TDMS Study 05187-09 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 09/16/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:28:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: MISSING CAS: 93-15-2 ------------------------------------------------------------------------------------------------------------------------------------ CORE STUDY REASONS FOR REMOVAL: 25022 Accidently Killed 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 MG/KG INCLUDE 002 0 MG/KG INCLUDE 003 37 MG/KG INCLUDE 004 37 MG/KG INCLUDE 005 75 MG/KG INCLUDE 006 75 MG/KG INCLUDE 007 150 MG/KG INCLUDE 008 150 MG/KG NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 09/16/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:28:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: MISSING CAS: 93-15-2 Rats(FISCHER 344) ----------------------------- 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 Brain Clitoral/Preputial Gland Heart Islets, Pancreatic Kidney Liver Lung Ovary Pancreas Parathyroid Gland Pituitary Gland Prostate Salivary Glands Spleen Testes Thymus Thyroid Gland NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 09/16/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:28:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: MISSING CAS: 93-15-2 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF METHYLEUGENOL =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Medulla Pheochromocytoma Benign Pheochromocytoma: Benign, Complex, Malignant, NOS Clitoral/Preputial Gland Adenoma Carcinoma Carcinoma or Adenoma Islets, Pancreatic Adenoma Carcinoma or Adenoma Kidney: Renal Tubule Adenoma Carcinoma or Adenoma Liver Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Mammary Gland Fibroadenoma Fibroma, Fibroadenoma or Adenoma Fibroma, Fibroadenoma, Carcinoma, or Adenoma Skin Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthom a, Trichoepitheliom Fibroma Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma Fibrosarcoma Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma Keratoacanthoma Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma Squamous Cell Papilloma, Papilloma, or Keratoacanthoma Stomach, Glandular Neuroendocrine Tumor, Benign Neuroendocrine Tumor, Malignant Testes Adenoma Thyroid Gland: C-Cell Adenoma Carcinoma or Adenoma All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Mesothelioma: Benign, Malignant, NOS Mesothelioma: Malignant Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Liver Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Hepatocholangiocarcinoma Pituitary Gland: Pars Distalis or Unspecified Site NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus METHYLEUGENOL DATE: 09/16/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:28:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: MISSING CAS: 93-15-2 Adenoma Stomach, Forestomach Squamous Cell Carcinoma or Papilloma Squamous Squamous Cell Papilloma Stomach, Glandular Neuroendocrine Tumor, Benign Neuroendocrine Tumor, Malignant All Organs Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 1 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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) | 24/50 (48%) 17/50 (34%) 11/50 (22%) 10/50 (20%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 54.5% 41.5% 28.2% 29.6% |2.5% 2.4% 4.8% 5.6% | |TERMINAL (d) | 9/20 (45%) 7/16 (44%) 4/15 (27%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | 588 575 619 625 |698 650 702 711 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.172 P=0.383N P=0.108N P=0.014 * |P=0.193 P=0.750N P=0.516 P=0.340 | |POLY 3 | P=0.007N** P=0.155N P=0.010N* P=0.019N* |P=0.297 P=0.751N P=0.518 P=0.469 | |POLY 1.5 | P=0.003N** P=0.133N P=0.007N** P=0.007N** |P=0.317 P=0.754N P=0.512 P=0.484 | |POLY 6 | P=0.026N* P=0.192N P=0.018N* P=0.088N |P=0.263 P=0.748N P=0.525 P=0.438 | |LOGISTIC REGRESSION| P=0.045N* P=0.180N P=0.016N* P=0.132N |P=0.271 P=0.760N P=0.526 P=0.400 | |COCH-ARM / FISHERS | P=0.002N** P=0.111N P=0.006N** P=0.003N** |P=0.330 P=0.753N P=0.500 P=0.492 | |=================================================================================================================================| | | | | | | 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, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 25/50 (50%) 17/50 (34%) 12/50 (24%) 11/50 (22%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 56.8% 41.5% 30.7% 32.1% |2.5% 2.4% 4.8% 8.2% | |TERMINAL (d) | 10/20 (50%) 7/16 (44%) 4/15 (27%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | 588 575 619 575 |698 650 702 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.110 P=0.326N P=0.127N P=0.008 ** |P=0.077 P=0.750N P=0.516 P=0.192 | |POLY 3 | P=0.009N** P=0.108N P=0.011N* P=0.019N* |P=0.141 P=0.751N P=0.518 P=0.278 | |POLY 1.5 | P=0.004N** P=0.092N P=0.008N** P=0.007N** |P=0.152 P=0.754N P=0.512 P=0.291 | |POLY 6 | P=0.031N* P=0.136N P=0.019N* P=0.085N |P=0.123 P=0.748N P=0.525 P=0.250 | |LOGISTIC REGRESSION| P=0.059N P=0.134N P=0.019N* P=0.129N |P=0.141 P=0.760N P=0.526 P=0.278 | |COCH-ARM / FISHERS | P=0.002N** P=0.078N P=0.006N** P=0.003N** |P=0.159 P=0.753N P=0.500 P=0.301 | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 2 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Brain | | Oligodendroglioma, Glioma, or Astrocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 5.1% 2.6% 0.0% |2.5% 0.0% 0.0% 2.7% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 344 431 467 --- |719 --- --- 667 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.339N P=0.472 P=0.756 P=0.504N |P=0.521 P=0.484N P=0.500N P=0.670 | |POLY 3 | P=0.327N P=0.475 P=0.737 P=0.559N |P=0.580 P=0.492N P=0.490N P=0.745 | |POLY 1.5 | P=0.290N P=0.485 P=0.746 P=0.532N |P=0.587 P=0.495N P=0.493N P=0.755 | |POLY 6 | P=0.403N P=0.460 P=0.722 P=0.606N |P=0.569 P=0.490N P=0.486N P=0.724 | |LOGISTIC REGRESSION| P=0.144N P=0.612 P=0.602N P=0.431N |P=0.576 P=0.487N P=0.484N P=0.733 | |COCH-ARM / FISHERS | P=0.247N P=0.500 P=0.753N P=0.500N |P=0.595 P=0.500N P=0.500N P=0.753N | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 16/50 (32%) 3/49 (6%) 8/50 (16%) |5/48 (10%) 8/46 (17%) 6/49 (12%) 3/46 (7%) | |POLY-3 ADJUSTED (b)| 21.2% 38.6% 8.0% 23.3% |13.1% 21.4% 14.6% 8.8% | |TERMINAL (d) | 4/20 (20%) 7/16 (44%) 1/15 (7%) 0/0 (0%) |3/21 (14%) 5/22 (23%) 3/22 (14%) 1/11 (9%) | |FIRST INCIDENCE | 610 542 568 502 |679 620 676 609 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.117 P=0.036 * P=0.147N P=0.024 * |P=0.495N P=0.312 P=0.541 P=0.611N | |POLY 3 | P=0.295N P=0.061 P=0.087N P=0.521 |P=0.249N P=0.255 