TDMS Study 05091-02 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: American Biogenics DIHYDROCOUMARIN DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 TIME: 13:18:28 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-45039 ROUTE: GAVAGE NTP C#: 55890B PATHOLOGIST: R. DAHLGREN S. EUSTIS CAS: 119-84-6 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: American Biogenics DIHYDROCOUMARIN DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 TIME: 13:18:28 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-45039 ROUTE: GAVAGE NTP C#: 55890B PATHOLOGIST: R. DAHLGREN S. EUSTIS CAS: 119-84-6 MICE(B6C3F1) ---------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED. ---------------- Adrenal Gland Bone Marrow Brain Clitoral Gland Epididymis Gallbladder Heart Islets, Pancreatic Kidney 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 DIHYDROCOUMARIN DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 TIME: 13:18:28 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-45039 ROUTE: GAVAGE NTP C#: 55890B PATHOLOGIST: R. DAHLGREN S. EUSTIS CAS: 119-84-6 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF THE STUDY OF DIHYDROCOUMARIN ==================================================================================================== MALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Intestine Small Carcinoma or Adenoma Liver Hepatoblastoma Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma All Organs Malignant Lymphoma And Histiocytic Sarcoma Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type Benign Tumors Malignant and Benign Tumors ==================================================================================================== FEMALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Liver Hemangiosarcoma Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Spleen Hemangiosarcoma All Organs Hemangiosarcoma Hemangiosarcoma or Hemangioma Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 1 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 5/60 (8%) 4/58 (7%) 2/56 (4%) 2/60 (3%) | 1/60 (2%) 3/56 (5%) 3/58 (5%) 1/61 (2%) | |ADJUSTED (b) | 11.9% 9.3% 5.4% 5.1% | 2.4% 7.2% 7.3% 3.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/7 (14%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 5/42 (12%) 2/39 (5%) 1/34 (3%) 1/38 (3%) | 0/36 (0%) 2/39 (5%) 3/41 (7%) 1/29 (3%) | |FIRST INCIDENCE (DAYS) | 729 (T) 456 (I) 675 722 | 674 671 729 (T) 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.168N P=0.561N P=0.303N P=0.259N | P=0.589N P=0.337 P=0.353 P=0.718 | |INCIDENTAL TUMOR | P=0.133N P=0.540N P=0.234N P=0.236N | P=0.535N P=0.318 P=0.342 P=0.754N | |LOGISTIC REGRESSION | P=0.142N P=0.519N P=0.247N P=0.246N | P=0.556N P=0.314 P=0.332 P=0.742 | |COCHRAN-ARMITAGE | P=0.135N | P=0.485N | |FISHER EXACT | P=0.522N P=0.249N P=0.219N | P=0.284 P=0.297 P=0.748N | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 5/60 (8%) 5/58 (9%) 2/56 (4%) 2/60 (3%) | 1/60 (2%) 3/56 (5%) 3/58 (5%) 1/61 (2%) | |ADJUSTED (b) | 11.9% 10.9% 5.4% 5.1% | 2.4% 7.2% 7.3% 3.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/7 (14%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 5/42 (12%) 2/39 (5%) 1/34 (3%) 1/38 (3%) | 0/36 (0%) 2/39 (5%) 3/41 (7%) 1/29 (3%) | |FIRST INCIDENCE (DAYS) | 729 (T) 438 675 722 | 674 671 729 (T) 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.145N P=0.568 P=0.303N P=0.259N | P=0.589N P=0.337 P=0.353 P=0.718 | |INCIDENTAL TUMOR | P=0.104N P=0.591 P=0.234N P=0.236N | P=0.535N P=0.318 P=0.342 P=0.754N | |LOGISTIC REGRESSION | P=0.117N P=0.610 P=0.247N P=0.246N | P=0.556N P=0.314 P=0.332 P=0.742 | |COCHRAN-ARMITAGE | P=0.114N | P=0.485N | |FISHER EXACT | P=0.607 P=0.249N P=0.219N | P=0.284 P=0.297 P=0.748N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 2 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Intestine Small | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/60 (7%) 0/58 (0%) 1/56 (2%) 0/60 (0%) | 0/60 (0%) 0/56 (0%) 0/58 (0%) 0/61 (0%) | |ADJUSTED (b) | 9.3% 0.0% 2.9% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 3/42 (7%) 0/39 (0%) 1/34 (3%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | 690 --- 729 (T) --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.050N* P=0.075N P=0.246N P=0.078N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.040N* P=0.062N P=0.171N P=0.065N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.044N* P=0.067N P=0.202N P=0.070N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.041N* | (e) | |FISHER EXACT | P=0.064N P=0.204N P=0.059N | (e) (e) (e) | |=================================================================================================================================| | | |Intestine Small: Jejunum | | Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 0/58 (0%) 0/56 (0%) 0/60 (0%) | 0/60 (0%) 0/56 (0%) 0/58 (0%) 0/61 (0%) | |ADJUSTED (b) | 4.8% 0.0% 0.0% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 2/42 (5%) 0/39 (0%) 0/34 (0%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) --- --- --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.130N P=0.255N P=0.286N P=0.261N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.130N P=0.255N P=0.286N P=0.261N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.130N P=0.255N P=0.286N P=0.261N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.117N | (e) | |FISHER EXACT | P=0.256N P=0.265N P=0.248N | (e) (e) (e) | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 3 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/59 (0%) 2/57 (4%) 0/54 (0%) 0/60 (0%) | 0/59 (0%) 1/56 (2%) 0/56 (0%) 0/56 (0%) | |ADJUSTED (b) | 0.0% 5.1% 0.0% 0.0% | 0.0% 2.6% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 2/39 (5%) 0/34 (0%) 0/38 (0%) | 0/36 (0%) 1/39 (3%) 0/41 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) --- --- | --- 729 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.428N P=0.222 (e) (e) | P=0.609N P=0.516 (e) (e) | |INCIDENTAL TUMOR | P=0.428N P=0.222 (e) (e) | P=0.609N P=0.516 (e) (e) | |LOGISTIC REGRESSION | P=0.428N P=0.222 (e) (e) | P=0.609N P=0.516 (e) (e) | |COCHRAN-ARMITAGE | P=0.403N | P=0.573N | |FISHER EXACT | P=0.239 (e) (e) | P=0.487 (e) (e) | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/58 (0%) 2/56 (4%) 0/59 (0%) | 0/57 (0%) 0/56 (0%) 0/56 (0%) 0/56 (0%) | |ADJUSTED (b) | 0.0% 0.0% 5.9% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 0/39 (0%) 2/34 (6%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- --- 729 (T) --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.572 (e) P=0.193 (e) | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.572 (e) P=0.193 (e) | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.572 (e) P=0.193 (e) | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.591 | (e) | |FISHER EXACT | (e) P=0.231 (e) | (e) (e) (e) | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 4 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/60 (0%) 1/58 (2%) 2/56 (4%) 1/59 (2%) | 0/57 (0%) 0/56 (0%) 0/56 (0%) 0/56 (0%) | |ADJUSTED (b) | 0.0% 2.6% 5.9% 2.6% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 1/39 (3%) 2/34 (6%) 1/38 (3%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) 729 (T) 729 (T) | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.340 P=0.485 P=0.193 P=0.480 | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.340 P=0.485 P=0.193 P=0.480 | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.340 P=0.485 P=0.193 P=0.480 | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.364 | (e) | |FISHER EXACT | P=0.492 P=0.231 P=0.496 | (e) (e) (e) | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/60 (3%) 0/58 (0%) 0/56 (0%) 0/60 (0%) | 0/60 (0%) 0/56 (0%) 0/58 (0%) 2/61 (3%) | |ADJUSTED (b) | 4.2% 0.0% 0.0% 0.0% | 0.0% 0.0% 0.0% 6.