TDMS Study 05121-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus SCOPOLAMINE HYDROBROMIDE TRIHYDRATE DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 TIME: 21:36:18 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01 ES 85227 ROUTE: GAVAGE NTP C#: 03098C PATHOLOGIST: M. RYAN CAS: 6533-68-2 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus SCOPOLAMINE HYDROBROMIDE TRIHYDRATE DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 TIME: 21:36:18 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01 ES 85227 ROUTE: GAVAGE NTP C#: 03098C PATHOLOGIST: M. RYAN CAS: 6533-68-2 RATS(FISCHER344) ---------------------------- 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 Cortex Adrenal Medulla Bone Marrow Brain Clitoral Gland Clitoral/Preputial Gland Epididymis 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: Battelle Columbus SCOPOLAMINE HYDROBROMIDE TRIHYDRATE DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 TIME: 21:36:18 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01 ES 85227 ROUTE: GAVAGE NTP C#: 03098C PATHOLOGIST: M. RYAN CAS: 6533-68-2 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF THE STUDY OF SCOPOLAMINE HYDROBROMIDE TRIHYDRATE ==================================================================================================== MALE RATS ------------- ORGAN MORPHOLOGY ------- ------------ Islets, Pancreatic Carcinoma or Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Testes Adenoma Thyroid Gland: Follicular Cell Carcinoma or Adenoma All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== FEMALE RATS ------------- ORGAN MORPHOLOGY ------- ------------ Mammary Gland Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Thyroid Gland: Follicular Cell Adenoma Carcinoma or Adenoma Uterus Polyp Stromal All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 1 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | 0/60 (0%) 0/60 (0%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 3.2% 0.0% 0.0% 0.0% | 0.0% 0.0% 6.8% 4.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 0/22 (0%) 0/28 (0%) | 0/34 (0%) 0/17 (0%) 1/26 (4%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | 671 --- --- --- | --- --- 680 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.547N P=0.535N P=0.507N P=0.470N | P=0.402 (e) P=0.201 P=0.413 | |INCIDENTAL TUMOR | P=0.689N P=0.500N P=0.550N P=0.617N | P=0.365 (e) P=0.262 P=0.413 | |LOGISTIC REGRESSION | P=0.581N P=0.517N P=0.496N P=0.498N | P=0.396 (e) P=0.216 P=0.413 | |COCHRAN-ARMITAGE | P=0.588N | P=0.460 | |FISHER EXACT | P=0.500N P=0.500N P=0.500N | (e) P=0.248 P=0.500 | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/60 (18%) 13/60 (22%) 12/60 (20%) 10/60 (17%) | 1/60 (2%) 0/60 (0%) 1/60 (2%) 1/60 (2%) | |ADJUSTED (b) | 41.4% 57.0% 37.7% 30.3% | 2.4% 0.0% 3.8% 3.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 5/20 (25%) 6/14 (43%) 4/22 (18%) 7/28 (25%) | 0/34 (0%) 0/17 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 673 585 589 456 (I) | 627 --- 726 (T) 499 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.096N P=0.156 P=0.532 P=0.268N | P=0.517 P=0.633N P=0.722 P=0.666 | |INCIDENTAL TUMOR | P=0.344N P=0.308 P=0.476 P=0.529N | P=0.570 P=0.398N P=0.760N P=0.664N | |LOGISTIC REGRESSION | P=0.246N P=0.233 P=0.522 P=0.451N | P=0.558 P=0.565N P=0.750 P=0.752N | |COCHRAN-ARMITAGE | P=0.352N | P=0.574 | |FISHER EXACT | P=0.410 P=0.500 P=0.500N | P=0.500N P=0.752N P=0.752N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 2 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/60 (18%) 13/60 (22%) 12/60 (20%) 10/60 (17%) | 1/60 (2%) 0/60 (0%) 1/60 (2%) 2/60 (3%) | |ADJUSTED (b) | 41.4% 57.0% 37.7% 30.3% | 2.4% 0.0% 3.8% 7.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 5/20 (25%) 6/14 (43%) 4/22 (18%) 7/28 (25%) | 0/34 (0%) 0/17 (0%) 1/26 (4%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | 673 585 589 456 (I) | 627 --- 726 (T) 499 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.096N P=0.156 P=0.532 P=0.268N | P=0.185 P=0.633N P=0.722 P=0.357 | |INCIDENTAL TUMOR | P=0.344N P=0.308 P=0.476 P=0.529N | P=0.229 P=0.398N P=0.760N P=0.551 | |LOGISTIC REGRESSION | P=0.246N P=0.233 P=0.522 P=0.451N | P=0.210 P=0.565N P=0.750 P=0.462 | |COCHRAN-ARMITAGE | P=0.352N | P=0.243 | |FISHER EXACT | P=0.410 P=0.500 P=0.500N | P=0.500N P=0.752N P=0.500 | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/60 (5%) 1/60 (2%) 4/58 (7%) 2/60 (3%) | 3/59 (5%) 2/60 (3%) 3/58 (5%) 1/60 (2%) | |ADJUSTED (b) | 11.1% 7.1% 11.1% 7.1% | 9.1% 11.8% 10.4% 4.