TDMS Study 88036-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ANTHRAQUINONE DATE: 02/25/99 EXPERIMENT: 88036 TEST: 03 TIME: 11:47:29 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-25337 ROUTE: DOSED FEED NTP C#: C88036 PATHOLOGIST: SINGER, A. CAS: 84-65-1 ------------------------------------------------------------------------------------------------------------------------------------ 2 YEAR CHRONIC RATS REASONS FOR REMOVAL: 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ANTHRAQUINONE DATE: 02/25/99 EXPERIMENT: 88036 TEST: 03 TIME: 11:47:29 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-25337 ROUTE: DOSED FEED NTP C#: C88036 PATHOLOGIST: SINGER, A. CAS: 84-65-1 Rats(FISCHER 344) ----------------------------- 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 Salivary Glands Spleen Testes Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ANTHRAQUINONE DATE: 02/25/99 EXPERIMENT: 88036 TEST: 03 TIME: 11:47:29 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-25337 ROUTE: DOSED FEED NTP C#: C88036 PATHOLOGIST: SINGER, A. CAS: 84-65-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ANTHRAQUINONE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Kidney: Renal Tubule Adenoma Carcinoma or Adenoma Mammary Gland Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Skin Keratoacanthoma Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma Squamous Cell Papilloma, Papilloma, or Keratoacanthoma Urinary Bladder Carcinoma or Papilloma Papilloma All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Mesothelioma: Benign, Malignant, NOS Mesothelioma: Malignant Malignant Tumors =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Clitoral/Preputial Gland Carcinoma or Adenoma Kidney: Renal Tubule Adenoma Carcinoma or Adenoma Liver Hepatocellular Adenoma Mammary Gland Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Thyroid Gland: C-Cell Adenoma Carcinoma or Adenoma Urinary Bladder Carcinoma or Papilloma All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 1 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 8/50 (16%) 10/50 (20%) 6/50 (12%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 19.5% 18.0% 23.1% 13.7% 26.5% | |TERMINAL (d) | 6/22 (27%) 4/23 (17%) 5/22 (23%) 5/26 (19%) 6/22 (27%) | |FIRST INCIDENCE | 681 642 643 727 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.297 P=0.536N P=0.454 P=0.252N P=0.328 | |POLY 3 | P=0.276 P=0.539N P=0.446 P=0.336N P=0.310 | |POLY 1.5 | P=0.276 P=0.570N P=0.421 P=0.361N P=0.299 | |POLY 6 | P=0.278 P=0.497N P=0.485 P=0.302N P=0.331 | |LOGISTIC REGRESSION| P=0.263 P=0.505N P=0.496 P=0.238N P=0.312 | |COCH-ARM / FISHERS | P=0.294 P=0.607N P=0.398 P=0.387N P=0.306 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.2% 2.1% 4.2% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 1/35 (3%) 1/37 (3%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 730 (T) 730 (T) 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.106 (e) P=0.584 P=0.595 P=0.281 | |POLY 3 | P=0.088 (e) P=0.509 P=0.518 P=0.263 | |POLY 1.5 | P=0.081 (e) P=0.503 P=0.509 P=0.248 | |POLY 6 | P=0.099 (e) P=0.520 P=0.531 P=0.287 | |LOGISTIC REGRESSION| P=0.056 (e) P=0.584 P=0.595 P=0.165 | |COCH-ARM / FISHERS | P=0.073 (e) P=0.500 P=0.500 P=0.242 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 2 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 9/50 (18%) 10/50 (20%) 7/50 (14%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 19.5% 20.2% 23.1% 16.0% 26.5% | |TERMINAL (d) | 6/22 (27%) 4/23 (17%) 5/22 (23%) 6/26 (23%) 6/22 (27%) | |FIRST INCIDENCE | 681 642 643 727 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.321 P=0.574 P=0.454 P=0.348N P=0.328 | |POLY 3 | P=0.301 P=0.574 P=0.446 P=0.446N P=0.310 | |POLY 1.5 | P=0.300 P=0.541 P=0.421 P=0.473N P=0.299 | |POLY 6 | P=0.304 P=0.598N P=0.485 P=0.409N P=0.331 | |LOGISTIC REGRESSION| P=0.286 P=0.603N P=0.496 P=0.331N P=0.312 | |COCH-ARM / FISHERS | P=0.318 P=0.500 P=0.398 P=0.500N P=0.306 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.4% 2.1% 4.2% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 2/35 (6%) 1/37 (3%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 730 (T) 730 (T) 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.177 (e) P=0.335 P=0.595 P=0.281 | |POLY 3 | P=0.148 (e) P=0.247 P=0.518 P=0.263 | |POLY 1.5 | P=0.136 (e) P=0.240 P=0.509 P=0.248 | |POLY 6 | P=0.168 (e) P=0.260 P=0.531 P=0.287 | |LOGISTIC REGRESSION| P=0.104 (e) P=0.335 P=0.595 P=0.165 | |COCH-ARM / FISHERS | P=0.124 (e) P=0.247 P=0.500 P=0.242 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 3 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Brain | | Astrocytoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 1/22 (5%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 312 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.516N (e) P=0.240 (e) (e) | |POLY 3 | P=0.510N (e) P=0.252 (e) (e) | |POLY 1.5 | P=0.515N (e) P=0.246 (e) (e) | |POLY 6 | P=0.503N (e) P=0.261 (e) (e) | |LOGISTIC REGRESSION| P=0.344N (e) P=0.284 (e) (e) | |COCH-ARM / FISHERS | P=0.516N (e) P=0.247 (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Brain | | Astrocytoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.2% 2.1% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 85 647 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.684N (e) P=0.500 P=0.523 (e) | |POLY 3 | P=0.676N (e) P=0.513 P=0.519 (e) | |POLY 1.5 | P=0.688N (e) P=0.507 P=0.510 (e) | |POLY 6 | P=0.658N (e) P=0.525 P=0.533 (e) | |LOGISTIC REGRESSION| P=0.563 (e) (e) P=0.403 (e) | |COCH-ARM / FISHERS | P=0.685 (e) P=0.500 P=0.500 (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 4 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Brain | | Oligodendroglioma, Glioma, or Astrocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.6% 0.0% 2.5% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 1/22 (5%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 312 --- 671 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.410 (e) P=0.240 (e) P=0.518 | |POLY 3 | P=0.404 (e) P=0.252 (e) P=0.501 | |POLY 1.5 | P=0.402 (e) P=0.246 (e) P=0.498 | |POLY 6 | P=0.407 (e) P=0.261 (e) P=0.504 | |LOGISTIC REGRESSION| P=0.535 (e) P=0.284 (e) P=0.500 | |COCH-ARM / FISHERS | P=0.408 (e) P=0.247 (e) P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Brain | | Oligodendroglioma, Glioma, or Astrocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.3% 2.1% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 85 647 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.582N (e) P=0.238 P=0.523 (e) | |POLY 3 | P=0.560N (e) P=0.256 P=0.519 (e) | |POLY 1.5 | P=0.577N (e) P=0.247 P=0.510 (e) | |POLY 6 | P=0.534N (e) P=0.271 P=0.533 (e) | |LOGISTIC REGRESSION| P=0.526 (e) (e) P=0.403 (e) | |COCH-ARM / FISHERS | P=0.598N (e) P=0.247 P=0.500 (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 5 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 9/49 (18%) 7/50 (14%) 4/49 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 7.3% 20.5% 16.2% 9.2% 4.9% | |TERMINAL (d) | 2/22 (9%) 5/23 (22%) 3/22 (14%) 2/25 (8%) 2/22 (9%) | |FIRST INCIDENCE | 565 597 643 628 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.096N P=0.087 P=0.196 P=0.567 P=0.498N | |POLY 3 | P=0.092N P=0.072 P=0.175 P=0.527 P=0.507N | |POLY 1.5 | P=0.094N P=0.064 P=0.166 P=0.508 P=0.508N | |POLY 6 | P=0.089N P=0.085 P=0.192 P=0.556 P=0.505N | |LOGISTIC REGRESSION| P=0.095N P=0.068 P=0.176 P=0.490 P=0.500N | |COCH-ARM / FISHERS | P=0.091N P=0.056 P=0.159 P=0.489 P=0.500N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/49 (6%) 3/46 (7%) 4/48 (8%) 2/49 (4%) 1/48 (2%) | |POLY-3 ADJUSTED (b)| 7.0% 6.9% 9.3% 4.3% 2.1% | |TERMINAL (d) | 1/23 (4%) 3/39 (8%) 3/34 (9%) 2/37 (5%) 0/38 (0%) | |FIRST INCIDENCE | 689 730 (T) 723 730 (T) 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.094N P=0.443N P=0.615N P=0.319N P=0.198N | |POLY 3 | P=0.132N P=0.655N P=0.503 P=0.467N P=0.275N | |POLY 1.5 | P=0.143N P=0.652 P=0.491 P=0.482N P=0.292N | |POLY 6 | P=0.116N P=0.624N P=0.528 P=0.441N P=0.248N | |LOGISTIC REGRESSION| P=0.149N P=0.608N P=0.564 P=0.429N P=0.394N | |COCH-ARM / FISHERS | P=0.157N P=0.631 P=0.488 P=0.500N P=0.316N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 6 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 2/50 (4%) 5/49 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.4% 2.3% 4.6% 11.7% 7.3% | |TERMINAL (d) | 0/22 (0%) 1/23 (4%) 0/22 (0%) 3/25 (12%) 1/22 (5%) | |FIRST INCIDENCE | 648 729 (T) 603 690 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.124 P=0.738N P=0.523 P=0.152 P=0.322 | |POLY 3 | P=0.114 P=0.750N P=0.518 P=0.111 P=0.306 | |POLY 1.5 | P=0.116 P=0.757N P=0.509 P=0.104 P=0.302 | |POLY 6 | P=0.112 P=0.742N P=0.530 P=0.122 P=0.312 | |LOGISTIC REGRESSION| P=0.119 P=0.764N P=0.493 P=0.123 P=0.305 | |COCH-ARM / FISHERS | P=0.127 P=0.747 P=0.500 P=0.098 P=0.309 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 1/46 (2%) 2/48 (4%) 0/49 (0%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 4.7% 2.3% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/39 (0%) 0/34 (0%) 0/37 (0%) 0/38 (0%) | |FIRST INCIDENCE | 702 645 571 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083N P=0.408N P=0.624N P=0.166N P=0.146N | |POLY 3 | P=0.097N P=0.491N P=0.685N P=0.221N P=0.220N | |POLY 1.5 | P=0.099N P=0.506N P=0.691 P=0.228N P=0.231N | |POLY 6 | P=0.095N P=0.465N P=0.664N P=0.208N P=0.204N | |LOGISTIC REGRESSION| P=0.113N P=0.559N P=0.692N P=0.216N P=0.221N | |COCH-ARM / FISHERS | P=0.102N P=0.524N P=0.684 P=0.247N P=0.253N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 7 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 10/49 (20%) 9/50 (18%) 9/49 (18%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 9.6% 22.8% 20.6% 20.7% 12.1% | |TERMINAL (d) | 2/22 (9%) 6/23 (26%) 3/22 (14%) 5/25 (20%) 3/22 (14%) | |FIRST INCIDENCE | 565 597 603 628 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.391N P=0.108 P=0.158 P=0.190 P=0.512 | |POLY 3 | P=0.399N P=0.086 P=0.133 P=0.131 P=0.495 | |POLY 1.5 | P=0.399N P=0.077 P=0.124 P=0.119 P=0.491 | |POLY 6 | P=0.398N P=0.099 P=0.149 P=0.151 P=0.501 | |LOGISTIC REGRESSION| P=0.397N P=0.081 P=0.124 P=0.123 P=0.496 | |COCH-ARM / FISHERS | P=0.376N P=0.068 P=0.117 P=0.109 P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 5/49 (10%) 4/46 (9%) 6/48 (13%) 2/49 (4%) 1/48 (2%) | |POLY-3 ADJUSTED (b)| 11.6% 9.1% 13.7% 4.3% 2.1% | |TERMINAL (d) | 1/23 (4%) 3/39 (8%) 3/34 (9%) 2/37 (5%) 0/38 (0%) | |FIRST INCIDENCE | 689 645 571 730 (T) 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.021N* P=0.275N P=0.547N P=0.095N P=0.043N* | |POLY 3 | P=0.032N* P=0.488N P=0.513 P=0.188N P=0.083N | |POLY 1.5 | P=0.036N* P=0.513N P=0.493 P=0.201N P=0.094N | |POLY 6 | P=0.027N* P=0.445N P=0.551 P=0.169N P=0.069N | |LOGISTIC REGRESSION| P=0.046N* P=0.506N P=0.489 P=0.162N P=0.149N | |COCH-ARM / FISHERS | P=0.042N* P=0.541N P=0.485 P=0.218N P=0.107N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 8 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.5% 0.0% 4.7% 0.0% 0.0% | |TERMINAL (d) | 0/21 (0%) 0/23 (0%) 2/22 (9%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 642 --- 729 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.274N P=0.471N P=0.520 P=0.485N P=0.505N | |POLY 3 | P=0.278N P=0.483N P=0.522 P=0.482N P=0.497N | |POLY 1.5 | P=0.278N P=0.488N P=0.515 P=0.489N P=0.498N | |POLY 6 | P=0.277N P=0.475N P=0.534 P=0.473N P=0.495N | |LOGISTIC REGRESSION| P=0.277N P=0.530N P=0.530 P=0.503N P=0.488N | |COCH-ARM / FISHERS | P=0.275N P=0.495N P=0.508 P=0.495N P=0.495N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 9 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 3/50 (6%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.9% 0.0% 7.0% 0.0% 0.0% | |TERMINAL (d) | 0/21 (0%) 0/23 (0%) 3/22 (14%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 562 --- 729 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.134N P=0.217N P=0.523 P=0.224N P=0.243N | |POLY 3 | P=0.139N P=0.221N P=0.523 P=0.220N P=0.236N | |POLY 1.5 | P=0.138N P=0.226N P=0.516 P=0.227N P=0.237N | |POLY 6 | P=0.139N P=0.214N P=0.534 P=0.212N P=0.236N | |LOGISTIC REGRESSION| P=0.135N P=0.295N P=0.509 P=0.224N P=0.196N | |COCH-ARM / FISHERS | P=0.136N P=0.242N P=0.510 P=0.242N P=0.242N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 1/40 (3%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 730 (T) 718 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.348N P=0.610 P=0.576 (e) (e) | |POLY 3 | P=0.386N P=0.518 P=0.512 (e) (e) | |POLY 1.5 | P=0.397N P=0.511 P=0.506 (e) (e) | |POLY 6 | P=0.370N P=0.531 P=0.523 (e) (e) | |LOGISTIC REGRESSION| P=0.368N P=0.610 P=0.530 (e) (e) | |COCH-ARM / FISHERS | P=0.408N P=0.505 P=0.505 (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 10 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Pelvis and Transitional Epithelium | | Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.7% 0.0% 2.5% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | --- --- 638 --- 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.399 (e) P=0.260 (e) P=0.500 | |POLY 3 | P=0.401 (e) P=0.249 (e) P=0.500 | |POLY 1.5 | P=0.400 (e) P=0.243 (e) P=0.498 | |POLY 6 | P=0.403 (e) P=0.259 (e) P=0.502 | |LOGISTIC REGRESSION| P=0.401 (e) P=0.238 (e) P=0.500 | |COCH-ARM / FISHERS | P=0.408 (e) P=0.247 (e) P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Pelvis and Transitional Epithelium | | Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 11 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 9/50 (18%) 5/50 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.5% 6.8% 20.7% 11.4% 7.3% | |TERMINAL (d) | 1/22 (5%) 1/23 (4%) 3/22 (14%) 3/26 (12%) 1/22 (5%) | |FIRST INCIDENCE | 729 (T) 669 648 690 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.474 P=0.339 P=0.018 * P=0.159 P=0.319 | |POLY 3 | P=0.474 P=0.333 P=0.010 * P=0.119 P=0.308 | |POLY 1.5 | P=0.469 P=0.320 P=0.009 ** P=0.110 P=0.303 | |POLY 6 | P=0.485 P=0.349 P=0.013 * P=0.133 P=0.316 | |LOGISTIC REGRESSION| P=0.467 P=0.351 P=0.013 * P=0.147 P=0.305 | |COCH-ARM / FISHERS | P=0.485 P=0.309 P=0.008 ** P=0.102 P=0.309 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 4/50 (8%) 9/50 (18%) 7/50 (14%) 12/49 (24%) | |POLY-3 ADJUSTED (b)| 0.0% 8.6% 19.8% 14.8% 25.2% | |TERMINAL (d) | 0/23 (0%) 4/40 (10%) 8/35 (23%) 5/37 (14%) 9/40 (23%) | |FIRST INCIDENCE | --- 730 (T) 570 635 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.005 ** P=0.153 P=0.011 * P=0.036 * P=0.007 ** | |POLY 3 | P<0.001 ** P=0.071 P=0.002 ** P=0.011 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.066 P=0.002 ** P=0.009 ** P<0.001 ** | |POLY 6 | P=0.002 ** P=0.081 P=0.003 ** P=0.015 * P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.153 P=0.003 ** P=0.014 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.059 P<0.001 ** P=0.006 ** P<0.001 ** | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 12 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 4.3% 0.0% 2.1% 4.2% | |TERMINAL (d) | 0/23 (0%) 2/40 (5%) 0/35 (0%) 0/37 (0%) 2/40 (5%) | |FIRST INCIDENCE | --- 730 (T) --- 611 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.284 P=0.367 (e) P=0.517 P=0.367 | |POLY 3 | P=0.242 P=0.255 (e) P=0.519 P=0.259 | |POLY 1.5 | P=0.228 P=0.246 (e) P=0.510 P=0.246 | |POLY 6 | P=0.266 P=0.271 (e) P=0.534 P=0.281 | |LOGISTIC REGRESSION| P=0.210 P=0.367 (e) P=0.354 P=0.367 | |COCH-ARM / FISHERS | P=0.211 P=0.247 (e) P=0.500 P=0.242 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 13 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 9/50 (18%) 5/50 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.5% 6.8% 20.7% 11.4% 7.3% | |TERMINAL (d) | 1/22 (5%) 1/23 (4%) 3/22 (14%) 3/26 (12%) 1/22 (5%) | |FIRST INCIDENCE | 729 (T) 669 648 690 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.474 P=0.339 P=0.018 * P=0.159 P=0.319 | |POLY 3 | P=0.474 P=0.333 P=0.010 * P=0.119 