TDMS Study 96007-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 05 TIME: 11:35:44 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3/CONTROL VS. TREATED GROUPS REASONS FOR REMOVAL: 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 NG/KG INCLUDE 002 6 NG/KG INCLUDE 003 20 NG/KG INCLUDE 004 44 NG/KG INCLUDE 005 92 NG/KG INCLUDE 006 200 NG/KG NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 05 TIME: 11:35:44 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4 Rats(SPRAGUE-DAWLEY) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Brain Clitoral/Preputial Gland Heart Islets, Pancreatic Kidney Liver Lung Nose Ovary Pancreas Parathyroid Gland Pituitary Gland Thyroid Gland NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 05 TIME: 11:35:44 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION( =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Liver Cholangiocarcinoma Hepatocellular Adenoma Mammary Gland Carcinoma Carcinoma or Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Carcinoma or Adenoma Thyroid Gland: C-Cell Carcinoma or Adenoma Uterus Adenoma All Organs Malignant Tumors =============================================================== Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 1 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 1/53 (2%) 0/53 (0%) 0/52 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 1/41.78 1/38.07 0/36.67 0/37.91 2/36.31 0/36.61 | |POLY-3 PERCENT (g) | 2.4% 2.6% 0.0% 0.0% 5.5% 0.0% | |TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 1/20 (5%) 0/23 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) --- --- 681 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.525N P=0.734 P=0.508N P=0.500N P=0.432 P=0.517N | |POLY 3 | P=0.522N P=0.740 P=0.526N P=0.519N P=0.451 P=0.526N | |POLY 1.5 | P=0.514N P=0.748 P=0.520N P=0.512N P=0.464 P=0.517N | |POLY 6 | P=0.529N P=0.731 P=0.531N P=0.528N P=0.445 P=0.535N | |LOGISTIC REGRESSION| P=0.535N P=0.734 (e) (e) P=0.441 (e) | |COCH-ARM / FISHERS | P=0.507N P=0.752N P=0.500N P=0.505N P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.356N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 5/53 (9%) 2/53 (4%) 6/52 (12%) 1/53 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 4/42.04 5/38.67 2/36.78 6/37.91 1/36.13 2/36.98 | |POLY-3 PERCENT (g) | 9.5% 12.9% 5.4% 15.8% 2.8% 5.4% | |TERMINAL (d) | 3/25 (12%) 2/22 (9%) 1/24 (4%) 6/25 (24%) 1/20 (5%) 1/23 (4%) | |FIRST INCIDENCE | 659 651 701 728 (T) 728 (T) 624 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.167N P=0.405 P=0.377N P=0.352 P=0.244N P=0.399N | |POLY 3 | P=0.164N P=0.447 P=0.400N P=0.304 P=0.227N P=0.397N | |POLY 1.5 | P=0.154N P=0.468 P=0.384N P=0.330 P=0.213N P=0.375N | |POLY 6 | P=0.173N P=0.428 P=0.412N P=0.274 P=0.236N P=0.418N | |LOGISTIC REGRESSION| P=0.171N P=0.420 P=0.411N P=0.276 P=0.231N P=0.411N | |COCH-ARM / FISHERS | P=0.138N P=0.500 P=0.339N P=0.359 P=0.181N P=0.339N | |ORDER RESTRICTED | P=0.226N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 2 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 5/53 (9%) 3/53 (6%) 6/52 (12%) 1/53 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 5/42.04 5/38.67 3/36.78 6/37.91 1/36.13 2/36.98 | |POLY-3 PERCENT (g) | 11.9% 12.9% 8.2% 15.8% 2.8% 5.4% | |TERMINAL (d) | 4/25 (16%) 2/22 (9%) 2/24 (8%) 6/25 (24%) 1/20 (5%) 1/23 (4%) | |FIRST INCIDENCE | 659 651 701 728 (T) 728 (T) 624 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.108N P=0.531 P=0.396N P=0.486 P=0.154N P=0.270N | |POLY 3 | P=0.105N P=0.578 P=0.431N P=0.427 P=0.139N P=0.270N | |POLY 1.5 | P=0.098N P=0.598 P=0.412N P=0.456 P=0.128N P=0.250N | |POLY 6 | P=0.111N P=0.558 P=0.446N P=0.392 P=0.146N P=0.288N | |LOGISTIC REGRESSION| P=0.110N P=0.546 P=0.447N P=0.397 P=0.143N P=0.287N | |COCH-ARM / FISHERS | P=0.087N P=0.629N P=0.358N