TDMS Study 88036-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ANTHRAQUINONE DATE: 12/11/98 EXPERIMENT: 88036 TEST: 04 TIME: 09:00:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-25337 ROUTE: DOSED FEED NTP C#: C88036 PATHOLOGIST: RYAN, M. CAS: 84-65-1 ------------------------------------------------------------------------------------------------------------------------------------ 2 YEAR CHRONIC MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ANTHRAQUINONE DATE: 12/11/98 EXPERIMENT: 88036 TEST: 04 TIME: 09:00:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: DOSED FEED NTP C#: C88036 PATHOLOGIST: RYAN, M. CAS: 84-65-1 Mice(B6C3F1) ----------------------------- 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 Bone Marrow Epididymis Islets, Pancreatic Kidney Liver Lung Ovary Pituitary Gland Salivary Glands Spleen Testes Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ANTHRAQUINONE DATE: 12/11/98 EXPERIMENT: 88036 TEST: 04 TIME: 09:00:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: DOSED FEED NTP C#: C88036 PATHOLOGIST: RYAN, M. CAS: 84-65-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ANTHRAQUINONE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Liver Hepatoblastoma Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Thyroid Gland: Follicular Cell Adenoma Carcinoma or Adenoma All Organs Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Thyroid Gland: Follicular Cell Carcinoma All Organs Benign Tumors Malignant and Benign Tumors =============================================================== Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 1 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 4/50 (8%) 4/50 (8%) |2/50 (4%) 3/50 (6%) 4/50 (8%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 6.1% 8.5% 8.4% 9.9% |4.5% 6.4% 8.9% 2.2% | |TERMINAL (d) | 1/45 (2%) 3/41 (7%) 3/43 (7%) 2/23 (9%) |2/35 (6%) 3/42 (7%) 3/35 (9%) 1/42 (2%) | |FIRST INCIDENCE | 550 662 662 647 |730 (T) 730 (T) 675 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.199 P=0.460 P=0.480 P=0.264 |P=0.262N P=0.583 P=0.338 P=0.436N | |POLY 3 | P=0.375 P=0.480 P=0.486 P=0.398 |P=0.299N P=0.518 P=0.339 P=0.491N | |POLY 1.5 | P=0.429 P=0.492 P=0.495 P=0.447 |P=0.307N P=0.512 P=0.341 P=0.498N | |POLY 6 | P=0.307 P=0.465 P=0.479 P=0.334 |P=0.286N P=0.527 P=0.335 P=0.481N | |LOGISTIC REGRESSION| P=0.517 P=0.488 P=0.486 P=0.531 |P=0.286N P=0.583 P=0.328 P=0.436N | |COCH-ARM / FISHERS | P=0.492 P=0.500 P=0.500 P=0.500 |P=0.305N P=0.500 P=0.339 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 4/50 (8%) 4/50 (8%) |2/50 (4%) 4/50 (8%) 4/50 (8%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 6.1% 8.5% 8.4% 9.9% |4.5% 8.6% 8.9% 2.2% | |TERMINAL (d) | 1/45 (2%) 3/41 (7%) 3/43 (7%) 2/23 (9%) |2/35 (6%) 4/42 (10%) 3/35 (9%) 1/42 (2%) | |FIRST INCIDENCE | 550 662 662 647 |730 (T) 730 (T) 675 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.199 P=0.460 P=0.480 P=0.264 |P=0.207N P=0.424 P=0.338 P=0.436N | |POLY 3 | P=0.375 P=0.480 P=0.486 P=0.398 |P=0.238N P=0.356 P=0.339 P=0.491N | |POLY 1.5 | P=0.429 P=0.492 P=0.495 P=0.447 |P=0.247N P=0.350 P=0.341 P=0.498N | |POLY 6 | P=0.307 P=0.465 P=0.479 P=0.334 |P=0.226N P=0.365 P=0.335 P=0.481N | |LOGISTIC REGRESSION| P=0.517 P=0.488 P=0.486 P=0.531 |P=0.227N P=0.424 P=0.328 P=0.436N | |COCH-ARM / FISHERS | P=0.492 P=0.500 P=0.500 P=0.500 |P=0.246N P=0.339 P=0.339 P=0.500N | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 2 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/42 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 4.2% 0.0% 2.