TDMS Study 05090-02 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: American Biogenics COUMARIN DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 TIME: 06:36:35 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-45039 ROUTE: GAVAGE NTP C#: 07103B PATHOLOGIST: R. DAHLGREN CAS: 91-64-5 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: American Biogenics COUMARIN DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 TIME: 06:36:35 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-45039 ROUTE: GAVAGE NTP C#: 07103B PATHOLOGIST: R. DAHLGREN CAS: 91-64-5 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 Epididymis Gallbladder Heart Islets, Pancreatic Kidney 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: American Biogenics COUMARIN DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 TIME: 06:36:35 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-45039 ROUTE: GAVAGE NTP C#: 07103B PATHOLOGIST: R. DAHLGREN CAS: 91-64-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF THE STUDY OF COUMARIN ==================================================================================================== MALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Liver Hepatoblastoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Stomach, Forestomach Squamous Cell Carcinoma or Papilloma Squamous Testes Adenoma Thyroid Gland: Follicular Cell Adenoma Carcinoma or Adenoma All Organs Malignant Lymphoma And Histiocytic Sarcoma 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 Uterus Sarcoma Stromal All Organs Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 1 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/59 (2%) 0/57 (0%) 0/55 (0%) 1/59 (2%) | 2/57 (4%) 0/55 (0%) 0/55 (0%) 0/59 (0%) | |ADJUSTED (b) | 2.3% 0.0% 0.0% 2.7% | 6.3% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 1/43 (2%) 0/47 (0%) 0/41 (0%) 1/37 (3%) | 2/32 (6%) 0/40 (0%) 0/42 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) --- --- 729 (T) | 729 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.558 P=0.482N P=0.510N P=0.728 | P=0.113N P=0.191N P=0.181N P=0.268N | |INCIDENTAL TUMOR | P=0.558 P=0.482N P=0.510N P=0.728 | P=0.113N P=0.191N P=0.181N P=0.268N | |LOGISTIC REGRESSION | P=0.558 P=0.482N P=0.510N P=0.728 | P=0.113N P=0.191N P=0.181N P=0.268N | |COCHRAN-ARMITAGE | P=0.595 | P=0.114N | |FISHER EXACT | P=0.509N P=0.518N P=0.752N | P=0.257N P=0.257N P=0.239N | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 1/58 (2%) 1/57 (2%) 1/60 (2%) | 1/60 (2%) 1/58 (2%) 1/58 (2%) 1/60 (2%) | |ADJUSTED (b) | 6.7% 2.1% 2.3% 1.9% | 3.0% 2.5% 2.2% 3.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 1/9 (11%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 2/43 (5%) 1/47 (2%) 0/42 (0%) 0/37 (0%) | 1/33 (3%) 1/40 (3%) 0/42 (0%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | 680 729 (T) 723 456 (I) | 729 (T) 729 (T) 679 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.290N P=0.280N P=0.320N P=0.357N | P=0.591 P=0.718N P=0.714N P=0.725 | |INCIDENTAL TUMOR | P=0.232N P=0.401N P=0.583N P=0.328N | P=0.625 P=0.718N P=0.745 P=0.725 | |LOGISTIC REGRESSION | P=0.247N P=0.299N P=0.330N P=0.297N | P=0.607 P=0.718N P=0.740N P=0.725 | |COCHRAN-ARMITAGE | P=0.243N | P=0.630N | |FISHER EXACT | P=0.322N P=0.329N P=0.309N | P=0.744 P=0.744 P=0.752N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 2 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Intestine Small | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 2/58 (3%) 0/57 (0%) 0/60 (0%) | 0/60 (0%) 0/58 (0%) 