P=0.486 P=0.103N P=0.219N | |ORDER RESTRICTED | P=0.175N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Heart | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/53 (4%) 0/52 (0%) 2/53 (4%) 0/53 (0%) 0/52 (0%) | |POLY-3 RATE (b) | 1/41.78 2/38.22 0/36.03 2/39.15 0/36.13 0/36.44 | |POLY-3 PERCENT (g) | 2.4% 5.2% 0.0% 5.1% 0.0% 0.0% | |TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 1/25 (4%) 0/20 (0%) 0/23 (0%) | |FIRST INCIDENCE | 728 (T) 689 --- 302 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.179N P=0.454 P=0.508N P=0.502 P=0.545N P=0.517N | |POLY 3 | P=0.185N P=0.469 P=0.529N P=0.477 P=0.529N P=0.527N | |POLY 1.5 | P=0.179N P=0.481 P=0.523N P=0.489 P=0.521N P=0.519N | |POLY 6 | P=0.190N P=0.456 P=0.533N P=0.463 P=0.533N P=0.535N | |LOGISTIC REGRESSION| P=0.173N P=0.443 (e) P=0.518 (e) (e) | |COCH-ARM / FISHERS | P=0.171N P=0.500 P=0.505N P=0.500 P=0.500N P=0.505N | |ORDER RESTRICTED | P=0.220N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 3 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 1/53 (2%) 1/52 (2%) 1/52 (2%) 2/52 (4%) | |POLY-3 RATE (b) | 0/41.78 0/38.07 1/36.67 1/37.91 1/35.47 2/36.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.7% 2.6% 2.8% 5.5% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 1/25 (4%) 0/20 (0%) 2/23 (9%) | |FIRST INCIDENCE | --- --- 728 (T) 728 (T) 721 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.087 (e) P=0.492 P=0.500 P=0.476 P=0.219 | |POLY 3 | P=0.082 (e) P=0.474 P=0.481 P=0.467 P=0.207 | |POLY 1.5 | P=0.086 (e) P=0.480 P=0.488 P=0.475 P=0.217 | |POLY 6 | P=0.078 (e) P=0.469 P=0.472 P=0.464 P=0.199 | |LOGISTIC REGRESSION| P=0.086 (e) P=0.492 P=0.500 P=0.464 P=0.219 | |COCH-ARM / FISHERS | P=0.094 (e) P=0.500 P=0.495 P=0.495 P=0.243 | |ORDER RESTRICTED | P=0.075 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 2/53 (4%) 1/52 (2%) 1/52 (2%) 2/52 (4%) | |POLY-3 RATE (b) | 0/41.78 0/38.07 2/36.67 1/37.91 1/35.47 2/36.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.5% 2.6% 2.8% 5.5% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 2/24 (8%) 1/25 (4%) 0/20 (0%) 2/23 (9%) | |FIRST INCIDENCE | --- --- 728 (T) 728 (T) 721 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.156 (e) P=0.228 P=0.500 P=0.476 P=0.219 | |POLY 3 | P=0.143 (e) P=0.209 P=0.481 P=0.467 P=0.207 | |POLY 1.5 | P=0.151 (e) P=0.216 P=0.488 P=0.475 P=0.217 | |POLY 6 | P=0.137 (e) P=0.204 P=0.472 P=0.464 P=0.199 | |LOGISTIC REGRESSION| P=0.154 (e) P=0.228 P=0.500 P=0.464 P=0.219 | |COCH-ARM / FISHERS | P=0.166 (e) P=0.248 P=0.495 P=0.495 P=0.243 | |ORDER RESTRICTED | P=0.101 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 4 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Cholangiocarcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 1/53 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 1/37.91 1/36.13 2/37.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.6% 2.8% 5.4% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 1/25 (4%) 1/20 (5%) 1/23 (4%) | |FIRST INCIDENCE | --- --- --- 728 (T) 728 (T) 608 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.034 * (e) (e) P=0.500 P=0.455 P=0.201 | |POLY 3 | P=0.036 * (e) (e) P=0.481 P=0.471 P=0.211 | |POLY 1.5 | P=0.038 * (e) (e) P=0.488 P=0.479 P=0.220 | |POLY 6 | P=0.035 * (e) (e) P=0.472 P=0.467 P=0.203 | |LOGISTIC REGRESSION| P=0.034 * (e) (e) P=0.500 P=0.455 P=0.219 | |COCH-ARM / FISHERS | P=0.041 * (e) (e) P=0.495 P=0.500 P=0.248 | |ORDER RESTRICTED | P=0.047 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/53 (0%) 1/53 (2%) 0/52 (0%) 2/53 (4%) 4/53 (8%) | |POLY-3 RATE (b) | 1/41.97 0/38.07 1/36.67 0/37.91 2/36.13 4/36.76 | |POLY-3 PERCENT (g) | 2.4% 0.0% 2.7% 0.0% 5.5% 10.9% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 0/25 (0%) 2/20 (10%) 3/23 (13%) | |FIRST INCIDENCE | 678 --- 728 (T) --- 728 (T) 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007 ** P=0.546N P=0.726 P=0.554N P=0.417 P=0.149 | |POLY 3 | P=0.006 ** P=0.519N P=0.730 P=0.520N P=0.448 P=0.140 | |POLY 1.5 | P=0.007 ** P=0.512N P=0.738 P=0.512N P=0.462 P=0.154 | |POLY 6 | P=0.006 ** P=0.528N P=0.724 P=0.530N P=0.439 P=0.127 | |LOGISTIC REGRESSION| P=0.005 ** P=0.514N P=0.730 P=0.515N P=0.441 P=0.127 | |COCH-ARM / FISHERS | P=0.008 ** P=0.500N P=0.752N P=0.505N P=0.500 P=0.181 | |ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 5 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 1/53 (2%) 2/53 (4%) 0/53 (0%) 1/53 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 1/41.78 1/38.07 2/36.67 0/38.22 1/36.13 0/36.61 | |POLY-3 PERCENT (g) | 2.4% 2.6% 5.5% 0.0% 2.8% 0.0% | |TERMINAL (d) | 1/25 (4%) 1/22 (5%) 2/24 (8%) 0/25 (0%) 1/20 (5%) 0/23 (0%) | |FIRST INCIDENCE | 728 (T) 728 (T) 728 (T) --- 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.254N P=0.734 P=0.486 P=0.500N P=0.712 P=0.517N | |POLY 3 | P=0.261N P=0.740 P=0.455 P=0.518N P=0.728 P=0.526N | |POLY 1.5 | P=0.255N P=0.748 P=0.466 P=0.509N P=0.737 P=0.517N | |POLY 6 | P=0.266N P=0.731 P=0.446 P=0.527N P=0.723 P=0.535N | |LOGISTIC REGRESSION| P=0.254N P=0.734 P=0.486 (e) P=0.712 (e) | |COCH-ARM / FISHERS | P=0.239N P=0.752N P=0.500 P=0.500N P=0.752N P=0.500N | |ORDER RESTRICTED | P=0.263N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 5/53 (9%) 12/53 (23%) 13/53 (25%) 2/53 (4%) 5/53 (9%) 3/53 (6%) | |POLY-3 RATE (b) | 5/42.44 12/40.22 13/40.44 2/38.22 5/37.02 3/38.06 | |POLY-3 PERCENT (g) | 11.8% 29.8% 32.2% 5.2% 13.5% 7.9% | |TERMINAL (d) | 3/25 (12%) 6/22 (27%) 7/24 (29%) 2/25 (8%) 4/20 (20%) 1/23 (4%) | |FIRST INCIDENCE | 619 420 219 728 (T) 348 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026N* P=0.034 * P=0.028 * P=0.247N P=0.505 P=0.430N | |POLY 3 | P=0.021N* P=0.036 * P=0.021 * P=0.259N P=0.543 P=0.417N | |POLY 1.5 | P=0.019N* P=0.042 * P=0.024 * P=0.238N P=0.568 P=0.395N | |POLY 6 | P=0.024N* P=0.030 * P=0.018 * P=0.286N P=0.524 P=0.440N | |LOGISTIC REGRESSION| P=0.018N* P=0.040 * P=0.035 * P=0.267N P=0.567 P=0.362N | |COCH-ARM / FISHERS | P=0.016N* P=0.055 P=0.034 * P=0.219N P=0.629N P=0.358N | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 6 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 6/53 (11%) 13/53 (25%) 14/53 (26%) 2/53 (4%) 6/53 (11%) 3/53 (6%) | |POLY-3 RATE (b) | 6/42.44 13/40.22 14/40.44 2/38.22 6/37.02 3/38.06 | |POLY-3 PERCENT (g) | 14.1% 32.3% 34.6% 5.2% 16.2% 7.9% | |TERMINAL (d) | 4/25 (16%) 7/22 (32%) 8/24 (33%) 2/25 (8%) 5/20 (25%) 1/23 (4%) | |FIRST INCIDENCE | 619 420 219 728 (T) 348 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016N* P=0.037 * P=0.031 * P=0.155N P=0.477 P=0.310N | |POLY 3 | P=0.012N* P=0.040 * P=0.024 * P=0.167N P=0.522 P=0.297N | |POLY 1.5 | P=0.011N* P=0.048 * P=0.027 * P=0.150N P=0.551 P=0.276N | |POLY 6 | P=0.014N* P=0.034 * P=0.021 * P=0.190N P=0.501 P=0.318N | |LOGISTIC REGRESSION| P=0.011N* P=0.042 * P=0.037 * P=0.177N P=0.535 P=0.258N | |COCH-ARM / FISHERS | P=0.010N* P=0.064 P=0.040 * P=0.135N P=0.620N P=0.244N | |ORDER RESTRICTED | P=0.014N* (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 34/53 (64%) 35/53 (66%) 30/53 (57%) 29/53 (55%) 34/53 (64%) 30/53 (57%) | |POLY-3 RATE (b) | 34/49.74 35/46.94 30/42.83 29/46.77 34/45.32 30/43.49 | |POLY-3 PERCENT (g) | 68.4% 74.6% 70.0% 62.0% 75.0% 69.0% | |TERMINAL (d) | 14/25 (56%) 13/22 (59%) 15/24 (63%) 11/25 (44%) 13/20 (65%) 15/23 (65%) | |FIRST INCIDENCE | 289 289 393 302 321 326 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.513 P=0.263 P=0.530N P=0.428N P=0.226 P=0.549 | |POLY 3 | P=0.536 P=0.321 P=0.521 P=0.325N P=0.307 P=0.565 | |POLY 1.5 | P=0.447N P=0.387 P=0.565N P=0.271N P=0.367 P=0.490N | |POLY 6 | P=0.436 P=0.277 P=0.467 P=0.383N P=0.283 