TDMS Study 05187-06 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98 EXPERIMENT: 05187 TEST: 06 TIME: 10:22:14 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: TOFT, J. CAS: 93-15-2 ------------------------------------------------------------------------------------------------------------------------------------ CORE STUDY REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98 EXPERIMENT: 05187 TEST: 06 TIME: 10:22:14 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: TOFT, J. CAS: 93-15-2 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 THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Bone Marrow Heart Islets, Pancreatic Kidney Liver Lung Ovary Pancreas Pituitary Gland Prostate Spleen Testes Thyroid Gland NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98 EXPERIMENT: 05187 TEST: 06 TIME: 10:22:14 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: TOFT, J. CAS: 93-15-2 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF METHYLEUGENOL =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Liver Hepatoblastoma Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Stomach, Glandular Neuroendocrine Tumor, Malignant All Organs Benign Tumors Malignant and Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Medulla Pheochromocytoma Benign Harderian Gland Carcinoma Carcinoma or Adenoma Liver Hepatoblastoma Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Hepatocholangiocarcinoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Ovary Cystadenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma Skin Fibrosarcoma All Organs Hemangiosarcoma or Hemangioma Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 1 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 3/50 (6%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 7.6% 3.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 0/35 (0%) |0/31 (0%) 0/18 (0%) 2/18 (11%) 1/2 (50%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 659 731 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.015 * (e) P=0.055 P=0.033 * | |POLY 3 | (e) (e) (e) (e) |P=0.149 (e) P=0.098 P=0.445 | |POLY 1.5 | (e) (e) (e) (e) |P=0.190 (e) P=0.107 P=0.469 | |POLY 6 | (e) (e) (e) (e) |P=0.093 (e) P=0.087 P=0.406 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.091 (e) P=0.088 P=0.033 * | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.241 (e) P=0.121 P=0.495 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 7/50 (14%) 6/50 (12%) |0/50 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.0% 2.2% 16.2% 13.7% |0.0% 5.2% 5.1% 0.0% | |TERMINAL (d) | 3/38 (8%) 1/36 (3%) 7/37 (19%) 5/35 (14%) |0/31 (0%) 1/18 (6%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 570 730 (T) 730 (T) 569 |--- 720 659 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.113 P=0.189N P=0.249 P=0.329 |P=0.397 P=0.146 P=0.155 (e) | |POLY 3 | P=0.123 P=0.168N P=0.247 P=0.362 |P=0.617N P=0.206 P=0.211 (e) | |POLY 1.5 | P=0.127 P=0.172N P=0.248 P=0.365 |P=0.560N P=0.221 P=0.223 (e) | |POLY 6 | P=0.119 P=0.168N P=0.246 P=0.358 |P=0.490 P=0.186 P=0.196 (e) | |LOGISTIC REGRESSION| P=0.126 P=0.178N P=0.256 P=0.366 |P=0.618 P=0.149 P=0.217 (e) | |COCH-ARM / FISHERS | P=0.137 P=0.181N P=0.262 P=0.370 |P=0.498N P=0.247 P=0.247 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 2 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |5/50 (10%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |11.