P=0.308 | |POLY 1.5 | P=0.469 P=0.320 P=0.009 ** P=0.110 P=0.303 | |POLY 6 | P=0.485 P=0.349 P=0.013 * P=0.133 P=0.316 | |LOGISTIC REGRESSION| P=0.467 P=0.351 P=0.013 * P=0.147 P=0.305 | |COCH-ARM / FISHERS | P=0.485 P=0.309 P=0.008 ** P=0.102 P=0.309 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 6/50 (12%) 9/50 (18%) 8/50 (16%) 14/49 (29%) | |POLY-3 ADJUSTED (b)| 0.0% 12.9% 19.8% 16.7% 29.5% | |TERMINAL (d) | 0/23 (0%) 6/40 (15%) 8/35 (23%) 5/37 (14%) 11/40 (28%) | |FIRST INCIDENCE | --- 730 (T) 570 611 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.067 P=0.011 * P=0.022 * P=0.003 ** | |POLY 3 | P<0.001 ** P=0.020 * P=0.002 ** P=0.006 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.018 * P=0.002 ** P=0.005 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.024 * P=0.003 ** P=0.008 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.067 P=0.003 ** P=0.004 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.013 * P<0.001 ** P=0.003 ** P<0.001 ** | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 14 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 4/50 (8%) 4/50 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.5% 6.9% 9.4% 9.1% 4.9% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 4/22 (18%) 4/26 (15%) 2/22 (9%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.545 P=0.318 P=0.174 P=0.229 P=0.500 | |POLY 3 | P=0.518 P=0.330 P=0.192 P=0.200 P=0.499 | |POLY 1.5 | P=0.518 P=0.319 P=0.185 P=0.190 P=0.496 | |POLY 6 | P=0.519 P=0.345 P=0.203 P=0.217 P=0.504 | |LOGISTIC REGRESSION| P=0.545 P=0.318 P=0.174 P=0.229 P=0.500 | |COCH-ARM / FISHERS | P=0.534 P=0.309 P=0.181 P=0.181 P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 6/50 (12%) 4/50 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 4.3% 13.3% 8.5% 6.4% | |TERMINAL (d) | 0/23 (0%) 2/40 (5%) 5/35 (14%) 3/37 (8%) 3/40 (8%) | |FIRST INCIDENCE | --- 730 (T) 676 723 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.397 P=0.367 P=0.048 * P=0.143 P=0.234 | |POLY 3 | P=0.298 P=0.255 P=0.018 * P=0.072 P=0.136 | |POLY 1.5 | P=0.267 P=0.246 P=0.016 * P=0.067 P=0.126 | |POLY 6 | P=0.351 P=0.271 P=0.022 * P=0.083 P=0.156 | |LOGISTIC REGRESSION| P=0.362 P=0.367 P=0.027 * P=0.121 P=0.234 | |COCH-ARM / FISHERS | P=0.236 P=0.247 P=0.013 * P=0.059 P=0.117 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 15 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 4/50 (8%) 5/50 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.5% 6.9% 9.4% 11.4% 7.3% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 4/22 (18%) 5/26 (19%) 2/22 (9%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.322 P=0.318 P=0.174 P=0.139 P=0.310 | |POLY 3 | P=0.310 P=0.330 P=0.192 P=0.118 P=0.307 | |POLY 1.5 | P=0.308 P=0.319 P=0.185 P=0.110 P=0.303 | |POLY 6 | P=0.314 P=0.345 P=0.203 P=0.130 P=0.314 | |LOGISTIC REGRESSION| P=0.292 P=0.318 P=0.174 P=0.139 P=0.306 | |COCH-ARM / FISHERS | P=0.321 P=0.309 P=0.181 P=0.102 P=0.309 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 6/50 (12%) 4/50 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 2.3% 4.3% 13.3% 8.5% 6.4% | |TERMINAL (d) | 0/23 (0%) 2/40 (5%) 5/35 (14%) 3/37 (8%) 3/40 (8%) | |FIRST INCIDENCE | 571 730 (T) 676 723 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.508 P=0.626 P=0.126 P=0.315 P=0.458 | |POLY 3 | P=0.398 P=0.523 P=0.062 P=0.203 P=0.335 | |POLY 1.5 | P=0.368 P=0.511 P=0.057 P=0.192 P=0.317 | |POLY 6 | P=0.448 P=0.543 P=0.071 P=0.223 P=0.367 | |LOGISTIC REGRESSION| P=0.392 P=0.457 P=0.060 P=0.156 P=0.247 | |COCH-ARM / FISHERS | P=0.336 P=0.500 P=0.056 P=0.181 P=0.301 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 16 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 4/50 (8%) 5/50 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.5% 6.9% 9.4% 11.4% 7.3% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 4/22 (18%) 5/26 (19%) 2/22 (9%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.322 P=0.318 P=0.174 P=0.139 P=0.310 | |POLY 3 | P=0.310 P=0.330 P=0.192 P=0.118 P=0.307 | |POLY 1.5 | P=0.308 P=0.319 P=0.185 P=0.110 P=0.303 | |POLY 6 | P=0.314 P=0.345 P=0.203 P=0.130 P=0.314 | |LOGISTIC REGRESSION| P=0.292 P=0.318 P=0.174 P=0.139 P=0.306 | |COCH-ARM / FISHERS | P=0.321 P=0.309 P=0.181 P=0.102 P=0.309 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 6/50 (12%) 4/50 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 2.3% 4.3% 13.3% 8.5% 6.4% | |TERMINAL (d) | 0/23 (0%) 2/40 (5%) 5/35 (14%) 3/37 (8%) 3/40 (8%) | |FIRST INCIDENCE | 571 730 (T) 676 723 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.508 P=0.626 P=0.126 P=0.315 P=0.458 | |POLY 3 | P=0.398 P=0.523 P=0.062 P=0.203 P=0.335 | |POLY 1.5 | P=0.368 P=0.511 P=0.057 P=0.192 P=0.317 | |POLY 6 | P=0.448 P=0.543 P=0.071 P=0.223 P=0.367 | |LOGISTIC REGRESSION| P=0.392 P=0.457 P=0.060 P=0.156 P=0.247 | |COCH-ARM / FISHERS | P=0.336 P=0.500 P=0.056 P=0.181 P=0.301 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 17 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.9% 4.6% 0.0% 4.6% 0.0% | |TERMINAL (d) | 1/22 (5%) 2/23 (9%) 0/22 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 665 729 (T) --- 719 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.180N P=0.670N P=0.230N P=0.629N P=0.233N | |POLY 3 | P=0.192N P=0.671N P=0.228N P=0.670N P=0.238N | |POLY 1.5 | P=0.191N P=0.681N P=0.233N P=0.682N P=0.240N | |POLY 6 | P=0.194N P=0.659N P=0.221N P=0.653N P=0.236N | |LOGISTIC REGRESSION| P=0.185N P=0.649N P=0.226N P=0.648N P=0.237N | |COCH-ARM / FISHERS | P=0.185N P=0.691N P=0.247N P=0.691N P=0.247N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.1% 4.4% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 2/35 (6%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 592 730 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.304N P=0.504 P=0.335 (e) (e) | |POLY 3 | P=0.328N P=0.517 P=0.247 (e) (e) | |POLY 1.5 | P=0.342N P=0.509 P=0.240 (e) (e) | |POLY 6 | P=0.306N P=0.532 P=0.260 (e) (e) | |LOGISTIC REGRESSION| P=0.381N P=0.484 P=0.335 (e) (e) | |COCH-ARM / FISHERS | P=0.359N P=0.500 P=0.247 (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 18 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.9% 4.6% 0.0% 4.6% 0.0% | |TERMINAL (d) | 1/22 (5%) 2/23 (9%) 0/22 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 665 729 (T) --- 719 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.180N P=0.670N P=0.230N P=0.629N P=0.233N | |POLY 3 | P=0.192N P=0.671N P=0.228N P=0.670N P=0.238N | |POLY 1.5 | P=0.191N P=0.681N P=0.233N P=0.682N P=0.240N | |POLY 6 | P=0.194N P=0.659N P=0.221N P=0.653N P=0.236N | |LOGISTIC REGRESSION| P=0.185N P=0.649N P=0.226N P=0.648N P=0.237N | |COCH-ARM / FISHERS | P=0.185N P=0.691N P=0.247N P=0.691N P=0.247N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 2/50 (4%) 0/50 (0%) 1/48 (2%) | |POLY-3 ADJUSTED (b)| 2.3% 4.2% 4.4% 0.0% 2.1% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 2/35 (6%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | 605 592 730 (T) --- 718 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.321N P=0.533 P=0.594 P=0.487N P=0.698N | |POLY 3 | P=0.375N P=0.528 P=0.512 P=0.484N P=0.743N | |POLY 1.5 | P=0.387N P=0.515 P=0.503 P=0.492N P=0.755N | |POLY 6 | P=0.356N P=0.552 P=0.530 P=0.472N P=0.721N | |LOGISTIC REGRESSION| P=0.450N P=0.423 P=0.500 P=0.653N P=0.633 | |COCH-ARM / FISHERS | P=0.402N P=0.500 P=0.500 P=0.500N P=0.742 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 19 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.7% 0.0% 0.0% 2.1% 0.0% | |TERMINAL (d) | 2/23 (9%) 0/40 (0%) 0/35 (0%) 1/37 (3%) 0/40 (0%) | |FIRST INCIDENCE | 730 (T) --- --- 730 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.209N P=0.127N P=0.151N P=0.336N P=0.127N | |POLY 3 | P=0.267N P=0.220N P=0.227N P=0.469N P=0.213N | |POLY 1.5 | P=0.264N P=0.229N P=0.234N P=0.483N P=0.225N | |POLY 6 | P=0.273N P=0.206N P=0.215N P=0.445N P=0.195N | |LOGISTIC REGRESSION| P=0.209N (e) (e) P=0.336N (e) | |COCH-ARM / FISHERS | P=0.264N