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 1/9 (11%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 0/21 (0%) 2/28 (7%) | 3/33 (9%) 2/17 (12%) 2/24 (8%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | 471 726 (T) 456 (I) 726 (T) | 726 (T) 726 (T) 547 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.395N P=0.406N P=0.492 P=0.391N | P=0.337N P=0.578 P=0.532 P=0.458N | |INCIDENTAL TUMOR | P=0.567N P=0.344N P=0.307 P=0.497N | P=0.338N P=0.578 P=0.560 P=0.458N | |LOGISTIC REGRESSION | P=0.532N P=0.326N P=0.480 P=0.495N | P=0.347N P=0.578 P=0.609 P=0.458N | |COCHRAN-ARMITAGE | P=0.541N | P=0.271N | |FISHER EXACT | P=0.309N P=0.481 P=0.500N | P=0.492N P=0.652 P=0.303N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 3 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/60 (5%) 2/60 (3%) 4/58 (7%) 2/60 (3%) | 3/59 (5%) 2/60 (3%) 3/58 (5%) 1/60 (2%) | |ADJUSTED (b) | 11.1% 9.1% 11.1% 7.1% | 9.1% 11.8% 10.4% 4.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 1/9 (11%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 0/21 (0%) 2/28 (7%) | 3/33 (9%) 2/17 (12%) 2/24 (8%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | 471 492 456 (I) 726 (T) | 726 (T) 726 (T) 547 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.328N P=0.594N P=0.492 P=0.391N | P=0.337N P=0.578 P=0.532 P=0.458N | |INCIDENTAL TUMOR | P=0.503N P=0.512N P=0.307 P=0.497N | P=0.338N P=0.578 P=0.560 P=0.458N | |LOGISTIC REGRESSION | P=0.455N P=0.504N P=0.480 P=0.495N | P=0.347N P=0.578 P=0.609 P=0.458N | |COCHRAN-ARMITAGE | P=0.458N | P=0.271N | |FISHER EXACT | P=0.500N P=0.481 P=0.500N | P=0.492N P=0.652 P=0.303N | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/60 (5%) 2/60 (3%) 1/60 (2%) 0/60 (0%) | 0/60 (0%) 0/60 (0%) 0/59 (0%) 1/60 (2%) | |ADJUSTED (b) | 15.0% 10.9% 4.5% 0.0% | 0.0% 0.0% 0.0% 4.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 3/20 (15%) 1/14 (7%) 1/22 (5%) 0/28 (0%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 726 (T) 678 726 (T) --- | --- --- --- 647 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.059N P=0.643N P=0.268N P=0.067N | P=0.195 (e) (e) P=0.398 | |INCIDENTAL TUMOR | P=0.069N P=0.630N P=0.268N P=0.067N | P=0.096 (e) (e) P=0.282 | |LOGISTIC REGRESSION | P=0.076N P=0.622N P=0.268N P=0.067N | P=0.217 (e) (e) P=0.455 | |COCHRAN-ARMITAGE | P=0.114N | P=0.237 | |FISHER EXACT | P=0.500N P=0.309N P=0.122N | (e) (e) P=0.500 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 4 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/60 (5%) 3/60 (5%) 1/60 (2%) 0/60 (0%) | 0/60 (0%) 0/60 (0%) 0/59 (0%) 1/60 (2%) | |ADJUSTED (b) | 15.0% 17.7% 4.5% 0.0% | 0.0% 0.0% 0.0% 4.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 3/20 (15%) 2/14 (14%) 1/22 (5%) 0/28 (0%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 726 (T) 678 726 (T) --- | --- --- --- 647 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.038N* P=0.508 P=0.268N P=0.067N | P=0.195 (e) (e) P=0.398 | |INCIDENTAL TUMOR | P=0.045N* P=0.520 P=0.268N P=0.067N | P=0.096 (e) (e) P=0.282 | |LOGISTIC REGRESSION | P=0.051N P=0.530 P=0.268N P=0.067N | P=0.217 (e) (e) P=0.455 | |COCHRAN-ARMITAGE | P=0.085N | P=0.237 | |FISHER EXACT | P=0.660N P=0.309N P=0.122N | (e) (e) P=0.500 | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/60 (3%) 0/60 (0%) 1/60 (2%) 0/60 (0%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 10.0% 0.0% 2.1% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/20 (10%) 0/14 (0%) 0/22 (0%) 0/28 (0%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 726 (T) --- 576 --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.251N P=0.318N P=0.465N P=0.167N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.267N P=0.318N P=0.380N P=0.167N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.306N P=0.318N P=0.492N P=0.167N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.318N | (e) | |FISHER EXACT | P=0.248N P=0.500N P=0.248N | (e) (e) (e) | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 5 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 