P=0.448 | |LOGISTIC REGRESSION| P=0.366N P=0.487 P=0.406N P=0.199N P=0.503 P=0.348N | |COCH-ARM / FISHERS | P=0.301N P=0.500 P=0.276N P=0.214N P=0.580N P=0.276N | |ORDER RESTRICTED | P=0.616 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 7 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 35/53 (66%) 36/53 (68%) 30/53 (57%) 29/53 (55%) 35/53 (66%) 30/53 (57%) | |POLY-3 RATE (b) | 35/49.74 36/46.94 30/42.83 29/46.77 35/45.32 30/43.49 | |POLY-3 PERCENT (g) | 70.4% 76.7% 70.0% 62.0% 77.2% 69.0% | |TERMINAL (d) | 15/25 (60%) 14/22 (64%) 15/24 (63%) 11/25 (44%) 14/20 (70%) 15/23 (65%) | |FIRST INCIDENCE | 289 289 393 302 321 326 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.502N P=0.257 P=0.473N P=0.374N P=0.215 P=0.512N | |POLY 3 | P=0.482N P=0.312 P=0.579N P=0.251N P=0.294 P=0.533N | |POLY 1.5 | P=0.386N P=0.381 P=0.482N P=0.204N P=0.357 P=0.406N | |POLY 6 | P=0.500 P=0.265 P=0.555 P=0.302N P=0.268 P=0.537 | |LOGISTIC REGRESSION| P=0.319N P=0.475 P=0.336N P=0.151N P=0.482 P=0.282N | |COCH-ARM / FISHERS | P=0.254N P=0.500 P=0.213N P=0.160N P=0.581N P=0.213N | |ORDER RESTRICTED | P=0.561N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 38/53 (72%) 40/53 (75%) 37/53 (70%) 31/53 (58%) 38/53 (72%) 31/53 (58%) | |POLY-3 RATE (b) | 38/50.41 40/48.33 37/46.22 31/46.77 38/46.22 31/44.27 | |POLY-3 PERCENT (g) | 75.4% 82.8% 80.1% 66.3% 82.2% 70.0% | |TERMINAL (d) | 16/25 (64%) 16/22 (73%) 18/24 (75%) 13/25 (52%) 16/20 (80%) 15/23 (65%) | |FIRST INCIDENCE | 289 289 219 302 321 326 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300N P=0.205 P=0.393 P=0.337N P=0.199 P=0.417N | |POLY 3 | P=0.209N P=0.249 P=0.376 P=0.215N P=0.278 P=0.357N | |POLY 1.5 | P=0.138N P=0.310 P=0.453 P=0.157N P=0.352 P=0.244N | |POLY 6 | P=0.314N P=0.201 P=0.316 P=0.293N P=0.229 P=0.495N | |LOGISTIC REGRESSION| P=0.086N P=0.392 P=0.581 P=0.110N P=0.477 P=0.152N | |COCH-ARM / FISHERS | P=0.065N P=0.413 P=0.500N P=0.111N P=0.585N P=0.111N | |ORDER RESTRICTED | P=0.228N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 8 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 3/53 (6%) | |POLY-3 RATE (b) | 1/41.78 2/38.16 1/37.31 0/38.22 1/36.17 3/36.83 | |POLY-3 PERCENT (g) | 2.4% 5.2% 2.7% 0.0% 2.8% 8.1% | |TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 2/23 (9%) | |FIRST INCIDENCE | 728 (T) 706 517 --- 717 668 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.150 P=0.448 P=0.746 P=0.500N P=0.722 P=0.264 | |POLY 3 | P=0.149 P=0.468 P=0.735 P=0.518N P=0.728 P=0.261 | |POLY 1.5 | P=0.155 P=0.481 P=0.741 P=0.509N P=0.737 P=0.277 | |POLY 6 | P=0.143 P=0.455 P=0.732 P=0.527N P=0.724 P=0.247 | |LOGISTIC REGRESSION| P=0.145 P=0.437 P=0.762N (e) P=0.725 P=0.240 | |COCH-ARM / FISHERS | P=0.167 P=0.500 P=0.752N P=0.500N P=0.752N P=0.309 | |ORDER RESTRICTED | P=0.134 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 3/53 (6%) | |POLY-3 RATE (b) | 1/41.78 2/38.16 1/37.31 0/38.22 1/36.17 3/36.83 | |POLY-3 PERCENT (g) | 2.4% 5.2% 2.7% 0.0% 2.8% 8.1% | |TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 2/23 (9%) | |FIRST INCIDENCE | 728 (T) 706 517 --- 717 668 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.150 P=0.448 P=0.746 P=0.500N P=0.722 P=0.264 | |POLY 3 | P=0.149 P=0.468 P=0.735 P=0.518N P=0.728 P=0.261 | |POLY 1.5 | P=0.155 P=0.481 P=0.741 P=0.509N P=0.737 P=0.277 | |POLY 6 | P=0.143 P=0.455 P=0.732 P=0.527N P=0.724 P=0.247 | |LOGISTIC REGRESSION| P=0.145 P=0.437 P=0.762N (e) P=0.725 P=0.240 | |COCH-ARM / FISHERS | P=0.167 P=0.500 P=0.752N P=0.500N P=0.752N P=0.309 | |ORDER RESTRICTED | P=0.134 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 9 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Oral Mucosa | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 3/53 (6%) | |POLY-3 RATE (b) | 1/41.78 2/38.16 1/37.31 0/38.22 