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/45 (4%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 0/42 (0%) | |FIRST INCIDENCE | 729 (T) --- 727 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.390N P=0.259N P=0.513N P=0.395N |(e) (e) (e) (e) | |POLY 3 | P=0.313N P=0.243N P=0.505N P=0.306N |(e) (e) (e) (e) | |POLY 1.5 | P=0.307N P=0.239N P=0.501N P=0.291N |(e) (e) (e) (e) | |POLY 6 | P=0.322N P=0.248N P=0.508N P=0.330N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.379N (e) P=0.509N (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.300N P=0.247N P=0.500N P=0.293N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/47 (0%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.1% 4.2% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/45 (0%) 1/41 (2%) 2/43 (5%) 0/23 (0%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.691N P=0.481 P=0.229 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.600N P=0.495 P=0.234 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.568N P=0.498 P=0.237 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.643N P=0.490 P=0.232 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.481 P=0.229 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.535N P=0.500 P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 3 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 6/50 (12%) 11/50 (22%) 37/49 (76%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 2.1% 12.8% 22.9% 79.2% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 1/45 (2%) 5/41 (12%) 10/43 (23%) 15/23 (65%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 1/42 (2%) | |FIRST INCIDENCE | 729 (T) 658 481 490 |--- --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.048 * P=0.002 ** P<0.001 ** |P=0.234 (e) (e) P=0.536 | |POLY 3 | P<0.001 ** P=0.053 P=0.002 ** P<0.001 ** |P=0.214 (e) (e) P=0.504 | |POLY 1.5 | P<0.001 ** P=0.056 P=0.002 ** P<0.001 ** |P=0.212 (e) (e) P=0.501 | |POLY 6 | P<0.001 ** P=0.050 P=0.002 ** P<0.001 ** |P=0.217 (e) (e) P=0.510 | |LOGISTIC REGRESSION| P<0.001 ** P=0.056 P=0.003 ** P<0.001 ** |(e) (e) (e) P=0.536 | |COCH-ARM / FISHERS | P<0.001 ** P=0.056 P=0.002 ** P<0.001 ** |P=0.213 (e) (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 21/50 (42%) 32/50 (64%) 38/50 (76%) 41/49 (84%) |6/49 (12%) 28/50 (56%) 27/50 (54%) 40/49 (82%) | |POLY-3 ADJUSTED (b)| 43.4% 68.0% 79.7% 89.4% |13.4% 59.5% 58.9% 87.2% | |TERMINAL (d) | 19/45 (42%) 30/41 (73%) 36/43 (84%) 22/23 (96%) |4/35 (11%) 27/42 (64%) 23/35 (66%) 38/42 (91%) | |FIRST INCIDENCE | 662 677 662 490 |519 611 626 549 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.007 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.007 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.008 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.022 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 4 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 13/50 (26%) 17/50 (34%) 21/49 (43%) |2/49 (4%) 3/50 (6%) 8/50 (16%) 8/49 (16%) | |POLY-3 ADJUSTED (b)| 16.6% 27.1% 35.9% 49.8% |4.5% 6.4% 17.4% 17.7% | |TERMINAL (d) | 7/45 (16%) 11/41 (27%) 17/43 (40%) 14/23 (61%) |1/35 (3%) 3/42 (7%) 4/35 (11%) 7/42 (17%) | |FIRST INCIDENCE | 702 464 729 (T) 456 |715 730 (T) 568 711 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.120 P=0.024 * P<0.001 ** |P=0.057 P=0.572 P=0.052 P=0.084 | |POLY 3 | P<0.001 ** P=0.160 P=0.026 * P<0.001 ** |P=0.031 * P=0.524 P=0.051 P=0.048 * | |POLY 1.5 | P<0.001 ** P=0.167 P=0.029 * P<0.001 ** |P=0.029 * P=0.519 P=0.051 P=0.045 * | |POLY 6 | P<0.001 ** P=0.150 P=0.024 * P<0.001 ** |P=0.035 * P=0.530 P=0.051 P=0.053 | |LOGISTIC REGRESSION| P<0.001 ** P=0.163 P=0.026 * P<0.001 ** |P=0.031 * P=0.541 P=0.051 P=0.058 | |COCH-ARM / FISHERS | P=0.004 ** P=0.163 P=0.032 * P=0.003 ** |P=0.031 * P=0.510 P=0.049 * P=0.046 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 18/50 (36%) 27/50 (54%) 45/49 (92%) |2/49 (4%) 3/50 (6%) 8/50 (16%) 8/49 (16%) | |POLY-3 ADJUSTED (b)| 18.7% 37.3% 56.2% 92.7% |4.5% 6.4% 17.4% 17.7% | |TERMINAL (d) | 8/45 (18%) 15/41 (37%) 26/43 (61%) 20/23 (87%) |1/35 (3%) 3/42 (7%) 4/35 (11%) 7/42 (17%) | |FIRST INCIDENCE | 702 464 481 456 |715 730 (T) 568 711 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** |P=0.057 P=0.572 P=0.052 P=0.084 | |POLY 3 | P<0.001 ** P=0.033 * P<0.001 ** P<0.001 ** |P=0.031 * P=0.524 P=0.051 P=0.048 * | |POLY 1.5 | P<0.001 ** P=0.036 * P<0.001 ** P<0.001 ** |P=0.029 * P=0.519 P=0.051 P=0.045 * | |POLY 6 | P<0.001 ** P=0.031 * P<0.001 ** P<0.001 ** |P=0.035 * P=0.530 P=0.051 P=0.053 | |LOGISTIC REGRESSION| P<0.001 ** P=0.036 * P<0.001 ** P<0.001 ** |P=0.031 * P=0.541 P=0.051 P=0.058 | |COCH-ARM / FISHERS | P<0.001 ** P=0.035 * P<0.001 ** P<0.001 ** |P=0.031 * P=0.510 P=0.049 * P=0.046 * | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 5 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 25/50 (50%) 34/50 (68%) 41/50 (82%) 46/49 (94%) |6/49 (12%) 30/50 (60%) 30/50 (60%) 41/49 (84%) | |POLY-3 ADJUSTED (b)| 51.7% 70.5% 86.0% 96.1% |13.4% 63.8% 64.2% 89.3% | |TERMINAL (d) | 23/45 (51%) 30/41 (73%) 39/43 (91%) 23/23 (100%)|4/35 (11%) 29/42 (69%) 24/35 (69%) 38/42 (91%) | |FIRST INCIDENCE | 662 464 662 456 |519 611 568 549 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.019 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.043 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.051 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.034 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.043 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.052 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 26/50 (52%) 35/50 (70%) 43/50 (86%) 48/49 (98%) |6/49 (12%) 30/50 (60%) 30/50 (60%) 41/49 (84%) | |POLY-3 ADJUSTED (b)| 53.8% 72.2% 88.9% 98.9% |13.4% 63.8% 64.2% 89.3% | |TERMINAL (d) | 24/45 (53%) 30/41 (73%) 40/43 (93%) 23/23 (100%)|4/35 (11%) 29/42 (69%) 24/35 (69%) 38/42 (91%) | |FIRST INCIDENCE | 662 464 481 456 |519 611 568 549 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.020 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.045 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.051 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.038 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.044 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.050 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 6 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 8/50 (16%) 6/50 (12%) 8/50 (16%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 22.7% 17.1% 12.7% 19.5% |2.2% 2.1% 4.5% 6.7% | |TERMINAL (d) | 8/45 (18%) 8/41 (20%) 6/43 (14%) 5/23 (22%) |1/35 (3%) 1/42 (2%) 2/35 (6%) 3/42 (7%) | |FIRST INCIDENCE | 662 729 (T) 729 (T) 490 |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.241 P=0.390N P=0.173N P=0.362 |P=0.221 P=0.721N P=0.500 P=0.372 | |POLY 3 | P=0.489N P=0.335N P=0.155N P=0.454N |P=0.179 P=0.752N P=0.500 P=0.308 | |POLY 1.5 | P=0.431N P=0.316N P=0.146N P=0.377N |P=0.174 