TDMS Study 05187-09 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:12:12 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 NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:12:12 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 Cortex Hyperplasia Focal Adrenal Medulla Hyperplasia Focal Blood Vessel Mineralization Blood Vessel: Aorta Mineralization Bone Fibrous Osteodystrophy Bone Marrow Hyperplasia Heart: Myocardium Degeneration Mineralization Intestine Large, Rectum Parasite Metazoan Intestine Small, Duodenum Ulcer Islets, Pancreatic Hyperplasia Kidney Inflammation Focal Nephropathy Kidney: Renal Tubule Hyperplasia Focal Hyperplasia Oncocytic Liver Basophilic Focus Degeneration Cystic Focal Eosinophilic Focus Hepatodiaphragmatic Nodule Mixed Cell Focus Liver: Bile Duct Hyperplasia Hyperplasia Atypical Focal Liver: Centrilobular Degeneration Liver: Hepatocyte Hypertrophy Liver: Oval Cell Hyperplasia Lung: Interstitium Mineralization Mammary Gland Dilatation Mesentery: Fat Necrosis Nose Inflammation Pancreas: Acinus Atrophy Pancreas: Artery Inflammation Chronic Parathyroid Gland Hyperplasia Pituitary Gland: Pars Distalis Hyperplasia Focal Preputial Gland Cyst Prostate Inflammation Chronic Salivary Glands: Submandibular Gland Cytoplasmic Alteration Seminal Vesicle Inflammation Spleen Fibrosis Hematopoietic Cell Proliferation Stomach, Forestomach Mineralization Ulcer Stomach, Glandular Atrophy Mineralization Stomach, Glandular: Neuroendocrine Cell Hyperplasia Testes: Interstitial Cell Hyperplasia Thyroid Gland: C-Cell Hyperplasia =============================================================== NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98 EXPERIMENT: 05187 TEST: 09 TIME: 09:12:12 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B PATHOLOGIST: MISSING CAS: 93-15-2 Female Rats ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Heart: Myocardium Degeneration Kidney Nephropathy Liver Basophilic Focus Clear Cell Focus Degeneration Cystic Focal Eosinophilic Focus Mixed Cell Focus Liver: Bile Duct Hyperplasia Liver: Hepatocyte Hypertrophy Liver: Oval Cell Hyperplasia Mammary Gland Hyperplasia Focal Pituitary Gland Angiectasis Pituitary Gland: Pars Distalis Hyperplasia Focal Salivary Glands: Submandibular Gland Cytoplasmic Alteration Spleen Fibrosis Hematopoietic Cell Proliferation Spleen: Red Pulp Necrosis Stomach, Glandular Atrophy Stomach, Glandular: Neuroendocrine Cell Hyperplasia Thyroid Gland: C-Cell Hyperplasia =============================================================== Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 1 Statistical Analysis of Non-neoplastic Lesions 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 Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 12/50 (24%) 6/50 (12%) 4/50 (8%) |13/50 (26%) 11/50 (22%) 7/50 (14%) 9/49 (18%) | |POLY-3 ADJUSTED (b)| 30.5% 30.2% 16.0% 12.4% |31.3% 26.7% 16.7% 24.2% | |TERMINAL (d) | 9/20 (45%) 6/16 (38%) 5/15 (33%) 0/0 (0%) |6/22 (27%) 8/25 (32%) 3/22 (14%) 3/11 (27%) | |FIRST INCIDENCE | 610 639 659 642 |459 683 637 572 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.445 P=0.456 P=0.171N P=0.275 |P=0.488 P=0.316N P=0.111N P=0.515 | |POLY 3 | P=0.019N* P=0.584N P=0.099N P=0.055N |P=0.224N P=0.412N P=0.091N P=0.325N | |POLY 1.5 | P=0.010N* P=0.548N P=0.082N P=0.030N* |P=0.199N P=0.406N P=0.095N P=0.279N | |POLY 6 | P=0.053N P=0.565 P=0.136N P=0.140N |P=0.275N P=0.427N P=0.089N P=0.423N | |LOGISTIC REGRESSION| P=0.112N P=0.558 P=0.142N P=0.176N |P=0.259N P=0.362N P=0.089N P=0.306N | |COCH-ARM / FISHERS | P=0.005N** P=0.500N P=0.062N P=0.016N* |P=0.183N P=0.408N P=0.105N P=0.251N | |=================================================================================================================================| | | | | | | 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 Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 2.6% 0.0% 0.0% |0.0% 4.9% 0.0% 2.8% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 588 650 --- --- |--- 724 --- 660 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.286N P=0.740 P=0.519N P=0.539N |P=0.415 P=0.268 (e) P=0.457 | |POLY 3 | P=0.251N P=0.744 P=0.523N P=0.557N |P=0.520 P=0.246 (e) P=0.484 | |POLY 1.5 | P=0.245N P=0.751 P=0.514N P=0.530N |P=0.530 P=0.243 (e) P=0.492 | |POLY 6 | P=0.266N P=0.734 P=0.538N P=0.604N |P=0.497 P=0.249 (e) P=0.468 | |LOGISTIC REGRESSION| P=0.208N P=0.740N P=0.456N P=0.426N |P=0.491 P=0.255 (e) P=0.495 | |COCH-ARM / FISHERS | P=0.236N P=0.753N P=0.500N P=0.500N |P=0.534 P=0.247 (e) P=0.495 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 2 Statistical Analysis of Non-neoplastic Lesions 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 | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 16/50 (32%) 20/50 (40%) 21/50 (42%) 21/50 (42%) |4/50 (8%) 9/50 (18%) 4/50 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 36.1% 46.9% 50.8% 54.9% |10.0% 20.6% 9.6% 8.3% | |TERMINAL (d) | 6/20 (30%) 6/16 (38%) 9/15 (60%) 0/0 (0%) |2/22 (9%) 3/25 (12%) 2/22 (9%) 2/11 (18%) | |FIRST INCIDENCE | 553 535 521 457 |609 443 627 679 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.136 P=0.064 P<0.001 ** |P=0.439N P=0.164 P=0.622N P=0.551 | |POLY 3 | P=0.049 * P=0.204 P=0.117 P=0.059 |P=0.265N P=0.150 P=0.620N P=0.556N | |POLY 1.5 | P=0.102 P=0.230 P=0.145 P=0.112 |P=0.238N P=0.137 P=0.628N P=0.528N | |POLY 6 | P=0.011 * P=0.172 P=0.081 P=0.016 * |P=0.319N P=0.165 P=0.614N P=0.609N | |LOGISTIC REGRESSION| P=0.098 P=0.249 P=0.153 P=0.144 |P=0.222N P=0.101 P=0.622N P=0.581N | |COCH-ARM / FISHERS | P=0.202 P=0.266 P=0.204 P=0.204 |P=0.223N P=0.117 P=0.643N 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 | |=================================================================================================================================| | | |Blood Vessel | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 7/50 (14%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 5.1% 7.8% 21.0% |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 | 662 596 568 568 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.454 P=0.273 P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P=0.003 ** P=0.481 P=0.278 P=0.012 * |(e) (e) (e) (e) | |POLY 1.5 | P=0.005 ** P=0.489 P=0.288 P=0.019 * |(e) (e) (e) (e) | |POLY 6 | P=0.002 ** P=0.469 P=0.262 P=0.005 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.012 * P=0.538 P=0.350 P=0.024 * |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.009 ** P=0.500 P=0.309 P=0.030 * |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 3 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 0/50 (0%) 9/50 (18%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 11.8% 0.0% 23.4% 18.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 2/15 (13%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 626 --- 664 650 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.059N P=0.073 P=0.003 ** |(e) (e) (e) (e) | |POLY 3 | P=0.070 P=0.038N* P=0.139 P=0.319 |(e) (e) (e) (e) | |POLY 1.5 | P=0.108 P=0.035N* P=0.159 P=0.403 |(e) (e) (e) (e) | |POLY 6 | P=0.030 * P=0.044N* P=0.113 P=0.194 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.028 * P=0.037N* P=0.130 P=0.193 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.169 P=0.028N* P=0.194 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 | |=================================================================================================================================| | | |Bone | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 2/50 (4%) 12/50 (24%) 14/50 (28%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 18.7% 5.1% 30.5% 39.9% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 3/15 (20%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 626 596 568 568 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.100N P=0.086 P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P=0.002 ** P=0.060N P=0.159 P=0.030 * |(e) (e) (e) (e) | |POLY 1.5 | P=0.005 ** P=0.053N P=0.183 P=0.059 |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** P=0.072N P=0.125 P=0.008 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.002 ** P=0.050N P=0.171 P=0.028 * |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.013 * P=0.046N* P=0.227 P=0.114 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 4 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Bone | | Hyperostosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 5/50 (10%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.5% 2.4% 11.5% 10.6% | |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 | --- --- --- --- |555 673 515 553 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.052 P=0.748N P=0.129 P=0.153 | |POLY 3 | (e) (e) (e) (e) |P=0.062 P=0.754N P=0.121 P=0.162 | |POLY 1.5 | (e) (e) (e) (e) |P=0.071 P=0.756N P=0.113 P=0.173 | |POLY 6 | (e) (e) (e) (e) |P=0.049 * P=0.752N P=0.131 P=0.142 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.079 P=0.746 P=0.073 P=0.166 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.078 P=0.753N P=0.102 P=0.181 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Bone | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 5.2% 0.0% 0.0% |0.0% 2.5% 4.8% 0.0% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 2/22 (9%) 0/11 (0%) | |FIRST INCIDENCE | 521 673 --- --- |--- 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.342N P=0.458 P=0.513N P=0.521N |P=0.543 P=0.525 P=0.237 (e) | |POLY 3 | P=0.227N P=0.472 P=0.524N P=0.558N |P=0.640 P=0.508 P=0.249 (e) | |POLY 1.5 | P=0.209N P=0.484 P=0.514N P=0.530N |P=0.630N P=0.505 P=0.245 (e) | |POLY 6 | P=0.265N P=0.455 P=0.539N P=0.605N |P=0.581 P=0.511 P=0.253 (e) | |LOGISTIC REGRESSION| P=0.174N P=0.523 P=0.413N P=0.386N |(e) P=0.525 P=0.237 (e) | |COCH-ARM / FISHERS | P=0.188N P=0.500 P=0.500N P=0.500N |P=0.616N P=0.500 P=0.247 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 5 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Bone Marrow | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 2/49 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 7.1% 0.0% 5.3% 0.0% |5.1% 0.0% 4.9% 5.5% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |1/22 (5%) 0/25 (0%) 1/22 (5%) 1/11 (9%) | |FIRST INCIDENCE | 521 --- 610 --- |641 --- 613 679 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.273N P=0.157N P=0.579N P=0.521N |P=0.280 P=0.226N P=0.681N P=0.508 | |POLY 3 | P=0.159N P=0.134N P=0.545N P=0.181N |P=0.405 P=0.230N P=0.680N P=0.665 | |POLY 1.5 | P=0.141N P=0.127N P=0.528N P=0.148N |P=0.426 P=0.232N P=0.688N P=0.683 | |POLY 6 | P=0.199N P=0.144N P=0.572N P=0.250N |P=0.372 P=0.228N P=0.671N P=0.629 | |LOGISTIC REGRESSION| P=0.115N P=0.115N P=0.477N P=0.123N |P=0.414 P=0.231N P=0.695N P=0.640 | |COCH-ARM / FISHERS | P=0.125N P=0.121N P=0.500N P=0.121N |P=0.444 P=0.247N P=0.684 P=0.691N | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 18/50 (36%) 14/50 (28%) 22/50 (44%) 23/50 (46%) |4/50 (8%) 15/50 (30%) 11/49 (22%) 20/50 (40%) | |POLY-3 ADJUSTED (b)| 41.4% 33.7% 53.6% 56.2% |10.1% 34.0% 26.8% 49.6% | |TERMINAL (d) | 10/20 (50%) 7/16 (44%) 10/15 (67%) 0/0 (0%) |3/22 (14%) 8/25 (32%) 8/22 (36%) 8/11 (73%) | |FIRST INCIDENCE | 564 406 522 409 |549 347 676 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.490N P=0.065 P<0.001 ** |P<0.001 ** P=0.013 * P=0.048 * P<0.001 ** | |POLY 3 | P=0.035 * P=0.304N P=0.174 P=0.115 |P<0.001 ** P=0.007 ** P=0.046 * P<0.001 ** | |POLY 1.5 | P=0.053 P=0.282N P=0.206 P=0.156 |P<0.001 ** P=0.006 ** P=0.044 * P<0.001 ** | |POLY 6 | P=0.015 * P=0.347N P=0.131 P=0.059 |P<0.001 ** P=0.009 ** P=0.049 * P<0.001 ** | |LOGISTIC REGRESSION| P=0.045 * P=0.302N P=0.150 P=0.234 |P<0.001 ** P=0.005 ** P=0.058 P<0.001 ** | |COCH-ARM / FISHERS | P=0.081 P=0.260N P=0.270 P=0.208 |P<0.001 ** P=0.005 ** P=0.041 * P<0.001 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 6 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Bone Marrow | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 4.9% 0.0% 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) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.539N P=0.266 (e) (e) | |POLY 3 | (e) (e) (e) (e) |P=0.406N P=0.245 (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.404N P=0.243 (e) (e) | |POLY 6 | (e) (e) (e) (e) |P=0.412N P=0.248 (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.266 (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.406N 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 | |=================================================================================================================================| | | |Bone Marrow | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/49 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 5.1% 5.3% 3.2% |0.0% 2.4% 0.0% 5.4% | |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 | --- 575 661 659 |--- 637 --- 589 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.188 P=0.219 P=0.164 P=0.367 |P=0.102 P=0.505 (e) P=0.194 | |POLY 3 | P=0.324 P=0.225 P=0.216 P=0.446 |P=0.132 P=0.509 (e) P=0.223 | |POLY 1.5 | P=0.392 P=0.230 P=0.224 P=0.472 |P=0.137 P=0.506 (e) P=0.232 | |POLY 6 | P=0.216 P=0.218 P=0.204 P=0.402 |P=0.124 P=0.514 (e) P=0.206 | |LOGISTIC REGRESSION| P=0.448 P=0.257 P=0.216 P=0.472 |P=0.145 P=0.491 (e) P=0.240 | |COCH-ARM / FISHERS | P=0.469 P=0.247 P=0.247 P=0.500 |P=0.140 P=0.500 (e) P=0.247 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 7 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Bone Marrow: Myeloid Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.5% 4.8% 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 | --- --- --- --- |641 606 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.213N P=0.522 P=0.495N P=0.550N | |POLY 3 | (e) (e) (e) (e) |P=0.192N P=0.517 P=0.494N P=0.518N | |POLY 1.5 | (e) (e) (e) (e) |P=0.190N P=0.511 P=0.497N P=0.507N | |POLY 6 | (e) (e) (e) (e) |P=0.196N P=0.524 P=0.490N P=0.538N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.190N P=0.481 P=0.514N P=0.498N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.189N P=0.500 P=0.505N 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 | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 3/50 (6%) 1/50 (2%) |4/50 (8%) 9/50 (18%) 3/50 (6%) 8/50 (16%) | |POLY-3 ADJUSTED (b)| 4.8% 7.6% 7.9% 3.1% |10.1% 21.8% 7.1% 20.9% | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 2/15 (13%) 0/0 (0%) |1/22 (5%) 7/25 (28%) 0/22 (0%) 1/11 (9%) | |FIRST INCIDENCE | 668 572 601 523 |597 637 557 541 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.452 P=0.442 P=0.390 P=0.643 |P=0.078 P=0.166 P=0.463N P=0.066 | |POLY 3 | P=0.475N P=0.476 P=0.456 P=0.592N |P=0.255 P=0.125 P=0.466N P=0.154 | |POLY 1.5 | P=0.411N P=0.487 P=0.473 P=0.548N |P=0.271 P=0.123 P=0.479N P=0.169 | |POLY 6 | P=0.540 P=0.462 P=0.426 P=0.667N |P=0.226 P=0.126 P=0.452N P=0.125 | |LOGISTIC REGRESSION| P=0.348N P=0.513 P=0.445 P=0.481N |P=0.245 P=0.134 P=0.500N P=0.167 | |COCH-ARM / FISHERS | P=0.343N P=0.500 P=0.500 P=0.500N |P=0.278 P=0.117 P=0.500N P=0.178 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 8 Statistical Analysis of Non-neoplastic Lesions 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 | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.1% 2.7% 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 | --- 650 658 684 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.255 P=0.220 P=0.469 P=0.202 |(e) (e) (e) (e) | |POLY 3 | P=0.375 P=0.224 P=0.481 P=0.446 |(e) (e) (e) (e) | |POLY 1.5 | P=0.434 P=0.229 P=0.488 P=0.472 |(e) (e) (e) (e) | |POLY 6 | P=0.279 P=0.217 P=0.469 P=0.401 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.454 P=0.240 P=0.502 P=0.384 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.500 P=0.247 P=0.500 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 | |=================================================================================================================================| | | |Brain: Hypothalamus | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |9/50 (18%) 12/50 (24%) 6/50 (12%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 2.6% 0.0% |22.4% 28.5% 14.0% 18.5% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |6/22 (27%) 8/25 (32%) 1/22 (5%) 1/11 (9%) | |FIRST INCIDENCE | --- 730 (T) 601 --- |597 609 541 541 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.624 P=0.455 P=0.476 (e) |P=0.546 P=0.415 P=0.269N P=0.442 | |POLY 3 | P=0.648 P=0.486 P=0.482 (e) |P=0.233N P=0.352 P=0.236N P=0.443N | |POLY 1.5 | P=0.633N P=0.492 P=0.489 (e) |P=0.213N P=0.338 P=0.256N P=0.410N | |POLY 6 | P=0.530 P=0.477 P=0.470 (e) |P=0.273N P=0.372 P=0.215N P=0.510N | |LOGISTIC REGRESSION| P=0.630N P=0.455 P=0.536 (e) |P=0.240N P=0.349 P=0.270N P=0.476N | |COCH-ARM / FISHERS | P=0.595N P=0.500 P=0.500 (e) |P=0.204N P=0.312 P=0.288N P=0.393N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 9 Statistical Analysis of Non-neoplastic Lesions 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 Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/48 (4%) 1/46 (2%) 2/49 (4%) 1/46 (2%) | |POLY-3 ADJUSTED (b)| |5.2% 2.7% 4.8% 3.0% | |TERMINAL (d) | |0/21 (0%) 1/22 (5%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | |597 730 (T) 557 611 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.555N P=0.492N P=0.679N P=0.579N | |POLY 3 | |P=0.479N P=0.515N P=0.670N P=0.547N | |POLY 1.5 | |P=0.465N P=0.514N P=0.676N P=0.528N | |POLY 6 | |P=0.501N P=0.518N P=0.663N P=0.579N | |LOGISTIC REGRESSION| |P=0.448N P=0.513N P=0.689 P=0.509N | |COCH-ARM / FISHERS | |P=0.454N P=0.516N P=0.684N P=0.516N | |=================================================================================================================================| | | | | | | 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 Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/48 (4%) 3/46 (7%) 1/49 (2%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| |5.3% 8.1% 2.5% 0.0% | |TERMINAL (d) | |1/21 (5%) 3/22 (14%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | |717 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.190N P=0.527 P=0.485N P=0.374N | |POLY 3 | |P=0.117N P=0.486 P=0.476N P=0.267N | |POLY 1.5 | |P=0.111N P=0.485 P=0.483N P=0.255N | |POLY 6 | |P=0.128N P=0.487 P=0.469N P=0.290N | |LOGISTIC REGRESSION| |P=0.167N P=0.503 P=0.464N P=0.340N | |COCH-ARM / FISHERS | |P=0.107N P=0.480 P=0.492N P=0.258N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 10 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Heart: Atrium | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 5/50 (10%) 4/50 (8%) 2/50 (4%) |0/50 (0%) 2/50 (4%) 1/49 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 14.1% 12.7% 10.5% 6.2% |0.0% 4.8% 2.5% 0.0% | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 553 575 596 502 |--- 520 712 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.542 P=0.614 P=0.561N P=0.660N |P=0.546N P=0.258 P=0.523 (e) | |POLY 3 | P=0.175N P=0.556N P=0.443N P=0.241N |P=0.483N P=0.249 P=0.508 (e) | |POLY 1.5 | P=0.131N P=0.531N P=0.414N P=0.184N |P=0.471N P=0.245 P=0.503 (e) | |POLY 6 | P=0.273N P=0.589N P=0.492N P=0.366N |P=0.507N P=0.254 P=0.513 (e) | |LOGISTIC REGRESSION| P=0.113N P=0.508N P=0.393N P=0.110N |P=0.465N P=0.220 P=0.513 (e) | |COCH-ARM / FISHERS | P=0.092N P=0.500N P=0.370N P=0.134N |P=0.467N P=0.247 P=0.495 (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 | |=================================================================================================================================| | | |Heart: Myocardium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 45/50 (90%) 41/50 (82%) 34/50 (68%) 37/50 (74%) |35/50 (70%) 30/50 (60%) 26/49 (53%) 20/49 (41%) | |POLY-3 ADJUSTED (b)| 92.7% 85.4% 72.4% 81.0% |77.5% 68.9% 59.3% 49.8% | |TERMINAL (d) | 19/20 (95%) 14/16 (88%) 9/15 (60%) 0/0 (0%) |16/22 (73%) 20/25 (80%) 15/22 (68%) 7/11 (64%) | |FIRST INCIDENCE | 521 403 438 409 |459 450 515 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.367 P=0.469N P<0.001 ** |P=0.333N P=0.121N P=0.074N P=0.331N | |POLY 3 | P=0.047N* P=0.187N P=0.005N** P=0.059N |P=0.002N** P=0.234N P=0.043N* P=0.003N** | |POLY 1.5 | P=0.033N* P=0.175N P=0.006N** P=0.040N* |P<0.001N** P=0.201N P=0.045N* P=0.002N** | |POLY 6 | P=0.093N P=0.228N P=0.007N** P=0.131N |P=0.006N** P=0.316N P=0.049N* P=0.012N* | |LOGISTIC REGRESSION| P=0.029N* P=0.219N P=0.009N** P=0.062N |P=0.003N** P=0.127N P=0.035N* P=0.004N** | |COCH-ARM / FISHERS | P=0.026N* P=0.194N P=0.006N** P=0.033N* |P=0.002N** P=0.201N P=0.063N P=0.003N** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 11 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Heart: Myocardium | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 2/50 (4%) 11/50 (22%) 9/50 (18%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 11.8% 5.1% 27.8% 26.