TDMS Study 05135-07 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOPRENE DATE: 10/02/97 EXPERIMENT: 05135 TEST: 07 TIME: 08:57:12 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: NO1-ES-25335 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 61825B PATHOLOGIST: GRUMBEIN, S. CAS: 78-79-5 Rats(FISCHER344) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED. ---------------- Adrenal Gland Adrenal Medulla Bone Marrow Brain Clitoral Gland Clitoral/Preputial Gland Epididymis Heart Islets, Pancreatic Kidney Liver Lung Nose Ovary Pancreas Parathyroid Gland Pituitary Gland Preputial Gland Prostate Salivary Glands Spleen Testes Thymus Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOPRENE DATE: 10/02/97 EXPERIMENT: 05135 TEST: 07 TIME: 08:57:12 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: NO1-ES-25335 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: 61825B PATHOLOGIST: GRUMBEIN, S. CAS: 78-79-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ISOPRENE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Medulla Hyperplasia Bone Fibrous Osteodystrophy Bone Marrow Necrosis Kidney: Renal Tubule Hyperplasia Liver Degeneration Cystic Regeneration Liver: Bile Duct Hyperplasia Nose Thrombosis Nose: Olfactory Epithelium Atrophy Metaplasia Parathyroid Gland Hyperplasia Spleen Fibrosis Testes: Artery Inflammation Chronic Testes: Interstitial Cell Hyperplasia =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Hyperplasia Liver: Bile Duct Hyperplasia Lung Inflammation Chronic Nose Foreign Body Inflammation Spleen Hematopoietic Cell Proliferation Thyroid Gland: C-Cell Hyperplasia =============================================================== Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.7% |2.4% 0.0% 2.4% 7.3% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 2/27 (7%) | |FIRST INCIDENCE | --- --- --- 733 (T) |714 --- 566 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.243 (e) (e) P=0.464 |P=0.076 P=0.500N P=0.751 P=0.280 | |POLY 3 | P=0.261 (e) (e) P=0.503 |P=0.081 P=0.494N P=0.759 P=0.294 | |POLY 1.5 | P=0.259 (e) (e) P=0.501 |P=0.083 P=0.496N P=0.758 P=0.296 | |POLY 6 | P=0.260 (e) (e) P=0.501 |P=0.079 P=0.492N P=0.760 P=0.292 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.464 |P=0.102 P=0.493N P=0.750N P=0.310 | |COCH-ARM / FISHERS | P=0.260 (e) (e) P=0.500 |P=0.089 P=0.500N P=0.753N P=0.309 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 23/50 (46%) 19/50 (38%) 20/50 (40%) |25/50 (50%) 17/50 (34%) 20/50 (40%) 13/50 (26%) | |POLY-3 ADJUSTED (b)| 56.8% 54.7% 46.8% 49.5% |55.6% 38.4% 47.5% 31.5% | |TERMINAL (d) | 12/18 (67%) 10/16 (63%) 7/15 (47%) 9/15 (60%) |17/29 (59%) 14/30 (47%) 16/28 (57%) 11/27 (41%) | |FIRST INCIDENCE | 440 455 510 478 |580 670 672 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.455N P=0.439 P=0.453N P=0.517N |P=0.062N P=0.065N P=0.261N P=0.025N* | |POLY 3 | P=0.387N P=0.514N P=0.239N P=0.325N |P=0.047N* P=0.072N P=0.290N P=0.017N* | |POLY 1.5 | P=0.398N P=0.528N P=0.240N P=0.339N |P=0.042N* P=0.072N P=0.260N P=0.014N* | |POLY 6 | P=0.386N P=0.518N P=0.255N P=0.330N |P=0.052N P=0.081N P=0.337N P=0.022N* | |LOGISTIC REGRESSION| P=0.362N P=0.541N P=0.248N P=0.313N |P=0.050N P=0.050N P=0.226N P=0.015N* | |COCH-ARM / FISHERS | P=0.369N P=0.579N P=0.272N P=0.343N |P=0.033N* P=0.078N P=0.211N P=0.011N* | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 11/50 (22%) 4/50 (8%) 4/50 (8%) |9/50 (18%) 14/50 (28%) 8/50 (16%) 14/50 (28%) | |POLY-3 ADJUSTED (b)| 21.5% 28.1% 10.8% 10.6% |21.2% 31.2% 18.8% 33.7% | |TERMINAL (d) | 5/18 (28%) 4/16 (25%) 2/15 (13%) 2/15 (13%) |9/29 (31%) 9/30 (30%) 6/28 (21%) 9/27 (33%) | |FIRST INCIDENCE | 652 588 712 581 |734 (T) 638 547 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.143N P=0.249 P=0.267N P=0.241N |P=0.138 P=0.199 P=0.533N P=0.125 | |POLY 3 | P=0.098N P=0.341 P=0.172N P=0.162N |P=0.160 P=0.205 P=0.498N P=0.146 | |POLY 1.5 | P=0.107N P=0.332 P=0.169N P=0.170N |P=0.169 P=0.190 P=0.505N P=0.149 | |POLY 6 | P=0.092N P=0.345 P=0.187N P=0.163N |P=0.155 P=0.226 P=0.485N P=0.149 | |LOGISTIC REGRESSION| P=0.103N P=0.304 P=0.204N P=0.172N |P=0.141 P=0.194 P=0.518N P=0.123 | |COCH-ARM / FISHERS | P=0.112N P=0.306 P=0.178N P=0.178N |P=0.200 P=0.171 P=0.500N P=0.171 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.7% 0.0% |4.7% 0.0% 0.0% 2.4% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- 692 --- |648 --- --- 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.757N (e) P=0.475 (e) |P=0.644 P=0.237N P=0.259N P=0.526N | |POLY 3 | P=0.739N (e) P=0.502 (e) |P=0.650 P=0.231N P=0.243N P=0.513N | |POLY 1.5 | P=0.741N (e) P=0.503 (e) |P=0.654 P=0.234N P=0.242N P=0.510N | |POLY 6 | P=0.740N (e) P=0.497 (e) |P=0.648 P=0.231N P=0.244N P=0.516N | |LOGISTIC REGRESSION| P=0.739N (e) P=0.498 (e) |P=0.697 P=0.238N P=0.239N P=0.455N | |COCH-ARM / FISHERS | P=0.740N (e) P=0.500 (e) |P=0.662 P=0.247N P=0.247N P=0.500N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 6/50 (12%) 3/50 (6%) 6/50 (12%) |4/50 (8%) 6/50 (12%) 4/50 (8%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 5.4% 15.7% 8.1% 15.8% |9.3% 13.5% 9.6% 14.7% | |TERMINAL (d) | 1/18 (6%) 3/16 (19%) 2/15 (13%) 1/15 (7%) |2/29 (7%) 5/30 (17%) 4/28 (14%) 4/27 (15%) | |FIRST INCIDENCE | 564 602 667 664 |630 587 734 (T) 713 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.217 P=0.126 P=0.461 P=0.128 |P=0.334 P=0.401 P=0.625 P=0.327 | |POLY 3 | P=0.231 P=0.138 P=0.499 P=0.136 |P=0.349 P=0.388 P=0.626 P=0.334 | |POLY 1.5 | P=0.224 P=0.139 P=0.505 P=0.134 |P=0.362 P=0.382 P=0.630 P=0.344 | |POLY 6 | P=0.238 P=0.133 P=0.484 P=0.135 |P=0.337 P=0.391 P=0.620 P=0.323 | |LOGISTIC REGRESSION| P=0.229 P=0.139 P=0.499 P=0.136 |P=0.341 P=0.383 P=0.634 P=0.336 | |COCH-ARM / FISHERS | P=0.227 P=0.134 P=0.500 P=0.134 |P=0.392 P=0.370 P=0.643N P=0.370 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 19/50 (38%) 19/50 (38%) 27/50 (54%) 21/50 (42%) |11/50 (22%) 6/50 (12%) 9/50 (18%) 9/50 (18%) | |POLY-3 ADJUSTED (b)| 48.5% 46.2% 64.2% 51.5% |25.1% 13.5% 21.0% 21.7% | |TERMINAL (d) | 11/18 (61%) 6/16 (38%) 11/15 (73%) 10/15 (67%) |3/29 (10%) 3/30 (10%) 5/28 (18%) 6/27 (22%) | |FIRST INCIDENCE | 468 398 454 517 |580 601 427 594 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.486 P=0.461 P=0.046 * P=0.280 |P=0.466 P=0.148N P=0.451N P=0.476N | |POLY 3 | P=0.548N P=0.507N P=0.099 P=0.483 |P=0.483 P=0.132N P=0.422N P=0.455N | |POLY 1.5 | P=0.560 P=0.528N P=0.094 P=0.444 |P=0.501 P=0.135N P=0.417N P=0.440N | |POLY 6 | P=0.529N P=0.492N P=0.104 P=0.517 |P=0.470 P=0.132N P=0.432N P=0.472N | |LOGISTIC REGRESSION| P=0.552N P=0.550N P=0.076 P=0.443 |P=0.512 P=0.136N P=0.412N P=0.437N | |COCH-ARM / FISHERS | P=0.558N P=0.582N P=0.080 P=0.419 |P=0.547 P=0.143N P=0.402N P=0.402N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/1 (0%) 0/0 (0%) 2/2 (100%) 3/3 (100%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 100.0% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 566 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.236 (e) P=0.227 P=0.222 |(e) P=0.486 (e) P=0.356 | |POLY 3 | P=1.000N (e) P=1.000 P=1.000N |(e) P=0.221 (e) P=0.269 | |POLY 1.5 | P=1.000N (e) P=1.000N P=1.000N |(e) P=0.173 (e) P=0.265 | |POLY 6 | P=1.000N (e) P=1.000N P=1.000N |(e) P=0.371 (e) P=0.279 | |LOGISTIC REGRESSION| P=0.852 (e) P=0.358 (e) |(e) P=0.313 (e) P=0.271 | |COCH-ARM / FISHERS | P=0.423 (e) P=0.333 P=0.250 |(e) P=0.167 (e) P=0.273 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Bone | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 6/50 (12%) 7/50 (14%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 5.4% 2.7% 15.8% 18.3% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 2/15 (13%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 539 657 566 611 |727 