TDMS Study 05214-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Mason TRANS-DELTA-9-TETRAHYDROCANNABINOL DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 TIME: 12:27:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-85212 ROUTE: GAVAGE NTP C#: 56371B PATHOLOGIST: K. MURTHY CAS: 1972-08-3 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Mason TRANS-DELTA-9-TETRAHYDROCANNABINOL DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 TIME: 12:27:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85212 ROUTE: GAVAGE NTP C#: 56371B PATHOLOGIST: K. MURTHY CAS: 1972-08-3 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: Mason TRANS-DELTA-9-TETRAHYDROCANNABINOL DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 TIME: 12:27:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85212 ROUTE: GAVAGE NTP C#: 56371B PATHOLOGIST: K. MURTHY CAS: 1972-08-3 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF THE STUDY OF TRANS-DELTA-9-TETRAHYDROCANNABINOL ==================================================================================================== MALE RATS ------------- ORGAN MORPHOLOGY ------- ------------ Adrenal Medulla Pheochromocytoma Benign Pheochromocytoma: Benign, Complex, Malignant, NOS Liver Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Mammary Gland Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Pancreas Adenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Carcinoma or Adenoma Skin Basal Cell Adenoma, Basosquamous Tumor Benign, or Trichoepithelioma Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous Tumor (benign, malignant or NOS), or Trichoepithelioma Testes Adenoma All Organs 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 Carcinoma or Adenoma Thyroid Gland: C-Cell Carcinoma or Adenoma Uterus Polyp Stromal Sarcoma Stromal or Polyp Stromal All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Benign Tumors Malignant and Benign Tumors ==================================================================================================== DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 1 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/62 (15%) 6/60 (10%) 4/61 (7%) 6/61 (10%) | 2/60 (3%) 2/60 (3%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 31.6% 15.7% 11.6% 16.7% | 8.7% 5.0% 6.1% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 4/22 (18%) 4/35 (11%) 3/33 (9%) 3/31 (10%) | 2/23 (9%) 2/40 (5%) 2/33 (6%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | 600 627 709 563 | 725 (T) 725 (T) 725 (T) 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.158N P=0.096N P=0.038N* P=0.146N | P=0.311N P=0.483N P=0.559N P=0.385N | |INCIDENTAL TUMOR | P=0.243N P=0.288N P=0.100N P=0.290N | P=0.311N P=0.483N P=0.559N P=0.385N | |LOGISTIC REGRESSION | P=0.207N P=0.177N P=0.064N P=0.220N | P=0.311N P=0.483N P=0.559N P=0.385N | |COCHRAN-ARMITAGE | P=0.254N | P=0.373N | |FISHER EXACT | P=0.315N P=0.126N P=0.303N | P=0.691N P=0.691N P=0.500N | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Malignant | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/62 (2%) 3/60 (5%) 0/61 (0%) 1/61 (2%) | 0/60 (0%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 2.9% 8.1% 0.0% 3.2% | 0.0% 2.5% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 2/35 (6%) 0/33 (0%) 1/31 (3%) | 0/23 (0%) 1/40 (3%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 647 676 --- 725 (T) | --- 725 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.352N P=0.437 P=0.458N P=0.704N | P=0.548N P=0.610 (e) (e) | |INCIDENTAL TUMOR | P=0.394N P=0.287 P=0.557N P=0.757N | P=0.548N P=0.610 (e) (e) | |LOGISTIC REGRESSION | P=0.389N P=0.353 P=0.500N P=0.747N | P=0.548N P=0.610 (e) (e) | |COCHRAN-ARMITAGE | P=0.412N | P=0.567N | |FISHER EXACT | P=0.297 P=0.504N P=0.748 | P=0.500 (e) (e) | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 2 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/62 (15%) 9/60 (15%) 4/61 (7%) 7/61 (11%) | 2/60 (3%) 3/60 (5%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 31.6% 23.2% 11.6% 19.7% | 8.7% 7.5% 6.1% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 4/22 (18%) 6/35 (17%) 3/33 (9%) 4/31 (13%) | 2/23 (9%) 3/40 (8%) 2/33 (6%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | 600 627 709 563 | 725 (T) 725 (T) 725 (T) 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.160N P=0.274N P=0.038N* P=0.209N | P=0.250N P=0.623N P=0.559N P=0.385N | |INCIDENTAL TUMOR | P=0.246N P=0.593N P=0.100N P=0.380N | P=0.250N P=0.623N P=0.559N