2/60 (3%) 2/60 (3%) 2/60 (3%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 4.5% 7.7% 6.7% 6.7% | 2.9% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 1/22 (5%) 1/28 (4%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 720 660 596 686 | 726 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.634N P=0.414 P=0.519 P=0.574 | P=0.619N P=0.638N P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.442 P=0.500 P=0.579 P=0.403 | P=0.619N P=0.638N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.566 P=0.453 P=0.508 P=0.530 | P=0.619N P=0.638N P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.534 | P=0.588N | |FISHER EXACT | P=0.500 P=0.500 P=0.500 | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/60 (3%) 3/60 (5%) 2/60 (3%) 2/60 (3%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 9.3% 14.3% 6.7% 6.7% | 2.9% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 1/22 (5%) 1/28 (4%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 720 660 596 686 | 726 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.388N P=0.371 P=0.669N P=0.603N | P=0.619N P=0.638N P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.569N P=0.435 P=0.625N P=0.655 | P=0.619N P=0.638N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.492N P=0.414 P=0.688N P=0.659N | P=0.619N P=0.638N P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.543N | P=0.588N | |FISHER EXACT | P=0.500 P=0.691N P=0.691N | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 6 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/60 (3%) 3/60 (5%) 2/60 (3%) 2/60 (3%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 9.3% 14.3% 6.7% 6.7% | 2.9% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 1/22 (5%) 1/28 (4%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 720 660 596 686 | 726 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.388N P=0.371 P=0.669N P=0.603N | P=0.619N P=0.638N P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.569N P=0.435 P=0.625N P=0.655 | P=0.619N P=0.638N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.492N P=0.414 P=0.688N P=0.659N | P=0.619N P=0.638N P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.543N | P=0.588N | |FISHER EXACT | P=0.500 P=0.691N P=0.691N | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 1/60 (2%) 2/60 (3%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 2.9% 5.9% 7.7% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 0/22 (0%) 0/28 (0%) | 1/34 (3%) 1/17 (6%) 2/26 (8%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | 726 (T) 726 (T) 726 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.355N P=0.600 P=0.406 P=0.587N | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.355N P=0.600 P=0.406 P=0.587N | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.355N P=0.600 P=0.406 P=0.587N | |COCHRAN-ARMITAGE | (e) | P=0.309N | |FISHER EXACT | (e) (e) (e) | P=0.752N P=0.500 P=0.500N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 7 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 8/60 (13%) 3/60 (5%) 3/60 (5%) | 29/60 (48%) 10/60 (17%) 19/60 (32%) 16/60 (27%) | |ADJUSTED (b) | 11.7% 31.5% 11.6% 10.7% | 70.4% 46.1% 59.8% 58.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 1/20 (5%) 3/14 (21%) 2/22 (9%) 3/28 (11%) | 22/34 (65%) 6/17 (35%) 14/26 (54%) 11/22 (50%) | |FIRST INCIDENCE (DAYS) | 673 404 646 726 (T) | 562 562 404 457 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.142N P=0.059 P=0.644N P=0.532N | P=0.476N P=0.134N P=0.242N P=0.322N | |INCIDENTAL TUMOR | P=0.252N P=0.088 P=0.627 P=0.651N | P=0.517N P=0.026N* P=0.092N P=0.251N | |LOGISTIC REGRESSION | P=0.264N P=0.097 P=0.656N P=0.620N | P=0.484N P=0.052N P=0.071N P=0.235N | |COCHRAN-ARMITAGE | P=0.278N | P=0.210N | |FISHER EXACT | P=0.102 P=0.660N P=0.660N | P<0.001N** P=0.047N* P=0.012N* | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 8/60 (13%) 3/60 (5%) 3/60 (5%) | 29/60 (48%) 10/60 (17%) 20/60 (33%) 16/60 (27%) | |ADJUSTED (b) | 11.7% 31.5% 11.6% 10.7% | 70.4% 46.1% 63.1% 58.