1/36.17 3/36.83 | |POLY-3 PERCENT (g) | 2.4% 5.2% 2.7% 0.0% 2.8% 8.1% | |TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 2/23 (9%) | |FIRST INCIDENCE | 728 (T) 706 517 --- 717 668 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.150 P=0.448 P=0.746 P=0.500N P=0.722 P=0.264 | |POLY 3 | P=0.149 P=0.468 P=0.735 P=0.518N P=0.728 P=0.261 | |POLY 1.5 | P=0.155 P=0.481 P=0.741 P=0.509N P=0.737 P=0.277 | |POLY 6 | P=0.143 P=0.455 P=0.732 P=0.527N P=0.724 P=0.247 | |LOGISTIC REGRESSION| P=0.145 P=0.437 P=0.762N (e) P=0.725 P=0.240 | |COCH-ARM / FISHERS | P=0.167 P=0.500 P=0.752N P=0.500N P=0.752N P=0.309 | |ORDER RESTRICTED | P=0.134 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Ovary | | Granulosa Cell Tumor: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 1/53 (2%) 0/52 (0%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/41.78 2/38.36 1/36.67 0/37.91 0/35.44 0/36.61 | |POLY-3 PERCENT (g) | 0.0% 5.2% 2.7% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/25 (0%) 1/22 (5%) 1/24 (4%) 0/25 (0%) 0/20 (0%) 0/23 (0%) | |FIRST INCIDENCE | --- 651 728 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.230N P=0.208 P=0.492 (e) (e) (e) | |POLY 3 | P=0.238N P=0.218 P=0.474 (e) (e) (e) | |POLY 1.5 | P=0.231N P=0.226 P=0.480 (e) (e) (e) | |POLY 6 | P=0.243N P=0.211 P=0.469 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.229N P=0.216 P=0.492 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.215N P=0.248 P=0.500 (e) (e) (e) | |ORDER RESTRICTED | P=0.279N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 10 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Pancreas | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 2/52 (4%) 0/52 (0%) | |POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/37.91 2/35.44 0/36.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.6% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 2/20 (10%) 0/23 (0%) | |FIRST INCIDENCE | --- --- --- --- 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.448 (e) (e) (e) P=0.190 (e) | |POLY 3 | P=0.442 (e) (e) (e) P=0.202 (e) | |POLY 1.5 | P=0.452 (e) (e) (e) P=0.210 (e) | |POLY 6 | P=0.426 (e) (e) (e) P=0.198 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.190 (e) | |COCH-ARM / FISHERS | P=0.458 (e) (e) (e) P=0.243 (e) | |ORDER RESTRICTED | P=0.152 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Parathyroid Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 2/51 (4%) 0/44 (0%) 0/51 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 0/38.63 2/37.50 0/31.58 0/37.26 0/34.13 0/33.79 | |POLY-3 PERCENT (g) | 0.0% 5.3% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/21 (5%) 0/22 (0%) 0/25 (0%) 0/19 (0%) 0/23 (0%) | |FIRST INCIDENCE | --- 503 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300N P=0.218 (e) (e) (e) (e) | |POLY 3 | P=0.299N P=0.230 (e) (e) (e) (e) | |POLY 1.5 | P=0.293N P=0.237 (e) (e) (e) (e) | |POLY 6 | P=0.306N P=0.222 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.284N P=0.254 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.287N P=0.258 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.209N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 11 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 21/53 (40%) 23/53 (43%) 23/53 (43%) 21/53 (40%) 16/53 (30%) | |POLY-3 RATE (b) | 15/43.22 21/40.29 23/40.24 23/41.13 21/40.54 16/39.31 | |POLY-3 PERCENT (g) | 34.7% 52.1% 57.2% 55.9% 51.8% 40.7% | |TERMINAL (d) | 8/25 (32%) 12/22 (55%) 13/24 (54%) 16/25 (64%) 8/20 (40%) 8/23 (35%) | |FIRST INCIDENCE | 603 600 420 470 420 549 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.420N P=0.070 P=0.046 * P=0.052 P=0.061 P=0.332 | |POLY 3 | P=0.344N P=0.075 P=0.027 * P=0.034 * P=0.081 P=0.367 | |POLY 1.5 | P=0.313N P=0.100 P=0.034 * P=0.050 P=0.090 P=0.411 | |POLY 6 | P=0.360N P=0.058 P=0.027 * P=0.022 * P=0.089 P=0.335 | |LOGISTIC REGRESSION| P=0.383N P=0.057 P=0.022 * P=0.024 * P=0.064 P=0.317 | |COCH-ARM / FISHERS | P=0.255N P=0.153 P=0.078 P=0.078 P=0.153 P=0.500 | |ORDER RESTRICTED | P=0.085 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 22/53 (42%) 23/53 (43%) 23/53 (43%) 21/53 (40%) 16/53 (30%) | |POLY-3 RATE (b) | 15/43.22 22/40.53 23/40.24 23/41.13 21/40.54 16/39.31 | |POLY-3 PERCENT (g) | 34.7% 54.3% 57.2% 55.9% 51.8% 40.7% | |TERMINAL (d) | 8/25 (32%) 12/22 (55%) 13/24 (54%) 16/25 (64%) 8/20 (40%) 8/23 (35%) | |FIRST INCIDENCE | 603 600 420 470 420 549 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.390N P=0.049 * P=0.046 * P=0.052 P=0.061 P=0.332 | |POLY 3 | P=0.311N P=0.050 P=0.027 * P=0.034 * P=0.081 P=0.367 | |POLY 1.5 | P=0.281N P=0.068 P=0.034 * P=0.050 P=0.090 P=0.411 | |POLY 6 | P=0.329N P=0.038 * P=0.027 * P=0.022 * P=0.089 P=0.335 | |LOGISTIC REGRESSION| P=0.348N P=0.037 * P=0.022 * P=0.024 * P=0.064 P=0.317 | |COCH-ARM / FISHERS | P=0.227N P=0.111 P=0.078 P=0.078 P=0.153 P=0.500 | |ORDER RESTRICTED | P=0.077 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 12 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 0/41.78 1/38.37 2/36.87 1/38.22 0/36.13 2/37.38 | |POLY-3 PERCENT (g) | 0.0% 2.6% 5.4% 2.6% 0.0% 5.4% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 1/25 (4%) 0/20 (0%) 1/23 (4%) | |FIRST INCIDENCE | --- 647 675 728 (T) --- 442 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.305 P=0.473 P=0.215 P=0.500 (e) P=0.228 | |POLY 3 | P=0.296 P=0.483 P=0.210 P=0.482 (e) P=0.213 | |POLY 1.5 | P=0.306 P=0.490 P=0.216 P=0.491 (e) P=0.221 | |POLY 6 | P=0.288 P=0.476 P=0.206 P=0.473 (e) P=0.205 | |LOGISTIC REGRESSION| P=0.317 P=0.498 P=0.206 P=0.500 (e) P=0.259 | |COCH-ARM / FISHERS | P=0.330 P=0.500 P=0.248 P=0.500 (e) P=0.248 | |ORDER RESTRICTED | P=0.105 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Skin | | Neurofibrosarcoma, Neurofibroma, or Schwannoma (benign, | | malignant or NOS) | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/41.78 2/38.22 0/36.67 0/38.22 0/36.13 0/36.61 | |POLY-3 PERCENT (g) | 0.0% 5.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/25 (0%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) | |FIRST INCIDENCE | --- 689 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.299N P=0.211 (e) (e) (e) (e) | |POLY 3 | P=0.304N P=0.217 (e) (e) (e) (e) | |POLY 1.5 | P=0.297N P=0.225 (e) (e) (e) (e) | |POLY 6 | P=0.309N P=0.209 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.303N P=0.206 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.288N P=0.248 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.197N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 13 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 13/53 (25%) 10/53 (19%) 9/51 (18%) 9/53 (17%) 6/51 (12%) 7/51 (14%) | |POLY-3 RATE (b) | 13/43.49 10/39.80 9/36.75 9/38.42 6/35.57 7/36.03 | |POLY-3 PERCENT (g) | 29.9% 25.1% 24.5% 23.4% 16.9% 19.4% | |TERMINAL (d) | 8/25 (32%) 5/22 (23%) 6/24 (25%) 8/25 (32%) 4/20 (20%) 5/23 (22%) | |FIRST INCIDENCE | 500 530 570 675 642 570 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.137N P=0.475N P=0.316N P=0.269N P=0.152N P=0.178N | |POLY 3 | P=0.149N P=0.404N P=0.386N P=0.340N P=0.138N P=0.207N | |POLY 1.5 | P=0.133N P=0.370N P=0.359N P=0.288N P=0.116N P=0.174N | |POLY 6 | P=0.163N P=0.437N P=0.398N P=0.406N P=0.152N P=0.238N | |LOGISTIC REGRESSION| P=0.154N P=0.392N P=0.369N P=0.342N P=0.126N P=0.197N | |COCH-ARM / FISHERS | P=0.108N P=0.319N P=0.269N P=0.237N P=0.076N P=0.125N | |ORDER RESTRICTED | P=0.179N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/53 (4%) 2/51 (4%) 2/53 (4%) 0/51 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 2/41.78 2/38.36 2/36.00 2/38.22 0/35.23 1/35.09 | |POLY-3 PERCENT (g) | 4.8% 5.2% 5.6% 5.2% 0.0% 