.311N P=0.528N P=0.264N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.316N (e) P=0.543N (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.294N P=0.237N P=0.500N P=0.237N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.080N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 0/7.30 0/9.02 0/8.51 |0/8.23 0/7.11 0/8.71 0/8.73 | |POLY-3 PERCENT (g) | 20.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/9 (11%) 0/6 (0%) 0/8 (0%) 0/7 (0%) |0/8 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 212 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.319N P=0.311N P=0.253N P=0.280N |(e) (e) (e) (e) | |POLY 3 | P=0.254N P=0.306N P=0.251N P=0.266N |(e) (e) (e) (e) | |POLY 1.5 | P=0.267N P=0.276N P=0.240N P=0.249N |(e) (e) (e) (e) | |POLY 6 | P=0.245N P=0.335N P=0.266N P=0.287N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.309N P=0.171N P=0.161N P=0.145N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.304N P=0.237N P=0.237N P=0.237N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.036N* (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 7/10 (70%) 7/10 (70%) 8/10 (80%) |4/10 (40%) 2/10 (20%) 3/10 (30%) 2/10 (20%) | |POLY-3 RATE (b) | 2/9.46 7/7.84 7/9.02 8/9.70 |4/8.23 2/7.93 3/8.71 2/8.73 | |POLY-3 PERCENT (g) | 21.1% 89.3% 77.6% 82.5% |48.6% 25.2% 34.4% 22.9% | |TERMINAL (d) | 2/9 (22%) 6/6 (100%) 7/8 (88%) 6/7 (86%) |4/8 (50%) 0/5 (0%) 3/6 (50%) 2/8 (25%) | |FIRST INCIDENCE | 274 (T) 212 274 (T) 174 |274 (T) 212 274 (T) 274 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.033 * P=0.005 ** P=0.016 * P=0.008 ** |P=0.274N P=0.498N P=0.699 P=0.309N | |POLY 3 | P=0.038 * P=0.002 ** P=0.011 * P=0.003 ** |P=0.332N P=0.328N P=0.462N P=0.278N | |POLY 1.5 | P=0.041 * P=0.004 ** P=0.016 * P=0.004 ** |P=0.343N P=0.338N P=0.478N P=0.295N | |POLY 6 | P=0.033 * P<0.001 ** P=0.007 ** P=0.003 ** |P=0.330N P=0.326N P=0.467N P=0.276N | |LOGISTIC REGRESSION| P=0.050 P=0.005 ** P=0.016 * P=0.014 * |P=0.319N P=0.366N P=0.699 P=0.309N | |COCH-ARM / FISHERS | P=0.058 P=0.035 * P=0.035 * P=0.012 * |P=0.375N P=0.314N P=0.500N P=0.314N | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.212N (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 4/10 (40%) 4/10 (40%) 4/10 (40%) |1/10 (10%) 2/10 (20%) 1/10 (10%) 1/10 (10%) | |POLY-3 RATE (b) | 1/9.46 4/7.30 4/9.02 4/8.95 |1/8.23 2/7.53 1/8.71 1/8.73 | |POLY-3 PERCENT (g) | 10.6% 54.8% 44.4% 44.7% |12.2% 26.6% 11.5% 11.5% | |TERMINAL (d) | 1/9 (11%) 4/6 (67%) 4/8 (50%) 3/7 (43%) |1/8 (13%) 0/5 (0%) 1/6 (17%) 1/8 (13%) | |FIRST INCIDENCE | 274 (T) 274 (T) 274 (T) 225 |274 (T) 246 274 (T) 274 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.247 P=0.053 P=0.118 P=0.110 |P=0.484N P=0.398 P=0.702 P=0.768 | |POLY 3 | P=0.285 P=0.067 P=0.127 P=0.125 |P=0.532N P=0.467 P=0.750N P=0.750N | |POLY 1.5 | P=0.295 P=0.090 P=0.136 P=0.133 |P=0.540N P=0.469 P=0.755N P=0.756N | |POLY 6 | P=0.273 P=0.050 P=0.116 P=0.118 |P=0.531N P=0.461 P=0.752N P=0.750N | |LOGISTIC REGRESSION| P=0.278 P=0.053 P=0.118 P=0.134 |P=0.517N P=0.456 P=0.702 P=0.768 | |COCH-ARM / FISHERS | P=0.303 P=0.152 P=0.152 