TDMS Study 55301-04 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: TSI Mason Research PYRIDINE DATE: 09/26/97 EXPERIMENT: 55301 TEST: 04 TIME: 13:39:39 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-95268 ROUTE: DOSED WATER NTP C#: 55301B PATHOLOGIST: F. VOELKER STEDHAM, MICHAEL CAS: 110-86-1 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 PRIMARY TUMORS REPORT: PEIRPT08 LAB: TSI Mason Research PYRIDINE DATE: 09/26/97 EXPERIMENT: 55301 TEST: 04 TIME: 13:39:39 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-95268 ROUTE: DOSED WATER NTP C#: 55301B PATHOLOGIST: F. VOELKER STEDHAM, MICHAEL CAS: 110-86-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF PYRIDINE =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Harderian Gland Carcinoma or Adenoma Liver Hepatoblastoma Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma All Organs Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Hepatoblastoma Hepatocellular Adenoma Hepatocellular Carcinoma Hepatocellular Carcinoma or Hepatoblastoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Ovary Cystadenoma Pituitary Gland: Pars Distalis or Unspecified Site Adenoma All Organs Hemangioma Hemangiosarcoma or Hemangioma Mesothelioma: Benign, Malignant, NOS Benign Tumors Malignant Tumors =============================================================== Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 1 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 0/49 (0%) 0/49 (0%) 1/49 (2%) |1/49 (2%) 0/50 (0%) 0/48 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.8% 0.0% 0.0% 2.4% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/35 (6%) 0/27 (0%) 0/34 (0%) 1/34 (3%) |1/32 (3%) 0/30 (0%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | 598 --- --- 722 (T) |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.244N P=0.164N P=0.129N P=0.318N |P=0.327N P=0.513N P=0.575N P=0.520N | |POLY 3 | P=0.234N P=0.134N P=0.126N P=0.321N |P=0.294N P=0.506N P=0.517N P=0.516N | |POLY 1.5 | P=0.239N P=0.128N P=0.124N P=0.322N |P=0.296N P=0.506N P=0.515N P=0.512N | |POLY 6 | P=0.229N P=0.142N P=0.127N P=0.318N |P=0.294N P=0.507N P=0.522N P=0.519N | |LOGISTIC REGRESSION| P=0.252N P=0.123N P=0.121N P=0.314N |P=0.327N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.247N P=0.121N P=0.121N P=0.309N |P=0.305N P=0.495N P=0.505N P=0.495N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 6.7% 0.0% 0.0% 2.3% |0.0% 2.5% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/28 (0%) 0/35 (0%) 1/35 (3%) |0/32 (0%) 1/30 (3%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | 633 --- --- 722 (T) |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.242N P=0.159N P=0.129N P=0.312N |P=0.583N P=0.487 (e) (e) | |POLY 3 | P=0.235N P=0.133N P=0.125N P=0.320N |P=0.582N P=0.489 (e) (e) | |POLY 1.5 | P=0.239N P=0.128N P=0.124N P=0.322N |P=0.579N P=0.490 (e) (e) | |POLY 6 | P=0.229N P=0.141N P=0.127N P=0.316N |P=0.586N P=0.488 (e) (e) | |LOGISTIC REGRESSION| P=0.252N P=0.126N P=0.123N P=0.316N |(e) P=0.487 (e) (e) | |COCH-ARM / FISHERS | P=0.247N P=0.121N P=0.121N P=0.309N |P=0.567N P=0.500 (e) (e) | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 2 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |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%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 4.5% 0.0% 0.0% 0.0% |2.3% 0.0% 0.0% 2.6% | |TERMINAL (d) | 2/35 (6%) 0/28 (0%) 0/35 (0%) 0/35 (0%) |1/32 (3%) 0/30 (0%) 0/22 (0%) 1/29 (3%) | |FIRST INCIDENCE | 722 (T) --- --- --- |729 (T) --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.112N P=0.288N P=0.238N P=0.238N |P=0.567 P=0.513N P=0.575N P=0.740 | |POLY 3 | P=0.108N P=0.253N P=0.244N P=0.244N |P=0.585 P=0.511N