TDMS Study 97013-96 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 10/08/03 EXPERIMENT: 97013 TEST: 96 TIME: 15:30:51 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 NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (BROMODICHLOROMETHANE) DATE: 10/08/03 EXPERIMENT: 97013 TEST: 96 TIME: 15:30:51 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 ----- ---------- Kidney Nephropathy Kidney: Renal Tubule Degeneration Vacuolization Cytoplasmic Liver Inflammation Necrosis Liver: Hepatocyte Fatty Change Spleen Atrophy Thymus Atrophy Cyst =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Kidney Casts Protein Nephropathy Liver: Hepatocyte Fatty Change =============================================================== Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODI CHLOR 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 | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 4/10 (40%) 2/10 (20%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 2/9.42 4/10.00 2/9.82 0/7.80 |0/9.90 0/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 21.2% 40.0% 20.4% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/9 (22%) 4/10 (40%) 2/9 (22%) 0/7 (0%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | 296 (T) 296 (T) 296 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.140N P=0.371 P=0.709 P=0.290N |(e) (e) (e) (e) | |POLY 3 | P=0.132N P=0.348 P=0.688N P=0.272N |(e) (e) (e) (e) | |POLY 1.5 | P=0.120N P=0.336 P=0.693N P=0.260N |(e) (e) (e) (e) | |POLY 6 | P=0.139N P=0.362 P=0.684N P=0.280N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.140N P=0.371 P=0.709 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.091N P=0.314 P=0.709N P=0.237N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.104N (e) (e) (e) |(e) (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 | | | | | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 2/10 (20%) 3/10 (30%) 2/10 (20%) |9/10 (90%) 10/10 (100%) 10/10 (100%) 8/10 (80%) | |POLY-3 RATE (b) | 2/9.42 2/10.00 3/9.82 2/7.80 |9/10.00 10/10.00 10/10.00 8/9.01 | |POLY-3 PERCENT (g) | 21.2% 20.0% 30.6% 25.7% |90.0% 100.0% 100.0% 88.8% | |TERMINAL (d) | 2/9 (22%) 2/10 (20%) 3/9 (33%) 2/7 (29%) |8/9 (89%) 9/9 (100%) 10/10 (100%) 7/8 (88%) | |FIRST INCIDENCE | 296 (T) 296 (T) 296 (T) 296 (T) |287 183 297 (T) 231 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.435 P=0.667N P=0.500 P=0.611 |P=0.542N P=0.488 P=0.749 P=0.686 | |POLY 3 | P=0.454 P=0.680N P=0.521 P=0.633 |P=0.577N P=0.500 P=0.500 P=0.735N | |POLY 1.5 | P=0.484 P=0.689N P=0.513 P=0.651 |P=0.545N P=0.500 P=0.500 P=0.718N | |POLY 6 | P=0.433 P=0.671N P=0.526 P=0.620 |P=0.579N P=0.500 P=0.500 P=0.737N | |LOGISTIC REGRESSION| P=0.435 P=0.667N P=0.500 P=0.611 |P=0.501N (e) P=0.749 P=0.773N | |COCH-ARM / FISHERS | P=0.576 P=0.709N P=0.500 P=0.709N |P=0.239N P=0.500 P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.573 (e) (e) (e) |P=0.363N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) |8/10 (80%) 1/10 (10%) 5/10 (50%) 3/10 (30%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 1/10.00 0/7.80 |8/9.90 1/9.23 5/10.00 3/9.01 | |POLY-3 PERCENT (g) | 0.0% 0.0% 10.0% 0.0% |80.8% 10.8% 50.0% 33.3% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |8/9 (89%) 1/9 (11%) 5/10 (50%) 2/8 (25%) | |FIRST INCIDENCE | --- --- 277 --- |297 (T) 297 (T) 297 (T) 231 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.671 (e) P=0.521 (e) |P=0.146N P=0.003N** P=0.098N P=0.073N | |POLY 3 | P=0.590 (e) P=0.512 (e) |P=0.094N P<0.001N** P=0.164N P=0.040N* | |POLY 1.5 | P=0.620 (e) P=0.507 (e) |P=0.098N P<0.001N** P=0.169N P=0.040N* | |POLY 6 | P=0.567 (e) P=0.517 (e) |P=0.088N P<0.001N** P=0.155N P=0.037N* | |LOGISTIC REGRESSION| P=0.729 (e) P=0.421 (e) |P=0.142N P=0.003N** P=0.098N P=0.053N | |COCH-ARM / FISHERS | P=0.696 (e) P=0.500 (e) |P=0.107N P=0.003N** P=0.175N P=0.035N* | |ORDER RESTRICTED | P=0.396 (e) (e) (e) |P=0.012N* (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 | | | | | |=================================================================================================================================| | | |Kidney | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |1/10 (10%) 4/10 (40%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 1/9.42 0/10.00 0/9.82 0/7.80 |1/9.90 4/9.23 0/10.00 1/8.48 | |POLY-3 PERCENT (g) | 10.6% 0.0% 0.0% 0.0% |10.1% 43.3% 0.0% 11.8% | |TERMINAL (d) | 1/9 (11%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |1/9 (11%) 4/9 (44%) 0/10 (0%) 1/8 (13%) | |FIRST INCIDENCE | 296 (T) --- --- --- |297 (T) 297 (T) --- 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.334N P=0.479N P=0.500N P=0.550N |P=0.360N P=0.153 P=0.479N P=0.741 | |POLY 3 | P=0.281N P=0.488N P=0.492N P=0.537N |P=0.360N P=0.123 P=0.498N P=0.726 | |POLY 1.5 | P=0.289N P=0.493N P=0.495N P=0.528N |P=0.353N P=0.131 P=0.499N P=0.732 | |POLY 6 | P=0.276N P=0.483N P=0.489N P=0.543N |P=0.364N P=0.120 P=0.496N P=0.721 | |LOGISTIC REGRESSION| P=0.334N (e) (e) (e) |P=0.360N P=0.153 (e) P=0.741 | |COCH-ARM / FISHERS | P=0.304N P=0.500N P=0.500N P=0.500N |P=0.327N P=0.152 P=0.500N P=0.763N | |ORDER RESTRICTED | P=0.155N (e) (e) (e) |P=0.163N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/10 (50%) 4/10 (40%) 9/10 (90%) 8/10 (80%) |3/10 (30%) 1/10 (10%) 8/10 (80%) 0/10 (0%) | |POLY-3 RATE (b) | 5/9.42 4/10.00 9/9.82 8/8.61 |3/10.00 1/10.00 8/10.00 0/8.48 | |POLY-3 PERCENT (g) | 53.1% 40.0% 91.7% 93.0% |30.0% 10.0% 80.0% 0.0% | |TERMINAL (d) | 5/9 (56%) 4/10 (40%) 9/9 (100%) 7/7 (100%) |2/9 (22%) 0/9 (0%) 8/10 (80%) 0/8 (0%) | |FIRST INCIDENCE | 296 (T) 296 (T) 296 (T) 170 |287 183 297 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.003 ** P=0.416N P=0.049 * P=0.041 * |P=0.302N P=0.315N P=0.078 P=0.147N | |POLY 3 | P=0.007 ** P=0.453N P=0.066 P=0.068 |P=0.355N P=0.292N P=0.024 * P=0.128N | |POLY 1.5 | P=0.011 * P=0.472N P=0.064 P=0.087 |P=0.316N P=0.292N P=0.024 * P=0.121N | |POLY 6 | P=0.005 ** P=0.432N P=0.066 P=0.057 |P=0.391N P=0.292N P=0.024 * P=0.135N | |LOGISTIC REGRESSION| P=0.010 * P=0.416N P=0.049 * P=0.066 |P=0.239N (e) P=0.078 P=0.127N | |COCH-ARM / FISHERS | P=0.046 * P=0.500N P=0.070 P=0.175 |P=0.242N P=0.291N P=0.035 * P=0.105N | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) |P=0.015N* (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 | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 6/10 (60%) 10/10 (100%)|0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 6/9.82 10/10.00 |0/9.90 0/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 0.0% 0.0% 61.1% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 6/9 (67%) 7/7 (100%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 296 (T) 95 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) P=0.008 ** P<0.001 ** |(e) (e) (e) (e) | |POLY 3 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |(e) (e) (e) (e) | |POLY 