TDMS Study 97013-98 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 11/04/03 EXPERIMENT: 97013 TEST: 98 TIME: 12:09:05 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: 97013K PATHOLOGIST: MISSING CAS: 75-27-4 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 11/04/03 EXPERIMENT: 97013 TEST: 98 TIME: 12:09:05 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: 97013K 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 ----- ---------- Kidney Nephropathy Kidney: Renal Tubule Degeneration Vacuolization Cytoplasmic Liver: Hepatocyte Fatty Change =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Inflammation Liver: Hepatocyte Fatty Change =============================================================== Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODI CHLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/10 (30%) 2/10 (20%) 2/10 (20%) 1/10 (10%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 3/10.00 2/9.02 2/10.00 1/10.00 |0/9.71 0/9.86 0/8.66 0/9.73 | |POLY-3 PERCENT (g) | 30.0% 22.2% 20.0% 10.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/10 (30%) 2/9 (22%) 2/10 (20%) 1/10 (10%) |0/9 (0%) 0/9 (0%) 0/8 (0%) 0/9 (0%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.204N P=0.553N P=0.500N P=0.293N |(e) (e) (e) (e) | |POLY 3 | P=0.207N P=0.551N P=0.500N P=0.292N |(e) (e) (e) (e) | |POLY 1.5 | P=0.208N P=0.544N P=0.500N P=0.292N |(e) (e) (e) (e) | |POLY 6 | P=0.207N P=0.552N P=0.500N P=0.292N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.204N P=0.555N P=0.500N P=0.293N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.211N P=0.500N P=0.500N P=0.291N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.219N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 1/10 (10%) 2/10 (20%) |10/10 (100%) 9/10 (90%) 9/10 (90%) 10/10 (100%) | |POLY-3 RATE (b) | 2/10.00 0/9.02 1/10.00 2/10.00 |10/10.00 9/9.86 9/9.00 10/10.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 10.0% 20.0% |100.0% 91.3% 100.0% 100.0% | |TERMINAL (d) | 2/10 (20%) 0/9 (0%) 1/10 (10%) 2/10 (20%) |9/9 (100%) 9/9 (100%) 8/8 (100%) 9/9 (100%) | |FIRST INCIDENCE | 288 (T) --- 288 (T) 288 (T) |258 289 (T) 252 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.481 P=0.257N P=0.500N P=0.707 |P=0.540 P=0.500N P=0.724 (e) | |POLY 3 | P=0.492 P=0.252N P=0.500N P=0.702 |P=0.617 P=0.561N P=1.000N (e) | |POLY 1.5 | P=0.489 P=0.248N P=0.500N P=0.702 |P=0.595 P=0.529N P=1.000N (e) | |POLY 6 | P=0.492 P=0.252N P=0.500N P=0.702 |P=0.666 P=0.629N P=1.000N (e) | |LOGISTIC REGRESSION| P=0.481 P=0.251N P=0.500N P=0.707 |P=0.558 P=0.356N (e) (e) | |COCH-ARM / FISHERS | P=0.468 P=0.237N P=0.500N P=0.709N |P=0.597 P=0.500N P=0.500N (e) | |ORDER RESTRICTED | P=0.413 (e) (e) (e) |P=0.380 (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 2/10 (20%) 0/10 (0%) 0/10 (0%) |7/10 (70%) 4/10 (40%) 6/10 (60%) 6/10 (60%) | |POLY-3 RATE (b) | 1/10.00 2/9.02 