NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Midwest Research Inst TETRANITROMETHANE DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 TIME: 03:29:00 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01ES38042 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 55947 PATHOLOGIST: M. STEDHAM CAS: 509-14-8 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Midwest Research Inst TETRANITROMETHANE DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 TIME: 03:29:00 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01ES38042 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 55947 PATHOLOGIST: M. STEDHAM CAS: 509-14-8 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 NUMBER OF ANIMALS NECROPSIED. ---------------- Adrenal Gland Bone Marrow Brain Clitoral Gland Epididymis Gallbladder Heart Islets, Pancreatic Kidney Larynx Liver Lung Nose Ovary Pancreas Parathyroid Gland Pituitary Gland Preputial Gland Prostate Salivary Glands Spleen Testes Thymus Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Midwest Research Inst TETRANITROMETHANE DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 TIME: 03:29:00 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01ES38042 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 55947 PATHOLOGIST: M. STEDHAM CAS: 509-14-8 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF THE STUDY OF TETRANITROMETHANE ==================================================================================================== MALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Liver Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma All Organs Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== FEMALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Liver Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Spleen Hemangiosarcoma All Organs Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 1 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Non-medullary, Non-cortical | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/49 (4%) 0/50 (0%) | 0/49 (0%) 0/49 (0%) 1/50 (2%) | |ADJUSTED (b) | 2.7% 6.9% 0.0% | 0.0% 0.0% 2.6% | |TERMINAL (d) | 1/37 (3%) 1/25 (4%) 0/15 (0%) | 0/31 (0%) 0/28 (0%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 678 --- | --- --- 666 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.498N P=0.388 P=0.680N | P=0.334 (e) P=0.539 | |INCIDENTAL TUMOR | P=0.415N P=0.410 P=0.680N | P=0.488 (e) P=0.826 | |LOGISTIC REGRESSION | P=0.407N P=0.425 P=0.680N | P=0.316 (e) P=0.507 | |COCHRAN-ARMITAGE | P=0.302N | P=0.315 | |FISHER EXACT | P=0.492 P=0.500N | (e) P=0.505 | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) | 1/50 (2%) 1/50 (2%) 0/50 (0%) | |ADJUSTED (b) | 5.3% 3.8% 6.7% | 3.2% 3.6% 0.0% | |TERMINAL (d) | 1/37 (3%) 1/26 (4%) 1/15 (7%) | 1/31 (3%) 1/28 (4%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | 698 729 (T) 729 (T) | 729 (T) 729 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.643 P=0.620N P=0.707 | P=0.417N P=0.739 P=0.551N | |INCIDENTAL TUMOR | P=0.665N P=0.581N P=0.672N | P=0.417N P=0.739 P=0.551N | |LOGISTIC REGRESSION | P=0.667N P=0.586N P=0.689N | P=0.417N