P=0.385N | |LOGISTIC REGRESSION | P=0.214N P=0.444N P=0.064N P=0.308N | P=0.250N P=0.623N P=0.559N P=0.385N | |COCHRAN-ARMITAGE | P=0.268N | P=0.313N | |FISHER EXACT | P=0.571 P=0.126N P=0.408N | P=0.500 P=0.691N P=0.500N | |=================================================================================================================================| | | |Brain | | Oligodendroglioma, Glioma, or Astrocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/62 (0%) 1/59 (2%) 1/61 (2%) 0/61 (0%) | 2/60 (3%) 0/60 (0%) 0/60 (0%) 1/60 (2%) | |ADJUSTED (b) | 0.0% 2.4% 2.2% 0.0% | 4.1% 0.0% 0.0% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | --- 674 592 --- | 405 --- --- 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.581N P=0.562 P=0.523 (e) | P=0.445N P=0.223N P=0.223N P=0.454N | |INCIDENTAL TUMOR | P=0.642N P=0.362 P=0.282 (e) | P=0.556N P=0.563N P=0.455N P=0.622N | |LOGISTIC REGRESSION | P=0.595N P=0.511 P=0.497 (e) | P=0.437N P=0.293N P=0.236N P=0.493N | |COCHRAN-ARMITAGE | P=0.595N | P=0.461N | |FISHER EXACT | P=0.488 P=0.496 (e) | P=0.248N P=0.248N P=0.500N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 3 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/62 (3%) 2/60 (3%) 1/61 (2%) 1/59 (2%) | 4/57 (7%) 4/55 (7%) 2/60 (3%) 5/59 (8%) | |ADJUSTED (b) | 8.2% 5.7% 1.8% 2.9% | 14.4% 11.1% 5.5% 14.4% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 1/9 (11%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 1/22 (5%) 2/35 (6%) 0/33 (0%) 0/31 (0%) | 2/21 (10%) 4/36 (11%) 1/33 (3%) 3/32 (9%) | |FIRST INCIDENCE (DAYS) | 715 725 (T) 448 (I) 688 | 374 725 (T) 650 651 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.291N P=0.535N P=0.438N P=0.411N | P=0.563 P=0.382N P=0.201N P=0.585N | |INCIDENTAL TUMOR | P=0.329N P=0.619N P=0.499N P=0.527N | P=0.496 P=0.598N P=0.305N P=0.522 | |LOGISTIC REGRESSION | P=0.340N P=0.580N P=0.505N P=0.452N | P=0.505 P=0.582N P=0.294N P=0.563 | |COCHRAN-ARMITAGE | P=0.351N | P=0.478 | |FISHER EXACT | P=0.678 P=0.506N P=0.519N | P=0.622 P=0.315N P=0.522 | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/62 (8%) 3/60 (5%) 4/61 (7%) 3/61 (5%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 1/59 (2%) | |ADJUSTED (b) | 18.6% 8.1% 11.5% 8.4% | 4.3% 0.0% 0.0% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 3/22 (14%) 2/35 (6%) 3/33 (9%) 2/31 (6%) | 1/23 (4%) 0/40 (0%) 0/33 (0%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | 585 675 668 531 | 725 (T) --- --- 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.252N P=0.181N P=0.306N P=0.228N | P=0.629 P=0.390N P=0.428N P=0.687N | |INCIDENTAL TUMOR | P=0.331N P=0.309N P=0.441N P=0.332N | P=0.629 P=0.390N P=0.428N P=0.687N | |LOGISTIC REGRESSION | P=0.316N P=0.277N P=0.427N P=0.325N | P=0.629 P=0.390N P=0.428N P=0.687N | |COCHRAN-ARMITAGE | P=0.347N | P=0.592 | |FISHER EXACT | P=0.377N P=0.510N P=0.368N | P=0.500N P=0.500N P=0.748 | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 4 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/62 (8%) 3/60 (5%) 4/61 (7%) 3/61 (5%) | 2/60 (3%) 0/60 (0%) 0/60 (0%) 1/59 (2%) | |ADJUSTED (b) | 18.6% 8.1% 11.5% 8.4% | 7.9% 0.0% 0.0% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 3/22 (14%) 2/35 (6%) 3/33 (9%) 2/31 (6%) | 1/23 (4%) 0/40 (0%) 0/33 (0%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | 585 675 668 531 | 676 --- --- 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.252N P=0.181N P=0.306N P=0.228N | P=0.428N P=0.139N P=0.169N P=0.401N | |INCIDENTAL TUMOR | P=0.331N P=0.309N P=0.441N P=0.332N | P=0.433N P=0.232N P=0.187N P=0.442N | |LOGISTIC REGRESSION | P=0.316N P=0.277N P=0.427N P=0.325N | P=0.440N P=0.177N P=0.187N P=0.435N | |COCHRAN-ARMITAGE | P=0.347N | P=0.465N | |FISHER EXACT | P=0.377N P=0.510N P=0.368N | P=0.248N P=0.248N P=0.506N | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/62 (5%) 1/60 (2%) 1/61 (2%) 2/61 (3%) | 0/60 (0%) 0/60 (0%) 3/60 (5%) 0/60 (0%) | |ADJUSTED (b) | 11.4% 1.7% 3.0% 5.8% | 0.0% 0.0% 7.6% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 0/35 (0%) 1/33 (3%) 1/31 (3%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 600 448 (I) 725 (T) 668 | --- --- 509 --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.426N P=0.225N P=0.200N P=0.386N | P=0.558 (e) P=0.176 (e) | |INCIDENTAL TUMOR | P=0.468N P=0.283N P=0.279N P=0.470N | P=0.475 (e) P=0.055 (e) | |LOGISTIC REGRESSION | P=0.472N P=0.322N P=0.269N P=0.463N | P=0.539 (e) P=0.123 (e) | |COCHRAN-ARMITAGE | P=0.477N | P=0.539 | |FISHER EXACT | P=0.322N P=0.316N P=0.508N | (e) P=0.122 (e) | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 5 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/62 (3%) 0/60 (0%) 0/61 (0%) 0/61 (0%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 9.1% 0.0% 0.0% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 725 (T) --- --- --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.087N P=0.143N P=0.154N P=0.166N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.087N P=0.143N P=0.154N P=0.166N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.087N P=0.143N P=0.154N P=0.166N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.116N | (e) | |FISHER EXACT | P=0.256N P=0.252N P=0.252N | (e) (e) (e) | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/62 (8%) 1/60 (2%) 1/61 (2%) 2/61 (3%) | 0/60 (0%) 0/60 (0%) 3/60 (5%) 0/60 (0%) | |ADJUSTED (b) | 20.2% 1.7% 3.0% 5.8% | 0.0% 0.0% 7.6% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 4/22 (18%) 0/35 (0%) 1/33 (3%) 1/31 (3%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 600 448 (I) 725 (T) 668 | --- --- 509 --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.149N P=0.048N* P=0.042N* P=0.121N | P=0.558 (e) P=0.176 (e) | |INCIDENTAL TUMOR | P=0.176N P=0.064N P=0.062N P=0.161N | P=0.475 (e) P=0.055 (e) | |LOGISTIC REGRESSION | P=0.187N P=0.097N P=0.072N P=0.172N | P=0.539 (e) P=0.123 (e) | |COCHRAN-ARMITAGE | P=0.197N | P=0.539 | |FISHER EXACT | P=0.111N P=0.107N P=0.226N | (e) P=0.122 (e) | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 6 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/62 (8%) 1/60 (2%) 1/61 (2%) 2/61 (3%) | 0/60 (0%) 0/60 (0%) 3/60 (5%) 0/60 (0%) | |ADJUSTED (b) | 20.2% 1.7% 3.0% 5.8% | 0.0% 0.0% 7.6% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 4/22 (18%) 0/35 (0%) 1/33 (3%) 1/31 (3%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 600 448 (I) 725 (T) 668 | --- --- 509 --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.149N P=0.048N* P=0.042N* P=0.121N | P=0.558 (e) P=0.176 (e) | |INCIDENTAL TUMOR | P=0.176N P=0.064N P=0.062N P=0.161N | P=0.475 (e) P=0.055 (e) | |LOGISTIC REGRESSION | P=0.187N P=0.097N P=0.072N P=0.172N | P=0.539 (e) P=0.123 (e) | |COCHRAN-ARMITAGE | P=0.197N | P=0.539 | |FISHER EXACT | P=0.111N P=0.107N P=0.226N | (e) P=0.122 (e) | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/62 (0%) 0/60 (0%) 0/61 (0%) 0/61 (0%) | 0/60 (0%) 2/60 (3%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 0.0% 5.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 0/23 (0%) 2/40 (5%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | --- 725 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.371N P=0.367 (e) (e) | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.371N P=0.367 (e) (e) | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.371N P=0.367 (e) (e) | |COCHRAN-ARMITAGE | (e) | P=0.405N | |FISHER EXACT | (e) (e) (e) | P=0.248 (e) (e) | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 7 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 1/62 (2%) 1/60 (2%) 0/61 (0%) 0/61 (0%) | 1/60 (2%) 3/60 (5%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 4.5% 2.9% 0.0% 0.0% | 4.3% 7.5% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 1/22 (5%) 1/35 (3%) 0/33 (0%) 0/31 (0%) | 1/23 (4%) 3/40 (8%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 725 (T) 725 (T) --- --- | 725 (T) 725 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.195N P=0.655N P=0.419N P=0.432N | P=0.118N P=0.517 P=0.428N P=0.434N | |INCIDENTAL TUMOR | P=0.195N P=0.655N P=0.419N P=0.432N | P=0.118N P=0.517 P=0.428N P=0.434N | |LOGISTIC REGRESSION | P=0.195N P=0.655N P=0.419N P=0.432N | P=0.118N P=0.517 P=0.428N P=0.434N | |COCHRAN-ARMITAGE | P=0.237N | P=0.153N | |FISHER EXACT | P=0.744 P=0.504N P=0.504N | P=0.309 P=0.500N P=0.500N | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/62 (5%) 0/60 (0%) 0/61 (0%) 0/61 (0%) | 16/60 (27%) 11/60 (18%) 11/60 (18%) 8/60 (13%) | |ADJUSTED (b) | 12.2% 0.0% 0.0% 0.0% | 41.9% 24.8% 30.3% 23.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 1/9 (11%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 4/23 (17%) 7/40 (18%) 9/33 (27%) 6/32 (19%) | |FIRST INCIDENCE (DAYS) | 683 --- --- --- | 454 (I) 584 562 659 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.033N* P=0.063N P=0.070N P=0.074N | P=0.028N* P=0.032N* P=0.055N P=0.019N* | |INCIDENTAL TUMOR | P=0.041N* P=0.095N P=0.091N P=0.098N | P=0.066N P=0.403N P=0.213N P=0.085N | |LOGISTIC REGRESSION | P=0.039N* P=0.083N P=0.088N P=0.093N | P=0.062N P=0.320N P=0.200N P=0.075N | |COCHRAN-ARMITAGE | P=0.048N* | P=0.054N | |FISHER EXACT | P=0.128N P=0.125N P=0.125N | P=0.191N P=0.191N P=0.054N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 8 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/62 (5%) 0/60 (0%) 0/61 (0%) 0/61 (0%) | 16/60 (27%) 13/60 (22%) 11/60 (18%) 8/60 (13%) | |ADJUSTED (b) | 12.2% 0.0% 0.0% 0.0% | 41.9% 29.4% 30.3% 23.