P=0.152 |P=0.552N P=0.500 P=0.763N P=0.763N | |ORDER RESTRICTED | P=0.062 (e) (e) (e) |P=0.527N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/10 (60%) 7/10 (70%) 5/10 (50%) 5/10 (50%) |9/10 (90%) 9/10 (90%) 8/10 (80%) 10/10 (100%) | |POLY-3 RATE (b) | 6/9.46 7/8.29 5/9.46 5/8.95 |9/9.08 9/9.00 8/9.00 10/10.00 | |POLY-3 PERCENT (g) | 63.4% 84.5% 52.8% 55.8% |99.1% 100.0% 88.9% 100.0% | |TERMINAL (d) | 6/9 (67%) 5/6 (83%) 4/8 (50%) 4/7 (57%) |8/8 (100%) 5/5 (100%) 6/6 (100%) 8/8 (100%) | |FIRST INCIDENCE | 274 (T) 212 225 225 |146 113 260 50 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.430N P=0.138 P=0.600N P=0.632 |P=0.518N P=0.149 P=0.528 P=0.514 | |POLY 3 | P=0.356N P=0.320 P=0.500N P=0.556N |P=0.734 P=1.000 P=0.528N P=1.000 | |POLY 1.5 | P=0.347N P=0.366 P=0.500N P=0.535N |P=0.654 P=0.994 P=0.558N P=0.992 | |POLY 6 | P=0.375N P=0.313 P=0.500N P=0.577N |P=0.759 P=1.000 P=0.511N P=1.000 | |LOGISTIC REGRESSION| P=0.340N P=0.205 P=0.550N P=0.630N |P=0.312 P=0.495 P=0.407N P=0.409 | |COCH-ARM / FISHERS | P=0.349N P=0.500 P=0.500N P=0.500N |P=0.310 P=0.763N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.310N (e) (e) (e) |P=0.405N (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 2/10 (20%) 6/10 (60%) |2/10 (20%) 1/10 (10%) 0/10 (0%) 5/10 (50%) | |POLY-3 RATE (b) | 1/9.46 0/7.30 2/9.02 6/9.55 |2/8.23 1/7.26 0/8.71 5/9.72 | |POLY-3 PERCENT (g) | 10.6% 0.0% 22.2% 62.8% |24.3% 13.8% 0.0% 51.4% | |TERMINAL (d) | 1/9 (11%) 0/6 (0%) 2/8 (25%) 4/7 (57%) |2/8 (25%) 0/5 (0%) 0/6 (0%) 4/8 (50%) | |FIRST INCIDENCE | 274 (T) --- 274 (T) 174 |274 (T) 260 --- 50 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.581N P=0.457 P=0.024 * |P=0.047 * P=0.643N P=0.298N P=0.186 | |POLY 3 | P<0.001 ** P=0.551N P=0.482 P=0.017 * |P=0.025 * P=0.546N P=0.210N P=0.249 | |POLY 1.5 | P<0.001 ** P=0.534N P=0.490 P=0.017 * |P=0.022 * P=0.538N P=0.216N P=0.229 | |POLY 6 | P<0.001 ** P=0.566N P=0.471 P=0.016 * |P=0.027 * P=0.564N P=0.211N P=0.250 | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.457 P=0.038 * |P=0.021 * P=0.573N (e) P=0.172 | |COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.500 P=0.029 * |P=0.020 * P=0.500N P=0.237N P=0.175 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.023 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/10 (90%) 7/10 (70%) 8/10 (80%) 10/10 (100%)|7/10 (70%) 6/10 (60%) 8/10 (80%) 10/10 (100%) | |POLY-3 RATE (b) | 9/9.46 7/7.84 8/9.02 10/10.00 |7/8.23 6/7.65 8/9.00 10/10.00 | |POLY-3 PERCENT (g) | 95.1% 89.3% 88.7% 100.0% |85.0% 78.5% 88.9% 100.0% | |TERMINAL (d) | 9/9 (100%) 6/6 (100%) 8/8 (100%) 7/7 (100%) |7/8 (88%) 5/5 (100%) 6/6 (100%) 8/8 (100%) | |FIRST INCIDENCE | 274 (T) 212 274 (T) 174 |274 (T) 212 260 50 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.047 * P=0.455 P=1.000N P=0.117 |P=0.200 P=0.291 P=0.151 P=0.131 | |POLY 3 | P=0.391 P=0.736N P=0.677N P=0.864 |P=0.175 P=0.627N P=0.684 P=0.362 | |POLY 1.5 | P=0.259 P=0.519N P=0.574N P=0.672 |P=0.111 P=0.615N P=0.601 P=0.227 | |POLY 6 | P=0.747 P=0.974N P=0.923N P=1.000 |P=0.231 P=0.689N P=0.727 P=0.443 | |LOGISTIC REGRESSION| P=0.078 P=0.761 P=1.000N P=0.290 |P=0.032 * P=0.707N P=0.699 P=0.080 | |COCH-ARM / FISHERS | P=0.157 P=0.291N P=0.500N P=0.500 |P=0.041 * P=0.500N P=0.500 P=0.105 | |ORDER RESTRICTED | P=0.199 (e) (e) (e) |P=0.146 (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.46 0/7.30 0/9.02 0/8.51 |2/8.23 0/7.11 0/8.71 0/8.