0/10.00 0/10.00 |7/10.00 4/10.00 6/10.00 6/10.00 | |POLY-3 PERCENT (g) | 10.0% 22.2% 0.0% 0.0% |70.0% 40.0% 60.0% 60.0% | |TERMINAL (d) | 1/10 (10%) 2/9 (22%) 0/10 (0%) 0/10 (0%) |6/9 (67%) 3/9 (33%) 4/8 (50%) 5/9 (56%) | |FIRST INCIDENCE | 288 (T) 288 (T) --- --- |258 275 10 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.180N P=0.461 P=0.500N P=0.500N |P=0.563N P=0.215N P=0.609N P=0.492N | |POLY 3 | P=0.183N P=0.463 P=0.500N P=0.500N |P=0.563N P=0.186N P=0.500N P=0.500N | |POLY 1.5 | P=0.182N P=0.467 P=0.500N P=0.500N |P=0.563N P=0.186N P=0.500N P=0.500N | |POLY 6 | P=0.183N P=0.462 P=0.500N P=0.500N |P=0.563N P=0.186N P=0.500N P=0.500N | |LOGISTIC REGRESSION| P=0.180N P=0.461 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.181N P=0.500 P=0.500N P=0.500N |P=0.564N P=0.185N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.138N (e) (e) (e) |P=0.367N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/10 (40%) 3/10 (30%) 4/10 (40%) 9/10 (90%) |2/10 (20%) 3/10 (30%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 4/10.00 3/9.02 4/10.00 9/10.00 |2/9.71 3/9.86 1/8.66 0/9.73 | |POLY-3 PERCENT (g) | 40.0% 33.3% 40.0% 90.0% |20.6% 30.4% 11.5% 0.0% | |TERMINAL (d) | 4/10 (40%) 3/9 (33%) 4/10 (40%) 9/10 (90%) |2/9 (22%) 3/9 (33%) 1/8 (13%) 0/9 (0%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) |289 (T) 289 (T) 289 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.012 * P=0.568N P=0.672 P=0.034 * |P=0.094N P=0.500 P=0.543N P=0.233N | |POLY 3 | P=0.007 ** P=0.565N P=0.667 P=0.018 * |P=0.091N P=0.508 P=0.541N P=0.226N | |POLY 1.5 | P=0.007 ** P=0.557N P=0.667 P=0.018 * |P=0.091N P=0.504 P=0.539N P=0.226N | |POLY 6 | P=0.007 ** P=0.566N P=0.667 P=0.018 * |P=0.091N P=0.512 P=0.543N P=0.225N | |LOGISTIC REGRESSION| P=0.012 * P=0.568N P=0.672 P=0.034 * |P=0.094N P=0.500 P=0.543N (e) | |COCH-ARM / FISHERS | P=0.009 ** P=0.500N P=0.675N P=0.029 * |P=0.089N P=0.500 P=0.500N P=0.237N | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) |P=0.090N (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 1/10 (10%) 0/10 (0%) 10/10 (100%)|0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 1/9.02 0/10.00 10/10.00 |0/9.71 0/9.86 0/8.66 0/9.73 | |POLY-3 PERCENT (g) | 0.0% 11.1% 0.0% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/10 (0%) 1/9 (11%) 0/10 (0%) 10/10 (100%)|0/9 (0%) 0/9 (0%) 0/8 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- 288 (T) --- 288 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.479 (e) P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P<0.001 ** P=0.479 (e) P<0.001N** |(e) (e) (e) (e) | |POLY 1.5 | P<0.001 ** P=0.482 (e) P<0.001N** |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** P=0.479 (e) P<0.001N** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.479 (e) P<0.001 ** |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 (e) P<0.001 ** |(e) (e) (e) (e) | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/10 (80%) 5/10 (50%) 1/10 (10%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 8/10.00 5/9.02 1/10.00 0/10.00 |0/9.71 0/9.86 0/8.66 0/9.73 | |POLY-3 PERCENT (g) | 80.0% 55.4% 10.