TDMS Study 97013-95 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 10/08/03 EXPERIMENT: 97013 TEST: 95 TIME: 10:09:45 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-65406 ROUTE: DOSED WATER NTP C#: 97013J PATHOLOGIST: MISSING CAS: 75-27-4 ------------------------------------------------------------------------------------------------------------------------------------ FINAL/MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 10/08/03 EXPERIMENT: 97013 TEST: 95 TIME: 10:09:45 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-65406 ROUTE: DOSED WATER NTP C#: 97013J PATHOLOGIST: MISSING CAS: 75-27-4 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. --------------- Adrenal Cortex Lung Salivary Glands NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 10/08/03 EXPERIMENT: 97013 TEST: 95 TIME: 10:09:45 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-65406 ROUTE: DOSED WATER NTP C#: 97013J PATHOLOGIST: MISSING CAS: 75-27-4 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF WATER DISINFECTION MODEL (BROMODICHLOR =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Skin Squamous Cell Papilloma =============================================================== Date: 10/08/03 EXPERIMENT: 97013 TEST: 95 Page 1 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (BROMODICHLOR Terminal Sacrifice at 43 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 2/10 (20%) 1/10 (10%) 1/10 (10%) |0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 0/7.67 2/9.09 1/8.76 1/9.83 |0/7.13 0/8.65 1/7.16 0/6.87 | |POLY-3 PERCENT (g) | 0.0% 22.0% 11.4% 10.2% |0.0% 0.0% 14.0% 0.0% | |TERMINAL (d) | 0/6 (0%) 2/9 (22%) 1/8 (13%) 1/9 (11%) |0/5 (0%) 0/8 (0%) 1/4 (25%) 0/4 (0%) | |FIRST INCIDENCE | --- 296 (T) 296 (T) 296 (T) |--- --- 296 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.589 P=0.327 P=0.557 P=0.581 |P=0.649 (e) P=0.455 (e) | |POLY 3 | P=0.616 P=0.266 P=0.527 P=0.549 |P=0.657 (e) P=0.501 (e) | |POLY 1.5 | P=0.579 P=0.250 P=0.518 P=0.533 |P=0.671 (e) P=0.503 (e) | |POLY 6 | P=0.644 P=0.286 P=0.533 P=0.562 |P=0.648 (e) P=0.487 (e) | |LOGISTIC REGRESSION| (e) P=0.327 P=0.557 P=0.581 |(e) (e) P=0.455 (e) | |COCH-ARM / FISHERS | P=0.500 P=0.237 P=0.500 P=0.500 |P=0.696 (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.290 (e) (e) (e) |P=0.379 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |Skin | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 8/10 (80%) 6/10 (60%) 8/10 (80%) 8/10 (80%) |6/10 (60%) 7/10 (70%) 7/10 (70%) 5/10 (50%) | |POLY-3 RATE (b) | 8/8.26 6/9.09 8/9.21 8/10.00 |6/8.05 7/9.17 7/8.16 5/7.21 | |POLY-3 PERCENT (g) | 96.9% 66.0% 86.8% 80.0% |74.6% 76.3% 85.8% 69.4% | |TERMINAL (d) | 6/6 (100%) 6/9 (67%) 7/8 (88%) 7/9 (78%) |4/5 (80%) 6/8 (75%) 4/4 (100%) 3/4 (75%) | |FIRST INCIDENCE | 247 296 (T) 242 278 |225 232 251 268 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.318N P=0.045N* P=0.311N P=0.168N |P=0.471 P=0.405N P=0.362 P=0.626N | |POLY 3 | P=0.487N P=0.140N P=0.548N P=0.352N |P=0.541N P=0.680 P=0.524 P=0.638N | |POLY 1.5 | P=0.566N P=0.188N P=0.612N P=0.475N |P=0.450N P=0.634 P=0.528 P=0.571N | |POLY 6 | P=0.447N P=0.118N