0/58 (0%) 0/60 (0%) | |ADJUSTED (b) | 4.7% 4.3% 0.0% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 2/43 (5%) 2/47 (4%) 0/42 (0%) 0/37 (0%) | 0/33 (0%) 0/40 (0%) 0/42 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) --- --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.102N P=0.662N P=0.244N P=0.272N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.102N P=0.662N P=0.244N P=0.272N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.102N P=0.662N P=0.244N P=0.272N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.088N | (e) | |FISHER EXACT | P=0.678 P=0.261N P=0.248N | (e) (e) (e) | |=================================================================================================================================| | | |Intestine Small: Jejunum | | Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/58 (2%) 0/57 (0%) 0/60 (0%) | 0/60 (0%) 0/58 (0%) 0/58 (0%) 0/60 (0%) | |ADJUSTED (b) | 4.7% 2.1% 0.0% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 2/43 (5%) 1/47 (2%) 0/42 (0%) 0/37 (0%) | 0/33 (0%) 0/40 (0%) 0/42 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) --- --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.115N P=0.469N P=0.244N P=0.272N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.115N P=0.469N P=0.244N P=0.272N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.115N P=0.469N P=0.244N P=0.272N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.102N | (e) | |FISHER EXACT | P=0.513N P=0.261N P=0.248N | (e) (e) (e) | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 3 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/59 (0%) 0/58 (0%) 3/57 (5%) 2/59 (3%) | 1/57 (2%) 2/56 (4%) 1/55 (2%) 0/56 (0%) | |ADJUSTED (b) | 0.0% 0.0% 7.1% 5.4% | 3.0% 5.0% 2.4% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 0/47 (0%) 3/42 (7%) 2/37 (5%) | 1/33 (3%) 2/40 (5%) 1/42 (2%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- --- 729 (T) 729 (T) | 729 (T) 729 (T) 729 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.067 (e) P=0.117 P=0.206 | P=0.277N P=0.567 P=0.707N P=0.533N | |INCIDENTAL TUMOR | P=0.067 (e) P=0.117 P=0.206 | P=0.277N P=0.567 P=0.707N P=0.533N | |LOGISTIC REGRESSION | P=0.067 (e) P=0.117 P=0.206 | P=0.277N P=0.567 P=0.707N P=0.533N | |COCHRAN-ARMITAGE | P=0.099 | P=0.252N | |FISHER EXACT | (e) P=0.115 P=0.248 | P=0.493 P=0.743 P=0.504N | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/59 (0%) 0/58 (0%) 3/57 (5%) 2/59 (3%) | 1/57 (2%) 3/56 (5%) 1/55 (2%) 0/56 (0%) | |ADJUSTED (b) | 0.0% 0.0% 7.1% 5.4% | 3.0% 7.0% 2.4% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 0/47 (0%) 3/42 (7%) 2/37 (5%) | 1/33 (3%) 2/40 (5%) 1/42 (2%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- --- 729 (T) 729 (T) | 729 (T) 635 729 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.067 (e) P=0.117 P=0.206 | P=0.225N P=0.377 P=0.707N P=0.533N | |INCIDENTAL TUMOR | P=0.067 (e) P=0.117 P=0.206 | P=0.234N P=0.359 P=0.707N P=0.533N | |LOGISTIC REGRESSION | P=0.067 (e) P=0.117 P=0.206 | P=0.210N P=0.353 P=0.707N P=0.533N | |COCHRAN-ARMITAGE | P=0.099 | P=0.205N | |FISHER EXACT | (e) P=0.115 P=0.248 | P=0.302 P=0.743 P=0.504N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 4 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Liver | | Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/58 (0%) 5/57 (9%) 1/60 (2%) | 0/58 (0%) 1/57 (2%) 0/58 (0%) 0/59 (0%) | |ADJUSTED (b) | 0.0% 0.0% 11.1% 2.7% | 0.0% 2.5% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 0/47 (0%) 4/42 (10%) 1/37 (3%) | 0/33 (0%) 1/40 (3%) 0/42 