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 8/10 (80%) 5/9 (56%) 1/10 (10%) 0/10 (0%) |0/9 (0%) 0/9 (0%) 0/8 (0%) 0/9 (0%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001N** P=0.263N P=0.004N** P<0.001N** |(e) (e) (e) (e) | |POLY 3 | P<0.001N** P=0.260N P<0.001N** P<0.001N** |(e) (e) (e) (e) | |POLY 1.5 | P<0.001N** P=0.246N P<0.001N** P<0.001N** |(e) (e) (e) (e) | |POLY 6 | P<0.001N** P=0.262N P<0.001N** P<0.001N** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P<0.001N** P=0.263N P=0.004N** (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001N** P=0.175N P=0.003N** P<0.001N** |(e) (e) (e) (e) | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 3/10 (30%) 1/10 (10%) 3/10 (30%) |3/10 (30%) 2/10 (20%) 3/10 (30%) 0/10 (0%) | |POLY-3 RATE (b) | 2/10.00 3/9.02 1/10.00 3/10.00 |3/10.00 2/9.86 3/8.66 0/9.73 | |POLY-3 PERCENT (g) | 20.0% 33.3% 10.0% 30.0% |30.0% 20.3% 34.6% 0.0% | |TERMINAL (d) | 2/10 (20%) 3/9 (33%) 1/10 (10%) 3/10 (30%) |2/9 (22%) 2/9 (22%) 3/8 (38%) 0/9 (0%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) |258 289 (T) 289 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.492 P=0.447 P=0.500N P=0.500 |P=0.103N P=0.500N P=0.608 P=0.119N | |POLY 3 | P=0.485 P=0.449 P=0.500N P=0.500 |P=0.096N P=0.507N P=0.606 P=0.100N | |POLY 1.5 | P=0.484 P=0.455 P=0.500N P=0.500 |P=0.094N P=0.504N P=0.615 P=0.098N | |POLY 6 | P=0.485 P=0.448 P=0.500N P=0.500 |P=0.100N P=0.513N P=0.592 P=0.104N | |LOGISTIC REGRESSION| P=0.492 P=0.445 P=0.500N P=0.500 |P=0.094N P=0.570N P=0.639 P=0.095N | |COCH-ARM / FISHERS | P=0.474 P=0.500 P=0.500N P=0.500 |P=0.091N P=0.500N P=0.686N P=0.105N | |ORDER RESTRICTED | P=0.474 (e) (e) (e) |P=0.071N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/10 (70%) 9/10 (90%) 9/10 (90%) 9/10 (90%) |6/10 (60%) 10/10 (100%) 7/10 (70%) 8/10 (80%) | |POLY-3 RATE (b) | 7/10.00 9/9.02 9/10.00 9/10.00 |6/9.71 10/10.00 7/8.66 8/10.00 | |POLY-3 PERCENT (g) | 70.0% 99.8% 90.0% 90.0% |61.8% 100.0% 80.8% 80.0% | |TERMINAL (d) | 7/10 (70%) 9/9 (100%) 9/10 (90%) 9/10 (90%) |6/9 (67%) 9/9 (100%) 7/8 (88%) 7/9 (78%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) |289 (T) 275 289 (T) 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.279 P=0.129 P=0.293 P=0.293 |P=0.406 P=0.061 P=0.335 P=0.333 | |POLY 3 | P=0.263 P=0.118 P=0.292 P=0.292 |P=0.442 P=0.037 * P=0.352 P=0.349 | |POLY 1.5 | P=0.257 P=0.134 P=0.292 P=0.292 |P=0.421 P=0.035 * P=0.362 P=0.334 | |POLY 6 | P=0.264 P=0.116 P=0.292 P=0.292 |P=0.478 P=0.043 * P=0.340 P=0.375 | |LOGISTIC REGRESSION| P=0.279 P=0.129 P=0.293 P=0.293 |P=0.377 P=0.056 P=0.335 P=0.314 | |COCH-ARM / FISHERS | P=0.227 P=0.291 P=0.291 P=0.291 |P=0.424 P=0.043 * P=0.500 P=0.314 | |ORDER RESTRICTED | P=0.090 (e) (e) (e) |P=0.099 (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) |0/10 (0%) 2/10 (20%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 0/10.00 0/9.02 0/10.00 1/10.00 |0/9.71 2/10.00 1/9.00 0/9.