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 2/15 (13%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 626 596 568 598 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.316N P=0.031 * P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P=0.013 * P=0.247N P=0.059 P=0.084 |(e) (e) (e) (e) | |POLY 1.5 | P=0.024 * P=0.233N P=0.067 P=0.128 |(e) (e) (e) (e) | |POLY 6 | P=0.004 ** P=0.268N P=0.048 * P=0.037 * |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.018 * P=0.223N P=0.068 P=0.069 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.050 P=0.218N P=0.086 P=0.194 |(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 | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 5/50 (10%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 5.1% 12.6% 3.1% |2.5% 0.0% 0.0% 2.8% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 1/11 (9%) | |FIRST INCIDENCE | 730 (T) 638 502 568 |719 --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.322 P=0.445 P=0.081 P=0.481 |P=0.476 P=0.484N P=0.500N P=0.618 | |POLY 3 | P=0.372 P=0.480 P=0.090 P=0.698 |P=0.579 P=0.492N P=0.490N P=0.743 | |POLY 1.5 | P=0.468 P=0.488 P=0.094 P=0.730 |P=0.587 P=0.495N P=0.493N P=0.754 | |POLY 6 | P=0.221 P=0.469 P=0.083 P=0.637 |P=0.568 P=0.490N P=0.486N P=0.721 | |LOGISTIC REGRESSION| P=0.534N P=0.485 P=0.135 P=0.774 |P=0.515 P=0.487N P=0.484N P=0.664 | |COCH-ARM / FISHERS | P=0.569 P=0.500 P=0.102 P=0.753N |P=0.595 P=0.500N P=0.500N P=0.753N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 12 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 3/49 (6%) 5/49 (10%) 4/50 (8%) |2/50 (4%) 4/50 (8%) 2/50 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.5% 7.7% 13.0% 12.1% |5.0% 9.8% 4.7% 5.4% | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 2/15 (13%) 0/0 (0%) |1/22 (5%) 4/25 (16%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 403 521 502 |619 730 (T) 541 548 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010 * P=0.246 P=0.071 P=0.030 * |P=0.549 P=0.388 P=0.665N P=0.605 | |POLY 3 | P=0.079 P=0.291 P=0.087 P=0.121 |P=0.480N P=0.350 P=0.672N P=0.672 | |POLY 1.5 | P=0.113 P=0.298 P=0.092 P=0.150 |P=0.465N P=0.347 P=0.680N P=0.686 | |POLY 6 | P=0.039 * P=0.280 P=0.079 P=0.081 |P=0.508N P=0.352 P=0.664N P=0.643 | |LOGISTIC REGRESSION| P=0.210 P=0.323 P=0.110 P=0.223 |P=0.458N P=0.362 P=0.680 P=0.692N | |COCH-ARM / FISHERS | P=0.162 P=0.309 P=0.102 P=0.187 |P=0.456N P=0.339 P=0.691N P=0.691N | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION 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%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 722 680 --- --- |--- 520 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.159N P=0.397N P=0.193N P=1.000 |P=0.562N P=0.509 (e) (e) | |POLY 3 | P=0.046N* P=0.329N P=0.138N P=0.177N |P=0.559N P=0.511 (e) (e) | |POLY 1.5 | P=0.045N* P=0.319N P=0.130N P=0.146N |P=0.562N P=0.507 (e) (e) | |POLY 6 | P=0.048N* P=0.344N P=0.151N P=0.244N |P=0.553N P=0.515 (e) (e) | |LOGISTIC REGRESSION| P=0.103N P=0.365N P=0.199N P=0.961N |P=0.621N P=0.437 (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) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 13 Statistical Analysis of Non-neoplastic Lesions 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 | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 4/50 (8%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 10.2% 2.6% 0.0% |2.5% 0.0% 0.0% 2.8% | |TERMINAL (d) | 0/20 (0%) 2/16 (13%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 1/11 (9%) | |FIRST INCIDENCE | --- 589 568 --- |616 --- --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.580N P=0.047 * P=0.496 (e) |P=0.515 P=0.495N P=0.485N P=0.664 | |POLY 3 | P=0.416N P=0.053 P=0.482 (e) |P=0.579 P=0.494N P=0.492N P=0.741 | |POLY 1.5 | P=0.356N P=0.056 P=0.489 (e) |P=0.587 P=0.496N P=0.494N P=0.753 | |POLY 6 | P=0.534N P=0.049 * P=0.471 (e) |P=0.567 P=0.493N P=0.489N P=0.717 | |LOGISTIC REGRESSION| P=0.304N P=0.058 P=0.556 (e) |P=0.591 P=0.517N P=0.518N P=0.754 | |COCH-ARM / FISHERS | P=0.296N P=0.059 P=0.500 (e) |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 | |=================================================================================================================================| | | |Kidney | | Hydronephrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.3% 0.0% |0.0% 4.8% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- --- 664 --- |--- 450 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.293 (e) P=0.165 (e) |P=0.460N P=0.256 (e) (e) | |POLY 3 | P=0.443 (e) P=0.216 (e) |P=0.406N P=0.250 (e) (e) | |POLY 1.5 | P=0.520 (e) P=0.224 (e) |P=0.404N P=0.246 (e) (e) | |POLY 6 | P=0.307 (e) P=0.204 (e) |P=0.411N P=0.254 (e) (e) | |LOGISTIC REGRESSION| P=0.516 (e) P=0.216 (e) |P=0.429N P=0.204 (e) (e) | |COCH-ARM / FISHERS | P=0.595 (e) P=0.247 (e) |P=0.409N P=0.247 (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 14 Statistical Analysis of Non-neoplastic Lesions 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 | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 3/50 (6%) 1/50 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 7.2% 2.4% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 520 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.449N P=0.136 P=0.500 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.386N P=0.130 P=0.510 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.374N P=0.126 P=0.507 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.412N P=0.136 P=0.514 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.370N P=0.106 P=0.500 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.372N P=0.121 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 | |=================================================================================================================================| | | |Kidney | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 2.7% 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 | --- 650 712 575 |--- --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.032 * P=0.483 P=0.388 P=0.129 |P=0.662 (e) P=0.520 (e) | |POLY 3 | P=0.104 P=0.487 P=0.480 P=0.184 |P=0.652 (e) P=0.511 (e) | |POLY 1.5 | P=0.126 P=0.493 P=0.488 P=0.208 |P=0.676 (e) P=0.507 (e) | |POLY 6 | P=0.074 P=0.480 P=0.467 P=0.148 |P=0.603 (e) P=0.516 (e) | |LOGISTIC REGRESSION| P=0.142 P=0.509 P=0.449 P=0.268 |P=0.687 (e) P=0.508 (e) | |COCH-ARM / FISHERS | P=0.153 P=0.500 P=0.500 P=0.247 |P=0.692 (e) P=0.500 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 15 Statistical Analysis of Non-neoplastic Lesions 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 | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 49/50 (98%) 46/50 (92%) 48/50 (96%) 50/50 (100%)|35/50 (70%) 42/50 (84%) 41/50 (82%) 44/49 (90%) | |POLY-3 ADJUSTED (b)| 99.8% 95.8% 98.5% 100.0% |80.5% 90.4% 87.7% 94.3% | |TERMINAL (d) | 20/20 (100%) 16/16 (100%) 15/15 (100%) 0/0 (0%) |22/22 (100%) 25/25 (100%) 22/22 (100%) 11/11 (100%) | |FIRST INCIDENCE | 521 403 438 337 |459 347 444 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.268 P=0.095 P<0.001 ** |P<0.001 ** P=0.349 P=0.244 P<0.001 ** | |POLY 3 | P=0.387 P=0.192N P=0.707N P=1.000 |P=0.029 * P=0.112 P=0.229 P=0.022 * | |POLY 1.5 | P=0.277 P=0.155N P=0.699N P=0.981 |P=0.023 * P=0.099 P=0.174 P=0.017 * | |POLY 6 | P=0.558 P=0.374N P=0.841N P=1.000 |P=0.044 * P=0.133 P=0.330 P=0.033 * | |LOGISTIC REGRESSION| P=0.066 P=0.255N P=0.773N P=0.431 |P=0.009 ** P=0.102 P=0.192 P=0.006 ** | |COCH-ARM / FISHERS | P=0.199 P=0.181N P=0.500N P=0.500 |P=0.016 * P=0.077 P=0.121 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 | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.2% 0.0% 0.0% |0.0% 0.0% 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 | --- 725 --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.752 P=0.193 (e) (e) |(e) (e) (e) (e) | |POLY 3 | P=0.464N P=0.221 (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.437N P=0.228 (e) (e) |(e) (e) (e) (e) | |POLY 6 | P=0.516N P=0.211 (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.746 P=0.180 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 16 Statistical Analysis of Non-neoplastic Lesions 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 | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 1/50 (2%) 7/50 (14%) 4/50 (8%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 11.9% 2.6% 18.6% 12.