P=0.755N P=0.502 P=0.300 | |POLY 6 | P=0.553 P=0.362N P=0.163N P=0.567N |P=0.187 P=0.747N P=0.496 P=0.320 | |LOGISTIC REGRESSION| P=0.513N P=0.333N P=0.148N P=0.382N |P=0.221 P=0.721N P=0.500 P=0.372 | |COCH-ARM / FISHERS | P=0.367N P=0.306N P=0.143N P=0.306N |P=0.175 P=0.753N P=0.500 P=0.301 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 12/50 (24%) 11/50 (22%) 4/50 (8%) |3/50 (6%) 0/50 (0%) 0/50 (0%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 16.7% 25.4% 23.2% 10.1% |6.6% 0.0% 0.0% 6.7% | |TERMINAL (d) | 8/45 (18%) 11/41 (27%) 9/43 (21%) 4/23 (17%) |2/35 (6%) 0/42 (0%) 0/35 (0%) 3/42 (7%) | |FIRST INCIDENCE | 729 (T) 601 711 729 (T) |613 --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.417N P=0.165 P=0.274 P=0.616N |P=0.335 P=0.102N P=0.123N P=0.589N | |POLY 3 | P=0.138N P=0.213 P=0.295 P=0.281N |P=0.284 P=0.113N P=0.120N P=0.661 | |POLY 1.5 | P=0.092N P=0.224 P=0.304 P=0.227N |P=0.282 P=0.115N P=0.119N P=0.653 | |POLY 6 | P=0.225N P=0.200 P=0.288 P=0.368N |P=0.287 P=0.111N P=0.123N P=0.651N | |LOGISTIC REGRESSION| P=0.256N P=0.202 P=0.281 P=0.616N |P=0.289 P=0.124N P=0.121N P=0.659 | |COCH-ARM / FISHERS | P=0.056N P=0.227 P=0.306 P=0.178N |P=0.289 P=0.121N P=0.121N P=0.651 | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 7 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 19/50 (38%) 17/50 (34%) 12/50 (24%) |4/50 (8%) 1/50 (2%) 2/50 (4%) 6/49 (12%) | |POLY-3 ADJUSTED (b)| 35.1% 40.2% 35.9% 29.2% |8.8% 2.1% 4.5% 13.3% | |TERMINAL (d) | 14/45 (31%) 18/41 (44%) 15/43 (35%) 9/23 (39%) |3/35 (9%) 1/42 (2%) 2/35 (6%) 6/42 (14%) | |FIRST INCIDENCE | 662 601 711 490 |613 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.285 P=0.297 P=0.523 P=0.277 |P=0.133 P=0.141N P=0.338N P=0.477 | |POLY 3 | P=0.235N P=0.379 P=0.554 P=0.356N |P=0.089 P=0.169N P=0.341N P=0.368 | |POLY 1.5 | P=0.157N P=0.407 P=0.575 P=0.264N |P=0.087 P=0.172N P=0.337N P=0.358 | |POLY 6 | P=0.375N P=0.344 P=0.533 P=0.505N |P=0.094 P=0.165N P=0.350N P=0.385 | |LOGISTIC REGRESSION| P=0.343N P=0.376 P=0.558 P=0.417N |P=0.100 P=0.175N P=0.337N P=0.375 | |COCH-ARM / FISHERS | P=0.095N P=0.418 P=0.583N P=0.189N |P=0.092 P=0.181N P=0.339N P=0.357 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |2/45 (4%) 0/50 (0%) 2/49 (4%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| |5.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | |2/33 (6%) 0/42 (0%) 2/34 (6%) 0/42 (0%) | |FIRST INCIDENCE | |730 (T) --- 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.248N P=0.187N P=0.685N P=0.187N | |POLY 3 | |P=0.273N P=0.205N P=0.664N P=0.212N | |POLY 1.5 | |P=0.275N P=0.208N P=0.661N P=0.217N | |POLY 6 | |P=0.268N P=0.202N P=0.671N P=0.206N | |LOGISTIC REGRESSION| |P=0.248N (e) P=0.685N (e) | |COCH-ARM / FISHERS | |P=0.271N P=0.222N P=0.659N P=0.226N | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 8 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/47 (2%) 0/46 (0%) |4/47 (9%) 7/50 (14%) 4/48 (8%) 6/46 (13%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.2% 0.0% |9.4% 15.0% 9.2% 14.1% | |TERMINAL (d) | 0/43 (0%) 0/39 (0%) 1/41 (2%) 0/22 (0%) |3/33 (9%) 6/42 (14%) 3/35 (9%) 5/39 (13%) | |FIRST INCIDENCE | --- --- 729 (T) --- |717 703 626 549 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.797 (e) P=0.490 (e) |P=0.500 P=0.397 P=0.622N P=0.461 | |POLY 3 | P=0.770 (e) P=0.493 (e) |P=0.428 P=0.318 P=0.632N P=0.372 | |POLY 1.5 | P=0.796 (e) P=0.496 (e) |P=0.415 P=0.311 P=0.629N P=0.359 | |POLY 6 | P=0.727 (e) P=0.492 (e) |P=0.451 P=0.328 