TDMS Study 88070-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOBUTENE DATE: 06/20/97 EXPERIMENT: 88070 TEST: 03 TIME: 09:50:34 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-15313 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: C88070 PATHOLOGIST: GRUMBEIN, S. CAS: 115-11-0007 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 ISOBUTENE DATE: 06/20/97 EXPERIMENT: 88070 TEST: 03 TIME: 09:50:34 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-15313 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: C88070 PATHOLOGIST: GRUMBEIN, S. CAS: 115-11-0007 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ISOBUTENE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Medulla Hyperplasia Heart: Atrium Thrombosis Islets, Pancreatic Hyperplasia Liver Cyst Regeneration Lung Inflammation Granulomatous Mammary Gland Galactocele Nose: Olfactory Epithelium Degeneration Hyaline Metaplasia Skin Inflammation Chronic Stomach, Forestomach Necrosis Testes Atrophy Thyroid Gland: C-Cell Hyperplasia =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Hyperplasia Bone Hyperostosis Intestine Large, Colon Parasite Metazoan Kidney Nephropathy Larynx: Epiglottis Metaplasia Liver: Centrilobular Necrosis Mesentery: Artery Inflammation Chronic Nose: Lateral Wall Metaplasia Nose: Olfactory Epithelium Degeneration Hyaline Ovary Cyst Pancreas Atrophy Spleen Fibrosis Testes: Artery Inflammation Chronic =============================================================== Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/50 (0%) 1/50 (2%) |2/50 (4%) 2/50 (4%) 4/49 (8%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.8% |5.0% 5.5% 9.3% 5.1% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 1/8 (13%) |1/23 (4%) 2/19 (11%) 4/33 (12%) 1/22 (5%) | |FIRST INCIDENCE | --- --- --- 733 (T) |715 733 (T) 733 (T) 720 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.280 (e) (e) P=0.527 |P=0.589N P=0.624 P=0.498 P=0.667 | |POLY 3 | P=0.245 (e) (e) P=0.513 |P=0.567N P=0.664 P=0.373 P=0.687 | |POLY 1.5 | P=0.239 (e) (e) P=0.508 |P=0.572N P=0.673 P=0.355 P=0.685 | |POLY 6 | P=0.252 (e) (e) P=0.518 |P=0.569N P=0.651 P=0.394 P=0.683 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.527 |P=0.599N P=0.632 P=0.438 P=0.671 | |COCH-ARM / FISHERS | P=0.229 (e) (e) P=0.500 |P=0.580N P=0.691N P=0.329 P=0.684 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 21/50 (42%) 23/49 (47%) 24/50 (48%) 23/50 (46%) |15/50 (30%) 16/50 (32%) 24/49 (49%) 21/49 (43%) | |POLY-3 ADJUSTED (b)| 55.0% 59.3% 62.6% 55.3% |35.9% 41.2% 52.3% 51.0% | |TERMINAL (d) | 3/7 (43%) 3/5 (60%) 4/6 (67%) 4/8 (50%) |11/23 (48%) 9/19 (47%) 16/33 (49%) 15/22 (68%) | |FIRST INCIDENCE | 539 482 500 505 |440 455 399 500 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.290N P=0.176 P=0.161 P=0.560N |P=0.139 P=0.293 P=0.319 P=0.107 | |POLY 3 | P=0.448N P=0.431 P=0.311 P=0.582 |P=0.148 P=0.397 P=0.088 P=0.115 | |POLY 1.5 | P=0.517N P=0.405 P=0.325 P=0.514 |P=0.144 P=0.425 P=0.065 P=0.117 | |POLY 6 | P=0.371N P=0.462 P=0.293 P=0.555N |P=0.142 P=0.367 P=0.125 P=0.107 | |LOGISTIC REGRESSION| P=0.439N P=0.303 P=0.207 P=0.549 |P=0.152 P=0.398 P=0.059 P=0.123 | |COCH-ARM / FISHERS | P=0.488 P=0.385 P=0.344 P=0.420 |P=0.142 P=0.500 P=0.042 * P=0.131 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 6/49 (12%) 7/50 (14%) 4/50 (8%) |11/50 (22%) 8/50 (16%) 9/49 (18%) 9/49 (18%) | |POLY-3 ADJUSTED (b)| 19.8% 18.8% 20.5% 10.9% |26.4% 21.4% 20.5% 22.9% | |TERMINAL (d) | 2/7 (29%) 2/5 (40%) 1/6 (17%) 1/8 (13%) |4/23 (17%) 5/19 (26%) 7/33 (21%) 7/22 (32%) | |FIRST INCIDENCE | 552 624 352 576 |390 565 607 668 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.133N P=0.569 P=0.498 P=0.221N |P=0.520N P=0.480N P=0.191N P=0.454N | |POLY 3 | P=0.163N P=0.584N P=0.593 P=0.231N |P=0.519N P=0.399N P=0.350N P=0.455N | |POLY 1.5 | P=0.185N P=0.552N P=0.604 P=0.242N |P=0.517N P=0.369N P=0.379N P=0.445N | |POLY 6 | P=0.140N P=0.619 P=0.574 P=0.226N |P=0.535N P=0.442N P=0.319N P=0.482N | |LOGISTIC REGRESSION| P=0.196N P=0.591N P=0.597N P=0.233N |P=0.499N P=0.367N P=0.379N P=0.424N | |COCH-ARM / FISHERS | P=0.221N P=0.516N P=0.613N P=0.262N |P=0.517N P=0.306N P=0.421N P=0.421N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/49 (2%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 3/49 (6%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 3.2% 3.2% 0.0% |4.9% 0.0% 6.8% 2.5% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 702 585 --- |529 --- 552 469 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.502N P=0.403 P=0.475 (e) |P=0.573N P=0.278N P=0.568 P=0.506N | |POLY 3 | P=0.502N P=0.484 P=0.487 (e) |P=0.545N P=0.260N P=0.537 P=0.507N | |POLY 1.5 | P=0.509N P=0.489 P=0.493 (e) |P=0.554N P=0.252N P=0.519 P=0.508N | |POLY 6 | P=0.496N P=0.474 P=0.479 (e) |P=0.540N P=0.270N P=0.559 P=0.511N | |LOGISTIC REGRESSION| P=0.506N P=0.446 P=0.516 (e) |P=0.569N P=0.221N P=0.415 P=0.464N | |COCH-ARM / FISHERS | P=0.520N P=0.495 P=0.500 (e) |P=0.572N P=0.247N P=0.490 P=0.508N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/49 (2%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 3.2% 9.4% 0.0% |0.0% 0.0% 0.0% 2.5% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 684 516 --- |--- --- --- 642 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.386N P=0.459 P=0.110 (e) |P=0.231 (e) (e) P=0.495 | |POLY 3 | P=0.396N P=0.484 P=0.108 (e) |P=0.232 (e) (e) P=0.497 | |POLY 1.5 | P=0.411N P=0.489 P=0.113 (e) |P=0.230 (e) (e) P=0.496 | |POLY 6 | P=0.381N P=0.475 P=0.102 (e) |P=0.234 (e) (e) P=0.497 | |LOGISTIC REGRESSION| P=0.432N P=0.463 P=0.124 (e) |P=0.226 (e) (e) P=0.499 | |COCH-ARM / FISHERS | P=0.435N P=0.495 P=0.121 (e) |P=0.225 (e) (e) P=0.495 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 15/50 (30%) 19/49 (39%) 30/50 (60%) 18/50 (36%) |10/50 (20%) 5/50 (10%) 6/49 (12%) 10/49 (20%) | |POLY-3 ADJUSTED (b)| 39.7% 49.6% 70.7% 44.2% |24.1% 13.5% 13.8% 24.9% | |TERMINAL (d) | 1/7 (14%) 1/5 (20%) 3/6 (50%) 4/8 (50%) |5/23 (22%) 2/19 (11%) 5/33 (15%) 6/22 (27%) | |FIRST INCIDENCE | 516 523 453 534 |552 662 626 580 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.270N P=0.131 P=0.003 ** P=0.442 |P=0.253 P=0.233N P=0.084N P=0.555 | |POLY 3 | P=0.370N P=0.250 P=0.002 ** P=0.427 |P=0.271 P=0.180N P=0.173N P=0.569 | |POLY 1.5 | P=0.417N P=0.241 P=0.002 ** P=0.391 |P=0.265 P=0.162N P=0.189N P=0.570 | |POLY 6 | P=0.348N P=0.267 P=0.004 ** P=0.457 |P=0.270 P=0.207N P=0.158N P=0.554 | |LOGISTIC REGRESSION| P=0.497N P=0.226 P=0.002 ** P=0.377 |P=0.261 P=0.168N P=0.178N P=0.576 | |COCH-ARM / FISHERS | P=0.507N P=0.240 P=0.002 ** P=0.335 |P=0.252 P=0.131N P=0.220N P=0.579 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/2 (100%) 2/2 (100%) 2/2 (100%) 2/2 (100%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 ADJUSTED (b)| 100.0% 100.0% 100.0% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 1/1 (100%) 0/0 (0%) 1/1 (100%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 639 684 480 700 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Bone | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 7/50 (14%) 9/50 (18%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 25.3% 21.5% 27.1% 16.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 1/6 (17%) 2/8 (25%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 539 624 558 664 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.180N P=0.580 P=0.405 P=0.277N |(e) (e) (e) (e) | |POLY 3 | P=0.216N P=0.465N P=0.544 P=0.257N |(e) (e) (e) (e) | |POLY 1.5 | P=0.244N P=0.433N P=0.572 P=0.266N |(e) (e) (e) (e) | |POLY 6 | P=0.195N P=0.521N P=0.502 P=0.260N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.178N P=0.491N P=0.508 P=0.224N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.293N P=0.393N P=0.602N P=0.288N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Bone | | Hyperostosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |9/50 (18%) 7/50 (14%) 11/50 (22%) 15/50 (30%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 3.2% 2.8% |22.1% 18.7% 24.2% 36.1% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |6/23 (26%) 4/19 (21%) 7/33 (21%) 7/22 (32%) | |FIRST INCIDENCE | --- --- 568 688 |608 580 534 547 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.423 (e) P=0.484 P=0.547 |P=0.036 * P=0.545N P=0.522N P=0.111 | |POLY 3 | P=0.382 (e) P=0.487 P=0.514 |P=0.046 * P=0.463N P=0.512 P=0.121 | |POLY 1.5 | P=0.369 (e) P=0.493 P=0.509 |P=0.042 * P=0.442N P=0.468 P=0.117 | |POLY 6 | P=0.398 (e) P=0.479 P=0.520 |P=0.049 * P=0.493N P=0.560 P=0.125 | |LOGISTIC REGRESSION| P=0.349 (e) P=0.522 P=0.517 |P=0.038 * P=0.481N P=0.468 P=0.109 | |COCH-ARM / FISHERS | P=0.348 (e) P=0.500 P=0.500 |P=0.040 * P=0.393N P=0.402 P=0.121 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/48 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/49 (0%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.5% 2.7% 0.0% 5.1% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 1/19 (5%) 0/33 (0%) 1/22 (5%) | |FIRST INCIDENCE | --- --- --- --- |720 733 (T) --- 692 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.302 P=0.705 P=0.454N P=0.474 | |POLY 3 | (e) (e) (e) (e) |P=0.314 P=0.742 P=0.485N P=0.493 | |POLY 1.5 | (e) (e) (e) (e) |P=0.313 P=0.748 P=0.492N P=0.492 | |POLY 6 | (e) (e) (e) (e) |P=0.311 P=0.734 P=0.476N P=0.490 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.308 P=0.726 P=0.472N P=0.485 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.312 P=0.753N P=0.505N P=0.492 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |1/50 (2%) 0/49 (0%) 5/47 (11%) 1/48 (2%) | |POLY-3 ADJUSTED (b)| |2.5% 0.0% 11.9% 2.7% | |TERMINAL (d) | |1/23 (4%) 0/18 (0%) 4/31 (13%) 1/22 (5%) | |FIRST INCIDENCE | |733 (T) --- 644 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.626N P=0.549N P=0.176 P=0.753 | |POLY 3 | |P=0.620N P=0.522N P=0.112 P=0.747 | |POLY 1.5 | |P=0.626N P=0.517N P=0.102 P=0.748 | |POLY 6 | |P=0.621N P=0.530N P=0.125 P=0.743 | |LOGISTIC REGRESSION| |P=0.641 (e) P=0.123 P=0.753 | |COCH-ARM / FISHERS | |P=0.636N P=0.505N P=0.088 P=0.742 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Esophagus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 3.0% 3.2% 6.3% 0.0% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 666 670 555 --- |--- --- 651 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.281N P=0.707 P=0.451 P=0.491N |P=0.771N (e) P=0.532 (e) | |POLY 3 | P=0.285N P=0.744 P=0.481 P=0.488N |P=0.768N (e) P=0.521 (e) | |POLY 1.5 | P=0.298N P=0.751 P=0.490 P=0.492N |P=0.769N (e) P=0.513 (e) | |POLY 6 | P=0.273N P=0.732 P=0.469 P=0.486N |P=0.769N (e) P=0.531 (e) | |LOGISTIC REGRESSION| P=0.324N P=0.736 P=0.517 P=0.487N |P=0.772N (e) P=0.476 (e) | |COCH-ARM / FISHERS | P=0.317N P=0.753N P=0.500 P=0.500N |P=0.772N (e) P=0.500 (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Eye | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/3 (67%) 0/0 (0%) 3/4 (75%) 0/0 (0%) |4/4 (100%) 3/4 (75%) 6/6 (100%) 4/4 (100%) | |POLY-3 ADJUSTED (b)| 75.1% 0.0% 83.6% 0.0% |100.0% 84.3% 100.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) |0/0 (0%) 1/1 (100%) 5/5 (100%) 2/2 (100%) | |FIRST INCIDENCE | 691 --- 650 --- |440 440 680 630 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.265N (e) P=0.597 (e) |P=0.435N P=0.385N (e) (e) | |POLY 3 | P=1.000N (e) P=0.776 (e) |P=0.876 P=0.757N (e) (e) | |POLY 1.5 | P=1.000N (e) P=0.732 (e) |P=0.753 P=0.617N (e) (e) | |POLY 6 | P=1.000N (e) P=0.882 (e) |P=0.995 P=0.974N (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.745 P=0.537N (e) (e) | |COCH-ARM / FISHERS | P=0.989 (e) P=0.714 (e) |P=0.626 P=0.500N (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Eye | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/3 (0%) 0/0 (0%) 2/4 (50%) 0/0 (0%) |0/4 (0%) 0/4 (0%) 0/6 (0%) 0/4 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 54.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) |0/0 (0%) 0/1 (0%) 0/5 (0%) 0/2 (0%) | |FIRST INCIDENCE | --- --- 614 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.598N (e) P=0.176 (e) |(e) (e) (e) (e) | |POLY 3 | P=1.000N (e) P=0.299 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=1.000N (e) P=0.284 (e) |(e) (e) (e) (e) | |POLY 6 | P=1.000N (e) P=0.332 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.883 (e) P=0.286 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.861 (e) P=0.286 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/3 (33%) 0/0 (0%) 3/4 (75%) 0/0 (0%) |3/4 (75%) 3/4 (75%) 6/6 (100%) 4/4 (100%) | |POLY-3 ADJUSTED (b)| 38.4% 0.0% 83.6% 0.0% |86.3% 84.3% 100.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) |0/0 (0%) 1/1 (100%) 5/5 (100%) 2/2 (100%) | |FIRST INCIDENCE | 691 --- 650 --- |440 440 680 630 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.412N (e) P=0.415 (e) |P=0.549N P=0.544N P=0.263N P=0.511N | |POLY 3 | P=1.000N (e) P=0.373 (e) |P=0.621 P=0.868N P=0.795 P=0.830 | |POLY 1.5 | P=1.000N (e) P=0.374 (e) |P=0.465 P=0.809N P=0.584 P=0.652 | |POLY 6 | P=1.000N (e) P=0.382 (e) |P=0.940 P=0.976N P=0.999 P=0.998 | |LOGISTIC REGRESSION| P=0.896 (e) P=0.316 (e) |P=0.503 P=0.781 P=0.821 P=0.752 | |COCH-ARM / FISHERS | P=0.887 (e) P=0.371 (e) |P=0.344 P=0.786N P=0.400 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 39/50 (78%) 39/50 (78%) 41/50 (82%) 41/50 (82%) |30/50 (60%) 29/50 (58%) 37/49 (76%) 31/50 (62%) | |POLY-3 ADJUSTED (b)| 86.8% 88.2% 90.7% 86.0% |69.4% 69.7% 82.8% 73.2% | |TERMINAL (d) | 6/7 (86%) 5/5 (100%) 6/6 (100%) 7/8 (88%) |19/23 (83%) 13/19 (68%) 30/33 (91%) 20/22 (91%) | |FIRST INCIDENCE | 379 389 453 490 |440 455 620 547 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.225N P=0.190 P=0.165 P=0.467N |P=0.441 P=0.306 P=0.332N P=0.395 | |POLY 3 | P=0.447N P=0.556 P=0.377 P=0.589N |P=0.466 P=0.588 P=0.090 P=0.438 | |POLY 1.5 | P=0.577 P=0.557 P=0.381 P=0.557 |P=0.479 P=0.589 P=0.081 P=0.448 | |POLY 6 | P=0.280N P=0.572 P=0.380 P=0.489N |P=0.426 P=0.593 P=0.107 P=0.411 | |LOGISTIC REGRESSION| P=0.570 P=0.466 P=0.290 P=0.484 |P=0.554 P=0.498 P=0.234 P=0.480 | |COCH-ARM / FISHERS | P=0.359 P=0.595N P=0.402 P=0.402 |P=0.505 P=0.500N P=0.075 P=0.500 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Heart: Artery | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 4/50 (8%) 5/50 (10%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 8.8% 12.7% 12.5% 13.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 2/8 (25%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 639 664 480 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.468 P=0.355 P=0.397 P=0.400 |(e) (e) (e) (e) | |POLY 3 | P=0.407 P=0.457 P=0.464 P=0.389 |(e) (e) (e) (e) | |POLY 1.5 | P=0.381 P=0.475 P=0.481 P=0.377 |(e) (e) (e) (e) | |POLY 6 | P=0.434 P=0.426 P=0.435 P=0.396 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.460 P=0.403 P=0.446 P=0.400 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.341 P=0.500 P=0.500 P=0.357 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Heart: Atrium | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 6/50 (12%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 3.2% 9.5% 16.4% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 2/8 (25%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 692 650 670 |--- --- 626 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.019 * P=0.433 P=0.096 P=0.026 * |P=0.764N (e) P=0.525 (e) | |POLY 3 | P=0.007 ** P=0.485 P=0.106 P=0.018 * |P=0.767N (e) P=0.517 (e) | |POLY 1.5 | P=0.006 ** P=0.491 P=0.112 P=0.017 * |P=0.768N (e) P=0.509 (e) | |POLY 6 | P=0.008 ** P=0.475 P=0.099 P=0.019 * |P=0.768N (e) P=0.528 (e) | |LOGISTIC REGRESSION| P=0.012 * P=0.456 P=0.098 P=0.019 * |P=0.769N (e) P=0.453 (e) | |COCH-ARM / FISHERS | P=0.005 ** P=0.500 P=0.121 P=0.013 * |P=0.771N (e) P=0.495 (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Intestine Large, Cecum | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 2/49 (4%) 1/49 (2%) |0/48 (0%) 0/49 (0%) 0/48 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 6.6% 2.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 620 688 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.494 (e) P=0.212 P=0.547 |(e) (e) (e) (e) | |POLY 3 | P=0.462 (e) P=0.221 P=0.517 |(e) (e) (e) (e) | |POLY 1.5 | P=0.448 (e) P=0.231 P=0.512 |(e) (e) (e) (e) | |POLY 6 | P=0.478 (e) P=0.208 P=0.521 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.465 (e) P=0.212 P=0.518 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.427 (e) P=0.253 P=0.505 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Intestine Large, Cecum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 2/47 (4%) 6/49 (12%) 4/49 (8%) |5/48 (10%) 2/49 (4%) 4/48 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 9.1% 6.6% 18.9% 11.1% |12.6% 5.6% 9.4% 7.5% | |TERMINAL (d) | 2/7 (29%) 1/5 (20%) 2/6 (33%) 2/8 (25%) |2/23 (9%) 2/19 (11%) 4/33 (12%) 0/22 (0%) | |FIRST INCIDENCE | 648 641 500 610 |488 733 (T) 733 (T) 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.578 P=0.622N P=0.167 P=0.580 |P=0.487N P=0.283N P=0.334N P=0.382N | |POLY 3 | P=0.509 P=0.536N P=0.216 P=0.551 |P=0.441N P=0.255N P=0.457N P=0.352N | |POLY 1.5 | P=0.476 P=0.523N P=0.233 P=0.535 |P=0.448N P=0.239N P=0.473N P=0.350N | |POLY 6 | P=0.552 P=0.561N P=0.193 P=0.567 |P=0.443N P=0.278N P=0.440N P=0.365N | |LOGISTIC REGRESSION| P=0.516 P=0.610N P=0.186 P=0.550 |P=0.464N P=0.219N P=0.499N P=0.331N | |COCH-ARM / FISHERS | P=0.430 P=0.510N P=0.254 P=0.512 |P=0.466N P=0.209N P=0.500N P=0.346N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 1/48 (2%) 2/48 (4%) 2/49 (4%) |5/49 (10%) 0/50 (0%) 1/49 (2%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 12.0% 3.2% 6.6% 5.7% |12.4% 0.0% 2.3% 2.6% | |TERMINAL (d) | 3/7 (43%) 0/5 (0%) 0/6 (0%) 2/8 (25%) |0/23 (0%) 0/19 (0%) 1/33 (3%) 1/22 (5%) | |FIRST INCIDENCE | 648 641 585 733 (T) |488 --- 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.362N P=0.259N P=0.425N P=0.252N |P=0.264N P=0.058N