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.053 P=0.507N P=0.120 P=0.079 |P=0.677N P=0.500N P=0.520N P=0.527N | |POLY 3 | P=0.046 * P=0.496N P=0.136 P=0.081 |P=0.661N P=0.494N P=0.504N P=0.509N | |POLY 1.5 | P=0.045 * P=0.495N P=0.138 P=0.079 |P=0.659N P=0.496N P=0.504N P=0.507N | |POLY 6 | P=0.048 * P=0.504N P=0.129 P=0.080 |P=0.663N P=0.492N P=0.504N P=0.511N | |LOGISTIC REGRESSION| P=0.047 * P=0.502N P=0.137 P=0.082 |P=0.671N P=0.493N P=0.503N P=0.514N | |COCH-ARM / FISHERS | P=0.048 * P=0.500N P=0.134 P=0.080 |P=0.657N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Bone | | Hyperostosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 2/50 (4%) |6/50 (12%) 8/50 (16%) 11/50 (22%) 8/50 (16%) | |POLY-3 ADJUSTED (b)| 0.0% 2.7% 2.7% 5.3% |13.9% 17.6% 25.8% 18.7% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |4/29 (14%) 2/30 (7%) 7/28 (25%) 3/27 (11%) | |FIRST INCIDENCE | --- 693 686 588 |657 587 508 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.242 P=0.500 P=0.476 P=0.228 |P=0.504 P=0.429 P=0.138 P=0.350 | |POLY 3 | P=0.258 P=0.505 P=0.502 P=0.242 |P=0.552 P=0.429 P=0.132 P=0.381 | |POLY 1.5 | P=0.254 P=0.505 P=0.503 P=0.239 |P=0.554 P=0.412 P=0.133 P=0.377 | |POLY 6 | P=0.259 P=0.502 P=0.497 P=0.242 |P=0.556 P=0.449 P=0.130 P=0.390 | |LOGISTIC REGRESSION| P=0.252 P=0.502 P=0.500 P=0.238 |P=0.568 P=0.386 P=0.132 P=0.390 | |COCH-ARM / FISHERS | P=0.252 P=0.500 P=0.500 P=0.247 |P=0.579 P=0.387 P=0.143 P=0.387 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 2/50 (4%) |0/49 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 5.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- --- 727 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.042 * (e) (e) P=0.208 |(e) (e) (e) (e) | |POLY 3 | P=0.046 * (e) (e) P=0.239 |(e) (e) (e) (e) | |POLY 1.5 | P=0.045 * (e) (e) P=0.238 |(e) (e) (e) (e) | |POLY 6 | P=0.046 * (e) (e) P=0.237 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.042 * (e) (e) P=0.207 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.047 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |2/47 (4%) 4/48 (8%) 2/46 (4%) 3/48 (6%) | |POLY-3 ADJUSTED (b)| |5.0% 9.5% 5.3% 7.7% | |TERMINAL (d) | |2/27 (7%) 3/29 (10%) 2/26 (8%) 3/26 (12%) | |FIRST INCIDENCE | |734 (T) 727 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.537 P=0.365 P=0.683 P=0.482 | |POLY 3 | |P=0.550 P=0.359 P=0.676 P=0.485 | |POLY 1.5 | |P=0.559 P=0.355 P=0.677 P=0.491 | |POLY 6 | |P=0.543 P=0.363 P=0.675 P=0.480 | |LOGISTIC REGRESSION| |P=0.533 P=0.355 P=0.683 P=0.482 | |COCH-ARM / FISHERS | |P=0.581 P=0.349 P=0.683 P=0.510 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Eye | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 1/3 (33%) 3/3 (100%) 2/2 (100%) |5/5 (100%) 3/4 (75%) 3/3 (100%) 4/6 (67%) | |POLY-3 ADJUSTED (b)| 100.0% 41.0% 100.0% 100.0% |100.0% 79.8% 100.0% 67.6% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 2/2 (100%) 1/1 (100%) |3/3 (100%) 1/1 (100%) 2/2 (100%) 3/4 (75%) | |FIRST INCIDENCE | 733 (T) 602 576 618 |629 601 727 709 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.602 P=0.517 (e) (e) |P=0.301N P=0.677N (e) P=0.356N | |POLY 3 | P=0.657 P=0.574N (e) (e) |P=0.213N P=0.569N (e) P=0.269N | |POLY 1.5 | P=0.576 P=0.538N (e) (e) |P=0.229N P=0.508N (e) P=0.265N | |POLY 6 | P=0.764 P=0.638N (e) (e) |P=0.190N P=0.709N (e) P=0.279N | |LOGISTIC REGRESSION| P=0.495 P=0.588N (e) (e) |P=0.216N P=0.527N (e) P=0.271N | |COCH-ARM / FISHERS | P=0.484 P=0.500N (e) (e) |P=0.239N P=0.444N (e) P=0.273N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 2/3 (67%) 3/3 (100%) 2/2 (100%) |5/5 (100%) 2/4 (50%) 3/3 (100%) 4/6 (67%) | |POLY-3 ADJUSTED (b)| 100.0% 79.5% 100.0% 100.0% |100.0% 59.2% 100.0% 67.6% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 2/2 (100%) 1/1 (100%) |3/3 (100%) 1/1 (100%) 2/2 (100%) 3/4 (75%) | |FIRST INCIDENCE | 733 (T) 602 576 618 |629 601 727 709 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.692 P=0.243 (e) (e) |P=0.371N P=0.486N (e) P=0.356N | |POLY 3 | P=0.928 P=0.885N (e) (e) |P=0.308N P=0.221N (e) P=0.269N | |POLY 1.5 | P=0.818 P=0.786N (e) (e) |P=0.352N P=0.173N (e) P=0.265N | |POLY 6 | P=0.999 P=0.995N (e) (e) |P=0.246N P=0.371N (e) P=0.279N | |LOGISTIC REGRESSION| P=0.952 (e) (e) (e) |P=0.238N P=0.313N (e) P=0.271N | |COCH-ARM / FISHERS | P=0.719 P=0.750N (e) (e) |P=0.409N P=0.167N (e) P=0.273N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 41/50 (82%) 44/50 (88%) 44/50 (88%) 38/50 (76%) |35/50 (70%) 33/50 (66%) 28/50 (56%) 37/50 (74%) | |POLY-3 ADJUSTED (b)| 88.4% 92.7% 91.4% 85.1% |76.7% 69.8% 63.6% 82.1% | |TERMINAL (d) | 17/18 (94%) 16/16 (100%) 14/15 (93%) 14/15 (93%) |25/29 (86%) 22/30 (73%) 21/28 (75%) 24/27 (89%) | |FIRST INCIDENCE | 235 398 454 517 |454 482 539 432 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.310N P=0.262 P=0.223 P=0.555N |P=0.076 P=0.340N P=0.171N P=0.260 | |POLY 3 | P=0.184N P=0.331 P=0.432 P=0.433N |P=0.090 P=0.295N P=0.118N P=0.340 | |POLY 1.5 | P=0.184N P=0.314 P=0.364 P=0.436N |P=0.104 P=0.345N P=0.120N P=0.344 | |POLY 6 | P=0.163N P=0.342 P=0.525 P=0.417N |P=0.082 P=0.241N P=0.114N P=0.356 | |LOGISTIC REGRESSION| P=0.100N P=0.331 P=0.311 P=0.300N |P=0.073 P=0.342N P=0.117N P=0.279 | |COCH-ARM / FISHERS | P=0.084N P=0.288 P=0.288 P=0.312N |P=0.159 P=0.415N P=0.107N P=0.412 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Heart: Artery | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 4/50 (8%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.7% 0.0% 5.3% 10.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 733 (T) --- 566 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.053 P=0.523N P=0.473 P=0.154 |(e) (e) (e) (e) | |POLY 3 | P=0.050 P=0.496N P=0.509 P=0.184 |(e) (e) (e) (e) | |POLY 1.5 | P=0.049 * P=0.496N P=0.508 P=0.180 |(e) (e) (e) (e) | |POLY 6 | P=0.051 P=0.500N P=0.504 P=0.183 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.051 (e) P=0.503 P=0.170 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.051 P=0.500N P=0.500 P=0.181 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Heart: Atrium | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 3/50 (6%) 5/50 (10%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 10.6% 7.8% 8.0% 13.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 1/15 (7%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 592 602 555 478 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.333 P=0.519N P=0.555N P=0.473 |(e) (e) (e) (e) | |POLY 3 | P=0.331 P=0.491N P=0.500N P=0.512 |(e) (e) (e) (e) | |POLY 1.5 | P=0.323 P=0.490N P=0.494N P=0.506 |(e) (e) (e) (e) | |POLY 6 | P=0.335 P=0.501N P=0.520N P=0.507 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.323 P=0.496N P=0.496N P=0.501 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.325 P=0.500N P=0.500N P=0.500 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Intestine Large, Rectum | | Inflammation Acute | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/49 (0%) 2/46 (4%) 0/50 (0%) |0/48 (0%) 0/47 (0%) 0/48 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.7% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/27 (0%) 0/30 (0%) 0/27 (0%) 0/26 (0%) | |FIRST INCIDENCE | --- --- 555 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.547N (e) P=0.245 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.540N (e) P=0.241 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.543N (e) P=0.240 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.541N (e) P=0.238 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.535N (e) P=0.218 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.544N (e) P=0.242 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 1/49 (2%) 2/48 (4%) 2/49 (4%) |0/49 (0%) 0/48 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.7% 2.7% 5.6% 5.