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 0/35 (0%) |2/31 (7%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- --- |652 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.038N* P=0.100N P=0.090N P=0.282N | |POLY 3 | (e) (e) (e) (e) |P=0.006N** P=0.046N* P=0.044N* P=0.061N | |POLY 1.5 | (e) (e) (e) (e) |P=0.007N** P=0.038N* P=0.037N* P=0.044N* | |POLY 6 | (e) (e) (e) (e) |P=0.006N** P=0.062N P=0.055N P=0.100N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.014N* P=0.044N* P=0.041N* P=0.065N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.009N** P=0.028N* P=0.028N* P=0.028N* | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 7/50 (14%) 6/50 (12%) |5/50 (10%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.0% 2.2% 16.2% 13.7% |11.1% 5.2% 5.1% 0.0% | |TERMINAL (d) | 3/38 (8%) 1/36 (3%) 7/37 (19%) 5/35 (14%) |2/31 (7%) 1/18 (6%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 570 730 (T) 730 (T) 569 |652 720 659 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.113 P=0.189N P=0.249 P=0.329 |P=0.184N P=0.451N P=0.422N P=0.282N | |POLY 3 | P=0.123 P=0.168N P=0.247 P=0.362 |P=0.033N* P=0.285N P=0.274N P=0.061N | |POLY 1.5 | P=0.127 P=0.172N P=0.248 P=0.365 |P=0.027N* P=0.250N P=0.247N P=0.044N* | |POLY 6 | P=0.119 P=0.168N P=0.246 P=0.358 |P=0.048N* P=0.340N P=0.312N P=0.100N | |LOGISTIC REGRESSION| P=0.126 P=0.178N P=0.256 P=0.366 |P=0.052N P=0.317N P=0.257N P=0.065N | |COCH-ARM / FISHERS | P=0.137 P=0.181N P=0.262 P=0.370 |P=0.022N* P=0.218N P=0.218N P=0.028N* | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 3 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 3/50 (6%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 6.5% 0.0% 4.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/38 (0%) 2/36 (6%) 0/37 (0%) 2/35 (6%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- 614 --- 730 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.333 P=0.125 (e) P=0.220 |(e) (e) (e) (e) | |POLY 3 | P=0.351 P=0.130 (e) P=0.236 |(e) (e) (e) (e) | |POLY 1.5 | P=0.353 P=0.128 (e) P=0.238 |(e) (e) (e) (e) | |POLY 6 | P=0.347 P=0.132 (e) P=0.234 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.350 P=0.118 (e) P=0.220 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.359 P=0.125 (e) P=0.253 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 1/50 (2%) 3/50 (6%) |0/50 (0%) 6/50 (12%) 11/49 (22%) 15/50 (30%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.3% 6.8% |0.0% 15.3% 27.4% 39.3% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 1/37 (3%) 1/35 (3%) |0/31 (0%) 2/18 (11%) 6/18 (33%) 2/2 (100%) | |FIRST INCIDENCE | --- --- 730 (T) 554 |--- 627 628 505 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.019 * (e) P=0.495 P=0.121 |P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.019 * (e) P=0.500 P=0.122 |P<0.001 ** P=0.009 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.019 * (e) P=0.500 P=0.122 |P<0.001 ** P=0.012 * P<0.001 ** P<0.001 ** | |POLY 6 | P=0.019 * (e) P=0.500 P=0.123 |P<0.001 ** P=0.007 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.022 * (e) P=0.495 P=0.138 |P<0.001 ** P=0.010 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.021 * (e) P=0.505 P=0.125 |P<0.001 ** P=0.013 * P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 4 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 26/49 (53%) 43/50 (86%) 38/50 (76%) 39/50 (78%) |20/50 (40%) 48/50 (96%) 46/49 (94%) 41/50 (82%) | |POLY-3 ADJUSTED (b)| 57.1% 91.1% 85.8% 84.0% |44.4% 96.6% 94.4% 86.5% | |TERMINAL (d) | 22/38 (58%) 35/36 (97%) 35/37 (95%) 30/35 (86%) |16/31 (52%) 18/18 (100%) 16/18 (89%) 1/2 (50%) | |FIRST INCIDENCE | 430 614 589 512 |665 477 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.008 ** P<0.001 ** P=0.005 ** P=0.004 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.006 ** P<0.001 ** P<0.001 ** P=0.003 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.010 * P<0.001 ** P=0.003 ** P=0.003 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.005 ** P<0.001 ** P<0.001 ** P=0.002 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.007 ** P<0.001 ** P=0.006 ** P=0.005 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.032 * P<0.001 ** P=0.014 * P=0.008 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/49 (20%) 20/50 (40%) 19/50 (38%) 