P=0.548 P=0.420N | |POLY 1.5 | P=0.223N P=0.069 P=0.078N P=0.603N |P=0.226N P=0.254 P=0.535 P=0.396N | |POLY 6 | P=0.437N P=0.050 P=0.107N P=0.361 |P=0.294N P=0.257 P=0.564 P=0.467N | |LOGISTIC REGRESSION| P=0.230N P=0.064 P=0.080N P=0.605N |P=0.310N P=0.255 P=0.575 P=0.457N | |COCH-ARM / FISHERS | P=0.162N P=0.083 P=0.065N P=0.500N |P=0.212N P=0.249 P=0.515 P=0.381N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 3 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 1/50 (2%) 2/49 (4%) 0/50 (0%) |1/48 (2%) 0/46 (0%) 1/49 (2%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 11.9% 2.6% 5.3% 0.0% |2.6% 0.0% 2.5% 0.0% | |TERMINAL (d) | 2/20 (10%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |1/21 (5%) 0/22 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 564 704 502 --- |730 (T) --- 721 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.141N P=0.170N P=0.327N P=0.497N |P=0.519N P=0.491N P=0.750N P=0.629N | |POLY 3 | P=0.037N* P=0.120N P=0.260N P=0.064N |P=0.423N P=0.506N P=0.745N P=0.526N | |POLY 1.5 | P=0.031N* P=0.112N P=0.247N P=0.045N* |P=0.416N P=0.506N P=0.749N P=0.516N | |POLY 6 | P=0.053N P=0.133N P=0.284N P=0.115N |P=0.432N P=0.505N P=0.740N P=0.545N | |LOGISTIC REGRESSION| P=0.027N* P=0.120N P=0.216N P=0.081N |P=0.487N (e) P=0.741N (e) | |COCH-ARM / FISHERS | P=0.026N* P=0.102N P=0.226N P=0.028N* |P=0.410N P=0.511N P=0.747N P=0.511N | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Clitoral/Preputial Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 17/50 (34%) 5/49 (10%) 8/50 (16%) |6/48 (13%) 8/46 (17%) 7/49 (14%) 3/46 (7%) | |POLY-3 ADJUSTED (b)| 32.4% 40.9% 12.9% 23.3% |15.7% 21.4% 17.1% 8.8% | |TERMINAL (d) | 6/20 (30%) 7/16 (44%) 1/15 (7%) 0/0 (0%) |4/21 (19%) 5/22 (23%) 3/22 (14%) 1/11 (9%) | |FIRST INCIDENCE | 564 542 502 502 |679 620 676 609 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.307 P=0.163 P=0.087N P=0.056 |P=0.436N P=0.426 P=0.543 P=0.510N | |POLY 3 | P=0.065N P=0.276 P=0.030N* P=0.261N |P=0.195N P=0.365 P=0.554 P=0.298N | |POLY 1.5 | P=0.041N* P=0.300 P=0.027N* P=0.179N |P=0.174N P=0.363 P=0.539 P=0.277N | |POLY 6 | P=0.131N P=0.244 P=0.039N* P=0.444N |P=0.236N P=0.369 P=0.572 P=0.342N | |LOGISTIC REGRESSION| P=0.043N* P=0.273 P=0.026N* P=0.220N |P=0.255N P=0.365 P=0.585 P=0.348N | |COCH-ARM / FISHERS | P=0.025N* P=0.333 P=0.022N* P=0.114N |P=0.162N P=0.354 P=0.516 P=0.265N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 4 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 2.6% 0.0% 0.0% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 704 730 (T) --- --- |--- 646 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.186N P=0.403N P=0.221N P=0.970N |P=0.599N P=0.523 (e) (e) | |POLY 3 | P=0.046N* P=0.332N P=0.138N P=0.178N |P=0.560N P=0.509 (e) (e) | |POLY 1.5 | P=0.045N* P=0.320N P=0.130N P=0.147N |P=0.562N P=0.506 (e) (e) | |POLY 6 | P=0.049N* P=0.350N P=0.153N P=0.246N |P=0.554N P=0.513 (e) (e) | |LOGISTIC REGRESSION| P=0.120N P=0.374N P=0.172N P=0.505N |P=0.564N P=0.494 (e) (e) | |COCH-ARM / FISHERS | P=0.044N* P=0.309N P=0.121N P=0.121N |P=0.567N P=0.500 (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 | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 2.6% 0.0% 0.0% |2.5% 2.4% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |1/22 (5%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 704 730 (T) --- --- |730 (T) 646 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.186N P=0.403N P=0.221N P=0.970N |P=0.286N P=0.733N P=0.500N P=0.638N | |POLY 3 | P=0.046N* P=0.332N P=0.138N P=0.178N |P=0.235N P=0.751N P=0.489N P=0.516N | |POLY 1.5 | P=0.045N* P=0.320N P=0.130N P=0.147N |P=0.236N P=0.754N P=0.493N P=0.506N | |POLY 6 | P=0.049N* P=0.350N P=0.153N P=0.246N |P=0.232N P=0.746N P=0.486N P=0.535N | |LOGISTIC REGRESSION| P=0.120N P=0.374N P=0.172N P=0.505N |P=0.242N P=0.756N (e) (e) | |COCH-ARM / FISHERS | P=0.044N* P=0.309N P=0.121N P=0.121N |P=0.236N P=0.753N P=0.500N P=0.500N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 5 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 6/50 (12%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 5.2% 15.8% 18.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 4/15 (27%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 712 673 596 598 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.596N P=0.106 P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P=0.046 * P=0.531N P=0.195 P=0.135 |(e) (e) (e) (e) | |POLY 1.5 | P=0.070 P=0.518N P=0.213 P=0.181 |(e) (e) (e) (e) | |POLY 6 | P=0.022 * P=0.551N P=0.167 P=0.075 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.007 ** P=0.568N P=0.138 P=0.034 * |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.107 P=0.500N P=0.243 P=0.243 |(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 | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 6/50 (12%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 9.6% 5.2% 15.8% 18.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/20 (10%) 0/16 (0%) 4/15 (27%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 712 673 596 598 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.443N P=0.182 P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P=0.090 P=0.368N P=0.310 P=0.226 |(e) (e) (e) (e) | |POLY 1.5 | P=0.127 P=0.355N P=0.333 P=0.291 |(e) (e) (e) (e) | |POLY 6 | P=0.048 * P=0.388N P=0.273 P=0.135 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.014 * P=0.413N P=0.222 P=0.049 * |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.179 P=0.339N P=0.370 P=0.370 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 6 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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) | 5/50 (10%) 12/50 (24%) 23/50 (46%) 38/50 (76%) |1/50 (2%) 8/50 (16%) 11/49 (22%) 33/49 (67%) | |POLY-3 ADJUSTED (b)| 12.0% 29.5% 55.1% 86.8% |2.5% 19.6% 26.3% 75.1% | |TERMINAL (d) | 2/20 (10%) 5/16 (31%) 8/15 (53%) 0/0 (0%) |1/22 (5%) 8/25 (32%) 5/22 (23%) 11/11 (100%) | |FIRST INCIDENCE | 715 431 522 467 |730 (T) 730 (T) 609 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.026 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P=0.005 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.042 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P=0.002 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.047 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P=0.002 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.037 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P=0.003 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.039 