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- --- 1 729 (T) | --- 729 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.196 (e) P=0.032 * P=0.470 | P=0.601N P=0.538 (e) (e) | |INCIDENTAL TUMOR | P=0.299 (e) P=0.060 P=0.470 | P=0.601N P=0.538 (e) (e) | |LOGISTIC REGRESSION | P=0.280 (e) P=0.037 * P=0.470 | P=0.601N P=0.538 (e) (e) | |COCHRAN-ARMITAGE | P=0.246 | P=0.564N | |FISHER EXACT | (e) P=0.025 * P=0.500 | P=0.496 (e) (e) | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 26/60 (43%) 31/58 (53%) 30/57 (53%) 30/60 (50%) | 9/58 (16%) 26/57 (46%) 29/58 (50%) 12/59 (20%) | |ADJUSTED (b) | 56.5% 60.8% 68.0% 65.9% | 24.8% 63.4% 62.9% 39.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 2/8 (25%) 1/7 (14%) 3/9 (33%) | 1/8 (13%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 23/43 (53%) 27/47 (57%) 28/42 (67%) 22/37 (59%) | 7/33 (21%) 25/40 (63%) 25/42 (60%) 10/28 (36%) | |FIRST INCIDENCE (DAYS) | 680 456 (I) 455 (I) 455 (I) | 455 (I) 722 564 684 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.068 P=0.364 P=0.222 P=0.101 | P=0.288 P=0.003 ** P=0.001 ** P=0.196 | |INCIDENTAL TUMOR | P=0.165 P=0.232 P=0.158 P=0.152 | P=0.389 P=0.002 ** P<0.001 ** P=0.253 | |LOGISTIC REGRESSION | P=0.156 P=0.237 P=0.154 P=0.159 | P=0.423 P=0.002 ** P<0.001 ** P=0.257 | |COCHRAN-ARMITAGE | P=0.335 | P=0.463N | |FISHER EXACT | P=0.180 P=0.206 P=0.292 | P<0.001 ** P<0.001 ** P=0.331 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 5 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/60 (18%) 11/58 (19%) 5/57 (9%) 3/60 (5%) | 0/58 (0%) 3/57 (5%) 3/58 (5%) 1/59 (2%) | |ADJUSTED (b) | 23.6% 22.0% 11.6% 7.5% | 0.0% 7.3% 6.7% 2.8% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 8/43 (19%) 8/47 (17%) 4/42 (10%) 2/37 (5%) | 0/33 (0%) 2/40 (5%) 1/42 (2%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | 541 532 636 558 | --- 715 672 655 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.018N* P=0.520N P=0.109N P=0.045N* | P=0.465 P=0.162 P=0.162 P=0.484 | |INCIDENTAL TUMOR | P=0.003N** P=0.505 P=0.099N P=0.011N* | P=0.570N P=0.132 P=0.101 P=0.594 | |LOGISTIC REGRESSION | P=0.002N** P=0.493 P=0.104N P=0.010N** | P=0.582N P=0.152 P=0.141 P=0.501 | |COCHRAN-ARMITAGE | P=0.007N** | P=0.535 | |FISHER EXACT | P=0.558 P=0.108N P=0.022N* | P=0.119 P=0.122 P=0.504 | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/60 (18%) 11/58 (19%) 9/57 (16%) 3/60 (5%) | 0/58 (0%) 4/57 (7%) 3/58 (5%) 1/59 (2%) | |ADJUSTED (b) | 23.6% 22.0% 20.0% 7.5% | 0.0% 9.7% 6.7% 2.8% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 8/43 (19%) 8/47 (17%) 7/42 (17%) 2/37 (5%) | 0/33 (0%) 3/40 (8%) 1/42 (2%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | 541 532 1 558 | --- 715 672 655 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.034N* P=0.520N P=0.441N P=0.045N* | P=0.533 P=0.094 P=0.162 P=0.484 | |INCIDENTAL TUMOR | P=0.004N** P=0.505 P=0.347N P=0.011N* | P=0.502N P=0.076 P=0.101 P=0.594 | |LOGISTIC REGRESSION | P=0.017N* P=0.493 P=0.460N P=0.010N** | P=0.571 P=0.086 P=0.141 P=0.501 | |COCHRAN-ARMITAGE | P=0.014N* | P=0.586N | |FISHER EXACT | P=0.558 P=0.453N P=0.022N* | P=0.057 P=0.122 P=0.504 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 6 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 35/60 (58%) 36/58 (62%) 32/57 (56%) 32/60 (53%) | 9/58 (16%) 27/57 (47%) 31/58 (53%) 13/59 (22%) | |ADJUSTED (b) | 71.4% 69.2% 71.0% 68.9% | 24.8% 64.3% 65.9% 41.