P=0.739 P=0.551N | |COCHRAN-ARMITAGE | P=0.480N | P=0.364N | |FISHER EXACT | P=0.500N P=0.500N | P=0.753N P=0.500N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 2 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/48 (0%) | 3/49 (6%) 0/50 (0%) 0/49 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% | 8.9% 0.0% 0.0% | |TERMINAL (d) | 0/37 (0%) 0/25 (0%) 0/15 (0%) | 2/31 (6%) 0/28 (0%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- | 627 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) | P=0.133N P=0.132N P=0.149N | |INCIDENTAL TUMOR | (e) (e) (e) | P=0.194N P=0.187N P=0.238N | |LOGISTIC REGRESSION | (e) (e) (e) | P=0.117N P=0.119N P=0.123N | |COCHRAN-ARMITAGE | (e) | P=0.115N | |FISHER EXACT | (e) (e) | P=0.117N P=0.121N | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 1/50 (2%) | 0/49 (0%) 0/50 (0%) 1/50 (2%) | |ADJUSTED (b) | 7.2% 10.9% 2.7% | 0.0% 0.0% 4.2% | |TERMINAL (d) | 1/37 (3%) 1/26 (4%) 0/15 (0%) | 0/31 (0%) 0/28 (0%) 1/24 (4%) | |FIRST INCIDENCE (DAYS) | 504 580 588 | --- --- 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.391N P=0.381 P=0.478N | P=0.271 (e) P=0.449 | |INCIDENTAL TUMOR | P=0.059N P=0.613N P=0.094N | P=0.271 (e) P=0.449 | |LOGISTIC REGRESSION | P=0.164N P=0.586 P=0.183N | P=0.271 (e) P=0.449 | |COCHRAN-ARMITAGE | P=0.206N | P=0.314 | |FISHER EXACT | P=0.500 P=0.309N | (e) P=0.505 | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 3 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 15/50 (30%) 2/50 (4%) | 9/49 (18%) 1/50 (2%) 4/50 (8%) | |ADJUSTED (b) | 25.4% 44.2% 8.5% | 23.4% 3.6% 14.7% | |TERMINAL (d) | 8/37 (22%) 9/26 (35%) 0/15 (0%) | 4/31 (13%) 1/28 (4%) 3/24 (13%) | |FIRST INCIDENCE (DAYS) | 674 566 671 | 563 729 (T) 645 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.149N P=0.043 * P=0.208N | P=0.277N P=0.014N* P=0.174N | |INCIDENTAL TUMOR | P=0.021N* P=0.118 P=0.085N | P=0.377N P=0.022N* P=0.246N | |LOGISTIC REGRESSION | P=0.017N* P=0.112 P=0.076N | P=0.207N P=0.009N** P=0.110N | |COCHRAN-ARMITAGE | P=0.005N** | P=0.205N | |FISHER EXACT | P=0.178 P=0.014N* | P=0.007N** P=0.109N | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 11/50 (22%) 11/50 (22%) | 4/49 (8%) 2/50 (4%) 3/50 (6%) | |ADJUSTED (b) | 30.7% 29.7% 41.0% | 12.3% 7.1% 11.9% | |TERMINAL (d) | 9/37 (24%) 4/26 (15%) 3/15 (20%) | 3/31 (10%) 2/28 (7%) 2/24 (8%) | |FIRST INCIDENCE (DAYS) | 639 534 546 | 655 729 (T) 714 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.134 P=0.465 P=0.132 | P=0.600 P=0.364N P=0.601N | |INCIDENTAL TUMOR | P=0.280N P=0.279N P=0.379N | P=0.512N P=0.279N P=0.378N | |LOGISTIC REGRESSION | P=0.484N P=0.409N P=0.547N | P=0.558N P=0.315N P=0.505N | |COCHRAN-ARMITAGE | P=0.418N | P=0.532N | |FISHER EXACT | P=0.408N P=0.408N | P=0.329N P=0.489N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 4 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 24/50 (48%) 12/50 (24%) | 13/49 (27%) 3/50 (6%) 7/50 (14%) | |ADJUSTED (b) | 52.9% 61.0% 43.5% | 33.9% 10.7% 25.8% | |TERMINAL (d) | 17/37 (46%) 12/26 (46%) 3/15 (20%) | 7/31 (23%) 3/28 (11%) 5/24 (21%) | |FIRST INCIDENCE (DAYS) | 639 534 546 | 563 729 (T) 645 