9/50 (18%) |7/50 (14%) 37/50 (74%) 47/49 (96%) 47/50 (94%) | |POLY-3 ADJUSTED (b)| 21.8% 41.8% 40.1% 20.4% |15.5% 79.5% 96.5% 96.4% | |TERMINAL (d) | 5/38 (13%) 10/36 (28%) 10/37 (27%) 6/35 (17%) |3/31 (10%) 13/18 (72%) 17/18 (94%) 2/2 (100%) | |FIRST INCIDENCE | 477 593 486 579 |665 493 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.325N P=0.043 * P=0.055 P=0.549N |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.309N P=0.030 * P=0.044 * P=0.539N |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.275N P=0.028 * P=0.040 * P=0.517N |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.350N P=0.031 * P=0.049 * P=0.566N |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.210N P=0.019 * P=0.054 P=0.466N |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.228N P=0.028 * P=0.044 * P=0.480N |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 5 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/49 (20%) 20/50 (40%) 20/50 (40%) 11/50 (22%) |7/50 (14%) 38/50 (76%) 48/49 (98%) 49/50 (98%) | |POLY-3 ADJUSTED (b)| 21.8% 41.8% 42.2% 24.6% |15.5% 81.0% 98.0% 99.7% | |TERMINAL (d) | 5/38 (13%) 10/36 (28%) 11/37 (30%) 7/35 (20%) |3/31 (10%) 13/18 (72%) 17/18 (94%) 2/2 (100%) | |FIRST INCIDENCE | 477 593 486 554 |665 493 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.502N P=0.043 * P=0.038 * P=0.451 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.490N P=0.030 * P=0.027 * P=0.471 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.458N P=0.028 * P=0.025 * P=0.490 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.526N P=0.031 * P=0.031 * P=0.449 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.380N P=0.019 * P=0.035 * P=0.540 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.404N P=0.028 * P=0.028 * P=0.521 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 31/49 (63%) 47/50 (94%) 46/50 (92%) 40/50 (80%) |25/50 (50%) 50/50 (100%) 49/49 (100%) 49/50 (98%) | |POLY-3 ADJUSTED (b)| 65.4% 97.4% 96.4% 85.6% |54.8% 100.0% 100.0% 99.7% | |TERMINAL (d) | 23/38 (61%) 36/36 (100%) 36/37 (97%) 30/35 (86%) |18/31 (58%) 18/18 (100%) 18/18 (100%) 2/2 (100%) | |FIRST INCIDENCE | 430 593 486 512 |665 477 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.069 P=0.002 ** P=0.004 ** P=0.036 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.018 * P<0.001 ** P<0.001 ** P=0.016 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.033 * P<0.001 ** P<0.001 ** P=0.024 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.012 * P<0.001 ** P<0.001 ** P=0.012 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.066 P<0.001 ** P<0.001 ** P=0.043 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.116 P<0.001 ** P<0.001 ** P=0.052 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 6 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 31/49 (63%) 47/50 (94%) 46/50 (92%) 41/50 (82%) |25/50 (50%) 50/50 (100%) 49/49 (100%) 49/50 (98%) | |POLY-3 ADJUSTED (b)| 65.4% 97.4% 96.4% 86.7% |54.8% 100.0% 100.0% 99.7% | |TERMINAL (d) | 23/38 (61%) 36/36 (100%) 36/37 (97%) 30/35 (86%) |18/31 (58%) 18/18 (100%) 18/18 (100%) 2/2 (100%) | |FIRST INCIDENCE | 430 593 486 512 |665 477 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.048 * P=0.002 ** P=0.004 ** P=0.026 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.012 * P<0.001 ** P<0.001 ** P=0.011 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.019 * P<0.001 ** P<0.001 ** P=0.014 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.009 ** P<0.001 ** P<0.001 ** P=0.009 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.036 * P<0.001 ** P<0.001 ** P=0.027 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.068 P<0.001 ** P<0.001 ** P=0.030 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Hepatocholangiocarcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 5.7% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 