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P=0.003 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.054 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.015 * P=0.002 ** 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) | 2/50 (4%) 3/50 (6%) 14/50 (28%) 25/50 (50%) |0/50 (0%) 0/50 (0%) 4/49 (8%) 8/49 (16%) | |POLY-3 ADJUSTED (b)| 4.8% 7.8% 34.7% 64.0% |0.0% 0.0% 9.7% 21.8% | |TERMINAL (d) | 1/20 (5%) 2/16 (13%) 5/15 (33%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 2/22 (9%) 5/11 (46%) | |FIRST INCIDENCE | 529 718 502 523 |--- --- 609 589 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.418 P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.073 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.461 P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.066 P=0.002 ** | |POLY 1.5 | P<0.001 ** P=0.478 P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.063 P=0.003 ** | |POLY 6 | P<0.001 ** P=0.437 P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.071 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.474 P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.065 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** |P<0.001 ** (e) P=0.056 P=0.003 ** | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 7 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 14/50 (28%) 28/50 (56%) 43/50 (86%) |1/50 (2%) 8/50 (16%) 14/49 (29%) 34/49 (69%) | |POLY-3 ADJUSTED (b)| 16.6% 34.4% 64.4% 94.0% |2.5% 19.6% 33.4% 76.6% | |TERMINAL (d) | 3/20 (15%) 7/16 (44%) 9/15 (60%) 0/0 (0%) |1/22 (5%) 8/25 (32%) 7/22 (32%) 11/11 (100%) | |FIRST INCIDENCE | 529 431 502 467 |730 (T) 730 (T) 609 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.030 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.049 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.057 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.040 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.051 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.070 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.015 * 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, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 14/50 (28%) 28/50 (56%) 43/50 (86%) |1/50 (2%) 8/50 (16%) 14/49 (29%) 34/49 (69%) | |POLY-3 ADJUSTED (b)| 16.6% 34.4% 64.4% 94.0% |2.5% 19.6% 33.4% 76.6% | |TERMINAL (d) | 3/20 (15%) 7/16 (44%) 9/15 (60%) 0/0 (0%) |1/22 (5%) 8/25 (32%) 7/22 (32%) 11/11 (100%) | |FIRST INCIDENCE | 529 431 502 467 |730 (T) 730 (T) 609 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.030 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.049 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.057 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.040 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.051 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.070 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 8 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Hepatocholangiocarcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.6% 3.1% |0.0% 0.0% 0.0% 8.2% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 2/11 (18%) | |FIRST INCIDENCE | --- --- 582 457 |--- --- --- 534 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.226 (e) P=0.486 P=0.496 |P=0.003 ** (e) (e) P=0.054 | |POLY 3 | P=0.175 (e) P=0.482 P=0.449 |P=0.010 * (e) (e) P=0.105 | |POLY 1.5 | P=0.204 (e) P=0.489 P=0.474 |P=0.010 * (e) (e) P=0.112 | |POLY 6 | P=0.130 (e) P=0.470 P=0.405 |P=0.009 ** (e) (e) P=0.092 | |LOGISTIC REGRESSION| P=0.291 (e) P=0.548 P=0.631 |P=0.011 * (e) (e) P=0.113 | |COCH-ARM / FISHERS | P=0.236 (e) P=0.500 P=0.500 |P=0.011 * (e) (e) P=0.117 | |=================================================================================================================================| | | | | | | 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 | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |2/50 (4%) 4/50 (8%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 5.4% 0.0% |5.1% 9.7% 2.4% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 2/15 (13%) 0/0 (0%) |2/22 (9%) 3/25 (12%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) --- |730 (T) 650 515 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.417 P=0.545N P=0.398 P=1.000N |P=0.156N P=0.394 P=0.493N P=0.400N | |POLY 3 | P=0.539N P=0.514N P=0.464 P=0.555N |P=0.093N P=0.358 P=0.476N P=0.255N | |POLY 1.5 | P=0.501N P=0.508N P=0.478 P=0.529N |P=0.088N P=0.351 P=0.485N P=0.244N | |POLY 6 | P=0.611N P=0.523N P=0.440 P=0.601N |P=0.104N P=0.367 P=0.467N P=0.277N | |LOGISTIC REGRESSION| P=0.417 (e) P=0.398 (e) |P=0.093N P=0.365 P=0.505N (e) | |COCH-ARM / FISHERS | P=0.461N P=0.500N P=0.500 P=0.500N |P=0.086N P=0.339 P=0.500N P=0.247N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 9 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |2/50 (4%) 4/50 (8%) 1/50 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 8.0% 0.0% |5.1% 9.7% 2.4% 2.7% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 3/15 (20%) 0/0 (0%) |2/22 (9%) 3/25 (12%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) --- |730 (T) 650 515 609 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.191 P=0.545N P=0.203 P=1.000N |P=0.378N P=0.394 P=0.493N P=0.669N | |POLY 3 | P=0.611N P=0.514N P=0.268 P=0.555N |P=0.245N P=0.358 P=0.476N P=0.524N | |POLY 1.5 | P=0.557N P=0.508N P=0.283 P=0.529N |P=0.236N P=0.351 P=0.485N P=0.509N | |POLY 6 | P=0.478 P=0.523N P=0.245 P=0.601N |P=0.261N P=0.367 P=0.467N P=0.553N | |LOGISTIC REGRESSION| P=0.191 (e) P=0.203 (e) |P=0.241N P=0.365 P=0.505N P=0.545N | |COCH-ARM / FISHERS | P=0.500N P=0.500N P=0.309 P=0.500N |P=0.232N P=0.339 P=0.500N 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 | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 5/50 (10%) 15/50 (30%) 13/50 (26%) |36/50 (72%) 36/50 (72%) 34/50 (68%) 31/50 (62%) | |POLY-3 ADJUSTED (b)| 12.0% 12.6% 38.3% 37.0% |78.7% 77.9% 75.9% 73.8% | |TERMINAL (d) | 4/20 (20%) 2/16 (13%) 8/15 (53%) 0/0 (0%) |15/22 (68%) 19/25 (76%) 18/22 (82%) 9/11 (82%) | |FIRST INCIDENCE | 610 579 568 546 |407 347 527 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.515 P=0.002 ** P<0.001 ** |P=0.075 P=0.373N P=0.370N P=0.136 | |POLY 3 | P<0.001 ** P=0.596 P=0.004 ** P=0.008 ** |P=0.306N P=0.567N P=0.474N P=0.376N | |POLY 1.5 | P=0.003 ** P=0.610 P=0.006 ** P=0.016 * |P=0.198N P=0.555N P=0.435N P=0.259N | |POLY 6 | P<0.001 ** P=0.577 P=0.003 ** P=0.002 ** |P=0.534N P=0.610N P=0.553N P=0.615N | |LOGISTIC REGRESSION| P<0.001 ** P=0.591 P=0.003 ** P=0.008 ** |P=0.198N P=0.530N P=0.298N P=0.258N | |COCH-ARM / FISHERS | P=0.009 ** P=0.630N P=0.011 * P=0.033 * |P=0.134N P=0.588N P=0.414N P=0.198N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 10 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 5/50 (10%) 16/50 (32%) 13/50 (26%) |36/50 (72%) 36/50 (72%) 34/50 (68%) 32/50 (64%) | |POLY-3 ADJUSTED (b)| 12.0% 12.6% 40.8% 37.0% |78.7% 77.9% 75.9% 75.4% | |TERMINAL (d) | 4/20 (20%) 2/16 (13%) 9/15 (60%) 0/0 (0%) |15/22 (68%) 19/25 (76%) 18/22 (82%) 9/11 (82%) | |FIRST INCIDENCE | 610 579 568 546 |407 347 527 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.515 P<0.001 ** P<0.001 ** |P=0.054 P=0.373N P=0.370N P=0.107 | |POLY 3 | P<0.001 ** P=0.596 P=0.002 ** P=0.008 ** |P=0.379N P=0.567N P=0.474N P=0.451N | |POLY 1.5 | P=0.002 ** P=0.610 P=0.003 ** P=0.016 * |P=0.264N P=0.555N P=0.435N P=0.330N | |POLY 6 | P<0.001 ** P=0.577 P<0.001 ** P=0.002 ** |P=0.511 P=0.610N P=0.553N P=0.569 | |LOGISTIC REGRESSION| P<0.001 ** P=0.591 P<0.001 ** P=0.008 ** |P=0.267N P=0.530N P=0.298N P=0.328N | |COCH-ARM / FISHERS | P=0.009 ** P=0.630N P=0.006 ** P=0.033 * |P=0.190N P=0.588N P=0.414N P=0.260N | |=================================================================================================================================| | | | | | | 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) | 5/50 (10%) 5/50 (10%) 16/50 (32%) 13/50 (26%) |37/50 (74%) 38/50 (76%) 35/50 (70%) 32/50 (64%) | |POLY-3 ADJUSTED (b)| 12.0% 12.6% 40.8% 37.0% |80.9% 81.7% 77.0% 75.4% | |TERMINAL (d) | 4/20 (20%) 2/16 (13%) 9/15 (60%) 0/0 (0%) |16/22 (73%) 20/25 (80%) 18/22 (82%) 9/11 (82%) | |FIRST INCIDENCE | 610 579 568 546 |407 347 515 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.515 P<0.001 ** P<0.001 ** |P=0.077 P=0.419N P=0.369N P=0.125 | |POLY 3 | P<0.001 ** P=0.596 P=0.002 ** P=0.008 ** |P=0.243N P=0.570 P=0.420N P=0.344N | |POLY 1.5 | P=0.002 ** P=0.610 P=0.003 ** P=0.016 * |P=0.158N P=0.562 P=0.403N P=0.242N | |POLY 6 | P<0.001 ** P=0.577 P<0.001 ** P=0.002 ** |P=0.440N P=0.553 P=0.473N P=0.565N | |LOGISTIC REGRESSION| P<0.001 ** P=0.591 P<0.001 ** P=0.008 ** |P=0.162N P=0.572 P=0.302N P=0.250N | |COCH-ARM / FISHERS | P=0.009 ** P=0.630N P=0.006 ** P=0.033 * |P=0.113N P=0.500 P=0.412N P=0.194N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 11 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Papilloma Squamous or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.1% 0.0% 6.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- 596 --- 633 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.071 P=0.204 (e) P=0.084 |(e) (e) (e) (e) | |POLY 3 | P=0.184 P=0.224 (e) P=0.183 |(e) (e) (e) (e) | |POLY 1.5 | P=0.212 P=0.229 (e) P=0.208 |(e) (e) (e) (e) | |POLY 6 | P=0.144 P=0.216 (e) P=0.146 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.219 P=0.241 (e) P=0.190 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.247 P=0.247 (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 | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.1% 0.0% 6.3% |0.0% 0.0% 2.4% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- 596 --- 633 |--- --- 637 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.071 P=0.204 (e) P=0.084 |P=0.671 (e) P=0.511 (e) | |POLY 3 | P=0.184 P=0.224 (e) P=0.183 |P=0.649 (e) P=0.512 (e) | |POLY 1.5 | P=0.212 P=0.229 (e) P=0.208 |P=0.675 (e) P=0.508 (e) | |POLY 6 | P=0.144 P=0.216 (e) P=0.146 |P=0.595 (e) P=0.517 (e) | |LOGISTIC REGRESSION| P=0.219 P=0.241 (e) P=0.190 |P=0.694 (e) P=0.489 (e) | |COCH-ARM / FISHERS | P=0.247 P=0.247 (e) P=0.247 |P=0.694 (e) P=0.500 (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 12 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Ovary | | Granulosa Cell Tumor Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 2/50 (4%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| |0.0% 4.9% 0.0% 0.0% | |TERMINAL (d) | |0/22 (0%) 1/25 (4%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | |--- 718 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.525N P=0.267 (e) (e) | |POLY 3 | |P=0.407N P=0.246 (e) (e) | |POLY 1.5 | |P=0.405N P=0.243 (e) (e) | |POLY 6 | |P=0.412N P=0.249 (e) (e) | |LOGISTIC REGRESSION| |P=0.483N P=0.253 (e) (e) | |COCH-ARM / FISHERS | |P=0.410N P=0.247 (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 | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 8/50 (16%) 8/50 (16%) 2/50 (4%) |22/50 (44%) 20/50 (40%) 21/50 (42%) 22/50 (44%) | |POLY-3 ADJUSTED (b)| 16.3% 19.4% 20.4% 6.3% |51.8% 46.2% 47.6% 53.0% | |TERMINAL (d) | 3/20 (15%) 1/16 (6%) 3/15 (20%) 0/0 (0%) |10/22 (46%) 13/25 (52%) 10/22 (46%) 5/11 (46%) | |FIRST INCIDENCE | 521 572 438 670 |549 520 541 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.521N P=0.399 P=0.335 P=0.654 |P=0.042 * P=0.293N P=0.448N P=0.101 | |POLY 3 | P=0.185N P=0.468 P=0.425 P=0.174N |P=0.439 P=0.378N P=0.429N P=0.544 | |POLY 1.5 | P=0.113N P=0.481 P=0.454 P=0.122N |P=0.478 P=0.388N P=0.453N P=0.579 | |POLY 6 | P=0.367N P=0.454 P=0.376 P=0.298N |P=0.362 P=0.376N P=0.409N P=0.460 | |LOGISTIC REGRESSION| P=0.057N P=0.547 P=0.505 P=0.130N |P=0.402 P=0.363N P=0.429N P=0.509 | |COCH-ARM / FISHERS | P=0.060N P=0.500 P=0.500 P=0.080N |P=0.490 P=0.420N P=0.500N P=0.580N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 13 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Basal Cell Adenoma, Basosquamous Tumor Benign, or | | Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 4.9% 2.4% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 2/25 (8%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 730 (T) 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.607N P=0.266 P=0.520 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.481N P=0.245 P=0.511 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.468N P=0.243 P=0.507 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.507N P=0.248 P=0.516 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.539N P=0.266 P=0.508 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.461N P=0.247 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 | |=================================================================================================================================| | | |Skin | | Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous | | Tumor (benign, malignant or NOS), or Trichoepithelioma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 0.0% 0.0% |0.0% 4.9% 2.4% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 2/25 (8%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- 725 --- --- |--- 730 (T) 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.861 P=0.458 (e) (e) |P=0.607N P=0.266 P=0.520 (e) | |POLY 