NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: TSI Mason Research PYRIDINE DATE: 09/26/97 EXPERIMENT: 55301 TEST: 06 TIME: 13:41:43 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-95268 ROUTE: DOSED WATER NTP C#: 55301B PATHOLOGIST: D. SAUER CAS: 110-86-1 Rats(WISTAR OUTBRED) ----------------------------- 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. ---------------- Kidney NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: TSI Mason Research PYRIDINE DATE: 09/26/97 EXPERIMENT: 55301 TEST: 06 TIME: 13:41:43 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: CONT: N01-ES-95268 ROUTE: DOSED WATER NTP C#: 55301B PATHOLOGIST: D. SAUER CAS: 110-86-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF PYRIDINE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Kidney, Renal Tubule (Step Section) Carcinoma and Adenoma Hyperplasia Hyperplasia and Adenoma Hyperplasia, Carcinoma or Adenoma Kidney, Renal Tubule (Step and Original Sections) Hyperplasia Hyperplasia and Adenoma Hyperplasia, Carcinoma or Adenoma Kidney: Renal Tubule Hyperplasia Hyperplasia and Adenoma Hyperplasia, Carcinoma or Adenoma Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 1 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step Section) | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.5% 5.6% 11.5% 6.9% | |TERMINAL (d) | 1/22 (5%) 0/14 (0%) 2/11 (18%) 0/7 (0%) | |FIRST INCIDENCE | 722 (T) 611 520 550 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.114 P=0.401 P=0.064 P=0.230 | |POLY 3 | P=0.209 P=0.459 P=0.136 P=0.388 | |POLY 1.5 | P=0.281 P=0.475 P=0.153 P=0.436 | |POLY 6 | P=0.129 P=0.441 P=0.118 P=0.325 | |LOGISTIC REGRESSION| P=0.283 P=0.461 P=0.140 P=0.394 | |COCH-ARM / FISHERS | P=0.387 P=0.500 P=0.181 P=0.500 | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step Section) | | Carcinoma and Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 5/50 (10%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 2.5% 5.6% 14.4% 6.9% | |TERMINAL (d) | 1/22 (5%) 0/14 (0%) 2/11 (18%) 0/7 (0%) | |FIRST INCIDENCE | 722 (T) 611 520 550 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.091 P=0.401 P=0.028 * P=0.230 | |POLY 3 | P=0.181 P=0.459 P=0.070 P=0.388 | |POLY 1.5 | P=0.257 P=0.475 P=0.082 P=0.436 | |POLY 6 | P=0.101 P=0.441 P=0.058 P=0.325 | |LOGISTIC REGRESSION| P=0.243 P=0.461 P=0.068 P=0.394 | |COCH-ARM / FISHERS | P=0.371 P=0.500 P=0.102 P=0.500 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 2 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step Section) | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 5/50 (10%) 13/50 (26%) 10/50 (20%) 9/50 (18%) | |POLY-3 ADJUSTED (b)| 12.0% 33.4% 27.0% 28.0% | |TERMINAL (d) | 1/22 (5%) 3/14 (21%) 3/11 (27%) 0/7 (0%) | |FIRST INCIDENCE | 557 352 486 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.023 * P=0.013 * P=0.035 * P=0.016 * | |POLY 3 | P=0.109 P=0.018 * P=0.078 P=0.074 | |POLY 1.5 | P=0.189 P=0.023 * P=0.098 P=0.115 | |POLY 6 | P=0.047 * P=0.014 * P=0.058 P=0.041 * | |LOGISTIC REGRESSION| P=0.369 P=0.041 * P=0.161 P=0.235 | |COCH-ARM / FISHERS | P=0.345 P=0.033 * P=0.131 P=0.194 | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step Section) | | Hyperplasia and Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 6/50 (12%) 15/50 (30%) 12/50 (24%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 14.4% 38.0% 31.6% 33.5% | |TERMINAL (d) | 2/22 (9%) 3/14 (21%) 3/11 (27%) 0/7 (0%) | |FIRST INCIDENCE | 557 352 486 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * P=0.008 ** P=0.020 * P=0.006 ** | |POLY 3 | P=0.074 P=0.012 * P=0.056 P=0.045 * | |POLY 1.5 | P=0.139 P=0.016 * P=0.070 P=0.076 | |POLY 6 | P=0.030 * P=0.010 * P=0.042 * P=0.022 * | |LOGISTIC REGRESSION| P=0.291 P=0.027 * P=0.123 P=0.146 | |COCH-ARM / FISHERS | P=0.282 P=0.024 * P=0.096 P=0.143 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 3 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step