P=0.515N P=0.738 | |POLY 1.5 | P=0.109N P=0.248N P=0.243N P=0.246N |P=0.587 P=0.510N P=0.511N P=0.742 | |POLY 6 | P=0.106N P=0.261N P=0.244N P=0.241N |P=0.582 P=0.512N P=0.521N P=0.735 | |LOGISTIC REGRESSION| P=0.112N (e) (e) (e) |P=0.567 (e) (e) P=0.740 | |COCH-ARM / FISHERS | P=0.115N P=0.247N P=0.247N P=0.247N |P=0.595 P=0.500N P=0.500N P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 5/50 (10%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 ADJUSTED (b)| 11.1% 0.0% 0.0% 2.3% |2.3% 2.5% 0.0% 2.6% | |TERMINAL (d) | 3/35 (9%) 0/28 (0%) 0/35 (0%) 1/35 (3%) |1/32 (3%) 1/30 (3%) 0/22 (0%) 1/29 (3%) | |FIRST INCIDENCE | 633 --- --- 722 (T) |729 (T) 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060N P=0.056N P=0.037N* P=0.109N |P=0.643N P=0.748 P=0.575N P=0.740 | |POLY 3 | P=0.052N P=0.038N* P=0.034N* P=0.111N |P=0.625N P=0.749 P=0.515N P=0.738 | |POLY 1.5 | P=0.055N P=0.035N* P=0.033N* P=0.112N |P=0.623N P=0.750 P=0.511N P=0.742 | |POLY 6 | P=0.050N P=0.041N* P=0.034N* P=0.108N |P=0.629N P=0.748 P=0.521N P=0.735 | |LOGISTIC REGRESSION| P=0.063N P=0.040N* P=0.035N* P=0.110N |P=0.643N P=0.748 (e) P=0.740 | |COCH-ARM / FISHERS | P=0.062N P=0.028N* P=0.028N* P=0.102N |P=0.616N P=0.753N P=0.500N P=0.753N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 3 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 2/48 (4%) 1/50 (2%) |1/49 (2%) 2/50 (4%) 0/47 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.4% 4.7% 2.3% |2.4% 4.9% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 1/28 (4%) 0/34 (0%) 1/35 (3%) |0/32 (0%) 1/30 (3%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | --- 722 (T) 513 722 (T) |554 696 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.376 P=0.455 P=0.235 P=0.500 |P=0.215N P=0.481 P=0.509N P=0.528N | |POLY 3 | P=0.361 P=0.490 P=0.231 P=0.498 |P=0.208N P=0.485 P=0.521N P=0.523N | |POLY 1.5 | P=0.354 P=0.495 P=0.230 P=0.496 |P=0.204N P=0.488 P=0.517N P=0.518N | |POLY 6 | P=0.371 P=0.484 P=0.234 P=0.501 |P=0.213N P=0.482 P=0.528N P=0.527N | |LOGISTIC REGRESSION| P=0.377 P=0.455 P=0.256 P=0.500 |P=0.193N P=0.505 P=0.489N P=0.469N | |COCH-ARM / FISHERS | P=0.370 P=0.505 P=0.242 P=0.505 |P=0.191N P=0.508 P=0.510N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/49 (0%) 0/50 (0%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.2% 4.7% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/28 (0%) 0/34 (0%) 0/35 (0%) |0/32 (0%) 0/30 (0%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | 706 532 --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.192N P=0.458 P=0.505N P=0.505N |(e) (e) (e) (e) | |POLY 3 | P=0.196N P=0.482 P=0.511N P=0.507N |(e) (e) (e) (e) | |POLY 1.5 | P=0.196N P=0.487 P=0.509N P=0.508N |(e) (e) (e) (e) | |POLY 6 | P=0.195N P=0.474 P=0.512N P=0.504N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.177N P=0.526 P=0.510N P=0.506N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.189N P=0.500 P=0.505N P=0.500N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 4 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 18/50 (36%) 22/49 (45%) 15/50 (30%) |1/49 (2%) 2/50 (4%) 9/50 (18%) 16/50 (32%) | |POLY-3 ADJUSTED (b)| 4.5% 41.2% 49.8% 34.4% |2.4% 4.9% 21.6% 39.6% | |TERMINAL (d) | 2/35 (6%) 11/28 (39%) 17/34 (50%) 13/35 (37%) |1/32 (3%) 1/30 (3%) 3/22 (14%) 12/29 (41%) | |FIRST INCIDENCE | 722 (T) 549 514 624 |729 (T) 599 564 510 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.025 * P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.482 P=0.005 ** P<0.001 ** | |POLY 3 | P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.493 P=0.007 ** P<0.001 ** | |POLY 1.5 | P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.492 P=0.007 ** P<0.001 ** | |POLY 6 | P=0.006 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.494 P=0.007 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.010 * P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.496 P=0.009 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.012 * P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.508 P=0.009 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 40/50 (80%) 34/49 (69%) 39/50 (78%) |37/49 (76%) 39/50 (78%) 43/50 (86%) 34/50 (68%) | |POLY-3 ADJUSTED (b)| 63.2% 88.0% 75.7% 84.9% |82.5% 87.9% 97.3% 79.1% | |TERMINAL (d) | 24/35 (69%) 27/28 (96%) 27/34 (79%) 31/35 (89%) |27/32 (84%) 27/30 (90%) 22/22 (100%) 23/29 (79%) | |FIRST INCIDENCE | 520 522 513 406 |554 419 509 430 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.179 P<0.001 ** P=0.165 P=0.035 * |P=0.417 P=0.267 P=0.003 ** P=0.520 | |POLY 3 | P=0.031 * P=0.003 ** P=0.134 P=0.011 * |P=0.372N P=0.336 P=0.015 * P=0.442N | |POLY 1.5 | P=0.025 * P=0.005 ** P=0.133 P=0.009 ** |P=0.350N P=0.326 P=0.022 * P=0.428N | |POLY 6 | P=0.044 * P=0.002 ** P=0.143 P=0.016 * |P=0.380N P=0.344 P=0.011 * P=0.448N | |LOGISTIC REGRESSION| P=0.025 * P=0.002 ** P=0.105 P=0.009 ** |P=0.450N P=0.288 P=0.023 * P=0.512N | |COCH-ARM / FISHERS | P=0.060 P=0.015 * P=0.166 P=0.026 * |P=0.210N P=0.478 P=0.142 P=0.272N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 5 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 15/50 (30%) 35/50 (70%) 41/49 (84%) 40/50 (80%) |13/49 (27%) 23/50 (46%) 33/50 (66%) 41/50 (82%) | |POLY-3 ADJUSTED (b)| 32.3% 78.7% 89.9% 85.1% |29.8% 55.0% 78.1% 97.1% | |TERMINAL (d) | 9/35 (26%) 23/28 (82%) 32/34 (94%) 28/35 (80%) |8/32 (25%) 18/30 (60%) 20/22 (91%) 29/29 (100%) | |FIRST INCIDENCE | 574 522 513 406 |476 573 556 479 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.022 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.014 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.021 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.035 * P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 42/50 (84%) 45/49 (92%) 42/50 (84%) |13/49 (27%) 23/50 (46%) 36/50 (72%) 43/50 (86%) | |POLY-3 ADJUSTED (b)| 36.7% 91.3% 96.8% 89.4% |29.8% 55.0% 82.8% 99.0% | |TERMINAL (d) | 11/35 (31%) 26/28 (93%) 34/34 (100%) 30/35 (86%) |8/32 (25%) 18/30 (60%) 20/22 (91%) 29/29 (100%) | |FIRST INCIDENCE | 574 522 513 406 |476 573 556 479 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.022 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.014 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.021 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.035 * P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 6 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 37/50 (74%) 45/50 (90%) 45/49 (92%) 47/50 (94%) |41/49 (84%) 42/50 (84%) 44/50 (88%) 44/50 (88%) | |POLY-3 ADJUSTED (b)| 78.0% 96.5% 96.8% 100.0% |89.9% 94.6% 98.4% 99.5% | |TERMINAL (d) | 28/35 (80%) 28/28 (100%) 34/34 (100%) 35/35 (100%)|29/32 (91%) 29/30 (97%) 22/22 (100%) 29/29 (100%) | |FIRST INCIDENCE | 520 522 513 406 |476 419 509 430 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.138 P=0.005 ** P=0.055 P=0.042 * |P=0.077 P=0.317 P=0.012 * P=0.120 | |POLY 3 | P<0.001 ** P=0.004 ** P=0.004 ** P<0.001 ** |P=0.011 * P=0.323 P=0.081 P=0.045 * | |POLY 1.5 | P<0.001 ** P=0.008 ** P=0.005 ** P<0.001 ** |P=0.020 * P=0.347 P=0.101 P=0.057 | |POLY 6 | P<0.001 ** P=0.003 ** P=0.004 ** P<0.001 ** |P=0.011 * P=0.297 P=0.070 P=0.050 | |LOGISTIC REGRESSION| P<0.001 ** P=0.006 ** P=0.005 ** P<0.001 ** |P=0.012 * P=0.349 P=0.120 P=0.038 * | |COCH-ARM / FISHERS | P=0.005 ** P=0.033 * P=0.017 * P=0.006 ** |P=0.279 P=0.590 P=0.371 P=0.371 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 