P=0.521N P=0.291N |P=0.579 P=0.707 P=0.467 P=0.707N | |LOGISTIC REGRESSION| P=0.393N P=0.090N P=0.501N P=0.245N |P=0.453N P=0.700 P=0.575 P=0.548N | |COCH-ARM / FISHERS | P=0.451 P=0.314N P=0.709N P=0.709N |P=0.350N P=0.500 P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.224N (e) (e) (e) |P=0.521N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 95 Page 2 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (BROMODICHLOR Terminal Sacrifice at 43 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 7/10 (70%) 6/10 (60%) 7/10 (70%) 6/10 (60%) |5/10 (50%) 3/10 (30%) 6/10 (60%) 5/10 (50%) | |POLY-3 RATE (b) | 7/8.26 6/9.09 7/8.76 6/10.00 |5/7.49 3/8.65 6/8.33 5/7.39 | |POLY-3 PERCENT (g) | 84.7% 66.0% 79.9% 60.0% |66.8% 34.7% 72.1% 67.7% | |TERMINAL (d) | 5/6 (83%) 6/9 (67%) 7/8 (88%) 5/9 (56%) |4/5 (80%) 3/8 (38%) 3/4 (75%) 3/4 (75%) | |FIRST INCIDENCE | 247 296 (T) 296 (T) 278 |256 296 (T) 232 268 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.162N P=0.143N P=0.344N P=0.162N |P=0.215 P=0.098N P=0.388 P=0.570 | |POLY 3 | P=0.238N P=0.366N P=0.652N P=0.262N |P=0.346 P=0.212N P=0.628 P=0.700 | |POLY 1.5 | P=0.296N P=0.411N P=0.646N P=0.328N |P=0.375 P=0.243N P=0.580 P=0.691 | |POLY 6 | P=0.210N P=0.340N P=0.697N P=0.232N |P=0.334 P=0.191N P=0.654 P=0.719 | |LOGISTIC REGRESSION| P=0.169N P=0.276N P=0.513N P=0.220N |P=0.323 P=0.161N P=0.531 P=0.671 | |COCH-ARM / FISHERS | P=0.455N P=0.500N P=0.686N P=0.500N |P=0.436 P=0.325N P=0.500 P=0.672N | |ORDER RESTRICTED | P=0.190N (e) (e) (e) |P=0.332 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |Tooth | | Odontogenic Tumor | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/10 (30%) 2/10 (20%) 3/10 (30%) 2/10 (20%) |3/10 (30%) 3/10 (30%) 3/10 (30%) 2/10 (20%) | |POLY-3 RATE (b) | 3/8.96 2/10.00 3/8.76 2/9.83 |3/8.05 3/10.00 3/9.00 2/7.85 | |POLY-3 PERCENT (g) | 33.5% 20.0% 34.3% 20.4% |37.3% 30.0% 33.3% 25.5% | |TERMINAL (d) | 1/6 (17%) 1/9 (11%) 3/8 (38%) 2/9 (22%) |1/5 (20%) 1/8 (13%) 0/4 (0%) 0/4 (0%) | |FIRST INCIDENCE | 150 134 296 (T) 296 (T) |225 164 96 136 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.346N P=0.426N P=0.576N P=0.368N |P=0.458N P=0.530N P=0.650N P=0.522N | |POLY 3 | P=0.431N P=0.445N P=0.673 P=0.454N |P=0.433N P=0.566N P=0.627N P=0.513N | |POLY 1.5 | P=0.436N P=0.462N P=0.679 P=0.467N |P=0.406N P=0.598N P=0.630N P=0.497N | |POLY 6 | P=0.432N P=0.431N P=0.664 P=0.446N |P=0.473N P=0.547N P=0.653N P=0.543N | |LOGISTIC REGRESSION| P=0.599 P=0.669N P=0.667 P=0.699N |P=0.319N P=0.609 P=0.675 P=0.497N | |COCH-ARM / FISHERS | P=0.451N P=0.500N P=0.686N P=0.500N |P=0.382N P=0.686N P=0.686N P=0.500N | |ORDER RESTRICTED | P=0.424N (e) (e) (e) |P=0.504N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 95 Page 3 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (BROMODICHLOR Terminal Sacrifice at 43 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 8/10 (80%) 9/10 (90%) 9/10 (90%) 9/10 (90%) |7/10 (70%) 8/10 (80%) 8/10 (80%) 7/10 (70%) | |POLY-3 RATE (b) | 8/8.26 9/9.09 9/9.21 9/10.00 |7/8.05 8/9.17 8/8.68 7/7.47 | |POLY-3 PERCENT (g) | 96.9% 99.0% 97.7% 90.0% |87.0% 87.2% 92.2% 93.8% | |TERMINAL (d) | 6/6 (100%) 9/9 (100%) 8/8 (100%) 8/9 (89%) |5/5 (100%) 7/8 (88%) 4/4 (100%) 4/4 (100%) | |FIRST INCIDENCE | 247 296 (T) 242 278 |225 232 232 268 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.214N P=0.200N P=0.471N P=0.257N |P=0.242 P=0.303N P=0.364 P=0.516 | |POLY 3 | P=0.348N P=1.000 P=0.999 P=0.643N |P=0.433 P=0.766 P=0.695 P=0.690 | |POLY 1.5 | P=0.563N P=0.808 P=0.828 P=0.767N |P=0.540 P=0.693 P=0.619 P=0.710 | |POLY 6 | P=0.239N P=1.000 P=1.000N P=0.558N |P=0.347 P=0.758N P=0.746 P=0.670 | |LOGISTIC REGRESSION| P=0.193N P=0.200N (e) P=0.494N |P=0.501 P=0.718N P=0.657 P=0.720 | |COCH-ARM / FISHERS | P=0.404 P=0.500 P=0.500 P=0.500 |P=0.549N P=0.500 P=0.500 P=0.686N | |ORDER RESTRICTED | P=0.270N (e) (e) (e) |P=0.497 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/10 (10%) 1/10 (10%) 1/10 (10%) 1/10 (10%) |2/10 (20%) 1/10 (10%) 1/10 (10%) 1/10 (10%) | |POLY-3 RATE (b) | 1/8.54 1/9.09 1/9.55 1/9.83 |2/8.96 1/8.65 1/7.16 1/7.64 | |POLY-3 PERCENT (g) | 11.7% 11.0% 10.5% 10.2% |22.3% 11.6% 14.0% 13.1% | |TERMINAL (d) | 0/6 (0%) 1/9 (11%) 0/8 (0%) 1/9 (11%) |0/5 (0%) 1/8 (13%) 1/4 (25%) 0/4 (0%) | |FIRST INCIDENCE | 150 296 (T) 177 296 (T) |126 296 (T) 296 (T) 183 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.575N P=0.729N P=0.736N P=0.716N |P=0.460N P=0.434N P=0.538N P=0.488N | |POLY 3 | P=0.603N P=0.748N P=0.737N P=0.729N |P=0.455N P=0.513N P=0.581N P=0.558N | |POLY 1.5 | P=0.612N P=0.755N P=0.745N P=0.740N |P=0.439N P=0.512N P=0.553N P=0.543N | |POLY 6 | P=0.597N P=0.737N P=0.729N P=0.719N |P=0.472N P=0.505N P=0.621N P=0.567N | |LOGISTIC REGRESSION| P=0.382 P=0.725 P=0.501 P=0.539 |P=0.357N P=0.779N P=0.552N P=0.508N | |COCH-ARM / FISHERS | P=0.639 P=0.763N P=0.763N P=0.763N |P=0.404N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.700N (e) (e) (e) |P=0.476N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 95 Page 4 Statistical Analysis of Primary Tumors in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (BROMODICHLOR Terminal Sacrifice at 43 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 175 MG/L 350 MG/L 700 MG/L |0 MG/L 175 MG/L 350 MG/L 700 MG/L | | | | | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%)|9/10 (90%) 10/10 (100%) 10/10 (100%) 9/10 (90%) | |POLY-3 RATE (b) | 10/10.00 10/10.00 10/10.00 10/10.00 |9/9.87 10/10.00 10/10.00 9/9.13 | |POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% |91.2% 100.0% 100.0% 98.6% | |TERMINAL (d) | 6/6 (100%) 9/9 (100%) 8/8 (100%) 9/9 (100%) |5/5 (100%) 8/8 (100%) 4/4 (100%) 4/4 (100%) | |FIRST INCIDENCE | 150 134 177 278 |126 164 96 136 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.275 P=0.281N P=0.386 P=0.526 | |POLY 3 | (e) (e) (e) (e) |P=0.419 P=0.554 P=0.554 P=0.630 | |POLY 1.5 | (e) (e) (e) (e) |P=0.542 P=0.526 P=0.526 P=0.676 | |POLY 6 | (e) (e) (e) (e) |P=0.383 P=0.616 P=0.616 P=0.643 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.616N P=0.466 P=0.509 P=0.773 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.597N P=0.500 P=0.500 P=0.763N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.159 (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).