3 | P=0.589N P=0.486 (e) (e) |P=0.481N P=0.245 P=0.511 (e) | |POLY 1.5 | P=0.580N P=0.492 (e) (e) |P=0.468N P=0.243 P=0.507 (e) | |POLY 6 | P=0.606N P=0.477 (e) (e) |P=0.507N P=0.248 P=0.516 (e) | |LOGISTIC REGRESSION| P=0.853 P=0.453 (e) (e) |P=0.539N P=0.266 P=0.508 (e) | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.461N P=0.247 P=0.500 (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 14 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor | | (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 4/50 (8%) 6/50 (12%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 10.3% 10.6% 18.1% |0.0% 4.9% 2.4% 0.0% | |TERMINAL (d) | 3/20 (15%) 2/16 (13%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 2/25 (8%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 704 674 584 |--- 730 (T) 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.375 P=0.323 P=0.002 ** |P=0.607N P=0.266 P=0.520 (e) | |POLY 3 | P=0.102 P=0.462 P=0.449 P=0.141 |P=0.481N P=0.245 P=0.511 (e) | |POLY 1.5 | P=0.137 P=0.479 P=0.469 P=0.185 |P=0.468N P=0.243 P=0.507 (e) | |POLY 6 | P=0.060 P=0.439 P=0.419 P=0.084 |P=0.507N P=0.248 P=0.516 (e) | |LOGISTIC REGRESSION| P=0.027 * P=0.366 P=0.352 P=0.092 |P=0.539N P=0.266 P=0.508 (e) | |COCH-ARM / FISHERS | P=0.184 P=0.500 P=0.500 P=0.243 |P=0.461N P=0.247 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 | |=================================================================================================================================| | | |Skin | | Fibroma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 9/50 (18%) 8/50 (16%) 5/50 (10%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.4% 22.3% 20.6% 15.3% |2.5% 0.0% 4.8% 5.5% | |TERMINAL (d) | 1/20 (5%) 3/16 (19%) 2/15 (13%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 535 619 607 |724 --- 676 620 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.006 ** P=0.008 ** P=0.004 ** |P=0.129 P=0.476N P=0.520 P=0.356 | |POLY 3 | P=0.108 P=0.006 ** P=0.011 * P=0.055 |P=0.217 P=0.492N P=0.520 P=0.476 | |POLY 1.5 | P=0.179 P=0.007 ** P=0.012 * P=0.075 |P=0.233 P=0.495N P=0.512 P=0.491 | |POLY 6 | P=0.038 * P=0.005 ** P=0.009 ** P=0.032 * |P=0.191 P=0.490N P=0.528 P=0.446 | |LOGISTIC REGRESSION| P=0.150 P=0.008 ** P=0.011 * P=0.051 |P=0.206 P=0.485N P=0.526 P=0.456 | |COCH-ARM / FISHERS | P=0.287 P=0.008 ** P=0.015 * P=0.102 |P=0.245 P=0.500N P=0.500 P=0.500 | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 15 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 13/50 (26%) 8/50 (16%) 8/50 (16%) |1/50 (2%) 0/50 (0%) 4/50 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.4% 31.9% 20.6% 23.7% |2.5% 0.0% 9.6% 5.5% | |TERMINAL (d) | 1/20 (5%) 4/16 (25%) 2/15 (13%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 2/22 (9%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 535 619 547 |724 --- 676 620 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P=0.008 ** P<0.001 ** |P=0.100 P=0.476N P=0.197 P=0.356 | |POLY 3 | P=0.046 * P<0.001 ** P=0.011 * P=0.005 ** |P=0.195 P=0.492N P=0.195 P=0.476 | |POLY 1.5 | P=0.084 P<0.001 ** P=0.012 * P=0.009 ** |P=0.217 P=0.495N P=0.189 P=0.491 | |POLY 6 | P=0.014 * P<0.001 ** P=0.009 ** P=0.002 ** |P=0.158 P=0.490N P=0.202 P=0.446 | |LOGISTIC REGRESSION| P=0.064 P<0.001 ** P=0.011 * P=0.011 * |P=0.174 P=0.485N P=0.201 P=0.456 | |COCH-ARM / FISHERS | P=0.158 P<0.001 ** P=0.015 * P=0.015 * |P=0.237 P=0.500N P=0.181 P=0.500 | |=================================================================================================================================| | | | | | | 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%) 3/50 (6%) 0/50 (0%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 7.7% 0.0% 9.3% |0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | --- 674 --- 547 |--- --- 717 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.011 * P=0.093 (e) P=0.035 * |P=0.479 (e) P=0.244 (e) | |POLY 3 | P=0.110 P=0.106 (e) P=0.080 |P=0.537 (e) P=0.249 (e) | |POLY 1.5 | P=0.132 P=0.112 (e) P=0.097 |P=0.570 (e) P=0.245 (e) | |POLY 6 | P=0.080 P=0.099 (e) P=0.057 |P=0.472 (e) P=0.253 (e) | |LOGISTIC REGRESSION| P=0.124 P=0.095 (e) P=0.147 |P=0.518 (e) P=0.252 (e) | |COCH-ARM / FISHERS | P=0.163 P=0.121 (e) P=0.121 |P=0.595 (e) P=0.247 (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 16 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 4/50 (8%) 0/50 (0%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 10.3% 0.0% 9.3% |0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | --- 664 --- 547 |--- --- 717 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.023 * P=0.047 * (e) P=0.035 * |P=0.479 (e) P=0.244 (e) | |POLY 3 | P=0.158 P=0.052 (e) P=0.080 |P=0.537 (e) P=0.249 (e) | |POLY 1.5 | P=0.191 P=0.056 (e) P=0.097 |P=0.570 (e) P=0.245 (e) | |POLY 6 | P=0.113 P=0.048 * (e) P=0.057 |P=0.472 (e) P=0.253 (e) | |LOGISTIC REGRESSION| P=0.188 P=0.050 (e) P=0.147 |P=0.518 (e) P=0.252 (e) | |COCH-ARM / FISHERS | P=0.237 P=0.059 (e) P=0.121 |P=0.595 (e) 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 | |=================================================================================================================================| | | |Skin | | Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 4/50 (8%) 5/50 (10%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 7.8% 10.6% 15.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/20 (15%) 2/16 (13%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 704 674 584 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.552 P=0.323 P=0.005 ** |(e) (e) (e) (e) | |POLY 3 | P=0.151 P=0.631 P=0.449 P=0.235 |(e) (e) (e) (e) | |POLY 1.5 | P=0.193 P=0.645 P=0.469 P=0.290 |(e) (e) (e) (e) | |POLY 6 | P=0.095 P=0.612 P=0.419 P=0.156 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.054 P=0.548 P=0.352 P=0.169 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.248 P=0.661N P=0.500 P=0.357 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 17 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Squamous Cell Papilloma, Papilloma, Squamous Cell | | Carcinoma or Keratoacanthoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 4/50 (8%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 7.8% 10.6% 18.