TDMS Study 97013-09 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (SODIUM BROMATE) DATE: 06/18/04 EXPERIMENT: 97013 TEST: 09 TIME: 11:08:17 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: DOSED WATER NTP C#: 97013A PATHOLOGIST: TOFT, JOHN CAS: 7789-38-0 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 MG/L INCLUDE 002 0 MG/L INCLUDE 003 80 MG/L INCLUDE 004 80 MG/L INCLUDE 005 400 MG/L INCLUDE 006 400 MG/L INCLUDE 007 800 MG/L INCLUDE 008 800 MG/L NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus WATER DISINFECTION MODEL (SODIUM BROMATE) DATE: 06/18/04 EXPERIMENT: 97013 TEST: 09 TIME: 11:08:17 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: DOSED WATER NTP C#: 97013A PATHOLOGIST: TOFT, JOHN CAS: 7789-38-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF WATER DISINFECTION MODEL (SODIUM BR =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Kidney Nephropathy Kidney: Renal Tubule Degeneration Hypertrophy Pituitary Gland: Pars Distalis Cyst Spleen Hematopoietic Cell Proliferation Thymus Cyst Thyroid Gland: Follicle Depletion Secretory Thyroid Gland: Follicular Cell Hypertrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Kidney Nephropathy Kidney: Artery Inflammation Chronic Kidney: Renal Tubule Degeneration Hypertrophy Liver: Hepatocyte Vacuolization Cytoplasmic Lymph Node, Mandibular Hyperplasia Lymphoid Pituitary Gland: Pars Distalis Hypertrophy Skin: Epidermis Hyperkeratosis Hyperplasia Focal Thyroid Gland Infiltration Cellular Lymphocyte Thyroid Gland: Follicle Depletion Secretory Thyroid Gland: Follicular Cell Hypertrophy =============================================================== Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SO DIUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/15 (27%) 6/15 (40%) 6/15 (40%) 4/15 (27%) |0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 4/13.82 6/14.58 6/14.49 4/14.62 |0/12.01 0/10.24 0/12.33 0/12.46 | |POLY-3 PERCENT (g) | 28.9% 41.2% 41.4% 27.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 4/13 (31%) 6/13 (46%) 6/14 (43%) 4/14 (29%) |0/10 (0%) 0/9 (0%) 0/10 (0%) 0/12 (0%) | |FIRST INCIDENCE | 183 (T) 183 (T) 183 (T) 183 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.386N P=0.346 P=0.403 P=0.615N |(e) (e) (e) (e) | |POLY 3 | P=0.423N P=0.389 P=0.384 P=0.623N |(e) (e) (e) (e) | |POLY 1.5 | P=0.423N P=0.391 P=0.388 P=0.622N |(e) (e) (e) (e) | |POLY 6 | P=0.425N P=0.384 P=0.379 P=0.626N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.386N P=0.346 P=0.403 P=0.615N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.458N P=0.350 P=0.350 P=0.659N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.464N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 1/15 (7%) 0/15 (0%) 1/15 (7%) |4/15 (27%) 6/15 (40%) 2/15 (13%) 2/15 (13%) | |POLY-3 RATE (b) | 1/13.82 1/14.58 0/14.49 1/14.62 |4/12.21 6/10.76 2/12.33 2/13.00 | |POLY-3 PERCENT (g) | 7.2% 6.9% 0.0% 6.8% |32.8% 55.8% 16.2% 15.4% | |TERMINAL (d) | 1/13 (8%) 1/13 (8%) 0/14 (0%) 1/14 (7%) |3/10 (30%) 5/9 (56%) 2/10 (20%) 1/12 (8%) | |FIRST INCIDENCE | 183 (T) 183 (T) --- 183 (T) |171 144 184 (T) 142 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.566N P=0.765 P=0.485N P=0.748N |P=0.051N P=0.264 P=0.334N P=0.273N | |POLY 3 | P=0.583N P=0.749N P=0.491N P=0.748N |P=0.057N P=0.246 P=0.317N P=0.292N | |POLY 1.5 | P=0.583N P=0.748N P=0.490N P=0.748N |P=0.066N P=0.281 P=0.312N P=0.309N | |POLY 6 | P=0.584N P=0.750N P=0.492N P=0.749N |P=0.052N P=0.229 P=0.328N P=0.279N | |LOGISTIC REGRESSION| P=0.566N P=0.765 (e) P=0.748N |P=0.062N P=0.225 P=0.311N P=0.316N | |COCH-ARM / FISHERS | P=0.589N P=0.759N P=0.500N P=0.759N |P=0.087N P=0.350 P=0.326N P=0.326N | |ORDER RESTRICTED | P=0.518N (e) (e) (e) |P=0.078N (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Epididymis | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 2/15 (13%) | | |POLY-3 RATE (b) | 0/13.82 0/14.58 2/14.49 2/14.62 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 13.8% 13.7% | | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 2/14 (14%) 2/14 (14%) | | |FIRST INCIDENCE | --- --- 183 (T) 183 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.076 (e) P=0.252 P=0.252 | | |POLY 3 | P=0.070 (e) P=0.242 P=0.244 | | |POLY 1.5 | P=0.070 (e) P=0.243 P=0.245 | | |POLY 6 | P=0.069 (e) P=0.240 P=0.243 | | |LOGISTIC REGRESSION| (e) (e) P=0.252 P=0.252 | | |COCH-ARM / FISHERS | P=0.065 (e) P=0.241 P=0.241 | | |ORDER RESTRICTED | P=0.115 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 7/15 (47%) 10/15 (67%) 14/15 (93%) |2/15 (13%) 2/15 (13%) 10/15 (67%) 13/15 (87%) | |POLY-3 RATE (b) | 1/13.82 7/14.58 10/14.49 14/14.62 |2/12.01 2/10.24 10/12.33 13/13.00 | |POLY-3 PERCENT (g) | 7.2% 48.0% 69.0% 95.8% |16.7% 19.5% 81.1% 100.0% | |TERMINAL (d) | 1/13 (8%) 7/13 (54%) 10/14 (71%) 14/14 (100%)|2/10 (20%) 2/9 (22%) 10/10 (100%) 12/12 (100%) | |FIRST INCIDENCE | 183 (T) 183 (T) 183 (T) 183 (T) |184 (T) 184 (T) 184 (T) 142 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.019 * P=0.002 ** P<0.001 ** |P<0.001 ** P=0.667 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.642 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.665 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.628 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.019 * P=0.002 ** P<0.001 ** |P<0.001 ** P=0.667 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.018 * P<0.001 ** P<0.001 ** |P<0.001 ** P=0.701N P=0.004 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Kidney: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) |2/15 (13%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.82 0/14.58 0/14.49 0/14.62 |2/12.21 0/10.24 0/12.33 0/12.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |16.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) |1/10 (10%) 0/9 (0%) 0/10 (0%) 0/12 (0%) | |FIRST INCIDENCE | --- --- --- --- |171 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.145N P=0.284N P=0.249N P=0.220N | |POLY 3 | (e) (e) (e) (e) |P=0.125N P=0.272N P=0.227N P=0.225N | |POLY 1.5 | (e) (e) (e) (e) |P=0.134N P=0.255N P=0.225N P=0.229N | |POLY 6 | (e) (e) (e) (e) |P=0.120N P=0.285N P=0.232N P=0.223N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.146N P=0.263N P=0.226N P=0.226N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.158N P=0.241N P=0.241N P=0.241N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.024N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 10/15 (67%) |0/15 (0%) 0/15 (0%) 2/15 (13%) 8/15 (53%) | |POLY-3 RATE (b) | 0/13.82 0/14.58 0/14.49 10/14.62 |0/12.01 0/10.24 2/12.33 8/12.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 68.4% |0.0% 0.0% 16.2% 64.2% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/14 (0%) 10/14 (71%) |0/10 (0%) 0/9 (0%) 2/10 (20%) 8/12 (67%) | |FIRST INCIDENCE | --- --- --- 183 (T) |--- --- 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** (e) P=0.234 P=0.003 ** | |POLY 3 | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** (e) P=0.235 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** (e) P=0.237 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** (e) P=0.232 P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) P<0.001 ** |(e) (e) P=0.234 P=0.003 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** (e) P=0.241 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) |1/15 (7%) 2/15 (13%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.82 0/14.58 1/14.49 0/14.62 |1/12.01 2/10.24 0/12.33 1/12.