0/35 (0%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 666 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.022 * (e) (e) P=0.118 | |POLY 3 | (e) (e) (e) (e) |P=0.039 * (e) (e) P=0.187 | |POLY 1.5 | (e) (e) (e) (e) |P=0.042 * (e) (e) P=0.210 | |POLY 6 | (e) (e) (e) (e) |P=0.035 * (e) (e) P=0.156 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.038 * (e) (e) P=0.207 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 7 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/49 (22%) 10/50 (20%) 19/50 (38%) 15/50 (30%) |6/50 (12%) 4/50 (8%) 1/48 (2%) 1/45 (2%) | |POLY-3 ADJUSTED (b)| 24.6% 21.8% 42.5% 33.1% |13.2% 10.1% 2.6% 3.2% | |TERMINAL (d) | 9/38 (24%) 9/36 (25%) 16/37 (43%) 10/35 (29%) |3/31 (10%) 1/18 (6%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 477 729 522 554 |632 562 628 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.092 P=0.544N P=0.059 P=0.207 |P=0.152N P=0.628 P=0.153N P=0.516N | |POLY 3 | P=0.120 P=0.474N P=0.056 P=0.256 |P=0.045N* P=0.455N P=0.089N P=0.140N | |POLY 1.5 | P=0.121 P=0.474N P=0.056 P=0.257 |P=0.036N* P=0.413N P=0.076N P=0.105N | |POLY 6 | P=0.125 P=0.484N P=0.056 P=0.260 |P=0.062N P=0.517N P=0.109N P=0.212N | |LOGISTIC REGRESSION| P=0.118 P=0.454N P=0.063 P=0.265 |P=0.030N* P=0.360N P=0.069N P=0.132N | |COCH-ARM / FISHERS | P=0.134 P=0.479N P=0.071 P=0.266 |P=0.029N* P=0.370N P=0.062N P=0.074N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/49 (10%) 4/50 (8%) 7/50 (14%) 6/50 (12%) |1/50 (2%) 0/50 (0%) 0/48 (0%) 1/45 (2%) | |POLY-3 ADJUSTED (b)| 11.3% 8.7% 15.8% 13.7% |2.2% 0.0% 0.0% 3.2% | |TERMINAL (d) | 3/38 (8%) 4/36 (11%) 4/37 (11%) 4/35 (11%) |1/31 (3%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 540 730 (T) 589 583 |731 (T) --- --- 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.314 P=0.514N P=0.377 P=0.464 |P=0.373 P=0.608N P=0.608N P=0.459 | |POLY 3 | P=0.331 P=0.481N P=0.377 P=0.491 |P=0.550 P=0.529N P=0.534N P=0.677 | |POLY 1.5 | P=0.341 P=0.481N P=0.377 P=0.500 |P=0.560 P=0.515N P=0.522N P=0.707 | |POLY 6 | P=0.323 P=0.488N P=0.379 P=0.481 |P=0.531 P=0.550N P=0.549N P=0.628 | |LOGISTIC REGRESSION| P=0.356 P=0.495N P=0.399 P=0.517 |P=0.483 (e) (e) P=0.641 | |COCH-ARM / FISHERS | P=0.361 P=0.487N P=0.394 P=0.514 |P=0.572 P=0.500N P=0.510N P=0.726 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 8 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 15/49 (31%) 13/50 (26%) 25/50 (50%) 20/50 (40%) |7/50 (14%) 4/50 (8%) 1/48 (2%) 2/45 (4%) | |POLY-3 ADJUSTED (b)| 32.8% 28.4% 54.7% 44.0% |15.4% 10.1% 2.6% 6.3% | |TERMINAL (d) | 11/38 (29%) 12/36 (33%) 19/37 (51%) 14/35 (40%) |4/31 (13%) 1/18 (6%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 477 729 522 554 |632 562 628 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.057 P=0.457N P=0.039 * P=0.165 |P=0.265N P=0.534N P=0.108N P=0.639 | |POLY 3 | P=0.063 P=0.408N P=0.026 * P=0.187 |P=0.071N P=0.341N P=0.053N P=0.199N | |POLY 1.5 | P=0.068 P=0.396N P=0.026 * P=0.198 |P=0.060N P=0.301N P=0.044N* P=0.150N | |POLY 6 | P=0.063 P=0.434N P=0.027 * P=0.180 |P=0.093N P=0.403N P=0.067N P=0.294N | |LOGISTIC REGRESSION| P=0.075 P=0.374N P=0.035 * P=0.220 |P=0.059N P=0.264N P=0.043N* P=0.219N | |COCH-ARM / FISHERS | P=0.087 P=0.387N P=0.039 * P=0.222 |P=0.050N P=0.262N P=0.034N* P=0.107N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 0/35 (0%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- --- |663 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.172N P=0.348N P=0.327N P=0.372N | |POLY 3 | (e) (e) (e) (e) |P=0.101N P=0.274N P=0.270N P=0.302N | |POLY 1.5 | (e) (e) (e) (e) |P=0.107N P=0.256N P=0.254N P=0.269N | |POLY 6 | (e) (e) (e) (e) |P=0.092N P=0.303N P=0.291N P=0.358N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.109N P=0.224N P=0.224N P=0.221N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.116N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 