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 1/9 (11%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 4/23 (17%) 9/40 (23%) 9/33 (27%) 6/32 (19%) | |FIRST INCIDENCE (DAYS) | 683 --- --- --- | 454 (I) 584 562 659 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.033N* P=0.063N P=0.070N P=0.074N | P=0.020N* P=0.065N P=0.055N P=0.019N* | |INCIDENTAL TUMOR | P=0.041N* P=0.095N P=0.091N P=0.098N | P=0.048N* P=0.543N P=0.213N P=0.085N | |LOGISTIC REGRESSION | P=0.039N* P=0.083N P=0.088N P=0.093N | P=0.044N* P=0.465N P=0.200N P=0.075N | |COCHRAN-ARMITAGE | P=0.048N* | P=0.040N* | |FISHER EXACT | P=0.128N P=0.125N P=0.125N | P=0.335N P=0.191N P=0.054N | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/62 (6%) 1/60 (2%) 0/61 (0%) 0/61 (0%) | 17/60 (28%) 14/60 (23%) 11/60 (18%) 8/60 (13%) | |ADJUSTED (b) | 16.6% 2.9% 0.0% 0.0% | 45.0% 31.6% 30.3% 23.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 1/9 (11%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 3/22 (14%) 1/35 (3%) 0/33 (0%) 0/31 (0%) | 5/23 (22%) 10/40 (25%) 9/33 (27%) 6/32 (19%) | |FIRST INCIDENCE (DAYS) | 683 725 (T) --- --- | 454 (I) 584 562 659 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.011N* P=0.078N P=0.028N* P=0.031N* | P=0.010N* P=0.056N P=0.034N* P=0.011N* | |INCIDENTAL TUMOR | P=0.013N* P=0.106N P=0.037N* P=0.042N* | P=0.026N* P=0.492N P=0.146N P=0.053N | |LOGISTIC REGRESSION | P=0.014N* P=0.108N P=0.039N* P=0.042N* | P=0.024N* P=0.424N P=0.134N P=0.045N* | |COCHRAN-ARMITAGE | P=0.020N* | P=0.023N* | |FISHER EXACT | P=0.193N P=0.061N P=0.061N | P=0.339N P=0.140N P=0.035N* | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 9 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Pancreas | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/62 (13%) 0/60 (0%) 2/61 (3%) 0/61 (0%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/59 (0%) | |ADJUSTED (b) | 33.8% 0.0% 5.7% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 7/22 (32%) 0/35 (0%) 1/33 (3%) 0/31 (0%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 647 --- 709 --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.001N** P<0.001N** P=0.010N** P<0.001N** | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.002N** P<0.001N** P=0.015N* P=0.001N** | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.002N** P=0.001N** P=0.019N* P=0.002N** | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.003N** | (e) | |FISHER EXACT | P=0.004N** P=0.050N P=0.003N** | (e) (e) (e) | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 22/62 (35%) 21/60 (35%) 16/60 (27%) 9/61 (15%) | 26/60 (43%) 28/60 (47%) 32/60 (53%) 19/60 (32%) | |ADJUSTED (b) | 71.0% 48.7% 37.4% 23.8% | 69.9% 60.6% 70.1% 51.5% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 2/9 (22%) 2/9 (22%) 0/9 (0%) | 3/9 (33%) 1/9 (11%) 1/9 (11%) 0/10 (0%) | |TERMINAL (d) | 14/22 (64%) 14/35 (40%) 8/33 (24%) 4/31 (13%) | 13/23 (57%) 22/40 (55%) 20/33 (61%) 15/32 (47%) | |FIRST INCIDENCE (DAYS) | 448 (I) 448 (I) 448 (I) 578 | 454 (I) 454 (I) 426 449 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001N** P=0.078N P=0.025N* P<0.001N** | P=0.030N* P=0.063N P=0.398N P=0.017N* | |INCIDENTAL TUMOR | P=0.002N** P=0.274N P=0.107N P=0.002N** | P=0.078N P=0.411N P=0.327 P=0.070N | |LOGISTIC REGRESSION | P=0.002N** P=0.350N P=0.125N P=0.002N** | P=0.089N P=0.477N P=0.282 P=0.097N | |COCHRAN-ARMITAGE | P=0.003N** | P=0.097N | |FISHER EXACT | P=0.553N P=0.196N P=0.007N** | P=0.427 P=0.181 P=0.129N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 10 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 22/62 (35%) 21/60 (35%) 16/60 (27%) 9/61 (15%) | 26/60 (43%) 28/60 (47%) 32/60 (53%) 20/60 (33%) | |ADJUSTED (b) | 71.0% 48.7% 37.4% 23.8% | 69.9% 60.6% 70.1% 54.4% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 2/9 (22%) 2/9 (22%) 0/9 (0%) | 3/9 (33%) 1/9 (11%) 1/9 (11%) 0/10 (0%) | |TERMINAL (d) | 14/22 (64%) 14/35 (40%) 8/33 (24%) 4/31 (13%) | 13/23 (57%) 22/40 (55%) 20/33 (61%) 16/32 (50%) | |FIRST INCIDENCE (DAYS) | 448 (I) 448 (I) 448 (I) 578 | 454 (I) 454 (I) 426 449 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001N** P=0.078N P=0.025N* P<0.001N** | P=0.046N* P=0.063N P=0.398N P=0.024N* | |INCIDENTAL TUMOR | P=0.002N** P=0.274N P=0.107N P=0.002N** | P=0.112N P=0.411N P=0.327 P=0.095N | |LOGISTIC REGRESSION | P=0.002N** P=0.350N P=0.125N P=0.002N** | P=0.127N P=0.477N P=0.282 P=0.132N | |COCHRAN-ARMITAGE | P=0.003N** | P=0.136N | |FISHER EXACT | P=0.553N P=0.196N P=0.007N** | P=0.427 P=0.181 P=0.174N | |=================================================================================================================================| | | |Skin | | Basal Cell Adenoma, Basosquamous Tumor Benign, or Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/62 (0%) 0/60 (0%) 0/61 (0%) 2/61 (3%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 6.5% | 4.3% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 0/35 (0%) 0/33 (0%) 2/31 (6%) | 1/23 (4%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- 725 (T) | 725 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.051 (e) (e) P=0.316 | P=0.279N P=0.390N P=0.428N P=0.434N | |INCIDENTAL TUMOR | P=0.051 (e) (e) P=0.316 | P=0.279N P=0.390N P=0.428N P=0.434N | |LOGISTIC REGRESSION | P=0.051 (e) (e) P=0.316 | P=0.279N P=0.390N P=0.428N P=0.434N | |COCHRAN-ARMITAGE | P=0.046 * | P=0.306N | |FISHER EXACT | (e) (e) P=0.244 | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 11 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Skin | | Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous Tumor (benign, | | malignant or NOS), or Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/62 (0%) 0/60 (0%) 0/61 (0%) 2/61 (3%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 6.5% | 4.3% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 0/35 (0%) 0/33 (0%) 2/31 (6%) | 1/23 (4%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- 725 (T) | 725 (T) --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.051 (e) (e) P=0.316 | P=0.279N P=0.390N P=0.428N P=0.434N | |INCIDENTAL TUMOR | P=0.051 (e) (e) P=0.316 | P=0.279N P=0.390N P=0.428N P=0.434N | |LOGISTIC REGRESSION | P=0.051 (e) (e) P=0.316 | P=0.279N P=0.390N P=0.428N P=0.434N | |COCHRAN-ARMITAGE | P=0.046 * | P=0.306N | |FISHER EXACT | (e) (e) P=0.244 | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | |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) | 4/62 (6%) 1/60 (2%) 3/61 (5%) 3/61 (5%) | 1/60 (2%) 2/60 (3%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 16.6% 2.9% 9.1% 8.8% | 4.3% 5.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 3/22 (14%) 1/35 (3%) 3/33 (9%) 2/31 (6%) | 1/23 (4%) 2/40 (5%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 683 725 (T) 725 (T) 659 | 725 (T) 725 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.465N P=0.078N P=0.300N P=0.337N | P=0.153N P=0.689 P=0.428N P=0.434N | |INCIDENTAL TUMOR | P=0.497N P=0.106N P=0.336N P=0.412N | P=0.153N P=0.689 P=0.428N P=0.434N | |LOGISTIC REGRESSION | P=0.513N P=0.108N P=0.369N P=0.418N | P=0.153N P=0.689 P=0.428N P=0.434N | |COCHRAN-ARMITAGE | P=0.566N | P=0.188N | |FISHER EXACT | P=0.193N P=0.509N P=0.509N | P=0.500 P=0.500N P=0.500N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 12 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 1/62 (2%) 1/60 (2%) 0/61 (0%) 2/61 (3%) | 1/60 (2%) 2/60 (3%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 3.8% 2.5% 0.0% 4.4% | 2.5% 4.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 715 675 --- 448 (I) | 590 276 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.392 P=0.694N P=0.452N P=0.544 | P=0.179N P=0.565 P=0.468N P=0.486N | |INCIDENTAL TUMOR | P=0.325 P=0.640 P=0.557N P=0.421 | P=0.178N P=0.349 P=0.590N P=0.621N | |LOGISTIC REGRESSION | P=0.365 P=0.733N P=0.458N P=0.492 | P=0.145N P=0.408 P=0.513N P=0.499N | |COCHRAN-ARMITAGE | P=0.365 | P=0.188N | |FISHER EXACT | P=0.744 P=0.504N P=0.494 | P=0.500 P=0.500N P=0.500N | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 1/62 (2%) 0/60 (0%) 0/61 (0%) 1/61 (2%) | 1/60 (2%) 2/60 (3%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 3.8% 0.0% 0.0% 2.7% | 2.5% 4.