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 468 702 681 548 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.474 P=0.758 P=0.489 P=0.516 |(e) (e) (e) (e) | |POLY 3 | P=0.483 P=0.759N P=0.492 P=0.513 |(e) (e) (e) (e) | |POLY 1.5 | P=0.477 P=0.758N P=0.496 P=0.509 |(e) (e) (e) (e) | |POLY 6 | P=0.486 P=0.760 P=0.483 P=0.511 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.465 P=0.739 P=0.478 P=0.469 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.469 P=0.753N P=0.492 P=0.500 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 0/49 (0%) |2/49 (4%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 2.7% 8.1% 0.0% |4.7% 0.0% 2.4% 4.9% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 3/15 (20%) 0/15 (0%) |1/29 (3%) 0/30 (0%) 1/28 (4%) 1/27 (4%) | |FIRST INCIDENCE | --- 703 733 (T) --- |539 --- 734 (T) 709 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.356N P=0.473 P=0.087 (e) |P=0.371 P=0.234N P=0.511N P=0.669 | |POLY 3 | P=0.331N P=0.505 P=0.118 (e) |P=0.378 P=0.229N P=0.506N P=0.679 | |POLY 1.5 | P=0.336N P=0.504 P=0.121 (e) |P=0.385 P=0.230N P=0.503N P=0.685 | |POLY 6 | P=0.332N P=0.502 P=0.112 (e) |P=0.373 P=0.230N P=0.510N P=0.673 | |LOGISTIC REGRESSION| P=0.341N P=0.499 P=0.087 (e) |P=0.394 P=0.249N P=0.487N P=0.690N | |COCH-ARM / FISHERS | P=0.341N P=0.500 P=0.121 (e) |P=0.402 P=0.242N P=0.492N P=0.684N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 4/50 (8%) 2/50 (4%) |1/50 (2%) 0/49 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 5.4% 0.0% 10.7% 5.4% |2.3% 0.0% 0.0% 2.5% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 3/15 (20%) 2/15 (13%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 604 --- 566 733 (T) |596 --- --- 713 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.593 P=0.237N P=0.309 P=0.676 |P=0.496 P=0.482N P=0.510N P=0.748 | |POLY 3 | P=0.605 P=0.236N P=0.336 P=0.694 |P=0.497 P=0.499N P=0.506N P=0.749 | |POLY 1.5 | P=0.602 P=0.234N P=0.342 P=0.693 |P=0.501 P=0.501N P=0.505N P=0.752 | |POLY 6 | P=0.604 P=0.243N P=0.318 P=0.685 |P=0.493 P=0.497N P=0.508N P=0.746 | |LOGISTIC REGRESSION| P=0.610 P=0.241N P=0.340 P=0.692N |P=0.527 P=0.530N P=0.465N P=0.755N | |COCH-ARM / FISHERS | P=0.607 P=0.247N P=0.339 P=0.691N |P=0.512 P=0.505N P=0.500N P=0.753N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 1/49 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.7% 2.7% 5.3% 0.0% |0.0% 2.3% 2.4% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 1/15 (7%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 1/28 (4%) 0/27 (0%) | |FIRST INCIDENCE | 564 693 555 --- |--- 622 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.295N P=0.752N P=0.491 P=0.475N |P=0.526N P=0.514 P=0.493 (e) | |POLY 3 | P=0.294N P=0.759N P=0.502 P=0.500N |P=0.519N P=0.505 P=0.496 (e) | |POLY 1.5 | P=0.296N P=0.758N P=0.505 P=0.501N |P=0.517N P=0.502 P=0.496 (e) | |POLY 6 | P=0.295N P=0.759 P=0.492 P=0.504N |P=0.522N P=0.510 P=0.496 (e) | |LOGISTIC REGRESSION| P=0.290N P=0.758 P=0.485 P=0.489N |P=0.507N P=0.474 P=0.493 (e) | |COCH-ARM / FISHERS | P=0.292N P=0.753N P=0.500 P=0.500N |P=0.509N P=0.495 P=0.500 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 3/50 (6%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.3% 8.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- 566 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.077 (e) P=0.233 P=0.113 |(e) (e) (e) (e) | |POLY 3 | P=0.073 (e) P=0.242 P=0.121 |(e) (e) (e) (e) | |POLY 1.5 | P=0.071 (e) P=0.242 P=0.120 |(e) (e) (e) (e) | |POLY 6 | P=0.073 (e) P=0.238 P=0.120 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.072 (e) P=0.232 P=0.119 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.073 (e) P=0.247 P=0.121 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 50/50 (100%) 50/50 (100%) 50/50 (100%) 49/50 (98%) |46/50 (92%) 47/49 (96%) 48/50 (96%) 47/50 (94%) | |POLY-3 ADJUSTED (b)| 100.0% 100.0% 100.0% 100.0% |95.9% 96.7% 99.1% 98.1% | |TERMINAL (d) | 18/18 (100%) 16/16 (100%) 15/15 (100%) 15/15 (100%)|29/29 (100%) 29/30 (97%) 28/28 (100%) 27/27 (100%) | |FIRST INCIDENCE | 235 398 454 222 |482 370 427 415 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.531 (e) (e) P=0.451 |P=0.281 P=0.512N P=0.339 P=0.305 | |POLY 3 | P=1.000N (e) (e) P=1.000N |P=0.535 P=0.646 P=0.323 P=0.481 | |POLY 1.5 | P=1.000N (e) (e) P=1.000N |P=0.551 P=0.525 P=0.266 P=0.437 | |POLY 6 | P=1.000N (e) (e) P=1.000N |P=0.519 P=0.761N P=0.423 P=0.547 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.408 P=0.422 P=0.191 P=0.253 | |COCH-ARM / FISHERS | P=0.260N (e) (e) P=0.500N |P=0.592N P=0.349 P=0.339 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 6/50 (12%) 8/50 (16%) |4/50 (8%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.3% 15.6% 20.8% |9.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 1/16 (6%) 2/15 (13%) 2/15 (13%) |4/29 (14%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- 702 518 548 |734 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.012 * P=0.222 P=0.018 * P=0.005 ** |P=0.218N P=0.058N P=0.066N P=0.071N | |POLY 3 | P=0.010 * P=0.241 P=0.017 * P=0.004 ** |P=0.210N P=0.057N P=0.062N P=0.066N | |POLY 1.5 | P=0.009 ** P=0.242 P=0.017 * P=0.004 ** |P=0.206N P=0.060N P=0.062N P=0.065N | |POLY 6 | P=0.010 * P=0.237 P=0.016 * P=0.004 ** |P=0.215N P=0.055N P=0.062N P=0.066N | |LOGISTIC REGRESSION| P=0.010 * P=0.226 P=0.018 * P=0.005 ** |P=0.218N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.010 * P=0.247 P=0.013 * P=0.003 ** |P=0.202N P=0.061N P=0.059N P=0.059N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 5/50 (10%) 3/50 (6%) |2/50 (4%) 2/50 (4%) 3/50 (6%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 5.4% 0.0% 13.3% 8.0% |4.6% 4.6% 7.1% 9.8% | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 1/15 (7%) 2/15 (13%) |1/29 (3%) 2/30 (7%) 1/28 (4%) 2/27 (7%) | |FIRST INCIDENCE | 723 --- 667 664 |539 734 (T) 604 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.409 P=0.282N P=0.184 P=0.438 |P=0.239 P=0.683N P=0.481 P=0.304 | |POLY 3 | P=0.436 P=0.232N P=0.223 P=0.509 |P=0.248 P=0.688N P=0.490 P=0.314 | |POLY 1.5 | P=0.428 P=0.232N P=0.224 P=0.504 |P=0.256 P=0.689N P=0.491 P=0.320 | |POLY 6 | P=0.441 P=0.236N P=0.218 P=0.508 |P=0.243 P=0.687N P=0.490 P=0.309 | |LOGISTIC REGRESSION| P=0.435 P=0.260N P=0.203 P=0.484 |P=0.262 P=0.692 P=0.508 P=0.332 | |COCH-ARM / FISHERS | P=0.431 P=0.247N P=0.218 P=0.500 |P=0.275 P=0.691N P=0.500 P=0.339 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 13/50 (26%) 13/50 (26%) 16/50 (32%) |36/50 (72%) 38/50 (76%) 33/50 (66%) 33/50 (66%) | |POLY-3 ADJUSTED (b)| 43.0% 33.5% 32.9% 41.0% |79.6% 81.2% 74.8% 75.5% | |TERMINAL (d) | 11/18 (61%) 7/16 (44%) 5/15 (33%) 10/15 (67%) |24/29 (83%) 27/30 (90%) 24/28 (86%) 22/27 (82%) | |FIRST INCIDENCE | 440 581 454 517 |552 587 510 482 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.345 P=0.358N P=0.386N P=0.508 |P=0.526N P=0.527 P=0.441N P=0.527N | |POLY 3 | P=0.395 P=0.257N P=0.236N P=0.523N |P=0.377N P=0.530 P=0.376N P=0.411N | |POLY 1.5 | P=0.388 P=0.249N P=0.235N P=0.520N |P=0.350N P=0.478 P=0.368N P=0.399N | |POLY 6 | P=0.396 P=0.283N P=0.256N P=0.550N |P=0.388N P=0.584 P=0.410N P=0.418N | |LOGISTIC REGRESSION| P=0.423 P=0.230N P=0.243N P=0.478N |P=0.458N P=0.564 P=0.383N P=0.465N | |COCH-ARM / FISHERS | P=0.416 P=0.257N P=0.257N P=0.500N |P=0.269N P=0.410 P=0.333N P=0.333N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 9/50 (18%) 7/50 (14%) 8/50 (16%) |9/50 (18%) 11/50 (22%) 10/50 (20%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 16.4% 23.8% 18.1% 21.3% |21.1% 24.9% 24.0% 27.1% | |TERMINAL (d) | 6/18 (33%) 7/16 (44%) 3/15 (20%) 6/15 (40%) |8/29 (28%) 9/30 (30%) 10/28 (36%) 11/27 (41%) | |FIRST INCIDENCE | 733 (T) 670 454 630 |705 670 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.414 