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 1/20 (5%) 3/14 (21%) 2/22 (9%) 3/28 (11%) | 22/34 (65%) 6/17 (35%) 15/26 (58%) 11/22 (50%) | |FIRST INCIDENCE (DAYS) | 673 404 646 726 (T) | 562 562 404 457 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.142N P=0.059 P=0.644N P=0.532N | P=0.463N P=0.134N P=0.315N P=0.322N | |INCIDENTAL TUMOR | P=0.252N P=0.088 P=0.627 P=0.651N | P=0.503N P=0.026N* P=0.136N P=0.251N | |LOGISTIC REGRESSION | P=0.264N P=0.097 P=0.656N P=0.620N | P=0.473N P=0.052N P=0.105N P=0.235N | |COCHRAN-ARMITAGE | P=0.278N | P=0.200N | |FISHER EXACT | P=0.102 P=0.660N P=0.660N | P<0.001N** P=0.068N P=0.012N* | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 8 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 8/60 (13%) 3/60 (5%) 3/60 (5%) | 29/60 (48%) 10/60 (17%) 21/60 (35%) 16/60 (27%) | |ADJUSTED (b) | 11.7% 31.5% 11.6% 10.7% | 70.4% 46.1% 66.5% 58.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | 1/20 (5%) 3/14 (21%) 2/22 (9%) 3/28 (11%) | 22/34 (65%) 6/17 (35%) 16/26 (62%) 11/22 (50%) | |FIRST INCIDENCE (DAYS) | 673 404 646 726 (T) | 562 562 404 457 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.142N P=0.059 P=0.644N P=0.532N | P=0.451N P=0.134N P=0.398N P=0.322N | |INCIDENTAL TUMOR | P=0.252N P=0.088 P=0.627 P=0.651N | P=0.489N P=0.026N* P=0.194N P=0.251N | |LOGISTIC REGRESSION | P=0.264N P=0.097 P=0.656N P=0.620N | P=0.462N P=0.052N P=0.149N P=0.235N | |COCHRAN-ARMITAGE | P=0.278N | P=0.190N | |FISHER EXACT | P=0.102 P=0.660N P=0.660N | P<0.001N** P=0.097N P=0.012N* | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/60 (0%) 1/60 (2%) 1/60 (2%) | 0/60 (0%) 0/60 (0%) 2/60 (3%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 0.0% 4.5% 3.6% | 0.0% 0.0% 6.4% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 1/22 (5%) 1/28 (4%) | 0/34 (0%) 0/17 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | --- --- 726 (T) 726 (T) | --- --- 631 --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.490 (e) P=0.519 P=0.567 | P=0.678N (e) P=0.205 (e) | |INCIDENTAL TUMOR | P=0.490 (e) P=0.519 P=0.567 | P=0.679N (e) P=0.240 (e) | |LOGISTIC REGRESSION | P=0.490 (e) P=0.519 P=0.567 | P=0.665N (e) P=0.224 (e) | |COCHRAN-ARMITAGE | P=0.376 | P=0.624N | |FISHER EXACT | (e) P=0.500 P=0.500 | (e) P=0.248 (e) | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 9 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 1/60 (2%) 1/60 (2%) 1/60 (2%) | 0/60 (0%) 0/60 (0%) 2/60 (3%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 4.0% 4.5% 3.6% | 0.0% 0.0% 6.4% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 1/22 (5%) 1/28 (4%) | 0/34 (0%) 0/17 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | --- 678 726 (T) 726 (T) | --- --- 631 --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.653 P=0.470 P=0.519 P=0.567 | P=0.678N (e) P=0.205 (e) | |INCIDENTAL TUMOR | P=0.595 P=0.500 P=0.519 P=0.567 | P=0.679N (e) P=0.240 (e) | |LOGISTIC REGRESSION | P=0.600 P=0.480 P=0.519 P=0.567 | P=0.665N (e) P=0.224 (e) | |COCHRAN-ARMITAGE | P=0.551 | P=0.624N | |FISHER EXACT | P=0.500 P=0.500 P=0.500 | (e) P=0.248 (e) | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 19/59 (32%) 17/58 (29%) 14/60 (23%) 11/60 (18%) | 21/60 (35%) 13/60 (22%) 15/60 (25%) 10/60 (17%) | |ADJUSTED (b) | 57.6% 51.9% 43.7% 27.9% | 51.4% 51.0% 39.2% 38.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 1/10 (10%) 1/10 (10%) | 1/10 (10%) 0/0 1/10 (10%) 0/10 (0%) | |TERMINAL (d) | 7/19 (37%) 2/14 (14%) 6/22 (27%) 5/28 (18%) | 15/34 (44%) 6/17 (35%) 5/26 (19%) 7/22 (32%) | |FIRST INCIDENCE (DAYS) | 471 446 456 (I) 351 | 457 (I) 408 457 (I) 520 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.016N* P=0.445 P=0.181N P=0.029N* | P=0.153N P=0.314 P=0.385N P=0.217N | |INCIDENTAL TUMOR | P=0.112N P=0.405N P=0.256N P=0.075N | P=0.123N P=0.548N P=0.158N P=0.125N | |LOGISTIC REGRESSION | P=0.051N P=0.415N P=0.155N P=0.061N | P=0.105N P=0.558N P=0.201N P=0.137N | |COCHRAN-ARMITAGE | P=0.060N | P=0.053N | |FISHER EXACT | P=0.445N P=0.191N P=0.063N | P=0.078N P=0.160N P=0.018N* | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 10 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal | | Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/60 (7%) 5/60 (8%) 3/60 (5%) 5/60 (8%) | 1/60 (2%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 18.7% 27.4% 12.0% 15.2% | 2.9% 3.3% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 3/20 (15%) 3/14 (21%) 2/22 (9%) 3/28 (11%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 713 589 666 456 (I) | 726 (T) 519 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.463N P=0.306 P=0.459N P=0.614N | P=0.418N P=0.632 P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.593 P=0.391 P=0.502N P=0.560 | P=0.357N P=0.742N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.537 P=0.374 P=0.499N P=0.521 | P=0.389N P=0.708 P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.468 | P=0.376N | |FISHER EXACT | P=0.500 P=0.500N P=0.500 | P=0.752N P=0.500N P=0.500N | |=================================================================================================================================| | | |Skin | | Fibroma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 5/60 (8%) 3/60 (5%) 3/60 (5%) 3/60 (5%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 15.7% 13.0% 11.8% 10.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 2/22 (9%) 2/28 (7%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 649 656 656 685 | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.278N P=0.454N P=0.359N P=0.267N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.489N P=0.404N P=0.423N P=0.489N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.390N P=0.407N P=0.344N P=0.341N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.441N | (e) | |FISHER EXACT | P=0.359N P=0.359N P=0.359N | (e) (e) (e) | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 11 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 6/60 (10%) 3/60 (5%) 4/60 (7%) 3/60 (5%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 17.8% 13.0% 14.3% 10.0% | 2.9% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 2/22 (9%) 2/28 (7%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 642 656 646 685 | 726 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.206N P=0.340N P=0.378N P=0.179N | P=0.619N P=0.638N P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.416N P=0.246N P=0.392N P=0.350N | P=0.619N P=0.638N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.507N P=0.226N P=0.356N P=0.232N | P=0.619N P=0.638N P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.341N | P=0.588N | |FISHER EXACT | P=0.245N P=0.372N P=0.245N | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/60 (7%) 3/60 (5%) 3/60 (5%) 2/60 (3%) | 1/60 (2%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 18.7% 18.6% 12.0% 6.8% | 2.9% 3.3% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 3/20 (15%) 2/14 (14%) 2/22 (9%) 1/28 (4%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 713 702 666 692 | 726 (T) 519 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.161N P=0.627 P=0.459N P=0.220N | P=0.418N P=0.632 P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.250N P=0.638N P=0.502N P=0.319N | P=0.357N P=0.742N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.223N P=0.651 P=0.499N P=0.274N | P=0.389N P=0.708 P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.331N | P=0.376N | |FISHER EXACT | P=0.500N P=0.500N P=0.340N | P=0.752N P=0.500N P=0.500N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 12 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 3/60 (5%) 0/60 (0%) 2/60 (3%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 16.6% 0.0% 5.3% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 2/14 (14%) 0/22 (0%) 1/28 (4%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | --- 589 --- 456 (I) | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.533 P=0.078 (e) P=0.276 | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.508 P=0.108 (e) P=0.276 | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.428 P=0.101 (e) P=0.242 | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.425 | (e) | |FISHER EXACT | P=0.122 (e) P=0.248 | (e) (e) (e) | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/60 (7%) 5/60 (8%) 3/60 (5%) 4/60 (7%) | 1/60 (2%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 18.7% 27.4% 12.0% 11.8% | 2.9% 3.3% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 3/20 (15%) 3/14 (21%) 2/22 (9%) 2/28 (7%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 713 589 666 456 (I) | 726 (T) 519 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.322N P=0.306 P=0.459N P=0.500N | P=0.418N P=0.632 P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.453N P=0.391 P=0.502N P=0.608N | P=0.357N P=0.742N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.498N