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.9% 0.0% |8.3% 19.5% 0.0% 8.0% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 1/14 (7%) 0/14 (0%) |1/10 (10%) 2/9 (22%) 0/10 (0%) 1/12 (8%) | |FIRST INCIDENCE | --- --- 183 (T) --- |184 (T) 184 (T) --- 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.660 (e) P=0.515 (e) |P=0.352N P=0.461 P=0.500N P=0.724N | |POLY 3 | P=0.662 (e) P=0.509 (e) |P=0.417N P=0.442 P=0.495N P=0.754N | |POLY 1.5 | P=0.662 (e) P=0.510 (e) |P=0.418N P=0.464 P=0.494N P=0.759N | |POLY 6 | P=0.661 (e) P=0.508 (e) |P=0.417N P=0.429 P=0.497N P=0.750N | |LOGISTIC REGRESSION| (e) (e) P=0.515 (e) |P=0.352N P=0.461 (e) P=0.724N | |COCH-ARM / FISHERS | P=0.650 (e) P=0.500 (e) |P=0.422N P=0.500 P=0.500N P=0.759N | |ORDER RESTRICTED | P=0.389 (e) (e) (e) |P=0.315N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) |0/15 (0%) 1/15 (7%) 5/15 (33%) 12/15 (80%) | |POLY-3 RATE (b) | 0/13.82 0/14.58 0/14.49 2/14.62 |0/12.01 1/10.24 5/12.33 12/12.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 13.7% |0.0% 9.8% 40.6% 96.3% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/14 (0%) 2/14 (14%) |0/10 (0%) 1/9 (11%) 5/10 (50%) 12/12 (100%) | |FIRST INCIDENCE | --- --- --- 183 (T) |--- 184 (T) 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.047 * (e) (e) P=0.252 |P<0.001 ** P=0.479 P=0.022 * P<0.001 ** | |POLY 3 | P=0.040 * (e) (e) P=0.244 |P<0.001 ** P=0.468 P=0.016 * P<0.001 ** | |POLY 1.5 | P=0.040 * (e) (e) P=0.245 |P<0.001 ** P=0.480 P=0.017 * P<0.001 ** | |POLY 6 | P=0.039 * (e) (e) P=0.243 |P<0.001 ** P=0.461 P=0.014 * P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) P=0.252 |(e) P=0.479 P=0.022 * P<0.001 ** | |COCH-ARM / FISHERS | P=0.041 * (e) (e) P=0.241 |P<0.001 ** P=0.500 P=0.021 * P<0.001 ** | |ORDER RESTRICTED | P=0.030 * (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/15 (60%) 4/15 (27%) 10/15 (67%) 7/15 (47%) |11/15 (73%) 9/15 (60%) 10/15 (67%) 12/15 (80%) | |POLY-3 RATE (b) | 9/15.00 4/14.58 10/15.00 7/14.62 |11/12.21 9/10.24 10/12.33 12/12.46 | |POLY-3 PERCENT (g) | 60.0% 27.4% 66.7% 47.9% |90.1% 87.9% 81.1% 96.3% | |TERMINAL (d) | 7/13 (54%) 4/13 (31%) 9/14 (64%) 7/14 (50%) |10/10 (100%) 9/9 (100%) 10/10 (100%) 12/12 (100%) | |FIRST INCIDENCE | 29 183 (T) 144 183 (T) |171 184 (T) 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.551 P=0.086N P=0.580 P=0.306N |P=0.338N P=0.557N P=0.517N P=0.500N | |POLY 3 | P=0.449 P=0.074N P=0.500 P=0.387N |P=0.398 P=0.737N P=0.475N P=0.588 | |POLY 1.5 | P=0.454 P=0.070N P=0.500 P=0.375N |P=0.301 P=0.520N P=0.449N P=0.517 | |POLY 6 | P=0.442 P=0.080N P=0.500 P=0.405N |P=0.479 P=0.798 P=0.549N P=0.647 | |LOGISTIC REGRESSION| P=0.422 P=0.090N (e) P=0.405N |P=0.707N P=0.833 P=0.549N P=0.808 | |COCH-ARM / FISHERS | P=0.461 P=0.070N P=0.500 P=0.358N |P=0.272 P=0.350N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.363 (e) (e) (e) |P=0.259 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/15 (40%) 4/15 (27%) 7/15 (47%) 4/15 (27%) |5/15 (33%) 0/15 (0%) 5/15 (33%) 5/15 (33%) | |POLY-3 RATE (b) | 6/13.82 4/14.58 7/14.49 4/14.62 |5/12.01 0/10.24 5/12.33 5/12.46 | |POLY-3 PERCENT (g) | 43.4% 27.4% 48.3% 27.4% |41.6% 0.0% 40.6% 40.1% | |TERMINAL (d) | 6/13 (46%) 4/13 (31%) 7/14 (50%) 4/14 (29%) |5/10 (50%) 0/9 (0%) 5/10 (50%) 5/12 (42%) | |FIRST INCIDENCE | 183 (T) 183 (T) 183 (T) 183 (T) |184 (T) --- 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.357N P=0.346N P=0.572 P=0.296N |P=0.290 P=0.029N* P=0.669 P=0.515N | |POLY 3 | P=0.404N P=0.312N P=0.545 P=0.311N |P=0.247 P=0.025N* P=0.638N P=0.628N | |POLY 1.5 | P=0.405N P=0.312N P=0.548 P=0.311N |P=0.206 P=0.020N* P=0.632N P=0.645N | |POLY 6 | P=0.405N P=0.316N P=0.539 P=0.313N |P=0.278 P=0.027N* P=0.648N P=0.614N | |LOGISTIC REGRESSION| P=0.357N P=0.346N P=0.572 P=0.296N |P=0.290 (e) P=0.669 P=0.515N | |COCH-ARM / FISHERS | P=0.432N P=0.350N P=0.500 P=0.350N |P=0.172 P=0.021N* P=0.650N P=0.650N | |ORDER RESTRICTED | P=0.302N (e) (e) (e) |P=0.254 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) |0/15 (0%) 3/15 (20%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.82 0/14.58 1/14.49 0/14.62 |0/12.01 3/10.24 0/12.33 1/13.