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 10.0% |0.0% 20.0% 11.1% 0.0% | |TERMINAL (d) | 0/10 (0%) 0/9 (0%) 0/10 (0%) 1/10 (10%) |0/9 (0%) 1/9 (11%) 0/8 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- 288 (T) |--- 275 252 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 (e) (e) P=0.500 |P=0.468N P=0.251 P=0.479 (e) | |POLY 3 | P=0.205 (e) (e) P=0.500 |P=0.460N P=0.233 P=0.485 (e) | |POLY 1.5 | P=0.204 (e) (e) P=0.500 |P=0.462N P=0.230 P=0.482 (e) | |POLY 6 | P=0.205 (e) (e) P=0.500 |P=0.458N P=0.238 P=0.489 (e) | |LOGISTIC REGRESSION| P=0.202 (e) (e) P=0.500 |P=0.456N P=0.171 P=0.533 (e) | |COCH-ARM / FISHERS | P=0.196 (e) (e) P=0.500 |P=0.460N P=0.237 P=0.500 (e) | |ORDER RESTRICTED | P=0.121 (e) (e) (e) |P=0.307N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/10 (60%) 6/10 (60%) 5/10 (50%) 10/10 (100%)|3/10 (30%) 3/10 (30%) 6/10 (60%) 9/10 (90%) | |POLY-3 RATE (b) | 6/10.00 6/9.02 5/10.00 10/10.00 |3/9.71 3/9.86 6/8.66 9/9.73 | |POLY-3 PERCENT (g) | 60.0% 66.5% 50.0% 100.0% |30.9% 30.4% 69.3% 92.5% | |TERMINAL (d) | 6/10 (60%) 6/9 (67%) 5/10 (50%) 10/10 (100%)|3/9 (33%) 3/9 (33%) 6/8 (75%) 9/9 (100%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) |289 (T) 289 (T) 289 (T) 289 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.049 * P=0.568 P=0.500N P=0.051 |P<0.001 ** P=0.686 P=0.116 P=0.008 ** | |POLY 3 | P=0.038 * P=0.568 P=0.500N P=0.033 * |P<0.001 ** P=0.672N P=0.113 P=0.002 ** | |POLY 1.5 | P=0.037 * P=0.582 P=0.500N P=0.033 * |P<0.001 ** P=0.675N P=0.118 P=0.002 ** | |POLY 6 | P=0.038 * P=0.566 P=0.500N P=0.033 * |P<0.001 ** P=0.668N P=0.107 P<0.001 ** | |LOGISTIC REGRESSION| P=0.046 * P=0.568 P=0.500N P=0.051 |P<0.001 ** P=0.686 P=0.116 P=0.008 ** | |COCH-ARM / FISHERS | P=0.038 * P=0.675N P=0.500N P=0.043 * |P=0.002 ** P=0.686N P=0.185 P=0.010 * | |ORDER RESTRICTED | P=0.023 * (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/10 (100%) 9/10 (90%) 10/10 (100%) 10/10 (100%)|9/10 (90%) 10/10 (100%) 9/10 (90%) 10/10 (100%) | |POLY-3 RATE (b) | 10/10.00 9/9.02 10/10.00 10/10.00 |9/9.71 10/10.00 9/9.00 10/10.00 | |POLY-3 PERCENT (g) | 100.0% 99.8% 100.0% 100.0% |92.7% 100.0% 100.0% 100.0% | |TERMINAL (d) | 10/10 (100%) 9/9 (100%) 10/10 (100%) 10/10 (100%)|9/9 (100%) 9/9 (100%) 8/8 (100%) 9/9 (100%) | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) |289 (T) 275 252 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=1.000 P=1.000 (e) (e) |P=0.386 P=0.521 P=0.479 P=0.521 | |POLY 3 | P=1.000 P=1.000N (e) (e) |P=0.422 P=0.650 P=0.669 P=0.650 | |POLY 1.5 | P=1.000 P=1.000N (e) (e) |P=0.362 P=0.570 P=0.593 P=0.570 | |POLY 6 | P=1.000 P=1.000N (e) (e) |P=0.581 