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 0/35 (0%) 0/33 (0%) 0/31 (0%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 715 --- --- 684 | 590 276 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.629 P=0.441N P=0.452N P=0.705N | P=0.179N P=0.565 P=0.468N P=0.486N | |INCIDENTAL TUMOR | P=0.555 P=0.607N P=0.557N P=0.700 | P=0.178N P=0.349 P=0.590N P=0.621N | |LOGISTIC REGRESSION | P=0.608 P=0.451N P=0.458N P=0.739N | P=0.145N P=0.408 P=0.513N P=0.499N | |COCHRAN-ARMITAGE | P=0.593 | P=0.188N | |FISHER EXACT | P=0.508N P=0.504N P=0.748 | P=0.500 P=0.500N P=0.500N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 13 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/62 (5%) 1/60 (2%) 3/61 (5%) 1/61 (2%) | 0/60 (0%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 13.6% 2.9% 9.1% 2.5% | 0.0% 2.5% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 3/22 (14%) 1/35 (3%) 3/33 (9%) 0/31 (0%) | 0/23 (0%) 1/40 (3%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 725 (T) 725 (T) 725 (T) 659 | --- 725 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.236N P=0.156N P=0.465N P=0.205N | P=0.548N P=0.610 (e) (e) | |INCIDENTAL TUMOR | P=0.251N P=0.156N P=0.465N P=0.241N | P=0.548N P=0.610 (e) (e) | |LOGISTIC REGRESSION | P=0.268N P=0.156N P=0.465N P=0.253N | P=0.548N P=0.610 (e) (e) | |COCHRAN-ARMITAGE | P=0.317N | P=0.567N | |FISHER EXACT | P=0.322N P=0.652 P=0.316N | P=0.500 (e) (e) | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 4/62 (6%) 1/60 (2%) 3/61 (5%) 1/61 (2%) | 0/60 (0%) 2/60 (3%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 16.6% 2.9% 9.1% 2.5% | 0.0% 5.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 3/22 (14%) 1/35 (3%) 3/33 (9%) 0/31 (0%) | 0/23 (0%) 2/40 (5%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 683 725 (T) 725 (T) 659 | --- 725 (T) --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.133N P=0.078N P=0.300N P=0.106N | P=0.371N P=0.367 (e) (e) | |INCIDENTAL TUMOR | P=0.155N P=0.106N P=0.336N P=0.152N | P=0.371N P=0.367 (e) (e) | |LOGISTIC REGRESSION | P=0.160N P=0.108N P=0.369N P=0.142N | P=0.371N P=0.367 (e) (e) | |COCHRAN-ARMITAGE | P=0.197N | P=0.405N | |FISHER EXACT | P=0.193N P=0.509N P=0.187N | P=0.248 (e) (e) | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 14 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/62 (0%) 1/60 (2%) 0/61 (0%) 2/61 (3%) | 1/60 (2%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 0.0% 2.9% 0.0% 6.2% | 3.4% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 1/35 (3%) 0/33 (0%) 1/31 (3%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | --- 725 (T) --- 697 | 647 --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.160 P=0.593 (e) P=0.301 | P=0.280N P=0.417N P=0.431N P=0.446N | |INCIDENTAL TUMOR | P=0.148 P=0.593 (e) P=0.243 | P=0.303N P=0.612N P=0.473N P=0.531N | |LOGISTIC REGRESSION | P=0.149 P=0.593 (e) P=0.271 | P=0.305N P=0.494N P=0.493N P=0.495N | |COCHRAN-ARMITAGE | P=0.140 | P=0.306N | |FISHER EXACT | P=0.492 (e) P=0.244 | P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| | | |Testes | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 55/62 (89%) 41/60 (68%) 36/61 (59%) 43/61 (70%) | | |ADJUSTED (b) | 98.1% 93.0% 92.2% 95.5% | | |INTERIM SACRIFICE 1 (c)| 9/10 (90%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | | |TERMINAL (d) | 21/22 (95%) 32/35 (91%) 30/33 (91%) 29/31 (94%) | | |FIRST INCIDENCE (DAYS) | 438 448 (I) 592 563 | | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.002N** P<0.001N** P<0.001N** P<0.001N** | | |INCIDENTAL TUMOR | P=0.005N** P<0.001N** P<0.001N** P=0.001N** | | |LOGISTIC REGRESSION | P=0.114N P=0.020N* P=0.001N** P=0.079N | | |COCHRAN-ARMITAGE | P=0.031N* | | |FISHER EXACT | P=0.005N** P<0.001N** P=0.011N* | | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 15 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/62 (5%) 7/59 (12%) 2/60 (3%) 4/59 (7%) | 3/60 (5%) 0/60 (0%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 11.4% 18.6% 4.8% 12.9% | 8.1% 0.0% 5.1% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/9 (11%) 1/9 (11%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 6/35 (17%) 1/33 (3%) 4/31 (13%) | 0/23 (0%) 0/40 (0%) 1/33 (3%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | 600 448 (I) 448 (I) 725 (T) | 620 --- 562 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.404N P=0.348 P=0.395N P=0.649N | P=0.304N P=0.091N P=0.395N P=0.249N | |INCIDENTAL TUMOR | P=0.421N P=0.302 P=0.491N P=0.629 | P=0.433N P=0.279N P=0.637N P=0.439N | |LOGISTIC REGRESSION | P=0.495N P=0.199 P=0.507N P=0.569 | P=0.415N P=0.123N P=0.668N P=0.295N | |COCHRAN-ARMITAGE | P=0.523N | P=0.337N | |FISHER EXACT | P=0.142 P=0.516N P=0.472 | P=0.122N P=0.500N P=0.309N | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/62 (5%) 7/59 (12%) 2/60 (3%) 4/59 (7%) | 4/60 (7%) 0/60 (0%) 2/60 (3%) 1/60 (2%) | |ADJUSTED (b) | 11.4% 18.6% 4.8% 12.9% | 12.1% 0.0% 5.1% 3.