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/20 (10%) 1/16 (6%) 5/15 (33%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 642 730 (T) 673 646 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.003 ** P=0.158N P=0.195 P=0.064 |(e) (e) (e) (e) | |POLY 3 | P=0.312 P=0.121N P=0.301 P=0.611 |(e) (e) (e) (e) | |POLY 1.5 | P=0.392 P=0.112N P=0.332 P=0.587N |(e) (e) (e) (e) | |POLY 6 | P=0.193 P=0.136N P=0.251 P=0.471 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.103 P=0.125N P=0.235 P=0.508 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.483 P=0.102N P=0.380 P=0.500N |(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 | | Hyperplasia Oncocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 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 | --- --- --- 642 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.019 * (e) (e) P=0.132 |(e) (e) (e) (e) | |POLY 3 | P=0.037 * (e) (e) P=0.183 |(e) (e) (e) (e) | |POLY 1.5 | P=0.041 * (e) (e) P=0.208 |(e) (e) (e) (e) | |POLY 6 | P=0.034 * (e) (e) P=0.147 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.041 * (e) (e) P=0.209 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.046 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 17 Statistical Analysis of Non-neoplastic Lesions 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 | | Pigmentation Lipofuscin | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 4/50 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.5% 2.4% 9.3% 8.0% | |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 | --- --- --- --- |569 569 515 534 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.143 P=0.751N P=0.212 P=0.304 | |POLY 3 | (e) (e) (e) (e) |P=0.139 P=0.752N P=0.202 P=0.285 | |POLY 1.5 | (e) (e) (e) (e) |P=0.151 P=0.755N P=0.193 P=0.295 | |POLY 6 | (e) (e) (e) (e) |P=0.116 P=0.750N P=0.213 P=0.262 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.123 P=0.728 P=0.137 P=0.209 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.157 P=0.753N P=0.181 P=0.301 | |=================================================================================================================================| | | | | | | 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 | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 21/50 (42%) 22/50 (44%) 7/50 (14%) |36/50 (72%) 36/50 (72%) 29/49 (59%) 17/49 (35%) | |POLY-3 ADJUSTED (b)| 52.4% 47.5% 52.6% 20.3% |80.9% 78.1% 66.5% 41.8% | |TERMINAL (d) | 14/20 (70%) 9/16 (56%) 11/15 (73%) 0/0 (0%) |21/22 (96%) 23/25 (92%) 20/22 (91%) 5/11 (46%) | |FIRST INCIDENCE | 564 403 467 337 |241 347 444 483 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.359 P=0.443 P=0.247 P=0.277 |P=0.079N P=0.321N P=0.097N P=0.120N | |POLY 3 | P=0.005N** P=0.398N P=0.583 P=0.002N** |P<0.001N** P=0.465N P=0.076N P<0.001N** | |POLY 1.5 | P<0.001N** P=0.402N P=0.560N P<0.001N** |P<0.001N** P=0.519N P=0.100N P<0.001N** | |POLY 6 | P=0.036N* P=0.408N P=0.520 P=0.013N* |P<0.001N** P=0.393N P=0.052N P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.438N P=0.526 P=0.003N** |P<0.001N** P=0.523N P=0.071N P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.420N P=0.500N P<0.001N** |P<0.001N** P=0.588N P=0.129N P<0.001N** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 18 Statistical Analysis of Non-neoplastic Lesions 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 | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 7/50 (14%) 3/50 (6%) |3/50 (6%) 10/50 (20%) 12/49 (24%) 4/49 (8%) | |POLY-3 ADJUSTED (b)| 9.5% 7.5% 18.0% 9.2% |7.5% 23.6% 29.3% 10.5% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 2/15 (13%) 0/0 (0%) |1/22 (5%) 7/25 (28%) 9/22 (41%) 0/11 (0%) | |FIRST INCIDENCE | 610 579 595 583 |549 347 690 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.166 P=0.589N P=0.140 P=0.246 |P=0.229 P=0.060 P=0.015 * P=0.426 | |POLY 3 | P=0.422 P=0.526N P=0.214 P=0.635N |P=0.526 P=0.041 * P=0.010 * P=0.472 | |POLY 1.5 | P=0.516 P=0.515N P=0.231 P=0.571N |P=0.547N P=0.039 * P=0.010 * P=0.486 | |POLY 6 | P=0.269 P=0.542N P=0.189 P=0.559 |P=0.442 P=0.042 * P=0.010 * P=0.438 | |LOGISTIC REGRESSION| P=0.509N P=0.469N P=0.225 P=0.515N |P=0.551N P=0.037 * P=0.015 * P=0.454 | |COCH-ARM / FISHERS | P=0.517N P=0.500N P=0.262 P=0.500N |P=0.533N P=0.036 * P=0.010 * P=0.489 | |=================================================================================================================================| | | | | | | 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 | | Degeneration Cystic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 25/50 (50%) 38/50 (76%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 4/49 (8%) | |POLY-3 ADJUSTED (b)| 9.5% 5.1% 59.1% 84.5% |0.0% 0.0% 2.5% 10.8% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 8/15 (53%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 626 650 502 409 |--- --- 717 611 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.421N P<0.001 ** P<0.001 ** |P=0.002 ** (e) P=0.508 P=0.039 * | |POLY 3 | P<0.001 ** P=0.375N P<0.001 ** P<0.001 ** |P=0.004 ** (e) P=0.508 P=0.052 | |POLY 1.5 | P<0.001 ** P=0.358N P<0.001 ** P<0.001 ** |P=0.005 ** (e) P=0.503 P=0.056 | |POLY 6 | P<0.001 ** P=0.400N P<0.001 ** P<0.001 ** |P=0.004 ** (e) P=0.513 P=0.045 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.357N P<0.001 ** P<0.001 ** |P=0.005 ** (e) P=0.514 P=0.060 | |COCH-ARM / FISHERS | P<0.001 ** P=0.339N P<0.001 ** P<0.001 ** |P=0.005 ** (e) P=0.495 P=0.056 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 19 Statistical Analysis of Non-neoplastic Lesions 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 | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 28/50 (56%) 43/50 (86%) 47/50 (94%) |10/50 (20%) 20/50 (40%) 27/49 (55%) 31/49 (63%) | |POLY-3 ADJUSTED (b)| 26.4% 62.9% 92.8% 96.6% |25.1% 47.9% 62.8% 71.2% | |TERMINAL (d) | 7/20 (35%) 11/16 (69%) 15/15 (100%) 0/0 (0%) |6/22 (27%) 16/25 (64%) 18/22 (82%) 6/11 (55%) | |FIRST INCIDENCE | 704 406 467 337 |679 618 444 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.049 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.024 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.022 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.027 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.024 * 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 | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |7/50 (14%) 2/50 (4%) 6/49 (12%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 9.4% 2.6% 0.0% 0.0% |17.0% 4.8% 14.2% 5.4% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |2/22 (9%) 1/25 (4%) 2/22 (9%) 0/11 (0%) | |FIRST INCIDENCE | 614 730 (T) --- --- |459 450 541 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.043N* P=0.229N P=0.085N P=0.142N |P=0.226N P=0.076N P=0.474N P=0.164N | |POLY 3 | P=0.020N* P=0.211N P=0.079N P=0.111N |P=0.157N P=0.074N P=0.479N P=0.104N | |POLY 1.5 | P=0.019N* P=0.196N P=0.071N P=0.083N |P=0.141N P=0.075N P=0.492N P=0.091N | |POLY 6 | P=0.023N* P=0.235N P=0.095N P=0.179N |P=0.189N P=0.076N P=0.466N P=0.134N | |LOGISTIC REGRESSION| P=0.017N* P=0.166N P=0.049N* P=0.041N* |P=0.131N P=0.092N P=0.546N P=0.085N | |COCH-ARM / FISHERS | P=0.019N* P=0.181N P=0.059N P=0.059N |P=0.131N P=0.080N P=0.516N P=0.085N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 20 Statistical Analysis of Non-neoplastic Lesions 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 | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 7/50 (14%) 14/50 (28%) 8/50 (16%) |6/50 (12%) 4/50 (8%) 19/49 (39%) 9/49 (18%) | |POLY-3 ADJUSTED (b)| 2.4% 17.2% 34.1% 22.2% |15.1% 9.6% 44.0% 23.3% | |TERMINAL (d) | 1/20 (5%) 3/16 (19%) 5/15 (33%) 0/0 (0%) |2/22 (9%) 2/25 (8%) 12/22 (55%) 3/11 (27%) | |FIRST INCIDENCE | 730 (T) 535 438 337 |683 564 444 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.022 * P<0.001 ** P=0.003 ** |P=0.007 ** P=0.316N P=0.005 ** P=0.096 | |POLY 3 | P=0.008 ** P=0.027 * P<0.001 ** P=0.007 ** |P=0.062 P=0.337N P=0.003 ** P=0.263 | |POLY 1.5 | P=0.017 * P=0.028 * P<0.001 ** P=0.011 * |P=0.075 P=0.348N P=0.002 ** P=0.276 | |POLY 6 | P=0.002 ** P=0.025 * P<0.001 ** P=0.003 ** |P=0.040 * P=0.324N P=0.004 ** P=0.229 | |LOGISTIC REGRESSION| P=0.082 P=0.036 * P<0.001 ** P=0.081 |P=0.076 P=0.345N P=0.003 ** P=0.256 | |COCH-ARM / FISHERS | P=0.035 * P=0.030 * P<0.001 ** P=0.015 * |P=0.090 P=0.370N P=0.002 ** P=0.274 | |=================================================================================================================================| | | | | | | 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 | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 5/50 (10%) 3/50 (6%) |0/50 (0%) 1/50 (2%) 1/49 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 4.8% 5.1% 12.9% 9.2% |0.0% 2.5% 2.5% 0.0% | |TERMINAL (d) | 2/20 (10%) 0/16 (0%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) 650 595 546 |--- 730 (T) 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.052 P=0.636 P=0.138 P=0.063 |P=0.678 P=0.525 P=0.500 (e) | |POLY 3 | P=0.211 P=0.674 P=0.188 P=0.392 |P=0.615N P=0.508 P=0.507 (e) | |POLY 1.5 | P=0.271 P=0.682 P=0.198 P=0.444 |P=0.604N P=0.505 P=0.503 (e) | |POLY 6 | P=0.126 P=0.663 P=0.172 P=0.306 |P=0.634N P=0.511 P=0.512 (e) | |LOGISTIC REGRESSION| P=0.344 P=0.668 P=0.202 P=0.508 |(e) P=0.525 P=0.500 (e) | |COCH-ARM / FISHERS | P=0.344 P=0.691N P=0.218 P=0.500 |P=0.600N P=0.500 P=0.495 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 21 Statistical Analysis of Non-neoplastic Lesions 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: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 36/50 (72%) 17/50 (34%) 16/50 (32%) 17/50 (34%) |11/50 (22%) 11/50 (22%) 17/49 (35%) 22/49 (45%) | |POLY-3 ADJUSTED (b)| 77.0% 40.8% 39.3% 46.4% |27.0% 26.2% 39.4% 54.3% | |TERMINAL (d) | 16/20 (80%) 6/16 (38%) 6/15 (40%) 0/0 (0%) |6/22 (27%) 7/25 (28%) 8/22 (36%) 9/11 (82%) | |FIRST INCIDENCE | 521 575 572 583 |569 609 444 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.135 P=0.020N* P=0.024N* P=0.014 * |P<0.001 ** P=0.491N P=0.180 P<0.001 ** | |POLY 3 | P=0.002N** P<0.001N** P<0.001N** P<0.001N** |P=0.002 ** P=0.568N P=0.160 P=0.008 ** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** |P=0.002 ** P=0.575N P=0.143 P=0.010 * | |POLY 6 | P=0.008N** P<0.001N** P<0.001N** P=0.013N* |P<0.001 ** P=0.565N P=0.180 P=0.004 ** | |LOGISTIC REGRESSION| P=0.008N** P<0.001N** P<0.001N** P=0.004N** |P=0.002 ** P=0.557N P=0.143 P=0.008 ** | |COCH-ARM / FISHERS | P<0.001N** P<0.001N** P<0.001N** P<0.001N** |P=0.003 ** P=0.595N P=0.119 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 | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia Atypical Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.6% 6.2% |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 | --- --- 438 502 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.047 * (e) P=0.500 P=0.155 |(e) (e) (e) (e) | |POLY 3 | P=0.048 * (e) P=0.483 P=0.185 |(e) (e) (e) (e) | |POLY 1.5 | P=0.058 (e) P=0.490 P=0.209 |(e) (e) (e) (e) | |POLY 6 | P=0.036 * (e) P=0.472 P=0.149 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.099 (e) P=0.645 P=0.321 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.070 (e) P=0.500 P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 22 Statistical Analysis of Non-neoplastic Lesions 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: Centrilobular | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 14.1% 2.6% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 553 703 --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.022N* P=0.105N P=0.043N* P=0.268N |(e) (e) (e) (e) | |POLY 3 | P=0.003N** P=0.071N P=0.023N* P=0.039N* |(e) (e) (e) (e) | |POLY 