9 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 0/35 (0%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- --- |663 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.172N P=0.348N P=0.327N P=0.372N | |POLY 3 | (e) (e) (e) (e) |P=0.101N P=0.274N P=0.270N P=0.302N | |POLY 1.5 | (e) (e) (e) (e) |P=0.107N P=0.256N P=0.254N P=0.269N | |POLY 6 | (e) (e) (e) (e) |P=0.092N P=0.303N P=0.291N P=0.358N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.109N P=0.224N P=0.224N P=0.221N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.116N P=0.247N P=0.247N P=0.247N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |3/50 (6%) 0/49 (0%) 0/48 (0%) 0/41 (0%) | |POLY-3 ADJUSTED (b)| |6.7% 0.0% 0.0% 0.0% | |TERMINAL (d) | |3/31 (10%) 0/17 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | |731 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.159N P=0.244N P=0.231N P=0.787N | |POLY 3 | |P=0.047N* P=0.153N P=0.153N P=0.221N | |POLY 1.5 | |P=0.050N P=0.137N P=0.140N P=0.188N | |POLY 6 | |P=0.043N* P=0.178N P=0.171N P=0.279N | |LOGISTIC REGRESSION| |P=0.159N (e) (e) (e) | |COCH-ARM / FISHERS | |P=0.057N P=0.125N P=0.129N P=0.161N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 10 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/45 (0%) 0/48 (0%) 0/44 (0%) 0/45 (0%) |5/48 (10%) 1/44 (2%) 0/44 (0%) 1/40 (3%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |11.6% 2.9% 0.0% 3.5% | |TERMINAL (d) | 0/36 (0%) 0/34 (0%) 0/34 (0%) 0/33 (0%) |4/30 (13%) 1/18 (6%) 0/17 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- --- |665 731 (T) --- 626 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.300N P=0.254N P=0.099N P=0.714N | |POLY 3 | (e) (e) (e) (e) |P=0.071N P=0.161N P=0.053N P=0.225N | |POLY 1.5 | (e) (e) (e) (e) |P=0.069N P=0.141N P=0.045N* P=0.186N | |POLY 6 | (e) (e) (e) (e) |P=0.074N P=0.191N P=0.064N P=0.295N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.123N P=0.202N P=0.067N P=0.257N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.070N P=0.123N P=0.035N* P=0.149N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skeletal Muscle | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% 2.3% 4.6% |0.0% 0.0% 2.5% 0.0% | |TERMINAL (d) | 1/38 (3%) 0/36 (0%) 1/37 (3%) 1/35 (3%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) 688 |--- --- 727 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.232 P=0.511N P=0.756 P=0.478 |P=0.483 (e) P=0.406 (e) | |POLY 3 | P=0.238 P=0.491N P=0.759 P=0.497 |P=0.596 (e) P=0.474 (e) | |POLY 1.5 | P=0.241 P=0.494N P=0.757 P=0.498 |P=0.645 (e) P=0.486 (e) | |POLY 6 | P=0.236 P=0.489N P=0.760 P=0.497 |P=0.501 (e) P=0.459 (e) | |LOGISTIC REGRESSION| P=0.236 (e) P=0.756 P=0.495 |P=0.551 (e) P=0.427 (e) | |COCH-ARM / FISHERS | P=0.246 P=0.500N P=0.753N P=0.500 |P=0.693 (e) P=0.500 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 11 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Skin | | Fibrosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 5/50 (10%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.3% |0.0% 12.6% 2.5% 0.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 0/35 (0%) |0/31 (0%) 2/18 (11%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- 604 |--- 578 484 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.191 (e) (e) P=0.500 |P=0.474N P=0.013 * P=0.496 (e) | |POLY 3 | P=0.196 (e) (e) P=0.500 |P=0.359N P=0.021 * P=0.478 (e) | |POLY 1.5 | P=0.197 (e) (e) P=0.500 |P=0.295N P=0.026 * P=0.488 (e) | |POLY 6 | P=0.195 (e) (e) P=0.500 |P=0.468N P=0.017 * P=0.464 (e) | |LOGISTIC REGRESSION| P=0.203 (e) (e) P=0.520 |P=0.195N P=0.037 * P=0.472 (e) | |COCH-ARM / FISHERS | P=0.198 (e) (e) P=0.500 |P=0.238N P=0.028 * P=0.500 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Spleen | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/49 