P=0.192 P=0.409 P=0.245 |P=0.349 P=0.430 P=0.467 P=0.323 | |POLY 3 | P=0.494 P=0.302 P=0.541 P=0.402 |P=0.380 P=0.435 P=0.478 P=0.351 | |POLY 1.5 | P=0.484 P=0.302 P=0.531 P=0.393 |P=0.401 P=0.422 P=0.481 P=0.364 | |POLY 6 | P=0.497 P=0.290 P=0.545 P=0.401 |P=0.359 P=0.446 P=0.474 P=0.336 | |LOGISTIC REGRESSION| P=0.499 P=0.200 P=0.497 P=0.318 |P=0.338 P=0.429 P=0.478 P=0.306 | |COCH-ARM / FISHERS | P=0.491 P=0.288 P=0.500 P=0.387 |P=0.450 P=0.402 P=0.500 P=0.402 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 9/50 (18%) 14/50 (28%) 17/50 (34%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 23.7% 23.3% 35.3% 43.0% |0.0% 2.3% 0.0% 2.4% | |TERMINAL (d) | 3/18 (17%) 2/16 (13%) 3/15 (20%) 6/15 (40%) |0/29 (0%) 1/30 (3%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 600 657 537 611 |--- 734 (T) --- 664 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.051 P=0.526 P=0.135 P=0.048 * |P=0.472 P=0.507 (e) P=0.495 | |POLY 3 | P=0.038 * P=0.591N P=0.187 P=0.053 |P=0.480 P=0.507 (e) P=0.492 | |POLY 1.5 | P=0.036 * P=0.588N P=0.186 P=0.051 |P=0.482 P=0.504 (e) P=0.494 | |POLY 6 | P=0.041 * P=0.609N P=0.178 P=0.053 |P=0.479 P=0.508 (e) P=0.491 | |LOGISTIC REGRESSION| P=0.040 * P=0.594N P=0.171 P=0.053 |P=0.481 P=0.507 (e) P=0.505 | |COCH-ARM / FISHERS | P=0.042 * P=0.602N P=0.171 P=0.055 |P=0.489 P=0.500 (e) P=0.500 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 3/50 (6%) 3/50 (6%) |2/50 (4%) 3/50 (6%) 1/50 (2%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 5.5% 10.5% 8.1% 8.0% |4.7% 6.8% 2.4% 9.8% | |TERMINAL (d) | 2/18 (11%) 1/16 (6%) 1/15 (7%) 2/15 (13%) |2/29 (7%) 2/30 (7%) 1/28 (4%) 3/27 (11%) | |FIRST INCIDENCE | 733 (T) 657 683 667 |734 (T) 664 734 (T) 625 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.585 P=0.305 P=0.435 P=0.436 |P=0.205 P=0.522 P=0.512N P=0.306 | |POLY 3 | P=0.624 P=0.352 P=0.507 P=0.509 |P=0.220 P=0.518 P=0.507N P=0.320 | |POLY 1.5 | P=0.616 P=0.349 P=0.509 P=0.504 |P=0.225 P=0.511 P=0.506N P=0.323 | |POLY 6 | P=0.626 P=0.350 P=0.499 P=0.509 |P=0.217 P=0.524 P=0.507N P=0.318 | |LOGISTIC REGRESSION| P=0.623 P=0.330 P=0.470 P=0.478 |P=0.207 P=0.518 P=0.512N P=0.311 | |COCH-ARM / FISHERS | P=0.618 P=0.339 P=0.500 P=0.500 |P=0.237 P=0.500 P=0.500N P=0.339 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 15/50 (30%) 12/50 (24%) 9/50 (18%) 11/50 (22%) |8/50 (16%) 6/50 (12%) 11/50 (22%) 9/50 (18%) | |POLY-3 ADJUSTED (b)| 35.4% 28.9% 23.0% 27.2% |17.8% 13.3% 24.9% 20.6% | |TERMINAL (d) | 1/18 (6%) 2/16 (13%) 2/15 (13%) 0/15 (0%) |1/29 (3%) 1/30 (3%) 1/28 (4%) 0/27 (0%) | |FIRST INCIDENCE | 440 420 518 581 |482 587 547 415 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.428N P=0.388N P=0.175N P=0.283N |P=0.397 P=0.361N P=0.301 P=0.455 | |POLY 3 | P=0.426N P=0.340N P=0.157N P=0.283N |P=0.428 P=0.381N P=0.286 P=0.474 | |POLY 1.5 | P=0.435N P=0.321N P=0.132N P=0.272N |P=0.434 P=0.383N P=0.288 P=0.478 | |POLY 6 | P=0.411N P=0.392N P=0.209N P=0.309N |P=0.427 P=0.384N P=0.289 P=0.473 | |LOGISTIC REGRESSION| P=0.394N P=0.369N P=0.130N P=0.246N |P=0.537 P=0.440N P=0.331 P=0.588 | |COCH-ARM / FISHERS | P=0.410N P=0.326N P=0.121N P=0.247N |P=0.460 P=0.387N P=0.306 P=0.500 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 4/50 (8%) 4/50 (8%) |2/50 (4%) 4/50 (8%) 5/50 (10%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 2.7% 2.7% 10.6% 10.4% |4.7% 9.1% 12.0% 14.3% | |TERMINAL (d) | 0/18 (0%) 1/16 (6%) 1/15 (7%) 1/15 (7%) |2/29 (7%) 3/30 (10%) 5/28 (18%) 4/27 (15%) | |FIRST INCIDENCE | 604 733 (T) 664 560 |734 (T) 670 734 (T) 482 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.190 P=0.754 P=0.170 P=0.197 |P=0.160 P=0.356 P=0.198 P=0.116 | |POLY 3 | P=0.195 P=0.760N P=0.180 P=0.188 |P=0.189 P=0.354 P=0.207 P=0.127 | |POLY 1.5 | P=0.186 P=0.758N P=0.183 P=0.183 |P=0.191 P=0.348 P=0.208 P=0.128 | |POLY 6 | P=0.203 P=0.758 P=0.172 P=0.189 |P=0.187 P=0.361 P=0.206 P=0.128 | |LOGISTIC REGRESSION| P=0.182 P=0.759N P=0.181 P=0.180 |P=0.180 P=0.354 P=0.198 P=0.136 | |COCH-ARM / FISHERS | P=0.184 P=0.753N P=0.181 P=0.181 |P=0.202 P=0.339 P=0.218 P=0.134 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |4/50 (8%) 10/50 (20%) 10/50 (20%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.7% |9.1% 22.0% 22.8% 12.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |1/29 (3%) 5/30 (17%) 6/28 (21%) 2/27 (7%) | |FIRST INCIDENCE | --- --- --- 733 (T) |552 626 510 432 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.243 (e) (e) P=0.464 |P=0.308N P=0.103 P=0.077 P=0.469 | |POLY 3 | P=0.261 (e) (e) P=0.503 |P=0.286N P=0.082 P=0.071 P=0.472 | |POLY 1.5 | P=0.259 (e) (e) P=0.501 |P=0.272N P=0.078 P=0.070 P=0.479 | |POLY 6 | P=0.260 (e) (e) P=0.501 |P=0.301N P=0.086 P=0.072 P=0.464 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.464 |P=0.220N P=0.066 P=0.083 P=0.543 | |COCH-ARM / FISHERS | P=0.260 (e) (e) P=0.500 |P=0.243N P=0.074 P=0.074 P=0.500 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Regeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 6/50 (12%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 5.5% 0.0% 5.3% 15.3% |0.0% 2.3% 4.8% 7.2% | |TERMINAL (d) | 2/18 (11%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 1/30 (3%) 2/28 (7%) 1/27 (4%) | |FIRST INCIDENCE | 733 (T) --- 510 361 |--- 734 (T) 734 (T) 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.012 * P=0.263N P=0.650 P=0.125 |P=0.124 P=0.507 P=0.230 P=0.117 | |POLY 3 | P=0.012 * P=0.232N P=0.686N P=0.151 |P=0.132 P=0.507 P=0.232 P=0.115 | |POLY 1.5 | P=0.011 * P=0.232N P=0.686N P=0.142 |P=0.133 P=0.504 P=0.233 P=0.115 | |POLY 6 | P=0.013 * P=0.235N P=0.694N P=0.157 |P=0.132 P=0.508 P=0.232 P=0.115 | |LOGISTIC REGRESSION| P=0.011 * (e) P=0.693N P=0.134 |P=0.145 P=0.507 P=0.230 P=0.144 | |COCH-ARM / FISHERS | P=0.011 * P=0.247N P=0.691N P=0.134 |P=0.140 P=0.500 P=0.247 P=0.121 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 25/50 (50%) 32/50 (64%) 36/50 (72%) 29/50 (58%) |3/50 (6%) 9/50 (18%) 9/50 (18%) 10/50 (20%) | |POLY-3 ADJUSTED (b)| 57.8% 74.2% 79.7% 67.0% |6.9% 19.9% 20.7% 23.1% | |TERMINAL (d) | 7/18 (39%) 13/16 (81%) 11/15 (73%) 9/15 (60%) |0/29 (0%) 5/30 (17%) 3/28 (11%) 2/27 (7%) | |FIRST INCIDENCE | 468 455 510 222 |539 601 427 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.506N P=0.129 P=0.042 * P=0.257 |P=0.152 P=0.083 P=0.066 P=0.039 * | |POLY 3 | P=0.453N P=0.070 P=0.016 * P=0.246 |P=0.159 P=0.067 P=0.057 P=0.032 * | |POLY 1.5 | P=0.459N P=0.093 P=0.018 * P=0.255 |P=0.160 P=0.064 P=0.057 P=0.031 * | |POLY 6 | P=0.470N P=0.044 * P=0.013 * P=0.216 |P=0.165 P=0.069 P=0.057 P=0.033 * | |LOGISTIC REGRESSION| P=0.454N P=0.130 P=0.022 * P=0.273 |P=0.204 P=0.052 P=0.069 P=0.046 * | |COCH-ARM / FISHERS | P=0.437N P=0.113 P=0.020 * P=0.274 |P=0.178 P=0.061 P=0.061 P=0.036 * | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 11/50 (22%) 10/50 (20%) 9/50 (18%) |5/50 (10%) 5/50 (10%) 8/50 (16%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 18.4% 26.7% 24.8% 22.1% |11.4% 10.9% 18.4% 7.3% | |TERMINAL (d) | 2/18 (11%) 0/16 (0%) 1/15 (7%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 1/28 (4%) 0/27 (0%) | |FIRST INCIDENCE | 592 535 537 361 |580 370 508 630 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.546N P=0.226 P=0.272 P=0.384 |P=0.246N P=0.597N P=0.271 P=0.395N | |POLY 3 | P=0.526N P=0.266 P=0.338 P=0.446 |P=0.244N P=0.600N P=0.270 P=0.389N | |POLY 1.5 | P=0.546N P=0.249 P=0.327 P=0.422 |P=0.230N P=0.610N P=0.269 P=0.380N | |POLY 6 | P=0.517N P=0.282 P=0.344 P=0.462 |P=0.258N P=0.595N P=0.271 P=0.399N | |LOGISTIC REGRESSION| P=0.544N P=0.217 P=0.297 P=0.393 |P=0.151N P=0.556 P=0.294 P=0.336N | |COCH-ARM / FISHERS | P=0.557N P=0.218 P=0.298 P=0.393 |P=0.197N P=0.630N P=0.277 P=0.357N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 20/49 (41%) 16/50 (32%) 22/50 (44%) 15/50 (30%) |31/50 (62%) 29/50 (58%) 25/50 (50%) 19/50 (38%) | |POLY-3 ADJUSTED (b)| 53.1% 38.8% 52.8% 39.1% |72.5% 63.4% 54.6% 42.4% | |TERMINAL (d) | 16/18 (89%) 7/16 (44%) 9/15 (60%) 8/15 (53%) |29/29 (100%) 21/30 (70%) 16/28 (57%) 11/27 (41%) | |FIRST INCIDENCE | 482 398 454 560 |671 587 427 114 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.262N P=0.374N P=0.221 P=0.365N |P=0.038N* P=0.309N P=0.183N P=0.022N* | |POLY 3 | P=0.217N P=0.136N P=0.583N P=0.147N |P=0.006N** P=0.229N P=0.053N P=0.002N** | |POLY 1.5 | P=0.213N P=0.171N P=0.547 P=0.166N |P=0.008N** P=0.311N P=0.095N P=0.005N** | |POLY 6 | P=0.231N P=0.104N P=0.520N P=0.129N |P=0.004N** P=0.133N P=0.020N* P<0.001N** | |LOGISTIC REGRESSION| P=0.169N P=0.225N P=0.433 P=0.171N |P=0.020N* P=0.269N P=0.172N P=0.019N* | |COCH-ARM / FISHERS | P=0.179N P=0.241N P=0.453 P=0.180N |P=0.013N* P=0.419N P=0.157N P=0.014N* | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.3% 5.