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.9% 0.0% |0.0% 29.3% 0.0% 7.4% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 1/14 (7%) 0/14 (0%) |0/10 (0%) 3/9 (33%) 0/10 (0%) 0/12 (0%) | |FIRST INCIDENCE | --- --- 183 (T) --- |--- 184 (T) --- 9 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.660 (e) P=0.515 (e) |P=0.420N P=0.093 (e) P=0.500 | |POLY 3 | P=0.662 (e) P=0.509 (e) |P=0.483N P=0.074 (e) P=0.523 | |POLY 1.5 | P=0.662 (e) P=0.510 (e) |P=0.474N P=0.084 (e) P=0.518 | |POLY 6 | P=0.661 (e) P=0.508 (e) |P=0.488N P=0.068 (e) P=0.527 | |LOGISTIC REGRESSION| (e) (e) P=0.515 (e) |P=0.480N P=0.093 (e) (e) | |COCH-ARM / FISHERS | P=0.650 (e) P=0.500 (e) |P=0.474N P=0.112 (e) P=0.500 | |ORDER RESTRICTED | P=0.389 (e) (e) (e) |P=0.223 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/15 (20%) 1/15 (7%) 3/15 (20%) 1/15 (7%) |0/15 (0%) 4/15 (27%) 2/15 (13%) 5/15 (33%) | |POLY-3 RATE (b) | 3/14.00 1/14.58 3/15.00 1/14.62 |0/12.01 4/10.24 2/12.66 5/12.46 | |POLY-3 PERCENT (g) | 21.4% 6.9% 20.0% 6.8% |0.0% 39.1% 15.8% 40.1% | |TERMINAL (d) | 2/13 (15%) 1/13 (8%) 2/14 (14%) 1/14 (7%) |0/10 (0%) 4/9 (44%) 1/10 (10%) 5/12 (42%) | |FIRST INCIDENCE | 171 183 (T) 144 183 (T) |--- 184 (T) 161 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.343N P=0.303N P=0.636N P=0.283N |P=0.128 P=0.039 * P=0.240 P=0.038 * | |POLY 3 | P=0.360N P=0.283N P=0.637N P=0.282N |P=0.065 P=0.024 * P=0.242 P=0.017 * | |POLY 1.5 | P=0.360N P=0.280N P=0.639N P=0.279N |P=0.062 P=0.030 * P=0.240 P=0.016 * | |POLY 6 | P=0.361N P=0.289N P=0.637N P=0.287N |P=0.068 P=0.021 * P=0.243 P=0.018 * | |LOGISTIC REGRESSION| P=0.380N P=0.281N P=0.669 P=0.280N |P=0.096 P=0.039 * P=0.236 P=0.038 * | |COCH-ARM / FISHERS | P=0.368N P=0.299N P=0.674N P=0.299N |P=0.069 P=0.050 P=0.241 P=0.021 * | |ORDER RESTRICTED | P=0.210N (e) (e) (e) |P=0.009 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Parathyroid Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/1 (100%) 0/0 (0%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 1/1.00 0/0.00 2/2.00 0/0.00 |0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 100.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 183 (T) --- 183 (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) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/14 (0%) 4/15 (27%) 0/15 (0%) |1/15 (7%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.82 0/13.98 4/15.00 0/14.62 |1/12.01 0/10.24 0/12.33 2/13.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 26.7% 0.0% |8.3% 0.0% 0.0% 15.4% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 3/14 (21%) 0/14 (0%) |1/10 (10%) 0/9 (0%) 0/10 (0%) 1/12 (8%) | |FIRST INCIDENCE | --- --- 144 --- |184 (T) --- --- 142 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.449 (e) P=0.071 (e) |P=0.258 P=0.521N P=0.500N P=0.552 | |POLY 3 | P=0.440 (e) P=0.056 (e) |P=0.242 P=0.532N P=0.495N P=0.528 | |POLY 1.5 | P=0.445 (e) P=0.054 (e) |P=0.226 P=0.520N P=0.494N P=0.514 | |POLY 6 | P=0.430 (e) P=0.057 (e) |P=0.255 P=0.539N P=0.497N P=0.543 | |LOGISTIC REGRESSION| P=0.405 (e) P=0.047 * (e) |P=0.212 (e) (e) P=0.502 | |COCH-ARM / FISHERS | P=0.433 (e) P=0.050 (e) |P=0.204 P=0.500N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.096 (e) (e) (e) |P=0.147 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) |0/15 (0%) 0/15 (0%) 0/15 (0%) 6/15 (40%) | |POLY-3 RATE (b) | 0/13.82 0/13.98 0/14.49 0/14.62 |0/12.01 0/10.24 0/12.33 6/12.