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/46 (0%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 4.6% 4.4% 0.0% 0.0% |0.0% 2.6% 0.0% 0.0% | |TERMINAL (d) | 1/38 (3%) 1/36 (3%) 0/37 (0%) 0/35 (0%) |0/31 (0%) 1/18 (6%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | 570 546 --- --- |--- 731 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.092N P=0.687N P=0.240N P=0.251N |P=0.823 P=0.392 (e) (e) | |POLY 3 | P=0.086N P=0.681N P=0.240N P=0.240N |P=0.604N P=0.471 (e) (e) | |POLY 1.5 | P=0.085N P=0.685N P=0.239N P=0.237N |P=0.593N P=0.485 (e) (e) | |POLY 6 | P=0.088N P=0.680N P=0.241N P=0.244N |P=0.614N P=0.450 (e) (e) | |LOGISTIC REGRESSION| P=0.073N P=0.623 P=0.215N P=0.220N |(e) P=0.392 (e) (e) | |COCH-ARM / FISHERS | P=0.083N P=0.691N P=0.242N P=0.242N |P=0.579N P=0.500 (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 12 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 4.6% |2.2% 2.6% 2.5% 0.0% | |TERMINAL (d) | 0/38 (0%) 1/36 (3%) 0/37 (0%) 2/35 (6%) |1/31 (3%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- 730 (T) --- 730 (T) |731 (T) 567 727 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.129 P=0.489 (e) P=0.220 |P=0.588N P=0.691 P=0.644 P=0.967N | |POLY 3 | P=0.137 P=0.509 (e) P=0.235 |P=0.365N P=0.730 P=0.731 P=0.551N | |POLY 1.5 | P=0.138 P=0.506 (e) P=0.236 |P=0.339N P=0.745 P=0.745 P=0.526N | |POLY 6 | P=0.136 P=0.511 (e) P=0.233 |P=0.409N P=0.707 P=0.712 P=0.589N | |LOGISTIC REGRESSION| (e) P=0.489 (e) P=0.220 |P=0.325N P=0.746N P=0.672 (e) | |COCH-ARM / FISHERS | P=0.140 P=0.500 (e) P=0.247 |P=0.311N P=0.753N P=0.753N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.2% 0.0% 4.6% |0.0% 2.6% 2.5% 0.0% | |TERMINAL (d) | 0/38 (0%) 1/36 (3%) 0/37 (0%) 2/35 (6%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- 730 (T) --- 730 (T) |--- 567 727 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.129 P=0.489 (e) P=0.220 |P=0.640 P=0.483 P=0.406 (e) | |POLY 3 | P=0.137 P=0.509 (e) P=0.235 |P=0.662N P=0.473 P=0.474 (e) | |POLY 1.5 | P=0.138 P=0.506 (e) P=0.236 |P=0.629N P=0.486 P=0.486 (e) | |POLY 6 | P=0.136 P=0.511 (e) P=0.233 |P=0.565 P=0.454 P=0.459 (e) | |LOGISTIC REGRESSION| (e) P=0.489 (e) P=0.220 |P=0.573N P=0.493 P=0.427 (e) | |COCH-ARM / FISHERS | P=0.140 P=0.500 (e) P=0.247 |P=0.594N P=0.500 P=0.500 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 13 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Neuroendocrine Tumor, Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 4.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 0/37 (0%) 2/35 (6%) |0/31 (0%) 0/18 (0%) 0/18 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- --- 730 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.042 * (e) (e) P=0.220 |(e) (e) (e) (e) | |POLY 3 | P=0.044 * (e) (e) P=0.235 |(e) (e) (e) (e) | |POLY 1.5 | P=0.044 * (e) (e) P=0.236 |(e) (e) (e) (e) | |POLY 6 | P=0.043 * (e) (e) P=0.233 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.220 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |2/50 (4%) 0/46 (0%) 1/46 (2%) 1/42 (2%) | |POLY-3 ADJUSTED (b)| 2.3% 0.0% 2.3% 2.3% |4.4% 0.0% 2.8% 3.4% | |TERMINAL (d) | 1/38 (3%) 0/36 (0%) 0/37 (0%) 1/35 (3%) |1/31 (3%) 0/18 (0%) 1/18 (6%) 0/2 (0%) | |FIRST INCIDENCE | 730 (T) --- 630 730 (T) |630 --- 731 (T) 692 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.523 P=0.511N P=0.760 P=0.743 |P=0.430 P=0.340N P=0.649N P=0.606 | |POLY 3 | P=0.528 P=0.489N P=0.759N P=0.760 |P=0.567N P=0.291N P=0.577N P=0.641N | |POLY 1.5 | P=0.533 P=0.491N P=0.760N P=0.759N |P=0.559N P=0.274N P=0.555N P=0.603N | |POLY 6 | P=0.524 P=0.489N P=0.758N P=0.758 |P=0.581N P=0.317N P=0.604N P=0.694N | |LOGISTIC REGRESSION| P=0.539 (e) P=0.757N P=0.743 |P=0.637N P=0.252N P=0.563N P=0.613N | |COCH-ARM / FISHERS | P=0.542 P=0.495N P=0.747N P=0.747N |P=0.550N P=0.269N P=0.532N