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |24.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/7 (0%) |2/8 (25%) 0/5 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- |274 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.274N P=0.341N P=0.298N P=0.232N | |POLY 3 | (e) (e) (e) (e) |P=0.271N P=0.258N P=0.210N P=0.210N | |POLY 1.5 | (e) (e) (e) (e) |P=0.277N P=0.251N P=0.216N P=0.217N | |POLY 6 | (e) (e) (e) (e) |P=0.259N P=0.276N P=0.211N P=0.209N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.274N (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.304N P=0.237N P=0.237N P=0.237N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.018N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 3/10 (30%) 1/10 (10%) 1/10 (10%) |2/10 (20%) 3/9 (33%) 3/10 (30%) 2/10 (20%) | |POLY-3 RATE (b) | 0/9.46 3/8.55 1/9.46 1/8.95 |2/9.08 3/7.93 3/9.00 2/9.01 | |POLY-3 PERCENT (g) | 0.0% 35.1% 10.6% 11.2% |22.0% 37.9% 33.3% 22.2% | |TERMINAL (d) | 0/9 (0%) 1/6 (17%) 0/8 (0%) 0/7 (0%) |1/8 (13%) 1/5 (20%) 1/6 (17%) 1/8 (13%) | |FIRST INCIDENCE | --- 160 225 225 |146 212 260 246 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.560N P=0.083 P=0.500 P=0.500 |P=0.432N P=0.394 P=0.469 P=0.684N | |POLY 3 | P=0.612N P=0.074 P=0.500 P=0.489 |P=0.487N P=0.431 P=0.496 P=0.702 | |POLY 1.5 | P=0.602N P=0.079 P=0.500 P=0.493 |P=0.496N P=0.437 P=0.491 P=0.696 | |POLY 6 | P=0.620N P=0.072 P=0.500 P=0.485 |P=0.480N P=0.423 P=0.498 P=0.704 | |LOGISTIC REGRESSION| P=0.623N P=0.186 P=0.577 P=0.646 |P=0.487N P=0.445 P=0.497 P=0.711 | |COCH-ARM / FISHERS | P=0.582N P=0.105 P=0.500 P=0.500 |P=0.487N P=0.444 P=0.500 P=0.709N | |ORDER RESTRICTED | P=0.186 (e) (e) (e) |P=0.537 (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery: Fat | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/1 (0%) 0/0 (0%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/1.00 0/0.00 2/2.00 0/0.00 |0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 100.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/1 (0%) 0/0 (0%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 274 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.961 (e) P=0.362 (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) P=0.333N (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) P=0.333N (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) P=0.333N (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.362 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.985 (e) P=0.333 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 0/0 (0%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 1/1.00 0/0.00 2/2.00 0/0.00 |0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 100.