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- 566 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.238 (e) P=0.233 P=0.239 |(e) (e) (e) (e) | |POLY 3 | P=0.229 (e) P=0.243 P=0.243 |(e) (e) (e) (e) | |POLY 1.5 | P=0.227 (e) P=0.245 P=0.241 |(e) (e) (e) (e) | |POLY 6 | P=0.231 (e) P=0.238 P=0.241 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.227 (e) P=0.238 P=0.241 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.228 (e) P=0.253 P=0.253 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/49 (14%) 11/50 (22%) 4/50 (8%) 10/50 (20%) |5/50 (10%) 5/50 (10%) 10/50 (20%) 8/50 (16%) | |POLY-3 ADJUSTED (b)| 18.6% 28.4% 10.4% 25.7% |11.7% 11.3% 23.9% 19.3% | |TERMINAL (d) | 3/18 (17%) 5/16 (31%) 1/15 (7%) 5/15 (33%) |4/29 (14%) 4/30 (13%) 9/28 (32%) 5/27 (19%) | |FIRST INCIDENCE | 547 588 469 478 |684 686 672 594 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.255 P=0.184 P=0.309N P=0.237 |P=0.280 P=0.603N P=0.115 P=0.237 | |POLY 3 | P=0.290 P=0.226 P=0.243N P=0.317 |P=0.307 P=0.610N P=0.117 P=0.253 | |POLY 1.5 | P=0.282 P=0.234 P=0.240N P=0.313 |P=0.316 P=0.618N P=0.120 P=0.257 | |POLY 6 | P=0.290 P=0.207 P=0.260N P=0.303 |P=0.303 P=0.605N P=0.115 P=0.252 | |LOGISTIC REGRESSION| P=0.284 P=0.225 P=0.249N P=0.310 |P=0.286 P=0.607N P=0.118 P=0.242 | |COCH-ARM / FISHERS | P=0.289 P=0.232 P=0.251N P=0.314 |P=0.350 P=0.630N P=0.131 P=0.277 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Lung: Artery, Mediastinum | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.3% 5.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- 566 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.227 (e) P=0.233 P=0.223 |(e) (e) (e) (e) | |POLY 3 | P=0.229 (e) P=0.243 P=0.242 |(e) (e) (e) (e) | |POLY 1.5 | P=0.226 (e) P=0.245 P=0.241 |(e) (e) (e) (e) | |POLY 6 | P=0.229 (e) P=0.238 P=0.240 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.227 (e) P=0.238 P=0.238 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.228 (e) P=0.253 P=0.253 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/46 (4%) 0/46 (0%) 0/44 (0%) |0/45 (0%) 0/47 (0%) 0/49 (0%) 0/46 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 5.7% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/13 (0%) |0/27 (0%) 0/28 (0%) 0/27 (0%) 0/25 (0%) | |FIRST INCIDENCE | --- 597 --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.464N P=0.246 (e) (e) |(e) (e) (e) (e) | |POLY 3 | P=0.478N P=0.232 (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.481N P=0.230 (e) (e) |(e) (e) (e) (e) | |POLY 6 | P=0.478N P=0.233 (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.481N P=0.223 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.480N P=0.232 (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Galactocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/42 (5%) 4/43 (9%) 2/47 (4%) 3/44 (7%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.4% 12.2% 5.7% 8.7% |2.4% 2.3% 2.4% 0.0% | |TERMINAL (d) | 2/16 (13%) 0/12 (0%) 1/15 (7%) 1/14 (7%) |1/29 (3%) 0/30 (0%) 1/28 (4%) 0/27 (0%) | |FIRST INCIDENCE | 733 (T) 604 683 621 |734 (T) 714 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.570 P=0.296 P=0.671 P=0.469 |P=0.377N P=0.757N P=0.754 P=0.514N | |POLY 3 | P=0.603 P=0.353 P=0.655N P=0.544 |P=0.368N P=0.753N P=0.757 P=0.509N | |POLY 1.5 | P=0.591 P=0.353 P=0.651N P=0.536 |P=0.364N P=0.756N P=0.757 P=0.507N | |POLY 6 | P=0.614 P=0.349 P=0.667N P=0.548 |P=0.372N P=0.751N P=0.757 P=0.511N | |LOGISTIC REGRESSION| P=0.593 P=0.335 P=0.697N P=0.531 |P=0.373N P=0.754N P=0.754 (e) | |COCH-ARM / FISHERS | P=0.575 P=0.349 P=0.648N P=0.522 |P=0.354N P=0.753N P=0.753N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/42 (0%) 0/43 (0%) 0/47 (0%) 0/44 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.3% 0.0% 0.0% 4.9% | |TERMINAL (d) | 0/16 (0%) 0/12 (0%) 0/15 (0%) 0/14 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 2/27 (7%) | |FIRST INCIDENCE | --- --- --- --- |596 --- --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.147 P=0.482N P=0.510N P=0.478 | |POLY 3 | (e) (e) (e) (e) |P=0.152 P=0.496N P=0.506N P=0.480 | |POLY 1.5 | (e) (e) (e) (e) |P=0.155 P=0.497N P=0.505N P=0.486 | |POLY 6 | (e) (e) (e) (e) |P=0.149 P=0.495N P=0.508N P=0.474 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.159 P=0.525N P=0.465N P=0.493 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.163 P=0.500N P=0.500N P=0.500 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Artery | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/8 (0%) 0/12 (0%) 1/11 (9%) 2/11 (18%) |0/9 (0%) 0/10 (0%) 0/8 (0%) 0/11 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 12.2% 20.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/2 (0%) 0/4 (0%) 0/3 (0%) 1/3 (33%) |0/5 (0%) 0/4 (0%) 0/2 (0%) 0/4 (0%) | |FIRST INCIDENCE | --- --- 566 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.145 (e) P=0.500 P=0.284 |(e) (e) (e) (e) | |POLY 3 | P=0.187 (e) P=0.576 P=0.367 |(e) (e) (e) (e) | |POLY 1.5 | P=0.164 (e) P=0.570 P=0.340 |(e) (e) (e) (e) | |POLY 6 | P=0.225 (e) P=0.586 P=0.400 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.123 (e) P=0.552 P=0.363 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.140 (e) P=0.579 P=0.322 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/8 (75%) 10/12 (83%) 8/11 (73%) 6/11 (55%) |9/9 (100%) 10/10 (100%) 8/8 (100%) 11/11 (100%) | |POLY-3 ADJUSTED (b)| 82.2% 90.0% 78.8% 59.5% |100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 2/2 (100%) 4/4 (100%) 2/3 (67%) 2/3 (67%) |5/5 (100%) 4/4 (100%) 2/2 (100%) 4/4 (100%) | |FIRST INCIDENCE | 454 581 521 680 |539 602 427 482 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.298N P=0.382 P=0.466 P=0.547N |(e) (e) (e) (e) | |POLY 3 | P=0.093N P=0.600 P=0.676N P=0.306N |(e) (e) (e) (e) | |POLY 1.5 | P=0.112N P=0.564 P=0.671N P=0.322N |(e) (e) (e) (e) | |POLY 6 | P=0.073N P=0.710 P=0.662N P=0.278N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.097N P=0.598 P=0.661N P=0.287N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.137N P=0.535 P=0.664N P=0.337N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) 3/49 (6%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 10.8% 10.5% 8.0% 5.4% |2.4% 2.3% 2.4% 9.8% | |TERMINAL (d) | 2/18 (11%) 3/16 (19%) 0/15 (0%) 2/15 (13%) |1/29 (3%) 1/30 (3%) 0/28 (0%) 3/27 (11%) | |FIRST INCIDENCE | 664 535 566 733 (T) |734 (T) 734 (T) 727 653 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.314N P=0.600 P=0.528N P=0.394N |P=0.046 * P=0.755N P=0.745 P=0.160 | |POLY 3 | P=0.294N P=0.633N P=0.497N P=0.335N |P=0.051 P=0.754N P=0.757 P=0.166 | |POLY 1.5 | P=0.296N P=0.631N P=0.497N P=0.337N |P=0.052 P=0.756N P=0.757 P=0.169 | |POLY 6 | P=0.298N P=0.647N P=0.504N P=0.344N |P=0.049 * P=0.752N P=0.757 P=0.164 | |LOGISTIC REGRESSION| P=0.285N P=0.639N P=0.505N P=0.341N |P=0.046 * P=0.755N P=0.760 P=0.162 | |COCH-ARM / FISHERS | P=0.288N P=0.643N P=0.511N P=0.339N |P=0.058 P=0.753N P=0.753N P=0.181 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 9/50 (18%) 10/49 (20%) 9/50 (18%) |5/50 (10%) 8/50 (16%) 8/50 (16%) 12/50 (24%) | |POLY-3 ADJUSTED (b)| 28.4% 23.0% 25.4% 22.7% |11.7% 17.8% 18.4% 28.0% | |TERMINAL (d) | 5/18 (28%) 5/16 (31%) 1/15 (7%) 3/15 (20%) |4/29 (14%) 5/30 (17%) 2/28 (7%) 6/27 (22%) | |FIRST INCIDENCE | 482 535 454 222 |630 602 566 114 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.487N P=0.464N P=0.563N P=0.483N |P=0.053 P=0.308 P=0.260 P=0.048 * | |POLY 3 | P=0.430N P=0.386N P=0.482N P=0.374N |P=0.056 P=0.308 P=0.283 P=0.049 * | |POLY 1.5 | P=0.440N P=0.384N P=0.489N P=0.384N |P=0.060 P=0.295 P=0.275 P=0.050 | |POLY 6 | P=0.432N P=0.408N P=0.487N P=0.385N |P=0.054 P=0.321 P=0.298 P=0.050 | |LOGISTIC REGRESSION| P=0.447N P=0.383N P=0.512N P=0.400N |P=0.071 P=0.285 P=0.273 P=0.057 | |COCH-ARM / FISHERS | P=0.443N P=0.402N P=0.521N P=0.402N |P=0.067 P=0.277 P=0.277 P=0.054 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 10/49 (20%) 5/50 (10%) |2/50 (4%) 2/50 (4%) 3/50 (6%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 5.4% 10.2% 25.7% 12.9% |4.7% 4.5% 7.2% 2.5% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 4/15 (27%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 592 535 537 478 |580 693 710 713 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.556 P=0.341 P=0.014 * P=0.217 |P=0.388N P=0.681N P=0.481 P=0.528N | |POLY 3 | P=0.583 P=0.359 P=0.014 * P=0.230 |P=0.377N P=0.684N P=0.487 P=0.520N | |POLY 1.5 | P=0.569 P=0.354 P=0.014 * P=0.223 |P=0.369N P=0.688N P=0.490 P=0.514N | |POLY 6 | P=0.592 P=0.361 P=0.014 * P=0.233 |P=0.385N P=0.682N P=0.486 P=0.525N | |LOGISTIC REGRESSION| P=0.566 P=0.319 P=0.015 * P=0.217 |P=0.360N P=0.685 P=0.495 P=0.498N | |COCH-ARM / FISHERS | P=0.562 P=0.339 P=0.013 * P=0.218 |P=0.348N P=0.691N P=0.500 P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 8/49 (16%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.7% 0.0% 20.6% 5.3% |0.0% 2.3% 4.8% 4.9% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 1/30 (3%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 664 --- 518 621 |--- 734 (T) 672 653 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.537N P=0.507N P=0.022 * P=0.510 |P=0.313 P=0.507 P=0.239 P=0.220 | |POLY 3 | P=0.522N P=0.497N P=0.017 * P=0.508 |P=0.326 P=0.507 P=0.234 P=0.229 | |POLY 1.5 | P=0.535N P=0.496N P=0.017 * P=0.503 |P=0.330 P=0.504 P=0.234 P=0.230 | |POLY 6 | P=0.510N P=0.503N P=0.018 * P=0.507 |P=0.324 P=0.508 P=0.235 P=0.228 | |LOGISTIC REGRESSION| P=0.537N P=0.497N P=0.016 * P=0.500 |P=0.331 P=0.507 P=0.234 P=0.234 | |COCH-ARM / FISHERS | P=0.538N P=0.500N P=0.014 * P=0.500 |P=0.345 P=0.500 P=0.247 P=0.247 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 2/50 (4%) 1/49 (2%) 2/50 (4%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 20.7% 5.3% 2.7% 5.4% |2.4% 4.5% 2.4% 2.5% | |TERMINAL (d) | 4/18 (22%) 2/16 (13%) 1/15 (7%) 2/15 (13%) |1/29 (3%) 0/30 (0%) 0/28 (0%) 1/27 (4%) | |FIRST INCIDENCE | 482 733 (T) 733 (T) 733 (T) |734 (T) 602 638 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.258N P=0.062N P=0.026N* P=0.068N |P=0.611N P=0.520 P=0.751 P=0.746 | |POLY 3 | P=0.221N P=0.046N* P=0.018N* P=0.047N* |P=0.603N P=0.518 P=0.758 P=0.751 | |POLY 1.5 | P=0.229N P=0.044N* P=0.017N* P=0.047N* |P=0.597N P=0.511 P=0.758 P=0.753 | |POLY 6 | P=0.211N P=0.053N P=0.021N* P=0.052N |P=0.608N P=0.526 P=0.760 P=0.749 | |LOGISTIC REGRESSION| P=0.227N P=0.045N* P=0.018N* P=0.046N* |P=0.574N P=0.479 P=0.762 P=0.746 | |COCH-ARM / FISHERS | P=0.229N P=0.046N* P=0.017N* P=0.046N* |P=0.586N P=0.500 P=0.753N P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/49 (4%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 5.3% 5.4% 5.2% |0.0% 2.3% 0.0% 2.4% | |TERMINAL (d) | 0/18 (0%) 1/16 (6%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 1/30 (3%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- 597 454 222 |--- 734 (T) --- 594 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.440 P=0.233 P=0.227 P=0.222 |P=0.478 P=0.507 (e) P=0.500 | |POLY 3 | P=0.471 P=0.244 P=0.239 P=0.246 |P=0.482 P=0.507 (e) P=0.493 | |POLY 1.5 | P=0.464 P=0.243 P=0.239 P=0.242 |P=0.483 P=0.504 (e) P=0.494 | |POLY 6 | P=0.471 P=0.241 P=0.235 P=0.244 |P=0.481 P=0.508 (e) P=0.493 | |LOGISTIC REGRESSION| P=0.515 P=0.240 P=0.205 P=0.271 |P=0.498 P=0.507 (e) P=0.542 | |COCH-ARM / FISHERS | P=0.456 P=0.247 P=0.242 P=0.247 |P=0.489 P=0.500 (e) P=0.500 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |5/50 (10%) 3/50 (6%) 5/50 (10%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| |11.4% 6.8% 12.0% 14.0% | |TERMINAL (d) | |2/29 (7%) 3/30 (10%) 4/28 (14%) 2/27 (7%) | |FIRST INCIDENCE | |539 734 (T) 699 464 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.281 P=0.339N P=0.609 P=0.457 | |POLY 3 | |P=0.314 P=0.357N P=0.599 P=0.481 | |POLY 1.5 | |P=0.316 P=0.356N P=0.608 P=0.485 | |POLY 6 | |P=0.313 P=0.363N P=0.588 P=0.474 | |LOGISTIC REGRESSION| |P=0.348 P=0.369N P=0.628 P=0.583 | |COCH-ARM / FISHERS | |P=0.328 P=0.357N P=0.630N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| |0.0% 2.3% 0.0% 4.9% | |TERMINAL (d) | |0/29 (0%) 1/30 (3%) 0/28 (0%) 2/27 (7%) | |FIRST INCIDENCE | |--- 734 (T) --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.135 P=0.507 (e) P=0.222 | |POLY 3 | |P=0.144 P=0.507 (e) P=0.227 | |POLY 1.5 | |P=0.147 P=0.504 (e) P=0.229 | |POLY 6 | |P=0.142 P=0.508 (e) P=0.224 | |LOGISTIC REGRESSION| |(e) P=0.507 (e) P=0.222 | |COCH-ARM / FISHERS | |P=0.153 P=0.500 (e) P=0.247 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 18/50 (36%) 23/50 (46%) 23/50 (46%) 15/50 (30%) |18/50 (36%) 13/50 (26%) 11/50 (22%) 20/50 (40%) | |POLY-3 ADJUSTED (b)| 44.9% 54.5% 55.8% 37.0% |40.7% 29.0% 25.9% 44.8% | |TERMINAL (d) | 8/18 (44%) 8/16 (50%) 9/15 (60%) 3/15 (20%) |11/29 (38%) 10/30 (33%) 9/28 (32%) 8/27 (30%) | |FIRST INCIDENCE | 482 559 547 548 |482 601 427 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.148N P=0.185 P=0.145 P=0.433N |P=0.068 P=0.175N P=0.121N P=0.345 | |POLY 3 | P=0.072N P=0.248 P=0.213 P=0.305N |P=0.098 P=0.169N P=0.104N P=0.432 | |POLY 1.5 | P=0.084N P=0.235 P=0.220 P=0.323N |P=0.091 P=0.178N P=0.101N P=0.411 | |POLY 6 | P=0.067N P=0.263 P=0.197 P=0.299N |P=0.119 P=0.165N P=0.112N P=0.472 | |LOGISTIC REGRESSION| P=0.085N P=0.228 P=0.216 P=0.325N |P=0.077 P=0.166N P=0.100N P=0.390 | |COCH-ARM / FISHERS | P=0.089N P=0.208 P=0.208 P=0.335N |P=0.098 P=0.194N P=0.093N P=0.418 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 1/50 (2%) 3/50 (6%) |1/50 (2%) 0/50 (0%) 3/50 (6%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.7% 10.6% 2.7% 8.0% |2.3% 0.0% 7.2% 7.4% | |TERMINAL (d) | 1/18 (6%) 3/16 (19%) 1/15 (7%) 2/15 (13%) |0/29 (0%) 0/30 (0%) 3/28 (11%) 3/27 (11%) | |FIRST INCIDENCE | 733 (T) 682 733 (T) 685 |671 --- 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.382 P=0.149 P=0.722 P=0.253 |P=0.181 P=0.489N P=0.299 P=0.282 | |POLY 3 | P=0.432 P=0.184 P=0.760N P=0.311 |P=0.185 P=0.495N P=0.296 P=0.286 | |POLY 1.5 | P=0.425 P=0.185 P=0.758N P=0.307 |P=0.192 P=0.496N P=0.298 P=0.292 | |POLY 6 | P=0.436 P=0.178 P=0.757 P=0.308 |P=0.179 P=0.494N P=0.293 P=0.281 | |LOGISTIC REGRESSION| P=0.417 P=0.153 P=0.722 P=0.283 |P=0.182 P=0.507N P=0.297 P=0.284 | |COCH-ARM / FISHERS | P=0.425 P=0.181 P=0.753N P=0.309 |P=0.210 P=0.500N P=0.309 P=0.309 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 6/50 (12%) 9/50 (18%) 7/50 (14%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 10.9% 16.0% 23.3% 18.1% |0.0% 4.5% 0.0% 0.0% | |TERMINAL (d) | 3/18 (17%) 5/16 (31%) 4/15 (27%) 4/15 (27%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 704 682 521 517 |--- 714 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.397 