TDMS Study 97013-11 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus WATER DISINFECTION MODEL (SODIUM BROMATE) DATE: 06/18/04 EXPERIMENT: 97013 TEST: 11 TIME: 09:19:01 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: SKIN APPLICATION NTP C#: 97013B PATHOLOGIST: TOFT, JOHN CAS: 7789-38-0 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 MG/KG INCLUDE 002 0 MG/KG INCLUDE 003 64 MG/KG INCLUDE 004 64 MG/KG INCLUDE 005 128 MG/KG INCLUDE 006 128 MG/KG INCLUDE 007 256 MG/KG INCLUDE 008 256 MG/KG NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus WATER DISINFECTION MODEL (SODIUM BROMATE) DATE: 06/18/04 EXPERIMENT: 97013 TEST: 11 TIME: 09:19:01 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: SKIN APPLICATION NTP C#: 97013B PATHOLOGIST: TOFT, JOHN CAS: 7789-38-0 Mice(TG.AC HETEROZYGOUS TRANSGENIC) ----------------------------- 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 THE NUMBER OF ANIMALS NECROPSIED. --------------- Ovary NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus WATER DISINFECTION MODEL (SODIUM BROMATE) DATE: 06/18/04 EXPERIMENT: 97013 TEST: 11 TIME: 09:19:01 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: SKIN APPLICATION NTP C#: 97013B PATHOLOGIST: TOFT, JOHN CAS: 7789-38-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF WATER DISINFECTION MODEL (SODIUM BR =============================================================== Male Mice ------------ Organ Morphology ----- ---------- All Organs Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Skin Squamous Cell Papilloma All Organs Malignant and Benign Tumors =============================================================== Date: 06/18/04 EXPERIMENT: 97013 TEST: 11 Page 1 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SODIUM BR Terminal Sacrifice at 26 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 2/15 (13%) 3/15 (20%) 2/15 (13%) 4/15 (27%) |5/15 (33%) 3/15 (20%) 4/15 (27%) 9/15 (60%) | |POLY-3 RATE (b) | 2/12.62 3/12.51 2/13.58 4/15.00 |5/13.44 3/11.94 4/12.60 9/11.71 | |POLY-3 PERCENT (g) | 15.9% 24.0% 14.7% 26.7% |37.2% 25.1% 31.8% 76.8% | |TERMINAL (d) | 2/12 (17%) 2/11 (18%) 2/13 (15%) 4/15 (27%) |4/11 (36%) 2/10 (20%) 4/11 (36%) 9/11 (82%) | |FIRST INCIDENCE | 181 (T) 176 181 (T) 181 (T) |146 152 182 (T) 182 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.406 P=0.467 P=0.673N P=0.439 |P=0.044 * P=0.407N P=0.519N P=0.112 | |POLY 3 | P=0.361 P=0.496 P=0.673N P=0.414 |P=0.019 * P=0.412N P=0.547N P=0.045 * | |POLY 1.5 | P=0.339 P=0.497 P=0.677N P=0.394 |P=0.026 * P=0.397N P=0.519N P=0.067 | |POLY 6 | P=0.377 P=0.496 P=0.672N P=0.428 |P=0.015 * P=0.410N P=0.577N P=0.037 * | |LOGISTIC REGRESSION| P=0.383 P=0.490 P=0.673N P=0.439 |P=0.024 * P=0.392N P=0.528N P=0.063 | |COCH-ARM / FISHERS | P=0.268 P=0.500 P=0.701N P=0.326 |P=0.045 * P=0.341N P=0.500N P=0.136 | |ORDER RESTRICTED | P=0.390 (e) (e) (e) |P=0.010 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/15 (20%) 6/15 (40%) 6/15 (40%) 7/15 (47%) |6/15 (40%) 6/15 (40%) 7/15 (47%) 8/15 (53%) | |POLY-3 RATE (b) | 3/13.10 6/13.36 6/13.58 7/15.00 |6/12.95 6/12.85 7/13.14 8/12.55 | |POLY-3 PERCENT (g) | 22.9% 44.9% 44.2% 46.7% |46.3% 46.7% 53.3% 63.7% | |TERMINAL (d) | 2/12 (17%) 5/11 (46%) 6/13 (46%) 7/15 (47%) |6/11 (55%) 4/10 (40%) 6/11 (55%) 7/11 (64%) | |FIRST INCIDENCE | 146 74 181 (T) 181 (T) |182 (T) 