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 2/8 (25%) 1/7 (14%) 3/9 (33%) | 1/8 (13%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 29/43 (67%) 31/47 (66%) 29/42 (69%) 23/37 (62%) | 7/33 (21%) 25/40 (63%) 26/42 (62%) 10/28 (36%) | |FIRST INCIDENCE (DAYS) | 541 456 (I) 455 (I) 455 (I) | 455 (I) 715 564 655 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.384 P=0.458N P=0.435N P=0.449 | P=0.217 P=0.002 ** P<0.001 ** P=0.140 | |INCIDENTAL TUMOR | P=0.345N P=0.399 P=0.517N P=0.447N | P=0.348 P<0.001 ** P<0.001 ** P=0.198 | |LOGISTIC REGRESSION | P=0.362N P=0.517 P=0.493N P=0.525N | P=0.340 P=0.001 ** P<0.001 ** P=0.188 | |COCHRAN-ARMITAGE | P=0.249N | P=0.536N | |FISHER EXACT | P=0.411 P=0.479N P=0.357N | P<0.001 ** P<0.001 ** P=0.253 | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 35/60 (58%) 36/58 (62%) 33/57 (58%) 32/60 (53%) | 9/58 (16%) 27/57 (47%) 31/58 (53%) 13/59 (22%) | |ADJUSTED (b) | 71.4% 69.2% 71.5% 68.9% | 24.8% 64.3% 65.9% 41.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 2/8 (25%) 1/7 (14%) 3/9 (33%) | 1/8 (13%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 29/43 (67%) 31/47 (66%) 29/42 (69%) 23/37 (62%) | 7/33 (21%) 25/40 (63%) 26/42 (62%) 10/28 (36%) | |FIRST INCIDENCE (DAYS) | 541 456 (I) 1 455 (I) | 455 (I) 715 564 655 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.377 P=0.458N P=0.512N P=0.449 | P=0.217 P=0.002 ** P<0.001 ** P=0.140 | |INCIDENTAL TUMOR | P=0.311N P=0.399 P=0.517N P=0.447N | P=0.348 P<0.001 ** P<0.001 ** P=0.198 | |LOGISTIC REGRESSION | P=0.438N P=0.517 P=0.541N P=0.525N | P=0.340 P=0.001 ** P<0.001 ** P=0.188 | |COCHRAN-ARMITAGE | P=0.255N | P=0.536N | |FISHER EXACT | P=0.411 P=0.555N P=0.357N | P<0.001 ** P<0.001 ** P=0.253 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 7 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/60 (23%) 10/58 (17%) 14/57 (25%) 27/60 (45%) | 2/59 (3%) 5/57 (9%) 8/56 (14%) 22/60 (37%) | |ADJUSTED (b) | 29.7% 20.2% 33.3% 60.6% | 5.8% 11.8% 18.0% 65.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 2/8 (25%) 0/7 (0%) 3/9 (33%) | 0/8 (0%) 0/8 (0%) 1/7 (14%) 2/9 (22%) | |TERMINAL (d) | 10/43 (23%) 8/47 (17%) 14/42 (33%) 20/37 (54%) | 1/33 (3%) 3/40 (8%) 6/42 (14%) 17/28 (61%) | |FIRST INCIDENCE (DAYS) | 653 456 (I) 729 (T) 455 (I) | 708 673 456 (I) 455 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.210N P=0.549 P=0.003 ** | P<0.001 ** P=0.301 P=0.092 P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P=0.413N P=0.324 P=0.005 ** | P<0.001 ** P=0.213 P=0.057 P<0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P=0.251N P=0.507 P=0.004 ** | P<0.001 ** P=0.281 P=0.060 P<0.001 ** | |COCHRAN-ARMITAGE | P=0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.277N P=0.524 P=0.010 * | P=0.205 P=0.039 * P<0.001 ** | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 1/58 (2%) 2/57 (4%) 1/60 (2%) | 0/59 (0%) 0/57 (0%) 0/56 (0%) 7/60 (12%) | |ADJUSTED (b) | 2.2% 2.1% 4.8% 2.7% | 0.0% 0.0% 0.0% 22.3% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 1/47 (2%) 2/42 (5%) 1/37 (3%) | 0/33 (0%) 0/40 (0%) 0/42 (0%) 5/28 (18%) | |FIRST INCIDENCE (DAYS) | 716 729 (T) 729 (T) 729 (T) | --- --- --- 615 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.530 P=0.746N P=0.489 P=0.722 | P<0.001 ** (e) (e) P=0.006 ** | |INCIDENTAL TUMOR | P=0.579 P=0.619 P=0.332 P=0.758N | P<0.001 ** (e) (e) P=0.007 ** | |LOGISTIC REGRESSION | P=0.541 P=0.757N P=0.478 P=0.736 | P<0.001 ** (e) (e) P=0.007 ** | |COCHRAN-ARMITAGE | P=0.592 | P<0.001 ** | |FISHER EXACT | P=0.744 P=0.481 P=0.752N | (e) (e) P=0.007 ** | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 8 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/60 (23%) 11/58 (19%) 15/57 (26%) 28/60 (47%) | 2/59 (3%) 5/57 (9%) 8/56 (14%) 29/60 (48%) | |ADJUSTED (b) | 29.7% 22.3% 35.7% 62.9% | 5.8% 11.8% 18.0% 82.