TDMS Study 88070-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Northwest ISOBUTENE DATE: 06/20/97 EXPERIMENT: 88070 TEST: 04 TIME: 10:04:20 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-15313 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: C88070 PATHOLOGIST: MILLER, R. CAS: 115-11-0007 Mice(B6C3F1) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS, RATES ARE BASED ON 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: 04 TIME: 10:04:20 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-15313 ROUTE: RESPIRATORY EXPOSURE WHOLE BODY NTP C#: C88070 PATHOLOGIST: MILLER, R. CAS: 115-11-0007 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ISOBUTENE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Hypertrophy Epididymis Granuloma Sperm Liver Degeneration Fatty Necrosis Lymph Node: Iliac Infiltration Cellular Plasma Cell Nose: Olfactory Epithelium Degeneration Hyaline Nose: Respiratory Epithelium Degeneration Hyaline =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Eosinophilic Focus Liver: Centrilobular Necrosis Mesentery: Fat Necrosis Nose: Olfactory Epithelium Degeneration Hyaline Nose: Respiratory Epithelium Degeneration Hyaline Ovary Angiectasis Spleen Hematopoietic Cell Proliferation Thyroid Gland: Follicular Cell Hyperplasia =============================================================== Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/49 (29%) 10/49 (20%) 15/50 (30%) 16/49 (33%) |3/49 (6%) 4/50 (8%) 3/49 (6%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 33.3% 23.0% 36.5% 40.6% |7.1% 9.2% 6.6% 10.9% | |TERMINAL (d) | 9/28 (32%) 8/32 (25%) 10/27 (37%) 13/28 (46%) |3/32 (9%) 3/31 (10%) 2/39 (5%) 5/33 (15%) | |FIRST INCIDENCE | 527 546 428 547 |735 (T) 639 686 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.166 P=0.161N P=0.453 P=0.399 |P=0.334 P=0.487 P=0.572N P=0.371 | |POLY 3 | P=0.128 P=0.205N P=0.468 P=0.323 |P=0.352 P=0.516 P=0.630N P=0.398 | |POLY 1.5 | P=0.152 P=0.217N P=0.493 P=0.349 |P=0.344 P=0.517 P=0.642N P=0.389 | |POLY 6 | P=0.113 P=0.195N P=0.438 P=0.305 |P=0.358 P=0.509 P=0.616N P=0.404 | |LOGISTIC REGRESSION| P=0.141 P=0.206N P=0.462 P=0.332 |P=0.366 P=0.500 P=0.618N P=0.371 | |COCH-ARM / FISHERS | P=0.215 P=0.241N P=0.526 P=0.413 |P=0.326 P=0.511 P=0.661N P=0.369 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 32/49 (65%) 24/49 (49%) 24/50 (48%) 29/49 (59%) |3/49 (6%) 1/50 (2%) 4/49 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 73.3% 53.8% 57.7% 70.4% |7.1% 2.3% 8.8% 4.3% | |TERMINAL (d) | 22/28 (79%) 19/32 (59%) 19/27 (70%) 22/28 (79%) |3/32 (9%) 0/31 (0%) 4/39 (10%) 0/33 (0%) | |FIRST INCIDENCE | 387 512 389 341 |735 (T) 594 735 (T) 672 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.306 P=0.027N* P=0.130N P=0.385N |P=0.529N P=0.311N P=0.608 P=0.471N | |POLY 3 | P=0.267 P=0.038N* P=0.083N P=0.477N |P=0.514N P=0.293N P=0.536 P=0.463N | |POLY 1.5 | P=0.319 P=0.049N* P=0.070N P=0.432N |P=0.526N P=0.293N P=0.523 P=0.472N | |POLY 6 | P=0.233 P=0.031N* P=0.110N P=0.515N |P=0.501N P=0.297N P=0.549 P=0.454N | |LOGISTIC REGRESSION| P=0.262 P=0.043N* P=0.091N P=0.479N |P=0.526N P=0.296N P=0.608 P=0.466N | |COCH-ARM / FISHERS | P=0.442 P=0.076N P=0.062N P=0.339N |P=0.544N P=0.301N P=0.500 P=0.490N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 0/49 (0%) 0/49 (0%) 0/50 (0%) 0/49 (0%) |1/49 (2%) 2/50 (4%) 1/49 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.4% 4.6% 2.2% 4.4% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 0/28 (0%) |1/32 (3%) 2/31 (7%) 1/39 (3%) 1/33 (3%) | |FIRST INCIDENCE | --- --- --- --- |735 (T) 735 (T) 735 (T) 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.504 P=0.489 P=0.717N P=0.522 | |POLY 3 | (e) (e) (e) (e) |P=0.513 P=0.507 P=0.746N P=0.527 | |POLY 1.5 | (e) (e) (e) (e) |P=0.506 P=0.510 P=0.751N P=0.521 | |POLY 6 | (e) (e) (e) (e) |P=0.519 P=0.501 P=0.740N P=0.532 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.521 P=0.489 P=0.717N P=0.530 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.492 P=0.508 P=0.753N P=0.508 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/49 (0%) 1/50 (2%) 1/49 (2%) |0/48 (0%) 3/49 (6%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.5% 2.6% |0.0% 6.9% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 0/28 (0%) |0/32 (0%) 2/31 (7%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- --- 555 562 |--- 639 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.322 (e) P=0.486 P=0.481 |P=0.260N P=0.120 (e) (e) | |POLY 3 | P=0.326 (e) P=0.496 P=0.491 |P=0.255N P=0.126 (e) (e) | |POLY 1.5 | P=0.332 (e) P=0.499 P=0.493 |P=0.257N P=0.126 (e) (e) | |POLY 6 | P=0.324 (e) P=0.494 P=0.492 |P=0.257N P=0.124 (e) (e) | |LOGISTIC REGRESSION| P=0.450 (e) P=0.531 P=0.553 |P=0.266N P=0.126 (e) (e) | |COCH-ARM / FISHERS | P=0.347 (e) P=0.505 P=0.500 |P=0.267N P=0.125 (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Epididymis | | Granuloma Sperm | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 5/50 (10%) | | |POLY-3 ADJUSTED (b)| 0.0% 2.3% 2.5% 12.5% | | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/27 (4%) 3/28 (11%) | | |FIRST INCIDENCE | --- 562 733 (T) 631 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.005 ** P=0.509 P=0.493 P=0.035 * | | |POLY 3 | P=0.004 ** P=0.513 P=0.491 P=0.027 * | | |POLY 1.5 | P=0.004 ** P=0.508 P=0.495 P=0.028 * | | |POLY 6 | P=0.004 ** P=0.518 P=0.488 P=0.028 * | | |LOGISTIC REGRESSION| P=0.005 ** P=0.429 P=0.493 P=0.029 * | | |COCH-ARM / FISHERS | P=0.005 ** P=0.500 P=0.500 P=0.028 * | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 21/50 (42%) 18/50 (36%) 16/50 (32%) 19/50 (38%) |10/50 (20%) 10/50 (20%) 12/50 (24%) 8/50 (16%) | |POLY-3 ADJUSTED (b)| 48.4% 40.7% 38.4% 44.2% |23.2% 22.4% 25.8% 17.3% | |TERMINAL (d) | 14/28 (50%) 13/32 (41%) 10/27 (37%) 12/28 (43%) |7/32 (22%) 6/31 (19%) 10/39 (26%) 5/33 (15%) | |FIRST INCIDENCE | 399 639 428 330 |639 567 509 653 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.477 P=0.201N P=0.266N P=0.447N |P=0.279N P=0.577 P=0.583 P=0.359N | |POLY 3 | P=0.556N P=0.300N P=0.232N P=0.426N |P=0.259N P=0.566N P=0.482 P=0.336N | |POLY 1.5 | P=0.553 P=0.315N P=0.220N P=0.436N |P=0.274N P=0.568N P=0.460 P=0.351N | |POLY 6 | P=0.533N P=0.285N P=0.248N P=0.401N |P=0.249N P=0.578N P=0.498 P=0.330N | |LOGISTIC REGRESSION| P=0.492 P=0.257N P=0.238N P=0.463N |P=0.266N P=0.580N P=0.472 P=0.330N | |COCH-ARM / FISHERS | P=0.532N P=0.341N P=0.204N P=0.419N |P=0.309N P=0.598N P=0.405 P=0.398N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/48 (0%) 1/50 (2%) 1/48 (2%) |1/47 (2%) 0/49 (0%) 1/48 (2%) 3/49 (6%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 2.5% 2.6% |2.3% 0.0% 2.2% 6.6% | |TERMINAL (d) | 1/28 (4%) 0/32 (0%) 1/27 (4%) 1/28 (4%) |0/32 (0%) 0/31 (0%) 1/39 (3%) 2/33 (6%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) 733 (T) |610 --- 735 (T) 596 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.549 P=0.473N P=0.754 P=0.762 |P=0.085 P=0.491N P=0.731N P=0.325 | |POLY 3 | P=0.530 P=0.494N P=0.751 P=0.745 |P=0.093 P=0.500N P=0.751N P=0.331 | |POLY 1.5 | P=0.537 P=0.499N P=0.755 P=0.746 |P=0.089 P=0.496N P=0.753N P=0.327 | |POLY 6 | P=0.524 P=0.489N P=0.747 P=0.746 |P=0.097 P=0.505N P=0.748N P=0.335 | |LOGISTIC REGRESSION| P=0.549 (e) P=0.754 P=0.762 |P=0.067 P=0.476N P=0.755 P=0.262 | |COCH-ARM / FISHERS | P=0.557 P=0.510N P=0.753N P=0.742 |P=0.084 P=0.490N P=0.747N P=0.324 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/49 (4%) 4/50 (8%) 0/50 (0%) |1/49 (2%) 2/50 (4%) 1/49 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 4.7% 9.9% 0.0% |2.3% 4.6% 2.2% 0.0% | |TERMINAL (d) | 1/28 (4%) 2/32 (6%) 1/27 (4%) 0/28 (0%) |0/32 (0%) 1/31 (3%) 1/39 (3%) 0/33 (0%) | |FIRST INCIDENCE | 733 (T) 733 (T) 499 --- |653 639 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.245N P=0.547 P=0.170 P=0.500N |P=0.225N P=0.493 P=0.730N P=0.481N | |POLY 3 | P=0.245N P=0.511 P=0.172 P=0.510N |P=0.228N P=0.509 P=0.747N P=0.486N | |POLY 1.5 | P=0.238N P=0.504 P=0.175 P=0.507N |P=0.230N P=0.511 P=0.751N P=0.488N | |POLY 6 | P=0.249N P=0.519 P=0.171 P=0.510N |P=0.228N P=0.501 P=0.743N P=0.485N | |LOGISTIC REGRESSION| P=0.226N P=0.547 P=0.181 (e) |P=0.242N P=0.498 P=0.761 P=0.534N | |COCH-ARM / FISHERS | P=0.219N P=0.492 P=0.181 P=0.500N |P=0.236N P=0.508 P=0.753N P=0.495N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/49 (0%) 0/50 (0%) 2/50 (4%) |1/49 (2%) 1/50 (2%) 2/49 (4%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 0.0% 0.0% 5.1% |2.4% 2.3% 4.4% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 2/28 (7%) |1/32 (3%) 1/31 (3%) 2/39 (5%) 0/33 (0%) | |FIRST INCIDENCE | 653 --- --- 733 (T) |735 (T) 735 (T) 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.164 P=0.495N P=0.528N P=0.490 |P=0.309N P=0.755 P=0.569 P=0.494N | |POLY 3 | P=0.163 P=0.495N P=0.510N P=0.481 |P=0.298N P=0.756N P=0.524 P=0.485N | |POLY 1.5 | P=0.167 P=0.498N P=0.506N P=0.486 |P=0.303N P=0.753N P=0.516 P=0.487N | |POLY 6 | P=0.160 P=0.492N P=0.515N P=0.478 |P=0.293N P=0.760N P=0.532 P=0.483N | |LOGISTIC REGRESSION| P=0.163 P=0.519N P=0.496N P=0.484 |P=0.309N P=0.755 P=0.569 (e) | |COCH-ARM / FISHERS | P=0.177 P=0.505N P=0.500N P=0.500 |P=0.314N P=0.747N P=0.500 P=0.495N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 36/50 (72%) 39/49 (80%) 38/50 (76%) 40/50 (80%) |13/49 (27%) 14/50 (28%) 18/49 (37%) 12/50 (24%) | |POLY-3 ADJUSTED (b)| 80.4% 86.1% 84.5% 87.6% |29.5% 30.6% 38.9% 25.0% | |TERMINAL (d) | 24/28 (86%) 31/32 (97%) 26/27 (96%) 27/28 (96%) |7/32 (22%) 7/31 (23%) 15/39 (39%) 7/33 (21%) | |FIRST INCIDENCE | 560 546 428 330 |608 567 600 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.157 P=0.469N P=0.305 P=0.251 |P=0.312N P=0.476 P=0.385 P=0.440N | |POLY 3 | P=0.288 P=0.312 P=0.397 P=0.237 |P=0.260N P=0.548 P=0.237 P=0.402N | |POLY 1.5 | P=0.274 P=0.295 P=0.405 P=0.221 |P=0.283N P=0.550 P=0.226 P=0.421N | |POLY 6 | P=0.318 P=0.322 P=0.378 P=0.260 |P=0.244N P=0.535 P=0.243 P=0.393N | |LOGISTIC REGRESSION| P=0.108 P=0.408 P=0.273 P=0.118 |P=0.349N P=0.526 P=0.229 P=0.513N | |COCH-ARM / FISHERS | P=0.313 P=0.259 P=0.410 P=0.241 |P=0.337N P=0.525 P=0.193 P=0.477N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Papilla | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/49 (6%) 6/50 (12%) 5/50 (10%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.0% 7.0% 14.4% 12.