P=0.566N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 14 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |2/50 (4%) 0/46 (0%) 1/46 (2%) 1/42 (2%) | |POLY-3 ADJUSTED (b)| 4.6% 0.0% 4.6% 2.3% |4.4% 0.0% 2.8% 3.4% | |TERMINAL (d) | 2/38 (5%) 0/36 (0%) 1/37 (3%) 1/35 (3%) |1/31 (3%) 0/18 (0%) 1/18 (6%) 0/2 (0%) | |FIRST INCIDENCE | 730 (T) --- 630 730 (T) |630 --- 731 (T) 692 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.554N P=0.250N P=0.688 P=0.529N |P=0.430 P=0.340N P=0.649N P=0.606 | |POLY 3 | P=0.542N P=0.225N P=0.692N P=0.501N |P=0.567N P=0.291N P=0.577N P=0.641N | |POLY 1.5 | P=0.537N P=0.228N P=0.693N P=0.498N |P=0.559N P=0.274N P=0.555N P=0.603N | |POLY 6 | P=0.545N P=0.225N P=0.690N P=0.505N |P=0.581N P=0.317N P=0.604N P=0.694N | |LOGISTIC REGRESSION| P=0.538N (e) P=0.695N P=0.529N |P=0.637N P=0.252N P=0.563N P=0.613N | |COCH-ARM / FISHERS | P=0.527N P=0.242N P=0.684N P=0.492N |P=0.550N P=0.269N P=0.532N P=0.566N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 4.6% 0.0% |0.0% 2.6% 2.5% 0.0% | |TERMINAL (d) | 0/38 (0%) 0/36 (0%) 2/37 (5%) 0/35 (0%) |0/31 (0%) 0/18 (0%) 1/18 (6%) 0/2 (0%) | |FIRST INCIDENCE | --- --- 730 (T) --- |--- 652 731 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.580 (e) P=0.232 (e) |P=0.604 P=0.424 P=0.392 (e) | |POLY 3 | P=0.582 (e) P=0.235 (e) |P=0.662N P=0.472 P=0.474 (e) | |POLY 1.5 | P=0.587 (e) P=0.234 (e) |P=0.630N P=0.486 P=0.486 (e) | |POLY 6 | P=0.577 (e) P=0.236 (e) |P=0.565 P=0.453 P=0.459 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.232 (e) |P=0.657N P=0.515 P=0.392 (e) | |COCH-ARM / FISHERS | P=0.594 (e) P=0.247 (e) |P=0.594N P=0.500 P=0.500 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 15 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 6/50 (12%) 2/50 (4%) 6/50 (12%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.0% 12.8% 4.5% 13.8% |0.0% 2.6% 5.1% 0.0% | |TERMINAL (d) | 3/38 (8%) 4/36 (11%) 1/37 (3%) 5/35 (14%) |0/31 (0%) 1/18 (6%) 1/18 (6%) 0/2 (0%) | |FIRST INCIDENCE | 570 546 326 688 |--- 731 (T) 727 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.368 P=0.368 P=0.347N P=0.328 |P=0.236 P=0.392 P=0.137 (e) | |POLY 3 | P=0.383 P=0.404 P=0.337N P=0.357 |P=0.556 P=0.471 P=0.209 (e) | |POLY 1.5 | P=0.389 P=0.392 P=0.340N P=0.362 |P=0.623 P=0.485 P=0.222 (e) | |POLY 6 | P=0.376 P=0.412 P=0.336N P=0.351 |P=0.437 P=0.450 P=0.194 (e) | |LOGISTIC REGRESSION| P=0.411 P=0.337 P=0.297N P=0.362 |P=0.317 P=0.392 P=0.152 (e) | |COCH-ARM / FISHERS | P=0.402 P=0.370 P=0.339N P=0.370 |P=0.615N P=0.500 P=0.247 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 6/50 (12%) 4/50 (8%) 6/50 (12%) |0/50 (0%) 2/50 (4%) 3/50 (6%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.0% 12.8% 9.0% 13.8% |0.0% 5.2% 7.6% 0.0% | |TERMINAL (d) | 3/38 (8%) 4/36 (11%) 3/37 (8%) 5/35 (14%) |0/31 (0%) 1/18 (6%) 2/18 (11%) 0/2 (0%) | |FIRST INCIDENCE | 570 546 326 688 |--- 652 727 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.339 P=0.368 P=0.631 P=0.328 |P=0.235 P=0.145 P=0.048 * (e) | |POLY 3 | P=0.353 P=0.404 P=0.643 P=0.357 |P=0.544 P=0.207 P=0.097 (e) | |POLY 1.5 | P=0.361 P=0.392 P=0.639 P=0.362 |P=0.601N P=0.221 P=0.107 (e) | |POLY 6 | P=0.344 P=0.412 P=0.643N P=0.351 |P=0.400 P=0.188 P=0.085 (e) | |LOGISTIC REGRESSION| P=0.380 P=0.337 P=0.625N P=0.362 |P=0.492 P=0.212 P=0.055 (e) | |COCH-ARM / FISHERS | P=0.376 P=0.370 P=0.643N P=0.370 |P=0.529N P=0.247 P=0.121 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 16 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 8/50 (16%) 6/50 (12%) |15/50 (30%) 8/50 (16%) 8/50 (16%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 6.8% 6.6% 18.0% 13.6% |31.9% 20.1% 19.8% 2.9% | |TERMINAL (d) | 2/38 (5%) 3/36 (8%) 6/37 (16%) 4/35 (11%) |6/31 (19%) 4/18 (22%) 1/18 (6%) 0/2 (0%) | |FIRST INCIDENCE | 693 730 (T) 522 543 |564 562 628 705 