P=0.823 P=0.835 P=0.823 | |LOGISTIC REGRESSION| P=1.000 P=1.000 (e) (e) |P=0.246 (e) P=0.393 (e) | |COCH-ARM / FISHERS | P=0.568 P=0.500N (e) (e) |P=0.403 P=0.500 P=0.763N P=0.500 | |ORDER RESTRICTED | P=0.371 (e) (e) (e) |P=0.118 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) |1/10 (10%) 2/10 (20%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 1/10.00 1/9.02 0/10.00 0/10.00 |1/9.71 2/9.86 1/8.66 0/9.73 | |POLY-3 PERCENT (g) | 10.0% 11.1% 0.0% 0.0% |10.3% 20.3% 11.5% 0.0% | |TERMINAL (d) | 1/10 (10%) 1/9 (11%) 0/10 (0%) 0/10 (0%) |1/9 (11%) 2/9 (22%) 1/8 (13%) 0/9 (0%) | |FIRST INCIDENCE | 288 (T) 288 (T) --- --- |289 (T) 289 (T) 289 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.230N P=0.743 P=0.500N P=0.500N |P=0.246N P=0.500 P=0.741 P=0.500N | |POLY 3 | P=0.235N P=0.737 P=0.500N P=0.500N |P=0.246N P=0.506 P=0.735 P=0.500N | |POLY 1.5 | P=0.235N P=0.740 P=0.500N P=0.500N |P=0.247N P=0.503 P=0.736 P=0.500N | |POLY 6 | P=0.235N P=0.737 P=0.500N P=0.500N |P=0.246N P=0.509 P=0.735 P=0.499N | |LOGISTIC REGRESSION| P=0.230N P=0.749 (e) (e) |P=0.246N P=0.500 P=0.741 (e) | |COCH-ARM / FISHERS | P=0.231N P=0.763N P=0.500N P=0.500N |P=0.238N P=0.500 P=0.763N P=0.500N | |ORDER RESTRICTED | P=0.231N (e) (e) (e) |P=0.217N (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/10 (0%) 0/10 (0%) 3/10 (30%) 1/10 (10%) | |POLY-3 RATE (b) | |0/9.71 0/9.86 3/8.66 1/9.73 | |POLY-3 PERCENT (g) | |0.0% 0.0% 34.6% 10.3% | |TERMINAL (d) | |0/9 (0%) 0/9 (0%) 3/8 (38%) 1/9 (11%) | |FIRST INCIDENCE | |--- --- 289 (T) 289 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.239 (e) P=0.089 P=0.500 | |POLY 3 | |P=0.230 (e) P=0.073 P=0.500 | |POLY 1.5 | |P=0.231 (e) P=0.074 P=0.500 | |POLY 6 | |P=0.229 (e) P=0.071 P=0.501 | |LOGISTIC REGRESSION| |(e) (e) P=0.089 P=0.500 | |COCH-ARM / FISHERS | |P=0.238 (e) P=0.105 P=0.500 | |ORDER RESTRICTED | |P=0.073 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Oviduct | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/2 (100%) 0/0 (0%) 1/1 (100%) 0/0 (0%) | |POLY-3 RATE (b) | |2/2.00 0/0.00 1/1.00 0/0.00 | |POLY-3 PERCENT (g) | |100.0% 0.0% 100.0% 0.0% | |TERMINAL (d) | |2/2 (100%) 0/0 (0%) 1/1 (100%) 0/0 (0%) | |FIRST INCIDENCE | |289 (T) --- 289 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |(e) (e) (e) (e) | |POLY 3 | |(e) (e) (e) (e) | |POLY 1.5 | |(e) (e) (e) (e) | |POLY 6 | |(e) (e) (e) (e) | |LOGISTIC REGRESSION| |(e) (e) (e) (e) | |COCH-ARM / FISHERS | |(e) (e) (e) (e) | |ORDER RESTRICTED | |(e) (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/10 (40%) 2/10 (20%) 3/10 (30%) 1/10 (10%) |0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) | |POLY-3 RATE (b) | 4/10.00 2/10.00 3/10.00 1/10.00 |0/9.71 0/9.86 1/8.66 0/9.73 | |POLY-3 PERCENT (g) | 40.0% 20.0% 30.0% 10.0% |0.0% 0.0% 11.5% 0.0% | |TERMINAL (d) | 4/10 (40%) 1/9 (11%) 3/10 (30%) 1/10 (10%) |0/9 (0%) 0/9 (0%) 1/8 (13%) 