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 1/42 (2%) 0/39 (0%) 0/34 (0%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 1/29 (3%) | |FIRST INCIDENCE (DAYS) | 456 --- --- --- | --- --- --- 703 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.125N P=0.256N P=0.272N P=0.253N | P=0.030 * (e) (e) P=0.198 | |INCIDENTAL TUMOR | P=0.106N P=0.248N P=0.309N P=0.194N | P=0.049 * (e) (e) P=0.246 | |LOGISTIC REGRESSION | P=0.120N P=0.249N P=0.258N P=0.244N | P=0.034 * (e) (e) P=0.207 | |COCHRAN-ARMITAGE | P=0.117N | P=0.051 | |FISHER EXACT | P=0.256N P=0.265N P=0.248N | (e) (e) P=0.252 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 5 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Liver | | Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/58 (0%) 0/56 (0%) 2/60 (3%) | 0/60 (0%) 0/56 (0%) 0/58 (0%) 0/61 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 5.3% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 0/39 (0%) 0/34 (0%) 2/38 (5%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- 729 (T) | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.044 * (e) (e) P=0.217 | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.044 * (e) (e) P=0.217 | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.044 * (e) (e) P=0.217 | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.049 * | (e) | |FISHER EXACT | (e) (e) P=0.248 | (e) (e) (e) | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 32/60 (53%) 27/58 (47%) 38/56 (68%) 34/60 (57%) | 12/60 (20%) 20/56 (36%) 24/58 (41%) 22/61 (36%) | |ADJUSTED (b) | 65.9% 58.1% 82.3% 73.3% | 30.4% 45.2% 54.1% 57.5% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 4/7 (57%) 2/5 (40%) 3/10 (30%) | 2/9 (22%) 0/6 (0%) 2/8 (25%) 2/9 (22%) | |TERMINAL (d) | 26/42 (62%) 20/39 (51%) 26/34 (76%) 26/38 (68%) | 10/36 (28%) 15/39 (38%) 21/41 (51%) 14/29 (48%) | |FIRST INCIDENCE (DAYS) | 449 455 (I) 455 (I) 438 | 455 (I) 594 455 (I) 420 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.114 P=0.431N P=0.014 * P=0.252 | P=0.005 ** P=0.103 P=0.028 * P=0.008 ** | |INCIDENTAL TUMOR | P=0.204 P=0.325N P=0.074 P=0.408 | P=0.014 * P=0.085 P=0.027 * P=0.016 * | |LOGISTIC REGRESSION | P=0.204 P=0.281N P=0.087 P=0.405 | P=0.021 * P=0.084 P=0.017 * P=0.024 * | |COCHRAN-ARMITAGE | P=0.228 | P=0.059 | |FISHER EXACT | P=0.290N P=0.079 P=0.427 | P=0.046 * P=0.010 ** P=0.038 * | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 6 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/60 (18%) 11/58 (19%) 11/56 (20%) 6/60 (10%) | 3/60 (5%) 2/56 (4%) 4/58 (7%) 6/61 (10%) | |ADJUSTED (b) | 24.3% 23.1% 25.5% 13.4% | 7.7% 4.8% 8.9% 15.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 8/42 (19%) 4/39 (10%) 4/34 (12%) 2/38 (5%) | 1/36 (3%) 1/39 (3%) 3/41 (7%) 2/29 (7%) | |FIRST INCIDENCE (DAYS) | 591 423 583 477 | 674 685 444 504 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.171N P=0.537 P=0.450 P=0.202N | P=0.068 P=0.455N P=0.559 P=0.178 | |INCIDENTAL TUMOR | P=0.033N* P=0.280N P=0.183N P=0.069N | P=0.292 P=0.485N P=0.618 P=0.456 | |LOGISTIC REGRESSION | P=0.037N* P=0.490N P=0.238N P=0.065N | P=0.154 P=0.484N P=0.503 P=0.275 | |COCHRAN-ARMITAGE | P=0.113N | P=0.125 | |FISHER EXACT | P=0.558 P=0.522 P=0.148N | P=0.533N P=0.481 P=0.254 | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/60 (18%) 11/58 (19%) 11/56 (20%) 7/60 (12%) | 3/60 (5%) 2/56 (4%) 4/58 (7%) 6/61 (10%) | |ADJUSTED (b) | 24.3% 23.1% 25.5% 15.8% | 7.7% 4.8% 8.9% 15.