TDMS Study 05068-10 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Microbiological Assoc. CODEINE DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 TIME: 01:16:25 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-75178 ROUTE: DOSED FEED NTP C#: 61541B PATHOLOGIST: MISSING CAS: 76-57-3 ------------------------------------------------------------------------------------------------------------------------------------ REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Microbiological Assoc. CODEINE DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 TIME: 01:16:25 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75178 ROUTE: DOSED FEED NTP C#: 61541B PATHOLOGIST: MISSING CAS: 76-57-3 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 Cortex Adrenal Medulla 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: Microbiological Assoc. CODEINE DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 TIME: 01:16:25 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75178 ROUTE: DOSED FEED NTP C#: 61541B PATHOLOGIST: MISSING CAS: 76-57-3 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF THE STUDY OF CODEINE ==================================================================================================== MALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Liver Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma All Organs Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type Benign Tumors Malignant Tumors Malignant and Benign Tumors ==================================================================================================== FEMALE MICE ------------- ORGAN MORPHOLOGY ------- ------------ Liver Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma All Organs Benign Tumors Malignant Tumors ==================================================================================================== DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 1 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 3/60 (5%) 5/60 (8%) 3/60 (5%) | 1/60 (2%) 3/60 (5%) 1/60 (2%) 2/59 (3%) | |ADJUSTED (b) | 7.3% 7.9% 11.1% 7.0% | 2.8% 8.3% 2.3% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 3/41 (7%) 3/38 (8%) 5/45 (11%) 3/43 (7%) | 1/36 (3%) 3/36 (8%) 1/43 (2%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) 729 (T) 729 (T) | 731 (T) 731 (T) 731 (T) 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.563N P=0.628 P=0.408 P=0.641N | P=0.524 P=0.305 P=0.722N P=0.490 | |INCIDENTAL TUMOR | P=0.563N P=0.628 P=0.408 P=0.641N | P=0.524 P=0.305 P=0.722N P=0.490 | |LOGISTIC REGRESSION | P=0.563N P=0.628 P=0.408 P=0.641N | P=0.524 P=0.305 P=0.722N P=0.490 | |COCHRAN-ARMITAGE | P=0.537 | P=0.519 | |FISHER EXACT | P=0.660N P=0.359 P=0.660N | P=0.309 P=0.752N P=0.494 | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 3/60 (5%) 3/60 (5%) 5/60 (8%) 3/60 (5%) | 1/60 (2%) 4/60 (7%) 1/60 (2%) 2/59 (3%) | |ADJUSTED (b) | 7.3% 7.9% 11.1% 7.0% | 2.8% 10.5% 2.3% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 3/41 (7%) 3/38 (8%) 5/45 (11%) 3/43 (7%) | 1/36 (3%) 3/36 (8%) 1/43 (2%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) 729 (T) 729 (T) | 731 (T) 616 731 (T) 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.563N P=0.628 P=0.408 P=0.641N | P=0.597N P=0.184 P=0.722N P=0.490 | |INCIDENTAL TUMOR | P=0.563N P=0.628 P=0.408 P=0.641N | P=0.594 P=0.164 P=0.722N P=0.490 | |LOGISTIC REGRESSION | P=0.563N P=0.628 P=0.408 P=0.641N | P=0.574N P=0.171 P=0.722N P=0.490 | |COCHRAN-ARMITAGE | P=0.537 | P=0.589 | |FISHER EXACT | P=0.660N P=0.359 P=0.660N | P=0.182 P=0.752N P=0.494 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 2 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 2/60 (3%) 1/60 (2%) 0/59 (0%) | |ADJUSTED (b) | 4.5% 2.6% 0.0% 0.0% | 2.1% 5.6% 2.3% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 1/41 (2%) 1/38 (3%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 2/36 (6%) 1/43 (2%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | 546 729 (T) --- --- | 497 731 (T) 731 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.096N P=0.518N P=0.225N P=0.237N | P=0.245N P=0.493 P=0.741N P=0.504N | |INCIDENTAL TUMOR | P=0.112N P=0.564N P=0.481N P=0.235N | P=0.293N P=0.533 P=0.535 P=0.581N | |LOGISTIC REGRESSION | P=0.100N P=0.502N P=0.241N P=0.238N | P=0.247N P=0.496 P=0.756 P=0.493N | |COCHRAN-ARMITAGE | P=0.101N | P=0.251N | |FISHER EXACT | P=0.500N P=0.248N P=0.248N | P=0.500 P=0.752N P=0.504N | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 26/60 (43%) 26/60 (43%) 18/60 (30%) 11/60 (18%) | 14/60 (23%) 11/60 (18%) 13/60 (22%) 5/59 (8%) | |ADJUSTED (b) | 55.8% 58.5% 37.7% 23.4% | 34.3% 26.6% 30.2% 14.3% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 1/10 (10%) 2/10 (20%) 1/10 (10%) | 2/10 (20%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 21/41 (51%) 20/38 (53%) 16/45 (36%) 8/43 (19%) | 11/36 (31%) 7/36 (19%) 13/43 (30%) 5/35 (14%) | |FIRST INCIDENCE (DAYS) | 456 (I) 456 (I) 456 (I) 456 (I) | 457 (I) 457 (I) 731 (T) 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P<0.001N** P=0.458 P=0.046N* P=0.002N** | P=0.022N* P=0.343N P=0.324N P=0.026N* | |INCIDENTAL TUMOR | P<0.001N** P=0.541 P=0.061N P=0.001N** | P=0.023N* P=0.359N P=0.407N P=0.029N* | |LOGISTIC REGRESSION | P<0.001N** P=0.559 P=0.069N P=0.002N** | P=0.018N* P=0.347N P=0.411N P=0.021N* | |COCHRAN-ARMITAGE | P<0.001N** | P=0.027N* | |FISHER EXACT | P=0.573N P=0.092N P=0.003N** | P=0.327N P=0.500N P=0.024N* | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 3 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 13/60 (22%) 8/60 (13%) 13/60 (22%) 8/60 (13%) | 5/60 (8%) 7/60 (12%) 6/60 (10%) 4/59 (7%) | |ADJUSTED (b) | 28.2% 17.8% 27.1% 17.0% | 12.5% 17.2% 14.0% 10.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 8/41 (20%) 3/38 (8%) 10/45 (22%) 5/43 (12%) | 3/36 (8%) 4/36 (11%) 6/43 (14%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 497 396 635 456 (I) | 565 457 (I) 731 (T) 720 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.183N P=0.214N P=0.480N P=0.153N | P=0.345N P=0.371 P=0.610 P=0.501N | |INCIDENTAL TUMOR | P=0.329N P=0.074N P=0.514 P=0.204N | P=0.305N P=0.317 P=0.447 P=0.463N | |LOGISTIC REGRESSION | P=0.298N P=0.155N P=0.493 P=0.242N | P=0.334N P=0.367 P=0.554 P=0.496N | |COCHRAN-ARMITAGE | P=0.228N | P=0.364N | |FISHER EXACT | P=0.168N P=0.588N P=0.168N | P=0.381 P=0.500 P=0.511N | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 13/60 (22%) 9/60 (15%) 13/60 (22%) 8/60 (13%) | 5/60 (8%) 7/60 (12%) 6/60 (10%) 4/59 (7%) | |ADJUSTED (b) | 28.2% 19.7% 27.1% 17.0% | 12.5% 17.2% 14.0% 10.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 0/10 (0%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 8/41 (20%) 3/38 (8%) 10/45 (22%) 5/43 (12%) | 3/36 (8%) 4/36 (11%) 6/43 (14%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 497 396 635 456 (I) | 565 457 (I) 731 (T) 720 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.163N P=0.290N P=0.480N P=0.153N | P=0.345N P=0.371 P=0.610 P=0.501N | |INCIDENTAL TUMOR | P=0.339N P=0.105N P=0.514 P=0.204N | P=0.305N P=0.317 P=0.447 P=0.463N | |LOGISTIC REGRESSION | P=0.289N P=0.218N P=0.493 P=0.242N | P=0.334N P=0.367 P=0.554 P=0.496N | |COCHRAN-ARMITAGE | P=0.205N | P=0.364N | |FISHER EXACT | P=0.240N P=0.588N P=0.168N | P=0.381 P=0.500 P=0.511N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 4 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 32/60 (53%) 30/60 (50%) 25/60 (42%) 18/60 (30%) | 18/60 (30%) 17/60 (28%) 15/60 (25%) 8/59 (14%) | |ADJUSTED (b) | 64.9% 63.3% 49.7% 36.3% | 42.3% 39.6% 34.9% 21.4% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 1/10 (10%) 2/10 (20%) 2/10 (20%) | 2/10 (20%) 2/9 (22%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 24/41 (59%) 21/38 (55%) 20/45 (44%) 12/43 (28%) | 13/36 (36%) 11/36 (31%) 15/43 (35%) 6/35 (17%) | |FIRST INCIDENCE (DAYS) | 456 (I) 396 456 (I) 456 (I) | 457 (I) 457 (I) 731 (T) 720 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.002N** P=0.550N P=0.073N P=0.008N** | P=0.013N* P=0.522N P=0.176N P=0.029N* | |INCIDENTAL TUMOR | P=0.003N** P=0.379N P=0.112N P=0.006N** | P=0.011N* P=0.566N P=0.318N P=0.026N* | |LOGISTIC REGRESSION | P=0.002N** P=0.443N P=0.095N P=0.007N** | P=0.010N** P=0.530N P=0.260N P=0.021N* | |COCHRAN-ARMITAGE | P=0.003N** | P=0.016N* | |FISHER EXACT | P=0.428N P=0.136N P=0.008N** | P=0.500N P=0.342N P=0.025N* | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 32/60 (53%) 31/60 (52%) 25/60 (42%) 18/60 (30%) | 18/60 (30%) 17/60 (28%) 15/60 (25%) 8/59 (14%) | |ADJUSTED (b) | 64.9% 64.1% 49.7% 36.3% | 42.3% 39.6% 34.9% 21.4% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 1/10 (10%) 2/10 (20%) 2/10 (20%) | 2/10 (20%) 2/9 (22%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 24/41 (59%) 21/38 (55%) 20/45 (44%) 12/43 (28%) | 13/36 (36%) 11/36 (31%) 15/43 (35%) 6/35 (17%) | |FIRST INCIDENCE (DAYS) | 456 (I) 396 456 (I) 456 (I) | 457 (I) 457 (I) 731 (T) 720 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.002N** P=0.516 P=0.073N P=0.008N** | P=0.013N* P=0.522N P=0.176N P=0.029N* | |INCIDENTAL TUMOR | P=0.004N** P=0.434N P=0.112N P=0.006N** | P=0.011N* P=0.566N P=0.318N P=0.026N* | |LOGISTIC REGRESSION | P=0.003N** P=0.519N P=0.095N P=0.007N** | P=0.010N** P=0.530N P=0.260N P=0.021N* | |COCHRAN-ARMITAGE | P=0.003N** | P=0.016N* | |FISHER EXACT | P=0.500N P=0.136N P=0.008N** | P=0.500N P=0.342N P=0.025N* | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 5 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 16/60 (27%) 8/60 (13%) 14/60 (23%) 9/60 (15%) | 3/60 (5%) 3/60 (5%) 6/60 (10%) 4/59 (7%) | |ADJUSTED (b) | 37.7% 20.1% 30.4% 19.1% | 6.1% 7.3% 13.5% 10.4% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 2/10 (20%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 15/41 (37%) 7/38 (18%) 13/45 (29%) 7/43 (16%) | 1/36 (3%) 2/36 (6%) 5/43 (12%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 456 (I) 474 727 401 | 457 (I) 457 (I) 724 711 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.105N P=0.073N P=0.304N P=0.069N | P=0.359 P=0.639 P=0.309 P=0.485 | |INCIDENTAL TUMOR | P=0.105N P=0.080N P=0.293N P=0.069N | P=0.402 P=0.639 P=0.281 P=0.529 | |LOGISTIC REGRESSION | P=0.130N P=0.054N P=0.309N P=0.081N | P=0.365 P=0.650N P=0.253 P=0.491 | |COCHRAN-ARMITAGE | P=0.155N | P=0.353 | |FISHER EXACT | P=0.054N P=0.417N P=0.088N | P=0.660N P=0.245 P=0.491 | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/60 (2%) 2/60 (3%) 2/60 (3%) 2/60 (3%) | 1/60 (2%) 1/60 (2%) 1/60 (2%) 0/59 (0%) | |ADJUSTED (b) | 2.4% 4.7% 4.4% 4.7% | 2.8% 2.8% 2.3% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 1/41 (2%) 1/38 (3%) 2/45 (4%) 2/43 (5%) | 1/36 (3%) 1/36 (3%) 1/43 (2%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 474 729 (T) 729 (T) | 731 (T) 731 (T) 731 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.452 P=0.482 P=0.533 P=0.517 | P=0.308N P=0.762 P=0.722N P=0.506N | |INCIDENTAL TUMOR | P=0.453 P=0.436 P=0.533 P=0.517 | P=0.308N P=0.762 P=0.722N P=0.506N | |LOGISTIC REGRESSION | P=0.430 P=0.501 P=0.533 P=0.517 | P=0.308N P=0.762 P=0.722N P=0.506N | |COCHRAN-ARMITAGE | P=0.423 | P=0.315N | |FISHER EXACT | P=0.500 P=0.500 P=0.500 | P=0.752N P=0.752N P=0.504N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 6 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 16/60 (27%) 9/60 (15%) 16/60 (27%) 11/60 (18%) | 4/60 (7%) 4/60 (7%) 7/60 (12%) 4/59 (7%) | |ADJUSTED (b) | 37.7% 22.7% 34.8% 23.6% | 8.8% 10.0% 15.8% 10.4% | |INTERIM SACRIFICE 1 (c)| 