P=0.294 P=0.082 P=0.207 |P=0.490N P=0.240 (e) (e) | |POLY 3 | P=0.475 P=0.381 P=0.128 P=0.285 |P=0.465N P=0.245 (e) (e) | |POLY 1.5 | P=0.453 P=0.382 P=0.126 P=0.273 |P=0.465N P=0.242 (e) (e) | |POLY 6 | P=0.495 P=0.368 P=0.125 P=0.291 |P=0.465N P=0.247 (e) (e) | |LOGISTIC REGRESSION| P=0.449 P=0.308 P=0.112 P=0.265 |P=0.480N P=0.246 (e) (e) | |COCH-ARM / FISHERS | P=0.443 P=0.370 P=0.117 P=0.262 |P=0.464N P=0.247 (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Metaplasia Hepatocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |0.0% 4.6% 0.0% 2.5% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 2/30 (7%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 734 (T) --- 713 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.611 P=0.245 (e) P=0.488 | |POLY 3 | (e) (e) (e) (e) |P=0.620 P=0.244 (e) P=0.491 | |POLY 1.5 | (e) (e) (e) (e) |P=0.622 P=0.242 (e) P=0.493 | |POLY 6 | (e) (e) (e) (e) |P=0.619 P=0.246 (e) P=0.490 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.610 P=0.245 (e) P=0.490 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.629 P=0.247 (e) P=0.500 | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/48 (10%) 6/46 (13%) 8/45 (18%) 13/47 (28%) |0/48 (0%) 0/43 (0%) 1/43 (2%) 0/45 (0%) | |POLY-3 ADJUSTED (b)| 13.7% 17.1% 23.7% 35.1% |0.0% 0.0% 2.7% 0.0% | |TERMINAL (d) | 2/17 (12%) 2/14 (14%) 4/13 (31%) 4/14 (29%) |0/29 (0%) 0/25 (0%) 1/25 (4%) 0/24 (0%) | |FIRST INCIDENCE | 539 597 566 548 |--- --- 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.023 * P=0.431 P=0.196 P=0.032 * |P=0.758N (e) P=0.470 (e) | |POLY 3 | P=0.019 * P=0.469 P=0.218 P=0.026 * |P=0.748N (e) P=0.476 (e) | |POLY 1.5 | P=0.017 * P=0.472 P=0.228 P=0.025 * |P=0.746N (e) P=0.476 (e) | |POLY 6 | P=0.021 * P=0.459 P=0.197 P=0.027 * |P=0.751N (e) P=0.477 (e) | |LOGISTIC REGRESSION| P=0.019 * P=0.464 P=0.212 P=0.027 * |(e) (e) P=0.470 (e) | |COCH-ARM / FISHERS | P=0.020 * P=0.470 P=0.235 P=0.029 * |P=0.740N (e) P=0.473 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 6/50 (12%) 9/50 (18%) 11/49 (22%) |12/50 (24%) 16/50 (32%) 7/50 (14%) 12/50 (24%) | |POLY-3 ADJUSTED (b)| 13.0% 15.9% 22.9% 27.8% |26.2% 36.0% 16.2% 28.0% | |TERMINAL (d) | 1/18 (6%) 4/16 (25%) 4/15 (27%) 1/15 (7%) |5/29 (17%) 12/30 (40%) 3/28 (11%) 7/27 (26%) | |FIRST INCIDENCE | 454 682 521 478 |398 622 539 415 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.094 P=0.443 P=0.171 P=0.095 |P=0.494 P=0.298 P=0.196N P=0.523 | |POLY 3 | P=0.094 P=0.487 P=0.197 P=0.087 |P=0.534 P=0.217 P=0.185N P=0.518 | |POLY 1.5 | P=0.082 P=0.498 P=0.201 P=0.080 |P=0.549 P=0.231 P=0.177N P=0.539 | |POLY 6 | P=0.111 P=0.461 P=0.187 P=0.094 |P=0.520 P=0.198 P=0.192N P=0.496 | |LOGISTIC REGRESSION| P=0.078 P=0.511 P=0.187 P=0.079 |P=0.553N P=0.246 P=0.127N P=0.548N | |COCH-ARM / FISHERS | P=0.079 P=0.500 P=0.194 P=0.079 |P=0.557N P=0.252 P=0.154N P=0.592N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 3/50 (6%) | | |POLY-3 ADJUSTED (b)| 5.4% 2.7% 2.7% 7.9% | | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 0/15 (0%) 0/15 (0%) | | |FIRST INCIDENCE | 547 702 521 611 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.272 P=0.513N P=0.510N P=0.504 | | |POLY 3 | P=0.262 P=0.497N P=0.497N P=0.508 | | |POLY 1.5 | P=0.257 P=0.495N P=0.495N P=0.503 | | |POLY 6 | P=0.269 P=0.506N P=0.508N P=0.509 | | |LOGISTIC REGRESSION| P=0.260 P=0.496N P=0.528N P=0.500 | | |COCH-ARM / FISHERS | P=0.258 P=0.500N P=0.500N P=0.500 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 13/50 (26%) 15/50 (30%) 17/50 (34%) | | |POLY-3 ADJUSTED (b)| 29.4% 34.3% 38.7% 42.3% | | |TERMINAL (d) | 7/18 (39%) 9/16 (56%) 8/15 (53%) 8/15 (53%) | | |FIRST INCIDENCE | 659 682 454 560 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.116 P=0.281 P=0.140 P=0.088 | | |POLY 3 | P=0.203 P=0.413 P=0.263 P=0.165 | | |POLY 1.5 | P=0.171 P=0.422 P=0.267 P=0.145 | | |POLY 6 | P=0.252 P=0.375 P=0.235 P=0.184 | | |LOGISTIC REGRESSION| P=0.158 P=0.337 P=0.213 P=0.132 | | |COCH-ARM / FISHERS | P=0.161 P=0.408 P=0.247 P=0.133 | | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 2/50 (4%) 1/50 (2%) 6/50 (12%) | | |POLY-3 ADJUSTED (b)| 13.3% 5.3% 2.7% 15.6% | | |TERMINAL (d) | 3/18 (17%) 1/16 (6%) 1/15 (7%) 3/15 (20%) | | |FIRST INCIDENCE | 235 702 733 (T) 566 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.105 P=0.265N P=0.144N P=0.437 | | |POLY 3 | P=0.126 P=0.214N P=0.103N P=0.516 | | |POLY 1.5 | P=0.119 P=0.214N P=0.101N P=0.503 | | |POLY 6 | P=0.137 P=0.221N P=0.110N P=0.526 | | |LOGISTIC REGRESSION| P=0.120 P=0.213N P=0.103N P=0.500 | | |COCH-ARM / FISHERS | P=0.121 P=0.218N P=0.102N P=0.500 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Skin | | Cyst Epithelial Inclusion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 5.4% 0.0% 0.0% 5.3% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |1/29 (3%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 723 --- --- 588 |734 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.295 P=0.282N P=0.289N P=0.647 |P=0.671N P=0.493N P=0.507N P=0.514N | |POLY 3 | P=0.308 P=0.232N P=0.235N P=0.686N |P=0.662N P=0.493N P=0.504N P=0.509N | |POLY 1.5 | P=0.303 P=0.232N P=0.234N P=0.690N |P=0.659N P=0.496N P=0.504N P=0.507N | |POLY 6 | P=0.315 P=0.236N P=0.241N P=0.686N |P=0.663N P=0.492N P=0.504N P=0.511N | |LOGISTIC REGRESSION| P=0.307 P=0.260N P=0.268N P=0.693N |P=0.671N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.305 P=0.247N P=0.247N P=0.691N |P=0.657N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Skin | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 2.6% 5.3% 0.0% |2.4% 4.6% 0.0% 4.8% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |1/29 (3%) 1/30 (3%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- 588 518 --- |734 (T) 727 --- 415 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.404N P=0.516 P=0.247 (e) |P=0.393 P=0.508 P=0.507N P=0.489 | |POLY 3 | P=0.406N P=0.507 P=0.243 (e) |P=0.410 P=0.512 P=0.504N P=0.494 | |POLY 1.5 | P=0.408N P=0.505 P=0.243 (e) |P=0.410 P=0.507 P=0.504N P=0.494 | |POLY 6 | P=0.407N P=0.505 P=0.240 (e) |P=0.410 P=0.515 P=0.504N P=0.495 | |LOGISTIC REGRESSION| P=0.379N P=0.477 P=0.212 (e) |P=0.444 P=0.507 (e) P=0.576 | |COCH-ARM / FISHERS | P=0.408N P=0.500 P=0.247 (e) |P=0.414 P=0.500 P=0.500N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 14/50 (28%) 24/50 (48%) 22/50 (44%) |4/50 (8%) 6/50 (12%) 10/50 (20%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 28.5% 35.0% 59.0% 54.3% |9.1% 13.3% 23.0% 9.7% | |TERMINAL (d) | 3/18 (17%) 5/16 (31%) 10/15 (67%) 10/15 (67%) |0/29 (0%) 3/30 (10%) 4/28 (14%) 1/27 (4%) | |FIRST INCIDENCE | 564 549 541 566 |539 370 508 594 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.071 P=0.283 P=0.005 ** P=0.017 * |P=0.335N P=0.395 P=0.082 P=0.604 | |POLY 3 | P=0.053 P=0.350 P=0.003 ** P=0.013 * |P=0.325N P=0.384 P=0.067 P=0.611 | |POLY 1.5 | P=0.050 P=0.347 P=0.004 ** P=0.013 * |P=0.310N P=0.381 P=0.068 P=0.619 | |POLY 6 | P=0.053 P=0.341 P=0.002 ** P=0.012 * |P=0.337N P=0.382 P=0.067 P=0.603 | |LOGISTIC REGRESSION| P=0.060 P=0.339 P=0.005 ** P=0.016 * |P=0.246N P=0.318 P=0.081 P=0.612N | |COCH-ARM / FISHERS | P=0.063 P=0.322 P=0.006 ** P=0.016 * |P=0.274N P=0.370 P=0.074 P=0.643N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 1/50 (2%) 5/50 (10%) |4/50 (8%) 5/50 (10%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 7.9% 7.7% 2.7% 12.7% |8.9% 11.1% 0.0% 2.5% | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 2/30 (7%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 454 398 684 478 |398 482 --- 714 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.180 P=0.652 P=0.326N P=0.368 |P=0.196N P=0.513 P=0.070N P=0.207N | |POLY 3 | P=0.178 P=0.652N P=0.311N P=0.376 |P=0.185N P=0.503 P=0.070N P=0.210N | |POLY 1.5 | P=0.169 