38/50 (76%) 47/50 (94%) 46/49 (94%) 47/50 (94%) |41/49 (84%) 42/50 (84%) 45/50 (90%) 44/50 (88%) | |POLY-3 ADJUSTED (b)| 80.1% 98.9% 98.5% 100.0% |89.9% 94.6% 99.6% 99.5% | |TERMINAL (d) | 29/35 (83%) 28/28 (100%) 34/34 (100%) 35/35 (100%)|29/32 (91%) 29/30 (97%) 22/22 (100%) 29/29 (100%) | |FIRST INCIDENCE | 520 522 513 406 |476 419 509 430 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.213 P=0.003 ** P=0.055 P=0.059 |P=0.075 P=0.317 P=0.008 ** P=0.120 | |POLY 3 | P<0.001 ** P=0.002 ** P=0.003 ** P<0.001 ** |P=0.009 ** P=0.323 P=0.042 * P=0.045 * | |POLY 1.5 | P<0.001 ** P=0.002 ** P=0.003 ** P<0.001 ** |P=0.015 * P=0.347 P=0.045 * P=0.057 | |POLY 6 | P<0.001 ** P=0.002 ** P=0.003 ** P<0.001 ** |P=0.009 ** P=0.297 P=0.049 * P=0.050 | |LOGISTIC REGRESSION| P<0.001 ** P=0.002 ** P=0.003 ** P<0.001 ** |P=0.010 * P=0.349 P=0.051 P=0.038 * | |COCH-ARM / FISHERS | P=0.011 * P=0.011 * P=0.013 * P=0.011 * |P=0.265 P=0.590 P=0.264 P=0.371 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 7 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 12/49 (24%) 5/50 (10%) 8/49 (16%) 8/50 (16%) |2/50 (4%) 3/50 (6%) 0/50 (0%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 27.0% 11.9% 18.5% 18.3% |4.7% 7.2% 0.0% 7.8% | |TERMINAL (d) | 9/35 (26%) 4/28 (14%) 6/34 (18%) 6/35 (17%) |2/32 (6%) 1/30 (3%) 0/22 (0%) 2/29 (7%) | |FIRST INCIDENCE | 520 546 526 639 |729 (T) 555 --- 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.278N P=0.124N P=0.258N P=0.235N |P=0.447 P=0.476 P=0.324N P=0.450 | |POLY 3 | P=0.303N P=0.065N P=0.245N P=0.239N |P=0.463 P=0.486 P=0.254N P=0.455 | |POLY 1.5 | P=0.317N P=0.059N P=0.243N P=0.244N |P=0.471 P=0.483 P=0.250N P=0.463 | |POLY 6 | P=0.279N P=0.075N P=0.245N P=0.227N |P=0.455 P=0.491 P=0.261N P=0.450 | |LOGISTIC REGRESSION| P=0.317N P=0.062N P=0.241N P=0.233N |P=0.473 P=0.493 (e) P=0.444 | |COCH-ARM / FISHERS | P=0.303N P=0.049N* P=0.226N P=0.212N |P=0.500 P=0.500 P=0.247N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 2/50 (4%) 1/49 (2%) 1/50 (2%) |2/50 (4%) 1/50 (2%) 2/50 (4%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 2.3% 4.8% 2.4% 2.3% |4.7% 2.5% 5.0% 7.6% | |TERMINAL (d) | 0/35 (0%) 2/28 (7%) 1/34 (3%) 1/35 (3%) |1/32 (3%) 1/30 (3%) 1/22 (5%) 0/29 (0%) | |FIRST INCIDENCE | 672 722 (T) 722 (T) 722 (T) |662 729 (T) 727 595 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.507N P=0.442 P=0.751 P=0.755N |P=0.278 P=0.524N P=0.580 P=0.455 | |POLY 3 | P=0.535N P=0.481 P=0.753 P=0.757 |P=0.287 P=0.521N P=0.665 P=0.460 | |POLY 1.5 | P=0.538N P=0.490 P=0.755 P=0.756 |P=0.291 P=0.518N P=0.672 P=0.466 | |POLY 6 | P=0.531N P=0.468 P=0.752 P=0.760 |P=0.285 P=0.524N P=0.652 P=0.458 | |LOGISTIC REGRESSION| P=0.518N P=0.475 P=0.758 P=0.761 |P=0.285 P=0.518N P=0.661 P=0.481 | |COCH-ARM / FISHERS | P=0.526N P=0.508 P=0.753N P=0.747N |P=0.313 P=0.500N P=0.691N P=0.500 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 8 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 13/49 (27%) 7/50 (14%) 9/49 (18%) 8/50 (16%) |4/50 (8%) 4/50 (8%) 2/50 (4%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 29.1% 16.6% 20.8% 18.3% |9.3% 9.6% 5.0% 12.7% | |TERMINAL (d) | 9/35 (26%) 6/28 (21%) 7/34 (21%) 6/35 (17%) |3/32 (9%) 2/30 (7%) 1/22 (5%) 2/29 (7%) | |FIRST INCIDENCE | 520 546 526 639 |662 555 727 595 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.175N P=0.221N P=0.270N P=0.172N |P=0.382 P=0.609 P=0.495N P=0.439 | |POLY 3 | P=0.197N P=0.130N P=0.258N P=0.174N |P=0.399 P=0.624 P=0.374N P=0.445 | |POLY 1.5 | P=0.208N P=0.116N P=0.254N P=0.178N |P=0.408 P=0.622 P=0.365N P=0.453 | |POLY 6 | P=0.179N P=0.151N P=0.262N P=0.167N |P=0.392 P=0.627 P=0.391N P=0.442 | |LOGISTIC