1.5 | P=0.003N** P=0.064N P=0.019N* P=0.025N* |(e) (e) (e) (e) | |POLY 6 | P=0.004N** P=0.083N P=0.029N* P=0.083N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.005N** P=0.063N P=0.019N* P=0.027N* |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.004N** P=0.056N P=0.013N* P=0.013N* |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Centrilobular | | Degeneration Fatty | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 3/50 (6%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 4.8% 0.0% 2.6% 0.0% |0.0% 7.2% 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 | 626 --- 596 --- |--- 606 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.233N P=0.264N P=0.533N P=0.321N |P=0.343N P=0.140 (e) (e) | |POLY 3 | P=0.208N P=0.257N P=0.538N P=0.309N |P=0.313N P=0.130 (e) (e) | |POLY 1.5 | P=0.198N P=0.248N P=0.523N P=0.273N |P=0.311N P=0.126 (e) (e) | |POLY 6 | P=0.232N P=0.271N P=0.563N P=0.380N |P=0.322N P=0.137 (e) (e) | |LOGISTIC REGRESSION| P=0.160N P=0.217N P=0.457N P=0.199N |P=0.322N P=0.106 (e) (e) | |COCH-ARM / FISHERS | P=0.188N P=0.247N P=0.500N P=0.247N |P=0.317N P=0.121 (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 23 Statistical Analysis of Non-neoplastic Lesions 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: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 10.1% 0.0% 3.2% |0.0% 0.0% 2.5% 2.8% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 1/11 (9%) | |FIRST INCIDENCE | 715 575 --- 575 |--- --- 712 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.621 P=0.136 P=0.610N P=0.477 |P=0.126 (e) P=0.523 P=0.362 | |POLY 3 | P=0.418N P=0.165 P=0.521N P=0.698 |P=0.208 (e) P=0.508 P=0.482 | |POLY 1.5 | P=0.379N P=0.171 P=0.513N P=0.729 |P=0.222 (e) P=0.503 P=0.491 | |POLY 6 | P=0.482N P=0.158 P=0.535N P=0.636 |P=0.183 (e) P=0.513 P=0.465 | |LOGISTIC REGRESSION| P=0.318N P=0.188 P=0.556N P=0.777N |P=0.161 (e) P=0.513 P=0.362 | |COCH-ARM / FISHERS | P=0.337N P=0.181 P=0.500N P=0.753N |P=0.232 (e) P=0.495 P=0.495 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 13/50 (26%) 25/50 (50%) 30/50 (60%) |1/50 (2%) 13/50 (26%) 16/49 (33%) 26/49 (53%) | |POLY-3 ADJUSTED (b)| 0.0% 30.1% 58.8% 70.4% |2.5% 30.6% 37.9% 61.1% | |TERMINAL (d) | 0/20 (0%) 4/16 (25%) 14/15 (93%) 0/0 (0%) |1/22 (5%) 10/25 (40%) 12/22 (55%) 7/11 (64%) | |FIRST INCIDENCE | --- 403 438 337 |730 (T) 347 444 483 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 24 Statistical Analysis of Non-neoplastic Lesions 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: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 17/50 (34%) 24/50 (48%) 34/50 (68%) |1/50 (2%) 15/50 (30%) 19/49 (39%) 35/49 (71%) | |POLY-3 ADJUSTED (b)| 31.5% 38.1% 52.9% 76.1% |2.5% 36.0% 44.3% 77.7% | |TERMINAL (d) | 5/20 (25%) 2/16 (13%) 6/15 (40%) 0/0 (0%) |1/22 (5%) 14/25 (56%) 12/22 (55%) 10/11 (91%) | |FIRST INCIDENCE | 521 431 438 337 |730 (T) 347 444 483 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.217 P=0.017 * P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.333 P=0.028 * P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.332 P=0.027 * P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.340 P=0.029 * P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.427 P=0.051 P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.333 P=0.032 * P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 7.6% 5.2% 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 | 639 542 568 699 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.444 P=0.264 P=0.467 P=0.512 |(e) (e) (e) (e) | |POLY 3 | P=0.574 P=0.284 P=0.468 P=0.693 |(e) (e) (e) (e) | |POLY 1.5 | P=0.541N P=0.294 P=0.480 P=0.727 |(e) (e) (e) (e) | |POLY 6 | P=0.443 P=0.272 P=0.448 P=0.627 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.451N P=0.329 P=0.542 P=0.727 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.474N P=0.309 P=0.500 P=0.753N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 25 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Lung | | Inflammation Acute | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 2/49 (4%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.5% 0.0% 4.9% 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 | --- --- --- --- |700 --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.552N P=0.493N P=0.531 P=0.577N | |POLY 3 | (e) (e) (e) (e) |P=0.496N P=0.493N P=0.515 P=0.518N | |POLY 1.5 | (e) (e) (e) (e) |P=0.479N P=0.495N P=0.506 P=0.509N | |POLY 6 | (e) (e) (e) (e) |P=0.526N P=0.491N P=0.525 P=0.537N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.490N P=0.491N P=0.510 P=0.539N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.467N P=0.500N P=0.492 P=0.505N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 1/49 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 4.8% 0.0% 5.3% 9.3% |2.5% 0.0% 2.5% 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 | 668 --- 610 502 |641 --- 724 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.052 P=0.288N P=0.610 P=0.071 |P=0.484N P=0.500N P=0.757N P=0.550N | |POLY 3 | P=0.179 P=0.254N P=0.662 P=0.386 |P=0.424N P=0.494N P=0.754N P=0.519N | |POLY 1.5 | P=0.205 P=0.247N P=0.674 P=0.440 |P=0.417N P=0.496N P=0.758N P=0.510N | |POLY 6 | P=0.142 P=0.266N P=0.641 P=0.295 |P=0.435N P=0.492N P=0.751N P=0.538N | |LOGISTIC REGRESSION| P=0.248 P=0.255N P=0.696N P=0.494 |P=0.417N P=0.508N P=0.761N P=0.503N | |COCH-ARM / FISHERS | P=0.237 P=0.247N P=0.691N P=0.500 |P=0.410N P=0.500N P=0.747 P=0.505N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 26 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 2/50 (4%) |2/50 (4%) 3/50 (6%) 7/49 (14%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 2.6% 6.2% |5.1% 7.3% 17.2% 8.0% | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |1/22 (5%) 2/25 (8%) 6/22 (27%) 0/11 (0%) | |FIRST INCIDENCE | --- 730 (T) 522 575 |644 588 717 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.059 P=0.455 P=0.487 P=0.190 |P=0.142 P=0.547 P=0.083 P=0.393 | |POLY 3 | P=0.105 P=0.486 P=0.483 P=0.185 |P=0.319 P=0.520 P=0.083 P=0.473 | |POLY 1.5 | P=0.126 P=0.492 P=0.489 P=0.209 |P=0.347 P=0.513 P=0.080 P=0.487 | |POLY 6 | P=0.075 P=0.477 P=0.471 P=0.149 |P=0.263 P=0.527 P=0.086 P=0.441 | |LOGISTIC REGRESSION| P=0.181 P=0.455 P=0.586 P=0.289 |P=0.329 P=0.512 P=0.095 P=0.489 | |COCH-ARM / FISHERS | P=0.153 P=0.500 P=0.500 P=0.247 |P=0.362 P=0.500 P=0.075 P=0.490 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung: Interstitium | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 4.8% 2.6% 5.3% 3.2% |0.0% 2.5% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 652 703 712 584 |--- 730 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.312 P=0.575N P=0.544 P=0.696 |P=0.678N P=0.525 (e) (e) | |POLY 3 | P=0.527N P=0.527N P=0.654 P=0.594N |P=0.563N P=0.508 (e) (e) | |POLY 1.5 | P=0.488N P=0.515N P=0.670 P=0.549N |P=0.566N P=0.505 (e) (e) | |POLY 6 | P=0.566 P=0.545N P=0.626 P=0.671N |P=0.558N P=0.511 (e) (e) | |LOGISTIC REGRESSION| P=0.569N P=0.519N P=0.638 P=0.502N |(e) P=0.525 (e) (e) | |COCH-ARM / FISHERS | P=0.444N P=0.500N P=0.691N P=0.500N |P=0.571N P=0.500 (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 27 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Lung: Interstitium | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 8/50 (16%) 10/50 (20%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 9.5% 2.6% 20.7% 29.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 2/15 (13%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 626 596 595 646 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.245N P=0.081 P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P=0.002 ** P=0.202N P=0.134 P=0.022 * |(e) (e) (e) (e) | |POLY 1.5 | P=0.004 ** P=0.192N P=0.150 P=0.040 * |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** P=0.219N P=0.111 P=0.007 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.002 ** P=0.172N P=0.143 P=0.011 * |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.009 ** P=0.181N P=0.178 P=0.074 |(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 | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.8% 0.0% 0.0% 0.0% |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 | 639 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.193N P=0.286N P=0.300N P=0.576N |(e) (e) (e) (e) | |POLY 3 | P=0.101N P=0.255N P=0.263N P=0.307N |(e) (e) (e) (e) | |POLY 1.5 | P=0.107N P=0.247N P=0.252N P=0.272N |(e) (e) (e) (e) | |POLY 6 | P=0.091N P=0.267N P=0.281N P=0.376N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.127N P=0.244N P=0.250N P=0.314N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.115N P=0.247N P=0.247N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 28 Statistical Analysis of Non-neoplastic Lesions 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 | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 13/49 (27%) 4/49 (8%) 7/45 (16%) |27/50 (54%) 22/50 (44%) 34/50 (68%) 20/50 (40%) | |POLY-3 ADJUSTED (b)| 29.6% 32.2% 10.6% 23.2% |60.7% 49.4% 74.3% 47.5% | |TERMINAL (d) | 4/20 (20%) 5/16 (31%) 1/15 (7%) 0/0 (0%) |11/22 (50%) 13/25 (52%) 18/22 (82%) 5/11 (46%) | |FIRST INCIDENCE | 521 572 467 575 |407 450 444 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.414 P=0.391 P=0.065N P=0.166 |P=0.183 P=0.156N P=0.225 P=0.479 | |POLY 3 | P=0.131N P=0.490 P=0.030N* P=0.367N |P=0.260N P=0.188N P=0.112 P=0.145N | |POLY 1.5 | P=0.089N P=0.522 P=0.024N* P=0.258N |P=0.209N P=0.188N P=0.113 P=0.119N | |POLY 6 | P=0.228N P=0.448 P=0.044N* P=0.571N |P=0.371N P=0.206N P=0.106 P=0.214N | |LOGISTIC REGRESSION| P=0.077N P=0.549 P=0.017N* P=0.225N |P=0.216N P=0.195N P=0.139 P=0.122N | |COCH-ARM / FISHERS | P=0.056N P=0.567 P=0.017N* P=0.160N |P=0.188N P=0.212N P=0.109 P=0.115N | |=================================================================================================================================| | | | | | | 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 | | Galactocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 0/49 (0%) 0/45 (0%) |10/50 (20%) 10/50 (20%) 7/50 (14%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 0.0% 0.0% |25.1% 23.4% 16.2% 15.7% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |7/22 (32%) 4/25 (16%) 