81 140 99 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.283 P=0.189 P=0.262 P=0.235 |P=0.271 P=0.565 P=0.494 P=0.348 | |POLY 3 | P=0.200 P=0.218 P=0.228 P=0.182 |P=0.217 P=0.644 P=0.515 P=0.313 | |POLY 1.5 | P=0.183 P=0.222 P=0.231 P=0.170 |P=0.230 P=0.633 P=0.517 P=0.323 | |POLY 6 | P=0.207 P=0.207 P=0.218 P=0.185 |P=0.221 P=0.632N P=0.519 P=0.330 | |LOGISTIC REGRESSION| P=0.163 P=0.212 P=0.243 P=0.165 |P=0.214 P=0.591 P=0.451 P=0.260 | |COCH-ARM / FISHERS | P=0.120 P=0.213 P=0.213 P=0.123 |P=0.255 P=0.645N P=0.500 P=0.358 | |ORDER RESTRICTED | P=0.156 (e) (e) (e) |P=0.303 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 11 Page 2 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SODIUM BR Terminal Sacrifice at 26 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Tooth | | Odontogenic Tumor | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/15 (20%) 1/15 (7%) 1/15 (7%) 3/15 (20%) |3/15 (20%) 2/15 (13%) 5/15 (33%) 4/15 (27%) | |POLY-3 RATE (b) | 3/13.10 1/12.51 1/13.58 3/15.00 |3/13.69 2/11.78 5/13.09 4/12.47 | |POLY-3 PERCENT (g) | 22.9% 8.0% 7.4% 20.0% |21.9% 17.0% 38.2% 32.1% | |TERMINAL (d) | 2/12 (17%) 0/11 (0%) 1/13 (8%) 3/15 (20%) |1/11 (9%) 1/10 (10%) 4/11 (36%) 3/11 (27%) | |FIRST INCIDENCE | 146 176 181 (T) 181 (T) |146 165 145 113 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.582N P=0.329N P=0.275N P=0.565N |P=0.303 P=0.547N P=0.320 P=0.468 | |POLY 3 | P=0.563 P=0.313N P=0.283N P=0.604N |P=0.271 P=0.572N P=0.312 P=0.444 | |POLY 1.5 | P=0.549 P=0.306N P=0.281N P=0.616N |P=0.285 P=0.553N P=0.331 P=0.462 | |POLY 6 | P=0.570 P=0.321N P=0.288N P=0.600N |P=0.265 P=0.580N P=0.291 P=0.437 | |LOGISTIC REGRESSION| P=0.557 P=0.297N P=0.282N P=0.647N |P=0.287 P=0.520N P=0.339 P=0.499 | |COCH-ARM / FISHERS | P=0.500 P=0.299N P=0.299N P=0.674N |P=0.303 P=0.500N P=0.341 P=0.500 | |ORDER RESTRICTED | P=0.337N (e) (e) (e) |P=0.297 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Leukemia: Erythrocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 1/15 (7%) 0/15 (0%) |0/15 (0%) 2/15 (13%) 1/15 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 0/12.62 2/13.09 1/14.05 0/15.00 |0/12.95 2/12.89 1/13.17 2/13.29 | |POLY-3 PERCENT (g) | 0.0% 15.3% 7.1% 0.0% |0.0% 15.5% 7.6% 15.0% | |TERMINAL (d) | 0/12 (0%) 0/11 (0%) 0/13 (0%) 0/15 (0%) |0/11 (0%) 0/10 (0%) 0/11 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- 136 146 --- |--- 67 137 99 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.413N P=0.240 P=0.515 (e) |P=0.229 P=0.238 P=0.500 P=0.223 | |POLY 3 | P=0.398N P=0.238 P=0.521 (e) |P=0.250 P=0.229 P=0.503 P=0.236 | |POLY 1.5 | P=0.412N P=0.235 P=0.516 (e) |P=0.245 P=0.227 P=0.504 P=0.233 | |POLY 6 | P=0.387N P=0.243 P=0.526 (e) |P=0.263 P=0.235 P=0.504 P=0.245 | |LOGISTIC REGRESSION| P=0.538N P=0.233 P=0.469 (e) |P=0.247 P=0.318 P=0.455 P=0.280 | |COCH-ARM / FISHERS | P=0.460N P=0.241 P=0.500 (e) |P=0.239 P=0.241 P=0.500 P=0.241 | |ORDER RESTRICTED | P=0.295N (e) (e) (e) |P=0.150 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 11 Page 3 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SODIUM BR Terminal Sacrifice at 26 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/15 (27%) 8/15 (53%) 7/15 (47%) 10/15 (67%) |8/15 (53%) 9/15 (60%) 8/15 (53%) 11/15 (73%) | |POLY-3 RATE (b) | 4/13.10 8/13.44 7/13.58 10/15.00 |8/13.44 9/12.85 8/13.14 