1.5 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** (e) P<0.001 ** P<0.001 ** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.008 ** P<0.001 ** |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.005 ** P<0.001 ** |(e) (e) (e) (e) | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 3/10 (30%) 2/10 (20%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 1/9.42 0/10.00 3/9.82 2/7.80 |0/9.90 0/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 10.6% 0.0% 30.6% 25.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/9 (11%) 0/10 (0%) 3/9 (33%) 2/7 (29%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | 296 (T) --- 296 (T) 296 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.141 P=0.479N P=0.291 P=0.407 |(e) (e) (e) (e) | |POLY 3 | P=0.145 P=0.488N P=0.307 P=0.431 |(e) (e) (e) (e) | |POLY 1.5 | P=0.164 P=0.493N P=0.301 P=0.449 |(e) (e) (e) (e) | |POLY 6 | P=0.132 P=0.483N P=0.311 P=0.420 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.141 (e) P=0.291 P=0.407 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.227 P=0.500N P=0.291 P=0.500 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.162 (e) (e) (e) |(e) (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 | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/10 (100%) 5/10 (50%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 10/10.00 5/10.00 0/9.82 0/7.80 |0/9.90 0/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 100.0% 50.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 9/9 (100%) 5/10 (50%) 0/9 (0%) 0/7 (0%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | 221 296 (T) --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001N** P=0.016N* P<0.001N** P<0.001N** |(e) (e) (e) (e) | |POLY 3 | P<0.001N** P=0.008N** P<0.001N** P<0.001N** |(e) (e) (e) (e) | |POLY 1.5 | P<0.001N** P=0.008N** P<0.001N** P<0.001N** |(e) (e) (e) (e) | |POLY 6 | P<0.001N** P=0.008N** P<0.001N** P<0.001N** |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P<0.001N** P=0.016N* P<0.001N** P<0.001N** |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001N** P=0.016N* P<0.001N** P<0.001N** |(e) (e) (e) (e) | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) |2/10 (20%) 1/10 (10%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 0/9.82 1/7.80 |2/10.00 1/10.00 0/10.00 1/9.01 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 12.8% |20.0% 10.0% 0.0% 11.1% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 1/7 (14%) |1/9 (11%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- 296 (T) |287 183 --- 231 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.158 (e) (e) P=0.450 |P=0.398N P=0.512N P=0.228N P=0.551N | |POLY 3 | P=0.172 (e) (e) P=0.462 |P=0.369N P=0.500N P=0.227N P=0.537N | |POLY 1.5 | P=0.179 (e) (e) P=0.472 |P=0.368N P=0.500N P=0.227N P=0.534N | |POLY 6 | P=0.168 (e) (e) P=0.456 |P=0.369N P=0.500N P=0.227N P=0.538N | |LOGISTIC REGRESSION| (e) (e) (e) P=0.450 |P=0.191N (e) (e) P=0.462N | |COCH-ARM / FISHERS | P=0.196 (e) (e) P=0.500 |P=0.361N P=0.500N P=0.237N P=0.500N | |ORDER RESTRICTED | P=0.092 (e) (e) (e) |P=0.245N (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 | | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 2/10 (20%) 0/10 (0%) 0/10 (0%) |2/10 (20%) 4/10 (40%) 4/10 (40%) 2/10 (20%) | |POLY-3 RATE (b) | 1/9.42 2/10.00 0/9.82 0/7.80 |2/9.90 4/9.23 4/10.00 2/8.48 | |POLY-3 PERCENT (g) | 10.6% 