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/20 (15%) 2/16 (13%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 704 674 584 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.552 P=0.323 P=0.002 ** |(e) (e) (e) (e) | |POLY 3 | P=0.080 P=0.631 P=0.449 P=0.141 |(e) (e) (e) (e) | |POLY 1.5 | P=0.107 P=0.645 P=0.469 P=0.185 |(e) (e) (e) (e) | |POLY 6 | P=0.048 * P=0.612 P=0.419 P=0.084 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.023 * P=0.548 P=0.352 P=0.092 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.145 P=0.661N P=0.500 P=0.243 |(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 | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma, Papilloma, or Keratoacanthoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 4/50 (8%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 7.8% 10.6% 18.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/20 (15%) 2/16 (13%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 704 674 584 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.552 P=0.323 P=0.002 ** |(e) (e) (e) (e) | |POLY 3 | P=0.080 P=0.631 P=0.449 P=0.141 |(e) (e) (e) (e) | |POLY 1.5 | P=0.107 P=0.645 P=0.469 P=0.185 |(e) (e) (e) (e) | |POLY 6 | P=0.048 * P=0.612 P=0.419 P=0.084 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.023 * P=0.548 P=0.352 P=0.092 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.145 P=0.661N P=0.500 P=0.243 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 18 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 0.0% 0.0% |0.0% 0.0% 2.4% 8.2% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 2/11 (18%) | |FIRST INCIDENCE | --- 730 (T) --- --- |--- --- 730 (T) 679 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.864 P=0.455 (e) (e) |P=0.003 ** (e) P=0.500 P=0.042 * | |POLY 3 | P=0.589N P=0.486 (e) (e) |P=0.016 * (e) P=0.510 P=0.105 | |POLY 1.5 | P=0.581N P=0.492 (e) (e) |P=0.018 * (e) P=0.507 P=0.113 | |POLY 6 | P=0.606N P=0.477 (e) (e) |P=0.014 * (e) P=0.514 P=0.090 | |LOGISTIC REGRESSION| (e) P=0.455 (e) (e) |P=0.007 ** (e) P=0.500 P=0.069 | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.020 * (e) P=0.500 P=0.121 | |=================================================================================================================================| | | | | | | 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%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 0.0% 0.0% |0.0% 0.0% 2.4% 5.5% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 1/11 (9%) | |FIRST INCIDENCE | --- 730 (T) --- --- |--- --- 730 (T) 679 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.864 P=0.455 (e) (e) |P=0.021 * (e) P=0.500 P=0.135 | |POLY 3 | P=0.589N P=0.486 (e) (e) |P=0.060 (e) P=0.510 P=0.220 | |POLY 1.5 | P=0.581N P=0.492 (e) (e) |P=0.065 (e) P=0.507 P=0.230 | |POLY 6 | P=0.606N P=0.477 (e) (e) |P=0.052 (e) P=0.514 P=0.201 | |LOGISTIC REGRESSION| (e) P=0.455 (e) (e) |P=0.039 * (e) P=0.500 P=0.185 | |COCH-ARM / FISHERS | P=0.567N P=0.500 (e) (e) |P=0.070 (e) P=0.500 P=0.247 | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 19 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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, Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 13/50 (26%) 9/50 (18%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 9.4% |0.0% 0.0% 31.0% 23.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 7/22 (32%) 1/11 (9%) | |FIRST INCIDENCE | --- --- --- 642 |--- --- 676 553 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.003 ** (e) (e) P=0.047 * |P<0.001 ** (e) P<0.001 ** P<0.001 ** | |POLY 3 | P=0.009 ** (e) (e) P=0.079 |P<0.001 ** (e) P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.009 ** (e) (e) P=0.096 |P<0.001 ** (e) P<0.001 ** P=0.002 ** | |POLY 6 | P=0.008 ** (e) (e) P=0.056 |P<0.001 ** (e) P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.009 ** (e) (e) P=0.092 |P<0.001 ** (e) P<0.001 ** P=0.003 ** | |COCH-ARM / FISHERS | P=0.012 * (e) (e) P=0.121 |P<0.001 ** (e) 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 | |=================================================================================================================================| | | |Stomach, Glandular | | Neuroendocrine Tumor, Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 4/50 (8%) |0/50 (0%) 1/50 (2%) 12/50 (24%) 26/50 (52%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 12.5% |0.0% 2.4% 28.9% 64.9% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 9/22 (41%) 9/11 (82%) | |FIRST INCIDENCE | --- --- --- 660 |--- 718 690 548 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.523 P<0.001 ** P<0.001 ** | |POLY 3 | P=0.002 ** (e) (e) P=0.033 * |P<0.001 ** P=0.508 P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.002 ** (e) (e) P=0.045 * |P<0.001 ** P=0.505 P<0.001 ** P<0.001 ** | |POLY 6 | P=0.002 ** (e) (e) P=0.020 * |P<0.001 ** P=0.511 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.015 * |P<0.001 ** P=0.513 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.003 ** (e) (e) P=0.059 |P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 20 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Testes | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 46/50 (92%) 48/49 (98%) 48/49 (98%) 50/50 (100%)| | |POLY-3 ADJUSTED (b)| 96.1% 98.0% 100.0% 100.0% | | |TERMINAL (d) | 20/20 (100%) 15/16 (94%) 15/15 (100%) 0/0 (0%) | | |FIRST INCIDENCE | 529 403 438 337 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.106 P=0.043 * P<0.001 ** | | |POLY 3 | P=0.080 P=0.529 P=0.204 P=0.194 | | |POLY 1.5 | P=0.042 * P=0.358 P=0.120 P=0.112 | | |POLY 6 | P=0.170 P=0.755 P=0.430 P=0.417 | | |LOGISTIC REGRESSION| P=0.008 ** P=0.126 P=0.037 * P=0.011 * | | |COCH-ARM / FISHERS | P=0.035 * P=0.187 P=0.187 P=0.059 | | |=================================================================================================================================| | | | | | | 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: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 4/50 (8%) 2/50 (4%) 3/48 (6%) |2/50 (4%) 4/49 (8%) 2/49 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 14.5% 10.4% 5.4% 9.8% |5.1% 9.8% 4.9% 0.0% | |TERMINAL (d) | 5/20 (25%) 4/16 (25%) 2/15 (13%) 0/0 (0%) |1/22 (5%) 2/25 (8%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | 704 730 (T) 730 (T) 600 |711 611 683 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.118 P=0.520N P=0.251N P=0.022 * |P=0.212N P=0.384 P=0.675N P=0.368N | |POLY 3 | P=0.256N P=0.416N P=0.167N P=0.409N |P=0.128N P=0.355 P=0.680N P=0.255N | |POLY 1.5 | P=0.222N P=0.395N P=0.153N P=0.336N |P=0.117N P=0.345 P=0.688N P=0.244N | |POLY 6 | P=0.317N P=0.447N P=0.193N P=0.547N |P=0.149N P=0.368 P=0.671N P=0.278N | |LOGISTIC REGRESSION| P=0.438 P=0.541N P=0.296N P=0.553 |P=0.135N P=0.352 P=0.672N P=0.322N | |COCH-ARM / FISHERS | P=0.185N P=0.370N P=0.134N P=0.264N |P=0.111N P=0.329 P=0.684 P=0.247N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 