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 274 (T) --- 274 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/10 (20%) 1/10 (10%) 1/10 (10%) 2/10 (20%) | |POLY-3 RATE (b) | |2/8.23 1/8.04 1/8.71 2/8.73 | |POLY-3 PERCENT (g) | |24.3% 12.4% 11.5% 22.9% | |TERMINAL (d) | |2/8 (25%) 0/5 (0%) 1/6 (17%) 2/8 (25%) | |FIRST INCIDENCE | |274 (T) 113 274 (T) 274 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.582 P=0.622N P=0.607N P=0.712 | |POLY 3 | |P=0.541 P=0.509N P=0.479N P=0.685N | |POLY 1.5 | |P=0.529 P=0.508N P=0.488N P=0.695N | |POLY 6 | |P=0.552 P=0.527N P=0.482N P=0.685N | |LOGISTIC REGRESSION| |P=0.520 P=0.476N P=0.607N P=0.712 | |COCH-ARM / FISHERS | |P=0.514 P=0.500N P=0.500N P=0.709N | |ORDER RESTRICTED | |P=0.516N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/9 (0%) 2/10 (20%) 1/9 (11%) 0/10 (0%) |1/10 (10%) 2/10 (20%) 2/9 (22%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.00 2/7.75 1/8.02 0/8.51 |1/8.23 2/7.65 2/7.86 0/8.73 | |POLY-3 PERCENT (g) | 0.0% 25.8% 12.5% 0.0% |12.2% 26.2% 25.5% 0.0% | |TERMINAL (d) | 0/9 (0%) 1/6 (17%) 1/7 (14%) 0/7 (0%) |1/8 (13%) 1/5 (20%) 2/6 (33%) 0/8 (0%) | |FIRST INCIDENCE | --- 225 274 (T) --- |274 (T) 212 274 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.372N P=0.171 P=0.450 (e) |P=0.185N P=0.390 P=0.393 P=0.500N | |POLY 3 | P=0.404N P=0.190 P=0.477 (e) |P=0.198N P=0.473 P=0.483 P=0.488N | |POLY 1.5 | P=0.381N P=0.208 P=0.487 (e) |P=0.207N P=0.473 P=0.472 P=0.494N | |POLY 6 | P=0.430N P=0.176 P=0.464 (e) |P=0.195N P=0.463 P=0.485 P=0.488N | |LOGISTIC REGRESSION| P=0.346N P=0.248 P=0.450 (e) |P=0.200N P=0.468 P=0.393 (e) | |COCH-ARM / FISHERS | P=0.346N P=0.263 P=0.500 (e) |P=0.220N P=0.500 P=0.458 P=0.500N | |ORDER RESTRICTED | P=0.279 (e) (e) (e) |P=0.174N (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |0/10 (0%) 0/10 (0%) 3/10 (30%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.46 0/7.30 0/9.02 2/8.51 |0/8.23 0/7.11 3/8.87 0/8.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 23.5% |0.0% 0.0% 33.8% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 2/7 (29%) |0/8 (0%) 0/5 (0%) 1/6 (17%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- 274 (T) |--- --- 260 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.033 * (e) (e) P=0.178 |P=0.533N (e) P=0.106 (e) | |POLY 3 | P=0.033 * (e) (e) P=0.200 |P=0.523N (e) P=0.105 (e) | |POLY 1.5 | P=0.034 * (e) (e) P=0.210 |P=0.548N (e) P=0.099 (e) | |POLY 6 | P=0.031 * (e) (e) P=0.187 |P=0.506N (e) P=0.107 (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.178 |P=0.550N (e) P=0.111 (e) | |COCH-ARM / FISHERS | P=0.039 * (e) (e) P=0.237 |P=0.584N (e) P=0.105 (e) | |ORDER RESTRICTED | P=0.016 * (e) (e) (e) |P=0.138 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 2/10 (20%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.46 0/7.30 0/9.02 0/8.51 |0/8.23 0/7.11 2/8.86 0/8.