2/22 (9%) 0/11 (0%) | |FIRST INCIDENCE | 642 --- --- --- |598 606 541 541 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.344N P=0.523N P=0.523N P=0.570N |P=0.395N P=0.497N P=0.287N P=0.550N | |POLY 3 | P=0.280N P=0.519N P=0.527N P=0.578N |P=0.148N P=0.531N P=0.231N P=0.226N | |POLY 1.5 | P=0.300N P=0.512N P=0.518N P=0.551N |P=0.135N P=0.558N P=0.257N P=0.210N | |POLY 6 | P=0.254N P=0.528N P=0.542N P=0.623N |P=0.176N P=0.492N P=0.204N P=0.266N | |LOGISTIC REGRESSION| P=0.306N P=0.492N P=0.492N P=0.514N |P=0.140N P=0.564N P=0.269N P=0.262N | |COCH-ARM / FISHERS | P=0.317N P=0.505N P=0.505N P=0.526N |P=0.130N P=0.598N P=0.298N P=0.207N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 29 Statistical Analysis of Non-neoplastic Lesions 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 | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/49 (0%) 0/45 (0%) |0/50 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 4.9% 4.8% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 665 625 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.635N P=0.264 P=0.254 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.535N P=0.247 P=0.251 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.514N P=0.244 P=0.246 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.575N P=0.251 P=0.256 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.524N P=0.246 P=0.241 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.500N P=0.247 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 | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/49 (2%) 0/49 (0%) 1/45 (2%) |8/50 (16%) 7/50 (14%) 9/50 (18%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 0.0% 3.6% |19.7% 16.8% 21.2% 5.4% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |2/22 (9%) 5/25 (20%) 3/22 (14%) 1/11 (9%) | |FIRST INCIDENCE | --- 703 --- 660 |597 569 627 553 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.146 P=0.451 (e) P=0.356 |P=0.205N P=0.424N P=0.532 P=0.161N | |POLY 3 | P=0.314 P=0.483 (e) P=0.425 |P=0.076N P=0.479N P=0.539 P=0.060N | |POLY 1.5 | P=0.346 P=0.489 (e) P=0.450 |P=0.060N P=0.484N P=0.526 P=0.051N | |POLY 6 | P=0.268 P=0.476 (e) P=0.382 |P=0.114N P=0.479N P=0.551 P=0.085N | |LOGISTIC REGRESSION| P=0.302 P=0.476 (e) P=0.447 |P=0.063N P=0.476N P=0.536 P=0.054N | |COCH-ARM / FISHERS | P=0.383 P=0.495 (e) P=0.474 |P=0.051N P=0.500N P=0.500 P=0.046N* | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 30 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/5 (100%) 6/6 (100%) 0/0 (0%) 0/1 (0%) |5/6 (83%) 5/5 (100%) 2/3 (67%) 3/3 (100%) | |POLY-3 ADJUSTED (b)| 100.0% 100.0% 0.0% 0.0% |90.1% 100.0% 85.1% 100.0% | |TERMINAL (d) | 2/2 (100%) 5/5 (100%) 0/0 (0%) 0/0 (0%) |1/1 (100%) 3/3 (100%) 1/1 (100%) 1/1 (100%) | |FIRST INCIDENCE | 553 639 --- --- |569 564 613 611 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.124N (e) (e) P=0.566N |P=0.374N P=0.312N P=0.176N P=0.481N | |POLY 3 | (e) (e) (e) P<0.001N** |P=0.711 P=0.797 P=0.885N P=0.861 | |POLY 1.5 | (e) (e) (e) P<0.001N** |P=0.615 P=0.658 P=0.750N P=0.745 | |POLY 6 | (e) (e) (e) P=1.000 |P=0.941 P=0.985 P=0.997N P=0.993 | |LOGISTIC REGRESSION| P=0.039N* (e) (e) P=0.205N |P=0.675 P=0.667 P=0.906 P=0.858 | |COCH-ARM / FISHERS | P=0.017N* (e) (e) P=0.167N |P=0.562 P=0.545 P=0.583N P=0.667 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 14/50 (28%) 20/50 (40%) 11/50 (22%) |8/50 (16%) 10/50 (20%) 14/50 (28%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 25.4% 33.0% 47.7% 31.3% |20.0% 23.0% 31.8% 8.1% | |TERMINAL (d) | 2/20 (10%) 3/16 (19%) 6/15 (40%) 0/0 (0%) |4/22 (18%) 3/25 (12%) 6/22 (27%) 1/11 (9%) | |FIRST INCIDENCE | 603 431 438 337 |609 520 515 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.194 P=0.013 * P=0.002 ** |P=0.343N P=0.480 P=0.153 P=0.321N | |POLY 3 | P=0.225 P=0.294 P=0.024 * P=0.373 |P=0.149N P=0.474 P=0.162 P=0.119N | |POLY 1.5 | P=0.369 P=0.308 P=0.028 * P=0.483 |P=0.116N P=0.444 P=0.141 P=0.106N | |POLY 6 | P=0.070 P=0.273 P=0.018 * P=0.203 |P=0.227N P=0.515 P=0.191 P=0.153N | |LOGISTIC REGRESSION| P=0.513 P=0.339 P=0.033 * P=0.574 |P=0.106N P=0.410 P=0.128 P=0.146N | |COCH-ARM / FISHERS | P=0.542 P=0.322 P=0.041 * P=0.595N |P=0.099N P=0.398 P=0.114 P=0.100N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 31 Statistical Analysis of Non-neoplastic Lesions 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 | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 7/50 (14%) 2/49 (4%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| |5.0% 16.4% 4.8% 5.5% | |TERMINAL (d) | |0/22 (0%) 3/25 (12%) 1/22 (5%) 1/11 (9%) | |FIRST INCIDENCE | |598 520 683 553 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.458N P=0.111 P=0.669N P=0.604 | |POLY 3 | |P=0.335N P=0.093 P=0.682N P=0.661 | |POLY 1.5 | |P=0.315N P=0.088 P=0.687N P=0.677 | |POLY 6 | |P=0.377N P=0.098 P=0.680N P=0.626 | |LOGISTIC REGRESSION| |P=0.305N P=0.070 P=0.674 P=0.686 | |COCH-ARM / FISHERS | |P=0.308N P=0.080 P=0.684 P=0.684 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Pancreas | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 7.2% 5.2% 2.7% 6.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/20 (10%) 2/16 (13%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 652 730 (T) 730 (T) 660 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.156 P=0.593N P=0.402N P=0.130 |(e) (e) (e) (e) | |POLY 3 | P=0.470N P=0.536N P=0.345N P=0.624N |(e) (e) (e) (e) | |POLY 1.5 | P=0.440N P=0.520N P=0.329N P=0.565N |(e) (e) (e) (e) | |POLY 6 | P=0.516N P=0.560N P=0.373N P=0.626 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.390 P=0.576N P=0.391N P=0.530 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.404N P=0.500N P=0.309N P=0.500N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 32 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 20/50 (40%) 15/50 (30%) 13/50 (26%) 9/50 (18%) |10/50 (20%) 11/50 (22%) 8/50 (16%) 6/49 (12%) | |POLY-3 ADJUSTED (b)| 45.6% 36.4% 32.1% 25.5% |24.6% 25.8% 18.7% 16.2% | |TERMINAL (d) | 9/20 (45%) 5/16 (31%) 5/15 (33%) 0/0 (0%) |4/22 (18%) 8/25 (32%) 3/22 (14%) 1/11 (9%) | |FIRST INCIDENCE | 553 575 502 502 |555 450 515 576 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.234 P=0.455N P=0.371N P=0.090 |P=0.430N P=0.584 P=0.371N P=0.542N | |POLY 3 | P=0.035N* P=0.256N P=0.141N P=0.048N* |P=0.166N P=0.548 P=0.350N P=0.262N | |POLY 1.5 | P=0.020N* P=0.232N P=0.125N P=0.025N* |P=0.145N P=0.534 P=0.366N P=0.233N | |POLY 6 | P=0.088N P=0.288N P=0.177N P=0.131N |P=0.212N P=0.554 P=0.335N P=0.328N | |LOGISTIC REGRESSION| P=0.026N* P=0.262N P=0.139N P=0.033N* |P=0.145N P=0.522 P=0.372N P=0.265N | |COCH-ARM / FISHERS | P=0.011N* P=0.201N P=0.101N P=0.013N* |P=0.132N P=0.500 P=0.398N P=0.220N | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Pancreas: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 9.7% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 4/20 (20%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 730 (T) --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.051N P=0.089N P=0.099N P=1.000N |(e) (e) (e) (e) | |POLY 3 | P=0.016N* P=0.069N P=0.073N P=0.104N |(e) (e) (e) (e) | |POLY 1.5 | P=0.017N* P=0.065N P=0.068N P=0.080N |(e) (e) (e) (e) | |POLY 6 | P=0.014N* P=0.075N P=0.083N P=0.163N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.051N (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.020N* P=0.059N P=0.059N P=0.059N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 33 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 17/48 (35%) 8/49 (16%) 22/48 (46%) 21/45 (47%) |0/44 (0%) 0/45 (0%) 1/41 (2%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 40.5% 20.6% 57.5% 63.4% |0.0% 0.0% 2.8% 0.0% | |TERMINAL (d) | 7/20 (35%) 2/16 (13%) 12/15 (80%) 0/0 (0%) |0/18 (0%) 0/24 (0%) 0/19 (0%) 0/10 (0%) | |FIRST INCIDENCE | 626 596 568 568 |--- --- 515 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.132N P=0.030 * P<0.001 ** |P=0.700 (e) P=0.513 (e) | |POLY 3 | P=0.002 ** P=0.041N* P=0.086 P=0.032 * |P=0.655 (e) P=0.510 (e) | |POLY 1.5 | P=0.006 ** P=0.033N* P=0.125 P=0.080 |P=0.680 (e) P=0.501 (e) | |POLY 6 | P<0.001 ** P=0.056N P=0.045 * P=0.006 ** |P=0.602 (e) P=0.519 (e) | |LOGISTIC REGRESSION| P<0.001 ** P=0.052N P=0.045 * P=0.002 ** |P=0.621 (e) P=0.337 (e) | |COCH-ARM / FISHERS | P=0.026 * P=0.027N* P=0.203 P=0.186 |P=0.696 (e) P=0.482 (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 | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/49 (0%) 0/48 (0%) 0/45 (0%) |0/44 (0%) 0/45 (0%) 0/41 (0%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 4.9% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/20 (5%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/18 (0%) 0/24 (0%) 0/19 (0%) 0/10 (0%) | |FIRST INCIDENCE | 668 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.216N P=0.279N P=0.299N P=0.718N |(e) (e) (e) (e) | |POLY 3 | P=0.103N P=0.253N P=0.265N P=0.327N |(e) (e) (e) (e) | |POLY 1.5 | P=0.111N P=0.244N P=0.254N P=0.290N |(e) (e) (e) (e) | |POLY 6 | P=0.094N P=0.267N P=0.284N P=0.398N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.154N P=0.256N P=0.271N P=0.439N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.119N P=0.242N P=0.247N P=0.264N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 34 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |4/50 (8%) 2/50 (4%) 2/50 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.8% 0.0% 0.0% 6.3% |9.9% 4.8% 4.8% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |1/22 (5%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | 529 --- --- 658 |616 611 595 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.228 P=0.275N P=0.297N P=0.276 |P=0.071N P=0.313N P=0.321N P=0.115N | |POLY 3 | P=0.473 P=0.257N P=0.264N P=0.588 |P=0.052N P=0.323N P=0.319N P=0.074N | |POLY 1.5 | P=0.484 P=0.248N P=0.253N P=0.640 |P=0.047N* P=0.327N P=0.325N P=0.066N | |POLY 6 | P=0.463 P=0.269N P=0.283N P=0.493 |P=0.062N P=0.320N P=0.316N P=0.092N | |LOGISTIC REGRESSION| P=0.503 P=0.214N P=0.209N P=0.703 |P=0.043N* P=0.345N P=0.342N P=0.063N | |COCH-ARM / FISHERS | P=0.500 P=0.247N P=0.247N P=0.691N |P=0.044N* P=0.339N P=0.339N P=0.059N | |=================================================================================================================================| | | | | | | 