20.0% 0.0% 0.0% |20.2% 43.3% 40.0% 23.6% | |TERMINAL (d) | 1/9 (11%) 2/10 (20%) 0/9 (0%) 0/7 (0%) |2/9 (22%) 4/9 (44%) 4/10 (40%) 2/8 (25%) | |FIRST INCIDENCE | 296 (T) 296 (T) --- --- |297 (T) 297 (T) 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.222N P=0.539 P=0.500N P=0.550N |P=0.565N P=0.314 P=0.371 P=0.665 | |POLY 3 | P=0.191N P=0.522 P=0.492N P=0.537N |P=0.569 P=0.279 P=0.322 P=0.644 | |POLY 1.5 | P=0.190N P=0.513 P=0.495N P=0.528N |P=0.581N P=0.291 P=0.320 P=0.656 | |POLY 6 | P=0.191N P=0.531 P=0.489N P=0.543N |P=0.554 P=0.274 P=0.327 P=0.636 | |LOGISTIC REGRESSION| P=0.222N P=0.539 (e) (e) |P=0.565N P=0.314 P=0.371 P=0.665 | |COCH-ARM / FISHERS | P=0.181N P=0.500 P=0.500N P=0.500N |P=0.500N P=0.314 P=0.314 P=0.709N | |ORDER RESTRICTED | P=0.208N (e) (e) (e) |P=0.386 (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/10 (90%) 5/10 (50%) 7/10 (70%) 6/10 (60%) |8/10 (80%) 7/10 (70%) 8/10 (80%) 7/10 (70%) | |POLY-3 RATE (b) | 9/9.42 5/10.00 7/9.82 6/8.61 |8/9.90 7/9.23 8/10.00 7/8.48 | |POLY-3 PERCENT (g) | 95.6% 50.0% 71.3% 69.7% |80.8% 75.8% 80.0% 82.6% | |TERMINAL (d) | 9/9 (100%) 5/10 (50%) 7/9 (78%) 5/7 (71%) |8/9 (89%) 7/9 (78%) 8/10 (80%) 7/8 (88%) | |FIRST INCIDENCE | 296 (T) 296 (T) 296 (T) 170 |297 (T) 297 (T) 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.571N P=0.029N* P=0.233N P=0.453N |P=0.601 P=0.500N P=0.539N P=0.741N | |POLY 3 | P=0.325N P=0.026N* P=0.194N P=0.180N |P=0.534 P=0.612N P=0.691N P=0.691 | |POLY 1.5 | P=0.305N P=0.037N* P=0.231N P=0.182N |P=0.567 P=0.575N P=0.696N P=0.705N | |POLY 6 | P=0.341N P=0.018N* P=0.161N P=0.171N |P=0.506 P=0.631N P=0.680N P=0.663 | |LOGISTIC REGRESSION| P=0.410N P=0.029N* P=0.233N P=0.311N |P=0.601 P=0.500N P=0.539N P=0.741N | |COCH-ARM / FISHERS | P=0.229N P=0.070N P=0.291N P=0.152N |P=0.451N P=0.500N P=0.709N P=0.500N | |ORDER RESTRICTED | P=0.094N (e) (e) (e) |P=0.642 (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 | | | | | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |3/10 (30%) 2/10 (20%) 1/10 (10%) 1/10 (10%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 0/9.82 2/9.57 |3/10.00 2/9.23 1/10.00 1/9.47 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 20.9% |30.0% 21.7% 10.0% 10.6% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |2/9 (22%) 2/9 (22%) 1/10 (10%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- 95 |287 297 (T) 297 (T) 57 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.043 * (e) (e) P=0.228 |P=0.216N P=0.510N P=0.272N P=0.347N | |POLY 3 | P=0.037 * (e) (e) P=0.230 |P=0.189N P=0.539N P=0.292N P=0.312N | |POLY 1.5 | P=0.038 * (e) (e) P=0.229 |P=0.187N P=0.526N P=0.292N P=0.304N | |POLY 6 | P=0.036 * (e) (e) P=0.229 |P=0.192N P=0.549N P=0.292N P=0.323N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.079N P=0.535N P=0.272N P=0.100N | |COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.237 |P=0.180N P=0.500N P=0.291N P=0.291N | |ORDER RESTRICTED | P=0.024 * (e) (e) (e) |P=0.212N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/10 (80%) 4/10 (40%) 3/10 (30%) 4/10 (40%) |2/10 (20%) 2/10 (20%) 3/10 (30%) 6/10 (60%) | |POLY-3 RATE (b) | 8/10.00 4/10.00 3/10.00 4/8.22 |2/9.90 2/10.00 3/10.00 6/8.48 | |POLY-3 PERCENT (g) | 80.0% 40.0% 30.0% 48.7% |20.2% 20.0% 30.0% 70.8% | |TERMINAL (d) | 7/9 (78%) 4/10 (40%) 2/9 (22%) 3/7 (43%) |2/9 (22%) 1/9 (11%) 3/10 (30%) 6/8 (75%) | |FIRST INCIDENCE | 221 296 (T) 277 246 |297 (T) 183 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.234N P=0.070N P=0.060N P=0.258N |P=0.020 * P=0.700 P=0.553 P=0.051 | |POLY 3 | P=0.131N P=0.077N P=0.024N* P=0.182N |P=0.014 * P=0.699N P=0.505 P=0.031 * | |POLY 1.5 | P=0.119N P=0.077N P=0.024N* P=0.147N |P=0.016 * P=0.700N P=0.502 P=0.038 * | |POLY 6 | P=0.137N P=0.077N P=0.024N* P=0.201N |P=0.012 * P=0.696N P=0.509 P=0.027 * | |LOGISTIC REGRESSION| P=0.116N P=0.070N (e) P=0.141N |P=0.024 * P=0.562N P=0.553 P=0.051 | |COCH-ARM / FISHERS | P=0.090N P=0.085N P=0.035N* P=0.085N |P=0.030 * P=0.709N P=0.500 P=0.085 | |ORDER RESTRICTED | P=0.057N (e) (e) (e) |P=0.013 * (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 | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/10 (90%) 10/10 (100%) 10/10 (100%) 9/10 (90%) |9/10 (90%) 9/10 (90%) 10/10 (100%) 8/10 (80%) | |POLY-3 RATE (b) | 9/9.42 10/10.00 10/10.00 9/9.19 |9/9.90 9/9.23 10/10.00 8/8.48 | |POLY-3 PERCENT (g) | 95.6% 100.0% 100.0% 97.9% |90.9% 97.5% 100.0% 94.4% | |TERMINAL (d) | 9/9 (100%) 10/10 (100%) 9/9 (100%) 7/7 (100%) |9/9 (100%) 9/9 (100%) 10/10 (100%) 8/8 (100%) | |FIRST INCIDENCE | 296 (T) 296 (T) 277 95 |297 (T) 297 (T) 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.054 P=1.000 P=0.521 P=0.227 |P=1.000 P=1.000 P=1.000 P=1.000 | |POLY 3 | P=0.836 P=0.909 P=0.909 P=0.946 |P=0.559 P=0.652 P=0.541 P=0.743 | |POLY 1.5 | P=0.763 P=0.699 P=0.699 P=0.838 |P=0.637 P=0.699 P=0.520 P=0.781 | |POLY 6 | P=0.997 P=1.000 P=1.000 P=1.000 |P=0.471 P=0.630 P=0.586 P=0.717 | |LOGISTIC REGRESSION| P=0.322 P=1.000 (e) P=0.540 |P=1.000 P=1.000 P=1.000 P=1.000 | |COCH-ARM / FISHERS | P=0.597N P=0.500 P=0.500 P=0.763N |P=0.361N P=0.763N P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.231 (e) (e) (e) |P=0.339 (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 2/10 (20%) |1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 1/9.42 0/10.00 0/9.82 2/9.03 |1/10.00 0/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 10.6% 0.0% 0.0% 22.1% |10.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/9 (11%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | 296 (T) --- --- 170 |287 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 P=0.479N P=0.500N P=0.446 |P=0.326N P=0.521N P=0.500N P=0.545N | |POLY 3 | P=0.227 P=0.488N P=0.492N P=0.485 |P=0.279N P=0.516N P=0.500N P=0.533N | |POLY 1.5 | P=0.229 P=0.493N P=0.495N P=0.482 |P=0.285N P=0.511N P=0.500N P=0.526N | |POLY 6 | P=0.226 P=0.483N P=0.489N P=0.493 |P=0.273N P=0.520N P=0.500N P=0.539N | |LOGISTIC REGRESSION| P=0.498 (e) (e) P=0.670 |P=0.300N P=0.486N (e) P=0.513N | |COCH-ARM / FISHERS | P=0.239 P=0.500N P=0.500N P=0.500 |P=0.304N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.106 (e) (e) (e) |P=0.151N (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 | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/10 (30%) 2/9 (22%) 1/10 (10%) 2/10 (20%) | |POLY-3 RATE (b) | |3/10.00 2/8.23 1/10.00 2/9.01 | |POLY-3 PERCENT (g) | |30.0% 24.3% 10.0% 22.2% | |TERMINAL (d) | |2/9 (22%) 2/8 (25%) 1/10 (10%) 1/8 (13%) | |FIRST INCIDENCE | |287 297 (T) 297 (T) 231 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.434N P=0.556N P=0.272N P=0.563N | |POLY 3 | |P=0.400N P=0.595N P=0.292N P=0.551N | |POLY 1.5 | |P=0.401N P=0.581N P=0.292N P=0.547N | |POLY 6 | |P=0.398N P=0.606N P=0.292N P=0.552N | |LOGISTIC REGRESSION| |P=0.387N P=0.596N P=0.272N P=0.503N | |COCH-ARM / FISHERS | |P=0.380N P=0.556N P=0.291N P=0.500N | |ORDER RESTRICTED | |P=0.367N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/10 (40%) 3/9 (33%) 3/10 (30%) 3/10 (30%) |1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 4/10.00 3/9.00 3/9.82 3/7.80 |1/9.90 0/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 40.0% 33.3% 30.6% 38.5% |10.