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 1/32 (3%) 0/27 (0%) 0/28 (0%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 399 639 512 251 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.288 P=0.627N P=0.227 P=0.343 |(e) (e) (e) (e) | |POLY 3 | P=0.289 P=0.659N P=0.226 P=0.335 |(e) (e) (e) (e) | |POLY 1.5 | P=0.299 P=0.661 P=0.231 P=0.340 |(e) (e) (e) (e) | |POLY 6 | P=0.286 P=0.653N P=0.225 P=0.336 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.455 P=0.577 P=0.281 P=0.467 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.326 P=0.651 P=0.243 P=0.357 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/49 (4%) 4/50 (8%) 4/50 (8%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 7.1% 4.6% 9.8% 9.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/27 (4%) 0/28 (0%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 387 512 499 457 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.316 P=0.457N P=0.474 P=0.466 |(e) (e) (e) (e) | |POLY 3 | P=0.337 P=0.489N P=0.483 P=0.484 |(e) (e) (e) (e) | |POLY 1.5 | P=0.344 P=0.497N P=0.489 P=0.485 |(e) (e) (e) (e) | |POLY 6 | P=0.338 P=0.479N P=0.481 P=0.491 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.508 P=0.603N P=0.545 P=0.584 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.369 P=0.510N P=0.500 P=0.500 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 8/50 (16%) 6/50 (12%) 5/49 (10%) |4/47 (9%) 4/50 (8%) 2/50 (4%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 16.3% 17.8% 14.7% 12.6% |9.3% 9.2% 4.4% 10.9% | |TERMINAL (d) | 4/28 (14%) 4/32 (13%) 4/27 (15%) 2/28 (7%) |3/32 (9%) 3/31 (10%) 1/39 (3%) 4/33 (12%) | |FIRST INCIDENCE | 387 546 387 508 |449 639 692 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.326N P=0.580 P=0.523N P=0.407N |P=0.405 P=0.635 P=0.268N P=0.528 | |POLY 3 | P=0.341N P=0.539 P=0.539N P=0.437N |P=0.412 P=0.635N P=0.307N P=0.541 | |POLY 1.5 | P=0.327N P=0.521 P=0.524N P=0.429N |P=0.407 P=0.624N P=0.310N P=0.539 | |POLY 6 | P=0.343N P=0.565 P=0.552N P=0.432N |P=0.417 P=0.641 P=0.301N P=0.543 | |LOGISTIC REGRESSION| P=0.242N P=0.438 P=0.465N P=0.364N |P=0.399 P=0.595N P=0.317N P=0.529 | |COCH-ARM / FISHERS | P=0.286N P=0.500 P=0.500N P=0.394N |P=0.400 P=0.607N P=0.310N P=0.540 | |=================================================================================================================================| | | | | | | 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) | 9/50 (18%) 4/50 (8%) 6/50 (12%) 10/49 (20%) |0/47 (0%) 4/50 (8%) 3/50 (6%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 21.8% 9.1% 15.2% 25.5% |0.0% 9.1% 6.6% 8.6% | |TERMINAL (d) | 9/28 (32%) 3/32 (9%) 6/27 (22%) 9/28 (32%) |0/32 (0%) 3/31 (10%) 3/39 (8%) 1/33 (3%) | |FIRST INCIDENCE | 733 (T) 649 733 (T) 508 |--- 594 735 (T) 596 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.132 P=0.070N P=0.302N P=0.498 |P=0.230 P=0.063 P=0.158 P=0.075 | |POLY 3 | P=0.121 P=0.091N P=0.316N P=0.448 |P=0.245 P=0.065 P=0.133 P=0.073 | |POLY 1.5 | P=0.132 P=0.100N P=0.305N P=0.452 |P=0.238 P=0.066 P=0.132 P=0.071 | |POLY 6 | P=0.116 P=0.081N P=0.327N P=0.456 |P=0.255 P=0.062 P=0.136 P=0.076 | |LOGISTIC REGRESSION| P=0.115 P=0.080N P=0.302N P=0.436 |P=0.224 P=0.070 P=0.158 P=0.059 | |COCH-ARM / FISHERS | P=0.161 P=0.117N P=0.288N P=0.480 |P=0.228 P=0.066 P=0.133 P=0.066 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 Fatty | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 5/49 (10%) |2/47 (4%) 1/50 (2%) 5/50 (10%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 2.3% 5.0% 12.2% |4.7% 2.3% 10.6% 2.2% | |TERMINAL (d) | 1/28 (4%) 1/32 (3%) 1/27 (4%) 1/28 (4%) |1/32 (3%) 0/31 (0%) 2/39 (5%) 0/33 (0%) | |FIRST INCIDENCE | 733 (T) 733 (T) 389 341 |621 639 543 596 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.024 * P=0.732N P=0.492 P=0.102 |P=0.390N P=0.501N P=0.273 P=0.481N | |POLY 3 | P=0.024 * P=0.749N P=0.492 P=0.098 |P=0.372N P=0.491N P=0.259 P=0.472N | |POLY 1.5 | P=0.024 * P=0.753N P=0.496 P=0.096 |P=0.381N P=0.485N P=0.251 P=0.474N | |POLY 6 | P=0.025 * P=0.745N P=0.488 P=0.103 |P=0.361N P=0.500N P=0.271 P=0.470N | |LOGISTIC REGRESSION| P=0.052 P=0.732N P=0.523 P=0.134 |P=0.479N P=0.457N P=0.223 P=0.536N | |COCH-ARM / FISHERS | P=0.026 * P=0.753N P=0.500 P=0.098 |P=0.395N P=0.477N P=0.244 P=0.477N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 11/50 (22%) 7/49 (14%) |17/47 (36%) 11/50 (22%) 12/50 (24%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 12.0% 9.2% 27.6% 18.2% |39.5% 25.1% 25.6% 15.2% | |TERMINAL (d) | 4/28 (14%) 3/32 (9%) 10/27 (37%) 7/28 (25%) |13/32 (41%) 8/31 (26%) 8/39 (21%) 6/33 (18%) | |FIRST INCIDENCE | 611 715 583 733 (T) |653 639 477 596 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.294 P=0.422N P=0.068 P=0.374 |P=0.029N* P=0.161N P=0.087N P=0.014N* | |POLY 3 | P=0.248 P=0.473N P=0.065 P=0.322 |P=0.019N* P=0.110N P=0.116N P=0.007N** | |POLY 1.5 | P=0.270 P=0.482N P=0.073 P=0.334 |P=0.022N* P=0.101N P=0.125N P=0.008N** | |POLY 6 | P=0.234 P=0.463N P=0.058 P=0.316 |P=0.017N* P=0.126N P=0.106N P=0.007N** | |LOGISTIC REGRESSION| P=0.265 P=0.455N P=0.062 P=0.333 |P=0.022N* P=0.123N P=0.131N P=0.009N** | |COCH-ARM / FISHERS | P=0.327 P=0.500N P=0.086 P=0.365 |P=0.027N* P=0.094N P=0.139N P=0.010N* | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 0/49 (0%) |0/47 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 0.0% 4.6% 2.5% 0.0% |0.0% 0.0% 0.0% 2.2% | |TERMINAL (d) | 0/28 (0%) 2/32 (6%) 1/27 (4%) 0/28 (0%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 1/33 (3%) | |FIRST INCIDENCE | --- 733 (T) 733 (T) --- |--- --- --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.380N P=0.268 P=0.493 (e) |P=0.227 (e) (e) P=0.506 | |POLY 3 | P=0.381N P=0.249 P=0.491 (e) |P=0.238 (e) (e) P=0.516 | |POLY 1.5 | P=0.379N P=0.244 P=0.495 (e) |P=0.236 (e) (e) P=0.515 | |POLY 6 | P=0.379N P=0.253 P=0.488 (e) |P=0.241 (e) (e) P=0.517 | |LOGISTIC REGRESSION| (e) P=0.268 P=0.493 (e) |(e) (e) (e) P=0.506 | |COCH-ARM / FISHERS | P=0.371N P=0.247 P=0.500 (e) |P=0.232 (e) (e) P=0.515 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 5/50 (10%) 2/50 (4%) 1/49 (2%) |0/47 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 2.4% 11.0% 5.0% 2.6% |0.0% 4.6% 6.4% 2.2% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/27 (4%) 0/28 (0%) |0/32 (0%) 1/31 (3%) 1/39 (3%) 1/33 (3%) | |FIRST INCIDENCE | 399 522 527 508 |--- 727 509 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.293N P=0.124 P=0.486 P=0.748 |P=0.604N P=0.240 P=0.144 P=0.506 | |POLY 3 | P=0.282N P=0.121 P=0.483 P=0.745 |P=0.592N P=0.243 P=0.138 P=0.516 | |POLY 1.5 | P=0.278N P=0.113 P=0.489 P=0.747 |P=0.596N P=0.247 P=0.135 P=0.515 | |POLY 6 | P=0.281N P=0.132 P=0.478 P=0.746 |P=0.587N P=0.238 P=0.143 P=0.517 | |LOGISTIC REGRESSION| P=0.133N P=0.032 * P=0.547 P=0.631N |P=0.641N P=0.231 P=0.113 P=0.506 | |COCH-ARM / FISHERS | P=0.264N P=0.102 P=0.500 P=0.747 |P=0.603N P=0.263 P=0.133 P=0.515 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Tension Lipidosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |1/47 (2%) 3/50 (6%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |2.4% 6.8% 2.2% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 0/28 (0%) |1/32 (3%) 0/31 (0%) 1/39 (3%) 0/33 (0%) | |FIRST INCIDENCE | --- --- --- --- |735 (T) 594 735 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.166N P=0.305 P=0.717N P=0.494N | |POLY 3 | (e) (e) (e) (e) |P=0.163N P=0.321 P=0.743N P=0.484N | |POLY 1.5 | (e) (e) (e) (e) |P=0.165N P=0.324 P=0.745N P=0.485N | |POLY 6 | (e) (e) (e) (e) |P=0.163N P=0.317 P=0.739N P=0.483N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.174N P=0.342 P=0.717N (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.167N P=0.332 P=0.737N P=0.485N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/47 (0%) 0/50 (0%) 1/50 (2%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 4.8% 0.0% 0.0% 0.0% |0.0% 0.0% 2.2% 6.5% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 0/28 (0%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 560 --- --- --- |--- --- 618 645 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.331N P=0.228N P=0.267N P=0.263N |P=0.031 * (e) P=0.518 P=0.141 | |POLY 3 | P=0.319N P=0.229N P=0.251N P=0.256N |P=0.028 * (e) P=0.518 P=0.136 | |POLY 1.5 | P=0.316N P=0.232N P=0.245N P=0.252N |P=0.027 * (e) P=0.515 P=0.134 | |POLY 6 | P=0.320N P=0.227N P=0.257N P=0.259N |P=0.030 * (e) P=0.522 P=0.140 | |LOGISTIC REGRESSION| P=0.283N P=0.266N P=0.225N P=0.222N |P=0.016 * (e) P=0.502 P=0.113 | |COCH-ARM / FISHERS | P=0.311N P=0.247N P=0.247N P=0.253N |P=0.026 * (e) P=0.515 P=0.133 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |0/49 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 7.2% 0.0% |0.0% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 0/28 (0%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- --- 387 --- |--- 483 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.603N (e) P=0.120 (e) |P=0.601N P=0.517 (e) (e) | |POLY 3 | P=0.615N (e) P=0.119 (e) |P=0.604N P=0.508 (e) (e) | |POLY 1.5 | P=0.606N (e) P=0.120 (e) |P=0.604N P=0.508 (e) (e) | |POLY 6 | P=0.620N (e) P=0.120 (e) |P=0.607N P=0.505 (e) (e) | |LOGISTIC REGRESSION| P=0.297N (e) P=0.129 (e) |P=0.861N P=0.289 (e) (e) | |COCH-ARM / FISHERS | P=0.581N (e) P=0.121 (e) |P=0.607N P=0.505 (e) (e) | |=================================================================================================================================| | | | | | | 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) | 5/50 (10%) 6/50 (12%) 4/50 (8%) 3/50 (6%) |4/49 (8%) 3/50 (6%) 