TDMS Study 99033-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03 EXPERIMENT: 99033 TEST: 01 TIME: 11:29:50 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: C99033 PATHOLOGIST: LANNING, LYNDA CAS: 22839-47-0 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3 TG.AC MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 VEHICLE CONTROL INCLUDE 002 3125 PPM INCLUDE 003 6250 PPM INCLUDE 004 12500 PPM INCLUDE 005 25000 PPM INCLUDE 006 50000 PPM INCLUDE 008 VEHICLE CONTROL INCLUDE 009 3125 PPM INCLUDE 010 6250 PPM INCLUDE 011 12500 PPM INCLUDE 012 25000 PPM INCLUDE 013 50000 PPM NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: BIORELIANCE TRANSGENIC MODEL EVALUATION II (ASPARTAME) DATE: 03/05/03 EXPERIMENT: 99033 TEST: 01 TIME: 11:29:50 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: DOSED FEED NTP C#: C99033 PATHOLOGIST: LANNING, LYNDA CAS: 22839-47-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANSGENIC MODEL EVALUATION II (ASPA =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Atrophy Hypertrophy Focal Bone Marrow Hyperplasia Kidney Nephropathy Liver Necrosis Focal Lymph Node, Mandibular Necrosis Spleen Hematopoietic Cell Proliferation Thymus Atrophy Focal Thyroid Gland: Follicle Cyst =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Atrophy Adrenal Cortex: Subcapsular Hyperplasia Focal Liver Necrosis Focal Liver: Hepatocyte Necrosis Focal Pituitary Gland Cyst Spleen Hematopoietic Cell Proliferation =============================================================== Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION I I (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/13 (77%) 12/15 (80%) 8/13 (62%) 9/14 (64%) 8/15 (53%) 6/13 (46%) | |POLY-3 RATE (b) | 10/11.96 12/14.31 8/10.06 9/13.39 8/12.70 6/10.92 | |POLY-3 PERCENT (g) | 83.6% 83.8% 79.5% 67.2% 63.0% 54.9% | |TERMINAL (d) | 9/9 (100%) 12/12 (100%) 8/8 (100%) 9/12 (75%) 8/11 (73%) 6/9 (67%) | |FIRST INCIDENCE | 271 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006N** P=0.469N P=0.557N P=0.086N P=0.082N P=0.061N | |POLY 3 | P=0.036N* P=0.697 P=0.625N P=0.311N P=0.237N P=0.138N | |POLY 1.5 | P=0.030N* P=0.689N P=0.470N P=0.307N P=0.202N P=0.105N | |POLY 6 | P=0.046N* P=0.675 P=0.694 P=0.329N P=0.275N P=0.187N | |LOGISTIC REGRESSION| (e) P=0.469N P=0.557N P=0.086N P=0.082N P=0.061N | |COCH-ARM / FISHERS | P=0.033N* P=0.600 P=0.336N P=0.385N P=0.184N P=0.113N | |ORDER RESTRICTED | P=0.097N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 2/12 (17%) 1/13 (8%) 4/13 (31%) 5/14 (36%) 5/15 (33%) | |POLY-3 RATE (b) | 3/13.74 2/12.00 1/9.84 4/11.37 5/13.92 5/10.74 | |POLY-3 PERCENT (g) | 21.8% 16.7% 10.2% 35.2% 35.9% 46.6% | |TERMINAL (d) | 1/11 (9%) 0/10 (0%) 1/9 (11%) 3/9 (33%) 3/11 (27%) 3/8 (38%) | |FIRST INCIDENCE | 200 198 275 (T) 165 269 184 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.039 * P=0.544N P=0.392N P=0.385 P=0.362 P=0.199 | |POLY 3 | P=0.043 * P=0.565N P=0.428N P=0.387 P=0.348 P=0.198 | |POLY 1.5 | P=0.053 P=0.576N P=0.412N P=0.398 P=0.336 P=0.228 | |POLY 6 | P=0.040 * P=0.555N P=0.442N P=0.380 P=0.357 P=0.185 | |LOGISTIC REGRESSION| P=0.074 P=0.698N P=0.373N P=0.423 P=0.281 P=0.253 | |COCH-ARM / FISHERS | P=0.100 P=0.612N P=0.356N P=0.412 P=0.298 P=0.341 | |ORDER