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 48.1% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) |0/10 (0%) 0/9 (0%) 0/10 (0%) 6/12 (50%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P<0.001 ** (e) (e) P=0.018 * | |POLY 3 | (e) (e) (e) (e) |P<0.001 ** (e) (e) P=0.005 ** | |POLY 1.5 | (e) (e) (e) (e) |P<0.001 ** (e) (e) P=0.004 ** | |POLY 6 | (e) (e) (e) (e) |P<0.001 ** (e) (e) P=0.005 ** | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.018 * | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P<0.001 ** (e) (e) P=0.008 ** | |ORDER RESTRICTED | (e) (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/2 (0%) 0/4 (0%) 1/3 (33%) |0/6 (0%) 0/5 (0%) 0/2 (0%) 2/7 (29%) | |POLY-3 RATE (b) | 0/0.00 0/1.98 0/4.00 1/3.00 |0/5.89 0/4.48 0/0.80 2/7.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 33.3% |0.0% 0.0% 0.0% 28.6% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/4 (0%) 1/3 (33%) |0/5 (0%) 0/4 (0%) 0/0 (0%) 2/7 (29%) | |FIRST INCIDENCE | --- --- --- 183 (T) |--- --- --- 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.357 (e) (e) P=1.000N |P=0.102 (e) (e) P=0.308 | |POLY 3 | (e) (e) (e) (e) |P=0.072 (e) (e) P=0.261 | |POLY 1.5 | (e) (e) (e) (e) |P=0.069 (e) (e) P=0.259 | |POLY 6 | (e) (e) (e) (e) |P=0.077 (e) (e) P=0.266 | |LOGISTIC REGRESSION| (e) (e) (e) P=1.000N |(e) (e) (e) P=0.308 | |COCH-ARM / FISHERS | P=0.293 (e) (e) P=1.000 |P=0.065 (e) (e) P=0.269 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.033 * (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/2 (0%) 1/4 (25%) 2/3 (67%) |0/6 (0%) 0/5 (0%) 0/2 (0%) 2/7 (29%) | |POLY-3 RATE (b) | 0/0.00 0/1.98 1/4.00 2/3.00 |0/5.89 0/4.48 0/0.80 2/7.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 25.0% 66.7% |0.0% 0.0% 0.0% 28.6% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 1/4 (25%) 2/3 (67%) |0/5 (0%) 0/4 (0%) 0/0 (0%) 2/7 (29%) | |FIRST INCIDENCE | --- --- 183 (T) 183 (T) |--- --- --- 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.227 (e) P=1.000N P=1.000N |P=0.102 (e) (e) P=0.308 | |POLY 3 | (e) (e) (e) (e) |P=0.072 (e) (e) P=0.261 | |POLY 1.5 | (e) (e) (e) (e) |P=0.069 (e) (e) P=0.259 | |POLY 6 | (e) (e) (e) (e) |P=0.077 (e) (e) P=0.266 | |LOGISTIC REGRESSION| (e) (e) P=1.000N P=1.000N |(e) (e) (e) P=0.308 | |COCH-ARM / FISHERS | P=0.138 (e) P=1.000 P=1.000 |P=0.065 (e) (e) P=0.269 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.033 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Spleen | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 1/15 (7%) 0/15 (0%) 1/15 (7%) |1/15 (7%) 1/15 (7%) 1/15 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 1/14.00 1/14.60 0/14.49 1/15.00 |1/13.01 1/10.80 1/13.32 2/14.46 | |POLY-3 PERCENT (g) | 7.1% 6.9% 0.0% 6.7% |7.7% 9.3% 7.5% 13.8% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) |0/10 (0%) 0/9 (0%) 0/10 (0%) 0/12 (0%) | |FIRST INCIDENCE | 171 182 --- 156 |28 140 28 9 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.577N P=0.752N P=0.500N P=0.753N |P=0.339 P=0.751 P=0.764 P=0.484 | |POLY 3 | P=0.583N P=0.751N P=0.493N P=0.745N |P=0.410 P=0.719 P=0.756N P=0.537 | |POLY 1.5 | P=0.583N P=0.750N P=0.491N P=0.746N |P=0.396 P=0.729 P=0.755N P=0.529 | |POLY 6 | P=0.583N P=0.755N P=0.497N P=0.745N |P=0.420 P=0.716 P=0.759N P=0.545 | |LOGISTIC REGRESSION| P=0.630N P=0.771N P=0.512N P=0.741 |P=0.354 P=0.767N (e) (e) | |COCH-ARM / FISHERS | P=0.589N P=0.759N P=0.500N P=0.759N |P=0.339 P=0.759N P=0.759N P=0.500 | |ORDER RESTRICTED | P=0.517N (e) (e) (e) |P=0.463 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 3/15 (20%) |2/15 (13%) 3/15 (20%) 1/15 (7%) 4/15 (27%) | |POLY-3 RATE (b) | 1/13.82 0/14.58 0/14.49 3/14.62 |2/12.01 3/12.20 1/12.33 4/12.46 | |POLY-3 PERCENT (g) | 7.2% 0.0% 0.0% 20.5% |16.7% 24.6% 8.1% 32.1% | |TERMINAL (d) | 1/13 (8%) 0/13 (0%) 0/14 (0%) 3/14 (21%) |2/10 (20%) 1/9 (11%) 1/10 (10%) 4/12 (33%) | |FIRST INCIDENCE | 183 (T) --- --- 183 (T) |184 (T) 49 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.076 P=0.500N P=0.485N P=0.325 |P=0.407 P=0.484 P=0.500N P=0.415 | |POLY 3 | P=0.061 P=0.489N P=0.491N P=0.319 |P=0.326 P=0.508 P=0.491N P=0.340 | |POLY 1.5 | P=0.062 P=0.489N P=0.490N P=0.319 |P=0.314 P=0.520 P=0.489N P=0.329 | |POLY 6 | P=0.061 P=0.491N P=0.492N P=0.317 |P=0.337 P=0.497 P=0.495N P=0.351 | |LOGISTIC REGRESSION| P=0.076 (e) (e) P=0.325 |P=0.314 P=0.540 P=0.500N P=0.415 | |COCH-ARM / FISHERS | P=0.065 P=0.500N P=0.500N P=0.299 |P=0.314 P=0.500 P=0.500N P=0.326 | |ORDER RESTRICTED | P=0.036 * (e) (e) (e) |P=0.270 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 1/15 (7%) 2/15 (13%) 0/15 (0%) |4/15 (27%) 3/15 (20%) 3/15 (20%) 7/15 (47%) | |POLY-3 RATE (b) | 1/14.00 1/14.60 2/15.00 0/14.62 |4/13.01 3/10.80 3/13.32 7/15.00 | |POLY-3 PERCENT (g) | 7.1% 6.9% 13.3% 0.0% |30.7% 27.8% 22.5% 46.7% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 1/14 (7%) 0/14 (0%) |3/10 (30%) 2/9 (22%) 2/10 (20%) 4/12 (33%) | |FIRST INCIDENCE | 171 182 144 --- |28 140 28 9 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.363N P=0.752N P=0.516 P=0.500N |P=0.189 P=0.550N P=0.500N P=0.320 | |POLY 3 | P=0.363N P=0.751N P=0.524 P=0.491N |P=0.192 P=0.612N P=0.486N P=0.322 | |POLY 1.5 | P=0.362N P=0.750N P=0.523 P=0.490N |P=0.165 P=0.586N P=0.483N P=0.294 | |POLY 6 | P=0.366N P=0.755N P=0.524 P=0.495N |P=0.215 P=0.620N P=0.492N P=0.350 | |LOGISTIC REGRESSION| P=0.409N P=0.771N P=0.456 P=0.514N |P=0.086 P=0.504N P=0.530N P=0.208 | |COCH-ARM / FISHERS | P=0.371N P=0.759N P=0.500 P=0.500N |P=0.101 P=0.500N P=0.500N P=0.225 | |ORDER RESTRICTED | P=0.273N (e) (e) (e) |P=0.199 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 1/15 (7%) 2/15 (13%) 2/15 (13%) |5/15 (33%) 3/15 (20%) 3/15 (20%) 8/15 (53%) | |POLY-3 RATE (b) | 1/13.82 1/14.60 2/15.00 2/14.62 |5/13.12 3/10.80 3/13.32 8/15.00 | |POLY-3 PERCENT (g) | 7.2% 6.9% 13.3% 13.7% |38.1% 27.8% 22.5% 53.3% | |TERMINAL (d) | 1/13 (8%) 0/13 (0%) 1/14 (7%) 2/14 (14%) |3/10 (30%) 2/9 (22%) 2/10 (20%) 5/12 (42%) | |FIRST INCIDENCE | 183 (T) 182 144 183 (T) |28 140 28 9 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.343 P=0.752N P=0.525 P=0.527 |P=0.177 P=0.410N P=0.351N P=0.347 | |POLY 3 | P=0.331 P=0.749N P=0.529 P=0.520 |P=0.168 P=0.462N P=0.329N P=0.337 | |POLY 1.5 | P=0.331 P=0.748N P=0.525 P=0.520 |P=0.142 P=0.431N P=0.325N P=0.308 | |POLY 6 | P=0.330 P=0.750N P=0.533 P=0.518 |P=0.188 P=0.476N P=0.338N P=0.364 | |LOGISTIC REGRESSION| P=0.297 P=0.758N P=0.474 P=0.527 |P=0.073 P=0.350N P=0.359N P=0.219 | |COCH-ARM / FISHERS | P=0.311 P=0.759N P=0.500 P=0.500 |P=0.085 P=0.341N P=0.341N P=0.231 | |ORDER RESTRICTED | P=0.455 (e) (e) (e) |P=0.135 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Testes | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 3/15 (20%) 0/15 (0%) | | |POLY-3 RATE (b) | 0/13.82 0/14.58 3/14.49 0/14.62 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 20.7% 0.0% | | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 3/14 (21%) 0/14 (0%) | | |FIRST INCIDENCE | --- --- 183 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.493 (e) P=0.128 (e) | | |POLY 3 | P=0.491 (e) P=0.114 (e) | | |POLY 1.5 | P=0.490 (e) P=0.115 (e) | | |POLY 6 | P=0.490 (e) P=0.113 (e) | | |LOGISTIC REGRESSION| (e) (e) P=0.128 (e) | | |COCH-ARM / FISHERS | P=0.470 (e) P=0.112 (e) | | |ORDER RESTRICTED | P=0.151 (e) (e) (e) | | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 3/15 (20%) 2/15 (13%) | | |POLY-3 RATE (b) | 1/13.82 0/14.58 3/14.49 2/14.62 | | |POLY-3 PERCENT (g) | 7.2% 0.0% 20.7% 13.7% | | |TERMINAL (d) | 1/13 (8%) 0/13 (0%) 3/14 (21%) 2/14 (14%) | | |FIRST INCIDENCE | 183 (T) --- 183 (T) 183 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.201 P=0.500N P=0.325 P=0.527 | | |POLY 3 | P=0.186 P=0.489N P=0.315 P=0.520 | | |POLY 1.5 | P=0.186 P=0.489N P=0.317 P=0.520 | | |POLY 6 | P=0.185 P=0.491N P=0.313 