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 2/8 (25%) 0/7 (0%) 3/9 (33%) | 0/8 (0%) 0/8 (0%) 1/7 (14%) 2/9 (22%) | |TERMINAL (d) | 10/43 (23%) 9/47 (19%) 15/42 (36%) 21/37 (57%) | 1/33 (3%) 3/40 (8%) 6/42 (14%) 22/28 (79%) | |FIRST INCIDENCE (DAYS) | 653 456 (I) 729 (T) 455 (I) | 708 673 456 (I) 455 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001 ** P=0.279N P=0.463 P=0.002 ** | P<0.001 ** P=0.301 P=0.092 P<0.001 ** | |INCIDENTAL TUMOR | P<0.001 ** P=0.504N P=0.247 P=0.003 ** | P<0.001 ** P=0.213 P=0.057 P<0.001 ** | |LOGISTIC REGRESSION | P<0.001 ** P=0.331N P=0.415 P=0.002 ** | P<0.001 ** P=0.281 P=0.060 P<0.001 ** | |COCHRAN-ARMITAGE | P<0.001 ** | P<0.001 ** | |FISHER EXACT | P=0.362N P=0.436 P=0.006 ** | P=0.205 P=0.039 * P<0.001 ** | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | | 2/59 (3%) 3/57 (5%) 4/57 (7%) 2/60 (3%) | |ADJUSTED (b) | | 6.1% 7.5% 9.5% 6.2% | |INTERIM SACRIFICE 1 (c)| | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | | 2/33 (6%) 3/40 (8%) 4/42 (10%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | | 729 (T) 729 (T) 729 (T) 637 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.519 P=0.588 P=0.453 P=0.644 | |INCIDENTAL TUMOR | | P=0.507 P=0.588 P=0.453 P=0.628 | |LOGISTIC REGRESSION | | P=0.555 P=0.588 P=0.453 P=0.677 | |COCHRAN-ARMITAGE | | P=0.549N | |FISHER EXACT | | P=0.484 P=0.323 P=0.684N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 9 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/52 (0%) 0/54 (0%) 0/47 (0%) 0/48 (0%) | 4/53 (8%) 3/53 (6%) 4/52 (8%) 0/57 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 10.7% 7.7% 10.8% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/37 (0%) 0/44 (0%) 0/35 (0%) 0/29 (0%) | 2/30 (7%) 3/39 (8%) 4/37 (11%) 0/26 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | 367 729 (T) 729 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.082N P=0.383N P=0.543N P=0.080N | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.072N P=0.428N P=0.567 P=0.052N | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.058N P=0.455N P=0.611N P=0.054N | |COCHRAN-ARMITAGE | (e) | P=0.056N | |FISHER EXACT | (e) (e) (e) | P=0.500N P=0.631 P=0.051N | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 1/58 (2%) 2/57 (4%) 0/60 (0%) | 0/60 (0%) 1/58 (2%) 1/58 (2%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 2.1% 3.9% 0.0% | 0.0% 2.5% 2.3% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 1/47 (2%) 0/42 (0%) 0/37 (0%) | 0/33 (0%) 1/40 (3%) 0/42 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) 1 --- | --- 729 (T) 694 --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.639N P=0.518 P=0.230 (e) | P=0.636N P=0.538 P=0.535 (e) | |INCIDENTAL TUMOR | P=0.289N P=0.518 (e) (e) | P=0.573N P=0.538 P=0.419 (e) | |LOGISTIC REGRESSION | P=0.498N P=0.518 P=0.477 (e) | P=0.620N P=0.538 P=0.517 (e) | |COCHRAN-ARMITAGE | P=0.613N | P=0.593N | |FISHER EXACT | P=0.492 P=0.235 (e) | P=0.492 P=0.492 (e) | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 10 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 9/58 (16%) 4/57 (7%) 0/60 (0%) | 1/60 (2%) 6/58 (10%) 3/58 (5%) 2/60 (3%) | |ADJUSTED (b) | 4.7% 19.1% 8.5% 0.0% | 2.4% 15.0% 7.0% 7.