P=0.637N P=0.393 | |LOGISTIC REGRESSION| (e) (e) P=0.490 (e) |P=0.415 P=0.340 P=0.639N P=0.356 | |COCH-ARM / FISHERS | P=0.792N (e) P=0.495 (e) |P=0.416 P=0.299 P=0.631N P=0.356 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 3/50 (6%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 6.4% 4.4% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |0/35 (0%) 2/42 (5%) 1/35 (3%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |617 648 627 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.110N P=0.550 P=0.686 P=0.224N | |POLY 3 | (e) (e) (e) (e) |P=0.117N P=0.517 P=0.693 P=0.234N | |POLY 1.5 | (e) (e) (e) (e) |P=0.120N P=0.511 P=0.692N P=0.237N | |POLY 6 | (e) (e) (e) (e) |P=0.113N P=0.524 P=0.689 P=0.229N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.113N P=0.482 P=0.683 P=0.233N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.118N P=0.500 P=0.691N P=0.247N | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 9 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 4.3% 2.2% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |0/35 (0%) 2/42 (5%) 0/35 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |617 730 (T) 627 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.135N P=0.648N P=0.507N P=0.224N | |POLY 3 | (e) (e) (e) (e) |P=0.142N P=0.683N P=0.501N P=0.234N | |POLY 1.5 | (e) (e) (e) (e) |P=0.144N P=0.686N P=0.499N P=0.237N | |POLY 6 | (e) (e) (e) (e) |P=0.139N P=0.679N P=0.505N P=0.229N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.137N P=0.693 P=0.529N P=0.233N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.142N P=0.691N P=0.500N P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 3/50 (6%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 6.4% 4.4% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |0/35 (0%) 2/42 (5%) 1/35 (3%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |617 648 627 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.110N P=0.550 P=0.686 P=0.224N | |POLY 3 | (e) (e) (e) (e) |P=0.117N P=0.517 P=0.693 P=0.234N | |POLY 1.5 | (e) (e) (e) (e) |P=0.120N P=0.511 P=0.692N P=0.237N | |POLY 6 | (e) (e) (e) (e) |P=0.113N P=0.524 P=0.689 P=0.229N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.113N P=0.482 P=0.683 P=0.233N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.118N P=0.500 P=0.691N P=0.247N | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 10 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Skin | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.2% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 1/43 (2%) 0/23 (0%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- 453 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.725 (e) P=0.237 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.684 (e) P=0.238 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.724 (e) P=0.239 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.616 (e) P=0.237 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.688N (e) P=0.178 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.695N (e) P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/49 (0%) 0/42 (0%) |0/45 (0%) 1/49 (2%) 0/48 (0%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 4.2% 0.0% 0.0% 0.0% |0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 1/45 (2%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 0/42 (0%) | |FIRST INCIDENCE | 710 --- --- --- |--- 611 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.322N P=0.260N P=0.247N P=0.399N |P=0.579N P=0.513 (e) (e) | |POLY 