REGRESSION| P=0.204N P=0.121N P=0.250N P=0.168N |P=0.407 P=0.627 P=0.395N P=0.448 | |COCH-ARM / FISHERS | P=0.193N P=0.096N P=0.234N P=0.150N |P=0.446 P=0.643N P=0.339N P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Mesentery | | Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 0.0% 2.4% 2.3% 0.0% |0.0% 4.9% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/28 (0%) 0/35 (0%) 0/35 (0%) |0/32 (0%) 0/30 (0%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | --- 561 637 --- |--- 599 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.593N P=0.487 P=0.495 (e) |P=0.423N P=0.231 (e) (e) | |POLY 3 | P=0.604N P=0.488 P=0.496 (e) |P=0.431N P=0.228 (e) (e) | |POLY 1.5 | P=0.606N P=0.492 P=0.496 (e) |P=0.427N P=0.228 (e) (e) | |POLY 6 | P=0.601N P=0.483 P=0.496 (e) |P=0.436N P=0.230 (e) (e) | |LOGISTIC REGRESSION| P=0.571N P=0.535 P=0.510 (e) |P=0.403N P=0.241 (e) (e) | |COCH-ARM / FISHERS | P=0.595N P=0.500 P=0.500 (e) |P=0.405N P=0.247 (e) (e) | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 9 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |4/47 (9%) 3/49 (6%) 1/46 (2%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| |9.9% 7.6% 2.7% 0.0% | |TERMINAL (d) | |4/32 (13%) 2/29 (7%) 1/21 (5%) 0/29 (0%) | |FIRST INCIDENCE | |729 (T) 696 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.038N* P=0.551N P=0.324N P=0.075N | |POLY 3 | |P=0.029N* P=0.513N P=0.210N P=0.069N | |POLY 1.5 | |P=0.028N* P=0.508N P=0.204N P=0.066N | |POLY 6 | |P=0.030N* P=0.520N P=0.220N P=0.072N | |LOGISTIC REGRESSION| |P=0.034N* P=0.535N P=0.324N (e) | |COCH-ARM / FISHERS | |P=0.024N* P=0.476N P=0.187N P=0.054N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/46 (0%) 0/47 (0%) 0/45 (0%) 0/49 (0%) |8/47 (17%) 9/44 (20%) 6/42 (14%) 2/46 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |19.7% 25.0% 17.1% 5.7% | |TERMINAL (d) | 0/34 (0%) 0/26 (0%) 0/32 (0%) 0/34 (0%) |8/31 (26%) 6/26 (23%) 5/21 (24%) 2/27 (7%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 608 700 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.044N* P=0.362 P=0.545 P=0.068N | |POLY 3 | (e) (e) (e) (e) |P=0.041N* P=0.391 P=0.502N P=0.071N | |POLY 1.5 | (e) (e) (e) (e) |P=0.037N* P=0.391 P=0.490N P=0.066N | |POLY 6 | (e) (e) (e) (e) |P=0.045N* P=0.395 P=0.520N P=0.075N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.041N* P=0.364 P=0.608N P=0.068N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.026N* P=0.440 P=0.477N P=0.049N* | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 10 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Skin | | Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 2/50 (4%) 3/50 (6%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 0.0% 0.0% |4.7% 4.9% 7.4% 9.9% | |TERMINAL (d) | 0/35 (0%) 0/28 (0%) 0/35 (0%) 0/35 (0%) |2/32 (6%) 1/30 (3%) 0/22 (0%) 1/29 (3%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 573 556 299 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.185 P=0.676 P=0.402 P=0.302 | |POLY 3 | (e) (e) (e) (e) |P=0.197 P=0.679 P=0.477 P=0.311 | |POLY 1.5 | (e) (e) (e) (e) |P=0.200 P=0.679 P=0.480 P=0.313 | |POLY 6 | (e) (e) (e) (e) |P=0.196 P=0.681 P=0.470 P=0.310 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.224 P=0.682 P=0.488 P=0.364 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.216 P=0.691N P=0.500 P=0.339 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 3/50 (6%) 1/47 (2%) 1/49 (2%) |0/49 (0%) 0/50 (0%) 0/48 (0%) 0/49 (0%) | |POLY-3 ADJUSTED (b)| 2.3% 7.1% 2.4% 2.