0/9 (0%) | |FIRST INCIDENCE | 288 (T) 77 288 (T) 288 (T) |--- --- 289 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.136N P=0.369N P=0.500N P=0.157N |P=0.690 (e) P=0.477 (e) | |POLY 3 | P=0.138N P=0.318N P=0.500N P=0.148N |P=0.701 (e) P=0.477 (e) | |POLY 1.5 | P=0.138N P=0.318N P=0.500N P=0.148N |P=0.701 (e) P=0.478 (e) | |POLY 6 | P=0.138N P=0.318N P=0.500N P=0.148N |P=0.701 (e) P=0.476 (e) | |LOGISTIC REGRESSION| P=0.136N (e) P=0.500N P=0.157N |(e) (e) P=0.477 (e) | |COCH-ARM / FISHERS | P=0.133N P=0.314N P=0.500N P=0.152N |P=0.696 (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.097N (e) (e) (e) |P=0.360 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Testes | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 2/10 (20%) 1/10 (10%) 0/10 (0%) | | |POLY-3 RATE (b) | 0/10.00 2/9.02 1/10.00 0/10.00 | | |POLY-3 PERCENT (g) | 0.0% 22.2% 10.0% 0.0% | | |TERMINAL (d) | 0/10 (0%) 2/9 (22%) 1/10 (10%) 0/10 (0%) | | |FIRST INCIDENCE | --- 288 (T) 288 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.451N P=0.210 P=0.500 (e) | | |POLY 3 | P=0.466N P=0.202 P=0.500 (e) | | |POLY 1.5 | P=0.465N P=0.205 P=0.500 (e) | | |POLY 6 | P=0.467N P=0.202 P=0.500 (e) | | |LOGISTIC REGRESSION| (e) P=0.204 P=0.500 (e) | | |COCH-ARM / FISHERS | P=0.460N P=0.237 P=0.500 (e) | | |ORDER RESTRICTED | P=0.293N (e) (e) (e) | | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 5/10 (50%) 2/10 (20%) 2/10 (20%) | | |POLY-3 RATE (b) | 2/10.00 5/9.02 2/10.00 2/10.00 | | |POLY-3 PERCENT (g) | 20.0% 55.4% 20.0% 20.0% | | |TERMINAL (d) | 2/10 (20%) 5/9 (56%) 2/10 (20%) 2/10 (20%) | | |FIRST INCIDENCE | 288 (T) 288 (T) 288 (T) 288 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.365N P=0.136 P=0.707 P=0.707 | | |POLY 3 | P=0.379N P=0.127 P=0.702 P=0.702 | | |POLY 1.5 | P=0.380N P=0.132 P=0.702 P=0.702 | | |POLY 6 | P=0.379N P=0.127 P=0.702 P=0.702 | | |LOGISTIC REGRESSION| P=0.365N P=0.136 P=0.707 P=0.707 | | |COCH-ARM / FISHERS | P=0.382N P=0.175 P=0.709N P=0.709N | | |ORDER RESTRICTED | P=0.314N (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/10 (0%) |1/9 (11%) 2/10 (20%) 2/10 (20%) 1/10 (10%) | |POLY-3 RATE (b) | 0/9.00 0/9.02 0/9.00 0/10.00 |1/9.00 2/10.00 2/9.00 1/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |11.1% 20.0% 22.2% 10.0% | |TERMINAL (d) | 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/10 (0%) |0/8 (0%) 1/9 (11%) 1/8 (13%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- |258 275 252 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.546N P=0.526 P=0.462 P=0.749N | |POLY 3 | (e) (e) (e) (e) |P=0.530N P=0.538 P=0.500 P=0.737N | |POLY 1.5 | (e) (e) (e) (e) |P=0.530N P=0.538 P=0.500 P=0.737N | |POLY 6 | (e) (e) (e) (e) |P=0.530N P=0.538 P=0.500 P=0.737N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.523N (e) P=0.553 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.528N P=0.542 P=0.542 