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 1/9 (11%) 1/9 (11%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 6/35 (17%) 1/33 (3%) 4/31 (13%) | 1/23 (4%) 0/40 (0%) 1/33 (3%) 1/32 (3%) | |FIRST INCIDENCE (DAYS) | 600 448 (I) 448 (I) 725 (T) | 620 --- 562 725 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.404N P=0.348 P=0.395N P=0.649N | P=0.168N P=0.035N* P=0.232N P=0.128N | |INCIDENTAL TUMOR | P=0.421N P=0.302 P=0.491N P=0.629 | P=0.259N P=0.114N P=0.417N P=0.243N | |LOGISTIC REGRESSION | P=0.495N P=0.199 P=0.507N P=0.569 | P=0.196N P=0.055N P=0.318N P=0.163N | |COCHRAN-ARMITAGE | P=0.523N | P=0.200N | |FISHER EXACT | P=0.142 P=0.516N P=0.472 | P=0.059N P=0.340N P=0.182N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 16 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/62 (2%) 0/59 (0%) 1/60 (2%) 2/59 (3%) | 1/60 (2%) 1/60 (2%) 0/60 (0%) 1/60 (2%) | |ADJUSTED (b) | 4.5% 0.0% 3.0% 5.4% | 2.2% 2.4% 0.0% 3.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 1/22 (5%) 0/35 (0%) 1/33 (3%) 1/31 (3%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 725 (T) --- 725 (T) 589 | 524 701 --- 717 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.282 P=0.407N P=0.669N P=0.590 | P=0.599N P=0.689N P=0.487N P=0.728N | |INCIDENTAL TUMOR | P=0.258 P=0.407N P=0.669N P=0.533 | P=0.623 P=0.474 P=0.795N P=0.654 | |LOGISTIC REGRESSION | P=0.250 P=0.407N P=0.669N P=0.514 | P=0.617N P=0.749 P=0.510N P=0.762N | |COCHRAN-ARMITAGE | P=0.239 | P=0.616N | |FISHER EXACT | P=0.512N P=0.744 P=0.481 | P=0.752N P=0.500N P=0.752N | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/62 (3%) 0/59 (0%) 1/60 (2%) 2/59 (3%) | 1/60 (2%) 1/60 (2%) 0/60 (0%) 1/60 (2%) | |ADJUSTED (b) | 8.2% 0.0% 3.0% 5.4% | 2.2% 2.4% 0.0% 3.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 1/22 (5%) 0/35 (0%) 1/33 (3%) 1/31 (3%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 715 --- 725 (T) 589 | 524 701 --- 717 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.520 P=0.161N P=0.380N P=0.605N | P=0.599N P=0.689N P=0.487N P=0.728N | |INCIDENTAL TUMOR | P=0.462 P=0.241N P=0.440N P=0.685 | P=0.623 P=0.474 P=0.795N P=0.654 | |LOGISTIC REGRESSION | P=0.480 P=0.176N P=0.406N P=0.673N | P=0.617N P=0.749 P=0.510N P=0.762N | |COCHRAN-ARMITAGE | P=0.457 | P=0.616N | |FISHER EXACT | P=0.260N P=0.512N P=0.672 | P=0.752N P=0.500N P=0.752N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 17 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 9/60 (15%) 5/60 (8%) 3/60 (5%) 3/60 (5%) | |ADJUSTED (b) | | 26.9% 12.1% 7.7% 8.0% | |INTERIM SACRIFICE 1 (c)| | 1/9 (11%) 0/9 (0%) 1/9 (11%) 1/10 (10%) | |TERMINAL (d) | | 3/23 (13%) 4/40 (10%) 2/33 (6%) 2/32 (6%) | |FIRST INCIDENCE (DAYS) | | 454 (I) 659 454 (I) 454 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.024N* P=0.051N P=0.026N* P=0.030N* | |INCIDENTAL TUMOR | | P=0.039N* P=0.224N P=0.064N P=0.072N | |LOGISTIC REGRESSION | | P=0.040N* P=0.144N P=0.060N P=0.061N | |COCHRAN-ARMITAGE | | P=0.041N* | |FISHER EXACT | | P=0.197N P=0.063N P=0.063N | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 9/60 (15%) 5/60 (8%) 3/60 (5%) 3/60 (5%) | |ADJUSTED (b) | | 26.9% 12.1% 7.7% 8.0% | |INTERIM SACRIFICE 1 (c)| | 1/9 (11%) 0/9 (0%) 1/9 (11%) 1/10 (10%) | |TERMINAL (d) | | 3/23 (13%) 4/40 (10%) 2/33 (6%) 2/32 (6%) | |FIRST INCIDENCE (DAYS) | | 454 (I) 659 454 (I) 454 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.024N* P=0.051N P=0.026N* P=0.030N* | |INCIDENTAL TUMOR | | P=0.039N* P=0.224N P=0.064N P=0.072N | |LOGISTIC REGRESSION | | P=0.040N* P=0.144N P=0.060N P=0.061N | |COCHRAN-ARMITAGE | | P=0.041N* | |FISHER EXACT | | P=0.197N P=0.063N P=0.063N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 18 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 14/62 (23%) 9/60 (15%) 10/61 (16%) 8/61 (13%) | 9/60 (15%) 17/60 (28%) 20/60 (33%) 13/60 (22%) | |ADJUSTED (b) | 35.3% 20.6% 26.5% 21.1% | 32.3% 38.1% 47.6% 32.