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 2/10 (20%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 15/41 (37%) 8/38 (21%) 15/45 (33%) 9/43 (21%) | 2/36 (6%) 3/36 (8%) 6/43 (14%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 456 (I) 474 727 401 | 457 (I) 457 (I) 724 711 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.217N P=0.117N P=0.461N P=0.155N | P=0.513 P=0.622 P=0.344 P=0.626 | |INCIDENTAL TUMOR | P=0.217N P=0.126N P=0.449N P=0.155N | P=0.553 P=0.622 P=0.318 P=0.619N | |LOGISTIC REGRESSION | P=0.260N P=0.088N P=0.468N P=0.176N | P=0.525 P=0.641N P=0.283 P=0.636 | |COCHRAN-ARMITAGE | P=0.298N | P=0.505 | |FISHER EXACT | P=0.088N P=0.582N P=0.191N | P=0.641N P=0.264 P=0.632 | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | 0/60 (0%) 0/60 (0%) 2/60 (3%) 2/59 (3%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 0.0% 0.0% 4.4% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 0/36 (0%) 1/43 (2%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | --- --- 643 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.083 (e) P=0.277 P=0.232 | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.090 (e) P=0.118 P=0.232 | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.089 (e) P=0.247 P=0.232 | |COCHRAN-ARMITAGE | (e) | P=0.084 | |FISHER EXACT | (e) (e) (e) | (e) P=0.248 P=0.244 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 7 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | | 2/58 (3%) 3/60 (5%) 0/59 (0%) 2/59 (3%) | |ADJUSTED (b) | | 5.6% 8.3% 0.0% 5.7% | |INTERIM SACRIFICE 1 (c)| | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | | 2/36 (6%) 3/36 (8%) 0/43 (0%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | | 731 (T) 731 (T) --- 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.476N P=0.500 P=0.200N P=0.685 | |INCIDENTAL TUMOR | | P=0.476N P=0.500 P=0.200N P=0.685 | |LOGISTIC REGRESSION | | P=0.476N P=0.500 P=0.200N P=0.685 | |COCHRAN-ARMITAGE | | P=0.471N | |FISHER EXACT | | P=0.516 P=0.244N P=0.684N | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/56 (0%) 0/59 (0%) 0/58 (0%) 0/55 (0%) | 11/58 (19%) 9/56 (16%) 17/58 (29%) 10/55 (18%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 29.7% 25.9% 39.4% 30.3% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/39 (0%) 0/37 (0%) 0/45 (0%) 0/42 (0%) | 10/36 (28%) 8/33 (24%) 16/42 (38%) 10/33 (30%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | 722 512 703 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.473 P=0.482N P=0.264 P=0.586N | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.480 P=0.455N P=0.231 P=0.571N | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.532N P=0.503N P=0.270 P=0.528N | |COCHRAN-ARMITAGE | (e) | P=0.463 | |FISHER EXACT | (e) (e) (e) | P=0.437N P=0.139 P=0.554N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 8 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/56 (0%) 0/59 (0%) 0/58 (0%) 0/55 (0%) | 11/58 (19%) 9/56 (16%) 18/58 (31%) 10/55 (18%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 29.7% 25.9% 41.7% 30.3% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/39 (0%) 0/37 (0%) 0/45 (0%) 0/42 (0%) | 10/36 (28%) 8/33 (24%) 17/42 (40%) 10/33 (30%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | 722 512 703 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.460 P=0.482N P=0.202 P=0.586N | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.468 P=0.455N P=0.174 P=0.571N | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.542N P=0.503N P=0.207 P=0.528N | |COCHRAN-ARMITAGE | (e) | P=0.451 | |FISHER EXACT | (e) (e) (e) | P=0.437N P=0.099 P=0.554N | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/56 (0%) 0/59 (0%) 0/58 (0%) 0/55 (0%) | 1/58 (2%) 1/56 (2%) 3/58 (5%) 1/55 (2%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 2.3% 2.7% 7.1% 3.