21 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/48 (0%) |0/50 (0%) 1/49 (2%) 2/49 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 2.5% 4.9% 5.5% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 2/22 (9%) 0/11 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 703 730 (T) 647 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.064 P=0.514 P=0.237 P=0.168 | |POLY 3 | (e) (e) (e) (e) |P=0.138 P=0.506 P=0.245 P=0.221 | |POLY 1.5 | (e) (e) (e) (e) |P=0.152 P=0.502 P=0.240 P=0.231 | |POLY 6 | (e) (e) (e) (e) |P=0.116 P=0.511 P=0.250 P=0.203 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.111 P=0.508 P=0.237 P=0.215 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.162 P=0.495 P=0.242 P=0.247 | |=================================================================================================================================| | | | | | | 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: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 4/50 (8%) 2/50 (4%) 3/48 (6%) |2/50 (4%) 5/49 (10%) 4/49 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 14.5% 10.4% 5.4% 9.8% |5.1% 12.2% 9.8% 5.5% | |TERMINAL (d) | 5/20 (25%) 4/16 (25%) 2/15 (13%) 0/0 (0%) |1/22 (5%) 2/25 (8%) 3/22 (14%) 0/11 (0%) | |FIRST INCIDENCE | 704 730 (T) 730 (T) 600 |711 611 683 647 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.118 P=0.520N P=0.251N P=0.022 * |P=0.456 P=0.260 P=0.353 P=0.525 | |POLY 3 | P=0.256N P=0.416N P=0.167N P=0.409N |P=0.487N P=0.232 P=0.355 P=0.669 | |POLY 1.5 | P=0.222N P=0.395N P=0.153N P=0.336N |P=0.459N P=0.223 P=0.345 P=0.684 | |POLY 6 | P=0.317N P=0.447N P=0.193N P=0.547N |P=0.539N P=0.244 P=0.366 P=0.637 | |LOGISTIC REGRESSION| P=0.438 P=0.541N P=0.296N P=0.553 |P=0.538N P=0.230 P=0.370 P=0.624 | |COCH-ARM / FISHERS | P=0.185N P=0.370N P=0.134N P=0.264N |P=0.440N P=0.210 P=0.329 P=0.691N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 22 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 1/48 (2%) |1/50 (2%) 1/49 (2%) 1/49 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.8% 2.6% 2.7% 3.3% |2.5% 2.5% 2.5% 2.8% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 1/22 (5%) 1/11 (9%) | |FIRST INCIDENCE | 626 535 674 547 |717 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.563N P=0.526N P=0.563N P=0.659N |P=0.457 P=0.733N P=0.756N P=0.621 | |POLY 3 | P=0.475N P=0.525N P=0.539N P=0.611N |P=0.601 P=0.755N P=0.753N P=0.743 | |POLY 1.5 | P=0.452N P=0.514N P=0.524N P=0.565N |P=0.619 P=0.758N P=0.757N P=0.754 | |POLY 6 | P=0.512N P=0.542N P=0.565N P=0.686N |P=0.567 P=0.752N P=0.748N P=0.721 | |LOGISTIC REGRESSION| P=0.357N P=0.453N P=0.491N P=0.423N |P=0.506 P=0.747N P=0.748N P=0.668 | |COCH-ARM / FISHERS | P=0.422N P=0.500N P=0.500N P=0.515N |P=0.632N P=0.747 P=0.747 P=0.753N | |=================================================================================================================================| | | | | | | 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) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 1/48 (2%) |1/50 (2%) 1/49 (2%) 1/49 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.8% 5.1% 5.3% 3.3% |2.5% 2.5% 2.5% 2.8% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 1/22 (5%) 1/11 (9%) | |FIRST INCIDENCE | 626 535 674 547 |717 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.546 P=0.651 P=0.611 P=0.659N |P=0.457 P=0.733N P=0.756N P=0.621 | |POLY 3 | P=0.488N P=0.669 P=0.655 P=0.611N |P=0.601 P=0.755N P=0.753N P=0.743 | |POLY 1.5 | P=0.441N P=0.680 P=0.670 P=0.565N |P=0.619 P=0.758N P=0.757N P=0.754 | |POLY 6 | P=0.571N P=0.652 P=0.628 P=0.686N |P=0.567 P=0.752N P=0.748N P=0.721 | |LOGISTIC REGRESSION| P=0.355N P=0.667N P=0.695 P=0.423N |P=0.506 P=0.747N P=0.748N P=0.668 | |COCH-ARM / FISHERS | P=0.388N P=0.691N P=0.691N P=0.515N |P=0.632N P=0.747 P=0.747 P=0.753N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 23 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Tongue | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.1% 0.0% 3.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- 596 --- 683 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.269 P=0.204 (e) P=0.227 |(e) (e) (e) (e) | |POLY 3 | P=0.442 P=0.224 (e) P=0.446 |(e) (e) (e) (e) | |POLY 1.5 | P=0.488 P=0.229 (e) P=0.472 |(e) (e) (e) (e) | |POLY 6 | P=0.366 P=0.216 (e) P=0.401 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.497 P=0.241 (e) P=0.389 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.539 P=0.247 (e) P=0.500 |(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 | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |4/50 (8%) 2/50 (4%) 3/50 (6%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| |10.0% 4.9% 7.2% 16.2% | |TERMINAL (d) | |1/22 (5%) 2/25 (8%) 1/22 (5%) 3/11 (27%) | |FIRST INCIDENCE | |641 730 (T) 627 600 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.050 P=0.306N P=0.477N P=0.146 | |POLY 3 | |P=0.165 P=0.327N P=0.476N P=0.319 | |POLY 1.5 | |P=0.181 P=0.329N P=0.484N P=0.349 | |POLY 6 | |P=0.142 P=0.327N P=0.470N P=0.263 | |LOGISTIC REGRESSION| |P=0.143 P=0.318N P=0.484N P=0.297 | |COCH-ARM / FISHERS | |P=0.194 P=0.339N P=0.500N P=0.370 | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 24 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | |=================================================================================================================================| | | |Uterus | | Sarcoma Stromal or Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |4/50 (8%) 3/50 (6%) 3/50 (6%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| |10.0% 7.4% 7.2% 16.2% | |TERMINAL (d) | |1/22 (5%) 3/25 (12%) 1/22 (5%) 3/11 (27%) | |FIRST INCIDENCE | |641 730 (T) 627 600 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.063 P=0.455N P=0.477N P=0.146 | |POLY 3 | |P=0.207 P=0.489N P=0.476N P=0.319 | |POLY 1.5 | |P=0.225 P=0.491N P=0.484N P=0.349 | |POLY 6 | |P=0.178 P=0.491N P=0.470N P=0.263 | |LOGISTIC REGRESSION| |P=0.174 P=0.475N P=0.484N P=0.297 | |COCH-ARM / FISHERS | |P=0.240 P=0.500N P=0.500N P=0.370 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Zymbal's Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 5.0% 0.0% 3.