TDMS Study 96021-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB 153) DATE: 12/15/03 EXPERIMENT: 96021 TEST: 01 TIME: 11:05:35 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: C96021 PATHOLOGIST: SELLS, DONALD CAS: 35065-27-1 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#4 RATS CTRL VS STOP REASONS FOR REMOVAL: 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 UG/KG INCLUDE 007 3000 UG/KG STOP NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB 153) DATE: 12/15/03 EXPERIMENT: 96021 TEST: 01 TIME: 11:05:35 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: C96021 PATHOLOGIST: SELLS, DONALD CAS: 35065-27-1 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 Medulla Bone Marrow Brain Heart Islets, Pancreatic Kidney Liver Lung Ovary Pancreas Parathyroid Gland Pituitary Gland Thyroid Gland NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB 153) DATE: 12/15/03 EXPERIMENT: 96021 TEST: 01 TIME: 11:05:35 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: C96021 PATHOLOGIST: SELLS, DONALD CAS: 35065-27-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION ( =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Medulla Pheochromocytoma Benign Pheochromocytoma: Benign, Complex, Malignant, NOS Islets, Pancreatic Carcinoma or Adenoma Liver Cholangioma Mammary Gland Adenoma Carcinoma Carcinoma or Adenoma Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Carcinoma or Adenoma Skin Fibroma Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma Fibrosarcoma Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma Thyroid Gland: C-Cell Adenoma Carcinoma Carcinoma or Adenoma Thyroid Gland: Follicular Cell Adenoma Uterus Polyp Stromal All Organs Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 1 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 6/50 (12%) | |POLY-3 RATE (b) | 2/39.13 6/37.40 | |POLY-3 PERCENT (g) | 5.1% 16.0% | |TERMINAL (d) | 1/24 (4%) 2/20 (10%) | |FIRST INCIDENCE | 701 591 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.113 | |POLY 3 | P=0.117 | |POLY 1.5 | P=0.114 | |POLY 6 | P=0.124 | |LOGISTIC REGRESSION| P=0.113 | |COCH-ARM / FISHERS | P=0.117 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 6/50 (12%) | |POLY-3 RATE (b) | 3/39.55 6/37.40 | |POLY-3 PERCENT (g) | 7.6% 16.0% | |TERMINAL (d) | 1/24 (4%) 2/20 (10%) | |FIRST INCIDENCE | 608 591 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.208 | |POLY 3 | P=0.214 | |POLY 1.5 | P=0.210 | |POLY 6 | P=0.222 | |LOGISTIC REGRESSION| P=0.208 | |COCH-ARM / FISHERS | P=0.216 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 2 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 1/39.01 2/36.65 | |POLY-3 PERCENT (g) | 2.6% 5.5% | |TERMINAL (d) | 1/24 (4%) 1/20 (5%) | |FIRST INCIDENCE | 731 (T) 656 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.458 | |POLY 3 | P=0.485 | |POLY 1.5 | P=0.483 | |POLY 6 | P=0.491 | |LOGISTIC REGRESSION| P=0.480 | |COCH-ARM / FISHERS | P=0.478 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Cholangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/39.01 2/36.38 | |POLY-3 PERCENT (g) | 0.0% 5.5% | |TERMINAL (d) | 0/24 (0%) 2/20 (10%) | |FIRST INCIDENCE | --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.198 | |POLY 3 | P=0.228 | |POLY 1.5 | P=0.228 | |POLY 6 | P=0.229 | |LOGISTIC REGRESSION| P=0.198 | |COCH-ARM / FISHERS | P=0.233 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 3 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/39.01 0/36.38 | |POLY-3 PERCENT (g) | 5.1% 0.0% | |TERMINAL (d) | 2/24 (8%) 0/20 (0%) | |FIRST INCIDENCE | 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.278N | |POLY 3 | P=0.260N | |POLY 1.5 | P=0.263N | |POLY 6 | P=0.254N | |LOGISTIC REGRESSION| (e) | |COCH-ARM / FISHERS | P=0.262N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 8/53 (15%) 10/50 (20%) | |POLY-3 RATE (b) | 8/39.57 10/38.41 | |POLY-3 PERCENT (g) | 20.2% 26.0% | |TERMINAL (d) | 6/24 (25%) 4/20 (20%) | |FIRST INCIDENCE | 608 245 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.296 | |POLY 3 | P=0.367 | |POLY 1.5 | P=0.352 | |POLY 6 | P=0.393 | |LOGISTIC REGRESSION| P=0.334 | |COCH-ARM / FISHERS | P=0.346 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 