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 2/43 (5%) 9/47 (19%) 2/42 (5%) 0/37 (0%) | 0/33 (0%) 6/40 (15%) 2/42 (5%) 2/28 (7%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) 1 --- | 589 729 (T) 694 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.100N P=0.039 * P=0.326 P=0.272N | P=0.575 P=0.095 P=0.376 P=0.456 | |INCIDENTAL TUMOR | P=0.042N* P=0.039 * P=0.686 P=0.272N | P=0.578N P=0.083 P=0.236 P=0.436 | |LOGISTIC REGRESSION | P=0.073N P=0.039 * P=0.372 P=0.272N | P=0.558N P=0.083 P=0.327 P=0.486 | |COCHRAN-ARMITAGE | P=0.069N | P=0.496N | |FISHER EXACT | P=0.023 * P=0.315 P=0.248N | P=0.052 P=0.297 P=0.500 | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 8/58 (14%) 2/57 (4%) 0/60 (0%) | 1/60 (2%) 5/58 (9%) 2/58 (3%) 2/60 (3%) | |ADJUSTED (b) | 4.7% 17.0% 4.8% 0.0% | 2.4% 12.5% 4.8% 7.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 2/43 (5%) 8/47 (17%) 2/42 (5%) 0/37 (0%) | 0/33 (0%) 5/40 (13%) 2/42 (5%) 2/28 (7%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) 729 (T) --- | 589 729 (T) 729 (T) 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.078N P=0.064 P=0.686 P=0.272N | P=0.552 P=0.152 P=0.566 P=0.456 | |INCIDENTAL TUMOR | P=0.078N P=0.064 P=0.686 P=0.272N | P=0.542 P=0.134 P=0.455 P=0.436 | |LOGISTIC REGRESSION | P=0.078N P=0.064 P=0.686 P=0.272N | P=0.583 P=0.135 P=0.521 P=0.486 | |COCHRAN-ARMITAGE | P=0.055N | P=0.540N | |FISHER EXACT | P=0.042 * P=0.671 P=0.248N | P=0.096 P=0.487 P=0.500 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 11 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Testes | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/59 (5%) 0/58 (0%) 0/57 (0%) 0/59 (0%) | | |ADJUSTED (b) | 7.0% 0.0% 0.0% 0.0% | | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | | |TERMINAL (d) | 3/43 (7%) 0/47 (0%) 0/42 (0%) 0/37 (0%) | | |FIRST INCIDENCE (DAYS) | 729 (T) --- --- --- | | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.054N P=0.106N P=0.125N P=0.149N | | |INCIDENTAL TUMOR | P=0.054N P=0.106N P=0.125N P=0.149N | | |LOGISTIC REGRESSION | P=0.054N P=0.106N P=0.125N P=0.149N | | |COCHRAN-ARMITAGE | P=0.048N* | | |FISHER EXACT | P=0.125N P=0.128N P=0.122N | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/59 (0%) 2/58 (3%) 0/57 (0%) 0/60 (0%) | 0/55 (0%) 0/57 (0%) 0/57 (0%) 0/56 (0%) | |ADJUSTED (b) | 0.0% 4.3% 0.0% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 2/47 (4%) 0/42 (0%) 0/37 (0%) | 0/32 (0%) 0/40 (0%) 0/42 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) --- --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.441N P=0.258 (e) (e) | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.441N P=0.258 (e) (e) | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.441N P=0.258 (e) (e) | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.402N | (e) | |FISHER EXACT | P=0.244 (e) (e) | (e) (e) (e) | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 12 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/59 (0%) 0/58 (0%) 0/57 (0%) 2/60 (3%) | 0/55 (0%) 0/57 (0%) 1/57 (2%) 1/56 (2%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 5.4% | 0.0% 0.0% 2.4% 3.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 0/47 (0%) 0/42 (0%) 2/37 (5%) | 0/32 (0%) 0/40 (0%) 1/42 (2%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | --- --- --- 729 (T) | --- --- 729 (T) 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.033 * (e) (e) P=0.206 | P=0.191 (e) P=0.554 P=0.473 | |INCIDENTAL TUMOR | P=0.033 * (e) (e) P=0.206 | P=0.191 (e) P=0.554 P=0.473 | |LOGISTIC REGRESSION | P=0.033 * (e) (e) P=0.206 | P=0.191 (e) P=0.554 P=0.473 | |COCHRAN-ARMITAGE | P=0.049 * | P=0.236 | |FISHER EXACT | (e) (e) P=0.252 | (e) P=0.509 P=0.505 | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/59 (0%) 0/58 (0%) 0/57 (0%) 2/60 (3%) | 1/55 (2%) 0/57 (0%) 1/57 (2%) 1/56 (2%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 5.4% | 3.1% 0.0% 2.4% 3.