3 | P=0.255N P=0.244N P=0.242N P=0.310N |P=0.577N P=0.522 (e) (e) | |POLY 1.5 | P=0.259N P=0.239N P=0.241N P=0.293N |P=0.579N P=0.521 (e) (e) | |POLY 6 | P=0.248N P=0.249N P=0.244N P=0.335N |P=0.574N P=0.524 (e) (e) | |LOGISTIC REGRESSION| P=0.276N P=0.240N P=0.241N P=0.323N |P=0.529N P=0.459 (e) (e) | |COCH-ARM / FISHERS | P=0.262N P=0.247N P=0.253N P=0.293N |P=0.581N P=0.521 (e) (e) | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 11 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |6.7% 0.0% 0.0% 2.2% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |3/35 (9%) 0/42 (0%) 0/35 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.409N P=0.091N P=0.121N P=0.242N | |POLY 3 | (e) (e) (e) (e) |P=0.450N P=0.112N P=0.119N P=0.297N | |POLY 1.5 | (e) (e) (e) (e) |P=0.449N P=0.114N P=0.118N P=0.304N | |POLY 6 | (e) (e) (e) (e) |P=0.450N P=0.108N P=0.121N P=0.286N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.409N (e) (e) P=0.242N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.443N P=0.121N P=0.121N P=0.309N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/49 (4%) 2/46 (4%) |1/45 (2%) 1/48 (2%) 2/48 (4%) 2/48 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.3% 5.3% |2.4% 2.2% 4.6% 4.5% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 2/43 (5%) 2/23 (9%) |1/35 (3%) 1/42 (2%) 2/35 (6%) 2/42 (5%) | |FIRST INCIDENCE | --- --- 729 (T) 729 (T) |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.031 * (e) P=0.229 P=0.107 |P=0.429 P=0.721N P=0.500 P=0.564 | |POLY 3 | P=0.078 (e) P=0.230 P=0.188 |P=0.393 P=0.741N P=0.519 P=0.522 | |POLY 1.5 | P=0.091 (e) P=0.233 P=0.203 |P=0.390 P=0.742N P=0.523 P=0.519 | |POLY 6 | P=0.063 (e) P=0.229 P=0.168 |P=0.399 P=0.739N P=0.513 P=0.528 | |LOGISTIC REGRESSION| (e) (e) P=0.229 P=0.107 |P=0.429 P=0.721N P=0.500 P=0.564 | |COCH-ARM / FISHERS | P=0.107 (e) P=0.242 P=0.227 |P=0.397 P=0.736N P=0.524 P=0.524 | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 12 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/46 (0%) |0/45 (0%) 0/48 (0%) 0/48 (0%) 2/48 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.5% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 0/43 (0%) 0/23 (0%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.052 (e) (e) P=0.279 | |POLY 3 | (e) (e) (e) (e) |P=0.042 * (e) (e) P=0.252 | |POLY 1.5 | (e) (e) (e) (e) |P=0.042 * (e) (e) P=0.250 | |POLY 6 | (e) (e) (e) (e) |P=0.043 * (e) (e) P=0.255 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.279 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.044 * (e) (e) P=0.264 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/49 (4%) 2/46 (4%) |1/45 (2%) 1/48 (2%) 2/48 (4%) 4/48 (8%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.3% 5.3% |2.4% 2.2% 4.6% 9.1% | |TERMINAL (d) | 0/45 (0%) 0/41 (0%) 2/43 (5%) 2/23 (9%) |1/35 (3%) 1/42 (2%) 2/35 (6%) 4/42 (10%) | |FIRST INCIDENCE | --- --- 729 (T) 729 (T) |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.031 * (e) P=0.229 P=0.107 |P=0.099 P=0.721N P=0.500 P=0.238 | |POLY 3 | P=0.078 (e) P=0.230 P=0.188 |P=0.078 P=0.741N P=0.519 P=0.198 | |POLY 1.5 | P=0.091 (e) P=0.233 P=0.203 |P=0.077 P=0.742N P=0.523 P=0.196 | |POLY 6 | P=0.063 (e) P=0.229 P=0.168 |P=0.080 P=0.739N P=0.513 P=0.204 | |LOGISTIC REGRESSION| (e) (e) P=0.229 P=0.107 |P=0.099 P=0.721N P=0.500 P=0.238 | |COCH-ARM / FISHERS | P=0.107 (e) P=0.242 P=0.227 |P=0.080 P=0.736N P=0.524 P=0.201 | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 13 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 