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.113 P=0.643 P=0.099 P=0.221 |P=0.084N P=0.386N P=0.348N P=0.087N | |POLY 3 | P=0.124 P=0.643N P=0.100 P=0.243 |P<0.001N** P=0.159N P=0.150N P<0.001N** | |POLY 1.5 | P=0.126 P=0.649N P=0.097 P=0.242 |P<0.001N** P=0.113N P=0.111N P<0.001N** | |POLY 6 | P=0.124 P=0.641N P=0.104 P=0.244 |P=0.005N** P=0.250N P=0.212N P=0.006N** | |LOGISTIC REGRESSION| P=0.126 P=0.643N P=0.097 P=0.239 |P<0.001N** P=0.089N P=0.090N P<0.001N** | |COCH-ARM / FISHERS | P=0.132 P=0.661N P=0.100 P=0.243 |P<0.001N** P=0.077N P=0.077N P<0.001N** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 33/50 (66%) 43/50 (86%) 42/50 (84%) 44/50 (88%) |29/50 (58%) 49/50 (98%) 46/50 (92%) 42/50 (84%) | |POLY-3 ADJUSTED (b)| 70.0% 91.1% 91.9% 92.1% |62.3% 98.5% 94.1% 88.5% | |TERMINAL (d) | 27/38 (71%) 35/36 (97%) 36/37 (97%) 32/35 (91%) |19/31 (61%) 18/18 (100%) 16/18 (89%) 1/2 (50%) | |FIRST INCIDENCE | 430 614 522 512 |630 477 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.008 ** P=0.018 * P=0.030 * P=0.011 * |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.003 ** P=0.005 ** P=0.004 ** P=0.004 ** |P=0.004 ** P<0.001 ** P<0.001 ** P=0.002 ** | |POLY 1.5 | P=0.003 ** P=0.009 ** P=0.007 ** P=0.004 ** |P=0.005 ** P<0.001 ** P<0.001 ** P=0.002 ** | |POLY 6 | P=0.004 ** P=0.003 ** P=0.003 ** P=0.005 ** |P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.003 ** P=0.035 * P=0.017 * P=0.006 ** |P=0.007 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.012 * P=0.017 * P=0.032 * P=0.008 ** |P=0.013 * P<0.001 ** P<0.001 ** P=0.004 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 06 Page 17 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLEUGENOL Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 23/50 (46%) 30/50 (60%) 32/50 (64%) 29/50 (58%) |27/50 (54%) 42/50 (84%) 48/50 (96%) 49/50 (98%) | |POLY-3 ADJUSTED (b)| 47.9% 61.4% 65.7% 61.5% |56.0% 88.6% 97.7% 99.7% | |TERMINAL (d) | 14/38 (37%) 18/36 (50%) 21/37 (57%) 18/35 (51%) |11/31 (36%) 15/18 (83%) 17/18 (94%) 2/2 (100%) | |FIRST INCIDENCE | 477 546 326 543 |564 493 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.161 P=0.165 P=0.088 P=0.151 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.138 P=0.127 P=0.057 P=0.129 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.147 P=0.123 P=0.050 P=0.136 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.132 P=0.131 P=0.062 P=0.125 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.190 P=0.086 P=0.058 P=0.162 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.180 P=0.115 P=0.054 P=0.158 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 41/50 (82%) 48/50 (96%) 49/50 (98%) 45/50 (90%) |41/50 (82%) 50/50 (100%) 49/50 (98%) 49/50 (98%) | |POLY-3 ADJUSTED (b)| 83.1% 98.3% 100.0% 93.1% |84.4% 100.0% 99.7% 99.7% | |TERMINAL (d) | 30/38 (79%) 36/36 (100%) 37/37 (100%) 32/35 (91%) |24/31 (77%) 18/18 (100%) 18/18 (100%) 2/2 (100%) | |FIRST INCIDENCE | 430 546 326 512 |564 477 465 450 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.169 P=0.102 P=0.076 P=0.165 |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P=0.079 P=0.008 ** P=0.003 ** P=0.108 |P<0.001 ** P=0.004 ** P=0.005 ** P=0.005 ** | |POLY 1.5 | P=0.098 P=0.013 * P=0.002 ** P=0.125 |P<0.001 ** P=0.003 ** P=0.006 ** P=0.006 ** | |POLY 6 | P=0.077 P=0.006 ** P=0.003 ** P=0.103 |P<0.001 ** P=0.005 ** P=0.005 ** P=0.005 ** | |LOGISTIC REGRESSION| P=0.157 P=0.035 * P=0.006 ** P=0.185 |P=0.002 ** P=0.002 ** P=0.004 ** P=0.003 ** | |COCH-ARM / FISHERS | P=0.209 P=0.026 * P=0.008 ** P=0.194 |P=0.005 ** P<0.001 ** P=0.008 ** P=0.008 ** | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Poly-3 adjusted lifetime tumor incidence. (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. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers 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).