P=0.069N P=0.127N | |POLY 3 | P=0.435N P=0.199N P=0.383N P=0.308N |P=0.238N P=0.038N* P=0.085N P=0.107N | |POLY 1.5 | P=0.458N P=0.193N P=0.366N P=0.319N |P=0.244N P=0.035N* P=0.091N P=0.105N | |POLY 6 | P=0.408N P=0.212N P=0.407N P=0.300N |P=0.233N P=0.043N* P=0.080N P=0.113N | |LOGISTIC REGRESSION| P=0.399N P=0.250N P=0.438N P=0.310N |P=0.257N P=0.033N* P=0.103N P=0.104N | |COCH-ARM / FISHERS | P=0.489N P=0.187N P=0.349N P=0.339N |P=0.261N P=0.027N* P=0.102N P=0.102N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 2/49 (4%) 3/49 (6%) 3/49 (6%) |8/47 (17%) 5/47 (11%) 5/47 (11%) 3/48 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 6.4% 9.7% 8.2% |20.8% 14.1% 12.2% 8.0% | |TERMINAL (d) | 0/6 (0%) 0/5 (0%) 1/6 (17%) 1/8 (13%) |6/22 (27%) 2/18 (11%) 4/30 (13%) 3/20 (15%) | |FIRST INCIDENCE | --- 469 574 534 |440 534 705 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.316 P=0.215 P=0.110 P=0.155 |P=0.139N P=0.394N P=0.134N P=0.119N | |POLY 3 | P=0.274 P=0.232 P=0.112 P=0.144 |P=0.125N P=0.329N P=0.231N P=0.104N | |POLY 1.5 | P=0.252 P=0.238 P=0.118 P=0.137 |P=0.122N P=0.315N P=0.248N P=0.100N | |POLY 6 | P=0.302 P=0.223 P=0.103 P=0.152 |P=0.135N P=0.348N P=0.213N P=0.114N | |LOGISTIC REGRESSION| P=0.189 P=0.270 P=0.121 P=0.100 |P=0.119N P=0.309N P=0.232N P=0.098N | |COCH-ARM / FISHERS | P=0.222 P=0.258 P=0.129 P=0.129 |P=0.121N P=0.276N P=0.276N P=0.093N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/49 (0%) 2/50 (4%) 0/49 (0%) |0/49 (0%) 0/50 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 6.0% 0.0% 6.2% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 706 --- 551 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.270N P=0.382N P=0.628 P=0.284N |(e) (e) (e) (e) | |POLY 3 | P=0.246N P=0.257N P=0.683 P=0.223N |(e) (e) (e) (e) | |POLY 1.5 | P=0.264N P=0.248N P=0.691 P=0.228N |(e) (e) (e) (e) | |POLY 6 | P=0.225N P=0.273N P=0.672 P=0.218N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.282N P=0.310N P=0.693 P=0.223N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.290N P=0.247N P=0.684N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 4/49 (8%) 3/50 (6%) 3/50 (6%) |0/50 (0%) 1/50 (2%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 12.4% 9.4% 8.3% |0.0% 2.7% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 1/6 (17%) 1/8 (13%) |0/23 (0%) 1/19 (5%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 526 512 636 |--- 733 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.506 P=0.048 * P=0.100 P=0.142 |P=0.618N P=0.462 (e) (e) | |POLY 3 | P=0.446 P=0.053 P=0.107 P=0.132 |P=0.631N P=0.483 (e) (e) | |POLY 1.5 | P=0.425 P=0.055 P=0.113 P=0.127 |P=0.625N P=0.488 (e) (e) | |POLY 6 | P=0.472 P=0.049 * P=0.099 P=0.137 |P=0.641N P=0.477 (e) (e) | |LOGISTIC REGRESSION| P=0.423 P=0.062 P=0.114 P=0.134 |(e) P=0.462 (e) (e) | |COCH-ARM / FISHERS | P=0.394 P=0.056 P=0.121 P=0.121 |P=0.611N P=0.500 (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 8.9% 9.6% 0.0% 2.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/7 (14%) 1/5 (20%) 0/6 (0%) 1/8 (13%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 683 664 --- 733 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.192N P=0.484 P=0.166N P=0.302N |(e) (e) (e) (e) | |POLY 3 | P=0.206N P=0.629 P=0.132N P=0.282N |(e) (e) (e) (e) | |POLY 1.5 | P=0.220N P=0.643 P=0.126N P=0.291N |(e) (e) (e) (e) | |POLY 6 | P=0.190N P=0.605 P=0.144N P=0.277N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.179N P=0.532 P=0.154N P=0.281N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.239N P=0.661N P=0.121N P=0.309N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 3.2% 0.0% 2.8% |2.5% 0.0% 0.0% 5.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |1/23 (4%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 389 --- 701 |733 (T) --- --- 469 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.492 P=0.500 (e) P=0.484 |P=0.175 P=0.538N P=0.428N P=0.494 | |POLY 3 | P=0.498 P=0.489 (e) P=0.514 |P=0.181 P=0.517N P=0.484N P=0.502 | |POLY 1.5 | P=0.490 P=0.494 (e) P=0.509 |P=0.178 P=0.512N P=0.492N P=0.497 | |POLY 6 | P=0.506 P=0.481 (e) P=0.519 |P=0.183 P=0.523N P=0.475N P=0.503 | |LOGISTIC REGRESSION| P=0.380 P=0.710 (e) P=0.515 |P=0.174 (e) (e) P=0.511 | |COCH-ARM / FISHERS | P=0.478 P=0.500 (e) P=0.500 |P=0.171 P=0.500N P=0.505N P=0.492 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 3/50 (6%) 4/50 (8%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 11.5% 6.4% 9.3% 11.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 2/8 (25%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 539 684 480 604 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.562 P=0.477N P=0.607N P=0.603N |(e) (e) (e) (e) | |POLY 3 | P=0.504 P=0.387N P=0.543N P=0.621N |(e) (e) (e) (e) | |POLY 1.5 | P=0.476 P=0.364N P=0.522N P=0.627N |(e) (e) (e) (e) | |POLY 6 | P=0.537 P=0.429N P=0.577N P=0.623N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.506 P=0.388N P=0.505N P=0.606N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.433 P=0.339N P=0.500N P=0.643N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 50/50 (100%) 48/50 (96%) 50/50 (100%) 50/50 (100%)|46/50 (92%) 46/50 (92%) 46/49 (94%) 46/49 (94%) | |POLY-3 ADJUSTED (b)| 100.0% 99.6% 100.0% 100.0% |95.7% 98.6% 95.9% 97.3% | |TERMINAL (d) | 7/7 (100%) 5/5 (100%) 6/6 (100%) 8/8 (100%) |22/23 (96%) 19/19 (100%) 33/33 (100%) 22/22 (100%) | |FIRST INCIDENCE | 379 460 352 490 |390 420 399 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.163N P=0.231 (e) (e) |P=0.486 P=0.194 P=0.032N* P=0.451 | |POLY 3 | P=1.000 P=1.000N (e) (e) |P=0.621 P=0.386 P=0.704 P=0.569 | |POLY 1.5 | P=0.904 P=0.830N (e) (e) |P=0.513 P=0.394 P=0.626 P=0.476 | |POLY 6 | P=1.000 P=1.000N (e) (e) |P=0.693 P=0.439 P=0.755N P=0.649 | |LOGISTIC REGRESSION| P=0.979 P=0.431N (e) (e) |P=0.487 P=0.358 P=0.633N P=0.440 | |COCH-ARM / FISHERS | P=0.390 P=0.247N (e) (e) |P=0.451 P=0.643N P=0.511 P=0.511 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation Acute | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 3.0% 3.2% 6.3% 2.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 670 389 628 604 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.557N P=0.737 P=0.412 P=0.736N |(e) (e) (e) (e) | |POLY 3 | P=0.592N P=0.749 P=0.477 P=0.746N |(e) (e) (e) (e) | |POLY 1.5 | P=0.608N P=0.754 P=0.487 P=0.751N |(e) (e) (e) (e) | |POLY 6 | P=0.573N P=0.738 P=0.462 P=0.742N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.652 P=0.711N P=0.475 P=0.762 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.632N P=0.753N P=0.500 P=0.753N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 3/50 (6%) 4/50 (8%) |0/50 (0%) 1/50 (2%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 5.8% 12.7% 9.5% 11.0% |0.0% 2.7% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 1/6 (17%) 2/8 (25%) |0/23 (0%) 1/19 (5%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 539 664 558 604 |--- 733 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.520 P=0.233 P=0.437 P=0.397 |P=0.618N P=0.462 (e) (e) | |POLY 3 | P=0.456 P=0.292 P=0.460 P=0.362 |P=0.631N P=0.483 (e) (e) | |POLY 1.5 | P=0.433 P=0.312 P=0.479 P=0.353 |P=0.625N P=0.488 (e) (e) | |POLY 6 | P=0.480 P=0.262 P=0.431 P=0.367 |P=0.641N P=0.477 (e) (e) | |LOGISTIC REGRESSION| P=0.490 P=0.287 P=0.483 P=0.355 |(e) P=0.462 (e) (e) | |COCH-ARM / FISHERS | P=0.398 P=0.339 P=0.500 P=0.339 |P=0.611N P=0.500 (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 3.0% 0.0% 0.0% 5.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 719 --- --- 604 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.233 P=0.638N P=0.602N P=0.513 |(e) (e) (e) (e) | |POLY 3 | P=0.203 P=0.516N P=0.516N P=0.528 |(e) (e) (e) (e) | |POLY 1.5 | P=0.191 P=0.509N P=0.509N P=0.517 |(e) (e) (e) (e) | |POLY 6 | P=0.221 P=0.529N P=0.529N P=0.541 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.215 P=0.576N P=0.543N P=0.527 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.175 P=0.500N P=0.500N P=0.500 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Larynx: Epiglottis | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/50 (0%) 1/49 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 2.8% |0.0% 0.0% 0.0% 5.1% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 2/22 (9%) | |FIRST INCIDENCE | --- --- --- 618 |--- --- --- 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.267 (e) (e) P=0.524 |P=0.034 * (e) (e) P=0.227 | |POLY 3 | P=0.243 (e) (e) P=0.511 |P=0.042 * (e) (e) P=0.233 | |POLY 1.5 | P=0.236 (e) (e) P=0.505 |P=0.041 * (e) (e) P=0.234 | |POLY 6 | P=0.252 (e) (e) P=0.518 |P=0.041 * (e) (e) P=0.230 | |LOGISTIC REGRESSION| P=0.217 (e) (e) P=0.480 |(e) (e) (e) P=0.227 | |COCH-ARM / FISHERS | P=0.225 (e) (e) P=0.495 |P=0.042 * (e) (e) P=0.247 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 3/50 (6%) 4/50 (8%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 8.8% 3.2% 0.0% 2.8% |2.5% 8.0% 9.0% 7.5% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |1/23 (4%) 1/19 (5%) 2/33 (6%) 0/22 (0%) | |FIRST INCIDENCE | 648 579 --- 610 |733 (T) 573 701 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.380N P=0.432N P=0.160N P=0.339N |P=0.422 P=0.254 P=0.279 P=0.293 | |POLY 3 | P=0.365N P=0.332N P=0.134N P=0.281N |P=0.446 P=0.283 P=0.211 P=0.304 | |POLY 1.5 | P=0.384N P=0.320N P=0.126N P=0.290N |P=0.436 P=0.288 P=0.198 P=0.300 | |POLY 6 | P=0.338N P=0.354N P=0.148N P=0.274N |P=0.452 P=0.277 P=0.228 P=0.307 | |LOGISTIC REGRESSION| P=0.379N P=0.339N P=0.149N P=0.280N |P=0.429 P=0.292 P=0.229 P=0.297 | |COCH-ARM / FISHERS | P=0.409N P=0.309N P=0.121N P=0.309N |P=0.426 P=0.309 P=0.181 P=0.301 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 14/50 (28%) 14/50 (28%) 22/50 (44%) |36/50 (72%) 36/50 (72%) 43/50 (86%) 36/49 (73%) | |POLY-3 ADJUSTED (b)| 45.5% 39.7% 41.8% 54.1% |81.9% 83.1% 92.5% 84.9% | |TERMINAL (d) | 5/7 (71%) 2/5 (40%) 6/6 (100%) 7/8 (88%) |22/23 (96%) 18/19 (95%) 33/33 (100%) 20/22 (91%) | |FIRST INCIDENCE | 476 526 520 490 |421 440 522 592 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.277 P=0.503 P=0.564N P=0.316 |P=0.546 P=0.194 P=0.227N P=0.450 | |POLY 3 | P=0.122 P=0.389N P=0.467N P=0.283 |P=0.501 P=0.563 P=0.073 P=0.460 | |POLY 1.5 | P=0.096 P=0.369N P=0.399N P=0.252 |P=0.517 P=0.526 P=0.070 P=0.457 | |POLY 6 | P=0.154 P=0.414N P=0.598N P=0.315 |P=0.487 P=0.625 P=0.078 P=0.477 | |LOGISTIC REGRESSION| P=0.167 P=0.429N P=0.498N P=0.290 |P=0.416N P=0.380 P=0.269 P=0.589 | |COCH-ARM / FISHERS | P=0.066 P=0.333N P=0.333N P=0.206 |P=0.556N P=0.588N P=0.070 P=0.525 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 3/50 (6%) 3/50 (6%) |6/50 (12%) 9/50 (18%) 12/50 (24%) 5/49 (10%) | |POLY-3 ADJUSTED (b)| 8.7% 3.2% 9.5% 8.3% |15.0% 24.0% 27.3% 12.8% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 2/6 (33%) 2/8 (25%) |5/23 (22%) 7/19 (37%) 12/33 (36%) 5/22 (23%) | |FIRST INCIDENCE | 539 469 558 664 |664 440 733 (T) 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.569 P=0.377N P=0.591 P=0.614N |P=0.218N P=0.168 P=0.298 P=0.532N | |POLY 3 | P=0.509 P=0.333N P=0.624 P=0.642N |P=0.227N P=0.234 P=0.132 P=0.521N | |POLY 1.5 | P=0.485 P=0.321N P=0.642 P=0.648N |P=0.232N P=0.250 P=0.116 P=0.520N | |POLY 6 | P=0.537 P=0.356N P=0.594 P=0.643N |P=0.234N P=0.211 P=0.149 P=0.533N | |LOGISTIC REGRESSION| P=0.509 P=0.288N P=0.618 P=0.626N |P=0.228N P=0.208 P=0.196 P=0.556N | |COCH-ARM / FISHERS | P=0.449 P=0.309N P=0.661N P=0.661N |P=0.240N P=0.288 P=0.096 P=0.514N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 5.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 1/8 (13%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- 534 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.065 (e) (e) P=0.262 |(e) (e) (e) (e) | |POLY 3 | P=0.049 * (e) (e) P=0.255 |(e) (e) (e) (e) | |POLY 1.5 | P=0.045 * (e) (e) P=0.248 |(e) (e) (e) (e) | |POLY 6 | P=0.053 (e) (e) P=0.262 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.044 * (e) (e) P=0.231 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 12/50 (24%) 10/50 (20%) 14/50 (28%) 16/50 (32%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 33.6% 28.8% 40.4% 41.5% |0.0% 0.0% 4.5% 0.0% | |TERMINAL (d) | 2/7 (29%) 0/5 (0%) 2/6 (33%) 5/8 (63%) |0/23 (0%) 0/19 (0%) 1/33 (3%) 0/22 (0%) | |FIRST INCIDENCE | 576 469 512 611 |--- --- 680 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.396 P=0.528 P=0.240 P=0.378 |P=0.670N (e) P=0.306 (e) | |POLY 3 | P=0.202 P=0.428N P=0.359 P=0.316 |P=0.643N (e) P=0.261 (e) | |POLY 1.5 | P=0.176 P=0.421N P=0.382 P=0.290 |P=0.649N (e) P=0.251 (e) | |POLY 6 | P=0.232 P=0.442N P=0.331 P=0.342 |P=0.641N (e) P=0.272 (e) | |LOGISTIC REGRESSION| P=0.268 P=0.485N P=0.268 P=0.343 |P=0.656N (e) P=0.258 (e) | |COCH-ARM / FISHERS | P=0.139 P=0.405N P=0.410 P=0.252 |P=0.657N (e) P=0.247 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Degeneration Fatty | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 18/50 (36%) 18/50 (36%) 14/50 (28%) |12/50 (24%) 10/50 (20%) 12/50 (24%) 12/49 (24%) | |POLY-3 ADJUSTED (b)| 36.1% 47.0% 44.9% 34.0% |27.8% 24.5% 25.0% 27.7% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 1/19 (5%) 1/33 (3%) 0/22 (0%) | |FIRST INCIDENCE | 476 460 496 490 |496 420 522 512 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.188N P=0.155 P=0.184 P=0.467N |P=0.482 P=0.530N P=0.419N P=0.556 | |POLY 3 | P=0.241N P=0.218 P=0.276 P=0.518N |P=0.489 P=0.463N P=0.474N P=0.593N | |POLY 1.5 | P=0.281N P=0.231 P=0.266 P=0.545N |P=0.471 P=0.449N P=0.520N P=0.580 | |POLY 6 | P=0.206N P=0.207 P=0.298 P=0.493N |P=0.499 P=0.487N P=0.425N P=0.586N | |LOGISTIC REGRESSION| P=0.512N P=0.288 P=0.340 P=0.484 |P=0.434 P=0.350N P=0.412 P=0.587 | |COCH-ARM / FISHERS | P=0.352N P=0.260 P=0.260 P=0.588N |P=0.447 P=0.405N P=0.592N P=0.570 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 2/50 (4%) 5/50 (10%) 5/50 (10%) |6/50 (12%) 6/50 (12%) 5/50 (10%) 9/49 (18%) | |POLY-3 ADJUSTED (b)| 17.1% 6.4% 15.5% 13.8% |14.6% 16.3% 11.2% 22.8% | |TERMINAL (d) | 1/7 (14%) 1/5 (20%) 1/6 (17%) 3/8 (38%) |4/23 (17%) 4/19 (21%) 4/33 (12%) 6/22 (27%) | |FIRST INCIDENCE | 580 692 558 658 |488 688 534 668 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.540N P=0.246N P=0.598 P=0.429N |P=0.159 P=0.503 P=0.308N P=0.259 | |POLY 3 | P=0.563 P=0.169N P=0.560N P=0.477N |P=0.168 P=0.546 P=0.440N P=0.257 | |POLY 1.5 | P=0.529 P=0.152N P=0.531N P=0.483N |P=0.169 P=0.570 P=0.463N P=0.261 | |POLY 6 | P=0.599N P=0.204N P=0.606N P=0.488N |P=0.162 P=0.516 P=0.415N P=0.246 | |LOGISTIC REGRESSION| P=0.587N P=0.173N P=0.552N P=0.440N |P=0.174 P=0.559 P=0.500N P=0.268 | |COCH-ARM / FISHERS | P=0.477 P=0.134N P=0.500N P=0.500N |P=0.169 P=0.620N P=0.500N P=0.274 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 1/50 (2%) 2/50 (4%) |4/50 (8%) 7/50 (14%) 5/50 (10%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 11.2% 6.4% 3.2% 5.5% |9.9% 18.3% 11.2% 7.5% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 0/8 (0%) |3/23 (13%) 4/19 (21%) 2/33 (6%) 1/22 (5%) | |FIRST INCIDENCE | 379 641 590 534 |573 440 620 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.353N P=0.422N P=0.212N P=0.314N |P=0.249N P=0.188 P=0.607N P=0.512N | |POLY 3 | P=0.373N P=0.398N P=0.216N P=0.321N |P=0.245N P=0.225 P=0.565 P=0.508N | |POLY 1.5 | P=0.398N P=0.371N P=0.199N P=0.327N |P=0.247N P=0.235 P=0.539 P=0.510N | |POLY 6 | P=0.344N P=0.443N P=0.244N P=0.320N |P=0.254N P=0.213 P=0.596 P=0.514N | |LOGISTIC REGRESSION| P=0.503N P=0.302N P=0.135N P=0.525N |P=0.249N P=0.236 P=0.526 P=0.511N | |COCH-ARM / FISHERS | P=0.431N P=0.339N P=0.181N P=0.339N |P=0.250N P=0.262 P=0.500 P=0.511N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 4/50 (8%) 0/50 (0%) |7/50 (14%) 11/50 (22%) 9/50 (18%) 8/49 (16%) | |POLY-3 ADJUSTED (b)| 8.8% 6.2% 12.3% 0.0% |17.4% 28.3% 20.1% 20.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |4/23 (17%) 3/19 (16%) 8/33 (24%) 5/22 (23%) | |FIRST INCIDENCE | 621 460 590 --- |642 455 399 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.085N P=0.583N P=0.360 P=0.117N |P=0.489N P=0.133 P=0.566N P=0.464 | |POLY 3 | P=0.083N P=0.529N P=0.474 P=0.108N |P=0.483N P=0.184 P=0.483 P=0.492 | |POLY 1.5 | P=0.092N P=0.516N P=0.485 P=0.112N |P=0.487N P=0.189 P=0.449 P=0.485 | |POLY 6 | P=0.075N P=0.553N P=0.460 P=0.107N |P=0.489N P=0.179 P=0.516 P=0.492 | |LOGISTIC REGRESSION| P=0.117N P=0.488N P=0.485 P=0.108N |P=0.477N P=0.169 P=0.469 P=0.477 | |COCH-ARM / FISHERS | P=0.107N P=0.500N P=0.500 P=0.121N |P=0.490N P=0.218 P=0.393 P=0.483 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) |2/50 (4%) 0/50 (0%) 2/50 (4%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 6.4% 9.3% 2.8% |4.9% 0.0% 4.5% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |1/23 (4%) 0/19 (0%) 1/33 (3%) 0/22 (0%) | |FIRST INCIDENCE | --- 614 496 700 |552 --- 686 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.569N P=0.169 P=0.111 P=0.500 |P=0.294N P=0.272N P=0.603N P=0.245N | |POLY 3 | P=0.575N P=0.221 P=0.109 P=0.514 |P=0.278N P=0.259N P=0.662N P=0.245N | |POLY 1.5 | P=0.591N P=0.228 P=0.113 P=0.509 |P=0.283N P=0.252N P=0.674N P=0.244N | |POLY 6 | P=0.560N P=0.211 P=0.102 P=0.519 |P=0.276N P=0.269N P=0.647N P=0.249N | |LOGISTIC REGRESSION| P=0.593N P=0.214 P=0.126 P=0.515 |P=0.293N P=0.231N P=0.691 P=0.238N | |COCH-ARM / FISHERS | P=0.615N P=0.247 P=0.121 P=0.500 |P=0.295N P=0.247N P=0.691N P=0.253N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Regeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 5.6% |2.5% 2.7% 4.5% 7.6% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 2/8 (25%) |0/23 (0%) 0/19 (0%) 2/33 (6%) 0/22 (0%) | |FIRST INCIDENCE | --- --- --- 733 (T) |608 722 733 (T) 630 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.070 (e) (e) P=0.262 |P=0.185 P=0.723 P=0.597 P=0.294 | |POLY 3 | P=0.047 * (e) (e) P=0.251 |P=0.200 P=0.740 P=0.531 P=0.299 | |POLY 1.5 | P=0.045 * (e) (e) P=0.246 |P=0.195 P=0.746 P=0.519 P=0.297 | |POLY 6 | P=0.050 (e) (e) P=0.254 |P=0.202 P=0.731 P=0.544 P=0.298 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.262 |P=0.189 P=0.757 P=0.514 P=0.300 | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |P=0.188 P=0.753N P=0.500 P=0.301 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 5.8% 0.0% 0.0% 0.0% |2.5% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 590 --- --- --- |720 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.280N P=0.261N P=0.280N P=0.213N |P=0.549N P=0.560N P=0.454N P=0.515N | |POLY 3 | P=0.273N P=0.260N P=0.260N P=0.227N |P=0.549N P=0.517N P=0.480N P=0.505N | |POLY 1.5 | P=0.289N P=0.250N P=0.249N P=0.230N |P=0.548N P=0.512N P=0.488N P=0.505N | |POLY 6 | P=0.250N P=0.280N P=0.280N P=0.227N |P=0.550N P=0.524N P=0.472N P=0.507N | |LOGISTIC REGRESSION| P=0.322N P=0.226N P=0.227N P=0.267N |P=0.552N P=0.529N P=0.468N P=0.511N | |COCH-ARM / FISHERS | P=0.308N P=0.247N P=0.247N P=0.247N |P=0.551N P=0.500N P=0.500N P=0.505N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 27/50 (54%) 23/50 (46%) 29/50 (58%) |9/50 (18%) 5/50 (10%) 7/50 (14%) 10/49 (20%) | |POLY-3 ADJUSTED (b)| 57.0% 67.6% 58.6% 68.4% |21.5% 13.4% 15.3% 24.7% | |TERMINAL (d) | 6/7 (86%) 5/5 (100%) 2/6 (33%) 5/8 (63%) |2/23 (9%) 2/19 (11%) 3/33 (9%) 2/22 (9%) | |FIRST INCIDENCE | 467 482 500 525 |552 635 534 630 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.487N P=0.100 P=0.323 P=0.338 |P=0.229 P=0.313N P=0.244N P=0.454 | |POLY 3 | P=0.235 P=0.205 P=0.538 P=0.178 |P=0.227 P=0.259N P=0.318N P=0.466 | |POLY 1.5 | P=0.213 P=0.229 P=0.550 P=0.171 |P=0.222 P=0.236N P=0.346N P=0.468 | |POLY 6 | P=0.268 P=0.176 P=0.560 P=0.193 |P=0.228 P=0.294N P=0.290N P=0.456 | |LOGISTIC REGRESSION| P=0.297 P=0.214 P=0.528 P=0.228 |P=0.216 P=0.224N P=0.448N P=0.476 | |COCH-ARM / FISHERS | P=0.179 P=0.274 P=0.579N P=0.158 |P=0.212 P=0.194N P=0.393N P=0.480 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 9/50 (18%) 10/50 (20%) 15/50 (30%) |4/50 (8%) 4/50 (8%) 5/50 (10%) 9/49 (18%) | |POLY-3 ADJUSTED (b)| 26.9% 25.7% 28.6% 38.3% |9.8% 10.5% 11.1% 20.9% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 1/6 (17%) 2/8 (25%) |0/23 (0%) 1/19 (5%) 2/33 (6%) 0/22 (0%) | |FIRST INCIDENCE | 467 460 453 525 |608 548 607 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.234 P=0.526 P=0.462 P=0.271 |P=0.059 P=0.560 P=0.614 P=0.127 | |POLY 3 | P=0.111 P=0.564N P=0.540 P=0.199 |P=0.062 P=0.602 P=0.557 P=0.132 | |POLY 1.5 | P=0.100 P=0.537N P=0.568 P=0.192 |P=0.054 P=0.613 P=0.535 P=0.120 | |POLY 6 | P=0.127 P=0.609N P=0.494 P=0.203 |P=0.069 P=0.585 P=0.580 P=0.142 | |LOGISTIC REGRESSION| P=0.082 P=0.464N P=0.577N P=0.196 |P=0.044 * P=0.641N P=0.477 P=0.120 | |COCH-ARM / FISHERS | P=0.082 P=0.500N P=0.598N P=0.178 |P=0.045 * P=0.643N P=0.500 P=0.109 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 3/50 (6%) 1/50 (2%) 5/50 (10%) |7/50 (14%) 5/50 (10%) 9/50 (18%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 24.6% 9.2% 3.1% 13.2% |16.9% 13.5% 20.2% 27.3% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |3/23 (13%) 3/19 (16%) 8/33 (24%) 6/22 (27%) | |FIRST INCIDENCE | 379 460 352 525 |488 603 534 650 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.372N P=0.137N P=0.027N* P=0.183N |P=0.085 P=0.491N P=0.580N P=0.199 | |POLY 3 | P=0.379N P=0.080N P=0.012N* P=0.162N |P=0.095 P=0.457N P=0.454 P=0.190 | |POLY 1.5 | P=0.422N P=0.071N P=0.010N* P=0.175N |P=0.096 P=0.431N P=0.431 P=0.198 | |POLY 6 | P=0.320N P=0.098N P=0.017N* P=0.151N |P=0.091 P=0.492N P=0.477 P=0.175 | |LOGISTIC REGRESSION| P=0.588N P=0.052N P=0.007N** P=0.243N |P=0.094 P=0.417N P=0.417 P=0.207 | |COCH-ARM / FISHERS | P=0.477N P=0.061N P=0.008N** P=0.194N |P=0.097 P=0.380N P=0.393 P=0.218 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 5.9% 6.4% 3.2% 2.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 639 684 700 700 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.331N P=0.564 P=0.592N P=0.496N |(e) (e) (e) (e) | |POLY 3 | P=0.371N P=0.665 P=0.531N P=0.479N |(e) (e) (e) (e) | |POLY 1.5 | P=0.387N P=0.678 P=0.516N P=0.487N |(e) (e) (e) (e) | |POLY 6 | P=0.352N P=0.643 P=0.555N P=0.475N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.338N P=0.616 P=0.559N P=0.470N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.410N P=0.691N P=0.500N P=0.500N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 5/50 (10%) 7/50 (14%) 5/50 (10%) |9/50 (18%) 9/50 (18%) 7/50 (14%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 24.7% 14.9% 21.2% 13.5% |22.1% 23.9% 15.9% 15.2% | |TERMINAL (d) | 2/7 (29%) 0/5 (0%) 2/6 (33%) 1/8 (13%) |5/23 (22%) 5/19 (26%) 7/33 (21%) 4/22 (18%) | |FIRST INCIDENCE | 495 389 520 604 |552 621 733 (T) 671 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.182N P=0.321N P=0.526N P=0.152N |P=0.241N P=0.439 P=0.165N P=0.326N | |POLY 3 | P=0.219N P=0.231N P=0.473N P=0.173N |P=0.238N P=0.531 P=0.327N P=0.304N | |POLY 1.5 | P=0.244N P=0.213N P=0.435N P=0.180N |P=0.236N P=0.551 P=0.352N P=0.300N | |POLY 6 | P=0.194N P=0.269N P=0.537N P=0.174N |P=0.251N P=0.507 P=0.302N P=0.320N | |LOGISTIC REGRESSION| P=0.287N P=0.167N P=0.416N P=0.186N |P=0.229N P=0.512 P=0.277N P=0.305N | |COCH-ARM / FISHERS | P=0.282N P=0.194N P=0.393N P=0.194N |P=0.233N P=0.602N P=0.393N P=0.288N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lung: Artery, Mediastinum | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 5.9% 6.4% 3.2% 2.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 639 684 480 700 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.337N P=0.564 P=0.588N P=0.496N |(e) (e) (e) (e) | |POLY 3 | P=0.373N P=0.665 P=0.524N P=0.479N |(e) (e) (e) (e) | |POLY 1.5 | P=0.388N P=0.678 P=0.512N P=0.487N |(e) (e) (e) (e) | |POLY 6 | P=0.355N P=0.643 P=0.544N P=0.475N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.366N P=0.616 P=0.493N P=0.470N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.410N P=0.691N P=0.500N P=0.500N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Galactocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/41 (5%) 7/41 (17%) 1/40 (3%) 4/44 (9%) |2/50 (4%) 2/50 (4%) 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 6.5% 24.3% 4.1% 12.7% |4.9% 5.5% 2.2% 5.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 1/4 (25%) 0/6 (0%) |0/23 (0%) 2/19 (11%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 650 547 733 (T) 664 |496 733 (T) 399 657 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.508N P=0.047 * P=0.621N P=0.396 |P=0.618 P=0.635 P=0.476N P=0.686 | |POLY 3 | P=0.587N P=0.055 P=0.577N P=0.344 |P=0.608 P=0.655 P=0.468N P=0.684 | |POLY 1.5 | P=0.582N P=0.064 P=0.546N P=0.356 |P=0.610 P=0.668 P=0.480N P=0.686 | |POLY 6 | P=0.600N P=0.042 * P=0.622N P=0.323 |P=0.603 P=0.637 P=0.456N P=0.676 | |LOGISTIC REGRESSION| P=0.574N P=0.061 P=0.634N P=0.324 |P=0.615 P=0.697 P=0.743N P=0.684N | |COCH-ARM / FISHERS | P=0.580N P=0.077 P=0.509N P=0.372 |P=0.613 P=0.691N P=0.500N P=0.691N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 1/10 (10%) 0/8 (0%) 1/11 (9%) |0/8 (0%) 0/10 (0%) 0/12 (0%) 2/7 (29%) | |POLY-3 ADJUSTED (b)| 0.0% 12.3% 0.0% 11.1% |0.0% 0.0% 0.0% 36.1% | |TERMINAL (d) | 0/5 (0%) 0/2 (0%) 0/3 (0%) 0/1 (0%) |0/2 (0%) 0/3 (0%) 0/5 (0%) 1/2 (50%) | |FIRST INCIDENCE | --- 692 --- 608 |--- --- --- 702 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.527 P=0.427 (e) P=0.523 |P=0.023 * (e) (e) P=0.228 | |POLY 3 | P=0.481 P=0.435 (e) P=0.458 |P=0.009 ** (e) (e) P=0.198 | |POLY 1.5 | P=0.471 P=0.429 (e) P=0.450 |P=0.010 * (e) (e) P=0.195 | |POLY 6 | P=0.487 P=0.439 (e) P=0.463 |P=0.008 ** (e) (e) P=0.195 | |LOGISTIC REGRESSION| P=0.431 P=0.429 (e) P=0.344 |P=0.008 ** (e) (e) P=0.162 | |COCH-ARM / FISHERS | P=0.452 P=0.400 (e) P=0.423 |P=0.016 * (e) (e) P=0.200 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/15 (93%) 9/10 (90%) 8/8 (100%) 8/11 (73%) |8/8 (100%) 10/10 (100%) 12/12 (100%) 6/7 (86%) | |POLY-3 ADJUSTED (b)| 97.2% 91.7% 100.0% 79.2% |100.0% 100.0% 100.0% 85.7% | |TERMINAL (d) | 5/5 (100%) 2/2 (100%) 3/3 (100%) 1/1 (100%) |2/2 (100%) 3/3 (100%) 5/5 (100%) 1/2 (50%) | |FIRST INCIDENCE | 477 604 555 604 |496 440 522 559 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.313N P=0.588N P=0.357N P=0.349N |P=0.259N (e) (e) P=0.417N | |POLY 3 | P=0.099N P=0.653N P=0.966 P=0.175N |P=0.168N (e) (e) P=0.473N | |POLY 1.5 | P=0.090N P=0.655N P=0.815 P=0.173N |P=0.168N (e) (e) P=0.473N | |POLY 6 | P=0.142N P=0.694N P=1.000 P=0.225N |P=0.168N (e) (e) P=0.473N | |LOGISTIC REGRESSION| P=0.058N P=0.588N P=0.858 P=0.102N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.092N P=0.650N P=0.652 P=0.188N |P=0.169N (e) (e) P=0.467N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/49 (29%) 11/49 (22%) 16/50 (32%) 9/49 (18%) |7/50 (14%) 2/50 (4%) 8/50 (16%) 8/49 (16%) | |POLY-3 ADJUSTED (b)| 37.4% 32.4% 43.9% 23.5% |16.6% 5.4% 18.0% 19.3% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 3/6 (50%) 0/8 (0%) |3/23 (13%) 0/19 (0%) 6/33 (18%) 3/22 (14%) | |FIRST