3/50 (6%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.2% 0.0% 2.1% 7.5% |2.2% 2.1% 0.0% 0.0% | |TERMINAL (d) | 1/45 (2%) 0/41 (0%) 1/43 (2%) 2/23 (9%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 0/42 (0%) | |FIRST INCIDENCE | 710 --- 729 (T) 647 |717 611 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.053 P=0.260N P=0.513N P=0.240 |P=0.301N P=0.747N P=0.516N P=0.480N | |POLY 3 | P=0.151 P=0.244N P=0.505N P=0.418 |P=0.305N P=0.750N P=0.500N P=0.495N | |POLY 1.5 | P=0.166 P=0.239N P=0.501N P=0.458 |P=0.307N P=0.754N P=0.499N P=0.499N | |POLY 6 | P=0.133 P=0.249N P=0.509N P=0.364 |P=0.303N P=0.745N P=0.503N P=0.490N | |LOGISTIC REGRESSION| P=0.134 P=0.240N P=0.504N P=0.407 |P=0.290N P=0.742 P=0.502N P=0.495N | |COCH-ARM / FISHERS | P=0.187 P=0.247N P=0.500N P=0.500 |P=0.305N P=0.753N P=0.500N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 3/50 (6%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.2% 0.0% 2.1% 7.5% |2.2% 4.3% 2.2% 0.0% | |TERMINAL (d) | 1/45 (2%) 0/41 (0%) 1/43 (2%) 2/23 (9%) |0/35 (0%) 1/42 (2%) 1/35 (3%) 0/42 (0%) | |FIRST INCIDENCE | 710 --- 729 (T) 647 |717 611 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.053 P=0.260N P=0.513N P=0.240 |P=0.222N P=0.535 P=0.751 P=0.480N | |POLY 3 | P=0.151 P=0.244N P=0.505N P=0.418 |P=0.231N P=0.517 P=0.760 P=0.495N | |POLY 1.5 | P=0.166 P=0.239N P=0.501N P=0.458 |P=0.235N P=0.511 P=0.760N P=0.499N | |POLY 6 | P=0.133 P=0.249N P=0.509N P=0.364 |P=0.225N P=0.525 P=0.757 P=0.490N | |LOGISTIC REGRESSION| P=0.134 P=0.240N P=0.504N P=0.407 |P=0.234N P=0.484 P=0.758 P=0.495N | |COCH-ARM / FISHERS | P=0.187 P=0.247N P=0.500N P=0.500 |P=0.235N P=0.500 P=0.753N P=0.500N | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 14 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |2/50 (4%) 1/50 (2%) 2/50 (4%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 2.1% 4.2% 2.5% |4.4% 2.1% 4.4% 2.2% | |TERMINAL (d) | 0/45 (0%) 1/41 (2%) 1/43 (2%) 0/23 (0%) |0/35 (0%) 0/42 (0%) 0/35 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- 729 (T) 685 623 |554 549 491 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.347 P=0.481 P=0.232 P=0.448 |P=0.470N P=0.497N P=0.686 P=0.479N | |POLY 3 | P=0.416 P=0.495 P=0.235 P=0.465 |P=0.482N P=0.489N P=0.692 P=0.499N | |POLY 1.5 | P=0.456 P=0.498 P=0.237 P=0.482 |P=0.484N P=0.492N P=0.692N P=0.502N | |POLY 6 | P=0.359 P=0.490 P=0.234 P=0.441 |P=0.477N P=0.484N P=0.687 P=0.492N | |LOGISTIC REGRESSION| P=0.514 P=0.481 P=0.237 P=0.510 |P=0.371N P=0.652N P=0.615 P=0.483N | |COCH-ARM / FISHERS | P=0.500 P=0.500 P=0.247 P=0.500 |P=0.476N P=0.500N P=0.691N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 2/50 (4%) 0/50 (0%) |14/50 (28%) 8/50 (16%) 8/50 (16%) 10/50 (20%) | |POLY-3 ADJUSTED (b)| 6.3% 6.4% 4.2% 0.0% |30.6% 16.7% 17.4% 21.6% | |TERMINAL (d) | 3/45 (7%) 3/41 (7%) 2/43 (5%) 0/23 (0%) |11/35 (31%) 6/42 (14%) 5/35 (14%) 9/42 (21%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |519 499 505 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.171N P=0.619 P=0.521N P=0.262N |P=0.313N P=0.060N P=0.128N P=0.130N | |POLY 3 | P=0.104N P=0.650 P=0.506N P=0.156N |P=0.413N P=0.089N P=0.107N P=0.229N | |POLY 1.5 | P=0.089N P=0.658 P=0.501N P=0.137N |P=0.419N P=0.097N P=0.107N P=0.242N | |POLY 6 | P=0.127N P=0.640 P=0.510N P=0.187N |P=0.398N P=0.081N P=0.110N P=0.208N | |LOGISTIC REGRESSION| P=0.171N P=0.619 P=0.521N (e) |P=0.402N P=0.117N P=0.113N P=0.229N | |COCH-ARM / FISHERS | P=0.074N P=0.661N P=0.500N