3/50 (6%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 12.1% 13.7% 9.9% 7.6% |9.4% 6.9% 6.6% 2.2% | |TERMINAL (d) | 4/28 (14%) 5/32 (16%) 2/27 (7%) 3/28 (11%) |4/32 (13%) 3/31 (10%) 3/39 (8%) 1/33 (3%) | |FIRST INCIDENCE | 664 601 387 733 (T) |735 (T) 735 (T) 735 (T) 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.269N P=0.584 P=0.531N P=0.357N |P=0.144N P=0.518N P=0.392N P=0.169N | |POLY 3 | P=0.276N P=0.540 P=0.514N P=0.386N |P=0.139N P=0.488N P=0.460N P=0.156N | |POLY 1.5 | P=0.265N P=0.525 P=0.507N P=0.378N |P=0.144N P=0.485N P=0.470N P=0.161N | |POLY 6 | P=0.283N P=0.555 P=0.520N P=0.389N |P=0.133N P=0.499N P=0.448N P=0.153N | |LOGISTIC REGRESSION| P=0.265N P=0.547 P=0.507N P=0.378N |P=0.144N P=0.518N P=0.392N P=0.169N | |COCH-ARM / FISHERS | P=0.237N P=0.500 P=0.500N P=0.357N |P=0.153N P=0.489N P=0.489N P=0.175N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/49 (0%) 1/48 (2%) 0/49 (0%) |1/46 (2%) 2/48 (4%) 0/47 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 2.5% 0.0% 2.6% 0.0% |2.5% 4.7% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/26 (4%) 0/28 (0%) |1/32 (3%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 695 --- 733 (T) --- |735 (T) 594 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.496N P=0.489N P=0.738 P=0.518N |P=0.227N P=0.495 P=0.461N P=0.494N | |POLY 3 | P=0.495N P=0.488N P=0.750 P=0.508N |P=0.232N P=0.517 P=0.482N P=0.481N | |POLY 1.5 | P=0.489N P=0.490N P=0.754 P=0.505N |P=0.231N P=0.518 P=0.487N P=0.482N | |POLY 6 | P=0.499N P=0.485N P=0.745 P=0.510N |P=0.234N P=0.514 P=0.477N P=0.480N | |LOGISTIC REGRESSION| P=0.493N P=0.492N P=0.749 P=0.505N |P=0.251N P=0.507 (e) (e) | |COCH-ARM / FISHERS | P=0.475N P=0.495N P=0.753N P=0.495N |P=0.232N P=0.516 P=0.495N P=0.484N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Iliac | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/4 (0%) 1/3 (33%) 2/7 (29%) 1/1 (100%) |0/7 (0%) 0/2 (0%) 0/5 (0%) 0/4 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 33.3% 35.8% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/2 (0%) 0/2 (0%) 0/0 (0%) 0/0 (0%) |0/5 (0%) 0/1 (0%) 0/3 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 639 499 667 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.542 P=0.520 P=0.240 P=0.494 |(e) (e) (e) (e) | |POLY 3 | P=0.181 P=0.481 P=0.344 P<0.001 ** |(e) (e) (e) (e) | |POLY 1.5 | P=0.171 P=0.462 P=0.353 P<0.001 ** |(e) (e) (e) (e) | |POLY 6 | P=0.197 P=0.512 P=0.321 P=0.002 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.170 P=0.316 P=0.579 P=0.210 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.164 P=0.429 P=0.382 P=0.200 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 3/4 (75%) 2/2 (100%) 4/4 (100%) 2/2 (100%) |7/7 (100%) 6/8 (75%) 6/8 (75%) 10/10 (100%) | |POLY-3 ADJUSTED (b)| 75.0% 100.0% 100.0% 100.0% |100.0% 82.4% 76.8% 100.0% | |TERMINAL (d) | 0/1 (0%) 2/2 (100%) 2/2 (100%) 2/2 (100%) |5/5 (100%) 6/7 (86%) 6/7 (86%) 6/6 (100%) | |FIRST INCIDENCE | 610 733 (T) 387 733 (T) |639 735 (T) 735 (T) 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.367N P=0.343N P=0.579 P=0.380N |P=0.047 * P=0.152N P=0.133N (e) | |POLY 3 | P=0.622 P=0.631 P=0.500 P=0.631 |P=0.339 P=0.400N P=0.278N (e) | |POLY 1.5 | P=0.622 P=0.631 P=0.500 P=0.631 |P=0.302 P=0.330N P=0.266N (e) | |POLY 6 | P=0.622 P=0.631 P=0.500 P=0.631 |P=0.380 P=0.470N P=0.303N (e) | |LOGISTIC REGRESSION| (e) P=0.343N (e) P=0.380N |P=0.206 P=0.330N P=0.186N (e) | |COCH-ARM / FISHERS | P=0.635 P=0.667 P=0.500 P=0.667 |P=0.256 P=0.267N P=0.267N (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/49 (4%) 2/50 (4%) 0/48 (0%) |0/47 (0%) 1/50 (2%) 1/49 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 4.6% 5.0% 0.0% |0.0% 2.3% 2.2% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/27 (4%) 0/28 (0%) |0/32 (0%) 1/31 (3%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 580 649 480 --- |--- 735 (T) 628 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.259N P=0.517 P=0.485 P=0.524N |P=0.511N P=0.494 P=0.514 (e) | |POLY 3 | P=0.258N P=0.512 P=0.486 P=0.517N |P=0.511N P=0.505 P=0.516 (e) | |POLY 1.5 | P=0.254N P=0.505 P=0.492 P=0.515N |P=0.512N P=0.509 P=0.512 (e) | |POLY 6 | P=0.262N P=0.521 P=0.480 P=0.518N |P=0.511N P=0.501 P=0.521 (e) | |LOGISTIC REGRESSION| P=0.202N P=0.443 P=0.531 P=0.474N |P=0.531N P=0.494 P=0.485 (e) | |COCH-ARM / FISHERS | P=0.241N P=0.492 P=0.500 P=0.510N |P=0.514N P=0.515 P=0.510 (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 1/50 (2%) 1/49 (2%) 1/50 (2%) 2/48 (4%) |0/47 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.4% 2.3% 2.5% 5.2% |0.0% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/27 (4%) 2/28 (7%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 527 652 733 (T) 733 (T) |--- 639 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.344 P=0.752N P=0.749 P=0.489 |P=0.594N P=0.505 (e) (e) | |POLY 3 | P=0.334 P=0.756N P=0.748 P=0.470 |P=0.607N P=0.507 (e) (e) | |POLY 1.5 | P=0.340 P=0.759N P=0.753 P=0.474 |P=0.605N