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/9 (33%) 3/9 (33%) 3/9 (33%) 3/7 (43%) |1/9 (11%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | 221 296 (T) 296 (T) 296 (T) |297 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.589N P=0.500N P=0.500N P=0.651N |P=0.314N P=0.500N P=0.479N P=0.523N | |POLY 3 | P=0.537N P=0.566N P=0.511N P=0.655N |P=0.280N P=0.514N P=0.498N P=0.531N | |POLY 1.5 | P=0.505N P=0.566N P=0.506N P=0.612N |P=0.286N P=0.510N P=0.499N P=0.525N | |POLY 6 | P=0.563N P=0.566N P=0.521N P=0.667 |P=0.275N P=0.516N P=0.496N P=0.535N | |LOGISTIC REGRESSION| P=0.498N P=0.500N P=0.577N P=0.588N |P=0.314N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.410N P=0.570N P=0.500N P=0.500N |P=0.304N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.622N (e) (e) (e) |P=0.149N (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 | | | | | |=================================================================================================================================| | | |Salivary Glands | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/2 (100%) |0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 2/2.00 |0/0.00 0/0.00 0/1.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 100.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/2 (100%) |0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 296 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Spleen | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 3/10 (30%) |0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 0/9.82 3/10.00 |0/9.90 0/9.23 0/10.00 1/9.47 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 30.0% |0.0% 0.0% 0.0% 10.6% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- 95 |--- --- --- 57 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010 * (e) (e) P=0.111 |P=0.199 (e) (e) P=0.500 | |POLY 3 | P=0.006 ** (e) (e) P=0.106 |P=0.196 (e) (e) P=0.491 | |POLY 1.5 | P=0.006 ** (e) (e) P=0.102 |P=0.198 (e) (e) P=0.495 | |POLY 6 | P=0.006 ** (e) (e) P=0.111 |P=0.195 (e) (e) P=0.488 | |LOGISTIC REGRESSION| P=0.091 (e) (e) P=0.310 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.010 * (e) (e) P=0.105 |P=0.196 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) |P=0.112 (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 | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |2/10 (20%) 1/10 (10%) 0/10 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 1/10.00 0/10.00 0/9.82 0/7.80 |2/10.00 1/10.00 0/10.00 2/9.01 | |POLY-3 PERCENT (g) | 10.0% 0.0% 0.0% 0.0% |20.0% 10.0% 0.0% 22.2% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |1/9 (11%) 0/9 (0%) 0/10 (0%) 1/8 (13%) | |FIRST INCIDENCE | 221 --- --- --- |287 183 --- 231 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.328N P=0.500N P=0.500N P=0.545N |P=0.555 P=0.512N P=0.228N P=0.643 | |POLY 3 | P=0.273N P=0.500N P=0.504N P=0.549N |P=0.573 P=0.500N P=0.227N P=0.663 | |POLY 1.5 | P=0.284N P=0.500N P=0.502N P=0.535N |P=0.575 P=0.500N P=0.227N P=0.667 | |POLY 6 | P=0.265N P=0.500N P=0.507N P=0.559N |P=0.573 P=0.500N P=0.227N P=0.663 | |LOGISTIC REGRESSION| P=0.102N (e) (e) P=0.354N |P=0.513N (e) (e) P=0.708N | |COCH-ARM / FISHERS | P=0.304N P=0.500N P=0.500N P=0.500N |P=0.596 P=0.500N P=0.237N P=0.709N | |ORDER RESTRICTED | P=0.169N (e) (e) (e) |P=0.352 (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) |0/10 (0%) 1/10 (10%) 0/10 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 0/9.82 0/7.80 |0/9.90 1/10.00 0/10.00 2/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 10.0% 0.0% 20.0% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |0/9 (0%) 0/9 (0%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 183 --- 57 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.131 P=0.500 (e) P=0.228 | |POLY 3 | (e) (e) (e) (e) |P=0.134 P=0.502 (e) P=0.229 | |POLY 1.5 | (e) (e) (e) (e) |P=0.133 P=0.501 (e) P=0.228 | |POLY 6 | (e) (e) (e) (e) |P=0.135 P=0.504 (e) P=0.231 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.132 P=0.500 (e) P=0.237 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.067 (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 | | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/10 (10%) 1/10 (10%) 1/10 (10%) 1/10 (10%) |0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) | |POLY-3 RATE (b) | 1/10.00 1/10.00 1/9.82 1/8.22 |0/9.90 2/9.23 0/10.00 0/8.48 | |POLY-3 PERCENT (g) | 10.0% 10.0% 10.2% 12.2% |0.0% 21.7% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 1/10 (10%) 1/9 (11%) 0/7 (0%) |0/9 (0%) 2/9 (22%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | 221 296 (T) 296 (T) 246 |--- 297 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.572 P=0.749N P=0.760 P=0.722 |P=0.423N P=0.233 (e) (e) | |POLY 3 | P=0.563 P=0.760 P=0.756 P=0.716 |P=0.430N P=0.209 (e) (e) | |POLY 1.5 | P=0.580 P=0.760 P=0.758 P=0.727 |P=0.424N P=0.215 (e) (e) | |POLY 6 | P=0.555 P=0.760 P=0.753 P=0.710 |P=0.432N P=0.207 (e) (e) | |LOGISTIC REGRESSION| P=0.507N P=0.749N P=0.592 P=0.682N |(e) P=0.233 (e) (e) | |COCH-ARM / FISHERS | P=0.639 P=0.763N P=0.763N P=0.763N |P=0.403N P=0.237 (e) (e) | |ORDER RESTRICTED | P=0.681 (e) (e) (e) |P=0.246N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/10 (20%) 2/10 (20%) 1/10 (10%) 3/10 (30%) | | |POLY-3 RATE (b) | 2/9.42 2/10.00 1/9.82 3/8.22 | | |POLY-3 PERCENT (g) | 21.2% 20.0% 10.2% 36.5% | | |TERMINAL (d) | 2/9 (22%) 2/10 (20%) 1/9 (11%) 2/7 (29%) | | |FIRST INCIDENCE | 296 (T) 296 (T) 296 (T) 246 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.280 P=0.667N P=0.500N P=0.392 | | |POLY 3 | P=0.345 P=0.680N P=0.485N P=0.432 | | |POLY 1.5 | P=0.354 P=0.689N P=0.490N P=0.443 | | |POLY 6 | P=0.343 P=0.671N P=0.481N P=0.433 | | |LOGISTIC REGRESSION| P=0.333 P=0.667N P=0.500N P=0.427 | | |COCH-ARM / FISHERS | P=0.395 P=0.709N P=0.500N P=0.500 | | |ORDER RESTRICTED | P=0.279 (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 | | | | | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/10 (0%) 0/10 (0%) 1/10 (10%) 3/10 (30%) |2/10 (20%) 1/9 (11%) 0/10 (0%) 2/10 (20%) | |POLY-3 RATE (b) | 0/9.42 0/10.00 1/10.00 3/10.00 |2/10.00 1/9.00 0/10.00 2/10.