P=0.518 | | |LOGISTIC REGRESSION| P=0.201 (e) P=0.325 P=0.527 | | |COCH-ARM / FISHERS | P=0.176 P=0.500N P=0.299 P=0.500 | | |ORDER RESTRICTED | P=0.184 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/15 (13%) 1/15 (7%) 1/14 (7%) 2/15 (13%) |3/15 (20%) 3/15 (20%) 3/15 (20%) 4/15 (27%) | |POLY-3 RATE (b) | 2/14.00 1/14.60 1/13.49 2/15.00 |3/13.02 3/12.16 3/14.53 4/15.00 | |POLY-3 PERCENT (g) | 14.3% 6.9% 7.4% 13.3% |23.0% 24.7% 20.7% 26.7% | |TERMINAL (d) | 1/13 (8%) 0/13 (0%) 1/13 (8%) 1/14 (7%) |0/10 (0%) 0/9 (0%) 0/10 (0%) 1/12 (8%) | |FIRST INCIDENCE | 171 182 183 (T) 156 |123 100 28 9 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.542 P=0.491N P=0.500N P=0.674N |P=0.450 P=0.581 P=0.658 P=0.521 | |POLY 3 | P=0.534 P=0.485N P=0.513N P=0.673N |P=0.509 P=0.640 P=0.618N P=0.582 | |POLY 1.5 | P=0.531 P=0.483N P=0.509N P=0.675N |P=0.494 P=0.653 P=0.617N P=0.575 | |POLY 6 | P=0.538 P=0.491N P=0.520N P=0.673N |P=0.512 P=0.635 P=0.628N P=0.583 | |LOGISTIC REGRESSION| P=0.504 P=0.491N P=0.515N P=0.693 |P=0.325 P=0.656N P=0.645 P=0.506 | |COCH-ARM / FISHERS | P=0.517 P=0.500N P=0.527N P=0.701N |P=0.390 P=0.674N P=0.674N P=0.500 | |ORDER RESTRICTED | P=0.525N (e) (e) (e) |P=0.628 (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/14 (0%) 0/15 (0%) |0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 2/13.82 0/14.58 0/13.49 0/14.62 |0/12.01 0/10.24 0/12.33 1/12.46 | |POLY-3 PERCENT (g) | 14.5% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 8.0% | |TERMINAL (d) | 2/13 (15%) 0/13 (0%) 0/13 (0%) 0/14 (0%) |0/10 (0%) 0/9 (0%) 0/10 (0%) 1/12 (8%) | |FIRST INCIDENCE | 183 (T) --- --- --- |--- --- --- 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.152N P=0.235N P=0.235N P=0.219N |P=0.220 (e) (e) P=0.536 | |POLY 3 | P=0.163N P=0.219N P=0.236N P=0.218N |P=0.202 (e) (e) P=0.507 | |POLY 1.5 | P=0.163N P=0.218N P=0.235N P=0.218N |P=0.195 (e) (e) P=0.503 | |POLY 6 | P=0.162N P=0.220N P=0.238N P=0.219N |P=0.208 (e) (e) P=0.512 | |LOGISTIC REGRESSION| P=0.152N (e) (e) (e) |(e) (e) (e) P=0.536 | |COCH-ARM / FISHERS | P=0.161N P=0.241N P=0.259N P=0.241N |P=0.185 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.022N* (e) (e) (e) |P=0.127 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Thymus: Thymocyte | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 1/15 (7%) |2/15 (13%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.82 0/14.58 0/13.49 1/15.00 |2/13.21 0/10.24 0/12.33 2/14.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.7% |15.1% 0.0% 0.0% 13.8% | |TERMINAL (d) | 0/13 (0%) 0/13 (0%) 0/13 (0%) 0/14 (0%) |0/10 (0%) 0/9 (0%) 0/10 (0%) 0/12 (0%) | |FIRST INCIDENCE | --- --- --- 156 |28 --- --- 9 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.197 (e) (e) P=0.514 |P=0.423 P=0.271N P=0.249N P=0.681 | |POLY 3 | P=0.196 (e) (e) P=0.516 |P=0.511 P=0.293N P=0.246N P=0.666N | |POLY 1.5 | P=0.194 (e) (e) P=0.514 |P=0.487 P=0.273N P=0.242N P=0.672N | |POLY 6 | P=0.198 (e) (e) P=0.519 |P=0.526 P=0.307N P=0.252N P=0.663N | |LOGISTIC REGRESSION| P=0.130 (e) (e) P=0.442 |P=0.477 P=0.199N P=0.253N P=0.760N | |COCH-ARM / FISHERS | P=0.186 (e) (e) P=0.500 |P=0.422 P=0.241N P=0.241N P=0.701N | |ORDER RESTRICTED | P=0.136 (e) (e) (e) |P=0.256N (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Thyroid Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/15 (0%) 1/14 (7%) 1/15 (7%) 2/15 (13%) |0/15 (0%) 0/13 (0%) 5/13 (38%) 11/15 (73%) | |POLY-3 RATE (b) | 0/13.82 1/13.98 1/14.49 2/14.62 |0/12.01 0/10.10 5/11.63 11/12.46 | |POLY-3 PERCENT (g) | 0.0% 7.2% 6.9% 13.7% |0.0% 0.0% 43.0% 88.3% | |TERMINAL (d) | 0/13 (0%) 1/13 (8%) 1/14 (7%) 2/14 (14%) |0/10 (0%) 0/9 (0%) 5/10 (50%) 11/12 (92%) | |FIRST INCIDENCE | --- 183 (T) 183 (T) 183 (T) |--- --- 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.181 P=0.500 P=0.515 