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 22.6% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/7 (0%) |0/8 (0%) 0/5 (0%) 1/6 (17%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 260 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.614N (e) P=0.220 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.613N (e) P=0.242 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.630N (e) P=0.234 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.602N (e) P=0.244 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.632N (e) P=0.236 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.655N (e) P=0.237 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.242 (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/10 (30%) 1/10 (10%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 1/10 (10%) 2/10 (20%) 0/10 (0%) | |POLY-3 RATE (b) | 3/9.46 1/7.30 0/9.02 0/8.51 |0/8.23 1/7.11 2/8.87 0/8.73 | |POLY-3 PERCENT (g) | 31.7% 13.7% 0.0% 0.0% |0.0% 14.1% 22.6% 0.0% | |TERMINAL (d) | 3/9 (33%) 1/6 (17%) 0/8 (0%) 0/7 (0%) |0/8 (0%) 1/5 (20%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 274 (T) 274 (T) --- --- |--- 274 (T) 260 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.136N P=0.454N P=0.130N P=0.155N |P=0.429N P=0.406 P=0.238 (e) | |POLY 3 | P=0.100N P=0.394N P=0.102N P=0.113N |P=0.439N P=0.471 P=0.242 (e) | |POLY 1.5 | P=0.103N P=0.357N P=0.098N P=0.105N |P=0.452N P=0.477 P=0.235 (e) | |POLY 6 | P=0.099N P=0.428N P=0.107N P=0.123N |P=0.436N P=0.457 P=0.244 (e) | |LOGISTIC REGRESSION| P=0.136N P=0.454N (e) (e) |P=0.439N P=0.406 P=0.236 (e) | |COCH-ARM / FISHERS | P=0.124N P=0.291N P=0.105N P=0.105N |P=0.472N P=0.500 P=0.237 (e) | |ORDER RESTRICTED | P=0.017N* (e) (e) (e) |P=0.292N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin: Site of Application - Epidermis | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 8/10 (80%) 9/10 (90%) 10/10 (100%)|5/10 (50%) 8/10 (80%) 9/10 (90%) 10/10 (100%) | |POLY-3 RATE (b) | 2/10.00 8/9.20 9/10.00 10/10.00 |5/9.08 8/9.00 9/10.00 10/10.00 | |POLY-3 PERCENT (g) | 20.0% 87.0% 90.0% 100.0% |55.1% 88.9% 90.0% 100.0% | |TERMINAL (d) | 1/9 (11%) 5/6 (83%) 7/8 (88%) 7/7 (100%) |4/8 (50%) 4/5 (80%) 5/6 (83%) 8/8 (100%) | |FIRST INCIDENCE | 212 121 212 174 |146 113 68 50 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.023 * P=0.009 ** P=0.009 ** P=0.002 ** |P=0.269 P=0.072 P=0.070 P=0.057 | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P=0.054 P=0.136 P=0.107 P=0.019 * | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P=0.044 * P=0.121 P=0.092 P=0.014 * | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P=0.058 P=0.142 P=0.113 P=0.022 * | |LOGISTIC REGRESSION| P=0.005 ** P=0.023 * (e) (e) |P=0.033 * P=0.134 P=0.071 P=0.020 * | |COCH-ARM / FISHERS | P=0.006 ** P=0.012 * P=0.003 ** P<0.001 ** |P=0.031 * P=0.175 P=0.070 P=0.016 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.002 ** (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin: Site of Application - Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 8/10 (80%) 9/10 (90%) |0/10 (0%) 0/10 (0%) 3/10 (30%) 6/10 (60%) | |POLY-3 RATE (b) | 0/9.46 0/7.30 8/9.55 9/9.26 |0/8.23 0/7.11 3/8.71 6/9.72 | |POLY-3 PERCENT (g) | 0.0% 0.0% 83.7% 97.2% |0.0% 0.0% 34.4% 61.7% | |TERMINAL (d) | 0/9 (0%) 0/6 (0%) 7/8 (88%) 7/7 (100%) |0/8 (0%) 0/5 (0%) 3/6 (50%) 5/8 (63%) | |FIRST INCIDENCE | --- --- 212 225 |--- --- 274 (T) 50 