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 8/42 (19%) 4/39 (10%) 4/34 (12%) 3/38 (8%) | 1/36 (3%) 1/39 (3%) 3/41 (7%) 2/29 (7%) | |FIRST INCIDENCE (DAYS) | 591 423 583 477 | 674 685 444 504 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.246N P=0.537 P=0.450 P=0.289N | P=0.068 P=0.455N P=0.559 P=0.178 | |INCIDENTAL TUMOR | P=0.066N P=0.280N P=0.183N P=0.122N | P=0.292 P=0.485N P=0.618 P=0.456 | |LOGISTIC REGRESSION | P=0.072N P=0.490N P=0.238N P=0.119N | P=0.154 P=0.484N P=0.503 P=0.275 | |COCHRAN-ARMITAGE | P=0.174N | P=0.125 | |FISHER EXACT | P=0.558 P=0.522 P=0.222N | P=0.533N P=0.481 P=0.254 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 7 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 39/60 (65%) 34/58 (59%) 42/56 (75%) 36/60 (60%) | 15/60 (25%) 21/56 (38%) 27/58 (47%) 26/61 (43%) | |ADJUSTED (b) | 76.1% 66.4% 84.0% 74.5% | 36.5% 46.5% 59.4% 61.6% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 4/7 (57%) 2/5 (40%) 3/10 (30%) | 2/9 (22%) 0/6 (0%) 2/8 (25%) 2/9 (22%) | |TERMINAL (d) | 30/42 (71%) 22/39 (56%) 26/34 (76%) 26/38 (68%) | 11/36 (31%) 15/39 (38%) 23/41 (56%) 14/29 (48%) | |FIRST INCIDENCE (DAYS) | 449 423 455 (I) 438 | 455 (I) 594 444 420 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.400 P=0.460N P=0.049 * P=0.563 | P=0.003 ** P=0.225 P=0.043 * P=0.008 ** | |INCIDENTAL TUMOR | P=0.375N P=0.187N P=0.445 P=0.292N | P=0.019 * P=0.176 P=0.046 * P=0.031 * | |LOGISTIC REGRESSION | P=0.384N P=0.289N P=0.288 P=0.365N | P=0.013 * P=0.179 P=0.021 * P=0.021 * | |COCHRAN-ARMITAGE | P=0.443N | P=0.033 * | |FISHER EXACT | P=0.300N P=0.166 P=0.353N | P=0.105 P=0.012 * P=0.031 * | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 39/60 (65%) 34/58 (59%) 42/56 (75%) 37/60 (62%) | 15/60 (25%) 21/56 (38%) 27/58 (47%) 26/61 (43%) | |ADJUSTED (b) | 76.1% 66.4% 84.0% 76.6% | 36.5% 46.5% 59.4% 61.6% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 4/7 (57%) 2/5 (40%) 3/10 (30%) | 2/9 (22%) 0/6 (0%) 2/8 (25%) 2/9 (22%) | |TERMINAL (d) | 30/42 (71%) 22/39 (56%) 26/34 (76%) 27/38 (71%) | 11/36 (31%) 15/39 (38%) 23/41 (56%) 14/29 (48%) | |FIRST INCIDENCE (DAYS) | 449 423 455 (I) 438 | 455 (I) 594 444 420 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.334 P=0.460N P=0.049 * P=0.491 | P=0.003 ** P=0.225 P=0.043 * P=0.008 ** | |INCIDENTAL TUMOR | P=0.459N P=0.187N P=0.445 P=0.366N | P=0.019 * P=0.176 P=0.046 * P=0.031 * | |LOGISTIC REGRESSION | P=0.470N P=0.289N P=0.288 P=0.441N | P=0.013 * P=0.179 P=0.021 * P=0.021 * | |COCHRAN-ARMITAGE | P=0.525N | P=0.033 * | |FISHER EXACT | P=0.300N P=0.166 P=0.425N | P=0.105 P=0.012 * P=0.031 * | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 8 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/60 (15%) 16/57 (28%) 17/56 (30%) 11/60 (18%) | 2/60 (3%) 5/56 (9%) 1/56 (2%) 3/60 (5%) | |ADJUSTED (b) | 20.5% 39.6% 43.8% 26.9% | 5.6% 12.3% 2.4% 9.5% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 1/7 (14%) 2/5 (40%) 1/10 (10%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 8/42 (19%) 15/39 (38%) 13/34 (38%) 9/38 (24%) | 2/36 (6%) 4/39 (10%) 1/41 (2%) 2/28 (7%) | |FIRST INCIDENCE (DAYS) | 456 (I) 455 (I) 455 (I) 456 (I) | 729 (T) 671 729 (T) 595 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.385 P=0.047 * P=0.010 ** P=0.322 | P=0.489 P=0.252 P=0.455N P=0.395 | |INCIDENTAL TUMOR | P=0.415 P=0.047 * P=0.016 * P=0.369 | P=0.517 P=0.246 P=0.455N P=0.409 | |LOGISTIC REGRESSION | P=0.468 P=0.065 P=0.041 * P=0.378 | P=0.534 P=0.247 P=0.455N P=0.444 | |COCHRAN-ARMITAGE | P=0.501 | P=0.554N | |FISHER EXACT | P=0.067 P=0.039 * P=0.404 | P=0.192 P=0.526N P=0.500 | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 3/57 (5%) 1/56 (2%) 3/60 (5%) | 0/60 (0%) 1/56 (2%) 0/56 (0%) 0/60 (0%) | |ADJUSTED (b) | 2.3% 7.2% 2.6% 7.2% | 0.0% 2.1% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 1/39 (3%) 0/34 (0%) 2/38 (5%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | 690 643 715 477 | --- 615 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.289 P=0.290 P=0.733 P=0.284 | P=0.593N P=0.513 (e) (e) | |INCIDENTAL TUMOR | P=0.398 P=0.404 P=0.530N P=0.360 | P=0.565N P=0.455 (e) (e) | |LOGISTIC REGRESSION | P=0.315 P=0.289 P=0.750 P=0.305 | P=0.558N P=0.463 (e) (e) | |COCHRAN-ARMITAGE | P=0.319 | P=0.564N | |FISHER EXACT | P=0.290 P=0.735 P=0.309 | P=0.483 (e) (e) | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 9 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/60 (17%) 19/57 (33%) 18/56 (32%) 14/60 (23%) | 2/60 (3%) 6/56 (11%) 1/56 (2%) 3/60 (5%) | |ADJUSTED (b) | 22.4% 44.9% 45.2% 33.3% | 5.6% 14.1% 2.4% 9.5% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 1/7 (14%) 2/5 (40%) 1/10 (10%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 8/42 (19%) 16/39 (41%) 13/34 (38%) 11/38 (29%) | 2/36 (6%) 4/39 (10%) 1/41 (2%) 2/28 (7%) | |FIRST INCIDENCE (DAYS) | 456 (I) 455 (I) 455 (I) 456 (I) | 729 (T) 615 729 (T) 595 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.274 P=0.023 * P=0.012 * P=0.182 | P=0.546 P=0.165 P=0.455N P=0.395 | |INCIDENTAL TUMOR | P=0.342 P=0.030 * P=0.029 * P=0.243 | P=0.573 P=0.148 P=0.455N P=0.409 | |LOGISTIC REGRESSION | P=0.353 P=0.028 * P=0.044 * P=0.229 | P=0.560N P=0.147 P=0.455N P=0.444 | |COCHRAN-ARMITAGE | P=0.386 | P=0.492N | |FISHER EXACT | P=0.030 * P=0.042 * P=0.247 | P=0.115 P=0.526N P=0.500 | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | | 1/59 (2%) 2/56 (4%) 1/57 (2%) 0/59 (0%) | |ADJUSTED (b) | | 2.8% 5.1% 2.4% 0.0% | |INTERIM SACRIFICE 1 (c)| | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | | 1/36 (3%) 2/39 (5%) 1/41 (2%) 0/28 (0%) | |FIRST INCIDENCE (DAYS) | | 729 (T) 729 (T) 729 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.295N P=0.528 P=0.733N P=0.550N | |INCIDENTAL TUMOR | | P=0.295N P=0.528 P=0.733N P=0.550N | |LOGISTIC REGRESSION | | P=0.294N P=0.528 P=0.733N P=0.550N | |COCHRAN-ARMITAGE | | P=0.246N | |FISHER EXACT | | P=0.480 P=0.743 P=0.500N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 10 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/57 (0%) 0/53 (0%) 1/50 (2%) 1/55 (2%) | 9/56 (16%) 5/54 (9%) 3/55 (5%) 3/56 (5%) | |ADJUSTED (b) | 0.0% 0.0% 3.1% 2.2% | 26.2% 12.4% 7.3% 9.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/40 (0%) 0/37 (0%) 1/32 (3%) 0/36 (0%) | 8/33 (24%) 3/37 (8%) 3/41 (7%) 2/28 (7%) | |FIRST INCIDENCE (DAYS) | --- --- 729 (T) 561 | 704 703 729 (T) 646 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.228 (e) P=0.455 P=0.496 | P=0.061N P=0.139N P=0.026N* P=0.108N | |INCIDENTAL TUMOR | P=0.265 (e) P=0.455 P=0.718 | P=0.057N P=0.146N P=0.034N* P=0.096N | |LOGISTIC REGRESSION | P=0.234 (e) P=0.455 P=0.471 | P=0.057N P=0.126N P=0.027N* P=0.097N | |COCHRAN-ARMITAGE | P=0.235 | P=0.040N* | |FISHER EXACT | (e) P=0.467 P=0.491 | P=0.217N P=0.066N P=0.062N | |=================================================================================================================================| | | |Spleen | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/59 (2%) 0/57 (0%) 1/51 (2%) 2/58 (3%) | 0/60 (0%) 0/56 (0%) 0/57 (0%) 2/55 (4%) | |ADJUSTED (b) | 2.4% 0.0% 2.9% 4.0% | 0.0% 0.0% 0.0% 5.9% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 1/42 (2%) 0/39 (0%) 1/34 (3%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | 729 (T) --- 729 (T) 417 | --- --- --- 583 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.237 P=0.515N P=0.714 P=0.482 | P=0.031 * (e) (e) P=0.198 | |INCIDENTAL TUMOR | P=0.268 P=0.515N P=0.714 P=0.546 | P=0.028 * (e) (e) P=0.161 | |LOGISTIC REGRESSION | P=0.245 P=0.515N P=0.714 P=0.486 | P=0.042 * (e) (e) P=0.214 | |COCHRAN-ARMITAGE | P=0.246 | P=0.043 * | |FISHER EXACT | P=0.509N P=0.715 P=0.494 | (e) (e) P=0.227 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 11 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 1/60 (2%) 1/58 (2%) 0/56 (0%) 2/60 (3%) | 0/60 (0%) 0/56 (0%) 0/58 (0%) 0/61 (0%) | |ADJUSTED (b) | 2.1% 2.6% 0.0% 5.1% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 1/39 (3%) 0/34 (0%) 1/38 (3%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | 528 729 (T) --- 722 | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.346 P=0.752 P=0.496N P=0.475 | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.414 P=0.752 P=0.581N P=0.580 | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.367 P=0.753 P=0.521N P=0.500 | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.369 | (e) | |FISHER EXACT | P=0.744 P=0.517N P=0.500 | (e) (e) (e) | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 1/58 (2%) 5/56 (9%) 4/60 (7%) | 2/60 (3%) 2/56 (4%) 1/58 (2%) 1/61 (2%) | |ADJUSTED (b) | 6.8% 2.6% 14.7% 10.3% | 5.6% 5.1% 2.4% 2.