P=0.252 |P<0.001 ** (e) P=0.022 * P<0.001 ** | |POLY 3 | P=0.183 P=0.502 P=0.509 P=0.244 |P<0.001 ** (e) P=0.011 * P<0.001 ** | |POLY 1.5 | P=0.184 P=0.500 P=0.510 P=0.245 |P<0.001 ** (e) P=0.010 * P<0.001 ** | |POLY 6 | P=0.181 P=0.504 P=0.508 P=0.243 |P<0.001 ** (e) P=0.012 * P<0.001 ** | |LOGISTIC REGRESSION| (e) P=0.500 P=0.515 P=0.252 |(e) (e) P=0.022 * P<0.001 ** | |COCH-ARM / FISHERS | P=0.169 P=0.483 P=0.500 P=0.241 |P<0.001 ** (e) P=0.013 * P<0.001 ** | |ORDER RESTRICTED | P=0.124 (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Depletion Secretory | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/15 (27%) 6/14 (43%) 15/15 (100%) 15/15 (100%)|7/15 (47%) 7/13 (54%) 11/13 (85%) 14/15 (93%) | |POLY-3 RATE (b) | 4/13.82 6/14.00 15/15.00 15/15.00 |7/12.32 7/10.62 11/12.62 14/14.00 | |POLY-3 PERCENT (g) | 28.9% 42.9% 100.0% 100.0% |56.8% 65.9% 87.2% 100.0% | |TERMINAL (d) | 4/13 (31%) 5/13 (39%) 14/14 (100%) 14/14 (100%)|5/10 (50%) 6/9 (67%) 10/10 (100%) 12/12 (100%) | |FIRST INCIDENCE | 183 (T) 182 144 156 |171 144 28 28 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.359 P<0.001 ** P<0.001 ** |P=0.015 * P=0.512 P=0.124 P=0.060 | |POLY 3 | P<0.001 ** P=0.359 P<0.001 ** P<0.001 ** |P=0.002 ** P=0.494 P=0.097 P=0.005 ** | |POLY 1.5 | P<0.001 ** P=0.352 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.516 P=0.088 P=0.003 ** | |POLY 6 | P<0.001 ** P=0.367 P<0.001 ** P<0.001 ** |P=0.003 ** P=0.470 P=0.089 P=0.007 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.386 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.459 P=0.055 P=0.004 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.300 P<0.001 ** P<0.001 ** |P=0.002 ** P=0.500 P=0.043 * P=0.007 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 06/18/04 EXPERIMENT: 97013 TEST: 09 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - WATER DISINFECTION MODEL (SOD IUM BR Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/15 (7%) 2/14 (14%) 12/15 (80%) 15/15 (100%)|2/15 (13%) 2/13 (15%) 11/13 (85%) 13/15 (87%) | |POLY-3 RATE (b) | 1/13.82 2/13.98 12/14.49 15/15.00 |2/12.01 2/10.10 11/12.62 13/13.46 | |POLY-3 PERCENT (g) | 7.2% 14.3% 82.8% 100.0% |16.7% 19.8% 87.2% 96.6% | |TERMINAL (d) | 1/13 (8%) 2/13 (15%) 12/14 (86%) 14/14 (100%)|2/10 (20%) 2/9 (22%) 10/10 (100%) 12/12 (100%) | |FIRST INCIDENCE | 183 (T) 183 (T) 183 (T) 156 |184 (T) 184 (T) 28 28 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.667 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.504 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.637 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.501 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.648 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.508 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.628 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.667 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.473 P<0.001 ** P<0.001 ** |P<0.001 ** P=0.644 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/L 80 MG/L 400 MG/L 800 MG/L |0 MG/L 80 MG/L 400 MG/L 800 MG/L | | | | | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |4/15 (27%) 7/15 (47%) 6/15 (40%) 3/15 (20%) | |POLY-3 RATE (b) | |4/12.01 7/10.24 6/12.33 3/12.46 | |POLY-3 PERCENT (g) | |33.3% 68.4% 48.7% 24.1% | |TERMINAL (d) | |4/10 (40%) 7/9 (78%) 6/10 (60%) 3/12 (25%) | |FIRST INCIDENCE | |184 (T) 184 (T) 184 (T) 184 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.088N P=0.121 P=0.331 P=0.388N | |POLY 3 | |P=0.156N P=0.102 P=0.361 P=0.478N | |POLY 1.5 | |P=0.185N P=0.140 P=0.366 P=0.492N | |POLY 6 | |P=0.135N P=0.080 P=0.350 P=0.465N | |LOGISTIC REGRESSION| |P=0.088N P=0.121 P=0.331 P=0.388N | |COCH-ARM / FISHERS | |P=0.233N P=0.225 P=0.350 P=0.500N | |ORDER RESTRICTED | |P=0.143N (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).