11/12.55 | |POLY-3 PERCENT (g) | 30.5% 59.5% 51.6% 66.7% |59.5% 70.0% 60.9% 87.6% | |TERMINAL (d) | 3/12 (25%) 6/11 (55%) 7/13 (54%) 10/15 (67%) |7/11 (64%) 7/10 (70%) 7/11 (64%) 10/11 (91%) | |FIRST INCIDENCE | 146 74 181 (T) 181 (T) |146 81 140 99 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.161 P=0.123 P=0.281 P=0.108 |P=0.196 P=0.385 P=0.622 P=0.194 | |POLY 3 | P=0.074 P=0.131 P=0.241 P=0.058 |P=0.099 P=0.439 P=0.628 P=0.106 | |POLY 1.5 | P=0.064 P=0.134 P=0.245 P=0.050 |P=0.127 P=0.448 P=0.646 P=0.139 | |POLY 6 | P=0.078 P=0.124 P=0.230 P=0.060 |P=0.087 P=0.453 P=0.610 P=0.096 | |LOGISTIC REGRESSION| P=0.068 P=0.128 P=0.262 P=0.060 |P=0.122 P=0.400 P=0.612 P=0.106 | |COCH-ARM / FISHERS | P=0.037 * P=0.132 P=0.225 P=0.033 * |P=0.186 P=0.500 P=0.642N P=0.225 | |ORDER RESTRICTED | P=0.036 * (e) (e) (e) |P=0.082 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 1/15 (7%) 0/15 (0%) |0/15 (0%) 2/15 (13%) 2/15 (13%) 3/15 (20%) | |POLY-3 RATE (b) | 0/12.62 2/13.09 1/14.05 0/15.00 |0/12.95 2/12.89 2/13.72 3/14.24 | |POLY-3 PERCENT (g) | 0.0% 15.3% 7.1% 0.0% |0.0% 15.5% 14.6% 21.1% | |TERMINAL (d) | 0/12 (0%) 0/11 (0%) 0/13 (0%) 0/15 (0%) |0/11 (0%) 0/10 (0%) 0/11 (0%) 0/11 (0%) | |FIRST INCIDENCE | --- 136 146 --- |--- 67 137 69 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.413N P=0.240 P=0.515 (e) |P=0.099 P=0.238 P=0.232 P=0.119 | |POLY 3 | P=0.398N P=0.238 P=0.521 (e) |P=0.124 P=0.229 P=0.244 P=0.123 | |POLY 1.5 | P=0.412N P=0.235 P=0.516 (e) |P=0.116 P=0.227 P=0.240 P=0.117 | |POLY 6 | P=0.387N P=0.243 P=0.526 (e) |P=0.135 P=0.235 P=0.249 P=0.132 | |LOGISTIC REGRESSION| P=0.538N P=0.233 P=0.469 (e) |P=0.091 P=0.318 P=0.182 P=0.119 | |COCH-ARM / FISHERS | P=0.460N P=0.241 P=0.500 (e) |P=0.098 P=0.241 P=0.241 P=0.112 | |ORDER RESTRICTED | P=0.295N (e) (e) (e) |P=0.078 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 11 Page 4 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SODIUM BR Terminal Sacrifice at 26 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 64 MG/KG 128 256 |0 MG/KG 64 MG/KG 128 256 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 6/15 (40%) 9/15 (60%) 9/15 (60%) 11/15 (73%) |9/15 (60%) 12/15 (80%) 12/15 (80%) 14/15 (93%) | |POLY-3 RATE (b) | 6/13.10 9/14.02 9/14.05 11/15.00 |9/13.69 12/14.06 12/14.21 14/15.00 | |POLY-3 PERCENT (g) | 45.8% 64.2% 64.0% 73.3% |65.7% 85.4% 84.5% 93.3% | |TERMINAL (d) | 5/12 (42%) 6/11 (55%) 8/13 (62%) 11/15 (73%) |7/11 (64%) 8/10 (80%) 9/11 (82%) 10/11 (91%) | |FIRST INCIDENCE | 146 74 146 181 (T) |146 67 137 69 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.279 P=0.213 P=0.314 P=0.219 |P=0.095 P=0.182 P=0.231 P=0.090 | |POLY 3 | P=0.128 P=0.286 P=0.288 P=0.135 |P=0.064 P=0.221 P=0.237 P=0.074 | |POLY 1.5 | P=0.113 P=0.272 P=0.279 P=0.119 |P=0.052 P=0.213 P=0.236 P=0.060 | |POLY 6 | P=0.133 P=0.291 P=0.291 P=0.140 |P=0.076 P=0.240 P=0.245 P=0.087 | |LOGISTIC REGRESSION| P=0.102 P=0.227 P=0.277 P=0.139 |P=0.028 * P=0.168 P=0.201 P=0.038 * | |COCH-ARM / FISHERS | P=0.061 P=0.233 P=0.233 P=0.070 |P=0.032 * P=0.213 P=0.213 P=0.040 * | |ORDER RESTRICTED | P=0.106 (e) (e) (e) |P=0.032 * (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (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. (g) Poly-3 adjusted lifetime tumor incidence. (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).