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 2/22 (9%) 2/35 (6%) 6/33 (18%) 4/31 (13%) | 6/23 (26%) 13/40 (33%) 12/33 (36%) 6/32 (19%) | |FIRST INCIDENCE (DAYS) | 505 456 651 531 | 524 534 509 454 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.085N P=0.079N P=0.114N P=0.066N | P=0.460 P=0.407 P=0.130 P=0.481 | |INCIDENTAL TUMOR | P=0.235N P=0.605 P=0.584N P=0.255N | P=0.275 P=0.106 P=0.026 * P=0.225 | |LOGISTIC REGRESSION | P=0.210N P=0.495N P=0.515N P=0.224N | P=0.277 P=0.152 P=0.043 * P=0.296 | |COCHRAN-ARMITAGE | P=0.134N | P=0.315 | |FISHER EXACT | P=0.201N P=0.262N P=0.128N | P=0.060 P=0.016 * P=0.240 | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/62 (3%) 2/60 (3%) 2/61 (3%) 0/61 (0%) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | |ADJUSTED (b) | 4.9% 4.9% 5.7% 0.0% | 0.0% 0.0% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 0/22 (0%) 1/35 (3%) 1/33 (3%) 0/31 (0%) | 0/23 (0%) 0/40 (0%) 0/33 (0%) 0/32 (0%) | |FIRST INCIDENCE (DAYS) | 508 527 674 --- | --- --- --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.139N P=0.620N P=0.622N P=0.223N | (e) (e) (e) (e) | |INCIDENTAL TUMOR | P=0.242N P=0.507 P=0.491 P=0.366N | (e) (e) (e) (e) | |LOGISTIC REGRESSION | P=0.166N P=0.661 P=0.691 P=0.249N | (e) (e) (e) (e) | |COCHRAN-ARMITAGE | P=0.166N | (e) | |FISHER EXACT | P=0.678 P=0.684 P=0.252N | (e) (e) (e) | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 19 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 60/62 (97%) 50/60 (83%) 49/61 (80%) 48/61 (79%) | 43/60 (72%) 38/60 (63%) 37/60 (62%) 27/60 (45%) | |ADJUSTED (b) | 100.0% 100.0% 100.0% 100.0% | 89.3% 79.1% 78.1% 66.7% | |INTERIM SACRIFICE 1 (c)| 10/10 (100%) 4/9 (44%) 4/9 (44%) 1/9 (11%) | 3/9 (33%) 1/9 (11%) 1/9 (11%) 1/10 (10%) | |TERMINAL (d) | 22/22 (100%) 35/35 (100%) 33/33 (100%) 31/31 (100%)| 18/23 (78%) 30/40 (75%) 23/33 (70%) 19/32 (59%) | |FIRST INCIDENCE (DAYS) | 438 448 (I) 448 (I) 448 (I) | 374 454 (I) 426 449 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.002N** P<0.001N** P<0.001N** P<0.001N** | P<0.001N** P<0.001N** P=0.009N** P<0.001N** | |INCIDENTAL TUMOR | P<0.001N** P<0.001N** P=0.001N** P<0.001N** | P=0.001N** P=0.135N P=0.150N P=0.002N** | |LOGISTIC REGRESSION | P=0.178N P=0.095N P=0.463N P=0.173N | P=0.001N** P=0.045N* P=0.114N P=0.001N** | |COCHRAN-ARMITAGE | P=0.007N** | P=0.002N** | |FISHER EXACT | P=0.013N* P=0.004N** P=0.002N** | P=0.218N P=0.166N P=0.003N** | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 22/62 (35%) 17/60 (28%) 17/61 (28%) 14/61 (23%) | 18/60 (30%) 23/60 (38%) 20/60 (33%) 15/60 (25%) | |ADJUSTED (b) | 53.0% 37.3% 40.1% 35.7% | 51.8% 47.3% 47.6% 37.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) | |TERMINAL (d) | 5/22 (23%) 7/35 (20%) 9/33 (27%) 7/31 (23%) | 8/23 (35%) 15/40 (38%) 12/33 (36%) 8/32 (25%) | |FIRST INCIDENCE (DAYS) | 505 456 324 531 | 524 276 509 454 (I) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.045N* P=0.059N P=0.075N P=0.031N* | P=0.112N P=0.326N P=0.309N P=0.130N | |INCIDENTAL TUMOR | P=0.143N P=0.543 P=0.558N P=0.168N | P=0.231N P=0.135 P=0.435 P=0.413N | |LOGISTIC REGRESSION | P=0.138N P=0.515N P=0.468N P=0.128N | P=0.217N P=0.346 P=0.487 P=0.401N | |COCHRAN-ARMITAGE | P=0.087N | P=0.199N | |FISHER EXACT | P=0.257N P=0.238N P=0.092N | P=0.221 P=0.422 P=0.342N | |=================================================================================================================================| DATE: 05/20/95 EXPERIMENT: 05214 TEST: 01 PAGE 20 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRANS-DELTA-9-TETRAHYDROCANNABINOL TERMINAL SACRIFICE AT 104 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 12.5 25 50 | 0 12.5 25 50 | | | MG/KG MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 61/62 (98%) 53/60 (88%) 52/61 (85%) 48/61 (79%) | 47/60 (78%) 43/60 (72%) 45/60 (75%) 36/60 (60%) | |ADJUSTED (b) | 100.0% 100.0% 100.0% 100.0% | 92.1% 82.6% 88.2% 79.6% | |INTERIM SACRIFICE 1 (c)| 10/10 (100%) 4/9 (44%) 4/9 (44%) 1/9 (11%) | 3/9 (33%) 1/9 (11%) 1/9 (11%) 1/10 (10%) | |TERMINAL (d) | 22/22 (100%) 35/35 (100%) 33/33 (100%) 31/31 (100%)| 19/23 (83%) 31/40 (78%) 27/33 (82%) 23/32 (72%) | |FIRST INCIDENCE (DAYS) | 438 448 (I) 211 448 (I) | 374 276 426 449 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.001N** P<0.001N** P=0.001N** P<0.001N** | P=0.010N* P=0.001N** P=0.025N* P=0.003N** | |INCIDENTAL TUMOR | P<0.001N** P=0.004N** P=0.013N* P<0.001N** | P=0.020N* P=0.388N P=0.445N P=0.027N* | |LOGISTIC REGRESSION | P=0.091N P=0.660N P=0.629 P=0.105N | P=0.013N* P=0.113N P=0.316N P=0.014N* | |COCHRAN-ARMITAGE | P<0.001N** | P=0.020N* | |FISHER EXACT | P=0.028N* P=0.008N** P<0.001N** | P=0.264N P=0.415N P=0.024N* | |=================================================================================================================================| (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): 448 Female interim sacrifices(days): 454 (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).