P=0.652N P=0.305N P=0.366 |P=0.179N P=0.501 P=0.067N P=0.200N | |POLY 6 | P=0.188 P=0.662N P=0.326N P=0.379 |P=0.189N P=0.506 P=0.072N P=0.218N | |LOGISTIC REGRESSION| P=0.197 P=0.609 P=0.318N P=0.364 |P=0.113N P=0.368 P=0.019N* P=0.086N | |COCH-ARM / FISHERS | P=0.167 P=0.661N P=0.309N P=0.357 |P=0.170N P=0.500 P=0.059N P=0.181N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 4/50 (8%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.7% 0.0% 0.0% 0.0% |2.3% 4.5% 9.3% 0.0% | |TERMINAL (d) | 1/18 (6%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 733 (T) --- --- --- |657 370 547 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.674N P=0.523N P=0.536N P=0.536N |P=0.182N P=0.515 P=0.174 P=0.516N | |POLY 3 | P=0.658N P=0.496N P=0.499N P=0.497N |P=0.182N P=0.517 P=0.179 P=0.511N | |POLY 1.5 | P=0.660N P=0.496N P=0.497N P=0.499N |P=0.176N P=0.511 P=0.177 P=0.508N | |POLY 6 | P=0.652N P=0.500N P=0.505N P=0.499N |P=0.189N P=0.521 P=0.182 P=0.514N | |LOGISTIC REGRESSION| P=0.674N (e) (e) (e) |P=0.121N P=0.439 P=0.194 P=0.492N | |COCH-ARM / FISHERS | P=0.657N P=0.500N P=0.500N P=0.500N |P=0.162N P=0.500 P=0.181 P=0.500N | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 8.0% 0.0% 5.3% 2.7% |2.3% 0.0% 0.0% 2.4% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 564 --- 537 668 |648 --- --- 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478N P=0.134N P=0.508N P=0.321N |P=0.499 P=0.495N P=0.516N P=0.750 | |POLY 3 | P=0.482N P=0.118N P=0.498N P=0.305N |P=0.499 P=0.495N P=0.505N P=0.753 | |POLY 1.5 | P=0.487N P=0.116N P=0.493N P=0.306N |P=0.502 P=0.497N P=0.504N P=0.754 | |POLY 6 | P=0.476N P=0.124N P=0.512N P=0.312N |P=0.497 P=0.494N P=0.507N P=0.751 | |LOGISTIC REGRESSION| P=0.477N P=0.121N P=0.510N P=0.305N |P=0.574 P=0.514N P=0.490N P=0.710N | |COCH-ARM / FISHERS | P=0.481N P=0.121N P=0.500N P=0.309N |P=0.511 P=0.500N P=0.500N P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.3% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | --- --- 566 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.552N (e) P=0.233 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.556N (e) P=0.242 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.558N (e) P=0.242 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.556N (e) P=0.238 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.553N (e) P=0.232 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.557N (e) P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 8/50 (16%) 10/50 (20%) 12/50 (24%) |5/50 (10%) 2/50 (4%) 7/50 (14%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 34.0% 19.9% 25.1% 29.2% |11.3% 4.5% 16.0% 7.2% | |TERMINAL (d) | 2/18 (11%) 0/16 (0%) 0/15 (0%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 440 510 518 478 |398 686 547 497 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.466 P=0.155N P=0.294N P=0.427N |P=0.410N P=0.210N P=0.365 P=0.398N | |POLY 3 | P=0.460 P=0.114N P=0.258N P=0.409N |P=0.402N P=0.218N P=0.367 P=0.394N | |POLY 1.5 | P=0.439 P=0.108N P=0.242N P=0.413N |P=0.390N P=0.217N P=0.366 P=0.383N | |POLY 6 | P=0.477 P=0.135N P=0.295N P=0.427N |P=0.414N P=0.219N P=0.373 P=0.404N | |LOGISTIC REGRESSION| P=0.453 P=0.123N P=0.248N P=0.409N |P=0.289N P=0.255N P=0.433 P=0.274N | |COCH-ARM / FISHERS | P=0.442 P=0.114N P=0.241N P=0.410N |P=0.358N P=0.218N P=0.380 P=0.357N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 1/50 (2%) 4/50 (8%) 4/50 (8%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 13.3% 2.7% 10.6% 10.6% |0.0% 0.0% 2.4% 0.0% | |TERMINAL (d) | 3/18 (17%) 1/16 (6%) 1/15 (7%) 1/15 (7%) |0/29 (0%) 0/30 (0%) 1/28 (4%) 0/27 (0%) | |FIRST INCIDENCE | 539 733 (T) 566 667 |--- --- 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.478 P=0.122N P=0.555N P=0.550N |P=0.754N (e) P=0.493 (e) | |POLY 3 | P=0.496 P=0.099N P=0.496N P=0.499N |P=0.749N (e) P=0.496 (e) | |POLY 1.5 | P=0.488 P=0.098N P=0.491N P=0.501N |P=0.746N (e) P=0.496 (e) | |POLY 6 | P=0.504 P=0.105N P=0.513N P=0.508N |P=0.751N (e) P=0.496 (e) | |LOGISTIC REGRESSION| P=0.498 P=0.099N P=0.496N P=0.494N |(e) (e) P=0.493 (e) | |COCH-ARM / FISHERS | P=0.494 P=0.102N P=0.500N P=0.500N |P=0.739N (e) P=0.500 (e) | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 3/50 (6%) 7/50 (14%) 9/50 (18%) |3/50 (6%) 3/49 (6%) 4/50 (8%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 15.6% 7.8% 17.8% 22.0% |6.9% 6.7% 9.4% 14.1% | |TERMINAL (d) | 0/18 (0%) 0/16 (0%) 0/15 (0%) 0/15 (0%) |0/29 (0%) 0/30 (0%) 0/28 (0%) 0/27 (0%) | |FIRST INCIDENCE | 539 538 518 361 |552 587 566 464 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.151 P=0.273N P=0.481 P=0.306 |P=0.151 P=0.633N P=0.496 P=0.224 | |POLY 3 | P=0.142 P=0.236N P=0.519 P=0.328 |P=0.158 P=0.652N P=0.487 P=0.230 | |POLY 1.5 | P=0.129 P=0.234N P=0.519 P=0.310 |P=0.162 P=0.660N P=0.489 P=0.232 | |POLY 6 | P=0.156 P=0.249N P=0.506 P=0.335 |P=0.154 P=0.645N P=0.485 P=0.229 | |LOGISTIC REGRESSION| P=0.135 P=0.250N P=0.489 P=0.290 |P=0.222 P=0.603 P=0.517 P=0.292 | |COCH-ARM / FISHERS | P=0.121 P=0.243N P=0.500 P=0.288 |P=0.174 P=0.651 P=0.500 P=0.243 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Testes: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 16.1% 5.3% 2.7% 0.0% | | |TERMINAL (d) | 3/18 (17%) 0/16 (0%) 0/15 (0%) 0/15 (0%) | | |FIRST INCIDENCE | 664 664 712 --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.063N P=0.170N P=0.088N P=0.026N* | | |POLY 3 | P=0.052N P=0.123N P=0.054N P=0.014N* | | |POLY 1.5 | P=0.055N P=0.124N P=0.053N P=0.015N* | | |POLY 6 | P=0.050N P=0.127N P=0.059N P=0.015N* | | |LOGISTIC REGRESSION| P=0.054N P=0.130N P=0.062N P=0.017N* | | |COCH-ARM / FISHERS | P=0.056N P=0.134N P=0.056N P=0.013N* | | |=================================================================================================================================| Date: 10/02/97 EXPERIMENT: 05135 TEST: 07 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOPRENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 15/50 (30%) 13/50 (26%) 8/50 (16%) 0/50 (0%) | | |POLY-3 ADJUSTED (b)| 36.1% 30.0% 19.8% 0.0% | | |TERMINAL (d) | 4/18 (22%) 2/16 (13%) 0/15 (0%) 0/15 (0%) | | |FIRST INCIDENCE | 454 398 454 --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001N** P=0.448N P=0.119N P<0.001N** | | |POLY 3 | P<0.001N** P=0.354N P=0.075N P<0.001N** | | |POLY 1.5 | P<0.001N** P=0.364N P=0.071N P<0.001N** | | |POLY 6 | P<0.001N** P=0.369N P=0.090N P<0.001N** | | |LOGISTIC REGRESSION| P<0.001N** P=0.476N P=0.089N P<0.001N** | | |COCH-ARM / FISHERS | P<0.001N** P=0.412N P=0.077N P<0.001N** | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 220 PPM 700 PPM 7000 PPM |CONTROL 220 PPM 700 PPM 7000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 30/49 (61%) 30/50 (60%) 30/49 (61%) 34/50 (68%) |40/48 (83%) 32/50 (64%) 38/49 (78%) 40/50 (80%) | |POLY-3 ADJUSTED (b)| 70.4% 67.5% 69.9% 76.2% |85.6% 67.6% 82.7% 89.7% | |TERMINAL (d) | 11/18 (61%) 9/16 (56%) 10/15 (67%) 10/15 (67%) |25/29 (86%) 19/30 (63%) 23/28 (82%) 25/27 (93%) | |FIRST INCIDENCE | 440 499 510 361 |398 482 427 490 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.243 P=0.464 P=0.414 P=0.228 |P=0.138 P=0.092N P=0.519N P=0.385 | |POLY 3 | P=0.227 P=0.471N P=0.577N P=0.349 |P=0.063 P=0.028N* P=0.457N P=0.381 | |POLY 1.5 | P=0.206 P=0.483N P=0.560N P=0.320 |P=0.109 P=0.027N* P=0.426N P=0.507 | |POLY 6 | P=0.238 P=0.470N P=0.595 P=0.358 |P=0.041 * P=0.030N* P=0.490N P=0.292 | |LOGISTIC REGRESSION| P=0.209 P=0.491N P=0.550N P=0.315 |P=0.179 P=0.024N* P=0.362N P=0.594N | |COCH-ARM / FISHERS | P=0.227 P=0.532N P=0.582N P=0.310 |P=0.293 P=0.026N* P=0.323N P=0.435N | |=================================================================================================================================| (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).