P=0.247N P=0.247N P=0.500N P=0.247N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 20 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% 2.2% 4.2% 6.2% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 1/35 (3%) 1/37 (3%) 1/40 (3%) | |FIRST INCIDENCE | 571 --- 730 (T) 638 712 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.108 P=0.500N P=0.720N P=0.565 P=0.449 | |POLY 3 | P=0.079 P=0.487N P=0.753N P=0.529 P=0.343 | |POLY 1.5 | P=0.074 P=0.493N P=0.759N P=0.516 P=0.325 | |POLY 6 | P=0.087 P=0.475N P=0.742N P=0.552 P=0.375 | |LOGISTIC REGRESSION| P=0.057 P=0.483N P=0.753N P=0.327 P=0.238 | |COCH-ARM / FISHERS | P=0.068 P=0.500N P=0.753N P=0.500 P=0.309 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 21 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/50 (2%) 3/50 (6%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 6.9% 0.0% 2.2% 6.3% 6.2% | |TERMINAL (d) | 2/23 (9%) 0/40 (0%) 1/35 (3%) 2/37 (5%) 1/40 (3%) | |FIRST INCIDENCE | 571 --- 730 (T) 638 712 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.354 P=0.065N P=0.205N P=0.504N P=0.451N | |POLY 3 | P=0.272 P=0.107N P=0.293N P=0.623N P=0.614N | |POLY 1.5 | P=0.263 P=0.113N P=0.303N P=0.641N P=0.637N | |POLY 6 | P=0.287 P=0.098N P=0.275N P=0.592N P=0.573N | |LOGISTIC REGRESSION| P=0.241 P=0.140N P=0.305N P=0.603 P=0.639 | |COCH-ARM / FISHERS | P=0.250 P=0.121N P=0.309N P=0.661N P=0.661N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 22 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 1/50 (2%) 8/50 (16%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 2.5% 11.3% 2.3% 17.9% 9.8% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 1/22 (5%) 2/26 (8%) 3/22 (14%) | |FIRST INCIDENCE | 729 (T) 477 729 (T) 653 677 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.160 P=0.117 P=0.763 P=0.044 * P=0.184 | |POLY 3 | P=0.143 P=0.122 P=0.750N P=0.022 * P=0.178 | |POLY 1.5 | P=0.144 P=0.113 P=0.756N P=0.019 * P=0.176 | |POLY 6 | P=0.142 P=0.133 P=0.743N P=0.029 * P=0.182 | |LOGISTIC REGRESSION| P=0.148 P=0.104 P=0.763 P=0.023 * P=0.179 | |COCH-ARM / FISHERS | P=0.161 P=0.102 P=0.753N P=0.015 * P=0.181 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 25/50 (50%) 26/50 (52%) 26/50 (52%) 24/50 (48%) 19/50 (38%) | |POLY-3 ADJUSTED (b)| 54.1% 53.9% 55.6% 49.7% 38.8% | |TERMINAL (d) | 11/23 (48%) 21/40 (53%) 18/35 (51%) 16/37 (43%) 14/40 (35%) | |FIRST INCIDENCE | 571 575 571 611 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007N** P=0.073N P=0.162N P=0.063N P=0.005N** | |POLY 3 | P=0.040N* P=0.575N P=0.528 P=0.411N P=0.095N | |POLY 1.5 | P=0.054N P=0.548 P=0.495 P=0.452N P=0.121N | |POLY 6 | P=0.026N* P=0.510N P=0.582N P=0.349N P=0.063N | |LOGISTIC REGRESSION| P=0.056N P=0.541 P=0.528 P=0.437N P=0.155N | |COCH-ARM / FISHERS | P=0.077N P=0.500 P=0.500 P=0.500N P=0.157N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 23 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 1/50 (2%) 8/50 (16%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 2.5% 11.3% 2.3% 17.9% 9.8% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 1/22 (5%) 2/26 (8%) 3/22 (14%) | |FIRST INCIDENCE | 729 (T) 477 729 (T) 653 677 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.160 P=0.117 P=0.763 P=0.044 * P=0.184 | |POLY 3 | P=0.143 P=0.122 P=0.750N P=0.022 * P=0.178 | |POLY 1.5 | P=0.144 P=0.113 P=0.756N P=0.019 * P=0.176 | |POLY 6 | P=0.142 P=0.133 P=0.743N P=0.029 * P=0.182 | |LOGISTIC REGRESSION| P=0.148 P=0.104 P=0.763 P=0.023 * P=0.179 | |COCH-ARM / FISHERS | P=0.161 P=0.102 P=0.753N P=0.015 * P=0.181 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 25/50 (50%) 26/50 (52%) 26/50 (52%) 25/50 (50%) 19/50 (38%) | |POLY-3 ADJUSTED (b)| 54.1% 53.9% 55.6% 51.8% 38.8% | |TERMINAL (d) | 11/23 (48%) 21/40 (53%) 18/35 (51%) 17/37 (46%) 14/40 (35%) | |FIRST INCIDENCE | 571 575 571 611 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007N** P=0.073N P=0.162N P=0.081N P=0.005N** | |POLY 3 | P=0.044N* P=0.575N P=0.528 P=0.491N P=0.095N | |POLY 1.5 | P=0.059N P=0.548 P=0.495 P=0.532N P=0.121N | |POLY 6 | P=0.028N* P=0.510N P=0.582N P=0.427N P=0.063N | |LOGISTIC REGRESSION| P=0.060N P=0.541 P=0.528 P=0.507N P=0.155N | |COCH-ARM / FISHERS | P=0.083N P=0.500 P=0.500 P=0.579N P=0.157N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 24 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 1/50 (2%) 8/50 (16%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 2.5% 11.3% 2.3% 17.9% 9.8% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 1/22 (5%) 2/26 (8%) 3/22 (14%) | |FIRST INCIDENCE | 729 (T) 477 729 (T) 653 677 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.160 P=0.117 P=0.763 P=0.044 * P=0.184 | |POLY 3 | P=0.143 P=0.122 P=0.750N P=0.022 * P=0.178 | |POLY 1.5 | P=0.144 P=0.113 P=0.756N P=0.019 * P=0.176 | |POLY 6 | P=0.142 P=0.133 P=0.743N P=0.029 * P=0.182 | |LOGISTIC REGRESSION| P=0.148 P=0.104 P=0.763 P=0.023 * P=0.179 | |COCH-ARM / FISHERS | P=0.161 P=0.102 P=0.753N P=0.015 * P=0.181 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 26/50 (52%) 26/50 (52%) 26/50 (52%) 27/50 (54%) 21/50 (42%) | |POLY-3 ADJUSTED (b)| 55.6% 53.9% 55.6% 55.5% 42.8% | |TERMINAL (d) | 11/23 (48%) 21/40 (53%) 18/35 (51%) 18/37 (49%) 15/40 (38%) | |FIRST INCIDENCE | 571 575 571 611 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017N* P=0.055N P=0.128N P=0.107N P=0.008N** | |POLY 3 | P=0.102N P=0.515N P=0.580N P=0.578N P=0.144N | |POLY 1.5 | P=0.126N P=0.546N P=0.563 P=0.546 P=0.174N | |POLY 6 | P=0.072N P=0.460N P=0.534N P=0.515N P=0.103N | |LOGISTIC REGRESSION| P=0.136N P=0.577N P=0.565N P=0.504 P=0.247N | |COCH-ARM / FISHERS | P=0.163N P=0.579N P=0.579N P=0.500 P=0.212N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 25 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 15/50 (30%) 15/50 (30%) 11/49 (22%) 11/50 (22%) 9/50 (18%) | |POLY-3 ADJUSTED (b)| 34.0% 32.0% 25.6% 24.3% 21.8% | |TERMINAL (d) | 5/22 (23%) 3/23 (13%) 6/22 (27%) 4/26 (15%) 6/22 (27%) | |FIRST INCIDENCE | 537 481 620 537 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.091N P=0.453N P=0.224N P=0.149N P=0.135N | |POLY 3 | P=0.100N P=0.509N P=0.266N P=0.216N P=0.151N | |POLY 1.5 | P=0.090N P=0.542N P=0.269N P=0.232N P=0.142N | |POLY 6 | P=0.117N P=0.465N P=0.262N P=0.198N P=0.168N | |LOGISTIC REGRESSION| P=0.071N P=0.484 P=0.262N P=0.267N P=0.124N | |COCH-ARM / FISHERS | P=0.070N P=0.586N P=0.266N P=0.247N P=0.121N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 20/50 (40%) 22/50 (44%) 23/50 (46%) 17/49 (35%) 19/49 (39%) | |POLY-3 ADJUSTED (b)| 44.4% 45.0% 50.1% 35.9% 39.5% | |TERMINAL (d) | 10/23 (44%) 16/40 (40%) 16/35 (46%) 10/36 (28%) 16/40 (40%) | |FIRST INCIDENCE | 550 513 625 550 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.050N P=0.156N P=0.272N P=0.055N P=0.034N* | |POLY 3 | P=0.220N P=0.559 P=0.369 P=0.264N P=0.395N | |POLY 1.5 | P=0.260N P=0.495 P=0.340 P=0.310N P=0.458N | |POLY 6 | P=0.170N P=0.509N P=0.432 P=0.201N P=0.302N | |LOGISTIC REGRESSION| P=0.256N P=0.412 P=0.442 P=0.327N P=0.323N | |COCH-ARM / FISHERS | P=0.318N P=0.420 P=0.343 P=0.368N P=0.532N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 26 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Basal Cell Adenoma, Basosquamous Tumor Benign, or | | Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.9% 2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/22 (5%) 1/23 (4%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 724 729 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.103N P=0.476N P=0.240N P=0.209N P=0.244N | |POLY 3 | P=0.106N P=0.476N P=0.227N P=0.221N P=0.237N | |POLY 1.5 | P=0.106N P=0.486N P=0.232N P=0.229N P=0.239N | |POLY 6 | P=0.106N P=0.462N P=0.219N P=0.210N P=0.234N | |LOGISTIC REGRESSION| P=0.102N P=0.455N P=0.210N P=0.192N P=0.239N | |COCH-ARM / FISHERS | P=0.106N P=0.500N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Basal Cell Adenoma, Basosquamous Tumor Benign, or | | Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173 (e) (e) (e) P=0.610 | |POLY 3 | P=0.154 (e) (e) (e) P=0.522 | |POLY 1.5 | P=0.150 (e) (e) (e) P=0.512 | |POLY 6 | P=0.160 (e) (e) (e) P=0.540 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.610 | |COCH-ARM / FISHERS | P=0.145 (e) (e) (e) P=0.500 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 27 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous | | Tumor (benign, malignant or NOS), or Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.9% 2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/22 (5%) 1/23 (4%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 724 729 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.103N P=0.476N P=0.240N P=0.209N P=0.244N | |POLY 3 | P=0.106N P=0.476N P=0.227N P=0.221N P=0.237N | |POLY 1.5 | P=0.106N P=0.486N P=0.232N P=0.229N P=0.239N | |POLY 6 | P=0.106N P=0.462N P=0.219N P=0.210N P=0.234N | |LOGISTIC REGRESSION| P=0.102N P=0.455N P=0.210N P=0.192N P=0.239N | |COCH-ARM / FISHERS | P=0.106N P=0.500N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous | | Tumor (benign, malignant or NOS), or Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173 (e) (e) (e) P=0.610 | |POLY 3 | P=0.154 (e) (e) (e) P=0.522 | |POLY 1.5 | P=0.150 (e) (e) (e) P=0.512 | |POLY 6 | P=0.160 (e) (e) (e) P=0.540 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.610 | |COCH-ARM / FISHERS | P=0.145 (e) (e) (e) P=0.500 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 28 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor | | (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 3/50 (6%) 2/50 (4%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 7.3% 6.8% 7.0% 4.6% 17.2% | |TERMINAL (d) | 1/22 (5%) 2/23 (9%) 2/22 (9%) 1/26 (4%) 5/22 (23%) | |FIRST INCIDENCE | 562 663 723 719 690 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.067 P=0.620N P=0.651N P=0.434N P=0.163 | |POLY 3 | P=0.064 P=0.634N P=0.647N P=0.473N P=0.149 | |POLY 1.5 | P=0.066 P=0.646N P=0.655N P=0.487N P=0.149 | |POLY 6 | P=0.063 P=0.617N P=0.635N P=0.453N P=0.149 | |LOGISTIC REGRESSION| P=0.059 P=0.651N P=0.638N P=0.482N P=0.160 | |COCH-ARM / FISHERS | P=0.071 P=0.661N P=0.661N P=0.500N P=0.159 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor | | (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 0.0% 2.1% | |TERMINAL (d) | 0/23 (0%) 1/40 (3%) 0/35 (0%) 0/37 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- 730 (T) --- --- 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.465 P=0.610 (e) (e) P=0.610 | |POLY 3 | P=0.431 P=0.515 (e) (e) P=0.522 | |POLY 1.5 | P=0.419 P=0.508 (e) (e) P=0.512 | |POLY 6 | P=0.451 P=0.529 (e) (e) P=0.540 | |LOGISTIC REGRESSION| (e) P=0.610 (e) (e) P=0.610 | |COCH-ARM / FISHERS | P=0.404 P=0.500 (e) (e) P=0.500 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 29 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Fibroma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 1/50 (2%) 5/50 (10%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 12.2% 9.1% 2.3% 11.1% 4.9% | |TERMINAL (d) | 3/22 (14%) 2/23 (9%) 1/22 (5%) 2/26 (8%) 0/22 (0%) | |FIRST INCIDENCE | 677 668 729 (T) 249 680 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.257N P=0.451N P=0.099N P=0.519N P=0.211N | |POLY 3 | P=0.272N P=0.455N P=0.091N P=0.571N P=0.214N | |POLY 1.5 | P=0.271N P=0.475N P=0.096N P=0.596N P=0.219N | |POLY 6 | P=0.272N P=0.429N P=0.083N P=0.535N P=0.205N | |LOGISTIC REGRESSION| P=0.262N P=0.415N P=0.075N P=0.614 P=0.210N | |COCH-ARM / FISHERS | P=0.260N P=0.500N P=0.102N P=0.630N P=0.218N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Fibroma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 703 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.607N (e) P=0.557 (e) (e) | |POLY 3 | P=0.640N (e) P=0.509 (e) (e) | |POLY 1.5 | P=0.645N (e) P=0.503 (e) (e) | |POLY 6 | P=0.632N (e) P=0.521 (e) (e) | |LOGISTIC REGRESSION| P=0.652N (e) P=0.505 (e) (e) | |COCH-ARM / FISHERS | P=0.649N (e) P=0.500 (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 30 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 2/50 (4%) 5/50 (10%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 12.2% 9.1% 4.7% 11.1% 7.3% | |TERMINAL (d) | 3/22 (14%) 2/23 (9%) 1/22 (5%) 2/26 (8%) 0/22 (0%) | |FIRST INCIDENCE | 677 668 705 249 680 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.399N P=0.451N P=0.202N P=0.519N P=0.349N | |POLY 3 | P=0.407N P=0.455N P=0.197N P=0.571N P=0.353N | |POLY 1.5 | P=0.407N P=0.475N P=0.207N P=0.596N P=0.360N | |POLY 6 | P=0.406N P=0.429N P=0.183N P=0.535N P=0.341N | |LOGISTIC REGRESSION| P=0.400N P=0.415N P=0.169N P=0.614 P=0.349N | |COCH-ARM / FISHERS | P=0.394N P=0.500N P=0.218N P=0.630N P=0.357N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 703 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.607N (e) P=0.557 (e) (e) | |POLY 3 | P=0.640N (e) P=0.509 (e) (e) | |POLY 1.5 | P=0.645N (e) P=0.503 (e) (e) | |POLY 6 | P=0.632N (e) P=0.521 (e) (e) | |LOGISTIC REGRESSION| P=0.652N (e) P=0.505 (e) (e) | |COCH-ARM / FISHERS | P=0.649N (e) P=0.500 (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 31 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 3/50 (6%) 2/50 (4%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 0.0% 4.6% 7.0% 4.6% 12.3% | |TERMINAL (d) | 0/22 (0%) 1/23 (4%) 2/22 (9%) 1/26 (4%) 4/22 (18%) | |FIRST INCIDENCE | --- 663 723 719 724 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026 * P=0.268 P=0.127 P=0.284 P=0.032 * | |POLY 3 | P=0.027 * P=0.254 P=0.127 P=0.253 P=0.029 * | |POLY 1.5 | P=0.027 * P=0.247 P=0.123 P=0.245 P=0.029 * | |POLY 6 | P=0.027 * P=0.265 P=0.133 P=0.266 P=0.030 * | |LOGISTIC REGRESSION| P=0.021 * P=0.249 P=0.137 P=0.282 P=0.028 * | |COCH-ARM / FISHERS | P=0.029 * P=0.247 P=0.121 P=0.247 P=0.028 * | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 1/40 (3%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 730 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.455N P=0.610 (e) (e) (e) | |POLY 3 | P=0.483N P=0.515 (e) (e) (e) | |POLY 1.5 | P=0.490N P=0.508 (e) (e) (e) | |POLY 6 | P=0.473N P=0.529 (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.610 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.497N P=0.500 (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 32 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Melanoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 6.8% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 2/26 (8%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- 593 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.426 (e) (e) P=0.150 (e) | |POLY 3 | P=0.387 (e) (e) P=0.134 (e) | |POLY 1.5 | P=0.396 (e) (e) P=0.126 (e) | |POLY 6 | P=0.373 (e) (e) P=0.145 (e) | |LOGISTIC REGRESSION| P=0.421 (e) (e) P=0.120 (e) | |COCH-ARM / FISHERS | P=0.423 (e) (e) P=0.121 (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Melanoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 33 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 0.0% 0.0% 4.9% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | 562 --- --- --- 690 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.153 P=0.487N P=0.491N P=0.487N P=0.512 | |POLY 3 | P=0.149 P=0.489N P=0.493N P=0.488N P=0.496 | |POLY 1.5 | P=0.150 P=0.494N P=0.497N P=0.494N P=0.494 | |POLY 6 | P=0.146 P=0.482N P=0.488N P=0.480N P=0.499 | |LOGISTIC REGRESSION| P=0.165 P=0.566N P=0.461N P=0.467N P=0.504 | |COCH-ARM / FISHERS | P=0.155 P=0.500N P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 34 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, Squamous Cell | | Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 2/50 (4%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 2.4% 4.6% 7.0% 4.6% 17.2% | |TERMINAL (d) | 0/22 (0%) 1/23 (4%) 2/22 (9%) 1/26 (4%) 5/22 (23%) | |FIRST INCIDENCE | 562 663 723 719 690 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008 ** P=0.537 P=0.318 P=0.552 P=0.035 * | |POLY 3 | P=0.008 ** P=0.522 P=0.317 P=0.521 P=0.027 * | |POLY 1.5 | P=0.008 ** P=0.512 P=0.311 P=0.510 P=0.028 * | |POLY 6 | P=0.007 ** P=0.535 P=0.327 P=0.536 P=0.027 * | |LOGISTIC REGRESSION| P=0.007 ** P=0.453 P=0.310 P=0.491 P=0.032 * | |COCH-ARM / FISHERS | P=0.009 ** P=0.500 P=0.309 P=0.500 P=0.030 * | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, Squamous Cell | | Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 1/40 (3%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 730 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.455N P=0.610 (e) (e) (e) | |POLY 3 | P=0.483N P=0.515 (e) (e) (e) | |POLY 1.5 | P=0.490N P=0.508 (e) (e) (e) | |POLY 6 | P=0.473N P=0.529 (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.610 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.497N P=0.500 (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 35 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, or Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 2/50 (4%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 2.4% 4.6% 7.0% 4.6% 17.2% | |TERMINAL (d) | 0/22 (0%) 1/23 (4%) 2/22 (9%) 1/26 (4%) 5/22 (23%) | |FIRST INCIDENCE | 562 663 723 719 690 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008 ** P=0.537 P=0.318 P=0.552 P=0.035 * | |POLY 3 | P=0.008 ** P=0.522 P=0.317 P=0.521 P=0.027 * | |POLY 1.5 | P=0.008 ** P=0.512 P=0.311 P=0.510 P=0.028 * | |POLY 6 | P=0.007 ** P=0.535 P=0.327 P=0.536 P=0.027 * | |LOGISTIC REGRESSION| P=0.007 ** P=0.453 P=0.310 P=0.491 P=0.032 * | |COCH-ARM / FISHERS | P=0.009 ** P=0.500 P=0.309 P=0.500 P=0.030 * | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, or Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 1/40 (3%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- 730 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.455N P=0.610 (e) (e) (e) | |POLY 3 | P=0.483N P=0.515 (e) (e) (e) | |POLY 1.5 | P=0.490N P=0.508 (e) (e) (e) | |POLY 6 | P=0.473N P=0.529 (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.610 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.497N P=0.500 (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 36 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Testes | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 46/50 (92%) 46/50 (92%) 47/50 (94%) 47/50 (94%) 48/50 (96%) | |POLY-3 ADJUSTED (b)| 95.8% 94.8% 98.0% 97.0% 98.2% | |TERMINAL (d) | 22/22 (100%) 23/23 (100%) 22/22 (100%) 25/26 (96%) 22/22 (100%) | |FIRST INCIDENCE | 485 477 561 583 421 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.381 P=0.323N P=0.469N P=0.195N P=0.480 | |POLY 3 | P=0.248 P=0.627N P=0.483 P=0.605 P=0.450 | |POLY 1.5 | P=0.162 P=0.637N P=0.448 P=0.500 P=0.303 | |POLY 6 | P=0.471 P=0.618N P=0.699 P=0.788N P=0.749 | |LOGISTIC REGRESSION| P=0.068 P=0.431N P=0.623 P=0.672N P=0.174 | |COCH-ARM / FISHERS | P=0.231 P=0.643N P=0.500 P=0.500 P=0.339 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Testes | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | | |POLY-3 ADJUSTED (b)| | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 37 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 6/50 (12%) 6/48 (13%) 7/50 (14%) 4/47 (9%) | |POLY-3 ADJUSTED (b)| 4.9% 13.6% 14.2% 16.0% 10.4% | |TERMINAL (d) | 1/22 (5%) 3/23 (13%) 1/22 (5%) 5/26 (19%) 4/22 (18%) | |FIRST INCIDENCE | 687 674 561 690 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.475 P=0.170 P=0.175 P=0.139 P=0.338 | |POLY 3 | P=0.403 P=0.159 P=0.143 P=0.095 P=0.307 | |POLY 1.5 | P=0.404 P=0.147 P=0.131 P=0.087 P=0.303 | |POLY 6 | P=0.403 P=0.176 P=0.162 P=0.108 P=0.313 | |LOGISTIC REGRESSION| P=0.414 P=0.164 P=0.120 P=0.127 P=0.325 | |COCH-ARM / FISHERS | P=0.427 P=0.134 P=0.121 P=0.080 P=0.310 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 5/50 (10%) 10/50 (20%) 9/49 (18%) | |POLY-3 ADJUSTED (b)| 11.5% 8.6% 11.0% 21.2% 18.8% | |TERMINAL (d) | 4/23 (17%) 4/40 (10%) 3/35 (9%) 8/37 (22%) 9/40 (23%) | |FIRST INCIDENCE | 550 730 (T) 638 689 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.157 P=0.218N P=0.409N P=0.400 P=0.559 | |POLY 3 | P=0.068 P=0.460N P=0.606N P=0.168 P=0.248 | |POLY 1.5 | P=0.057 P=0.480N P=0.624N P=0.150 P=0.216 | |POLY 6 | P=0.088 P=0.423N P=0.569N P=0.204 P=0.305 | |LOGISTIC REGRESSION| P=0.087 P=0.447N P=0.620N P=0.191 P=0.290 | |COCH-ARM / FISHERS | P=0.045 * P=0.500N P=0.630N P=0.131 P=0.183 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 38 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/48 (0%) 0/50 (0%) 0/47 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 2/23 (9%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 729 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.298N P=0.247 (e) (e) (e) | |POLY 3 | P=0.292N P=0.253 (e) (e) (e) | |POLY 1.5 | P=0.300N P=0.246 (e) (e) (e) | |POLY 6 | P=0.280N P=0.262 (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.247 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.312N P=0.247 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- --- 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173 (e) (e) (e) P=0.610 | |POLY 3 | P=0.152 (e) (e) (e) P=0.521 | |POLY 1.5 | P=0.148 (e) (e) (e) P=0.509 | |POLY 6 | P=0.159 (e) (e) (e) P=0.539 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.610 | |COCH-ARM / FISHERS | P=0.142 (e) (e) (e) P=0.495 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 39 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 7/50 (14%) 6/48 (13%) 7/50 (14%) 4/47 (9%) | |POLY-3 ADJUSTED (b)| 4.9% 15.8% 14.2% 16.0% 10.4% | |TERMINAL (d) | 1/22 (5%) 4/23 (17%) 1/22 (5%) 5/26 (19%) 4/22 (18%) | |FIRST INCIDENCE | 687 674 561 690 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.536 P=0.107 P=0.175 P=0.139 P=0.338 | |POLY 3 | P=0.465 P=0.098 P=0.143 P=0.095 P=0.307 | |POLY 1.5 | P=0.464 P=0.089 P=0.131 P=0.087 P=0.303 | |POLY 6 | P=0.466 P=0.111 P=0.162 P=0.108 P=0.313 | |LOGISTIC REGRESSION| P=0.474 P=0.106 P=0.120 P=0.127 P=0.325 | |COCH-ARM / FISHERS | P=0.486 P=0.080 P=0.121 P=0.080 P=0.310 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 5/50 (10%) 10/50 (20%) 10/49 (20%) | |POLY-3 ADJUSTED (b)| 11.5% 8.6% 11.0% 21.2% 20.9% | |TERMINAL (d) | 4/23 (17%) 4/40 (10%) 3/35 (9%) 8/37 (22%) 10/40 (25%) | |FIRST INCIDENCE | 550 730 (T) 638 689 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.097 P=0.218N P=0.409N P=0.400 P=0.471 | |POLY 3 | P=0.036 * P=0.460N P=0.606N P=0.168 P=0.175 | |POLY 1.5 | P=0.029 * P=0.480N P=0.624N P=0.150 P=0.148 | |POLY 6 | P=0.047 * P=0.423N P=0.569N P=0.204 P=0.225 | |LOGISTIC REGRESSION| P=0.049 * P=0.447N P=0.620N P=0.191 P=0.220 | |COCH-ARM / FISHERS | P=0.023 * P=0.500N P=0.630N P=0.131 P=0.122 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 40 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 4/48 (8%) 1/50 (2%) 1/47 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 9.7% 2.3% 2.6% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 2/22 (9%) 1/26 (4%) 1/22 (5%) | |FIRST INCIDENCE | 674 --- 704 729 (T) 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.576N P=0.471N P=0.214 P=0.719N P=0.754N | |POLY 3 | P=0.597N P=0.487N P=0.179 P=0.746N P=0.747 | |POLY 1.5 | P=0.598N P=0.493N P=0.172 P=0.753N P=0.744 | |POLY 6 | P=0.594N P=0.480N P=0.190 P=0.735N P=0.751 | |LOGISTIC REGRESSION| P=0.593N P=0.508N P=0.195 P=0.746N P=0.753 | |COCH-ARM / FISHERS | P=0.588N P=0.500N P=0.168 P=0.753N P=0.737 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 1/23 (4%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 1/40 (3%) | |FIRST INCIDENCE | 730 (T) --- --- --- 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.564 P=0.390N P=0.416N P=0.405N P=0.633N | |POLY 3 | P=0.505 P=0.485N P=0.491N P=0.482N P=0.736N | |POLY 1.5 | P=0.504 P=0.492N P=0.497N P=0.491N P=0.750N | |POLY 6 | P=0.504 P=0.471N P=0.479N P=0.469N P=0.714N | |LOGISTIC REGRESSION| P=0.564 (e) (e) (e) P=0.633N | |COCH-ARM / FISHERS | P=0.500 P=0.500N P=0.500N P=0.500N P=0.747 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 41 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 