2.9% | |TERMINAL (d) | 2/25 (8%) 1/22 (5%) 1/24 (4%) 2/25 (8%) 0/20 (0%) 1/23 (4%) | |FIRST INCIDENCE | 728 (T) 651 636 728 (T) --- 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263N P=0.644 P=0.665 P=0.697 P=0.288N P=0.529N | |POLY 3 | P=0.271N P=0.664 P=0.640 P=0.662 P=0.276N P=0.561N | |POLY 1.5 | P=0.263N P=0.675 P=0.647 P=0.677 P=0.268N P=0.544N | |POLY 6 | P=0.276N P=0.652 P=0.638 P=0.645 P=0.281N P=0.575N | |LOGISTIC REGRESSION| P=0.274N P=0.644 P=0.634 P=0.697 (e) P=0.529N | |COCH-ARM / FISHERS | P=0.245N P=0.691N P=0.676 P=0.691N P=0.257N P=0.515N | |ORDER RESTRICTED | P=0.363N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 14 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 12/53 (23%) 10/51 (20%) 10/53 (19%) 6/51 (12%) 7/51 (14%) | |POLY-3 RATE (b) | 15/43.49 12/40.09 10/36.75 10/38.42 6/35.57 7/36.03 | |POLY-3 PERCENT (g) | 34.5% 29.9% 27.2% 26.0% 16.9% 19.4% | |TERMINAL (d) | 10/25 (40%) 6/22 (27%) 7/24 (29%) 9/25 (36%) 4/20 (20%) 5/23 (22%) | |FIRST INCIDENCE | 500 530 570 675 642 570 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.052N P=0.500N P=0.249N P=0.201N P=0.075N P=0.087N | |POLY 3 | P=0.055N P=0.415N P=0.322N P=0.275N P=0.063N P=0.104N | |POLY 1.5 | P=0.048N* P=0.381N P=0.295N P=0.226N P=0.051N P=0.083N | |POLY 6 | P=0.062N P=0.445N P=0.332N P=0.341N P=0.070N P=0.123N | |LOGISTIC REGRESSION| P=0.059N P=0.421N P=0.313N P=0.287N P=0.059N P=0.105N | |COCH-ARM / FISHERS | P=0.038N* P=0.328N P=0.210N P=0.180N P=0.031N* P=0.056N | |ORDER RESTRICTED | P=0.069N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/41.97 0/38.07 0/36.67 0/38.22 0/36.13 0/36.61 | |POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) | |FIRST INCIDENCE | 678 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.262N P=0.280N P=0.274N P=0.269N P=0.295N P=0.275N | |POLY 3 | P=0.225N P=0.259N P=0.268N P=0.258N P=0.272N P=0.268N | |POLY 1.5 | P=0.234N P=0.250N P=0.260N P=0.248N P=0.262N P=0.257N | |POLY 6 | P=0.215N P=0.270N P=0.275N P=0.270N P=0.278N P=0.280N | |LOGISTIC REGRESSION| P=0.261N P=0.265N P=0.270N P=0.265N P=0.273N P=0.274N | |COCH-ARM / FISHERS | P=0.248N P=0.248N P=0.248N P=0.248N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.013N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 15 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 5/53 (9%) 2/53 (4%) | |POLY-3 RATE (b) | 1/41.97 1/38.16 0/36.67 1/38.22 5/36.27 2/36.98 | |POLY-3 PERCENT (g) | 2.4% 2.6% 0.0% 2.6% 13.8% 5.4% | |TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 1/25 (4%) 2/20 (10%) 1/23 (4%) | |FIRST INCIDENCE | 678 706 --- 728 (T) 707 624 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.107 P=0.713 P=0.554N P=0.731 P=0.071 P=0.438 | |POLY 3 | P=0.103 P=0.740 P=0.527N P=0.740 P=0.070 P=0.456 | |POLY 1.5 | P=0.110 P=0.748 P=0.520N P=0.750 P=0.078 P=0.472 | |POLY 6 | P=0.096 P=0.730 P=0.532N P=0.728 P=0.065 P=0.441 | |LOGISTIC REGRESSION| P=0.097 P=0.741 P=0.521N P=0.735 P=0.067 P=0.464 | |COCH-ARM / FISHERS | P=0.121 P=0.752N P=0.500N P=0.752N P=0.103 P=0.500 | |ORDER RESTRICTED | P=0.062 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 9/53 (17%) 3/53 (6%) 6/53 (11%) 5/53 (9%) 7/53 (13%) 4/53 (8%) | |POLY-3 RATE (b) | 9/43.07 3/38.73 6/36.87 5/38.22 7/36.66 4/37.55 | |POLY-3 PERCENT (g) | 20.9% 7.8% 16.3% 13.1% 19.1% 10.7% | |TERMINAL (d) | 4/25 (16%) 1/22 (5%) 5/24 (21%) 5/25 (20%) 3/20 (15%) 2/23 (9%) | |FIRST INCIDENCE | 588 547 675 728 (T) 667 498 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.370N P=0.118N P=0.376N P=0.243N P=0.561N P=0.196N | |POLY 3 | P=0.343N P=0.084N P=0.405N P=0.261N P=0.532N P=0.172N | |POLY 1.5 | P=0.329N P=0.073N P=0.370N P=0.227N P=0.491N P=0.149N | |POLY 6 | P=0.354N P=0.099N P=0.441N P=0.311N P=0.561N P=0.198N | |LOGISTIC REGRESSION| P=0.374N P=0.079N P=0.395N P=0.267N P=0.522N