INCIDENCE | 477 527 480 525 |421 565 620 5 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.099N P=0.567N P=0.253 P=0.146N |P=0.197 P=0.123N P=0.507N P=0.481 | |POLY 3 | P=0.088N P=0.419N P=0.366 P=0.133N |P=0.232 P=0.109N P=0.549 P=0.489 | |POLY 1.5 | P=0.116N P=0.373N P=0.402 P=0.145N |P=0.222 P=0.099N P=0.530 P=0.490 | |POLY 6 | P=0.064N P=0.504N P=0.307 P=0.130N |P=0.236 P=0.123N P=0.572 P=0.479 | |LOGISTIC REGRESSION| P=0.142N P=0.366N P=0.407 P=0.178N |P=0.188 P=0.068N P=0.472 P=0.515 | |COCH-ARM / FISHERS | P=0.169N P=0.322N P=0.440 P=0.170N |P=0.190 P=0.080N P=0.500 P=0.483 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 7/49 (14%) 10/50 (20%) 6/49 (12%) |2/50 (4%) 3/50 (6%) 2/50 (4%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 11.6% 20.7% 28.3% 16.2% |5.0% 7.9% 4.5% 7.4% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 1/8 (13%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 590 514 496 505 |663 548 607 512 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.436N P=0.196 P=0.052 P=0.437 |P=0.494 P=0.443 P=0.641N P=0.483 | |POLY 3 | P=0.519N P=0.241 P=0.068 P=0.411 |P=0.494 P=0.474 P=0.654N P=0.503 | |POLY 1.5 | P=0.548N P=0.250 P=0.073 P=0.396 |P=0.488 P=0.479 P=0.670N P=0.496 | |POLY 6 | P=0.493N P=0.220 P=0.064 P=0.421 |P=0.493 P=0.467 P=0.636N P=0.505 | |LOGISTIC REGRESSION| P=0.493 P=0.283 P=0.094 P=0.364 |P=0.480 P=0.512 P=0.658 P=0.509 | |COCH-ARM / FISHERS | P=0.559 P=0.262 P=0.080 P=0.370 |P=0.479 P=0.500 P=0.691N P=0.490 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose: Lateral Wall | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/49 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 3.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 7.5% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 2/22 (9%) | |FIRST INCIDENCE | 467 --- --- --- |--- --- --- 5 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.540N P=0.508N P=0.504N P=0.496N |P=0.007 ** (e) (e) P=0.117 | |POLY 3 | P=0.523N P=0.519N P=0.518N P=0.491N |P=0.008 ** (e) (e) P=0.118 | |POLY 1.5 | P=0.535N P=0.510N P=0.507N P=0.494N |P=0.007 ** (e) (e) P=0.118 | |POLY 6 | P=0.504N P=0.534N P=0.533N P=0.490N |P=0.007 ** (e) (e) P=0.116 | |LOGISTIC REGRESSION| P=0.712N P=0.403N P=0.441N P=0.793N |P=0.010 * (e) (e) P=0.152 | |COCH-ARM / FISHERS | P=0.547N P=0.500N P=0.495N P=0.500N |P=0.008 ** (e) (e) P=0.117 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 0/49 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 8.9% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 636 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.158N P=0.175N P=0.176N P=0.105N |(e) (e) (e) (e) | |POLY 3 | P=0.154N P=0.132N P=0.131N P=0.108N |(e) (e) (e) (e) | |POLY 1.5 | P=0.167N P=0.126N P=0.123N P=0.112N |(e) (e) (e) (e) | |POLY 6 | P=0.133N P=0.147N P=0.147N P=0.106N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.166N P=0.145N P=0.143N P=0.106N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.187N P=0.121N P=0.117N P=0.121N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Degeneration Hyaline | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 43/49 (88%) 45/49 (92%) 46/50 (92%) 49/49 (100%)|44/50 (88%) 47/50 (94%) 48/50 (96%) 47/49 (96%) | |POLY-3 ADJUSTED (b)| 93.0% 94.8% 96.2% 100.0% |90.8% 99.5% 96.2% 97.9% | |TERMINAL (d) | 7/7 (100%) 5/5 (100%) 6/6 (100%) 8/8 (100%) |21/23 (91%) 19/19 (100%) 32/33 (97%) 22/22 (100%) | |FIRST INCIDENCE | 379 244 352 490 |390 440 399 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.338N P=0.125 P=0.141 P=0.450 |P=0.400 P=0.108 P=0.133N P=0.301 | |POLY 3 | P=0.033 * P=0.535 P=0.385 P=0.042 * |P=0.265 P=0.049 * P=0.240 P=0.128 | |POLY 1.5 | P=0.023 * P=0.449 P=0.366 P=0.024 * |P=0.197 P=0.055 P=0.192 P=0.096 | |POLY 6 | P=0.075 P=0.693 P=0.462 P=0.136 |P=0.336 P=0.059 P=0.294 P=0.174 | |LOGISTIC REGRESSION| P=0.026 * P=0.341 P=0.296 P=0.027 * |P=0.182 P=0.086 P=0.154 P=0.106 | |COCH-ARM / FISHERS | P=0.019 * P=0.370 P=0.357 P=0.013 * |P=0.201 P=0.243 P=0.134 P=0.141 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 0/49 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 11.9% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/7 (29%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 636 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.092N P=0.104N P=0.097N P=0.049N* |(e) (e) (e) (e) | |POLY 3 | P=0.087N P=0.069N P=0.068N P=0.052N |(e) (e) (e) (e) | |POLY 1.5 | P=0.098N P=0.065N P=0.063N P=0.055N |(e) (e) (e) (e) | |POLY 6 | P=0.071N P=0.078N P=0.078N P=0.049N* |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.098N P=0.087N P=0.083N P=0.051N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.117N P=0.059N P=0.056N P=0.059N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |9/50 (18%) 4/50 (8%) 4/50 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| |21.3% 10.8% 9.0% 5.0% | |TERMINAL (d) | |3/23 (13%) 2/19 (11%) 3/33 (9%) 1/22 (5%) | |FIRST INCIDENCE | |552 688 522 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.060N P=0.201N P=0.059N P=0.038N* | |POLY 3 | |P=0.051N P=0.170N P=0.092N P=0.029N* | |POLY 1.5 | |P=0.052N P=0.149N P=0.100N P=0.027N* | |POLY 6 | |P=0.053N P=0.202N P=0.087N P=0.034N* | |LOGISTIC REGRESSION| |P=0.057N P=0.134N P=0.141N P=0.025N* | |COCH-ARM / FISHERS | |P=0.057N P=0.117N P=0.117N P=0.026N* | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 22/50 (44%) 17/50 (34%) 26/50 (52%) 18/50 (36%) |9/50 (18%) 11/50 (22%) 17/49 (35%) 10/49 (20%) | |POLY-3 ADJUSTED (b)| 55.1% 47.7% 65.2% 44.7% |20.5% 28.8% 38.4% 23.9% | |TERMINAL (d) | 3/7 (43%) 3/5 (60%) 5/6 (83%) 2/8 (25%) |2/23 (9%) 5/19 (26%) 13/33 (39%) 3/22 (14%) | |FIRST INCIDENCE | 476 514 352 534 |440 534 534 500 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.147N P=0.561N P=0.143 P=0.254N |P=0.492N P=0.292 P=0.212 P=0.489 | |POLY 3 | P=0.174N P=0.327N P=0.225 P=0.223N |P=0.481N P=0.269 P=0.050 P=0.452 | |POLY 1.5 | P=0.227N P=0.271N P=0.248 P=0.240N |P=0.491N P=0.311 P=0.049 * P=0.459 | |POLY 6 | P=0.120N P=0.424N P=0.197 P=0.209N |P=0.487N P=0.225 P=0.052 P=0.435 | |LOGISTIC REGRESSION| P=0.211N P=0.275N P=0.231 P=0.221N |P=0.503N P=0.414 P=0.033 * P=0.505 | |COCH-ARM / FISHERS | P=0.320N P=0.206N P=0.274 P=0.270N |P=0.505N P=0.402 P=0.048 * P=0.480 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 2/50 (4%) |1/50 (2%) 4/50 (8%) 3/49 (6%) 2/49 (4%) | |POLY-3 ADJUSTED (b)| 3.0% 3.2% 3.2% 5.5% |2.5% 10.7% 6.9% 5.1% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 1/6 (17%) 1/8 (13%) |0/23 (0%) 2/19 (11%) 2/33 (6%) 2/22 (9%) | |FIRST INCIDENCE | 733 (T) 706 733 (T) 650 |488 534 706 733 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.450 P=0.660 P=0.735 P=0.554 |P=0.547N P=0.152 P=0.394 P=0.490 | |POLY 3 | P=0.412 P=0.745 P=0.744 P=0.526 |P=0.552N P=0.154 P=0.328 P=0.486 | |POLY 1.5 | P=0.394 P=0.751 P=0.752 P=0.516 |P=0.548N P=0.161 P=0.316 P=0.487 | |POLY 6 | P=0.435 P=0.734 P=0.732 P=0.537 |P=0.564N P=0.146 P=0.343 P=0.480 | |LOGISTIC REGRESSION| P=0.445 P=0.682 P=0.735 P=0.524 |P=0.537N P=0.187 P=0.273 P=0.496 | |COCH-ARM / FISHERS | P=0.368 P=0.753N P=0.753N P=0.500 |P=0.540N P=0.181 P=0.301 P=0.492 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 4/50 (8%) 3/50 (6%) |0/50 (0%) 1/50 (2%) 1/49 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 11.8% 9.5% 12.6% 8.1% |0.0% 2.7% 2.3% 0.0% | |TERMINAL (d) | 1/7 (14%) 1/5 (20%) 1/6 (17%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 1/33 (3%) 0/22 (0%) | |FIRST INCIDENCE | 666 583 500 534 |--- 719 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.384N P=0.652 P=0.523 P=0.461N |P=0.528N P=0.450 P=0.572 (e) | |POLY 3 | P=0.408N P=0.541N P=0.610 P=0.454N |P=0.531N P=0.484 P=0.516 (e) | |POLY 1.5 | P=0.443N P=0.523N P=0.626 P=0.472N |P=0.530N P=0.488 P=0.508 (e) | |POLY 6 | P=0.363N P=0.572N P=0.583 P=0.436N |P=0.536N P=0.477 P=0.525 (e) | |LOGISTIC REGRESSION| P=0.406N P=0.604N P=0.558 P=0.463N |P=0.531N P=0.472 P=0.572 (e) | |COCH-ARM / FISHERS | P=0.491N P=0.500N P=0.643N P=0.500N |P=0.527N P=0.500 P=0.495 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/49 (18%) 11/50 (22%) 12/49 (24%) 10/47 (21%) |0/48 (0%) 0/48 (0%) 0/49 (0%) 0/48 (0%) | |POLY-3 ADJUSTED (b)| 25.9% 33.5% 35.8% 28.