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 10.0% 30.0% |20.0% 11.1% 0.0% 20.0% | |TERMINAL (d) | 0/9 (0%) 0/10 (0%) 0/9 (0%) 0/7 (0%) |1/9 (11%) 1/9 (11%) 0/10 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- 277 95 |287 297 (T) --- 57 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.014 * (e) P=0.521 P=0.111 |P=0.564 P=0.512N P=0.228N P=0.652 | |POLY 3 | P=0.014 * (e) P=0.512 P=0.106 |P=0.605 P=0.538N P=0.227N P=0.702 | |POLY 1.5 | P=0.014 * (e) P=0.507 P=0.102 |P=0.605 P=0.538N P=0.227N P=0.702 | |POLY 6 | P=0.015 * (e) P=0.517 P=0.111 |P=0.605 P=0.538N P=0.227N P=0.702 | |LOGISTIC REGRESSION| P=0.133 (e) P=0.421 P=0.310 |(e) P=0.512N (e) (e) | |COCH-ARM / FISHERS | P=0.016 * (e) P=0.500 P=0.105 |P=0.607 P=0.542N P=0.237N P=0.709N | |ORDER RESTRICTED | P=0.016 * (e) (e) (e) |P=0.401N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/10 (80%) 7/10 (70%) 3/10 (30%) 4/10 (40%) |7/10 (70%) 6/9 (67%) 8/10 (80%) 8/10 (80%) | |POLY-3 RATE (b) | 8/9.42 7/10.00 3/10.00 4/9.57 |7/10.00 6/9.00 8/10.00 8/8.48 | |POLY-3 PERCENT (g) | 85.0% 70.0% 30.0% 41.8% |70.0% 66.7% 80.0% 94.4% | |TERMINAL (d) | 8/9 (89%) 7/10 (70%) 2/9 (22%) 2/7 (29%) |6/9 (67%) 6/9 (67%) 8/10 (80%) 8/8 (100%) | |FIRST INCIDENCE | 296 (T) 296 (T) 277 95 |287 297 (T) 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.131N P=0.333N P=0.045N* P=0.243N |P=0.158 P=0.509N P=0.631 P=0.311 | |POLY 3 | P=0.023N* P=0.405N P=0.012N* P=0.055N |P=0.129 P=0.626N P=0.500 P=0.226 | |POLY 1.5 | P=0.025N* P=0.444N P=0.016N* P=0.062N |P=0.164 P=0.626N P=0.500 P=0.283 | |POLY 6 | P=0.023N* P=0.363N P=0.008N** P=0.051N |P=0.103 P=0.626N P=0.500 P=0.177 | |LOGISTIC REGRESSION| P=0.015N* P=0.333N P=0.024N* P=0.058N |P=0.091 P=0.509N P=0.631 P=0.170 | |COCH-ARM / FISHERS | P=0.034N* P=0.500N P=0.035N* P=0.085N |P=0.339 P=0.630N P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.015N* (e) (e) (e) |P=0.151 (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 | | | | | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/10 (20%) 1/10 (10%) 2/10 (20%) 1/10 (10%) | |POLY-3 RATE (b) | |2/9.90 1/9.23 2/10.00 1/8.48 | |POLY-3 PERCENT (g) | |20.2% 10.8% 20.0% 11.8% | |TERMINAL (d) | |2/9 (22%) 1/9 (11%) 2/10 (20%) 1/8 (13%) | |FIRST INCIDENCE | |297 (T) 297 (T) 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.480N P=0.500N P=0.667N P=0.543N | |POLY 3 | |P=0.482N P=0.525N P=0.699N P=0.556N | |POLY 1.5 | |P=0.477N P=0.517N P=0.700N P=0.545N | |POLY 6 | |P=0.486N P=0.529N P=0.696N P=0.563N | |LOGISTIC REGRESSION| |P=0.480N P=0.500N P=0.667N P=0.543N | |COCH-ARM / FISHERS | |P=0.441N P=0.500N P=0.709N P=0.500N | |ORDER RESTRICTED | |P=0.507N (e) (e) (e) | |=================================================================================================================================| Date: 10/08/03 EXPERIMENT: 97013 TEST: 96 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(P53 Heterozygous Transgenic) - WATER DISINFECTION MODEL (BROMODIC HLOR 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 | | | | | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |8/10 (80%) 8/10 (80%) 8/10 (80%) 6/10 (60%) | |POLY-3 RATE (b) | |8/9.90 8/9.23 8/10.00 6/8.48 | |POLY-3 PERCENT (g) | |80.8% 86.6% 80.0% 70.8% | |TERMINAL (d) | |8/9 (89%) 8/9 (89%) 8/10 (80%) 6/8 (75%) | |FIRST INCIDENCE | |297 (T) 297 (T) 297 (T) 297 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.286N P=0.767 P=0.539N P=0.457N | |POLY 3 | |P=0.356N P=0.606 P=0.691N P=0.518N | |POLY 1.5 | |P=0.328N P=0.641 P=0.696N P=0.475N | |POLY 6 | |P=0.378N P=0.589 P=0.680N P=0.552N | |LOGISTIC REGRESSION| |P=0.286N P=0.767 P=0.539N P=0.457N | |COCH-ARM / FISHERS | |P=0.194N P=0.709N P=0.709N P=0.314N | |ORDER RESTRICTED | |P=0.403N (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).