P=0.158N | |COCH-ARM / FISHERS | P=0.305N P=0.061N P=0.289N P=0.195N P=0.393N P=0.118N | |ORDER RESTRICTED | P=0.155N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 16 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 9/53 (17%) 4/53 (8%) 6/53 (11%) 5/53 (9%) 7/53 (13%) 4/53 (8%) | |POLY-3 RATE (b) | 9/43.07 4/39.40 6/36.87 5/38.22 7/36.66 4/37.55 | |POLY-3 PERCENT (g) | 20.9% 10.2% 16.3% 13.1% 19.1% 10.7% | |TERMINAL (d) | 4/25 (16%) 1/22 (5%) 5/24 (21%) 5/25 (20%) 3/20 (15%) 2/23 (9%) | |FIRST INCIDENCE | 588 503 675 728 (T) 667 498 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.323N P=0.199N P=0.376N P=0.243N P=0.561N P=0.196N | |POLY 3 | P=0.303N P=0.149N P=0.405N P=0.261N P=0.532N P=0.172N | |POLY 1.5 | P=0.286N P=0.135N P=0.370N P=0.227N P=0.491N P=0.149N | |POLY 6 | P=0.317N P=0.168N P=0.441N P=0.311N P=0.561N P=0.198N | |LOGISTIC REGRESSION| P=0.320N P=0.135N P=0.395N P=0.267N P=0.522N P=0.158N | |COCH-ARM / FISHERS | P=0.260N P=0.118N P=0.289N P=0.195N P=0.393N P=0.118N | |ORDER RESTRICTED | P=0.161N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 45/53 (85%) 45/53 (85%) 43/53 (81%) 42/53 (79%) 45/53 (85%) 41/53 (77%) | |POLY-3 RATE (b) | 45/50.55 45/48.80 43/45.62 42/47.71 45/46.75 41/46.25 | |POLY-3 PERCENT (g) | 89.0% 92.2% 94.3% 88.0% 96.3% 88.6% | |TERMINAL (d) | 21/25 (84%) 20/22 (91%) 22/24 (92%) 22/25 (88%) 19/20 (95%) 20/23 (87%) | |FIRST INCIDENCE | 289 289 393 302 321 326 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.473 P=0.245 P=0.409 P=0.543 P=0.152 P=0.467 | |POLY 3 | P=0.472N P=0.414 P=0.278 P=0.571N P=0.146 P=0.613N | |POLY 1.5 | P=0.344N P=0.497 P=0.371 P=0.431N P=0.229 P=0.457N | |POLY 6 | P=0.552 P=0.345 P=0.279 P=0.564 P=0.131 P=0.545 | |LOGISTIC REGRESSION| P=0.342N P=0.513 P=0.455 P=0.366N P=0.265 P=0.391N | |COCH-ARM / FISHERS | P=0.215N P=0.607N P=0.398N P=0.307N P=0.607N P=0.229N | |ORDER RESTRICTED | P=0.450 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 17 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 12/53 (23%) 20/53 (38%) 21/53 (40%) 13/53 (25%) 16/53 (30%) 16/53 (30%) | |POLY-3 RATE (b) | 12/43.55 20/42.49 21/43.07 13/41.30 16/40.31 16/43.29 | |POLY-3 PERCENT (g) | 27.6% 47.1% 48.8% 31.5% 39.7% 37.0% | |TERMINAL (d) | 7/25 (28%) 8/22 (36%) 10/24 (42%) 8/25 (32%) 6/20 (30%) 5/23 (22%) | |FIRST INCIDENCE | 377 420 196 302 113 329 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.505 P=0.041 * P=0.036 * P=0.445 P=0.136 P=0.178 | |POLY 3 | P=0.454N P=0.044 * P=0.030 * P=0.437 P=0.168 P=0.236 | |POLY 1.5 | P=0.460N P=0.051 P=0.033 * P=0.471 P=0.192 P=0.238 | |POLY 6 | P=0.434N P=0.041 * P=0.030 * P=0.396 P=0.154 P=0.244 | |LOGISTIC REGRESSION| P=0.450N P=0.050 P=0.046 * P=0.473 P=0.227 P=0.281 | |COCH-ARM / FISHERS | P=0.448N P=0.069 P=0.046 * P=0.500 P=0.255 P=0.255 | |ORDER RESTRICTED | P=0.155 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 | | | NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 48/53 (91%) 49/53 (92%) 49/53 (92%) 44/53 (83%) 48/53 (91%) 46/53 (87%) | |POLY-3 RATE (b) | 48/51.69 49/50.68 49/49.46 44/49.02 48/49.59 46/49.29 | |POLY-3 PERCENT (g) | 92.9% 96.7% 99.1% 89.8% 96.8% 93.3% | |TERMINAL (d) | 22/25 (88%) 21/22 (96%) 24/24 (100%) 22/25 (88%) 19/20 (95%) 21/23 (91%) | |FIRST INCIDENCE | 289 289 196 302 113 326 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.408 P=0.200 P=0.250 P=0.521N P=0.152 P=0.348 | |POLY 3 | P=0.415N P=0.325 P=0.121 P=0.414N P=0.317 P=0.626 | |POLY 1.5 | P=0.352N P=0.386 P=0.183 P=0.291N P=0.406 P=0.601N | |POLY 6 | P=0.492N P=0.287 P=0.103 P=0.566N P=0.283 P=0.550 | |LOGISTIC REGRESSION| P=0.342N P=0.430 P=0.255 P=0.224N P=0.452 P=0.512N | |COCH-ARM / FISHERS | P=0.253N P=0.500 P=0.500 P=0.195N P=0.629N P=0.380N | |ORDER RESTRICTED | P=0.422N (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).