0/48 (0%) 1/50 (2%) 0/47 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 6.8% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 562 477 --- 690 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.167N P=0.339 P=0.491N P=0.718N P=0.500N | |POLY 3 | P=0.168N P=0.332 P=0.501N P=0.747N P=0.515N | |POLY 1.5 | P=0.172N P=0.321 P=0.505N P=0.754N P=0.516N | |POLY 6 | P=0.164N P=0.347 P=0.495N P=0.737N P=0.512N | |LOGISTIC REGRESSION| P=0.140N P=0.216 P=0.468N P=0.762 P=0.456N | |COCH-ARM / FISHERS | P=0.173N P=0.309 P=0.510N P=0.753N P=0.515N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 1/35 (3%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- 730 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.607N (e) P=0.584 (e) (e) | |POLY 3 | P=0.643N (e) P=0.509 (e) (e) | |POLY 1.5 | P=0.648N (e) P=0.503 (e) (e) | |POLY 6 | P=0.635N (e) P=0.520 (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.584 (e) (e) | |COCH-ARM / FISHERS | P=0.652N (e) P=0.500 (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 42 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 4/48 (8%) 2/50 (4%) 1/47 (2%) | |POLY-3 ADJUSTED (b)| 4.8% 6.8% 9.7% 4.6% 2.6% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 2/22 (9%) 1/26 (4%) 1/22 (5%) | |FIRST INCIDENCE | 562 477 704 690 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.244N P=0.543 P=0.381 P=0.624N P=0.493N | |POLY 3 | P=0.267N P=0.532 P=0.333 P=0.674N P=0.527N | |POLY 1.5 | P=0.267N P=0.518 P=0.325 P=0.684N P=0.528N | |POLY 6 | P=0.264N P=0.548 P=0.345 P=0.659N P=0.525N | |LOGISTIC REGRESSION| P=0.256N P=0.403 P=0.325 P=0.684 P=0.515N | |COCH-ARM / FISHERS | P=0.256N P=0.500 P=0.319 P=0.691N P=0.523N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% 2.2% 0.0% 2.1% | |TERMINAL (d) | 1/23 (4%) 0/40 (0%) 1/35 (3%) 0/37 (0%) 1/40 (3%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) --- 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.649 P=0.390N P=0.665N P=0.405N P=0.633N | |POLY 3 | P=0.590 P=0.485N P=0.751N P=0.482N P=0.736N | |POLY 1.5 | P=0.583 P=0.492N P=0.758N P=0.491N P=0.750N | |POLY 6 | P=0.599 P=0.471N P=0.738N P=0.469N P=0.714N | |LOGISTIC REGRESSION| P=0.649 (e) P=0.665N (e) P=0.633N | |COCH-ARM / FISHERS | P=0.574 P=0.500N P=0.753N P=0.500N P=0.747 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 43 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Carcinoma or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 7/50 (14%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 2.3% 7.0% 15.5% 7.6% | |TERMINAL (d) | 0/22 (0%) 1/23 (4%) 3/22 (14%) 3/26 (12%) 3/22 (14%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) 537 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.069 P=0.509 P=0.118 P=0.017 * P=0.118 | |POLY 3 | P=0.053 P=0.514 P=0.127 P=0.011 * P=0.113 | |POLY 1.5 | P=0.055 P=0.508 P=0.123 P=0.009 ** P=0.113 | |POLY 6 | P=0.050 P=0.522 P=0.133 P=0.014 * P=0.115 | |LOGISTIC REGRESSION| P=0.060 P=0.509 P=0.118 P=0.008 ** P=0.118 | |COCH-ARM / FISHERS | P=0.067 P=0.500 P=0.121 P=0.006 ** P=0.117 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Carcinoma or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/49 (0%) 0/49 (0%) 1/50 (2%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.1% 4.2% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 1/37 (3%) 2/40 (5%) | |FIRST INCIDENCE | --- --- --- 730 (T) 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.050 (e) (e) P=0.595 P=0.367 | |POLY 3 | P=0.037 * (e) (e) P=0.522 P=0.264 | |POLY 1.5 | P=0.035 * (e) (e) P=0.514 P=0.251 | |POLY 6 | P=0.041 * (e) (e) P=0.536 P=0.287 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.595 P=0.367 | |COCH-ARM / FISHERS | P=0.033 * (e) (e) P=0.505 P=0.247 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 44 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 7/50 (14%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 2.3% 7.0% 15.5% 7.6% | |TERMINAL (d) | 0/22 (0%) 1/23 (4%) 3/22 (14%) 3/26 (12%) 3/22 (14%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) 537 729 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.069 P=0.509 P=0.118 P=0.017 * P=0.118 | |POLY 3 | P=0.053 P=0.514 P=0.127 P=0.011 * P=0.113 | |POLY 1.5 | P=0.055 P=0.508 P=0.123 P=0.009 ** P=0.113 | |POLY 6 | P=0.050 P=0.522 P=0.133 P=0.014 * P=0.115 | |LOGISTIC REGRESSION| P=0.060 P=0.509 P=0.118 P=0.008 ** P=0.118 | |COCH-ARM / FISHERS | P=0.067 P=0.500 P=0.121 P=0.006 ** P=0.117 | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Urinary Bladder | | Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/49 (0%) 0/49 (0%) 0/49 (0%) 1/50 (2%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.1% 2.1% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 1/37 (3%) 1/40 (3%) | |FIRST INCIDENCE | --- --- --- 730 (T) 730 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.201 (e) (e) P=0.595 P=0.610 | |POLY 3 | P=0.178 (e) (e) P=0.522 P=0.523 | |POLY 1.5 | P=0.170 (e) (e) P=0.514 P=0.512 | |POLY 6 | P=0.191 (e) (e) P=0.536 P=0.541 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.595 P=0.610 | |COCH-ARM / FISHERS | P=0.160 (e) (e) P=0.505 P=0.500 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 45 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Uterus | | Leiomyosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | | |POLY-3 ADJUSTED (b)| | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Uterus | | Leiomyosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 4.2% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 1/37 (3%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- 635 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.544 (e) (e) P=0.302 (e) | |POLY 3 | P=0.545 (e) (e) P=0.259 (e) | |POLY 1.5 | P=0.526 (e) (e) P=0.249 (e) | |POLY 6 | P=0.575 (e) (e) P=0.277 (e) | |LOGISTIC REGRESSION| P=0.485 (e) (e) P=0.189 (e) | |COCH-ARM / FISHERS | P=0.504 (e) (e) P=0.247 (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 46 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | | |POLY-3 ADJUSTED (b)| | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 7/50 (14%) 9/50 (18%) 9/50 (18%) 4/50 (8%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 15.7% 19.2% 19.9% 8.4% 10.4% | |TERMINAL (d) | 2/23 (9%) 8/40 (20%) 8/35 (23%) 3/37 (8%) 3/40 (8%) | |FIRST INCIDENCE | 605 592 655 638 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.506N P=0.574N P=0.137N P=0.164N | |POLY 3 | P=0.104N P=0.437 P=0.405 P=0.226N P=0.323N | |POLY 1.5 | P=0.118N P=0.416 P=0.391 P=0.243N P=0.350N | |POLY 6 | P=0.085N P=0.475 P=0.434 P=0.202N P=0.281N | |LOGISTIC REGRESSION| P=0.127N P=0.365 P=0.400 P=0.365N P=0.472N | |COCH-ARM / FISHERS | P=0.136N P=0.393 P=0.393 P=0.262N P=0.380N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 47 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | | |POLY-3 ADJUSTED (b)| | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 7/50 (14%) 9/50 (18%) 9/50 (18%) 4/50 (8%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 15.7% 19.2% 19.9% 8.4% 10.4% | |TERMINAL (d) | 2/23 (9%) 8/40 (20%) 8/35 (23%) 3/37 (8%) 3/40 (8%) | |FIRST INCIDENCE | 605 592 655 638 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.506N P=0.574N P=0.137N P=0.164N | |POLY 3 | P=0.104N P=0.437 P=0.405 P=0.226N P=0.323N | |POLY 1.5 | P=0.118N P=0.416 P=0.391 P=0.243N P=0.350N | |POLY 6 | P=0.085N P=0.475 P=0.434 P=0.202N P=0.281N | |LOGISTIC REGRESSION| P=0.127N P=0.365 P=0.400 P=0.365N P=0.472N | |COCH-ARM / FISHERS | P=0.136N P=0.393 P=0.393 P=0.262N P=0.380N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 48 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Zymbal's Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/22 (0%) 0/23 (0%) 0/22 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 477 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.528N (e) P=0.249 (e) (e) | |POLY 3 | P=0.510N (e) P=0.253 (e) (e) | |POLY 1.5 | P=0.515N (e) P=0.245 (e) (e) | |POLY 6 | P=0.502N (e) P=0.264 (e) (e) | |LOGISTIC REGRESSION| P=0.395N (e) P=0.260 (e) (e) | |COCH-ARM / FISHERS | P=0.516N (e) P=0.247 (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |Zymbal's Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.3% 2.