P=0.374 P=0.499N P=0.630N | P=0.389N P=0.708 P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.561N | P=0.376N | |FISHER EXACT | P=0.500 P=0.500N P=0.641N | P=0.752N P=0.500N P=0.500N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 13 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/60 (7%) 5/60 (8%) 3/60 (5%) 4/60 (7%) | 1/60 (2%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 18.7% 27.4% 12.0% 11.8% | 2.9% 3.3% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 3/20 (15%) 3/14 (21%) 2/22 (9%) 2/28 (7%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 713 589 666 456 (I) | 726 (T) 519 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.322N P=0.306 P=0.459N P=0.500N | P=0.418N P=0.632 P=0.553N P=0.587N | |INCIDENTAL TUMOR | P=0.453N P=0.391 P=0.502N P=0.608N | P=0.357N P=0.742N P=0.554N P=0.587N | |LOGISTIC REGRESSION | P=0.498N P=0.374 P=0.499N P=0.630N | P=0.389N P=0.708 P=0.554N P=0.587N | |COCHRAN-ARMITAGE | P=0.561N | P=0.376N | |FISHER EXACT | P=0.500 P=0.500N P=0.641N | P=0.752N P=0.500N P=0.500N | |=================================================================================================================================| | | |Testes | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 52/60 (87%) 50/60 (83%) 55/60 (92%) 53/60 (88%) | | |ADJUSTED (b) | 100.0% 100.0% 100.0% 100.0% | | |INTERIM SACRIFICE 1 (c)| 9/10 (90%) 8/10 (80%) 9/10 (90%) 9/10 (90%) | | |TERMINAL (d) | 20/20 (100%) 14/14 (100%) 22/22 (100%) 28/28 (100%)| | |FIRST INCIDENCE (DAYS) | 443 404 456 (I) 456 (I) | | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.028N* P=0.167 P=0.499 P=0.115N | | |INCIDENTAL TUMOR | P=0.385 P=0.563N P=0.561 P=0.374 | | |LOGISTIC REGRESSION | P=0.278 P=0.460N P=0.321 P=0.362 | | |COCHRAN-ARMITAGE | P=0.405 | | |FISHER EXACT | P=0.399N P=0.279 P=0.500 | | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 14 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 4/60 (7%) 3/60 (5%) 2/60 (3%) | 3/60 (5%) 1/60 (2%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 3.1% 16.1% 9.9% 5.3% | 8.8% 5.9% 7.7% 4.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 1/14 (7%) 0/22 (0%) 1/28 (4%) | 3/34 (9%) 1/17 (6%) 2/26 (8%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | 663 504 646 456 (I) | 726 (T) 726 (T) 726 (T) 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.398N P=0.141 P=0.307 P=0.555 | P=0.448N P=0.572N P=0.622N P=0.470N | |INCIDENTAL TUMOR | P=0.609 P=0.176 P=0.213 P=0.472 | P=0.448N P=0.572N P=0.622N P=0.470N | |LOGISTIC REGRESSION | P=0.515N P=0.167 P=0.313 P=0.501 | P=0.448N P=0.572N P=0.622N P=0.470N | |COCHRAN-ARMITAGE | P=0.519N | P=0.377N | |FISHER EXACT | P=0.182 P=0.309 P=0.500 | P=0.309N P=0.500N P=0.309N | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 0/60 (0%) 3/60 (5%) 0/60 (0%) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 5.0% 0.0% 13.6% 0.0% | 5.9% 5.9% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 0/14 (0%) 3/22 (14%) 0/28 (0%) | 2/34 (6%) 1/17 (6%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 726 (T) --- 726 (T) --- | 726 (T) 726 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.253N P=0.571N P=0.337 P=0.433N | P=0.273N P=0.734 P=0.299N P=0.338N | |INCIDENTAL TUMOR | P=0.253N P=0.571N P=0.337 P=0.433N | P=0.273N P=0.734 P=0.299N P=0.338N | |LOGISTIC REGRESSION | P=0.253N P=0.571N P=0.337 P=0.433N | P=0.273N P=0.734 P=0.299N P=0.338N | |COCHRAN-ARMITAGE | P=0.383N | P=0.241N | |FISHER EXACT | P=0.500N P=0.309 P=0.500N | P=0.500N P=0.248N P=0.248N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 15 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/60 (3%) 4/60 (7%) 6/60 (10%) 2/60 (3%) | 5/60 (8%) 2/60 (3%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 8.0% 16.1% 22.2% 5.3% | 14.7% 11.8% 7.7% 4.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 3/22 (14%) 1/28 (4%) | 5/34 (15%) 2/17 (12%) 2/26 (8%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | 663 504 646 456 (I) | 726 (T) 726 (T) 726 (T) 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.202N P=0.258 P=0.155 P=0.618N | P=0.214N P=0.557N P=0.334N P=0.226N | |INCIDENTAL TUMOR | P=0.366N P=0.306 P=0.110 P=0.687N | P=0.214N P=0.557N P=0.334N P=0.226N | |LOGISTIC REGRESSION | P=0.326N P=0.307 P=0.138 P=0.694 | P=0.214N P=0.557N P=0.334N P=0.226N | |COCHRAN-ARMITAGE | P=0.347N | P=0.165N | |FISHER EXACT | P=0.340 P=0.136 P=0.691N | P=0.219N P=0.219N P=0.103N | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/60 (5%) 2/60 (3%) 1/60 (2%) 0/60 (0%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 3/60 (5%) | |ADJUSTED (b) | 8.9% 10.9% 4.2% 0.0% | 2.9% 0.0% 0.0% 13.