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.553N P=0.117 P=0.491 | P=0.329N P=0.011N* P=0.193N | |INCIDENTAL TUMOR | P=0.010N* P=0.495 P=0.045N* | P=0.330N P=0.011N* P=0.147N | |LOGISTIC REGRESSION | P=0.022N* P=0.404 P=0.076N | P=0.216N P=0.007N** P=0.102N | |COCHRAN-ARMITAGE | P=0.007N** | P=0.208N | |FISHER EXACT | P=0.500 P=0.018N* | P=0.005N** P=0.096N | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 24/50 (48%) 12/50 (24%) | 13/49 (27%) 3/50 (6%) 7/50 (14%) | |ADJUSTED (b) | 52.9% 61.0% 43.5% | 33.9% 10.7% 25.8% | |TERMINAL (d) | 17/37 (46%) 12/26 (46%) 3/15 (20%) | 7/31 (23%) 3/28 (11%) 5/24 (21%) | |FIRST INCIDENCE (DAYS) | 639 534 546 | 563 729 (T) 645 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.553N P=0.117 P=0.491 | P=0.329N P=0.011N* P=0.193N | |INCIDENTAL TUMOR | P=0.010N* P=0.495 P=0.045N* | P=0.330N P=0.011N* P=0.147N | |LOGISTIC REGRESSION | P=0.022N* P=0.404 P=0.076N | P=0.216N P=0.007N** P=0.102N | |COCHRAN-ARMITAGE | P=0.007N** | P=0.208N | |FISHER EXACT | P=0.500 P=0.018N* | P=0.005N** P=0.096N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 5 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 17/50 (34%) 34/50 (68%) | 1/49 (2%) 19/50 (38%) 41/50 (82%) | |ADJUSTED (b) | 17.5% 53.7% 90.5% | 3.2% 56.6% 93.0% | |TERMINAL (d) | 5/37 (14%) 12/26 (46%) 12/15 (80%) | 1/31 (3%) 14/28 (50%) 21/24 (88%) | |FIRST INCIDENCE (DAYS) | 662 534 376 | 729 (T) 601 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.002 ** P<0.001 ** | P<0.001 ** P<0.001 ** P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P=0.003 ** P<0.001 ** | P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P=0.005 ** P<0.001 ** | P<0.001 ** P<0.001 ** P<0.001 ** | |COCHRAN-ARMITAGE | P<0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.017 * P<0.001 ** | P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 16/50 (32%) 46/50 (92%) | 3/49 (6%) 11/50 (22%) 45/50 (90%) | |ADJUSTED (b) | 15.7% 45.6% 100.0% | 8.8% 34.2% 97.8% | |TERMINAL (d) | 5/37 (14%) 8/26 (31%) 15/15 (100%) | 2/31 (6%) 8/28 (29%) 23/24 (96%) | |FIRST INCIDENCE (DAYS) | 691 566 485 | 619 601 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.002 ** P<0.001 ** | P<0.001 ** P=0.017 * P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P=0.010 * P<0.001 ** | P<0.001 ** P=0.016 * P<0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P=0.007 ** P<0.001 ** | P<0.001 ** P=0.023 * P<0.001 ** | |COCHRAN-ARMITAGE | P<0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.014 * P<0.001 ** | P=0.022 * P<0.001 ** | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 6 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 12/50 (24%) 27/50 (54%) 47/50 (94%) | 4/49 (8%) 24/50 (48%) 49/50 (98%) | |ADJUSTED (b) | 29.7% 70.3% 100.0% | 11.9% 69.7% 100.0% | |TERMINAL (d) | 9/37 (24%) 15/26 (58%) 15/15 (100%) | 3/31 (10%) 18/28 (64%) 24/24 (100%) | |FIRST INCIDENCE (DAYS) | 662 534 376 | 619 601 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** | P<0.001 ** P<0.001 ** P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P<0.001 ** P<0.001 ** | P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P<0.001 ** P<0.001 ** | P<0.001 ** P<0.001 ** P<0.001 ** | |COCHRAN-ARMITAGE | P<0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.002 ** P<0.001 ** | P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) | 18/49 (37%) 19/49 (39%) 14/48 (29%) | |ADJUSTED (b) | 0.0% 0.0% 2.0% | 51.0% 56.9% 48.1% | |TERMINAL (d) | 0/37 (0%) 0/24 (0%) 0/14 (0%) | 14/31 (45%) 14/28 (50%) 9/23 (39%) | |FIRST INCIDENCE (DAYS) | --- --- 145 | 590 592 674 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.315 (e) P=0.500 | P=0.484N P=0.401 P=0.532N | |INCIDENTAL TUMOR | P=0.500 (e) (e) | P=0.194N P=0.569 P=0.219N | |LOGISTIC REGRESSION | P=0.260 (e) (e) | P=0.219N P=0.543 P=0.278N | |COCHRAN-ARMITAGE | P=0.311 | P=0.216N | |FISHER EXACT | (e) P=0.500 | P=0.500 P=0.282N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 7 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/48 (0%) | 2/49 (4%) 0/49 (0%) 0/48 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% | 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/37 (0%) 0/24 (0%) 0/14 (0%) | 0/31 (0%) 0/28 (0%) 0/23 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- | 563 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) | P=0.228N P=0.245N P=0.247N | |INCIDENTAL TUMOR | (e) (e) (e) | P=0.458N P=0.444N P=0.573N | |LOGISTIC REGRESSION | (e) (e) (e) | P=0.219N P=0.183N P=0.201N | |COCHRAN-ARMITAGE | (e) | P=0.225N | |FISHER EXACT | (e) (e) | P=0.247N P=0.253N | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 1/48 (2%) | 20/49 (41%) 19/49 (39%) 14/48 (29%) | |ADJUSTED (b) | 0.0% 0.0% 2.0% | 53.2% 56.9% 48.1% | |TERMINAL (d) | 0/37 (0%) 0/24 (0%) 0/14 (0%) | 14/31 (45%) 14/28 (50%) 9/23 (39%) | |FIRST INCIDENCE (DAYS) | --- --- 145 | 563 592 674 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.315 (e) P=0.500 | P=0.356N P=0.559 P=0.373N | |INCIDENTAL TUMOR | P=0.500 (e) (e) | P=0.150N P=0.505N P=0.172N | |LOGISTIC REGRESSION | P=0.260 (e) (e) | P=0.132N P=0.494N P=0.159N | |COCHRAN-ARMITAGE | P=0.311 | P=0.132N | |FISHER EXACT | (e) P=0.500 | P=0.500N P=0.161N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 8 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Skin: Subcutaneous Tissue | | Neurofibrosarcoma, Fibrosarcoma, Sarcoma, | | Neurofibroma, or Fibroma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) | 0/50 (0%) 0/50 (0%) 2/50 (4%) | |ADJUSTED (b) | 0.0% 3.8% 0.0% | 0.0% 0.0% 5.6% | |TERMINAL (d) | 0/37 (0%) 1/26 (4%) 0/15 (0%) | 0/31 (0%) 0/28 (0%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) --- | --- --- 673 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.827N P=0.430 (e) | P=0.097 (e) P=0.262 | |INCIDENTAL TUMOR | P=0.827N P=0.430 (e) | P=0.240 (e) P=0.643 | |LOGISTIC REGRESSION | P=0.827N P=0.430 (e) | P=0.092 (e) P=0.238 | |COCHRAN-ARMITAGE | P=0.689N | P=0.092 | |FISHER EXACT | P=0.500 (e) | (e) P=0.247 | |=================================================================================================================================| | | |Skin: Subcutaneous Tissue | | Neurofibrosarcoma, Fibrosarcoma, or Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) | 0/50 (0%) 0/50 (0%) 2/50 (4%) | |ADJUSTED (b) | 0.0% 3.8% 0.0% | 0.0% 0.0% 5.6% | |TERMINAL (d) | 0/37 (0%) 1/26 (4%) 0/15 (0%) | 0/31 (0%) 0/28 (0%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) --- | --- --- 673 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.827N P=0.430 (e) | P=0.097 (e) P=0.262 | |INCIDENTAL TUMOR | P=0.827N P=0.430 (e) | P=0.240 (e) P=0.643 | |LOGISTIC REGRESSION | P=0.827N P=0.430 (e) | P=0.092 (e) P=0.238 | |COCHRAN-ARMITAGE | P=0.689N | P=0.092 | |FISHER EXACT | P=0.500 (e) | (e) P=0.247 | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 9 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/49 (6%) 1/50 (2%) | 0/48 (0%) 0/49 (0%) 4/50 (8%) | |ADJUSTED (b) | 4.6% 10.0% 6.7% | 0.0% 0.0% 14.7% | |TERMINAL (d) | 0/37 (0%) 2/26 (8%) 1/15 (7%) | 0/31 (0%) 0/28 (0%) 3/24 (13%) | |FIRST INCIDENCE (DAYS) | 629 622 729 (T) | --- --- 666 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.622N P=0.370 P=0.719N | P=0.006 ** (e) P=0.047 * | |INCIDENTAL TUMOR | P=0.319N P=0.681 P=0.380N | P=0.011 * (e) P=0.071 | |LOGISTIC REGRESSION | P=0.411N P=0.494 P=0.547N | P=0.009 ** (e) P=0.061 | |COCHRAN-ARMITAGE | P=0.354N | P=0.011 * | |FISHER EXACT | P=0.490 P=0.500N | (e) P=0.064 | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/48 (0%) 1/50 (2%) | 3/48 (6%) 2/50 (4%) 3/50 (6%) | |ADJUSTED (b) | 4.8% 0.0% 5.3% | 9.6% 6.9% 12.5% | |TERMINAL (d) | 1/37 (3%) 0/26 (0%) 0/15 (0%) | 2/30 (7%) 1/28 (4%) 3/24 (13%) | |FIRST INCIDENCE (DAYS) | 646 --- 717 | 704 718 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.669 P=0.310N P=0.730N | P=0.468 P=0.525N P=0.561 | |INCIDENTAL TUMOR | P=0.589N P=0.278N P=0.539N | P=0.628 P=0.294N P=0.650N | |LOGISTIC REGRESSION | P=0.641N P=0.224N P=0.594N | P=0.546 P=0.462N P=0.650 | |COCHRAN-ARMITAGE | P=0.564N | P=0.586 | |FISHER EXACT | P=0.258N P=0.500N | P=0.480N P=0.641N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 10 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # | |----------- | | | |OVERALL (a) | | 2/50 (4%) 1/50 (2%) 1/50 (2%) | |ADJUSTED (b) | | 6.2% 2.6% 2.9% | |TERMINAL (d) | | 1/31 (3%) 0/28 (0%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | | 657 692 684 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.492N P=0.470N P=0.500N | |INCIDENTAL TUMOR | | P=0.230N P=0.219N P=0.189N | |LOGISTIC REGRESSION | | P=0.480N P=0.499N P=0.500N | |COCHRAN-ARMITAGE | | P=0.480N | |FISHER EXACT | | P=0.500N P=0.500N | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # | |----------- | | | |OVERALL (a) | | 1/50 (2%) 3/50 (6%) 1/50 (2%) | |ADJUSTED (b) | | 3.2% 9.5% 4.2% | |TERMINAL (d) | | 1/31 (3%) 2/28 (7%) 1/24 (4%) | |FIRST INCIDENCE (DAYS) | | 729 (T) 665 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.582N P=0.298 P=0.704 | |INCIDENTAL TUMOR | | P=0.508N P=0.384 P=0.704 | |LOGISTIC REGRESSION | | P=0.527N P=0.317 P=0.704 | |COCHRAN-ARMITAGE | | P=0.518N | |FISHER EXACT | | P=0.309 P=0.753N | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 11 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 7/50 (14%) 2/50 (4%) | 3/50 (6%) 2/50 (4%) 6/50 (12%) | |ADJUSTED (b) | 9.1% 21.6% 9.2% | 9.3% 5.1% 21.1% | |TERMINAL (d) | 1/37 (3%) 4/26 (15%) 1/15 (7%) | 2/31 (6%) 0/28 (0%) 4/24 (17%) | |FIRST INCIDENCE (DAYS) | 504 580 588 | 657 665 666 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.500N P=0.145 P=0.594N | P=0.101 P=0.466N P=0.190 | |INCIDENTAL TUMOR | P=0.103N P=0.427 P=0.103N | P=0.263 P=0.186N P=0.392 | |LOGISTIC REGRESSION | P=0.180N P=0.295 P=0.235N | P=0.125 P=0.498N P=0.239 | |COCHRAN-ARMITAGE | P=0.189N | P=0.128 | |FISHER EXACT | P=0.262 P=0.339N | P=0.500N P=0.243 | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 7/50 (14%) 2/50 (4%) | 3/50 (6%) 3/50 (6%) 6/50 (12%) | |ADJUSTED (b) | 11.6% 21.6% 9.2% | 9.3% 8.5% 21.1% | |TERMINAL (d) | 2/37 (5%) 4/26 (15%) 1/15 (7%) | 2/31 (6%) 1/28 (4%) 4/24 (17%) | |FIRST INCIDENCE (DAYS) | 504 580 588 | 657 665 666 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.423N P=0.219 P=0.497N | P=0.127 P=0.639N P=0.190 | |INCIDENTAL TUMOR | P=0.077N P=0.537 P=0.077N | P=0.303 P=0.381N P=0.392 | |LOGISTIC REGRESSION | P=0.129N P=0.409 P=0.156N | P=0.160 P=0.659N P=0.239 | |COCHRAN-ARMITAGE | P=0.130N | P=0.165 | |FISHER EXACT | P=0.380 P=0.218N | P=0.661N P=0.243 | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 12 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) | 0/50 (0%) 0/50 (0%) 0/50 (0%) | |ADJUSTED (b) | 5.4% 2.1% 0.0% | 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/37 (5%) 0/26 (0%) 0/15 (0%) | 0/31 (0%) 0/28 (0%) 0/24 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 426 --- | --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.310N P=0.586N P=0.452N | (e) (e) (e) | |INCIDENTAL TUMOR | P=0.161N P=0.504N P=0.452N | (e) (e) (e) | |LOGISTIC REGRESSION | P=0.163N P=0.420N P=0.452N | (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.195N | (e) | |FISHER EXACT | P=0.500N P=0.247N | (e) (e) | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma And Histiocytic Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) 2/50 (4%) | 11/50 (22%) 13/50 (26%) 15/50 (30%) | |ADJUSTED (b) | 10.8% 13.2% 11.6% | 29.9% 33.4% 40.6% | |TERMINAL (d) | 4/37 (11%) 0/26 (0%) 1/15 (7%) | 7/31 (23%) 4/28 (14%) 6/24 (25%) | |FIRST INCIDENCE (DAYS) | 729 (T) 426 717 | 480 263 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.571N P=0.344 P=0.603 | P=0.168 P=0.394 P=0.185 | |INCIDENTAL TUMOR | P=0.222N P=0.543 P=0.674N | P=0.428 P=0.549N P=0.212 | |LOGISTIC REGRESSION | P=0.262N P=0.543 P=0.677N | P=0.237 P=0.408 P=0.247 | |COCHRAN-ARMITAGE | P=0.240N | P=0.238 | |FISHER EXACT | P=0.500 P=0.339N | P=0.408 P=0.247 | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 13 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 2/50 (4%) | 11/50 (22%) 13/50 (26%) 15/50 (30%) | |ADJUSTED (b) | 5.4% 11.4% 11.6% | 29.9% 33.4% 40.6% | |TERMINAL (d) | 2/37 (5%) 0/26 (0%) 1/15 (7%) | 7/31 (23%) 4/28 (14%) 6/24 (25%) | |FIRST INCIDENCE (DAYS) | 729 (T) 643 717 | 480 263 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.433 P=0.227 P=0.372 | P=0.168 P=0.394 P=0.185 | |INCIDENTAL TUMOR | P=0.512N P=0.382 P=0.470 | P=0.428 P=0.549N P=0.212 | |LOGISTIC REGRESSION | P=0.627N P=0.323 P=0.437 | P=0.237 P=0.408 P=0.247 | |COCHRAN-ARMITAGE | P=0.514N | P=0.238 | |FISHER EXACT | P=0.339 P=0.691N | P=0.408 P=0.247 | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 20/50 (40%) 26/50 (52%) 37/50 (74%) | 29/50 (58%) 36/50 (72%) 45/50 (90%) | |ADJUSTED (b) | 46.2% 70.9% 91.6% | 70.2% 92.2% 97.8% | |TERMINAL (d) | 14/37 (38%) 16/26 (62%) 12/15 (80%) | 19/31 (61%) 25/28 (89%) 23/24 (96%) | |FIRST INCIDENCE (DAYS) | 646 534 145 | 544 592 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.016 * P<0.001 ** | P<0.001 ** P=0.086 P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P=0.066 P=0.001 ** | P<0.001 ** P=0.141 P=0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P=0.073 P<0.001 ** | P<0.001 ** P=0.093 P<0.001 ** | |COCHRAN-ARMITAGE | P<0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.158 P<0.001 ** | P=0.104 P<0.001 ** | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 14 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | CONTROL 0.5 PPM 2 PPM | CONTROL 0.5 PPM 2 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 25/50 (50%) 31/50 (62%) 46/50 (92%) | 22/50 (44%) 24/50 (48%) 47/50 (94%) | |ADJUSTED (b) | 54.9% 66.9% 100.0% | 52.7% 56.0% 100.0% | |TERMINAL (d) | 17/37 (46%) 11/26 (42%) 15/15 (100%) | 12/31 (39%) 10/28 (36%) 24/24 (100%) | |FIRST INCIDENCE (DAYS) | 504 426 485 | 480 263 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.026 * P<0.001 ** | P<0.001 ** P=0.408 P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P=0.365 P<0.001 ** | P<0.001 ** P=0.527N P<0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P=0.169 P<0.001 ** | P<0.001 ** P=0.420 P<0.001 ** | |COCHRAN-ARMITAGE | P<0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.157 P<0.001 ** | P=0.421 P<0.001 ** | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # | # # # | |----------- | | | |OVERALL (a) | 39/50 (78%) 40/50 (80%) 48/50 (96%) | 40/50 (80%) 44/50 (88%) 49/50 (98%) | |ADJUSTED (b) | 81.2% 85.1% 100.0% | 85.0% 97.7% 100.0% | |TERMINAL (d) | 28/37 (76%) 19/26 (73%) 15/15 (100%) | 24/31 (77%) 27/28 (96%) 24/24 (100%) | |FIRST INCIDENCE (DAYS) | 504 426 145 | 480 263 444 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.039 * P<0.001 ** | P=0.012 * P=0.216 P=0.022 * | |INCIDENTAL TUMOR | P=0.011 * P=0.513 P=0.018 * | P=0.010 ** P=0.169 P=0.007 ** | |LOGISTIC REGRESSION | P=0.002 ** P=0.351 P=0.004 ** | P=0.004 ** P=0.162 P=0.003 ** | |COCHRAN-ARMITAGE | P=0.006 ** | P=0.005 ** | |FISHER EXACT | P=0.500 P=0.007 ** | P=0.207 P=0.004 ** | |=================================================================================================================================| DATE: 09/09/94 EXPERIMENT: 05072 TEST: 02 PAGE 15 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE TERMINAL SACRIFICE AT 105 WEEKS (a) Number of tumor-bearing animals / number of animals examined at site. (b) Kaplan-Meier estimated lifetime tumor incidence after adjustment for intercurrent mortality. (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. The incidental tumor test regards these lesions as non-fatal. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fisher's 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).