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 712 542 --- 654 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.606 P=0.459 P=0.612N P=0.422 |(e) (e) (e) (e) | |POLY 3 | P=0.546N P=0.484 P=0.521N P=0.696 |(e) (e) (e) (e) | |POLY 1.5 | P=0.526N P=0.491 P=0.513N P=0.728 |(e) (e) (e) (e) | |POLY 6 | P=0.573N P=0.474 P=0.535N P=0.633 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.456N P=0.545 P=0.551N P=0.675 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.500N P=0.500 P=0.500N P=0.753N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 25 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Leukemia: Lymphocytic, Monocytic, Mononuclear, or | | Undifferentiated | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 26/50 (52%) 27/50 (54%) 15/50 (30%) 13/50 (26%) |17/50 (34%) 20/50 (40%) 19/50 (38%) 28/50 (56%) | |POLY-3 ADJUSTED (b)| 56.0% 65.2% 36.4% 36.1% |38.3% 45.3% 42.4% 64.8% | |TERMINAL (d) | 8/20 (40%) 12/16 (75%) 5/15 (33%) 0/0 (0%) |5/22 (23%) 8/25 (32%) 6/22 (27%) 6/11 (55%) | |FIRST INCIDENCE | 521 602 521 467 |448 520 515 541 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.131 P=0.204 P=0.210N P=0.051 |P<0.001 ** P=0.461 P=0.484 P=0.004 ** | |POLY 3 | P=0.008N** P=0.246 P=0.047N* P=0.051N |P=0.007 ** P=0.324 P=0.426 P=0.008 ** | |POLY 1.5 | P=0.003N** P=0.351 P=0.033N* P=0.019N* |P=0.011 * P=0.334 P=0.426 P=0.013 * | |POLY 6 | P=0.042N* P=0.138 P=0.078N P=0.195N |P=0.004 ** P=0.313 P=0.424 P=0.004 ** | |LOGISTIC REGRESSION| P=0.006N** P=0.382 P=0.023N* P=0.010N* |P=0.017 * P=0.326 P=0.390 P=0.023 * | |COCH-ARM / FISHERS | P<0.001N** P=0.500 P=0.021N* P=0.007N** |P=0.017 * P=0.339 P=0.418 P=0.022 * | |=================================================================================================================================| | | | | | | 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 | | Mesothelioma: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 5/50 (10%) 12/50 (24%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 7.7% 12.7% 32.9% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 564 639 582 409 |--- 443 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.257 P=0.091 P<0.001 ** |P=0.562N P=0.504 (e) (e) | |POLY 3 | P<0.001 ** P=0.279 P=0.085 P<0.001 ** |P=0.559N P=0.512 (e) (e) | |POLY 1.5 | P<0.001 ** P=0.290 P=0.091 P<0.001 ** |P=0.562N P=0.508 (e) (e) | |POLY 6 | P<0.001 ** P=0.263 P=0.077 P<0.001 ** |P=0.553N P=0.516 (e) (e) | |LOGISTIC REGRESSION| P<0.001 ** P=0.313 P=0.133 P=0.007 ** |P=0.699N P=0.386 (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.309 P=0.102 P<0.001 ** |P=0.567N P=0.500 (e) (e) | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 26 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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 | | Mesothelioma: Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 5/50 (10%) 12/50 (24%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 7.7% 12.7% 32.9% |0.0% 2.4% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 564 639 582 409 |--- 443 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.257 P=0.091 P<0.001 ** |P=0.562N P=0.504 (e) (e) | |POLY 3 | P<0.001 ** P=0.279 P=0.085 P<0.001 ** |P=0.559N P=0.512 (e) (e) | |POLY 1.5 | P<0.001 ** P=0.290 P=0.091 P<0.001 ** |P=0.562N P=0.508 (e) (e) | |POLY 6 | P<0.001 ** P=0.263 P=0.077 P<0.001 ** |P=0.553N P=0.516 (e) (e) | |LOGISTIC REGRESSION| P<0.001 ** P=0.313 P=0.133 P=0.007 ** |P=0.699N P=0.386 (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.309 P=0.102 P<0.001 ** |P=0.567N P=0.500 (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 | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 49/50 (98%) 50/50 (100%) 48/50 (96%) 50/50 (100%)|43/50 (86%) 44/50 (88%) 43/50 (86%) 43/50 (86%) | |POLY-3 ADJUSTED (b)| 99.8% 100.0% 98.9% 100.0% |91.9% 91.2% 91.2% 92.1% | |TERMINAL (d) | 20/20 (100%) 16/16 (100%) 15/15 (100%) 0/0 (0%) |20/22 (91%) 22/25 (88%) 20/22 (91%) 11/11 (100%) | |FIRST INCIDENCE | 521 403 438 337 |407 347 527 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.131 P=0.094 P<0.001 ** |P=0.006 ** P=0.390N P=0.468N P=0.019 * | |POLY 3 | P=0.878 P=1.000 P=0.843N P=1.000 |P=0.553 P=0.608N P=0.610N P=0.661 | |POLY 1.5 | P=0.698 P=0.981 P=0.763N P=0.981 |P=0.530N P=0.640N P=0.607N P=0.615N | |POLY 6 | P=0.986N P=1.000 P=0.992N P=1.000 |P=0.423 P=0.585N P=0.617N P=0.567 | |LOGISTIC REGRESSION| P=0.281 (e) P=0.775N P=0.431 |P=0.532N P=0.595 P=0.464N P=0.609N | |COCH-ARM / FISHERS | P=0.461 P=0.500 P=0.500N P=0.500 |P=0.514N P=0.500 P=0.613N P=0.613N | |=================================================================================================================================| Date: 09/16/98 EXPERIMENT: 05187 TEST: 09 Page 27 Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 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) | 33/50 (66%) 32/50 (64%) 34/50 (68%) 39/50 (78%) |22/50 (44%) 28/50 (56%) 27/50 (54%) 34/50 (68%) | |POLY-3 ADJUSTED (b)| 68.9% 73.1% 74.1% 85.7% |48.5% 60.0% 59.1% 76.9% | |TERMINAL (d) | 12/20 (60%) 12/16 (75%) 10/15 (67%) 0/0 (0%) |7/22 (32%) 11/25 (44%) 10/22 (46%) 9/11 (82%) | |FIRST INCIDENCE | 344 431 467 409 |407 443 515 534 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.279 P=0.134 P<0.001 ** |P<0.001 ** P=0.321 P=0.320 P<0.001 ** | |POLY 3 | P=0.026 * P=0.413 P=0.369 P=0.035 * |P=0.004 ** P=0.178 P=0.205 P=0.003 ** | |POLY 1.5 | P=0.042 * P=0.517 P=0.395 P=0.063 |P=0.007 ** P=0.172 P=0.207 P=0.006 ** | |POLY 6 | P=0.013 * P=0.300 P=0.345 P=0.014 * |P=0.002 ** P=0.187 P=0.210 P<0.001 ** | |LOGISTIC REGRESSION| P=0.044 * P=0.550N P=0.500 P=0.200 |P=0.014 * P=0.137 P=0.202 P=0.013 * | |COCH-ARM / FISHERS | P=0.081 P=0.500N P=0.500 P=0.133 |P=0.014 * P=0.159 P=0.212 P=0.013 * | |=================================================================================================================================| | | | | | | 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) | 50/50 (100%) 50/50 (100%) 48/50 (96%) 50/50 (100%)|47/50 (94%) 49/50 (98%) 48/50 (96%) 47/50 (94%) | |POLY-3 ADJUSTED (b)| 100.0% 100.0% 98.9% 100.0% |95.8% 98.0% 99.4% 97.8% | |TERMINAL (d) | 20/20 (100%) 16/16 (100%) 15/15 (100%) 0/0 (0%) |20/22 (91%) 24/25 (96%) 22/22 (100%) 11/11 (100%) | |FIRST INCIDENCE | 344 403 438 337 |407 347 515 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) P=0.119 (e) |P=0.007 ** P=0.436N P=0.511N P=0.022 * | |POLY 3 | P=0.861N (e) P=0.796N (e) |P=0.384 P=0.485 P=0.305 P=0.514 | |POLY 1.5 | P=0.774N (e) P=0.634N (e) |P=0.580 P=0.450 P=0.385 P=0.634 | |POLY 6 | P=0.984N (e) P=0.991N (e) |P=0.186 P=0.493 P=0.254 P=0.347 | |LOGISTIC REGRESSION| P=0.707 (e) P=0.465N (e) |P=0.367N P=0.338 P=0.652 P=0.583N | |COCH-ARM / FISHERS | P=0.595N (e) P=0.247N (e) |P=0.477N P=0.309 P=0.500 P=0.661N | |=================================================================================================================================| (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).