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 1/20 (5%) 1/14 (7%) 0/22 (0%) 0/28 (0%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 3/22 (14%) | |FIRST INCIDENCE (DAYS) | 430 678 713 --- | 726 (T) --- --- 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.081N P=0.598N P=0.303N P=0.110N | P=0.028 * P=0.638N P=0.553N P=0.164 | |INCIDENTAL TUMOR | P=0.135N P=0.486N P=0.366N P=0.125N | P=0.028 * P=0.638N P=0.554N P=0.164 | |LOGISTIC REGRESSION | P=0.112N P=0.513N P=0.306N P=0.118N | P=0.028 * P=0.638N P=0.554N P=0.164 | |COCHRAN-ARMITAGE | P=0.114N | P=0.045 * | |FISHER EXACT | P=0.500N P=0.309N P=0.122N | P=0.500N P=0.500N P=0.309 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 16 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/60 (7%) 2/60 (3%) 1/60 (2%) 0/60 (0%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 3/60 (5%) | |ADJUSTED (b) | 13.7% 10.9% 4.2% 0.0% | 2.9% 0.0% 0.0% 13.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 2/20 (10%) 1/14 (7%) 0/22 (0%) 0/28 (0%) | 1/34 (3%) 0/17 (0%) 0/26 (0%) 3/22 (14%) | |FIRST INCIDENCE (DAYS) | 430 678 713 --- | 726 (T) --- --- 726 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.050N* P=0.454N P=0.175N P=0.048N* | P=0.028 * P=0.638N P=0.553N P=0.164 | |INCIDENTAL TUMOR | P=0.083N P=0.352N P=0.209N P=0.055N | P=0.028 * P=0.638N P=0.554N P=0.164 | |LOGISTIC REGRESSION | P=0.075N P=0.361N P=0.177N P=0.064N | P=0.028 * P=0.638N P=0.554N P=0.164 | |COCHRAN-ARMITAGE | P=0.079N | P=0.045 * | |FISHER EXACT | P=0.340N P=0.182N P=0.059N | P=0.500N P=0.500N P=0.309 | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 7/60 (12%) 1/60 (2%) 4/60 (7%) 4/60 (7%) | |ADJUSTED (b) | | 19.1% 2.6% 13.5% 12.8% | |INTERIM SACRIFICE 1 (c)| | 1/10 (10%) 0/0 0/10 (0%) 1/10 (10%) | |TERMINAL (d) | | 6/34 (18%) 0/17 (0%) 3/26 (12%) 1/22 (5%) | |FIRST INCIDENCE (DAYS) | | 457 (I) 379 471 457 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.583 P=0.229N P=0.400N P=0.486N | |INCIDENTAL TUMOR | | P=0.558N P=0.144N P=0.398N P=0.383N | |LOGISTIC REGRESSION | | P=0.580 P=0.091N P=0.297N P=0.389N | |COCHRAN-ARMITAGE | | P=0.571N | |FISHER EXACT | | P=0.031N* P=0.264N P=0.264N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 17 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |Zymbal's Gland | | Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 2/60 (3%) 2/60 (3%) 2/60 (3%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 5.3% 7.5% 4.9% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 1/22 (5%) 0/28 (0%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | --- 583 660 516 | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.473 P=0.220 P=0.247 P=0.262 | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.291 P=0.371 P=0.222 P=0.139 | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.290 P=0.244 P=0.242 P=0.241 | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.411 | (e) | |FISHER EXACT | P=0.248 P=0.248 P=0.248 | (e) (e) (e) | |=================================================================================================================================| | | |All Organs | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 34/60 (57%) 21/60 (35%) 26/60 (43%) 24/60 (40%) | 20/60 (33%) 6/60 (10%) 13/60 (22%) 4/60 (7%) | |ADJUSTED (b) | 86.2% 73.3% 66.5% 59.3% | 47.3% 26.9% 38.8% 13.5% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 15/20 (75%) 8/14 (57%) 10/22 (45%) 12/28 (43%) | 13/34 (38%) 2/17 (12%) 7/26 (27%) 2/22 (9%) | |FIRST INCIDENCE (DAYS) | 443 533 463 504 | 374 519 555 392 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.029N* P=0.195N P=0.111N P=0.013N* | P=0.021N* P=0.147N P=0.306N P=0.010N* | |INCIDENTAL TUMOR | P=0.313N P=0.014N* P=0.092N P=0.067N | P=0.014N* P=0.023N* P=0.114N P=0.002N** | |LOGISTIC REGRESSION | P=0.290N P=0.021N* P=0.061N P=0.049N* | P=0.011N* P=0.040N* P=0.144N P=0.002N** | |COCHRAN-ARMITAGE | P=0.249N | P=0.006N** | |FISHER EXACT | P=0.014N* P=0.101N P=0.050N* | P=0.002N** P=0.110N P<0.001N** | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 18 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 1/60 (2%) 1/60 (2%) 4/60 (7%) 3/60 (5%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 3.7% 3.6% 10.9% 10.7% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 0/20 (0%) 0/14 (0%) 1/22 (5%) 3/28 (11%) | 0/34 (0%) 0/17 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE (DAYS) | 698 666 565 726 (T) | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.422 P=0.715 P=0.201 P=0.406 | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.279 P=0.763 P=0.340 P=0.342 | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.313 P=0.739 P=0.183 P=0.354 | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.293 | (e) | |FISHER EXACT | P=0.752N P=0.182 P=0.309 | (e) (e) (e) | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 57/60 (95%) 57/60 (95%) 58/60 (97%) 57/60 (95%) | 39/60 (65%) 19/60 (32%) 33/60 (55%) 30/60 (50%) | |ADJUSTED (b) | 100.0% 100.0% 100.0% 100.0% | 84.4% 65.7% 83.8% 87.9% | |INTERIM SACRIFICE 1 (c)| 9/10 (90%) 8/10 (80%) 10/10 (100%) 9/10 (90%) | 2/10 (20%) 0/0 1/10 (10%) 2/10 (20%) | |TERMINAL (d) | 20/20 (100%) 14/14 (100%) 22/22 (100%) 28/28 (100%)| 27/34 (79%) 8/17 (47%) 20/26 (77%) 18/22 (82%) | |FIRST INCIDENCE (DAYS) | 430 404 456 (I) 351 | 457 (I) 379 404 457 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.020N* P=0.115 P=0.498N P=0.110N | P=0.207 P=0.547N P=0.479 P=0.235 | |INCIDENTAL TUMOR | P=0.313 P=0.647 P=0.579 P=0.397 | P=0.206 P=0.037N* P=0.316N P=0.454 | |LOGISTIC REGRESSION | P=0.311 P=0.666 P=0.545 P=0.408 | P=0.218 P=0.088N P=0.264N P=0.442 | |COCHRAN-ARMITAGE | P=0.587N | P=0.532N | |FISHER EXACT | P=0.660N P=0.500 P=0.660N | P<0.001N** P=0.176N P=0.070N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 19 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | O MG/KG 1 MG/KG 5 MG/KG 25 MG/KG | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 39/60 (65%) 27/60 (45%) 31/60 (52%) 29/60 (48%) | 23/60 (38%) 9/60 (15%) 16/60 (27%) 6/60 (10%) | |ADJUSTED (b) | 92.4% 84.1% 76.1% 65.2% | 54.8% 41.5% 45.7% 19.5% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 0/0 0/10 (0%) 0/10 (0%) | |TERMINAL (d) | 17/20 (85%) 10/14 (71%) 13/22 (59%) 13/28 (46%) | 16/34 (47%) 5/17 (29%) 8/26 (31%) 3/22 (14%) | |FIRST INCIDENCE (DAYS) | 443 492 463 456 (I) | 374 519 555 391 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.020N* P=0.310N P=0.113N P=0.014N* | P=0.022N* P=0.283N P=0.361N P=0.014N* | |INCIDENTAL TUMOR | P=0.303N P=0.014N* P=0.057N P=0.082N | P=0.014N* P=0.079N P=0.128N P=0.002N** | |LOGISTIC REGRESSION | P=0.299N P=0.013N* P=0.027N* P=0.050N* | P=0.010N* P=0.118N P=0.166N P=0.003N** | |COCHRAN-ARMITAGE | P=0.224N | P=0.005N** | |FISHER EXACT | P=0.022N* P=0.097N P=0.048N* | P=0.003N** P=0.121N P<0.001N** | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 58/60 (97%) 57/60 (95%) 59/60 (98%) 57/60 (95%) | 50/60 (83%) 23/60 (38%) 40/60 (67%) 33/60 (55%) | |ADJUSTED (b) | 100.0% 100.0% 100.0% 100.0% | 96.1% 78.4% 92.8% 88.7% | |INTERIM SACRIFICE 1 (c)| 9/10 (90%) 8/10 (80%) 10/10 (100%) 9/10 (90%) | 2/10 (20%) 0/0 1/10 (10%) 2/10 (20%) | |TERMINAL (d) | 20/20 (100%) 14/14 (100%) 22/22 (100%) 28/28 (100%)| 32/34 (94%) 11/17 (65%) 23/26 (88%) 18/22 (82%) | |FIRST INCIDENCE (DAYS) | 430 404 456 (I) 351 | 374 379 404 391 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.017N* P=0.142 P=0.495N P=0.088N | P=0.488 P=0.391N P=0.490N P=0.537N | |INCIDENTAL TUMOR | P=0.404 P=0.500N P=0.500 P=0.621 | P=0.556N P<0.001N** P=0.026N* P=0.054N | |LOGISTIC REGRESSION | P=0.433 P=0.530N P=0.570 P=0.630 | P=0.476N P=0.006N** P=0.040N* P=0.093N | |COCHRAN-ARMITAGE | P=0.457N | P=0.169N | |FISHER EXACT | P=0.500N P=0.500 P=0.500N | P<0.001N** P=0.028N* P<0.001N** | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05121 TEST: 05 PAGE 20 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- SCOPOLAMINE HYDROBROMIDE TRIHYDRATE TERMINAL SACRIFICE AT 104 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. (c) Observed incidence at interim kill. Male interim sacrifices(days): 456 Female interim sacrifices(days): 457 (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).