RESTRICTED | P=0.083 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/13 (69%) 5/15 (33%) 5/13 (38%) 6/14 (43%) 7/15 (47%) 5/13 (38%) | |POLY-3 RATE (b) | 9/11.92 5/14.31 5/10.06 6/13.39 7/12.70 5/10.92 | |POLY-3 PERCENT (g) | 75.5% 34.9% 49.7% 44.8% 55.1% 45.8% | |TERMINAL (d) | 9/9 (100%) 5/12 (42%) 5/8 (63%) 6/12 (50%) 7/11 (64%) 5/9 (56%) | |FIRST INCIDENCE | 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.350N P=0.011N* P=0.089N P=0.024N* P=0.077N P=0.049N* | |POLY 3 | P=0.415N P=0.038N* P=0.204N P=0.118N P=0.261N P=0.145N | |POLY 1.5 | P=0.378N P=0.038N* P=0.149N P=0.118N P=0.231N P=0.116N | |POLY 6 | P=0.454N P=0.039N* P=0.268N P=0.122N P=0.290N P=0.184N | |LOGISTIC REGRESSION| P=0.350N P=0.011N* P=0.089N P=0.024N* P=0.077N P=0.049N* | |COCH-ARM / FISHERS | P=0.334N P=0.064N P=0.119N P=0.161N P=0.207N P=0.119N | |ORDER RESTRICTED | P=0.135N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/12 (0%) 0/13 (0%) 0/13 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.08 0/11.33 0/9.84 0/10.59 0/13.80 0/9.98 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/14 (0%) 0/15 (0%) 1/13 (8%) | |POLY-3 RATE (b) | 0/11.92 0/14.31 0/10.06 0/13.39 0/12.70 1/10.92 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 9.2% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.093 (e) (e) (e) (e) P=0.500 | |POLY 3 | P=0.095 (e) (e) (e) (e) P=0.482 | |POLY 1.5 | P=0.097 (e) (e) (e) (e) P=0.493 | |POLY 6 | P=0.092 (e) (e) (e) (e) P=0.472 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.500 | |COCH-ARM / FISHERS | P=0.099 (e) (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.052 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/15 (80%) 6/12 (50%) 6/13 (46%) 5/13 (38%) 6/14 (43%) 6/15 (40%) | |POLY-3 RATE (b) | 12/14.06 6/11.37 6/11.03 5/10.59 6/13.80 6/10.68 | |POLY-3 PERCENT (g) | 85.3% 52.8% 54.4% 47.2% 43.5% 56.2% | |TERMINAL (d) | 9/11 (82%) 5/10 (50%) 4/9 (44%) 5/9 (56%) 6/11 (55%) 5/8 (63%) | |FIRST INCIDENCE | 200 271 200 275 (T) 275 (T) 184 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.304N P=0.085N P=0.166N P=0.060N P=0.037N* P=0.222N | |POLY 3 | P=0.149N P=0.078N P=0.100N P=0.046N* P=0.019N* P=0.117N | |POLY 1.5 | P=0.130N P=0.077N P=0.098N P=0.030N* P=0.022N* P=0.073N | |POLY 6 | P=0.166N P=0.088N P=0.099N P=0.066N P=0.020N* P=0.159N | |LOGISTIC REGRESSION| P=0.176N P=0.065N P=0.114N P=0.036N* P=0.023N* P=0.101N | |COCH-ARM / FISHERS | P=0.086N P=0.109N P=0.071N P=0.031N* P=0.046N* P=0.030N* | |ORDER RESTRICTED | P=0.044N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex: Zona Reticularis | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/13 (0%) 0/15 (0%) 0/13 (0%) 0/14 (0%) 0/15 (0%) 0/13 (0%) | |POLY-3 RATE (b) | 0/11.92 0/14.31 0/10.06 0/13.39 0/12.70 0/10.92 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex: Zona Reticularis | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/15 (80%) 9/12 (75%) 6/13 (46%) 8/13 (62%) 9/14 (64%) 8/15 (53%) | |POLY-3 RATE (b) | 12/13.45 9/11.33 6/9.84 8/10.59 9/13.85 8/12.10 | |POLY-3 PERCENT (g) | 89.2% 79.4% 61.0% 75.6% 65.0% 66.1% | |TERMINAL (d) | 10/11 (91%) 9/10 (90%) 6/9 (67%) 8/9 (89%) 8/11 (73%) 4/8 (50%) | |FIRST INCIDENCE | 242 275 (T) 275 (T) 275 (T) 270 151 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.548 