P=0.509 (e) (e) | |POLY 6 | P=0.329 P=0.751N P=0.742 P=0.468 |P=0.611N P=0.503 (e) (e) | |LOGISTIC REGRESSION| P=0.353 P=0.708 P=0.752N P=0.488 |P=0.644N P=0.528 (e) (e) | |COCH-ARM / FISHERS | P=0.355 P=0.747 P=0.753N P=0.485 |P=0.603N P=0.515 (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) | 6/50 (12%) 7/49 (14%) 16/50 (32%) 17/48 (35%) |17/47 (36%) 19/50 (38%) 24/49 (49%) 27/50 (54%) | |POLY-3 ADJUSTED (b)| 14.1% 16.3% 39.8% 43.0% |39.0% 42.4% 52.5% 56.9% | |TERMINAL (d) | 3/28 (11%) 5/32 (16%) 11/27 (41%) 12/28 (43%) |12/32 (38%) 13/31 (42%) 23/39 (59%) 16/33 (49%) | |FIRST INCIDENCE | 580 649 645 508 |449 594 600 583 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.004 ** P=0.577 P=0.013 * P=0.010 * |P=0.053 P=0.396 P=0.321 P=0.079 | |POLY 3 | P<0.001 ** P=0.509 P=0.006 ** P=0.003 ** |P=0.054 P=0.455 P=0.139 P=0.062 | |POLY 1.5 | P=0.002 ** P=0.501 P=0.009 ** P=0.003 ** |P=0.048 * P=0.477 P=0.139 P=0.060 | |POLY 6 | P<0.001 ** P=0.516 P=0.005 ** P=0.002 ** |P=0.067 P=0.429 P=0.144 P=0.071 | |LOGISTIC REGRESSION| P=0.002 ** P=0.508 P=0.009 ** P=0.004 ** |P=0.057 P=0.467 P=0.171 P=0.065 | |COCH-ARM / FISHERS | P=0.004 ** P=0.484 P=0.014 * P=0.006 ** |P=0.043 * P=0.510 P=0.144 P=0.059 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Degeneration Hyaline | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 19/49 (39%) 29/50 (58%) 39/48 (81%) |21/47 (45%) 39/50 (78%) 41/49 (84%) 48/50 (96%) | |POLY-3 ADJUSTED (b)| 14.2% 42.1% 68.4% 89.5% |47.7% 82.3% 86.4% 96.9% | |TERMINAL (d) | 4/28 (14%) 12/32 (38%) 22/27 (82%) 27/28 (96%) |16/32 (50%) 25/31 (81%) 36/39 (92%) 33/33 (100%) | |FIRST INCIDENCE | 580 546 387 330 |541 567 477 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.010 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P=0.003 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |0/48 (0%) 1/50 (2%) 0/48 (0%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| |0.0% 2.3% 0.0% 6.6% | |TERMINAL (d) | |0/32 (0%) 0/31 (0%) 0/38 (0%) 3/33 (9%) | |FIRST INCIDENCE | |--- 615 --- 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.043 * P=0.505 (e) P=0.126 | |POLY 3 | |P=0.045 * P=0.507 (e) P=0.133 | |POLY 1.5 | |P=0.044 * P=0.508 (e) P=0.131 | |POLY 6 | |P=0.045 * P=0.504 (e) P=0.134 | |LOGISTIC REGRESSION| |P=0.044 * P=0.475 (e) P=0.126 | |COCH-ARM / FISHERS | |P=0.044 * P=0.510 (e) P=0.129 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |13/48 (27%) 14/50 (28%) 11/48 (23%) 8/50 (16%) | |POLY-3 ADJUSTED (b)| |29.9% 31.7% 24.6% 17.0% | |TERMINAL (d) | |8/32 (25%) 11/31 (36%) 10/38 (26%) 5/33 (15%) | |FIRST INCIDENCE | |621 611 620 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.084N P=0.473 P=0.262N P=0.147N | |POLY 3 | |P=0.060N P=0.517 P=0.377N P=0.114N | |POLY 1.5 | |P=0.068N P=0.537 P=0.386N P=0.120N | |POLY 6 | |P=0.054N P=0.478 P=0.370N P=0.111N | |LOGISTIC REGRESSION| |P=0.072N P=0.526 P=0.367N P=0.144N | |COCH-ARM / FISHERS | |P=0.084N P=0.550 P=0.407N P=0.138N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/48 (2%) 0/50 (0%) 0/47 (0%) |1/47 (2%) 2/50 (4%) 0/48 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.4% 0.0% 0.0% |2.4% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 1/32 (3%) 0/27 (0%) 0/27 (0%) |1/32 (3%) 2/31 (7%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- 733 (T) --- --- |735 (T) 735 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.624N P=0.527 (e) (e) |P=0.232N P=0.489 P=0.461N P=0.494N | |POLY 3 | P=0.608N P=0.506 (e) (e) |P=0.237N P=0.509 P=0.490N P=0.486N | |POLY 1.5 | P=0.611N P=0.501 (e) (e) |P=0.236N P=0.515 P=0.492N P=0.488N | |POLY 6 | P=0.604N P=0.511 (e) (e) |P=0.238N P=0.501 P=0.485N P=0.484N | |LOGISTIC REGRESSION| (e) P=0.527 (e) (e) |P=0.232N P=0.489 (e) (e) | |COCH-ARM / FISHERS | P=0.617N P=0.490 (e) (e) |P=0.237N P=0.523 P=0.495N P=0.490N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 1/50 (2%) 4/48 (8%) 3/49 (6%) 4/48 (8%) |13/49 (27%) 15/49 (31%) 19/49 (39%) 14/49 (29%) | |POLY-3 ADJUSTED (b)| 2.4% 9.4% 7.8% 10.2% |29.7% 34.2% 41.8% 30.5% | |TERMINAL (d) | 1/28 (4%) 4/32 (13%) 2/27 (7%) 3/28 (11%) |9/32 (28%) 10/31 (32%) 17/39 (44%) 10/33 (30%) | |FIRST INCIDENCE | 733 (T) 733 (T) 708 682 |541 611 620 596 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.272 P=0.220 P=0.291 P=0.178 |P=0.459N P=0.393 P=0.324 P=0.550 | |POLY 3 | P=0.276 P=0.186 P=0.282 P=0.161 |P=0.434N P=0.408 P=0.163 P=0.557 | |POLY 1.5 | P=0.278 P=0.179 P=0.288 P=0.161 |P=0.459N P=0.417 P=0.156 P=0.541 | |POLY 6 | P=0.278 P=0.194 P=0.277 P=0.163 |P=0.412N P=0.390 P=0.173 P=0.568 | |LOGISTIC REGRESSION| P=0.267 P=0.220 P=0.275 P=0.163 |P=0.427N P=0.420 P=0.179 P=0.547 | |COCH-ARM / FISHERS | P=0.291 P=0.168 P=0.301 P=0.168 |P=0.507N P=0.412 P=0.141 P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/48 (0%) 2/50 (4%) 1/50 (2%) | | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 5.1% 2.5% | | |TERMINAL (d) | 0/28 (0%) 0/31 (0%) 2/27 (7%) 1/28 (4%) | | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.408 (e) P=0.230 P=0.500 | | |POLY 3 | P=0.390 (e) P=0.227 P=0.490 | | |POLY 1.5 | P=0.399 (e) P=0.231 P=0.493 | | |POLY 6 | P=0.384 (e) P=0.223 P=0.490 | | |LOGISTIC REGRESSION| (e) (e) P=0.230 P=0.500 | | |COCH-ARM / FISHERS | P=0.424 (e) P=0.247 P=0.500 | | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 0/50 (0%) 2/48 (4%) 0/50 (0%) 3/50 (6%) | | |POLY-3 ADJUSTED (b)| 0.0% 4.8% 0.0% 7.6% | | |TERMINAL (d) | 0/28 (0%) 2/31 (7%) 0/27 (0%) 3/28 (11%) | | |FIRST INCIDENCE | --- 733 (T) --- 733 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.096 P=0.261 (e) P=0.120 | | |POLY 3 | P=0.099 P=0.239 (e) P=0.109 | | |POLY 1.5 | P=0.100 P=0.235 (e) P=0.112 | | |POLY 6 | P=0.098 P=0.243 (e) P=0.109 | | |LOGISTIC REGRESSION| (e) P=0.261 (e) P=0.120 | | |COCH-ARM / FISHERS | P=0.107 P=0.237 (e) P=0.121 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 2/46 (4%) 4/47 (9%) 4/48 (8%) | | |POLY-3 ADJUSTED (b)| 0.0% 4.8% 10.3% 10.1% | | |TERMINAL (d) | 0/27 (0%) 0/32 (0%) 0/26 (0%) 0/28 (0%) | | |FIRST INCIDENCE | --- 639 628 631 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.103 P=0.263 P=0.062 P=0.062 | | |POLY 3 | P=0.109 P=0.248 P=0.056 P=0.059 | | |POLY 1.5 | P=0.111 P=0.240 P=0.056 P=0.058 | | |POLY 6 | P=0.111 P=0.257 P=0.056 P=0.061 | | |LOGISTIC REGRESSION| P=0.132 P=0.186 P=0.060 P=0.064 | | |COCH-ARM / FISHERS | P=0.122 P=0.237 P=0.056 P=0.059 | | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Skin: Prepuce | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 7/49 (14%) 6/50 (12%) 13/50 (26%) 9/50 (18%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 16.6% 13.4% 29.3% 20.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/27 (0%) 1/32 (3%) 2/27 (7%) 1/28 (4%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 387 562 387 251 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.308 P=0.436N P=0.108 P=0.367 |(e) (e) (e) (e) | |POLY 3 | P=0.348 P=0.456N P=0.122 P=0.410 |(e) (e) (e) (e) | |POLY 1.5 | P=0.352 P=0.467N P=0.119 P=0.406 |(e) (e) (e) (e) | |POLY 6 | P=0.352 P=0.445N P=0.128 P=0.419 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.539 P=0.543N P=0.138 P=0.511 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.371 P=0.484N P=0.115 P=0.410 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | 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) | 4/50 (8%) 3/49 (6%) 5/50 (10%) 4/48 (8%) |4/49 (8%) 12/50 (24%) 6/50 (12%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 9.5% 7.0% 12.2% 10.0% |9.2% 26.2% 12.9% 10.6% | |TERMINAL (d) | 0/28 (0%) 2/32 (6%) 1/27 (4%) 0/28 (0%) |1/32 (3%) 4/31 (13%) 4/39 (10%) 0/33 (0%) | |FIRST INCIDENCE | 608 583 512 508 |541 567 600 527 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.496 P=0.456N P=0.460 P=0.609 |P=0.237N P=0.037 * P=0.463 P=0.540 | |POLY 3 | P=0.502 P=0.487N P=0.484 P=0.614 |P=0.211N P=0.033 * P=0.415 P=0.554 | |POLY 1.5 | P=0.506 P=0.495N P=0.490 P=0.613 |P=0.224N P=0.032 * P=0.404 P=0.540 | |POLY 6 | P=0.505 P=0.480N P=0.480 P=0.621 |P=0.201N P=0.033 * P=0.428 P=0.565 | |LOGISTIC REGRESSION| P=0.558 P=0.516N P=0.511 P=0.637 |P=0.331N P=0.027 * P=0.347 P=0.389 | |COCH-ARM / FISHERS | P=0.526 P=0.511N P=0.500 P=0.619 |P=0.253N P=0.030 * P=0.383 P=0.513 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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 | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/49 (0%) 1/50 (2%) 1/48 (2%) |2/48 (4%) 4/49 (8%) 1/49 (2%) 1/49 (2%) | |POLY-3 ADJUSTED (b)| 4.8% 0.0% 2.5% 2.6% |4.7% 9.2% 2.2% 2.2% | |TERMINAL (d) | 1/28 (4%) 0/32 (0%) 1/27 (4%) 1/28 (4%) |0/32 (0%) 1/31 (3%) 1/39 (3%) 1/33 (3%) | |FIRST INCIDENCE | 695 --- 733 (T) 733 (T) |608 649 735 (T) 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.675N P=0.216N P=0.523N P=0.511N |P=0.233N P=0.329 P=0.460N P=0.482N | |POLY 3 | P=0.675 P=0.227N P=0.517N P=0.527N |P=0.240N P=0.345 P=0.481N P=0.484N | |POLY 1.5 | P=0.680N P=0.232N P=0.510N P=0.524N |P=0.241N P=0.348 P=0.485N P=0.486N | |POLY 6 | P=0.670 P=0.223N P=0.524N P=0.527N |P=0.241N P=0.339 P=0.476N P=0.485N | |LOGISTIC REGRESSION| P=0.684N P=0.223N P=0.523N P=0.523N |P=0.254N P=0.336 P=0.516N P=0.516N | |COCH-ARM / FISHERS | P=0.665N P=0.253N P=0.500N P=0.515N |P=0.245N P=0.349 P=0.492N P=0.492N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Acute | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 1/50 (2%) 1/48 (2%) |1/48 (2%) 2/49 (4%) 0/49 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.5% 2.6% |2.4% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 1/27 (4%) 1/28 (4%) |0/32 (0%) 1/31 (3%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) |709 731 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.336 (e) P=0.493 P=0.500 |P=0.230N P=0.486 P=0.479N P=0.484N | |POLY 3 | P=0.319 (e) P=0.491 P=0.486 |P=0.236N P=0.505 P=0.487N P=0.489N | |POLY 1.5 | P=0.325 (e) P=0.495 P=0.487 |P=0.236N P=0.508 P=0.490N P=0.491N | |POLY 6 | P=0.316 (e) P=0.488 P=0.486 |P=0.238N P=0.499 P=0.483N P=0.488N | |LOGISTIC REGRESSION| (e) (e) P=0.493 P=0.500 |P=0.228N P=0.497 P=0.493N P=0.493N | |COCH-ARM / FISHERS | P=0.340 (e) P=0.500 P=0.490 |P=0.238N P=0.508 P=0.495N P=0.495N | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - 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) | 0/49 (0%) 2/47 (4%) 1/49 (2%) 0/46 (0%) |0/46 (0%) 0/48 (0%) 1/48 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 4.7% 2.5% 0.0% |0.0% 0.0% 2.2% 0.0% | |TERMINAL (d) | 0/28 (0%) 0/32 (0%) 0/27 (0%) 0/28 (0%) |0/32 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | --- 601 389 --- |--- --- 509 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.387N P=0.253 P=0.500 (e) |P=0.762N (e) P=0.513 (e) | |POLY 3 | P=0.383N P=0.247 P=0.496 (e) |P=0.762N (e) P=0.516 (e) | |POLY 1.5 | P=0.383N P=0.240 P=0.498 (e) |P=0.763N (e) P=0.513 (e) | |POLY 6 | P=0.381N P=0.256 P=0.494 (e) |P=0.760N (e) P=0.522 (e) | |LOGISTIC REGRESSION| P=0.241N P=0.160 P=0.581 (e) |P=0.879 (e) P=0.476 (e) | |COCH-ARM / FISHERS | P=0.378N P=0.237 P=0.500 (e) |P=0.766N (e) P=0.511 (e) | |=================================================================================================================================| | | | | | | 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) | 5/50 (10%) 6/50 (12%) 3/50 (6%) 3/49 (6%) |25/48 (52%) 16/50 (32%) 29/49 (59%) 30/50 (60%) | |POLY-3 ADJUSTED (b)| 12.0% 13.6% 7.6% 7.8% |57.5% 36.1% 62.1% 63.4% | |TERMINAL (d) | 3/28 (11%) 3/32 (9%) 3/27 (11%) 3/28 (11%) |20/32 (63%) 11/31 (36%) 25/39 (64%) 22/33 (67%) | |FIRST INCIDENCE | 653 512 733 (T) 733 (T) |610 615 477 583 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.282N P=0.575 P=0.391N P=0.369N |P=0.062 P=0.072N P=0.509N P=0.298 | |POLY 3 | P=0.295N P=0.542 P=0.386N P=0.400N |P=0.070 P=0.032N* P=0.407 P=0.358 | |POLY 1.5 | P=0.284N P=0.527 P=0.374N P=0.392N |P=0.059 P=0.030N* P=0.371 P=0.331 | |POLY 6 | P=0.302N P=0.557 P=0.401N P=0.405N |P=0.088 P=0.036N* P=0.447 P=0.387 | |LOGISTIC REGRESSION| P=0.294N P=0.523 P=0.390N P=0.391N |P=0.075 P=0.041N* P=0.408 P=0.359 | |COCH-ARM / FISHERS | P=0.257N P=0.500 P=0.357N P=0.369N |P=0.047 * P=0.035N* P=0.309 P=0.279 | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Tooth | | Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 6/7 (86%) 12/14 (86%) 7/9 (78%) 14/16 (88%) |0/0 (0%) 0/0 (0%) 1/1 (100%) 1/1 (100%) | |POLY-3 ADJUSTED (b)| 94.2% 89.6% 77.8% 87.5% |0.0% 0.0% 100.0% 100.0% | |TERMINAL (d) | 4/4 (100%) 12/12 (100%) 5/7 (71%) 12/14 (86%) |0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) | |FIRST INCIDENCE | 592 733 (T) 480 670 |--- --- 735 (T) 596 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.585N P=0.224N P=0.455N P=0.540N |(e) (e) (e) (e) | |POLY 3 | P=0.614N P=0.723N P=0.437N P=0.616N |(e) (e) (e) (e) | |POLY 1.5 | P=0.626 P=0.719N P=0.502N P=0.690N |(e) (e) (e) (e) | |POLY 6 | P=0.533N P=0.790N P=0.367N P=0.528N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.626N P=0.171N P=0.570N P=0.513N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.534 P=0.726 P=0.600N P=0.684 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | 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) | 4/49 (8%) 3/47 (6%) 7/49 (14%) 6/46 (13%) |0/45 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 9.4% 7.1% 16.7% 15.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/28 (0%) 1/32 (3%) 0/27 (0%) 0/28 (0%) |0/31 (0%) 0/31 (0%) 0/39 (0%) 0/33 (0%) | |FIRST INCIDENCE | 399 639 499 457 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.245 P=0.464N P=0.243 P=0.350 |(e) (e) (e) (e) | |POLY 3 | P=0.221 P=0.501N P=0.252 P=0.320 |(e) (e) (e) (e) | |POLY 1.5 | P=0.227 P=0.508N P=0.255 P=0.322 |(e) (e) (e) (e) | |POLY 6 | P=0.221 P=0.494N P=0.251 P=0.325 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.316 P=0.651 P=0.299 P=0.358 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.244 P=0.524N P=0.262 P=0.330 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 06/20/97 EXPERIMENT: 88070 TEST: 04 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ISOBUTENE Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | CONTROL 500 PPM 2000 PPM 8000 PPM |CONTROL 500 PPM 2000 PPM 8000 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |6/49 (12%) 7/50 (14%) 3/50 (6%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| |13.9% 15.6% 6.5% 8.7% | |TERMINAL (d) | |5/32 (16%) 3/31 (10%) 2/39 (5%) 4/33 (12%) | |FIRST INCIDENCE | |541 572 628 735 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.257N P=0.491 P=0.171N P=0.347N | |POLY 3 | |P=0.256N P=0.531 P=0.209N P=0.331N | |POLY 1.5 | |P=0.260N P=0.529 P=0.217N P=0.338N | |POLY 6 | |P=0.255N P=0.529 P=0.199N P=0.328N | |LOGISTIC REGRESSION| |P=0.274N P=0.512 P=0.228N P=0.326N | |COCH-ARM / FISHERS | |P=0.271N P=0.516 P=0.233N P=0.357N | |=================================================================================================================================| (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).