P=0.121N |P=0.400N P=0.114N P=0.114N P=0.241N | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 15 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 27/50 (54%) 34/50 (68%) 41/50 (82%) 43/50 (86%) |13/50 (26%) 31/50 (62%) 32/50 (64%) 40/50 (80%) | |POLY-3 ADJUSTED (b)| 55.1% 71.9% 86.0% 91.7% |28.5% 65.7% 69.5% 85.7% | |TERMINAL (d) | 23/45 (51%) 31/41 (76%) 38/43 (88%) 22/23 (96%) |10/35 (29%) 29/42 (69%) 27/35 (77%) 38/42 (91%) | |FIRST INCIDENCE | 550 662 662 490 |519 611 626 549 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.046 * P=0.002 ** P<0.001 ** |P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.064 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.087 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.043 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.078 P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.109 P=0.002 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 18/50 (36%) 28/50 (56%) 33/50 (66%) 45/50 (90%) |21/50 (42%) 17/50 (34%) 18/50 (36%) 25/50 (50%) | |POLY-3 ADJUSTED (b)| 37.4% 57.8% 67.3% 91.9% |44.1% 34.6% 37.6% 52.2% | |TERMINAL (d) | 16/45 (36%) 24/41 (59%) 28/43 (65%) 20/23 (87%) |13/35 (37%) 12/42 (29%) 9/35 (26%) 21/42 (50%) | |FIRST INCIDENCE | 702 464 453 456 |519 499 491 186 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.018 * P=0.003 ** P<0.001 ** |P=0.232 P=0.158N P=0.374N P=0.521 | |POLY 3 | P<0.001 ** P=0.033 * P=0.002 ** P<0.001 ** |P=0.099 P=0.227N P=0.327N P=0.281 | |POLY 1.5 | P<0.001 ** P=0.036 * P=0.002 ** P<0.001 ** |P=0.100 P=0.238N P=0.325N P=0.274 | |POLY 6 | P<0.001 ** P=0.029 * P=0.002 ** P<0.001 ** |P=0.100 P=0.215N P=0.339N P=0.291 | |LOGISTIC REGRESSION| P<0.001 ** P=0.033 * P=0.003 ** P<0.001 ** |P=0.116 P=0.315N P=0.351N P=0.274 | |COCH-ARM / FISHERS | P<0.001 ** P=0.035 * P=0.002 ** P<0.001 ** |P=0.110 P=0.268N P=0.341N P=0.274 | |=================================================================================================================================| Date: 12/11/98 EXPERIMENT: 88036 TEST: 04 Page 16 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - ANTHRAQUINONE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 833 PPM 2500 PPM 7500 PPM |0 PPM 833 PPM 2500 PPM 7500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 35/50 (70%) 38/50 (76%) 47/50 (94%) 48/50 (96%) |28/50 (56%) 38/50 (76%) 41/50 (82%) 44/50 (88%) | |POLY-3 ADJUSTED (b)| 71.4% 78.0% 95.3% 98.0% |58.8% 77.2% 83.9% 91.5% | |TERMINAL (d) | 31/45 (69%) 32/41 (78%) 41/43 (95%) 23/23 (100%)|19/35 (54%) 32/42 (76%) 29/35 (83%) 39/42 (93%) | |FIRST INCIDENCE | 550 464 453 456 |519 499 491 186 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.157 P=0.004 ** P<0.001 ** |P=0.056 P=0.238 P=0.021 * P=0.038 * | |POLY 3 | P<0.001 ** P=0.305 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.039 * P=0.004 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.336 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.035 * P=0.004 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.269 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.043 * P=0.004 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.322 P=0.002 ** P<0.001 ** |P<0.001 ** P=0.032 * P=0.005 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.326 P=0.002 ** P<0.001 ** |P<0.001 ** P=0.028 * P=0.004 ** P<0.001 ** | |=================================================================================================================================| (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).