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 2/42 (5%) 1/39 (3%) 5/34 (15%) 3/38 (8%) | 2/36 (6%) 2/39 (5%) 1/41 (2%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | 528 729 (T) 729 (T) 722 | 729 (T) 729 (T) 729 (T) 529 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.226 P=0.327N P=0.262 P=0.453 | P=0.397N P=0.666N P=0.455N P=0.557N | |INCIDENTAL TUMOR | P=0.258 P=0.327N P=0.237 P=0.522 | P=0.251N P=0.666N P=0.455N P=0.350N | |LOGISTIC REGRESSION | P=0.246 P=0.316N P=0.327 P=0.485 | P=0.354N P=0.666N P=0.454N P=0.505N | |COCHRAN-ARMITAGE | P=0.269 | P=0.327N | |FISHER EXACT | P=0.322N P=0.320 P=0.500 | P=0.664 P=0.513N P=0.494N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 12 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 0/58 (0%) 5/56 (9%) 2/60 (3%) | 2/60 (3%) 2/56 (4%) 1/58 (2%) 1/61 (2%) | |ADJUSTED (b) | 4.8% 0.0% 14.7% 5.3% | 5.6% 5.1% 2.4% 2.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 2/42 (5%) 0/39 (0%) 5/34 (15%) 2/38 (5%) | 2/36 (6%) 2/39 (5%) 1/41 (2%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) --- 729 (T) 729 (T) | 729 (T) 729 (T) 729 (T) 529 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.344 P=0.255N P=0.139 P=0.658 | P=0.397N P=0.666N P=0.455N P=0.557N | |INCIDENTAL TUMOR | P=0.344 P=0.255N P=0.139 P=0.658 | P=0.251N P=0.666N P=0.455N P=0.350N | |LOGISTIC REGRESSION | P=0.344 P=0.255N P=0.139 P=0.658 | P=0.354N P=0.666N P=0.454N P=0.505N | |COCHRAN-ARMITAGE | P=0.390 | P=0.327N | |FISHER EXACT | P=0.256N P=0.192 P=0.691N | P=0.664 P=0.513N P=0.494N | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/59 (2%) 0/56 (0%) 0/54 (0%) 2/60 (3%) | 0/57 (0%) 1/56 (2%) 1/57 (2%) 1/58 (2%) | |ADJUSTED (b) | 1.9% 0.0% 0.0% 5.3% | 0.0% 2.3% 2.4% 3.6% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 0/39 (0%) 0/33 (0%) 2/38 (5%) | 0/36 (0%) 0/39 (0%) 1/41 (2%) 1/28 (4%) | |FIRST INCIDENCE (DAYS) | 456 (I) --- --- 729 (T) | --- 703 729 (T) 729 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.246 P=0.571N P=0.638N P=0.477 | P=0.320 P=0.525 P=0.526 P=0.450 | |INCIDENTAL TUMOR | P=0.246 P=0.571N P=0.638N P=0.477 | P=0.379 P=0.536 P=0.526 P=0.450 | |LOGISTIC REGRESSION | P=0.256 P=0.533N P=0.619N P=0.507 | P=0.337 P=0.514 P=0.526 P=0.450 | |COCHRAN-ARMITAGE | P=0.255 | P=0.391 | |FISHER EXACT | P=0.513N P=0.522N P=0.506 | P=0.496 P=0.500 P=0.504 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 13 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 0/60 (0%) 2/56 (4%) 0/58 (0%) 0/61 (0%) | |ADJUSTED (b) | | 0.0% 5.1% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | | 0/36 (0%) 2/39 (5%) 0/41 (0%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | | --- 729 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.445N P=0.256 (e) (e) | |INCIDENTAL TUMOR | | P=0.445N P=0.256 (e) (e) | |LOGISTIC REGRESSION | | P=0.445N P=0.256 (e) (e) | |COCHRAN-ARMITAGE | | P=0.399N | |FISHER EXACT | | P=0.231 (e) (e) | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 1/60 (2%) 2/56 (4%) 0/58 (0%) 0/61 (0%) | |ADJUSTED (b) | | 2.8% 5.1% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | | 1/36 (3%) 2/39 (5%) 0/41 (0%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | | 729 (T) 729 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.213N P=0.528 P=0.474N P=0.543N | |INCIDENTAL TUMOR | | P=0.213N P=0.528 P=0.474N P=0.543N | |LOGISTIC REGRESSION | | P=0.213N P=0.528 P=0.474N P=0.543N | |COCHRAN-ARMITAGE | | P=0.185N | |FISHER EXACT | | P=0.474 P=0.508N P=0.496N | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 14 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 