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/39 (0%) 0/37 (0%) 0/45 (0%) 0/42 (0%) | 0/36 (0%) 0/33 (0%) 3/42 (7%) 1/33 (3%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | 570 677 731 (T) 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.556 P=0.752 P=0.357 P=0.753 | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.550 P=0.703 P=0.234 P=0.719 | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.553 P=0.762 P=0.320 P=0.751 | |COCHRAN-ARMITAGE | (e) | P=0.540 | |FISHER EXACT | (e) (e) (e) | P=0.743 P=0.309 P=0.739 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 9 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Carcinoma or Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/56 (2%) 0/59 (0%) 0/58 (0%) 0/55 (0%) | 1/58 (2%) 1/56 (2%) 3/58 (5%) 1/55 (2%) | |ADJUSTED (b) | 2.1% 0.0% 0.0% 0.0% | 2.3% 2.7% 7.1% 3.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/9 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/39 (0%) 0/37 (0%) 0/45 (0%) 0/42 (0%) | 0/36 (0%) 0/33 (0%) 3/42 (7%) 1/33 (3%) | |FIRST INCIDENCE (DAYS) | 546 --- --- --- | 570 677 731 (T) 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.307N P=0.500N P=0.492N P=0.504N | P=0.556 P=0.752 P=0.357 P=0.753 | |INCIDENTAL TUMOR | P=0.399N P=0.581N (e) P=0.581N | P=0.550 P=0.703 P=0.234 P=0.719 | |LOGISTIC REGRESSION | P=0.313N P=0.455N P=0.471N P=0.517N | P=0.553 P=0.762 P=0.320 P=0.751 | |COCHRAN-ARMITAGE | P=0.308N | P=0.540 | |FISHER EXACT | P=0.487N P=0.491N P=0.505N | P=0.743 P=0.309 P=0.739 | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 4/60 (7%) 1/60 (2%) 2/59 (3%) | |ADJUSTED (b) | 3.9% 2.2% 0.0% 0.0% | 2.8% 10.6% 2.2% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 1/36 (3%) 3/36 (8%) 0/43 (0%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 227 566 --- --- | 731 (T) 647 727 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.099N P=0.505N P=0.230N P=0.237N | P=0.595N P=0.180 P=0.715N P=0.490 | |INCIDENTAL TUMOR | P=0.221N P=0.378N P=0.353N P=0.500N | P=0.550N P=0.168 P=0.756 P=0.490 | |LOGISTIC REGRESSION | P=0.085N P=0.431N P=0.182N P=0.168N | P=0.572N P=0.170 P=0.722N P=0.490 | |COCHRAN-ARMITAGE | P=0.101N | P=0.589 | |FISHER EXACT | P=0.500N P=0.248N P=0.248N | P=0.182 P=0.752N P=0.494 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 10 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | 0/60 (0%) 2/60 (3%) 0/60 (0%) 0/59 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 0.0% 5.2% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 1/36 (3%) 0/43 (0%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | --- 647 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.399N P=0.237 (e) (e) | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.365N P=0.215 (e) (e) | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.401N P=0.232 (e) (e) | |COCHRAN-ARMITAGE | (e) | P=0.408N | |FISHER EXACT | (e) (e) (e) | P=0.248 (e) (e) | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 4/60 (7%) 1/60 (2%) 2/59 (3%) | |ADJUSTED (b) | 3.9% 2.2% 0.0% 0.0% | 2.8% 10.6% 2.2% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 1/36 (3%) 3/36 (8%) 0/43 (0%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 227 566 --- --- | 731 (T) 647 727 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.099N P=0.505N P=0.230N P=0.237N | P=0.595N P=0.180 P=0.715N P=0.490 | |INCIDENTAL TUMOR | P=0.221N P=0.378N P=0.353N P=0.500N | P=0.550N P=0.168 P=0.756 P=0.490 | |LOGISTIC REGRESSION | P=0.085N P=0.431N P=0.182N P=0.168N | P=0.572N P=0.170 P=0.722N P=0.490 | |COCHRAN-ARMITAGE | P=0.101N | P=0.589 | |FISHER EXACT | P=0.500N P=0.248N P=0.248N | P=0.182 P=0.752N P=0.494 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 11 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Skin | | Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 2/60 (3%) 1/60 (2%) 2/59 (3%) | |ADJUSTED (b) | 3.9% 2.2% 