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 | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 2/50 (4%) 4/50 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |7.5% 4.8% 9.5% 5.5% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |2/22 (9%) 0/25 (0%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | --- --- --- --- |569 450 515 660 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.529 P=0.467N P=0.516 P=0.668 | |POLY 3 | (e) (e) (e) (e) |P=0.533N P=0.474N P=0.532 P=0.539N | |POLY 1.5 | (e) (e) (e) (e) |P=0.505N P=0.483N P=0.520 P=0.516N | |POLY 6 | (e) (e) (e) (e) |P=0.565 P=0.465N P=0.543 P=0.582N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.470N P=0.543N P=0.505 P=0.541N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.479N P=0.500N P=0.500 P=0.500N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 35 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 9/50 (18%) 8/50 (16%) 2/50 (4%) |11/50 (22%) 17/50 (34%) 14/50 (28%) 15/50 (30%) | |POLY-3 ADJUSTED (b)| 26.1% 22.7% 20.9% 6.3% |27.0% 40.3% 32.5% 37.5% | |TERMINAL (d) | 8/20 (40%) 5/16 (31%) 6/15 (40%) 0/0 (0%) |6/22 (27%) 11/25 (44%) 7/22 (32%) 6/11 (55%) | |FIRST INCIDENCE | 529 575 521 584 |459 606 515 483 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.490 P=0.592 P=0.574N P=0.387 |P=0.026 * P=0.221 P=0.366 P=0.035 * | |POLY 3 | P=0.025N* P=0.459N P=0.386N P=0.026N* |P=0.287 P=0.142 P=0.376 P=0.213 | |POLY 1.5 | P=0.013N* P=0.434N P=0.354N P=0.014N* |P=0.317 P=0.139 P=0.356 P=0.238 | |POLY 6 | P=0.068N P=0.492N P=0.444N P=0.068N |P=0.227 P=0.146 P=0.395 P=0.164 | |LOGISTIC REGRESSION| P=0.061N P=0.507N P=0.462N P=0.093N |P=0.254 P=0.157 P=0.361 P=0.222 | |COCH-ARM / FISHERS | P=0.007N** P=0.402N P=0.306N P=0.007N** |P=0.326 P=0.133 P=0.322 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 | |=================================================================================================================================| | | |Preputial Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 2/50 (4%) 0/49 (0%) 6/50 (12%) | | |POLY-3 ADJUSTED (b)| 12.0% 5.2% 0.0% 18.4% | | |TERMINAL (d) | 3/20 (15%) 0/16 (0%) 0/15 (0%) 0/0 (0%) | | |FIRST INCIDENCE | 668 703 --- 638 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.004 ** P=0.322N P=0.071N P<0.001 ** | | |POLY 3 | P=0.276 P=0.246N P=0.042N* P=0.330 | | |POLY 1.5 | P=0.298 P=0.233N P=0.038N* P=0.409 | | |POLY 6 | P=0.247 P=0.267N P=0.049N* P=0.210 | | |LOGISTIC REGRESSION| P=0.097 P=0.281N P=0.057N P=0.116 | | |COCH-ARM / FISHERS | P=0.331 P=0.218N P=0.030N* P=0.500 | | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 36 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Preputial Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 6/49 (12%) 4/50 (8%) | | |POLY-3 ADJUSTED (b)| 7.2% 10.1% 15.8% 12.0% | | |TERMINAL (d) | 2/20 (10%) 0/16 (0%) 2/15 (13%) 0/0 (0%) | | |FIRST INCIDENCE | 642 625 521 467 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.056 P=0.432 P=0.132 P=0.134 | | |POLY 3 | P=0.255 P=0.473 P=0.194 P=0.379 | | |POLY 1.5 | P=0.328 P=0.484 P=0.208 P=0.437 | | |POLY 6 | P=0.150 P=0.461 P=0.171 P=0.282 | | |LOGISTIC REGRESSION| P=0.427 P=0.498 P=0.197 P=0.608 | | |COCH-ARM / FISHERS | P=0.414 P=0.500 P=0.233 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 | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 15/50 (30%) 8/49 (16%) 12/50 (24%) | | |POLY-3 ADJUSTED (b)| 20.1% 34.4% 20.1% 31.3% | | |TERMINAL (d) | 2/20 (10%) 1/16 (6%) 2/15 (13%) 0/0 (0%) | | |FIRST INCIDENCE | 521 406 467 409 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.093 P=0.095 P=0.586 P=0.091 | | |POLY 3 | P=0.273 P=0.099 P=0.604N P=0.177 | | |POLY 1.5 | P=0.357 P=0.107 P=0.571N P=0.239 | | |POLY 6 | P=0.149 P=0.093 P=0.560 P=0.090 | | |LOGISTIC REGRESSION| P=0.281N P=0.186 P=0.392N P=0.301N | | |COCH-ARM / FISHERS | P=0.452 P=0.121 P=0.518N P=0.312 | | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 37 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 16/50 (32%) 18/50 (36%) 13/49 (27%) 15/49 (31%) | | |POLY-3 ADJUSTED (b)| 35.3% 40.2% 31.2% 42.3% | | |TERMINAL (d) | 4/20 (20%) 5/16 (31%) 1/15 (7%) 0/0 (0%) | | |FIRST INCIDENCE | 521 403 438 467 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.026 * P=0.265 P=0.571N P=0.003 ** | | |POLY 3 | P=0.389 P=0.395 P=0.427N P=0.341 | | |POLY 1.5 | P=0.524 P=0.411 P=0.399N P=0.482 | | |POLY 6 | P=0.209 P=0.363 P=0.479N P=0.153 | | |LOGISTIC REGRESSION| P=0.218N P=0.547 P=0.264N P=0.516N | | |COCH-ARM / FISHERS | P=0.389N P=0.417 P=0.353N P=0.527N | | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |Salivary Glands: Submandibular Gland | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 50/50 (100%) 49/50 (98%) 48/48 (100%)|1/50 (2%) 48/48 (100%) 49/49 (100%) 49/49 (100%) | |POLY-3 ADJUSTED (b)| 9.2% 100.0% 98.0% 100.0% |2.5% 100.0% 100.0% 100.0% | |TERMINAL (d) | 0/20 (0%) 16/16 (100%) 14/15 (93%) 0/0 (0%) |0/22 (0%) 25/25 (100%) 22/22 (100%) 11/11 (100%) | |FIRST INCIDENCE | 344 403 15 337 |555 347 297 483 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 38 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Seminal Vesicle | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 6/50 (12%) | | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 5.3% 18.2% | | |TERMINAL (d) | 0/20 (0%) 1/16 (6%) 0/15 (0%) 0/0 (0%) | | |FIRST INCIDENCE | --- 730 (T) 664 568 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.455 P=0.184 P<0.001 ** | | |POLY 3 | P<0.001 ** P=0.486 P=0.216 P=0.006 ** | | |POLY 1.5 | P<0.001 ** P=0.492 P=0.224 P=0.010 * | | |POLY 6 | P<0.001 ** P=0.477 P=0.204 P=0.003 ** | | |LOGISTIC REGRESSION| P<0.001 ** P=0.455 P=0.221 P=0.011 * | | |COCH-ARM / FISHERS | P=0.002 ** P=0.500 P=0.247 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 | |=================================================================================================================================| | | |Skin | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.7% 0.0% 0.0% 0.0% |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 | 564 --- --- --- |--- --- 595 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.132N P=0.262N P=0.258N P=0.286N |P=0.682 (e) P=0.509 (e) | |POLY 3 | P=0.100N P=0.258N P=0.266N P=0.311N |P=0.648 (e) P=0.513 (e) | |POLY 1.5 | P=0.107N P=0.249N P=0.254N P=0.274N |P=0.675 (e) P=0.508 (e) | |POLY 6 | P=0.093N P=0.273N P=0.286N P=0.382N |P=0.595 (e) P=0.518 (e) | |LOGISTIC REGRESSION| P=0.088N P=0.199N P=0.182N P=0.153N |P=0.686 (e) P=0.474 (e) | |COCH-ARM / FISHERS | P=0.115N P=0.247N P=0.247N P=0.247N |P=0.694 (e) P=0.500 (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 39 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 11/50 (22%) 12/50 (24%) 12/50 (24%) |3/50 (6%) 3/50 (6%) 5/50 (10%) 12/49 (24%) | |POLY-3 ADJUSTED (b)| 19.3% 27.7% 31.1% 35.4% |7.5% 7.3% 12.0% 32.4% | |TERMINAL (d) | 4/20 (20%) 6/16 (38%) 8/15 (53%) 0/0 (0%) |1/22 (5%) 1/25 (4%) 4/22 (18%) 6/11 (55%) | |FIRST INCIDENCE | 714 596 522 642 |641 618 690 600 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.156 P=0.063 P<0.001 ** |P<0.001 ** P=0.622N P=0.376 P<0.001 ** | |POLY 3 | P=0.071 P=0.258 P=0.163 P=0.088 |P<0.001 ** P=0.647N P=0.378 P=0.005 ** | |POLY 1.5 | P=0.125 P=0.278 P=0.187 P=0.143 |P<0.001 ** P=0.652N P=0.371 P=0.007 ** | |POLY 6 | P=0.023 * P=0.235 P=0.128 P=0.033 * |P<0.001 ** P=0.644N P=0.382 P=0.002 ** | |LOGISTIC REGRESSION| P=0.003 ** P=0.181 P=0.084 P<0.001 ** |P<0.001 ** P=0.653N P=0.391 P=0.003 ** | |COCH-ARM / FISHERS | P=0.216 P=0.306 P=0.227 P=0.227 |P<0.001 ** P=0.661N P=0.357 P=0.010 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 9/50 (18%) 2/50 (4%) 13/50 (26%) |0/50 (0%) 7/50 (14%) 6/50 (12%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 4.8% 21.4% 5.3% 34.6% |0.0% 16.3% 14.2% 5.4% | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 1/25 (4%) 3/22 (14%) 0/11 (0%) | |FIRST INCIDENCE | 729 406 619 409 |--- 606 444 534 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.021 * P=0.623 P<0.001 ** |P=0.343 P=0.015 * P=0.022 * P=0.229 | |POLY 3 | P<0.001 ** P=0.025 * P=0.664 P<0.001 ** |P=0.465 P=0.010 * P=0.019 * P=0.223 | |POLY 1.5 | P=0.002 ** P=0.025 * P=0.675 P<0.001 ** |P=0.495 P=0.009 ** P=0.018 * P=0.230 | |POLY 6 | P<0.001 ** P=0.025 * P=0.646 P<0.001 ** |P=0.398 P=0.012 * P=0.021 * P=0.208 | |LOGISTIC REGRESSION| P=0.015 * P=0.037 * P=0.675 P=0.013 * |P=0.512 P=0.008 ** P=0.018 * P=0.195 | |COCH-ARM / FISHERS | P=0.004 ** P=0.026 * P=0.691N P=0.002 ** |P=0.506 P=0.006 ** P=0.013 * P=0.242 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 40 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Spleen | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 4.9% 2.4% 2.8% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 2/25 (8%) 1/22 (5%) 0/11 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 730 (T) 730 (T) 620 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.339 P=0.266 P=0.500 P=0.477 | |POLY 3 | (e) (e) (e) (e) |P=0.469 P=0.245 P=0.510 P=0.485 | |POLY 1.5 | (e) (e) (e) (e) |P=0.486 P=0.243 P=0.507 P=0.492 | |POLY 6 | (e) (e) (e) (e) |P=0.435 P=0.248 P=0.514 P=0.469 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.446 P=0.266 P=0.500 P=0.492 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.494 P=0.247 P=0.500 P=0.495 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Spleen: Red Pulp | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 5.5% | |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 | --- --- --- --- |--- --- --- 553 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.032 * (e) (e) P=0.197 | |POLY 3 | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.221 | |POLY 1.5 | (e) (e) (e) (e) |P=0.043 * (e) (e) P=0.229 | |POLY 6 | (e) (e) (e) (e) |P=0.039 * (e) (e) P=0.206 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.229 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.242 | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 41 Statistical Analysis of Non-neoplastic Lesions 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 | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/50 (2%) 6/50 (12%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.1% 0.0% 2.7% 18.