2/58 (3%) 1/56 (2%) 1/60 (2%) | 0/60 (0%) 0/56 (0%) 1/58 (2%) 0/61 (0%) | |ADJUSTED (b) | 0.0% 5.1% 2.9% 1.7% | 0.0% 0.0% 2.4% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 2/39 (5%) 1/34 (3%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 1/41 (2%) 0/29 (0%) | |FIRST INCIDENCE (DAYS) | --- 729 (T) 729 (T) 417 | --- --- 729 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.478 P=0.222 P=0.458 P=0.503 | P=0.676 (e) P=0.526 (e) | |INCIDENTAL TUMOR | P=0.520 P=0.222 P=0.458 P=0.602 | P=0.676 (e) P=0.526 (e) | |LOGISTIC REGRESSION | P=0.501 P=0.222 P=0.458 P=0.407 | P=0.676 (e) P=0.526 (e) | |COCHRAN-ARMITAGE | P=0.501 | P=0.697 | |FISHER EXACT | P=0.239 P=0.483 P=0.500 | (e) P=0.492 (e) | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 0/58 (0%) 1/56 (2%) 2/60 (3%) | 0/60 (0%) 0/56 (0%) 0/58 (0%) 4/61 (7%) | |ADJUSTED (b) | 6.5% 0.0% 2.9% 4.0% | 0.0% 0.0% 0.0% 12.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 2/42 (5%) 0/39 (0%) 1/34 (3%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 0/41 (0%) 2/29 (7%) | |FIRST INCIDENCE (DAYS) | 456 --- 729 (T) 417 | --- --- --- 583 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.576N P=0.137N P=0.372N P=0.524N | P=0.001 ** (e) (e) P=0.045 * | |INCIDENTAL TUMOR | P=0.486N P=0.132N P=0.403N P=0.400N | P=0.004 ** (e) (e) P=0.060 | |LOGISTIC REGRESSION | P=0.557N P=0.128N P=0.330N P=0.512N | P=0.003 ** (e) (e) P=0.055 | |COCHRAN-ARMITAGE | P=0.554N | P=0.004 ** | |FISHER EXACT | P=0.128N P=0.336N P=0.500N | (e) (e) P=0.061 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 15 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 2/58 (3%) 2/56 (4%) 2/60 (3%) | 0/60 (0%) 0/56 (0%) 1/58 (2%) 4/61 (7%) | |ADJUSTED (b) | 6.5% 5.1% 5.9% 4.0% | 0.0% 0.0% 2.4% 12.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 0/5 (0%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 2/42 (5%) 2/39 (5%) 2/34 (6%) 0/38 (0%) | 0/36 (0%) 0/39 (0%) 1/41 (2%) 2/29 (7%) | |FIRST INCIDENCE (DAYS) | 456 729 (T) 729 (T) 417 | --- --- 729 (T) 583 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.466N P=0.534N P=0.583N P=0.524N | P=0.002 ** (e) P=0.526 P=0.045 * | |INCIDENTAL TUMOR | P=0.393N P=0.527N P=0.612N P=0.400N | P=0.006 ** (e) P=0.526 P=0.060 | |LOGISTIC REGRESSION | P=0.431N P=0.514N P=0.528N P=0.512N | P=0.004 ** (e) P=0.526 P=0.055 | |COCHRAN-ARMITAGE | P=0.431N | P=0.007 ** | |FISHER EXACT | P=0.516N P=0.533N P=0.500N | (e) P=0.492 P=0.061 | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma And Histiocytic Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 1/58 (2%) 4/56 (7%) 4/60 (7%) | 5/60 (8%) 8/56 (14%) 4/58 (7%) 7/61 (11%) | |ADJUSTED (b) | 0.0% 2.4% 9.9% 9.6% | 11.9% 17.9% 9.0% 20.3% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 1/5 (20%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 0/39 (0%) 1/34 (3%) 2/38 (5%) | 2/36 (6%) 3/39 (8%) 2/41 (5%) 4/29 (14%) | |FIRST INCIDENCE (DAYS) | --- 673 456 (I) 613 | 587 590 538 419 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.029 * P=0.491 P=0.035 * P=0.058 | P=0.312 P=0.343 P=0.445N P=0.276 | |INCIDENTAL TUMOR | P=0.033 * P=0.557 P=0.082 P=0.111 | P=0.521N P=0.251 P=0.618 P=0.448 | |LOGISTIC REGRESSION | P=0.037 * P=0.494 P=0.054 P=0.062 | P=0.469 P=0.277 P=0.505 P=0.358 | |COCHRAN-ARMITAGE | P=0.031 * | P=0.470 | |FISHER EXACT | P=0.492 P=0.051 P=0.059 | P=0.236 P=0.522N P=0.393 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 16 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/58 (0%) 4/56 (7%) 4/60 (7%) | 4/60 (7%) 8/56 (14%) 4/58 (7%) 7/61 (11%) | |ADJUSTED (b) | 0.0% 0.0% 9.9% 9.6% | 9.3% 17.9% 9.0% 20.3% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 1/5 (20%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 0/42 (0%) 0/39 (0%) 1/34 (3%) 2/38 (5%) | 1/36 (3%) 3/39 (8%) 2/41 (5%) 4/29 (14%) | |FIRST INCIDENCE (DAYS) | --- --- 456 (I) 613 | 587 590 538 419 