P=0.312N P=0.090N P=0.309N P=0.209N P=0.508N | |POLY 3 | P=0.152N P=0.452N P=0.119N P=0.358N P=0.139N P=0.168N | |POLY 1.5 | P=0.179N P=0.474N P=0.103N P=0.299N P=0.177N P=0.170N | |POLY 6 | P=0.117N P=0.456N P=0.141N P=0.417N P=0.118N P=0.147N | |LOGISTIC REGRESSION| P=0.423N P=0.361N P=0.115N P=0.338N P=0.088N P=0.313N | |COCH-ARM / FISHERS | P=0.173N P=0.557N P=0.071N P=0.255N P=0.298N P=0.123N | |ORDER RESTRICTED | P=0.125N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/14 (14%) | |POLY-3 RATE (b) | 0/12.30 0/0.00 0/0.00 0/0.00 0/0.00 2/13.36 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 15.0% | |TERMINAL (d) | 0/9 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 180 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.012 * (e) (e) (e) (e) P=0.252 | |POLY 3 | (e) (e) (e) (e) (e) P=0.250 | |POLY 1.5 | (e) (e) (e) (e) (e) P=0.246 | |POLY 6 | (e) (e) (e) (e) (e) P=0.252 | |LOGISTIC REGRESSION| P=0.058 (e) (e) (e) (e) P=0.126 | |COCH-ARM / FISHERS | P=0.136 (e) (e) (e) (e) P=0.241 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/12 (0%) | |POLY-3 RATE (b) | 0/13.08 0/0.00 0/0.00 0/0.00 0/0.00 0/9.88 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/11 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Epididymis: Unilateral | | Aspermia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 3/15 (20%) 4/15 (27%) 2/15 (13%) 3/15 (20%) 2/15 (13%) | |POLY-3 RATE (b) | 1/12.63 3/14.31 4/11.74 2/13.81 3/13.57 2/12.09 | |POLY-3 PERCENT (g) | 7.9% 21.0% 34.1% 14.5% 22.1% 16.5% | |TERMINAL (d) | 0/9 (0%) 3/12 (25%) 2/8 (25%) 1/12 (8%) 2/11 (18%) 1/10 (10%) | |FIRST INCIDENCE | 271 274 (T) 78 271 138 271 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.531N P=0.398 P=0.146 P=0.552 P=0.334 P=0.492 | |POLY 3 | P=0.570N P=0.345 P=0.133 P=0.532 P=0.323 P=0.484 | |POLY 1.5 | P=0.552N P=0.333 P=0.143 P=0.526 P=0.315 P=0.494 | |POLY 6 | P=0.565 P=0.353 P=0.129 P=0.534 P=0.329 P=0.476 | |LOGISTIC REGRESSION| P=0.528N P=0.357 P=0.188 P=0.536 P=0.294 P=0.476 | |COCH-ARM / FISHERS | P=0.531N P=0.299 P=0.165 P=0.500 P=0.299 P=0.500 | |ORDER RESTRICTED | P=0.373 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Epididymis: Unilateral | | Aspermia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Epididymis: Unilateral | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/12.59 0/14.31 2/10.77 0/13.78 0/12.70 0/12.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 18.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 1/8 (13%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- --- 207 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.384N (e) P=0.207 (e) (e) (e) | |POLY 3 | P=0.431N (e) P=0.194 (e) (e) (e) | |POLY 1.5 | P=0.418N (e) P=0.204 (e) (e) (e) | |POLY 6 | P=0.437N (e) P=0.190 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.379N (e) P=0.222 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.381N (e) P=0.241 (e) (e) (e) | |ORDER RESTRICTED | P=0.364N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Epididymis: Unilateral | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/12 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 14/14 (100%) | |POLY-3 RATE (b) | 12/12.00 0/0.00 0/0.00 0/0.00 0/0.00 14/14.