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 2/28 (7%) 1/34 (3%) 1/35 (3%) |0/32 (0%) 0/30 (0%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | 722 (T) 532 722 (T) 722 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.429N P=0.247 P=0.755 P=0.762 |(e) (e) (e) (e) | |POLY 3 | P=0.459N P=0.292 P=0.748 P=0.755 |(e) (e) (e) (e) | |POLY 1.5 | P=0.463N P=0.299 P=0.748 P=0.752 |(e) (e) (e) (e) | |POLY 6 | P=0.451N P=0.283 P=0.750 P=0.759 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.454N P=0.309 P=0.755 P=0.762 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.449N P=0.316 P=0.742 P=0.753N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 11 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 2/49 (4%) 2/50 (4%) |3/50 (6%) 2/50 (4%) 3/50 (6%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 4.6% 4.8% 4.7% 4.6% |7.0% 4.9% 7.6% 7.8% | |TERMINAL (d) | 2/35 (6%) 1/28 (4%) 2/34 (6%) 2/35 (6%) |3/32 (9%) 1/30 (3%) 3/22 (14%) 3/29 (10%) | |FIRST INCIDENCE | 722 (T) 677 722 (T) 722 (T) |729 (T) 674 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.565N P=0.625 P=0.685 P=0.695 |P=0.462 P=0.526N P=0.481 P=0.618 | |POLY 3 | P=0.595N P=0.678 P=0.683 P=0.690 |P=0.472 P=0.522N P=0.628 P=0.615 | |POLY 1.5 | P=0.588 P=0.686 P=0.685 P=0.687 |P=0.483 P=0.522N P=0.636 P=0.624 | |POLY 6 | P=0.586N P=0.667 P=0.682 P=0.693N |P=0.463 P=0.522N P=0.614 P=0.609 | |LOGISTIC REGRESSION| P=0.572N P=0.662 P=0.685 P=0.695 |P=0.456 P=0.527N P=0.481 P=0.618 | |COCH-ARM / FISHERS | P=0.591N P=0.684N P=0.691N P=0.684N |P=0.521 P=0.500N P=0.661N P=0.661N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| |4.6% 2.5% 0.0% 0.0% | |TERMINAL (d) | |0/32 (0%) 1/30 (3%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | |151 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.118N P=0.519N P=0.275N P=0.259N | |POLY 3 | |P=0.105N P=0.527N P=0.259N P=0.266N | |POLY 1.5 | |P=0.103N P=0.524N P=0.255N P=0.261N | |POLY 6 | |P=0.106N P=0.530N P=0.267N P=0.270N | |LOGISTIC REGRESSION| |P=0.084N P=0.443N P=0.165N P=0.154N | |COCH-ARM / FISHERS | |P=0.101N P=0.500N P=0.247N P=0.247N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 12 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 0.0% 7.2% 4.6% 2.3% |0.0% 0.0% 2.5% 7.7% | |TERMINAL (d) | 0/35 (0%) 1/28 (4%) 2/35 (6%) 1/35 (3%) |0/32 (0%) 0/30 (0%) 1/22 (5%) 2/29 (7%) | |FIRST INCIDENCE | --- 680 722 (T) 722 (T) |--- --- 729 (T) 615 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.580 P=0.095 P=0.238 P=0.500 |P=0.018 * (e) P=0.425 P=0.105 | |POLY 3 | P=0.536 P=0.107 P=0.231 P=0.493 |P=0.017 * (e) P=0.485 P=0.103 | |POLY 1.5 | P=0.531 P=0.111 P=0.232 P=0.492 |P=0.017 * (e) P=0.489 P=0.105 | |POLY 6 | P=0.545 P=0.102 P=0.230 P=0.497 |P=0.016 * (e) P=0.479 P=0.101 | |LOGISTIC REGRESSION| P=0.566 P=0.103 P=0.238 P=0.500 |P=0.017 * (e) P=0.425 P=0.107 | |COCH-ARM / FISHERS | P=0.556 P=0.121 P=0.247 P=0.500 |P=0.020 * (e) P=0.500 P=0.121 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 4/50 (8%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 4.5% 9.4% 4.6% 2.3% |0.0% 0.0% 2.5% 0.0% | |TERMINAL (d) | 1/35 (3%) 2/28 (7%) 1/35 (3%) 1/35 (3%) |0/32 (0%) 0/30 (0%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | 706 532 630 722 (T) |--- --- 723 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.254N P=0.265 P=0.688 P=0.503N |P=0.674 (e) P=0.443 (e) | |POLY 3 | P=0.276N P=0.313 P=0.686 P=0.512N |P=0.659 (e) P=0.485 (e) | |POLY 1.5 | P=0.279N P=0.321 P=0.686 P=0.514N |P=0.666 (e) P=0.489 (e) | |POLY 6 | P=0.269N P=0.303 P=0.687 P=0.507N |P=0.656 (e) P=0.479 (e) | |LOGISTIC REGRESSION| P=0.268N P=0.333 P=0.688 P=0.501N |P=0.677 (e) P=0.464 (e) | |COCH-ARM / FISHERS | P=0.263N P=0.339 P=0.691N P=0.500N |P=0.694 (e) P=0.500 (e) | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 13 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/50 (4%) 7/50 (14%) 4/50 (8%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 4.5% 16.4% 9.2% 2.3% |0.0% 0.0% 5.0% 7.7% | |TERMINAL (d) | 1/35 (3%) 3/28 (11%) 3/35 (9%) 1/35 (3%) |0/32 (0%) 0/30 (0%) 1/22 (5%) 2/29 (7%) | |FIRST INCIDENCE | 706 532 630 722 (T) |--- --- 723 615 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.188N P=0.053 P=0.336 P=0.503N |P=0.025 * (e) P=0.171 P=0.105 | |POLY 3 | P=0.215N P=0.067 P=0.327 P=0.512N |P=0.022 * (e) P=0.221 P=0.103 | |POLY 1.5 | P=0.219N P=0.071 P=0.328 P=0.514N |P=0.023 * (e) P=0.225 P=0.105 | |POLY 6 | P=0.206N P=0.062 P=0.327 P=0.507N |P=0.022 * (e) P=0.214 P=0.101 | |LOGISTIC REGRESSION| P=0.207N P=0.073 P=0.324 P=0.501N |P=0.023 * (e) P=0.187 P=0.107 | |COCH-ARM / FISHERS | P=0.200N P=0.080 P=0.339 P=0.500N |P=0.028 * (e) P=0.247 P=0.121 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 ADJUSTED (b)| 2.2% 4.7% 2.3% 0.0% |4.5% 4.9% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/28 (0%) 1/35 (3%) 0/35 (0%) |0/32 (0%) 2/30 (7%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | 653 237 722 (T) --- |375 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.245N P=0.477 P=0.755 P=0.500N |P=0.105N P=0.666 P=0.252N P=0.266N | |POLY 3 | P=0.258N P=0.483 P=0.753 P=0.508N |P=0.096N P=0.664 P=0.260N P=0.267N | |POLY 1.5 | P=0.259N P=0.490 P=0.755 P=0.509N |P=0.094N P=0.669 P=0.254N P=0.260N | |POLY 6 | P=0.255N P=0.473 P=0.752 P=0.506N |P=0.100N P=0.659 P=0.270N P=0.273N | |LOGISTIC REGRESSION| P=0.200N P=0.588 P=0.760 P=0.495N |P=0.081N P=0.679N P=0.187N P=0.179N | |COCH-ARM / FISHERS | P=0.247N P=0.500 P=0.753N P=0.500N |P=0.086N P=0.691N P=0.247N P=0.247N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 14 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma And Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) 4/50 (8%) 1/50 (2%) |8/50 (16%) 9/50 (18%) 4/50 (8%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 8.8% 11.5% 9.0% 2.3% |18.0% 22.0% 9.8% 15.3% | |TERMINAL (d) | 2/35 (6%) 0/28 (0%) 3/35 (9%) 1/35 (3%) |2/32 (6%) 7/30 (23%) 0/22 (0%) 5/29 (17%) | |FIRST INCIDENCE | 542 237 226 722 (T) |375 599 624 510 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.111N P=0.437 P=0.633 P=0.187N |P=0.328N P=0.441 P=0.285N P=0.481N | |POLY 3 | P=0.125N P=0.474 P=0.629 P=0.194N |P=0.298N P=0.428 P=0.221N P=0.483N | |POLY 1.5 | P=0.126N P=0.484 P=0.634 P=0.195N |P=0.282N P=0.440 P=0.211N P=0.462N | |POLY 6 | P=0.122N P=0.461 P=0.623 P=0.193N |P=0.316N P=0.413 P=0.237N P=0.505N | |LOGISTIC REGRESSION| P=0.086N P=0.568 P=0.613N P=0.179N |P=0.267N P=0.469 P=0.181N P=0.418N | |COCH-ARM / FISHERS | P=0.112N P=0.500 P=0.643N P=0.181N |P=0.231N P=0.500 P=0.178N P=0.387N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 3/50 (6%) 1/50 (2%) |6/50 (12%) 7/50 (14%) 4/50 (8%) 6/50 (12%) | |POLY-3 ADJUSTED (b)| 6.6% 7.1% 6.8% 2.3% |13.9% 17.1% 9.8% 15.3% | |TERMINAL (d) | 2/35 (6%) 0/28 (0%) 2/35 (6%) 1/35 (3%) |2/32 (6%) 5/30 (17%) 0/22 (0%) 5/29 (17%) | |FIRST INCIDENCE | 542 595 226 722 (T) |687 599 624 510 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.215N P=0.602 P=0.656 P=0.312N |P=0.535 P=0.450 P=0.499N P=0.535 | |POLY 3 | P=0.233N P=0.632 P=0.653 P=0.322N |P=0.546N P=0.460 P=0.407N P=0.554 | |POLY 1.5 | P=0.236N P=0.642 P=0.656 P=0.323N |P=0.533N P=0.463 P=0.401N P=0.566 | |POLY 6 | P=0.227N P=0.621 P=0.651 P=0.318N |P=0.557 P=0.455 P=0.420N P=0.542 | |LOGISTIC REGRESSION| P=0.201N P=0.650N P=0.627N P=0.308N |P=0.543N P=0.458 P=0.401N P=0.557 | |COCH-ARM / FISHERS | P=0.221N P=0.661N P=0.661N P=0.309N |P=0.485N P=0.500 P=0.370N P=0.620N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 15 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Mesothelioma: Benign, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 0.0% 0.0% 2.3% 2.3% |0.0% 0.0% 0.0% 5.1% | |TERMINAL (d) | 0/35 (0%) 0/28 (0%) 1/35 (3%) 0/35 (0%) |0/32 (0%) 0/30 (0%) 0/22 (0%) 0/29 (0%) | |FIRST INCIDENCE | --- --- 722 (T) 699 |--- --- --- 615 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.252 (e) P=0.500 P=0.500 |P=0.043 * (e) (e) P=0.220 | |POLY 3 | P=0.234 (e) P=0.494 P=0.494 |P=0.042 * (e) (e) P=0.218 | |POLY 1.5 | P=0.230 (e) P=0.495 P=0.492 |P=0.043 * (e) (e) P=0.221 | |POLY 6 | P=0.243 (e) P=0.494 P=0.497 |P=0.042 * (e) (e) P=0.218 | |LOGISTIC REGRESSION| P=0.240 (e) P=0.500 P=0.494 |P=0.046 * (e) (e) P=0.236 | |COCH-ARM / FISHERS | P=0.236 (e) P=0.500 P=0.500 |P=0.046 * (e) (e) P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 35/50 (70%) 42/50 (84%) 36/50 (72%) 39/50 (78%) |40/50 (80%) 41/50 (82%) 43/50 (86%) 36/50 (72%) | |POLY-3 ADJUSTED (b)| 74.7% 91.2% 77.4% 84.9% |85.5% 91.5% 97.3% 83.7% | |TERMINAL (d) | 27/35 (77%) 27/28 (96%) 28/35 (80%) 31/35 (89%) |28/32 (88%) 28/30 (93%) 22/22 (100%) 25/29 (86%) | |FIRST INCIDENCE | 520 522 513 406 |151 419 509 430 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.504N P=0.009 ** P=0.479 P=0.276 |P=0.476 P=0.325 P=0.013 * P=0.569N | |POLY 3 | P=0.275 P=0.023 * P=0.476 P=0.157 |P=0.445N P=0.275 P=0.035 * P=0.527N | |POLY 1.5 | P=0.248 P=0.033 * P=0.465 P=0.145 |P=0.397N P=0.259 P=0.052 P=0.495N | |POLY 6 | P=0.313 P=0.016 * P=0.492 P=0.175 |P=0.473N P=0.307 P=0.026 * P=0.540N | |LOGISTIC REGRESSION| P=0.240 P=0.018 * P=0.418 P=0.131 |P=0.385N P=0.303 P=0.105 P=0.467N | |COCH-ARM / FISHERS | P=0.368 P=0.077 P=0.500 P=0.247 |P=0.169N P=0.500 P=0.298 P=0.241N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 04 Page 16 Statistical Analysis of Primary Tumors in Mice(B6C3F1) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 22/50 (44%) 46/50 (92%) 47/50 (94%) 42/50 (84%) |26/50 (52%) 30/50 (60%) 40/50 (80%) 44/50 (88%) | |POLY-3 ADJUSTED (b)| 46.5% 94.8% 96.4% 89.4% |56.0% 69.7% 90.1% 99.2% | |TERMINAL (d) | 13/35 (37%) 26/28 (93%) 34/35 (97%) 30/35 (86%) |14/32 (44%) 20/30 (67%) 20/22 (91%) 29/29 (100%) | |FIRST INCIDENCE | 542 237 226 406 |375 573 556 299 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.018 * P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.217 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.128 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.145 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.117 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.190 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.273 P=0.003 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 250 PPM 500 PPM 1000 PPM |0 PPM 125 PPM 250 PPM 500 PPM | | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 43/50 (86%) 49/50 (98%) 48/50 (96%) 47/50 (94%) |47/50 (94%) 45/50 (90%) 45/50 (90%) 45/50 (90%) | |POLY-3 ADJUSTED (b)| 88.7% 100.0% 98.0% 100.0% |96.5% 99.7% 99.6% 99.7% | |TERMINAL (d) | 31/35 (89%) 28/28 (100%) 34/35 (97%) 35/35 (100%)|31/32 (97%) 30/30 (100%) 22/22 (100%) 29/29 (100%) | |FIRST INCIDENCE | 520 237 226 406 |151 419 509 299 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.531 P=0.015 * P=0.212 P=0.280 |P=0.273 P=0.509 P=0.069 P=0.382 | |POLY 3 | P=0.009 ** P=0.018 * P=0.069 P=0.021 * |P=0.174 P=0.348 P=0.366 P=0.347 | |POLY 1.5 | P=0.008 ** P=0.015 * P=0.060 P=0.018 * |P=0.270 P=0.416 P=0.442 P=0.418 | |POLY 6 | P=0.012 * P=0.022 * P=0.084 P=0.025 * |P=0.164 P=0.358 P=0.364 P=0.357 | |LOGISTIC REGRESSION| P=0.023 * P=0.010 * P=0.043 * P=0.022 * |P=0.427 P=0.691N P=0.657N P=0.637 | |COCH-ARM / FISHERS | P=0.178 P=0.030 * P=0.080 P=0.159 |P=0.338N P=0.357N P=0.357N 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).