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.015 * (e) P=0.035 * P=0.058 | P=0.228 P=0.235 P=0.592N P=0.187 | |INCIDENTAL TUMOR | P=0.016 * (e) P=0.082 P=0.111 | P=0.501 P=0.148 P=0.448 P=0.333 | |LOGISTIC REGRESSION | P=0.018 * (e) P=0.054 P=0.062 | P=0.373 P=0.175 P=0.319 P=0.249 | |COCHRAN-ARMITAGE | P=0.015 * | P=0.369 | |FISHER EXACT | (e) P=0.051 P=0.059 | P=0.149 P=0.622 P=0.274 | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 39/60 (65%) 36/58 (62%) 43/56 (77%) 40/60 (67%) | 19/60 (32%) 29/56 (52%) 29/58 (50%) 27/61 (44%) | |ADJUSTED (b) | 79.1% 73.1% 89.4% 82.9% | 46.6% 65.8% 65.5% 67.7% | |INTERIM SACRIFICE 1 (c)| 4/10 (40%) 6/7 (86%) 4/5 (80%) 3/10 (30%) | 2/9 (22%) 0/6 (0%) 2/8 (25%) 2/9 (22%) | |TERMINAL (d) | 32/42 (76%) 26/39 (67%) 29/34 (85%) 30/38 (79%) | 15/36 (42%) 24/39 (62%) 26/41 (63%) 17/29 (59%) | |FIRST INCIDENCE (DAYS) | 449 455 (I) 455 (I) 417 | 455 (I) 594 455 (I) 420 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.167 P=0.498 P=0.010 ** P=0.274 | P=0.017 * P=0.077 P=0.103 P=0.021 * | |INCIDENTAL TUMOR | P=0.310 P=0.534N P=0.058 P=0.504 | P=0.055 P=0.056 P=0.094 P=0.057 | |LOGISTIC REGRESSION | P=0.329 P=0.432N P=0.129 P=0.480 | P=0.065 P=0.056 P=0.061 P=0.059 | |COCHRAN-ARMITAGE | P=0.349 | P=0.193 | |FISHER EXACT | P=0.444N P=0.117 P=0.500 | P=0.022 * P=0.033 * P=0.107 | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 17 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | VEHICLE 200MG/KG 400MG/KG 800MG/KG | VEHICLE 200MG/KG 400MG/KG 800MG/KG | | | CONTROL | CONTROL | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 17/60 (28%) 17/58 (29%) 16/56 (29%) 20/60 (33%) | 9/60 (15%) 11/56 (20%) 11/58 (19%) 16/61 (26%) | |ADJUSTED (b) | 35.9% 34.3% 36.2% 41.2% | 20.6% 23.6% 22.8% 40.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/7 (0%) 1/5 (20%) 0/10 (0%) | 0/9 (0%) 0/6 (0%) 0/8 (0%) 0/9 (0%) | |TERMINAL (d) | 12/42 (29%) 7/39 (18%) 7/34 (21%) 10/38 (26%) | 3/36 (8%) 4/39 (10%) 5/41 (12%) 7/29 (24%) | |FIRST INCIDENCE (DAYS) | 456 423 456 (I) 417 | 587 590 444 419 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.236 P=0.504 P=0.443 P=0.270 | P=0.027 * P=0.483 P=0.501 P=0.047 * | |INCIDENTAL TUMOR | P=0.494 P=0.302N P=0.229N P=0.580N | P=0.235 P=0.343 P=0.277 P=0.178 | |LOGISTIC REGRESSION | P=0.432 P=0.531N P=0.314N P=0.494 | P=0.109 P=0.224 P=0.157 P=0.098 | |COCHRAN-ARMITAGE | P=0.305 | P=0.082 | |FISHER EXACT | P=0.534 P=0.570 P=0.346 | P=0.339 P=0.371 P=0.096 | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 46/60 (77%) 46/58 (79%) 48/56 (86%) 47/60 (78%) | 26/60 (43%) 36/56 (64%) 38/58 (66%) 40/61 (66%) | |ADJUSTED (b) | 88.3% 83.6% 92.3% 90.3% | 56.0% 73.5% 75.7% 83.0% | |INTERIM SACRIFICE 1 (c)| 4/10 (40%) 6/7 (86%) 4/5 (80%) 3/10 (30%) | 2/9 (22%) 0/6 (0%) 2/8 (25%) 2/9 (22%) | |TERMINAL (d) | 36/42 (86%) 30/39 (77%) 30/34 (88%) 33/38 (87%) | 16/36 (44%) 26/39 (67%) 29/41 (71%) 21/29 (72%) | |FIRST INCIDENCE (DAYS) | 449 423 455 (I) 417 | 455 (I) 590 444 419 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.220 P=0.271 P=0.024 * P=0.250 | P<0.001 ** P=0.131 P=0.104 P=0.002 ** | |INCIDENTAL TUMOR | P=0.529 P=0.560 P=0.331 P=0.573N | P=0.013 * P=0.039 * P=0.026 * P=0.011 * | |LOGISTIC REGRESSION | P=0.500 P=0.464 P=0.178 P=0.489 | P=0.006 ** P=0.028 * P=0.026 * P=0.004 ** | |COCHRAN-ARMITAGE | P=0.441 | P=0.020 * | |FISHER EXACT | P=0.451 P=0.157 P=0.500 | P=0.019 * P=0.013 * P=0.011 * | |=================================================================================================================================| DATE: 09/12/94 EXPERIMENT: 05091 TEST: 02 PAGE 18 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN TERMINAL SACRIFICE AT 105 WEEKS (a) Number of tumor-bearing animals / number of animals examined at site. (b) Kaplan-Meier estimated lifetime tumor incidence after adjustment for intercurrent mortality. (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).