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/7 (14%) 2/5 (40%) 1/5 (20%) 2/8 (25%) |0/21 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 539 624 480 647 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.342N P=0.173 P=0.176 P=0.552 |(e) (e) (e) (e) | |POLY 3 | P=0.492N P=0.335 P=0.261 P=0.522 |(e) (e) (e) (e) | |POLY 1.5 | P=0.540N P=0.372 P=0.284 P=0.498 |(e) (e) (e) (e) | |POLY 6 | P=0.437N P=0.281 P=0.227 P=0.546 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.404N P=0.262 P=0.219 P=0.558 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.522 P=0.421 P=0.312 P=0.459 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 5/49 (10%) 3/50 (6%) 6/49 (12%) |7/50 (14%) 7/49 (14%) 11/50 (22%) 5/49 (10%) | |POLY-3 ADJUSTED (b)| 13.9% 15.5% 9.4% 16.5% |16.4% 18.7% 24.6% 12.2% | |TERMINAL (d) | 1/7 (14%) 2/5 (40%) 0/6 (0%) 2/8 (25%) |2/23 (9%) 3/18 (17%) 8/33 (24%) 1/22 (5%) | |FIRST INCIDENCE | 379 523 520 604 |440 420 607 512 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.541 P=0.526 P=0.415N P=0.563 |P=0.264N P=0.500 P=0.427 P=0.385N | |POLY 3 | P=0.438 P=0.565 P=0.420N P=0.508 |P=0.253N P=0.510 P=0.244 P=0.408N | |POLY 1.5 | P=0.415 P=0.587 P=0.391N P=0.500 |P=0.261N P=0.538 P=0.234 P=0.406N | |POLY 6 | P=0.467 P=0.526 P=0.463N P=0.514 |P=0.252N P=0.474 P=0.258 P=0.417N | |LOGISTIC REGRESSION| P=0.380 P=0.617N P=0.315N P=0.443 |P=0.274N P=0.574N P=0.178 P=0.354N | |COCH-ARM / FISHERS | P=0.383 P=0.617 P=0.357N P=0.486 |P=0.271N P=0.597 P=0.218 P=0.394N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/49 (4%) 1/50 (2%) | | |POLY-3 ADJUSTED (b)| 5.8% 3.2% 6.5% 2.8% | | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 1/6 (17%) 0/8 (0%) | | |FIRST INCIDENCE | 539 624 620 667 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.409N P=0.547N P=0.615 P=0.473N | | |POLY 3 | P=0.441N P=0.534N P=0.656 P=0.484N | | |POLY 1.5 | P=0.459N P=0.519N P=0.670 P=0.489N | | |POLY 6 | P=0.421N P=0.559N P=0.633 P=0.483N | | |LOGISTIC REGRESSION| P=0.469N P=0.482N P=0.681 P=0.535N | | |COCH-ARM / FISHERS | P=0.486N P=0.500N P=0.684 P=0.500N | | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 0/49 (0%) 2/50 (4%) | | |POLY-3 ADJUSTED (b)| 8.7% 9.5% 0.0% 5.5% | | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) | | |FIRST INCIDENCE | 574 671 --- 667 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.414N P=0.518 P=0.182N P=0.493N | | |POLY 3 | P=0.434N P=0.622 P=0.139N P=0.478N | | |POLY 1.5 | P=0.452N P=0.639 P=0.131N P=0.485N | | |POLY 6 | P=0.412N P=0.593 P=0.155N P=0.475N | | |LOGISTIC REGRESSION| P=0.412N P=0.616 P=0.129N P=0.480N | | |COCH-ARM / FISHERS | P=0.476N P=0.661N P=0.125N P=0.500N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 6/49 (12%) 6/50 (12%) 7/50 (14%) | | |POLY-3 ADJUSTED (b)| 17.0% 18.6% 18.6% 18.6% | | |TERMINAL (d) | 2/7 (29%) 2/5 (40%) 2/6 (33%) 3/8 (38%) | | |FIRST INCIDENCE | 540 583 568 525 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.522N P=0.461 P=0.507 P=0.566 | | |POLY 3 | P=0.542 P=0.560 P=0.562 P=0.554 | | |POLY 1.5 | P=0.502 P=0.580 P=0.589 P=0.533 | | |POLY 6 | P=0.588N P=0.527 P=0.523 P=0.573 | | |LOGISTIC REGRESSION| P=0.530 P=0.565 P=0.564 P=0.515 | | |COCH-ARM / FISHERS | P=0.444 P=0.606 P=0.620N P=0.500 | | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 4/49 (8%) 4/50 (8%) 6/50 (12%) | | |POLY-3 ADJUSTED (b)| 11.5% 12.5% 12.2% 16.2% | | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 1/8 (13%) | | |FIRST INCIDENCE | 539 537 480 636 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.432 P=0.526 P=0.517 P=0.437 | | |POLY 3 | P=0.339 P=0.603 P=0.613 P=0.409 | | |POLY 1.5 | P=0.315 P=0.616 P=0.627 P=0.394 | | |POLY 6 | P=0.369 P=0.580 P=0.593 P=0.422 | | |LOGISTIC REGRESSION| P=0.314 P=0.616 P=0.641N P=0.407 | | |COCH-ARM / FISHERS | P=0.279 P=0.631 P=0.643N P=0.370 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Skin | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 5/50 (10%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 3.0% 0.0% 3.2% 13.6% |2.5% 0.0% 2.3% 5.1% | |TERMINAL (d) | 1/7 (14%) 0/5 (0%) 0/6 (0%) 2/8 (25%) |1/23 (4%) 0/19 (0%) 1/33 (3%) 0/22 (0%) | |FIRST INCIDENCE | 733 (T) --- 680 608 |733 (T) --- 733 (T) 681 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.021 * P=0.567N P=0.709 P=0.139 |P=0.216 P=0.538N P=0.679N P=0.471 | |POLY 3 | P=0.009 ** P=0.516N P=0.746 P=0.121 |P=0.249 P=0.517N P=0.738N P=0.498 | |POLY 1.5 | P=0.007 ** P=0.509N P=0.753 P=0.113 |P=0.246 P=0.512N P=0.747N P=0.497 | |POLY 6 | P=0.011 * P=0.528N P=0.736 P=0.131 |P=0.251 P=0.523N P=0.728N P=0.495 | |LOGISTIC REGRESSION| P=0.014 * (e) P=0.719 P=0.121 |P=0.232 (e) P=0.679N P=0.491 | |COCH-ARM / FISHERS | P=0.006 ** P=0.500N P=0.753N P=0.102 |P=0.238 P=0.500N P=0.753N P=0.500 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 6/49 (12%) 10/50 (20%) 11/50 (22%) |0/50 (0%) 3/50 (6%) 6/49 (12%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 25.5% 19.0% 30.0% 29.3% |0.0% 8.2% 13.7% 5.1% | |TERMINAL (d) | 3/7 (43%) 2/5 (40%) 3/6 (50%) 4/8 (50%) |0/23 (0%) 3/19 (16%) 4/33 (12%) 1/22 (5%) | |FIRST INCIDENCE | 580 660 520 611 |--- 733 (T) 607 657 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.442 P=0.505N P=0.340 P=0.496 |P=0.582 P=0.087 P=0.041 * P=0.235 | |POLY 3 | P=0.317 P=0.361N P=0.442 P=0.460 |P=0.607 P=0.103 P=0.020 * P=0.235 | |POLY 1.5 | P=0.277 P=0.333N P=0.469 P=0.438 |P=0.601 P=0.108 P=0.018 * P=0.235 | |POLY 6 | P=0.372 P=0.418N P=0.400 P=0.479 |P=0.607 P=0.097 P=0.024 * P=0.233 | |LOGISTIC REGRESSION| P=0.383 P=0.416N P=0.381 P=0.489 |P=0.593 P=0.087 P=0.021 * P=0.234 | |COCH-ARM / FISHERS | P=0.225 P=0.303N P=0.500 P=0.402 |P=0.592 P=0.121 P=0.012 * P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 5/49 (10%) 4/50 (8%) 3/50 (6%) |5/50 (10%) 2/50 (4%) 3/49 (6%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 5.8% 15.4% 12.1% 8.1% |11.8% 5.2% 6.9% 4.9% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 2/33 (6%) 0/22 (0%) | |FIRST INCIDENCE | 539 469 496 540 |488 216 706 407 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.412N P=0.170 P=0.297 P=0.546 |P=0.309N P=0.261N P=0.273N P=0.231N | |POLY 3 | P=0.463N P=0.185 P=0.310 P=0.531 |P=0.297N P=0.257N P=0.343N P=0.231N | |POLY 1.5 | P=0.486N P=0.195 P=0.322 P=0.519 |P=0.299N P=0.242N P=0.352N P=0.226N | |POLY 6 | P=0.436N P=0.167 P=0.293 P=0.544 |P=0.300N P=0.280N P=0.334N P=0.244N | |LOGISTIC REGRESSION| P=0.592 P=0.227 P=0.394 P=0.357 |P=0.287N P=0.095N P=0.473N P=0.157N | |COCH-ARM / FISHERS | P=0.521N P=0.210 P=0.339 P=0.500 |P=0.303N P=0.218N P=0.369N P=0.218N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.9% 3.2% 0.0% 2.8% |2.5% 0.0% 0.0% 4.9% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 590 716 --- 702 |720 --- --- 469 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.686 P=0.697 P=0.532N P=0.753 |P=0.180 P=0.560N P=0.454N P=0.499 | |POLY 3 | P=0.694 P=0.740 P=0.519N P=0.749N |P=0.186 P=0.517N P=0.485N P=0.507 | |POLY 1.5 | P=0.683 P=0.748 P=0.510N P=0.753N |P=0.183 P=0.512N P=0.492N P=0.503 | |POLY 6 | P=0.706 P=0.726 P=0.534N P=0.748N |P=0.187 P=0.524N P=0.476N P=0.507 | |LOGISTIC REGRESSION| P=0.700 P=0.745 P=0.486N P=0.759N |P=0.188 P=0.529N P=0.472N P=0.550 | |COCH-ARM / FISHERS | P=0.669 P=0.747 P=0.500N P=0.753N |P=0.176 P=0.500N P=0.505N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 6.3% 2.8% |2.5% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 627 631 |648 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.495 (e) P=0.186 P=0.532 |P=0.541N P=0.530N P=0.474N P=0.500N | |POLY 3 | P=0.465 (e) P=0.222 P=0.515 |P=0.544N P=0.518N P=0.486N P=0.504N | |POLY 1.5 | P=0.447 (e) P=0.229 P=0.509 |P=0.544N P=0.513N P=0.493N P=0.503N | |POLY 6 | P=0.488 (e) P=0.214 P=0.522 |P=0.543N P=0.526N P=0.478N P=0.509N | |LOGISTIC REGRESSION| P=0.433 (e) P=0.226 P=0.494 |P=0.546N P=0.499N P=0.530N P=0.498N | |COCH-ARM / FISHERS | P=0.421 (e) P=0.247 P=0.500 |P=0.546N P=0.500N P=0.505N P=0.500N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 16/50 (32%) 19/50 (38%) 10/50 (20%) |7/50 (14%) 7/50 (14%) 6/50 (12%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 42.8% 43.5% 50.2% 26.0% |16.6% 17.9% 13.0% 12.1% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 1/19 (5%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 379 469 480 604 |390 494 399 500 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.033N* P=0.424 P=0.259 P=0.091N |P=0.325N P=0.511 P=0.398N P=0.400N | |POLY 3 | P=0.032N* P=0.571 P=0.326 P=0.084N |P=0.317N P=0.558 P=0.426N P=0.387N | |POLY 1.5 | P=0.038N* P=0.574N P=0.362 P=0.084N |P=0.318N P=0.570 P=0.455N P=0.388N | |POLY 6 | P=0.031N* P=0.528 P=0.294 P=0.092N |P=0.324N P=0.543 P=0.396N P=0.393N | |LOGISTIC REGRESSION| P=0.049N* P=0.497N P=0.423 P=0.099N |P=0.312N P=0.572N P=0.548 P=0.345N | |COCH-ARM / FISHERS | P=0.053N P=0.500N P=0.418 P=0.088N |P=0.316N P=0.613N P=0.500N P=0.380N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/49 (6%) 5/50 (10%) 4/50 (8%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 8.7% 9.6% 15.4% 11.0% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/7 (0%) 1/5 (20%) 0/6 (0%) 1/8 (13%) |0/23 (0%) 0/19 (0%) 1/33 (3%) 0/22 (0%) | |FIRST INCIDENCE | 539 664 480 688 |--- --- 733 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.590 P=0.528 P=0.263 P=0.532 |P=0.786N (e) P=0.572 (e) | |POLY 3 | P=0.534 P=0.618 P=0.318 P=0.528 |P=0.770N (e) P=0.520 (e) | |POLY 1.5 | P=0.507 P=0.634 P=0.336 P=0.518 |P=0.772N (e) P=0.512 (e) | |POLY 6 | P=0.562 P=0.589 P=0.294 P=0.534 |P=0.770N (e) P=0.529 (e) | |LOGISTIC REGRESSION| P=0.553 P=0.613 P=0.337 P=0.542 |(e) (e) P=0.572 (e) | |COCH-ARM / FISHERS | P=0.468 P=0.651 P=0.357 P=0.500 |P=0.776N (e) P=0.500 (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 5/49 (10%) 11/50 (22%) 9/50 (18%) |3/50 (6%) 2/50 (4%) 1/50 (2%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 22.0% 15.1% 31.1% 23.8% |7.5% 5.4% 2.3% 2.5% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 1/8 (13%) |0/23 (0%) 1/19 (5%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 516 523 516 604 |663 494 626 630 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.528 P=0.416N P=0.191 P=0.552 |P=0.291N P=0.586N P=0.247N P=0.324N | |POLY 3 | P=0.425 P=0.328N P=0.268 P=0.538 |P=0.305N P=0.534N P=0.270N P=0.312N | |POLY 1.5 | P=0.395 P=0.311N P=0.283 P=0.525 |P=0.305N P=0.524N P=0.284N P=0.314N | |POLY 6 | P=0.459 P=0.365N P=0.256 P=0.545 |P=0.309N P=0.549N P=0.256N P=0.316N | |LOGISTIC REGRESSION| P=0.349 P=0.271N P=0.311 P=0.531 |P=0.307N P=0.514N P=0.301N P=0.314N | |COCH-ARM / FISHERS | P=0.349 P=0.290N P=0.306 P=0.500 |P=0.306N P=0.500N P=0.309N P=0.316N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Testes | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 0/50 (0%) 3/50 (6%) 5/50 (10%) | | |POLY-3 ADJUSTED (b)| 19.5% 0.0% 9.4% 13.5% | | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 1/6 (17%) 1/8 (13%) | | |FIRST INCIDENCE | 552 --- 590 490 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.494 P=0.024N* P=0.259N P=0.365N | | |POLY 3 | P=0.487 P=0.012N* P=0.202N P=0.350N | | |POLY 1.5 | P=0.440 P=0.010N* P=0.180N P=0.358N | | |POLY 6 | P=0.550 P=0.017N* P=0.246N P=0.357N | | |LOGISTIC REGRESSION| P=0.425 P=0.010N* P=0.175N P=0.372N | | |COCH-ARM / FISHERS | P=0.380 P=0.006N** P=0.159N P=0.380N | | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Testes | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 1/50 (2%) | | |POLY-3 ADJUSTED (b)| 0.0% 9.3% 0.0% 2.8% | | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 1/8 (13%) | | |FIRST INCIDENCE | --- 537 --- 733 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.564N P=0.097 (e) P=0.527 | | |POLY 3 | P=0.605N P=0.109 (e) P=0.513 | | |POLY 1.5 | P=0.614N P=0.113 (e) P=0.508 | | |POLY 6 | P=0.595N P=0.103 (e) P=0.518 | | |LOGISTIC REGRESSION| P=0.612N P=0.126 (e) P=0.527 | | |COCH-ARM / FISHERS | P=0.624N P=0.121 (e) P=0.500 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Testes: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 1/50 (2%) 3/50 (6%) | | |POLY-3 ADJUSTED (b)| 11.7% 6.3% 3.2% 8.1% | | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 1/6 (17%) 0/8 (0%) | | |FIRST INCIDENCE | 648 583 733 (T) 583 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.536N P=0.459N P=0.251N P=0.467N | | |POLY 3 | P=0.584N P=0.372N P=0.207N P=0.458N | | |POLY 1.5 | P=0.612N P=0.357N P=0.193N P=0.474N | | |POLY 6 | P=0.544N P=0.401N P=0.236N P=0.444N | | |LOGISTIC REGRESSION| P=0.595N P=0.382N P=0.230N P=0.483N | | |COCH-ARM / FISHERS | P=0.591 P=0.339N P=0.181N P=0.500N | | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) 4/50 (8%) 2/50 (4%) | | |POLY-3 ADJUSTED (b)| 11.5% 12.4% 12.0% 5.5% | | |TERMINAL (d) | 1/7 (14%) 1/5 (20%) 0/6 (0%) 0/8 (0%) | | |FIRST INCIDENCE | 560 469 352 607 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.180N P=0.554 P=0.553 P=0.273N | | |POLY 3 | P=0.204N P=0.605 P=0.620 P=0.312N | | |POLY 1.5 | P=0.223N P=0.622 P=0.632 P=0.321N | | |POLY 6 | P=0.185N P=0.575 P=0.600 P=0.307N | | |LOGISTIC REGRESSION| P=0.312N P=0.642 P=0.594N P=0.356N | | |COCH-ARM / FISHERS | P=0.250N P=0.643N P=0.643N P=0.339N | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 32/48 (67%) 36/48 (75%) 34/48 (71%) 26/50 (52%) |37/50 (74%) 34/50 (68%) 38/49 (78%) 35/49 (71%) | |POLY-3 ADJUSTED (b)| 73.6% 86.3% 77.1% 59.9% |77.3% 74.4% 81.1% 79.2% | |TERMINAL (d) | 3/7 (43%) 5/5 (100%) 2/6 (33%) 3/8 (38%) |17/23 (74%) 12/19 (63%) 27/33 (82%) 17/22 (77%) | |FIRST INCIDENCE | 476 460 352 490 |390 420 399 512 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.027N* P=0.096 P=0.209 P=0.161N |P=0.513N P=0.438 P=0.106N P=0.523N | |POLY 3 | P=0.007N** P=0.090 P=0.443 P=0.111N |P=0.424 P=0.467N P=0.416 P=0.512 | |POLY 1.5 | P=0.008N** P=0.138 P=0.431 P=0.101N |P=0.477 P=0.443N P=0.428 P=0.565 | |POLY 6 | P=0.009N** P=0.052 P=0.470 P=0.141N |P=0.371 P=0.497N P=0.391 P=0.454 | |LOGISTIC REGRESSION| P=0.015N* P=0.191 P=0.495 P=0.112N |P=0.517N P=0.352N P=0.449 P=0.492N | |COCH-ARM / FISHERS | P=0.015N* P=0.250 P=0.413 P=0.102N |P=0.529N P=0.330N P=0.430 P=0.475N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 0/48 (0%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 6.6% 0.0% 2.8% |0.0% 5.4% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 1/19 (5%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 684 --- 631 |--- 718 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.689N P=0.191 (e) P=0.532 |P=0.393N P=0.197 (e) (e) | |POLY 3 | P=0.661 P=0.218 (e) P=0.520 |P=0.417N P=0.219 (e) (e) | |POLY 1.5 | P=0.654 P=0.226 (e) P=0.515 |P=0.410N P=0.224 (e) (e) | |POLY 6 | P=0.668 P=0.207 (e) P=0.524 |P=0.429N P=0.212 (e) (e) | |LOGISTIC REGRESSION| P=0.671 P=0.194 (e) P=0.502 |P=0.394N P=0.201 (e) (e) | |COCH-ARM / FISHERS | P=0.644 P=0.247 (e) P=0.510 |P=0.394N P=0.247 (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Tooth | | Developmental Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/2 (100%) 1/3 (33%) 0/1 (0%) 1/1 (100%) |0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) | |POLY-3 ADJUSTED (b)| 100.0% 46.8% 0.0% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 560 244 --- 702 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.190N P=0.549N P=0.324N (e) |(e) (e) (e) (e) | |POLY 3 | P=0.791 P=0.448N P=1.000N (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.708 P=0.354N P=1.000N (e) |(e) (e) (e) (e) | |POLY 6 | P=0.907 P=0.655N P=1.000N (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.648 P=0.172N (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.620 P=0.300N P=0.333N (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Tooth | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/2 (0%) 2/3 (67%) 1/1 (100%) 0/1 (0%) |0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 98.2% 100.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 537 352 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.358N P=0.194 P=0.486 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.424N P=0.168 P=0.346 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.559N P=0.147 P=0.002 ** (e) |(e) (e) (e) (e) | |POLY 6 | P=0.260N P=0.561 P=0.889 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.648N P=0.172 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.620N P=0.300 P=0.333 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Trachea | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 5.9% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 636 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.274N P=0.291N P=0.314N P=0.217N |(e) (e) (e) (e) | |POLY 3 | P=0.275N P=0.258N P=0.258N P=0.225N |(e) (e) (e) (e) | |POLY 1.5 | P=0.289N P=0.249N P=0.248N P=0.229N |(e) (e) (e) (e) | |POLY 6 | P=0.252N P=0.276N P=0.276N P=0.224N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.292N P=0.253N P=0.253N P=0.229N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.308N P=0.247N P=0.247N P=0.247N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 03 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER344) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/49 (2%) 3/50 (6%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 3.2% 9.3% 5.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 604 480 604 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.419 P=0.488 P=0.098 P=0.288 |(e) (e) (e) (e) | |POLY 3 | P=0.368 P=0.486 P=0.110 P=0.256 |(e) (e) (e) (e) | |POLY 1.5 | P=0.346 P=0.490 P=0.114 P=0.248 |(e) (e) (e) (e) | |POLY 6 | P=0.396 P=0.478 P=0.104 P=0.265 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.272 P=0.503 P=0.133 P=0.223 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.316 P=0.495 P=0.121 P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/49 (2%) 1/50 (2%) 3/50 (6%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 3.0% 3.2% 3.2% 8.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/7 (0%) 0/5 (0%) 0/6 (0%) 0/8 (0%) |0/23 (0%) 0/19 (0%) 0/33 (0%) 0/22 (0%) | |FIRST INCIDENCE | 719 641 614 604 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.239 P=0.670 P=0.680 P=0.337 |(e) (e) (e) (e) | |POLY 3 | P=0.192 P=0.745 P=0.747 P=0.336 |(e) (e) (e) (e) | |POLY 1.5 | P=0.178 P=0.750 P=0.753 P=0.323 |(e) (e) (e) (e) | |POLY 6 | P=0.212 P=0.737 P=0.738 P=0.352 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.190 P=0.727 P=0.738 P=0.329 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.159 P=0.747 P=0.753N P=0.309 |(e) (e) (e) (e) | |=================================================================================================================================| (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).