0.0% 0.0% | 2.8% 5.6% 2.2% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 1/36 (3%) 2/36 (6%) 0/43 (0%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 227 566 --- --- | 731 (T) 731 (T) 727 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.099N P=0.505N P=0.230N P=0.237N | P=0.444 P=0.500 P=0.715N P=0.490 | |INCIDENTAL TUMOR | P=0.221N P=0.378N P=0.353N P=0.500N | P=0.470 P=0.500 P=0.756 P=0.490 | |LOGISTIC REGRESSION | P=0.085N P=0.431N P=0.182N P=0.168N | P=0.471 P=0.500 P=0.722N P=0.490 | |COCHRAN-ARMITAGE | P=0.101N | P=0.438 | |FISHER EXACT | P=0.500N P=0.248N P=0.248N | P=0.500 P=0.752N P=0.494 | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/59 (2%) 2/60 (3%) 2/60 (3%) 2/60 (3%) | 1/58 (2%) 4/60 (7%) 3/60 (5%) 2/59 (3%) | |ADJUSTED (b) | 2.4% 5.3% 4.4% 4.7% | 1.7% 11.1% 7.0% 5.7% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 1/10 (10%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 1/41 (2%) 2/38 (5%) 2/45 (4%) 2/43 (5%) | 0/34 (0%) 4/36 (11%) 3/43 (7%) 2/35 (6%) | |FIRST INCIDENCE (DAYS) | 729 (T) 729 (T) 729 (T) 729 (T) | 457 (I) 731 (T) 731 (T) 731 (T) | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.456 P=0.473 P=0.533 P=0.517 | P=0.557 P=0.189 P=0.361 P=0.495 | |INCIDENTAL TUMOR | P=0.456 P=0.473 P=0.533 P=0.517 | P=0.557 P=0.189 P=0.361 P=0.495 | |LOGISTIC REGRESSION | P=0.456 P=0.473 P=0.533 P=0.517 | P=0.577 P=0.186 P=0.322 P=0.506 | |COCHRAN-ARMITAGE | P=0.428 | P=0.548 | |FISHER EXACT | P=0.506 P=0.506 P=0.506 | P=0.193 P=0.322 P=0.506 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 12 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | # # # # | |----------- | | | |OVERALL (a) | | 4/60 (7%) 0/60 (0%) 2/60 (3%) 0/59 (0%) | |ADJUSTED (b) | | 10.6% 0.0% 4.7% 0.0% | |INTERIM SACRIFICE 1 (c)| | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | | 3/36 (8%) 0/36 (0%) 2/43 (5%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | | 651 --- 731 (T) --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | | P=0.057N P=0.066N P=0.263N P=0.067N | |INCIDENTAL TUMOR | | P=0.054N P=0.072N P=0.288N P=0.056N | |LOGISTIC REGRESSION | | P=0.054N P=0.066N P=0.281N P=0.059N | |COCHRAN-ARMITAGE | | P=0.064N | |FISHER EXACT | | P=0.059N P=0.340N P=0.061N | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 1/60 (2%) 2/60 (3%) 1/59 (2%) | |ADJUSTED (b) | 4.9% 2.1% 0.0% 0.0% | 2.6% 2.6% 4.4% 2.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 2/41 (5%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 0/36 (0%) 1/43 (2%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 559 --- --- | 713 664 703 506 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.095N P=0.515N P=0.218N P=0.228N | P=0.610 P=0.754 P=0.567 P=0.757N | |INCIDENTAL TUMOR | P=0.139N P=0.459N P=0.218N P=0.228N | P=0.608N P=0.723 P=0.468 P=0.757 | |LOGISTIC REGRESSION | P=0.100N P=0.502N P=0.218N P=0.228N | P=0.524 P=0.757 P=0.428 P=0.759 | |COCHRAN-ARMITAGE | P=0.101N | P=0.585 | |FISHER EXACT | P=0.500N P=0.248N P=0.248N | P=0.752N P=0.500 P=0.748 | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 13 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 2/60 (3%) 1/60 (2%) 0/60 (0%) 0/60 (0%) | 1/60 (2%) 2/60 (3%) 3/60 (5%) 1/59 (2%) | |ADJUSTED (b) | 4.9% 2.1% 0.0% 0.0% | 2.6% 5.3% 6.7% 2.1% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 2/41 (5%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 1/36 (3%) 2/43 (5%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | 729 (T) 559 --- --- | 713 664 703 506 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.095N P=0.515N P=0.218N P=0.228N | P=0.562N P=0.494 P=0.377 P=0.757N | |INCIDENTAL TUMOR | P=0.139N P=0.459N P=0.218N P=0.228N | P=0.543N P=0.446 P=0.293 P=0.757 | |LOGISTIC REGRESSION | P=0.100N P=0.502N P=0.218N P=0.228N | P=0.574N P=0.491 P=0.352 P=0.759 | |COCHRAN-ARMITAGE | P=0.101N | P=0.584N | |FISHER EXACT | P=0.500N P=0.248N P=0.248N | P=0.500 P=0.309 P=0.748 | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 2/60 (3%) 0/60 (0%) 2/60 (3%) | 2/60 (3%) 2/60 (3%) 0/60 (0%) 1/59 (2%) | |ADJUSTED (b) | 0.0% 5.0% 0.0% 4.7% | 4.8% 4.9% 0.0% 2.2% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 1/38 (3%) 0/45 (0%) 2/43 (5%) | 1/36 (3%) 0/36 (0%) 0/43 (0%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | --- 716 --- 729 (T) | 530 625 --- 598 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.269 P=0.231 (e) P=0.249 | P=0.282N P=0.685 P=0.218N P=0.495N | |INCIDENTAL TUMOR | P=0.271 P=0.304 (e) P=0.249 | P=0.325N P=0.673 P=0.465N P=0.550N | |LOGISTIC REGRESSION | P=0.263 P=0.234 (e) P=0.249 | P=0.423N P=0.680 P=0.242N P=0.506N | |COCHRAN-ARMITAGE | P=0.248 | P=0.301N | |FISHER EXACT | P=0.248 (e) P=0.248 | P=0.691N P=0.248N P=0.506N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 14 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated | | Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 7/60 (12%) 1/60 (2%) 1/60 (2%) 0/60 (0%) | 8/60 (13%) 5/60 (8%) 6/60 (10%) 8/59 (14%) | |ADJUSTED (b) | 15.1% 2.6% 2.2% 0.0% | 18.8% 12.1% 12.8% 19.6% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 1/10 (10%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 4/41 (10%) 1/38 (3%) 1/45 (2%) 0/43 (0%) | 4/36 (11%) 3/36 (8%) 2/43 (5%) 4/35 (11%) | |FIRST INCIDENCE (DAYS) | 450 729 (T) 729 (T) --- | 457 (I) 348 703 556 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.003N** P=0.043N* P=0.028N* P=0.010N** | P=0.477 P=0.294N P=0.281N P=0.599 | |INCIDENTAL TUMOR | P=0.007N** P=0.029N* P=0.089N P=0.032N* | P=0.521 P=0.278N P=0.586N P=0.592N | |LOGISTIC REGRESSION | P=0.003N** P=0.034N* P=0.034N* P=0.010N** | P=0.461 P=0.283N P=0.356N P=0.535 | |COCHRAN-ARMITAGE | P=0.003N** | P=0.445 | |FISHER EXACT | P=0.031N* P=0.031N* P=0.006N** | P=0.279N P=0.389N P=0.591 | |=================================================================================================================================| | | |All Organs | | Osteosarcoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | 0/60 (0%) 2/60 (3%) 0/60 (0%) 0/59 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 0.0% 4.5% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 1/36 (3%) 0/43 (0%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | --- 359 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.406N P=0.238 (e) (e) | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.422N P=0.314 (e) (e) | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.410N P=0.251 (e) (e) | |COCHRAN-ARMITAGE | (e) | P=0.408N | |FISHER EXACT | (e) (e) (e) | P=0.248 (e) (e) | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 15 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Osteosarcoma or Osteoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 0/60 (0%) 0/60 (0%) 0/60 (0%) 0/60 (0%) | 0/60 (0%) 2/60 (3%) 0/60 (0%) 0/59 (0%) | |ADJUSTED (b) | 0.0% 0.0% 0.0% 0.0% | 0.0% 4.5% 0.0% 0.0% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 0/41 (0%) 0/38 (0%) 0/45 (0%) 0/43 (0%) | 0/36 (0%) 1/36 (3%) 0/43 (0%) 0/35 (0%) | |FIRST INCIDENCE (DAYS) | --- --- --- --- | --- 359 --- --- | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | (e) (e) (e) (e) | P=0.406N P=0.238 (e) (e) | |INCIDENTAL TUMOR | (e) (e) (e) (e) | P=0.422N P=0.314 (e) (e) | |LOGISTIC REGRESSION | (e) (e) (e) (e) | P=0.410N P=0.251 (e) (e) | |COCHRAN-ARMITAGE | (e) | P=0.408N | |FISHER EXACT | (e) (e) (e) | P=0.248 (e) (e) | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 37/60 (62%) 33/60 (55%) 32/60 (53%) 24/60 (40%) | 30/60 (50%) 27/60 (45%) 33/60 (55%) 19/59 (32%) | |ADJUSTED (b) | 78.4% 74.7% 65.0% 48.1% | 67.1% 62.2% 73.3% 51.1% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 1/10 (10%) 2/10 (20%) 3/10 (30%) | 4/10 (40%) 2/9 (22%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 31/41 (76%) 27/38 (71%) 28/45 (62%) 18/43 (42%) | 22/36 (61%) 20/36 (56%) 31/43 (72%) 17/35 (49%) | |FIRST INCIDENCE (DAYS) | 456 (I) 456 (I) 456 (I) 401 | 457 (I) 457 (I) 703 711 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.003N** P=0.441N P=0.093N P=0.009N** | P=0.027N* P=0.389N P=0.428N P=0.037N* | |INCIDENTAL TUMOR | P=0.004N** P=0.363N P=0.176N P=0.005N** | P=0.019N* P=0.415N P=0.536 P=0.028N* | |LOGISTIC REGRESSION | P=0.005N** P=0.290N P=0.137N P=0.011N* | P=0.015N* P=0.402N P=0.528 P=0.022N* | |COCHRAN-ARMITAGE | P=0.010N* | P=0.041N* | |FISHER EXACT | P=0.289N P=0.230N P=0.014N* | P=0.357N P=0.357 P=0.037N* | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 16 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE TERMINAL SACRIFICE AT 105 WEEKS |=================================================================================================================================| | | | | | | MALES | FEMALES | | | | | |DOSE | 0 PPM 750 PPM 1500 PPM 3000 PPM | 0 PPM 750 PPM 1500 PPM 3000 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 20/60 (33%) 15/60 (25%) 15/60 (25%) 11/60 (18%) | 16/60 (27%) 25/60 (42%) 17/60 (28%) 19/59 (32%) | |ADJUSTED (b) | 39.6% 31.1% 31.2% 23.6% | 35.4% 52.4% 34.5% 41.5% | |INTERIM SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | 1/10 (10%) 1/9 (11%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 11/41 (27%) 6/38 (16%) 12/45 (27%) 8/43 (19%) | 8/36 (22%) 14/36 (39%) 11/43 (26%) 9/35 (26%) | |FIRST INCIDENCE (DAYS) | 227 396 635 456 (I) | 457 (I) 348 329 397 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.038N* P=0.280N P=0.153N P=0.049N* | P=0.519N P=0.079 P=0.459N P=0.357 | |INCIDENTAL TUMOR | P=0.124N P=0.077N P=0.421N P=0.079N | P=0.507N P=0.041 * P=0.231 P=0.333 | |LOGISTIC REGRESSION | P=0.044N* P=0.208N P=0.194N P=0.047N* | P=0.524 P=0.055 P=0.546 P=0.241 | |COCHRAN-ARMITAGE | P=0.047N* | P=0.501 | |FISHER EXACT | P=0.211N P=0.211N P=0.047N* | P=0.062 P=0.500 P=0.322 | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | # # # # | |----------- | | | |OVERALL (a) | 44/60 (73%) 40/60 (67%) 38/60 (63%) 32/60 (53%) | 38/60 (63%) 39/60 (65%) 38/60 (63%) 31/59 (53%) | |ADJUSTED (b) | 82.8% 81.4% 75.8% 61.0% | 75.5% 77.6% 77.5% 67.1% | |INTERIM SACRIFICE 1 (c)| 3/10 (30%) 1/10 (10%) 2/10 (20%) 4/10 (40%) | 4/10 (40%) 3/9 (33%) 0/9 (0%) 0/9 (0%) | |TERMINAL (d) | 32/41 (78%) 29/38 (76%) 33/45 (73%) 23/43 (53%) | 24/36 (67%) 25/36 (69%) 32/43 (74%) 20/35 (57%) | |FIRST INCIDENCE (DAYS) | 227 396 456 (I) 401 | 457 (I) 348 329 397 | |-----------------------| | | |STATISTICAL TESTS (f) | | | |-----------------------| | | |LIFE TABLE | P=0.007N** P=0.460N P=0.067N P=0.021N* | P=0.107N P=0.462 P=0.211N P=0.197N | |INCIDENTAL TUMOR | P=0.015N* P=0.223N P=0.207N P=0.022N* | P=0.056N P=0.440 P=0.431 P=0.122N | |LOGISTIC REGRESSION | P=0.008N** P=0.286N P=0.102N P=0.017N* | P=0.063N P=0.446 P=0.444N P=0.132N | |COCHRAN-ARMITAGE | P=0.013N* | P=0.102N | |FISHER EXACT | P=0.275N P=0.163N P=0.018N* | P=0.500 P=0.575N P=0.157N | |=================================================================================================================================| DATE: 04/03/96 EXPERIMENT: 05068 TEST: 10 PAGE 17 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE 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): 456 Female interim sacrifices(days): 457 (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. The incidental tumor test regards these lesions as non-fatal. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fisher's exact tests compare directly the overall incidence rates. For all tests, a negative trend is indicated by "N". (e) Value of Statistic cannot be computed. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).