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 0/47 (0%) 0/42 (0%) 2/37 (5%) | 1/32 (3%) 0/40 (0%) 1/42 (2%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | --- --- --- 729 (T) | 729 (T) --- 729 (T) 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.033 * (e) (e) P=0.206 | P=0.498 P=0.455N P=0.700N P=0.732 | |INCIDENTAL TUMOR | P=0.033 * (e) (e) P=0.206 | P=0.498 P=0.455N P=0.700N P=0.732 | |LOGISTIC REGRESSION | P=0.033 * (e) (e) P=0.206 | P=0.498 P=0.455N P=0.700N P=0.734 | |COCHRAN-ARMITAGE | P=0.049 * | P=0.542 | |FISHER EXACT | (e) (e) P=0.252 | P=0.491N P=0.743N P=0.748N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 13 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 0/60 (0%) 0/58 (0%) 0/58 (0%) 2/60 (3%) | |ADJUSTED (b) | | 0.0% 0.0% 0.0% 6.0% | |INTERIM SACRIFICE 1 (c)| | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | | 0/33 (0%) 0/40 (0%) 0/42 (0%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | | --- --- --- 615 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.032 * (e) (e) P=0.219 | |INCIDENTAL TUMOR | | P=0.036 * (e) (e) P=0.198 | |LOGISTIC REGRESSION | | P=0.042 * (e) (e) P=0.231 | |COCHRAN-ARMITAGE | | P=0.048 * | |FISHER EXACT | | (e) (e) P=0.248 | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 0/60 (0%) 1/58 (2%) 0/58 (0%) 2/60 (3%) | |ADJUSTED (b) | | 0.0% 2.5% 0.0% 6.0% | |INTERIM SACRIFICE 1 (c)| | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | | 0/33 (0%) 1/40 (3%) 0/42 (0%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | | --- 729 (T) --- 615 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.106 P=0.538 (e) P=0.219 | |INCIDENTAL TUMOR | | P=0.107 P=0.538 (e) P=0.198 | |LOGISTIC REGRESSION | | P=0.124 P=0.538 (e) P=0.231 | |COCHRAN-ARMITAGE | | P=0.143 | |FISHER EXACT | | P=0.492 (e) P=0.248 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 14 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma And Histiocytic Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 3/58 (5%) 4/57 (7%) 4/60 (7%) | 6/60 (10%) 12/58 (21%) 8/58 (14%) 5/60 (8%) | |ADJUSTED (b) | 0.0% 6.4% 9.2% 10.5% | 15.6% 26.8% 18.5% 17.9% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 3/47 (6%) 3/42 (7%) 3/37 (8%) | 3/33 (9%) 8/40 (20%) 7/42 (17%) 5/28 (18%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) 567 712 | 550 495 672 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.047 * P=0.138 P=0.062 P=0.047 * | P=0.367N P=0.200 P=0.550 P=0.598N | |INCIDENTAL TUMOR | P=0.082 P=0.138 P=0.117 P=0.056 | P=0.307N P=0.103 P=0.379 P=0.593N | |LOGISTIC REGRESSION | P=0.059 P=0.138 P=0.055 P=0.047 * | P=0.299N P=0.121 P=0.459 P=0.539N | |COCHRAN-ARMITAGE | P=0.082 | P=0.243N | |FISHER EXACT | P=0.116 P=0.053 P=0.059 | P=0.087 P=0.363 P=0.500N | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 3/58 (5%) 4/57 (7%) 3/60 (5%) | 5/60 (8%) 11/58 (19%) 8/58 (14%) 5/60 (8%) | |ADJUSTED (b) | 0.0% 6.4% 9.2% 7.9% | 13.3% 25.3% 18.5% 17.9% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 0/43 (0%) 3/47 (6%) 3/42 (7%) 2/37 (5%) | 3/33 (9%) 8/40 (20%) 7/42 (17%) 5/28 (18%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) 567 712 | 550 635 672 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.111 P=0.138 P=0.062 P=0.097 | P=0.496N P=0.176 P=0.427 P=0.536 | |INCIDENTAL TUMOR | P=0.175 P=0.138 P=0.117 P=0.116 | P=0.465N P=0.111 P=0.288 P=0.516 | |LOGISTIC REGRESSION | P=0.132 P=0.138 P=0.055 P=0.099 | P=0.432N P=0.133 P=0.339 P=0.594 | |COCHRAN-ARMITAGE | P=0.167 | P=0.351N | |FISHER EXACT | P=0.116 P=0.053 P=0.122 | P=0.078 P=0.257 P=0.628N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 15 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 38/60 (63%) 38/58 (66%) 37/57 (65%) 44/60 (73%) | 21/60 (35%) 33/58 (57%) 34/58 (59%) 28/60 (47%) | |ADJUSTED (b) | 79.2% 73.0% 82.1% 86.0% | 51.6% 76.7% 70.7% 79.