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 588 --- 730 (T) 568 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.151N P=0.400N P=0.027 * |(e) (e) (e) (e) | |POLY 3 | P=0.035 * P=0.135N P=0.350N P=0.134 |(e) (e) (e) (e) | |POLY 1.5 | P=0.040 * P=0.128N P=0.332N P=0.181 |(e) (e) (e) (e) | |POLY 6 | P=0.028 * P=0.147N P=0.382N P=0.076 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.039 * P=0.110N P=0.312N P=0.222 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.050 P=0.121N P=0.309N 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 | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/49 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 16.7% 2.6% 0.0% 0.0% |0.0% 4.9% 0.0% 0.0% | |TERMINAL (d) | 3/20 (15%) 1/16 (6%) 0/15 (0%) 0/0 (0%) |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 639 730 (T) --- --- |--- 609 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.014N* P=0.069N P=0.032N* P=0.484N |P=0.464N P=0.261 (e) (e) | |POLY 3 | P<0.001N** P=0.038N* P=0.011N* P=0.022N* |P=0.403N P=0.243 (e) (e) | |POLY 1.5 | P<0.001N** P=0.035N* P=0.010N* P=0.013N* |P=0.401N P=0.239 (e) (e) | |POLY 6 | P<0.001N** P=0.045N* P=0.015N* P=0.053N |P=0.409N P=0.248 (e) (e) | |LOGISTIC REGRESSION| P=0.005N** P=0.048N* P=0.017N* P=0.086N |P=0.404N P=0.232 (e) (e) | |COCH-ARM / FISHERS | P=0.002N** P=0.030N* P=0.006N** P=0.006N** |P=0.404N P=0.242 (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 42 Statistical Analysis of Non-neoplastic Lesions 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 | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 14/50 (28%) 32/50 (64%) 37/50 (74%) |3/50 (6%) 41/50 (82%) 45/50 (90%) 39/48 (81%) | |POLY-3 ADJUSTED (b)| 0.0% 34.6% 72.3% 81.2% |7.3% 86.0% 93.2% 84.1% | |TERMINAL (d) | 0/20 (0%) 7/16 (44%) 12/15 (80%) 0/0 (0%) |0/22 (0%) 21/25 (84%) 20/22 (91%) 8/11 (73%) | |FIRST INCIDENCE | --- 431 438 337 |407 347 444 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 37 MG/KG 75 MG/KG 150 |0 MG/KG 37 MG/KG 75 MG/KG 150 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Inflammation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 4.7% 7.6% 0.0% 0.0% |0.0% 0.0% 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 | 588 606 --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.155N P=0.439 P=0.277N P=0.372N |(e) (e) (e) (e) | |POLY 3 | P=0.101N P=0.468 P=0.265N P=0.309N |(e) (e) (e) (e) | |POLY 1.5 | P=0.086N P=0.482 P=0.253N P=0.273N |(e) (e) (e) (e) | |POLY 6 | P=0.134N P=0.449 P=0.284N P=0.380N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.066N P=0.523 P=0.211N P=0.193N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.073N P=0.500 P=0.247N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 43 Statistical Analysis of Non-neoplastic Lesions 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 | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 4/50 (8%) 15/50 (30%) 14/50 (28%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 23.1% 10.1% 37.7% 39.5% |0.0% 0.0% 2.4% 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 | 588 596 568 523 |--- --- 690 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.160N P=0.058 P<0.001 ** |P=0.662 (e) P=0.520 (e) | |POLY 3 | P=0.012 * P=0.097N P=0.109 P=0.087 |P=0.656 (e) P=0.511 (e) | |POLY 1.5 | P=0.025 * P=0.086N P=0.132 P=0.147 |P=0.677 (e) P=0.507 (e) | |POLY 6 | P=0.003 ** P=0.118N P=0.079 P=0.031 * |P=0.609 (e) P=0.516 (e) | |LOGISTIC REGRESSION| P=0.015 * P=0.077N P=0.126 P=0.124 |P=0.686 (e) P=0.508 (e) | |COCH-ARM / FISHERS | P=0.055 P=0.074N P=0.178 P=0.241 |P=0.690 (e) 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 | |=================================================================================================================================| | | |Stomach, Glandular | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 3/50 (6%) 2/50 (4%) |3/50 (6%) 4/50 (8%) 4/50 (8%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 9.3% 5.1% 7.9% 6.3% |7.5% 9.7% 9.5% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 1/15 (7%) 0/0 (0%) |1/22 (5%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | 521 664 596 658 |598 650 557 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.535 P=0.401N P=0.571N P=0.525N |P=0.179N P=0.547 P=0.529 P=0.189N | |POLY 3 | P=0.431N P=0.386N P=0.569N P=0.486N |P=0.123N P=0.519 P=0.528 P=0.139N | |POLY 1.5 | P=0.377N P=0.364N P=0.541N P=0.413N |P=0.109N P=0.513 P=0.518 P=0.130N | |POLY 6 | P=0.526N P=0.417N P=0.612N P=0.609N |P=0.154N P=0.526 P=0.537 P=0.159N | |LOGISTIC REGRESSION| P=0.295N P=0.290N P=0.442N P=0.236N |P=0.105N P=0.510 P=0.502 P=0.128N | |COCH-ARM / FISHERS | P=0.319N P=0.339N P=0.500N P=0.339N |P=0.103N P=0.500 P=0.500 P=0.129N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 44 Statistical Analysis of Non-neoplastic Lesions 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 Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 8/50 (16%) |0/50 (0%) 5/50 (10%) 11/50 (22%) 9/48 (19%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.7% 24.1% |0.0% 12.3% 25.6% 22.9% | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 1/15 (7%) 0/0 (0%) |0/22 (0%) 5/25 (20%) 5/22 (23%) 1/11 (9%) | |FIRST INCIDENCE | --- --- 730 (T) 598 |--- 730 (T) 527 508 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) P=0.443 P<0.001 ** |P<0.001 ** P=0.042 * P<0.001 ** P=0.002 ** | |POLY 3 | P<0.001 ** (e) P=0.479 P<0.001 ** |P=0.003 ** P=0.033 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.487 P=0.002 ** |P=0.003 ** P=0.032 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.466 P<0.001 ** |P=0.002 ** P=0.033 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.443 P<0.001 ** |P=0.003 ** P=0.042 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.500 P=0.003 ** |P=0.003 ** P=0.028 * 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 | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/49 (2%) 0/49 (0%) 3/50 (6%) | | |POLY-3 ADJUSTED (b)| 7.1% 2.6% 0.0% 9.2% | | |TERMINAL (d) | 1/20 (5%) 1/16 (6%) 0/15 (0%) 0/0 (0%) | | |FIRST INCIDENCE | 521 730 (T) --- 502 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.285 P=0.362N P=0.153N P=0.409 | | |POLY 3 | P=0.480 P=0.343N P=0.145N P=0.538 | | |POLY 1.5 | P=0.501 P=0.330N P=0.136N P=0.599 | | |POLY 6 | P=0.449 P=0.363N P=0.161N P=0.430 | | |LOGISTIC REGRESSION| P=0.588 P=0.300N P=0.103N P=0.525N | | |COCH-ARM / FISHERS | P=0.528 P=0.316N P=0.125N P=0.661N | | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 45 Statistical Analysis of Non-neoplastic Lesions 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: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 7.0% 0.0% 0.0% 0.0% | | |TERMINAL (d) | 0/20 (0%) 0/16 (0%) 0/15 (0%) 0/0 (0%) | | |FIRST INCIDENCE | 521 --- --- --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.065N P=0.141N P=0.146N P=0.191N | | |POLY 3 | P=0.041N* P=0.139N P=0.147N P=0.184N | | |POLY 1.5 | P=0.043N* P=0.132N P=0.137N P=0.150N | | |POLY 6 | P=0.038N* P=0.151N P=0.164N P=0.258N | | |LOGISTIC REGRESSION| P=0.034N* P=0.100N P=0.089N P=0.067N | | |COCH-ARM / FISHERS | P=0.048N* P=0.125N P=0.125N P=0.121N | | |=================================================================================================================================| | | | | | | 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 | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 22/50 (44%) 25/50 (50%) 25/50 (50%) 10/48 (21%) |32/50 (64%) 33/49 (67%) 30/49 (61%) 32/50 (64%) | |POLY-3 ADJUSTED (b)| 50.8% 58.3% 60.1% 30.3% |71.4% 73.4% 67.0% 73.1% | |TERMINAL (d) | 14/20 (70%) 12/16 (75%) 13/15 (87%) 0/0 (0%) |18/22 (82%) 19/25 (76%) 15/22 (68%) 10/11 (91%) | |FIRST INCIDENCE | 610 431 502 502 |407 443 444 534 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.017 * P=0.111 P=0.062 P=0.011 * |P=0.016 * P=0.424N P=0.374N P=0.030 * | |POLY 3 | P=0.051N P=0.308 P=0.250 P=0.051N |P=0.524 P=0.508 P=0.411N P=0.523 | |POLY 1.5 | P=0.018N* P=0.324 P=0.281 P=0.025N* |P=0.512N P=0.488 P=0.429N P=0.568 | |POLY 6 | P=0.207N P=0.285 P=0.198 P=0.151N |P=0.441 P=0.532 P=0.395N P=0.445 | |LOGISTIC REGRESSION| P=0.084N P=0.232 P=0.165 P=0.209N |P=0.530 P=0.512 P=0.399N P=0.530 | |COCH-ARM / FISHERS | P=0.006N** P=0.344 P=0.344 P=0.012N* |P=0.477N P=0.445 P=0.469N P=0.582N | |=================================================================================================================================| Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 46 Statistical Analysis of Non-neoplastic Lesions 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 | |=================================================================================================================================| | | |Urinary Bladder | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 1/50 (2%) 2/49 (4%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 2.6% 5.4% 0.0% |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 | 617 660 664 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.631N P=0.739 P=0.410 P=0.557N |(e) (e) (e) (e) | |POLY 3 | P=0.470N P=0.747 P=0.463 P=0.559N |(e) (e) (e) (e) | |POLY 1.5 | P=0.421N P=0.755 P=0.478 P=0.531N |(e) (e) (e) (e) | |POLY 6 | P=0.569N P=0.736 P=0.441 P=0.606N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.391N P=0.742N P=0.501 P=0.454N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.368N P=0.747N P=0.500 P=0.500N |(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 | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| |5.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | |0/22 (0%) 0/25 (0%) 0/22 (0%) 0/11 (0%) | |FIRST INCIDENCE | |549 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.131N P=0.225N P=0.235N P=0.301N | |POLY 3 | |P=0.109N P=0.231N P=0.229N P=0.258N | |POLY 1.5 | |P=0.113N P=0.233N P=0.233N P=0.246N | |POLY 6 | |P=0.102N P=0.230N P=0.226N P=0.284N | |LOGISTIC REGRESSION| |P=0.119N P=0.247N P=0.265N P=0.235N | |COCH-ARM / FISHERS | |P=0.116N P=0.247N P=0.253N P=0.247N | |=================================================================================================================================| (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).