Section) | | Hyperplasia, Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 6/50 (12%) 15/50 (30%) 13/50 (26%) 11/50 (22%) | |POLY-3 ADJUSTED (b)| 14.4% 38.0% 34.1% 33.5% | |TERMINAL (d) | 2/22 (9%) 3/14 (21%) 3/11 (27%) 0/7 (0%) | |FIRST INCIDENCE | 557 352 486 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** P=0.008 ** P=0.011 * P=0.006 ** | |POLY 3 | P=0.067 P=0.012 * P=0.032 * P=0.045 * | |POLY 1.5 | P=0.130 P=0.016 * P=0.042 * P=0.076 | |POLY 6 | P=0.026 * P=0.010 * P=0.023 * P=0.022 * | |LOGISTIC REGRESSION| P=0.270 P=0.027 * P=0.076 P=0.146 | |COCH-ARM / FISHERS | P=0.274 P=0.024 * P=0.062 P=0.143 | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step and Original Sections) | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 3/50 (6%) 6/50 (12%) 5/50 (10%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 7.4% 16.5% 14.4% 13.6% | |TERMINAL (d) | 1/22 (5%) 1/14 (7%) 2/11 (18%) 0/7 (0%) | |FIRST INCIDENCE | 576 610 520 550 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.104 P=0.134 P=0.142 P=0.130 | |POLY 3 | P=0.288 P=0.187 P=0.271 P=0.328 | |POLY 1.5 | P=0.391 P=0.208 P=0.306 P=0.400 | |POLY 6 | P=0.172 P=0.168 P=0.231 P=0.241 | |LOGISTIC REGRESSION| P=0.345 P=0.204 P=0.286 P=0.369 | |COCH-ARM / FISHERS | P=0.533 P=0.243 P=0.357 P=0.500 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 4 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step and Original Sections) | | Carcinoma and Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 3/50 (6%) 6/50 (12%) 6/50 (12%) 4/50 (8%) | |POLY-3 ADJUSTED (b)| 7.4% 16.5% 17.2% 13.6% | |TERMINAL (d) | 1/22 (5%) 1/14 (7%) 2/11 (18%) 0/7 (0%) | |FIRST INCIDENCE | 576 610 520 550 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.087 P=0.134 P=0.076 P=0.130 | |POLY 3 | P=0.258 P=0.187 P=0.167 P=0.328 | |POLY 1.5 | P=0.365 P=0.208 P=0.197 P=0.400 | |POLY 6 | P=0.144 P=0.168 P=0.135 P=0.241 | |LOGISTIC REGRESSION| P=0.308 P=0.204 P=0.170 P=0.369 | |COCH-ARM / FISHERS | P=0.516 P=0.243 P=0.243 P=0.500 | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step and Original Sections) | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 10/50 (20%) 22/50 (44%) 14/50 (28%) 13/50 (26%) | |POLY-3 ADJUSTED (b)| 23.7% 52.0% 36.5% 37.8% | |TERMINAL (d) | 5/22 (23%) 5/14 (36%) 5/11 (46%) 0/7 (0%) | |FIRST INCIDENCE | 468 352 354 463 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.037 * P=0.002 ** P=0.040 * P=0.017 * | |POLY 3 | P=0.256 P=0.005 ** P=0.149 P=0.133 | |POLY 1.5 | P=0.387 P=0.005 ** P=0.186 P=0.197 | |POLY 6 | P=0.137 P=0.004 ** P=0.111 P=0.079 | |LOGISTIC REGRESSION| P=0.411N P=0.013 * P=0.278 P=0.388 | |COCH-ARM / FISHERS | P=0.490N P=0.009 ** P=0.241 P=0.318 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 5 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step and Original Sections) | | Hyperplasia and Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 12/50 (24%) 25/50 (50%) 16/50 (32%) 16/50 (32%) | |POLY-3 ADJUSTED (b)| 28.3% 58.0% 40.7% 45.4% | |TERMINAL (d) | 6/22 (27%) 5/14 (36%) 5/11 (46%) 0/7 (0%) | |FIRST INCIDENCE | 468 352 354 463 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * P=0.002 ** P=0.036 * P=0.005 ** | |POLY 3 | P=0.203 P=0.003 ** P=0.166 P=0.087 | |POLY 1.5 | P=0.321 P=0.004 ** P=0.200 P=0.139 | |POLY 6 | P=0.107 P=0.004 ** P=0.132 P=0.048 * | |LOGISTIC REGRESSION| P=0.514N P=0.008 ** P=0.285 P=0.236 | |COCH-ARM / FISHERS | P=0.530 P=0.006 ** P=0.252 P=0.252 | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney, Renal Tubule (Step and Original Sections) | | Hyperplasia, Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # | |----------- | | |OVERALL (a) | 12/50 (24%) 25/50 (50%) 17/50 (34%) 16/50 (32%) | |POLY-3 ADJUSTED (b)| 28.3% 58.0% 43.2% 45.4% | |TERMINAL (d) | 6/22 (27%) 5/14 (36%) 5/11 (46%) 0/7 (0%) | |FIRST INCIDENCE | 468 352 354 463 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.013 * P=0.002 ** P=0.022 * P=0.005 ** | |POLY 3 | P=0.189 P=0.003 ** P=0.114 P=0.087 | |POLY 1.5 | P=0.306 P=0.004 ** P=0.143 P=0.139 | |POLY 6 | P=0.096 P=0.004 ** P=0.086 P=0.048 * | |LOGISTIC REGRESSION| P=0.538N P=0.008 ** P=0.206 P=0.236 | |COCH-ARM / FISHERS | P=0.520 P=0.006 ** P=0.189 P=0.252 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 6 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 5/50 (10%) 1/50 (2%) 2/50 (4%) | |POLY-3 ADJUSTED (b)| 4.9% 13.9% 3.0% 7.0% | |TERMINAL (d) | 0/22 (0%) 1/14 (7%) 0/11 (0%) 0/7 (0%) | |FIRST INCIDENCE | 576 610 721 606 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.417 P=0.128 P=0.656N P=0.381 | |POLY 3 | P=0.531N P=0.167 P=0.564N P=0.562 | |POLY 1.5 | P=0.459N P=0.186 P=0.537N P=0.622 | |POLY 6 | P=0.499 P=0.149 P=0.599N P=0.477 | |LOGISTIC REGRESSION| P=0.539N P=0.186 P=0.547N P=0.640 | |COCH-ARM / FISHERS | P=0.371N P=0.218 P=0.500N P=0.691N | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 5/50 (10%) 1/50 (2%) 3/50 (6%) | |POLY-3 ADJUSTED (b)| 4.9% 13.9% 3.0% 10.4% | |TERMINAL (d) | 0/22 (0%) 1/14 (7%) 0/11 (0%) 0/7 (0%) | |FIRST INCIDENCE | 576 610 721 606 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.206 P=0.128 P=0.656N P=0.161 | |POLY 3 | P=0.420 P=0.167 P=0.564N P=0.348 | |POLY 1.5 | P=0.501 P=0.186 P=0.537N P=0.413 | |POLY 6 | P=0.316 P=0.149 P=0.599N P=0.268 | |LOGISTIC REGRESSION| P=0.414 P=0.186 P=0.547N P=0.372 | |COCH-ARM / FISHERS | P=0.562N P=0.218 P=0.500N P=0.500 | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 7 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 17/50 (34%) 8/50 (16%) 5/50 (10%) | |POLY-3 ADJUSTED (b)| 14.5% 41.6% 22.0% 16.2% | |TERMINAL (d) | 4/22 (18%) 3/14 (21%) 3/11 (27%) 0/7 (0%) | |FIRST INCIDENCE | 468 445 354 463 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.430 P=0.003 ** P=0.122 P=0.315 | |POLY 3 | P=0.390N P=0.004 ** P=0.288 P=0.552 | |POLY 1.5 | P=0.255N P=0.005 ** P=0.330 P=0.617N | |POLY 6 | P=0.489 P=0.005 ** P=0.239 P=0.438 | |LOGISTIC REGRESSION| P=0.093N P=0.012 * P=0.430 P=0.434N | |COCH-ARM / FISHERS | P=0.131N P=0.008 ** P=0.387 P=0.500N | |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia and Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 20/50 (40%) 8/50 (16%) 7/50 (14%) | |POLY-3 ADJUSTED (b)| 16.9% 48.4% 22.0% 22.3% | |TERMINAL (d) | 4/22 (18%) 4/14 (29%) 3/11 (27%) 0/7 (0%) | |FIRST INCIDENCE | 468 445 354 463 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.293 P<0.001 ** P=0.182 P=0.138 | |POLY 3 | P=0.443N P<0.001 ** P=0.390 P=0.392 | |POLY 1.5 | P=0.299N P=0.002 ** P=0.438 P=0.486 | |POLY 6 | P=0.436 P<0.001 ** P=0.333 P=0.281 | |LOGISTIC REGRESSION| P=0.150N P=0.004 ** P=0.531 P=0.621N | |COCH-ARM / FISHERS | P=0.159N P=0.003 ** P=0.500 P=0.613N | |=================================================================================================================================| Date: 09/26/97 EXPERIMENT: 55301 TEST: 06 Page 8 Statistical Analysis of Primary Tumors in Rats(WISTAR OUTBRED) - PYRIDINE Terminal Sacrifice at 103 weeks |=================================================================================================================================| | | | | | | Males | |Dose | 0 PPM 100 PPM | 200 PPM 400 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia, Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 7/50 (14%) 20/50 (40%) 8/50 (16%) 8/50 (16%) | |POLY-3 ADJUSTED (b)| 16.9% 48.4% 22.0% 25.4% | |TERMINAL (d) | 4/22 (18%) 4/14 (29%) 3/11 (27%) 0/7 (0%) | |FIRST INCIDENCE | 468 445 354 463 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.198 P<0.001 ** P=0.182 P=0.071 | |POLY 3 | P=0.533 P<0.001 ** P=0.390 P=0.278 | |POLY 1.5 | P=0.403N P=0.002 ** P=0.438 P=0.367 | |POLY 6 | P=0.333 P<0.001 ** P=0.333 P=0.182 | |LOGISTIC REGRESSION| P=0.235N P=0.004 ** P=0.531 P=0.472 | |COCH-ARM / FISHERS | P=0.234N P=0.003 ** P=0.500 P=0.500 | |=================================================================================================================================| (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).