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 3/8 (38%) 1/7 (14%) 6/9 (67%) | 1/8 (13%) 0/8 (0%) 1/7 (14%) 2/9 (22%) | |TERMINAL (d) | 33/43 (77%) 33/47 (70%) 34/42 (81%) 30/37 (81%) | 14/33 (42%) 30/40 (75%) 28/42 (67%) 21/28 (75%) | |FIRST INCIDENCE (DAYS) | 653 456 (I) 455 (I) 455 (I) | 367 673 456 (I) 455 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.006 ** P=0.371N P=0.569 P=0.026 * | P=0.031 * P=0.125 P=0.130 P=0.044 * | |INCIDENTAL TUMOR | P=0.027 * P=0.553 P=0.308 P=0.048 * | P=0.056 P=0.054 P=0.013 * P=0.057 | |LOGISTIC REGRESSION | P=0.027 * P=0.558N P=0.436 P=0.048 * | P=0.067 P=0.067 P=0.027 * P=0.067 | |COCHRAN-ARMITAGE | P=0.138 | P=0.229 | |FISHER EXACT | P=0.478 P=0.506 P=0.163 | P=0.014 * P=0.008 ** P=0.133 | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 15/60 (25%) 14/58 (24%) 16/57 (28%) 8/60 (13%) | 8/60 (13%) 19/58 (33%) 13/58 (22%) 14/60 (23%) | |ADJUSTED (b) | 31.1% 28.0% 34.4% 20.2% | 19.5% 40.2% 28.9% 42.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/9 (0%) | |TERMINAL (d) | 10/43 (23%) 11/47 (23%) 12/42 (29%) 6/37 (16%) | 3/33 (9%) 12/40 (30%) 10/42 (24%) 10/28 (36%) | |FIRST INCIDENCE (DAYS) | 541 532 1 558 | 474 495 672 615 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.175N P=0.416N P=0.456 P=0.164N | P=0.138 P=0.059 P=0.330 P=0.073 | |INCIDENTAL TUMOR | P=0.023N* P=0.494 P=0.585N P=0.054N | P=0.225 P=0.008 ** P=0.084 P=0.081 | |LOGISTIC REGRESSION | P=0.096N P=0.503N P=0.416 P=0.053N | P=0.211 P=0.015 * P=0.130 P=0.096 | |COCHRAN-ARMITAGE | P=0.073N | P=0.292 | |FISHER EXACT | P=0.542N P=0.434 P=0.082N | P=0.010 * P=0.147 P=0.119 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05090 TEST: 02 PAGE 16 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | VEHICLE 50 MG/KG 100MG/KG 200MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 42/60 (70%) 43/58 (74%) 43/57 (75%) 45/60 (75%) | 26/60 (43%) 41/58 (71%) 37/58 (64%) 36/60 (60%) | |ADJUSTED (b) | 85.7% 81.1% 89.5% 88.0% | 57.2% 87.2% 75.5% 92.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 3/8 (38%) 1/7 (14%) 6/9 (67%) | 1/8 (13%) 0/8 (0%) 1/7 (14%) 2/9 (22%) | |TERMINAL (d) | 36/43 (84%) 37/47 (79%) 37/42 (88%) 31/37 (84%) | 14/33 (42%) 34/40 (85%) 30/42 (71%) 25/28 (89%) | |FIRST INCIDENCE (DAYS) | 541 456 (I) 1 455 (I) | 367 495 456 (I) 455 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.023 * P=0.418N P=0.386 P=0.066 | P=0.013 * P=0.089 P=0.271 P=0.017 * | |INCIDENTAL TUMOR | P=0.170 P=0.428 P=0.384 P=0.147 | P=0.018 * P=0.005 ** P=0.008 ** P=0.011 * | |LOGISTIC REGRESSION | P=0.102 P=0.518 P=0.277 P=0.136 | P=0.024 * P=0.018 * P=0.059 P=0.017 * | |COCHRAN-ARMITAGE | P=0.321 | P=0.135 | |FISHER EXACT | P=0.384 P=0.326 P=0.342 | P=0.002 ** P=0.020 * P=0.050 * | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Kaplan-Meier estimated lifetime tumor incidence after adjustment for intercurrent mortality. (c) Observed incidence at interim kill. Male interim sacrifices(days): 455 Female interim sacrifices(days): 455 (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).