P=0.737N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.514N (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/9 (67%) 7/10 (70%) 6/9 (67%) 4/10 (40%) |6/9 (67%) 8/10 (80%) 8/10 (80%) 8/10 (80%) | |POLY-3 RATE (b) | 6/9.00 7/10.00 6/9.00 4/10.00 |6/8.71 8/9.86 8/9.00 8/10.00 | |POLY-3 PERCENT (g) | 66.7% 70.0% 66.7% 40.0% |68.9% 81.1% 88.9% 80.0% | |TERMINAL (d) | 6/9 (67%) 6/9 (67%) 6/9 (67%) 4/10 (40%) |6/8 (75%) 8/9 (89%) 7/8 (88%) 7/9 (78%) | |FIRST INCIDENCE | 288 (T) 77 288 (T) 288 (T) |289 (T) 289 (T) 252 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.122N P=0.500 P=0.686 P=0.247N |P=0.378 P=0.457 P=0.289 P=0.465 | |POLY 3 | P=0.131N P=0.626 P=0.681 P=0.245N |P=0.420 P=0.472 P=0.326 P=0.493 | |POLY 1.5 | P=0.131N P=0.626 P=0.681 P=0.245N |P=0.395 P=0.461 P=0.309 P=0.471 | |POLY 6 | P=0.131N P=0.626 P=0.681 P=0.245N |P=0.462 P=0.489 P=0.359 P=0.527 | |LOGISTIC REGRESSION| P=0.122N (e) P=0.686 P=0.247N |P=0.357 P=0.457 P=0.271 P=0.455 | |COCH-ARM / FISHERS | P=0.125N P=0.630 P=0.690N P=0.242N |P=0.383 P=0.444 P=0.444 P=0.444 | |ORDER RESTRICTED | P=0.167N (e) (e) (e) |P=0.335 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/10 (20%) 2/10 (20%) 1/10 (10%) 1/10 (10%) | |POLY-3 RATE (b) | |2/9.71 2/9.86 1/8.66 1/9.73 | |POLY-3 PERCENT (g) | |20.6% 20.3% 11.5% 10.3% | |TERMINAL (d) | |2/9 (22%) 2/9 (22%) 1/8 (13%) 1/9 (11%) | |FIRST INCIDENCE | |289 (T) 289 (T) 289 (T) 289 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.334N P=0.709 P=0.543N P=0.500N | |POLY 3 | |P=0.341N P=0.697N P=0.541N P=0.499N | |POLY 1.5 | |P=0.340N P=0.699N P=0.539N P=0.500N | |POLY 6 | |P=0.341N P=0.694N P=0.543N P=0.499N | |LOGISTIC REGRESSION| |P=0.334N P=0.709 P=0.543N P=0.500N | |COCH-ARM / FISHERS | |P=0.327N P=0.709N P=0.500N P=0.500N | |ORDER RESTRICTED | |P=0.431N (e) (e) (e) | |=================================================================================================================================| Date: 11/04/03 EXPERIMENT: 97013 TEST: 98 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR Terminal Sacrifice at 42 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 |0 MG/KG 25 MG/KG 50 MG/KG 100 | | | MG/KG | MG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |9/10 (90%) 8/10 (80%) 8/10 (80%) 10/10 (100%) | |POLY-3 RATE (b) | |9/9.71 8/10.00 8/8.66 10/10.00 | |POLY-3 PERCENT (g) | |92.7% 80.0% 92.4% 100.0% | |TERMINAL (d) | |9/9 (100%) 7/9 (78%) 8/8 (100%) 9/9 (100%) | |FIRST INCIDENCE | |289 (T) 275 289 (T) 260 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.253 P=0.488N P=1.000N P=0.521 | |POLY 3 | |P=0.259 P=0.435N P=0.833N P=0.650 | |POLY 1.5 | |P=0.252 P=0.466N P=0.783N P=0.570 | |POLY 6 | |P=0.276 P=0.383N P=0.919 P=0.823 | |LOGISTIC REGRESSION| |P=0.180 P=0.374N P=1.000N (e) | |COCH-ARM / FISHERS | |P=0.286 P=0.500N P=0.500N P=0.500 | |ORDER RESTRICTED | |P=0.196 (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).