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | 676 589 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.206N P=0.733N P=0.468N P=0.459N P=0.437N | |POLY 3 | P=0.221N P=0.742N P=0.492N P=0.483N P=0.479N | |POLY 1.5 | P=0.221N P=0.751N P=0.498N P=0.491N P=0.489N | |POLY 6 | P=0.221N P=0.726N P=0.481N P=0.471N P=0.462N | |LOGISTIC REGRESSION| P=0.241N P=0.722 P=0.498N P=0.550N P=0.542N | |COCH-ARM / FISHERS | P=0.222N P=0.753N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 49 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or | | Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 25/50 (50%) 2/50 (4%) 1/50 (2%) 5/50 (10%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 56.4% 4.5% 2.3% 11.4% 16.7% | |TERMINAL (d) | 12/22 (55%) 0/23 (0%) 0/22 (0%) 3/26 (12%) 3/22 (14%) | |FIRST INCIDENCE | 499 668 705 674 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P=0.003N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P=0.004N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P=0.003N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.010N* P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P=0.009N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or | | Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 18/50 (36%) 1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 38.0% 2.2% 2.2% 4.2% 0.0% | |TERMINAL (d) | 2/23 (9%) 1/40 (3%) 1/35 (3%) 1/37 (3%) 0/40 (0%) | |FIRST INCIDENCE | 571 730 (T) 730 (T) 634 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 50 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) 5/50 (10%) 4/50 (8%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.7% 9.0% 11.5% 9.0% 0.0% | |TERMINAL (d) | 2/22 (9%) 0/23 (0%) 0/22 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 617 645 603 593 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.570N P=0.556 P=0.558N P=0.066N | |POLY 3 | P=0.053N P=0.601N P=0.533 P=0.602N P=0.062N | |POLY 1.5 | P=0.052N P=0.620N P=0.516 P=0.622N P=0.062N | |POLY 6 | P=0.055N P=0.576N P=0.559 P=0.573N P=0.061N | |LOGISTIC REGRESSION| P=0.043N* P=0.618 P=0.499 P=0.634 P=0.064N | |COCH-ARM / FISHERS | P=0.047N* P=0.643N P=0.500 P=0.643N P=0.059N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 51 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) 5/50 (10%) 4/50 (8%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.7% 9.0% 11.5% 9.0% 0.0% | |TERMINAL (d) | 2/22 (9%) 0/23 (0%) 0/22 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 617 645 603 593 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051N P=0.570N P=0.556 P=0.558N P=0.066N | |POLY 3 | P=0.053N P=0.601N P=0.533 P=0.602N P=0.062N | |POLY 1.5 | P=0.052N P=0.620N P=0.516 P=0.622N P=0.062N | |POLY 6 | P=0.055N P=0.576N P=0.559 P=0.573N P=0.061N | |LOGISTIC REGRESSION| P=0.043N* P=0.618 P=0.499 P=0.634 P=0.064N | |COCH-ARM / FISHERS | P=0.047N* P=0.643N P=0.500 P=0.643N P=0.059N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/40 (0%) 0/35 (0%) 0/37 (0%) 0/40 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 52 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 50/50 (100%) 50/50 (100%) 48/50 (96%) 50/50 (100%) 48/50 (96%) | |POLY-3 ADJUSTED (b)| 100.0% 100.0% 99.3% 100.0% 98.2% | |TERMINAL (d) | 22/22 (100%) 23/23 (100%) 22/22 (100%) 26/26 (100%) 22/22 (100%) | |FIRST INCIDENCE | 485 477 561 249 421 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.438N (e) P=0.307N (e) P=0.412N | |POLY 3 | P=0.212N (e) P=0.985N (e) P=0.549N | |POLY 1.5 | P=0.251N (e) P=0.619N (e) P=0.511N | |POLY 6 | P=0.205N (e) P=1.000N (e) P=0.608N | |LOGISTIC REGRESSION| P=0.440N (e) (e) (e) P=0.437N | |COCH-ARM / FISHERS | P=0.137N (e) P=0.247N (e) P=0.247N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 39/50 (78%) 45/50 (90%) 44/50 (88%) 40/50 (80%) 41/50 (82%) | |POLY-3 ADJUSTED (b)| 81.1% 90.6% 92.0% 80.6% 83.2% | |TERMINAL (d) | 18/23 (78%) 36/40 (90%) 32/35 (91%) 28/37 (76%) 33/40 (83%) | |FIRST INCIDENCE | 550 513 570 550 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010N* P=0.046N* P=0.130N P=0.029N* P=0.006N** | |POLY 3 | P=0.303N P=0.137 P=0.090 P=0.575N P=0.499 | |POLY 1.5 | P=0.346N P=0.110 P=0.088 P=0.574 P=0.449 | |POLY 6 | P=0.241N P=0.186 P=0.109 P=0.498N P=0.581 | |LOGISTIC REGRESSION| P=0.286N P=0.107 P=0.137 P=0.535 P=0.551 | |COCH-ARM / FISHERS | P=0.409N P=0.086 P=0.143 P=0.500 P=0.402 | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 53 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 30/50 (60%) 14/50 (28%) 15/50 (30%) 18/50 (36%) 14/50 (28%) | |POLY-3 ADJUSTED (b)| 64.8% 30.4% 32.1% 39.8% 31.9% | |TERMINAL (d) | 13/22 (59%) 3/23 (13%) 3/22 (14%) 9/26 (35%) 4/22 (18%) | |FIRST INCIDENCE | 485 477 312 593 466 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.045N* P=0.003N** P=0.007N** P=0.007N** P=0.006N** | |POLY 3 | P=0.026N* P<0.001N** P<0.001N** P=0.011N* P<0.001N** | |POLY 1.5 | P=0.025N* P<0.001N** P<0.001N** P=0.012N* P<0.001N** | |POLY 6 | P=0.027N* P<0.001N** P<0.001N** P=0.010N* P<0.001N** | |LOGISTIC REGRESSION| P=0.018N* P=0.002N** P=0.003N** P=0.012N* P<0.001N** | |COCH-ARM / FISHERS | P=0.022N* P<0.001N** P=0.002N** P=0.014N* P<0.001N** | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 24/50 (48%) 9/50 (18%) 11/50 (22%) 9/50 (18%) 10/50 (20%) | |POLY-3 ADJUSTED (b)| 50.3% 19.0% 23.0% 18.5% 20.7% | |TERMINAL (d) | 4/23 (17%) 6/40 (15%) 5/35 (14%) 4/37 (11%) 7/40 (18%) | |FIRST INCIDENCE | 571 589 85 611 709 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006N** P<0.001N** P=0.003N** P<0.001N** P<0.001N** | |POLY 3 | P=0.013N* P<0.001N** P=0.004N** P<0.001N** P=0.002N** | |POLY 1.5 | P=0.015N* P<0.001N** P=0.004N** P<0.001N** P=0.002N** | |POLY 6 | P=0.012N* P<0.001N** P=0.004N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.062N P=0.004N** P=0.009N** P=0.012N* P=0.010N* | |COCH-ARM / FISHERS | P=0.019N* P<0.001N** P=0.006N** P<0.001N** P=0.003N** | |=================================================================================================================================| Date: 02/25/99 EXPERIMENT: 88036 TEST: 03 Page 54 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 50/50 (100%) 50/50 (100%) 50/50 (100%) 50/50 (100%) 49/50 (98%) | |POLY-3 ADJUSTED (b)| 100.0% 100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 22/22 (100%) 23/23 (100%) 22/22 (100%) 26/26 (100%) 22/22 (100%) | |FIRST INCIDENCE | 485 477 312 249 421 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.480N (e) (e) (e) P=0.467N | |POLY 3 | P=1.000N (e) (e) (e) P=1.000N | |POLY 1.5 | P=1.000N (e) (e) (e) P=1.000N | |POLY 6 | P=1.000N (e) (e) (e) P=1.000N | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.145N (e) (e) (e) P=0.500N | |=================================================================================================================================| | | | | | Females | |Dose | 0 PPM 469 PPM 938 PPM 1875 PPM 3750 PPM | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 46/50 (92%) 46/50 (92%) 47/50 (94%) 42/50 (84%) 45/50 (90%) | |POLY-3 ADJUSTED (b)| 92.0% 92.0% 94.0% 84.0% 91.3% | |TERMINAL (d) | 19/23 (83%) 36/40 (90%) 32/35 (91%) 29/37 (78%) 37/40 (93%) | |FIRST INCIDENCE | 550 513 85 550 536 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006N** P=0.005N** P=0.047N* P=0.004N** P<0.001N** | |POLY 3 | P=0.360N P=0.642 P=0.500 P=0.179N P=0.596N | |POLY 1.5 | P=0.329N P=0.642 P=0.500 P=0.179N P=0.561N | |POLY 6 | P=0.390N P=0.642 P=0.500 P=0.179N P=0.627N | |LOGISTIC REGRESSION| P=0.369N (e) (e) (e) P=0.484N | |COCH-ARM / FISHERS | P=0.276N P=0.643N P=0.500 P=0.178N P=0.500N | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Poly-3 adjusted lifetime tumor incidence. (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. (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).