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P=0.002 ** (e) P=0.062 P=0.010 * | |POLY 3 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.101 P=0.003 ** | |POLY 1.5 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.097 P=0.002 ** | |POLY 6 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.099 P=0.003 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.062 P=0.007 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.105 P=0.005 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Testes | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/10 (30%) 1/10 (10%) 1/10 (10%) 0/10 (0%) | | |POLY-3 RATE (b) | 3/10.00 1/7.30 1/9.02 0/8.51 | | |POLY-3 PERCENT (g) | 30.0% 13.7% 11.1% 0.0% | | |TERMINAL (d) | 2/9 (22%) 1/6 (17%) 1/8 (13%) 0/7 (0%) | | |FIRST INCIDENCE | 212 274 (T) 274 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.145N P=0.438N P=0.332N P=0.157N | | |POLY 3 | P=0.115N P=0.419N P=0.332N P=0.127N | | |POLY 1.5 | P=0.115N P=0.372N P=0.314N P=0.113N | | |POLY 6 | P=0.118N P=0.463N P=0.355N P=0.145N | | |LOGISTIC REGRESSION| P=0.126N P=0.323N P=0.255N P=0.074N | | |COCH-ARM / FISHERS | P=0.126N P=0.291N P=0.291N P=0.105N | | |ORDER RESTRICTED | P=0.041N* (e) (e) (e) | | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/10 (30%) 2/10 (20%) 1/10 (10%) 8/10 (80%) | | |POLY-3 RATE (b) | 3/10.00 2/8.22 1/9.02 8/8.95 | | |POLY-3 PERCENT (g) | 30.0% 24.3% 11.1% 89.4% | | |TERMINAL (d) | 2/9 (22%) 1/6 (17%) 1/8 (13%) 7/7 (100%) | | |FIRST INCIDENCE | 212 121 274 (T) 225 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.632N P=0.332N P=0.018 * | | |POLY 3 | P<0.001 ** P=0.597N P=0.332N P=0.005 ** | | |POLY 1.5 | P<0.001 ** P=0.559N P=0.314N P=0.010 * | | |POLY 6 | P<0.001 ** P=0.636N P=0.355N P=0.002 ** | | |LOGISTIC REGRESSION| P=0.002 ** P=0.298N P=0.255N P=0.027 * | | |COCH-ARM / FISHERS | P=0.002 ** P=0.500N P=0.291N P=0.035 * | | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/9 (0%) 3/10 (30%) 1/10 (10%) 4/9 (44%) |3/10 (30%) 3/10 (30%) 2/9 (22%) 1/10 (10%) | |POLY-3 RATE (b) | 0/8.46 3/9.46 1/9.46 4/7.95 |3/10.00 3/8.07 2/8.02 1/9.01 | |POLY-3 PERCENT (g) | 0.0% 31.7% 10.6% 50.3% |30.0% 37.2% 25.0% 11.1% | |TERMINAL (d) | 0/8 (0%) 0/6 (0%) 0/8 (0%) 3/6 (50%) |1/8 (13%) 0/5 (0%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- 121 225 225 |118 212 260 246 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.088 P=0.104 P=0.500 P=0.033 * |P=0.190N P=0.564 P=0.535N P=0.307N | |POLY 3 | P=0.042 * P=0.113 P=0.522 P=0.020 * |P=0.209N P=0.567 P=0.608N P=0.333N | |POLY 1.5 | P=0.046 * P=0.114 P=0.522 P=0.023 * |P=0.209N P=0.582 P=0.602N P=0.329N | |POLY 6 | P=0.039 * P=0.113 P=0.523 P=0.017 * |P=0.208N P=0.563 P=0.609N P=0.333N | |LOGISTIC REGRESSION| P=0.042 * P=0.558 P=0.583 P=0.038 * |P=0.208N P=0.633N P=0.573N P=0.282N | |COCH-ARM / FISHERS | P=0.062 P=0.124 P=0.526 P=0.041 * |P=0.196N P=0.686N P=0.556N P=0.291N | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) |P=0.210N (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/9 (33%) 4/10 (40%) 2/10 (20%) 3/9 (33%) |5/10 (50%) 2/10 (20%) 2/9 (22%) 3/10 (30%) | |POLY-3 RATE (b) | 3/8.46 4/7.30 2/9.46 3/7.95 |5/8.23 2/7.11 2/7.87 3/8.73 | |POLY-3 PERCENT (g) | 35.5% 54.8% 21.1% 37.7% |60.7% 28.1% 25.4% 34.4% | |TERMINAL (d) | 3/8 (38%) 4/6 (67%) 1/8 (13%) 2/6 (33%) |5/8 (63%) 2/5 (40%) 1/6 (17%) 3/8 (38%) | |FIRST INCIDENCE | 274 (T) 274 (T) 225 225 |274 (T) 274 (T) 260 274 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.606 P=0.301 P=0.500N P=0.554 |P=0.385N P=0.416N P=0.297N P=0.314N | |POLY 3 | P=0.609N P=0.399 P=0.444N P=0.655 |P=0.432N P=0.220N P=0.174N P=0.276N | |POLY 1.5 | P=0.602N P=0.459 P=0.445N P=0.665 |P=0.458N P=0.208N P=0.192N P=0.298N | |POLY 6 | P=0.619N P=0.346 P=0.442N P=0.644 |P=0.412N P=0.256N P=0.169N P=0.274N | |LOGISTIC REGRESSION| P=0.618N P=0.301 P=0.442N P=0.647 |P=0.401N P=0.416N P=0.185N P=0.314N | |COCH-ARM / FISHERS | P=0.604N P=0.570 P=0.444N P=0.690N |P=0.513N P=0.175N P=0.220N P=0.325N | |ORDER RESTRICTED | P=0.408N (e) (e) (e) |P=0.135N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 2/10 (20%) 2/10 (20%) 2/10 (20%) |2/10 (20%) 6/10 (60%) 2/10 (20%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 2/7.84 2/9.02 2/8.95 |2/9.08 6/8.07 2/8.87 0/8.73 | |POLY-3 PERCENT (g) | 20.0% 25.5% 22.2% 22.3% |22.0% 74.3% 22.6% 0.0% | |TERMINAL (d) | 1/9 (11%) 1/6 (17%) 2/8 (25%) 1/7 (14%) |1/8 (13%) 3/5 (60%) 0/6 (0%) 0/8 (0%) | |FIRST INCIDENCE | 212 212 274 (T) 225 |146 212 260 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.613 P=0.578 P=0.668 P=0.639 |P=0.036N* P=0.054 P=0.665 P=0.240N | |POLY 3 | P=0.629 P=0.609 P=0.664 P=0.662 |P=0.019N* P=0.034 * P=0.696 P=0.234N | |POLY 1.5 | P=0.637 P=0.641 P=0.681 P=0.678 |P=0.019N* P=0.035 * P=0.695 P=0.234N | |POLY 6 | P=0.616 P=0.583 P=0.642 P=0.644 |P=0.020N* P=0.034 * P=0.694 P=0.238N | |LOGISTIC REGRESSION| P=0.643 P=0.665N P=0.686N P=0.618N |P=0.029N* P=0.069 P=0.708 P=0.220N | |COCH-ARM / FISHERS | P=0.645 P=0.709N P=0.709N P=0.709N |P=0.031N* P=0.085 P=0.709N P=0.237N | |ORDER RESTRICTED | P=0.667 (e) (e) (e) |P=0.009N** (e) (e) (e) | |=================================================================================================================================| Date: 12/05/03 EXPERIMENT: 97013 TEST: 89 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (DICHLO ROACET Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 31.25 125MG/KG 500MG/KG |0 MG/KG 31.25 125MG/KG 500MG/KG | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |9/10 (90%) 8/10 (80%) 8/10 (80%) 8/10 (80%) | |POLY-3 RATE (b) | |9/9.08 8/8.07 8/8.87 8/8.73 | |POLY-3 PERCENT (g) | |99.1% 99.1% 90.2% 91.6% | |TERMINAL (d) | |8/8 (100%) 5/5 (100%) 6/6 (100%) 8/8 (100%) | |FIRST INCIDENCE | |146 212 260 274 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.151N P=0.262 P=0.498 P=0.500N | |POLY 3 | |P=0.503N P=1.000 P=0.591N P=0.674N | |POLY 1.5 | |P=0.505N P=0.989N P=0.587N P=0.641N | |POLY 6 | |P=0.589N P=1.000 P=0.640N P=0.808N | |LOGISTIC REGRESSION| |P=0.240N (e) P=0.386N P=0.377N | |COCH-ARM / FISHERS | |P=0.519N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | |P=0.290N (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).