4 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 9/53 (17%) 10/50 (20%) | |POLY-3 RATE (b) | 9/39.57 10/38.41 | |POLY-3 PERCENT (g) | 22.8% 26.0% | |TERMINAL (d) | 7/24 (29%) 4/20 (20%) | |FIRST INCIDENCE | 608 245 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.381 | |POLY 3 | P=0.472 | |POLY 1.5 | P=0.453 | |POLY 6 | P=0.502 | |LOGISTIC REGRESSION| P=0.432 | |COCH-ARM / FISHERS | P=0.444 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 41/53 (77%) 30/50 (60%) | |POLY-3 RATE (b) | 41/49.26 30/43.00 | |POLY-3 PERCENT (g) | 83.2% 69.8% | |TERMINAL (d) | 19/24 (79%) 11/20 (55%) | |FIRST INCIDENCE | 399 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.195N | |POLY 3 | P=0.091N | |POLY 1.5 | P=0.077N | |POLY 6 | P=0.096N | |LOGISTIC REGRESSION| P=0.052N | |COCH-ARM / FISHERS | P=0.045N* | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 5 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 41/53 (77%) 30/50 (60%) | |POLY-3 RATE (b) | 41/49.26 30/43.00 | |POLY-3 PERCENT (g) | 83.2% 69.8% | |TERMINAL (d) | 19/24 (79%) 11/20 (55%) | |FIRST INCIDENCE | 399 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.195N | |POLY 3 | P=0.091N | |POLY 1.5 | P=0.077N | |POLY 6 | P=0.096N | |LOGISTIC REGRESSION| P=0.052N | |COCH-ARM / FISHERS | P=0.045N* | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 43/53 (81%) 37/50 (74%) | |POLY-3 RATE (b) | 43/49.39 37/44.76 | |POLY-3 PERCENT (g) | 87.1% 82.7% | |TERMINAL (d) | 20/24 (83%) 14/20 (70%) | |FIRST INCIDENCE | 399 245 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.468N | |POLY 3 | P=0.378N | |POLY 1.5 | P=0.358N | |POLY 6 | P=0.367N | |LOGISTIC REGRESSION| P=0.307N | |COCH-ARM / FISHERS | P=0.264N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 6 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 18/53 (34%) 23/50 (46%) | |POLY-3 RATE (b) | 18/41.75 23/39.65 | |POLY-3 PERCENT (g) | 43.1% 58.0% | |TERMINAL (d) | 10/24 (42%) 14/20 (70%) | |FIRST INCIDENCE | 211 437 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.107 | |POLY 3 | P=0.120 | |POLY 1.5 | P=0.117 | |POLY 6 | P=0.131 | |LOGISTIC REGRESSION| P=0.125 | |COCH-ARM / FISHERS | P=0.148 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 18/53 (34%) 24/50 (48%) | |POLY-3 RATE (b) | 18/41.75 24/40.16 | |POLY-3 PERCENT (g) | 43.1% 59.8% | |TERMINAL (d) | 10/24 (42%) 14/20 (70%) | |FIRST INCIDENCE | 211 437 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.080 | |POLY 3 | P=0.088 | |POLY 1.5 | P=0.082 | |POLY 6 | P=0.103 | |LOGISTIC REGRESSION| P=0.087 | |COCH-ARM / FISHERS | P=0.106 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 7 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Skin | | Fibroma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/39.01 2/37.14 | |POLY-3 PERCENT (g) | 0.0% 5.4% | |TERMINAL (d) | 0/24 (0%) 1/20 (5%) | |FIRST INCIDENCE | --- 452 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.213 | |POLY 3 | P=0.231 | |POLY 1.5 | P=0.230 | |POLY 6 | P=0.233 | |LOGISTIC REGRESSION| P=0.233 | |COCH-ARM / FISHERS | P=0.233 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 0/53 (0%) 7/50 (14%) | |POLY-3 RATE (b) | 0/39.01 7/38.88 | |POLY-3 PERCENT (g) | 0.0% 18.0% | |TERMINAL (d) | 0/24 (0%) 2/20 (10%) | |FIRST INCIDENCE | --- 183 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008 ** | |POLY 3 | P=0.007 ** | |POLY 1.5 | P=0.006 ** | |POLY 6 | P=0.008 ** | |LOGISTIC REGRESSION| P=0.009 ** | |COCH-ARM / FISHERS | P=0.005 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 8 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 0/53 (0%) 4/50 (8%) | |POLY-3 RATE (b) | 0/39.01 4/37.78 | |POLY-3 PERCENT (g) | 0.0% 10.6% | |TERMINAL (d) | 0/24 (0%) 1/20 (5%) | |FIRST INCIDENCE | --- 183 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.054 | |POLY 3 | P=0.056 | |POLY 1.5 | P=0.055 | |POLY 6 | P=0.058 | |LOGISTIC REGRESSION| P=0.063 | |COCH-ARM / FISHERS | P=0.052 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 0/53 (0%) 5/50 (10%) | |POLY-3 RATE (b) | 0/39.01 5/38.11 | |POLY-3 PERCENT (g) | 0.0% 13.1% | |TERMINAL (d) | 0/24 (0%) 1/20 (5%) | |FIRST INCIDENCE | --- 183 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.030 * | |POLY 3 | P=0.028 * | |POLY 1.5 | P=0.027 * | |POLY 6 | P=0.030 * | |LOGISTIC REGRESSION| P=0.032 * | |COCH-ARM / FISHERS | P=0.024 * | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 9 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 16/51 (31%) 18/49 (37%) | |POLY-3 RATE (b) | 16/39.99 18/37.75 | |POLY-3 PERCENT (g) | 40.0% 47.7% | |TERMINAL (d) | 10/24 (42%) 11/20 (55%) | |FIRST INCIDENCE | 555 437 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.260 | |POLY 3 | P=0.323 | |POLY 1.5 | P=0.324 | |POLY 6 | P=0.329 | |LOGISTIC REGRESSION| P=0.327 | |COCH-ARM / FISHERS | P=0.361 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/51 (4%) 3/49 (6%) | |POLY-3 RATE (b) | 2/38.11 3/36.14 | |POLY-3 PERCENT (g) | 5.3% 8.3% | |TERMINAL (d) | 2/24 (8%) 1/20 (5%) | |FIRST INCIDENCE | 731 (T) 669 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.444 | |POLY 3 | P=0.480 | |POLY 1.5 | P=0.477 | |POLY 6 | P=0.489 | |LOGISTIC REGRESSION| P=0.477 | |COCH-ARM / FISHERS | P=0.481 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 10 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 18/51 (35%) 19/49 (39%) | |POLY-3 RATE (b) | 18/39.99 19/37.90 | |POLY-3 PERCENT (g) | 45.0% 50.1% | |TERMINAL (d) | 12/24 (50%) 11/20 (55%) | |FIRST INCIDENCE | 555 437 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.317 | |POLY 3 | P=0.410 | |POLY 1.5 | P=0.404 | |POLY 6 | P=0.430 | |LOGISTIC REGRESSION| P=0.406 | |COCH-ARM / FISHERS | P=0.439 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 0/38.11 2/35.75 | |POLY-3 PERCENT (g) | 0.0% 5.6% | |TERMINAL (d) | 0/24 (0%) 2/20 (10%) | |FIRST INCIDENCE | --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.198 | |POLY 3 | P=0.229 | |POLY 1.5 | P=0.229 | |POLY 6 | P=0.230 | |LOGISTIC REGRESSION| P=0.198 | |COCH-ARM / FISHERS | P=0.238 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 11 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 7/53 (13%) 4/50 (8%) | |POLY-3 RATE (b) | 7/39.74 4/37.16 | |POLY-3 PERCENT (g) | 17.6% 10.8% | |TERMINAL (d) | 4/24 (17%) 1/20 (5%) | |FIRST INCIDENCE | 590 624 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.324N | |POLY 3 | P=0.301N | |POLY 1.5 | P=0.309N | |POLY 6 | P=0.287N | |LOGISTIC REGRESSION| P=0.297N | |COCH-ARM / FISHERS | P=0.298N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/39.53 0/36.38 | |POLY-3 PERCENT (g) | 5.1% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/20 (0%) | |FIRST INCIDENCE | 571 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263N | |POLY 3 | P=0.265N | |POLY 1.5 | P=0.266N | |POLY 6 | P=0.263N | |LOGISTIC REGRESSION| P=0.252N | |COCH-ARM / FISHERS | P=0.262N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 12 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 50/53 (94%) 44/50 (88%) | |POLY-3 RATE (b) | 50/51.13 44/45.72 | |POLY-3 PERCENT (g) | 97.8% 96.2% | |TERMINAL (d) | 24/24 (100%) 19/20 (95%) | |FIRST INCIDENCE | 211 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.520N | |POLY 3 | P=0.593N | |POLY 1.5 | P=0.520N | |POLY 6 | P=0.561N | |LOGISTIC REGRESSION| P=0.341N | |COCH-ARM / FISHERS | P=0.216N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 12/53 (23%) 23/50 (46%) | |POLY-3 RATE (b) | 12/41.43 23/43.60 | |POLY-3 PERCENT (g) | 29.0% 52.8% | |TERMINAL (d) | 7/24 (29%) 7/20 (35%) | |FIRST INCIDENCE | 442 183 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017 * | |POLY 3 | P=0.018 * | |POLY 1.5 | P=0.014 * | |POLY 6 | P=0.026 * | |LOGISTIC REGRESSION| P=0.012 * | |COCH-ARM / FISHERS | P=0.011 * | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 12/15/03 EXPERIMENT: 96021 TEST: 01 Page 13 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 3000 UG/ | | | KG STOP | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # | |----------- | | |OVERALL (a) | 52/53 (98%) 49/50 (98%) | |POLY-3 RATE (b) | 52/52.21 49/50.00 | |POLY-3 PERCENT (g) | 99.6% 98.0% | |TERMINAL (d) | 24/24 (100%) 19/20 (95%) | |FIRST INCIDENCE | 211 183 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.420 | |POLY 3 | P=0.581N | |POLY 1.5 | P=0.658N | |POLY 6 | P=0.518N | |LOGISTIC REGRESSION| P=0.763N | |COCH-ARM / FISHERS | P=0.738N | |ORDER RESTRICTED | (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).