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 9/9 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) | |FIRST INCIDENCE | 271 --- --- --- --- 180 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/15 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) | |POLY-3 RATE (b) | 15/15.00 0/0.00 0/0.00 0/0.00 0/0.00 10/10.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 11/11 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 8/8 (100%) | |FIRST INCIDENCE | 109 --- --- --- --- 184 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 0/15 (0%) 0/13 (0%) 0/15 (0%) 0/14 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 3/12.66 0/14.31 0/10.06 0/13.78 0/12.66 1/12.06 | |POLY-3 PERCENT (g) | 23.7% 0.0% 0.0% 0.0% 0.0% 8.3% | |TERMINAL (d) | 1/9 (11%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 1/10 (10%) | |FIRST INCIDENCE | 271 --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.485N P=0.088N P=0.164N P=0.096N P=0.118N P=0.300N | |POLY 3 | P=0.473N P=0.083N P=0.147N P=0.089N P=0.103N P=0.313N | |POLY 1.5 | P=0.476N P=0.088N P=0.139N P=0.092N P=0.106N P=0.302N | |POLY 6 | P=0.469N P=0.080N P=0.156N P=0.088N P=0.101N P=0.323N | |LOGISTIC REGRESSION| P=0.494N P=0.086N P=0.156N P=0.094N P=0.107N P=0.317N | |COCH-ARM / FISHERS | P=0.470N P=0.112N P=0.139N P=0.112N P=0.125N P=0.299N | |ORDER RESTRICTED | P=0.008N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/12 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) 1/14 (7%) | |POLY-3 RATE (b) | 1/13.08 0/11.33 0/9.84 0/10.80 0/13.80 1/9.94 | |POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 0.0% 10.1% | |TERMINAL (d) | 1/11 (9%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 1/8 (13%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.375 P=0.519N P=0.540N P=0.540N P=0.500N P=0.693 | |POLY 3 | P=0.410 P=0.529N P=0.556N P=0.538N P=0.489N P=0.698 | |POLY 1.5 | P=0.413 P=0.533N P=0.552N P=0.529N P=0.497N P=0.711 | |POLY 6 | P=0.408 P=0.525N P=0.558N P=0.542N P=0.483N P=0.691 | |LOGISTIC REGRESSION| P=0.375 (e) (e) (e) (e) P=0.693 | |COCH-ARM / FISHERS | P=0.422 P=0.556N P=0.536N P=0.517N P=0.517N P=0.741 | |ORDER RESTRICTED | P=0.217 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 1/13 (8%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 1/12.59 0/14.31 1/10.06 0/13.78 0/12.66 0/12.06 | |POLY-3 PERCENT (g) | 7.9% 0.0% 9.9% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/9 (11%) 0/12 (0%) 1/8 (13%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | 274 (T) --- 274 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.278N P=0.443N P=0.741 P=0.443N P=0.460N P=0.479N | |POLY 3 | P=0.300N P=0.474N P=0.711 P=0.482N P=0.499N P=0.509N | |POLY 1.5 | P=0.297N P=0.481N P=0.720 P=0.485N P=0.502N P=0.503N | |POLY 6 | P=0.302N P=0.470N P=0.703 P=0.481N P=0.497N P=0.513N | |LOGISTIC REGRESSION| P=0.278N (e) P=0.741 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.285N P=0.500N P=0.722 P=0.500N P=0.517N P=0.500N | |ORDER RESTRICTED | P=0.198N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/12 (17%) 1/13 (8%) 0/14 (0%) 0/14 (0%) 1/14 (7%) | |POLY-3 RATE (b) | 1/13.08 2/11.33 1/9.84 0/10.80 0/13.80 1/9.94 | |POLY-3 PERCENT (g) | 7.7% 17.7% 10.2% 0.0% 0.0% 10.1% | |TERMINAL (d) | 1/11 (9%) 2/10 (20%) 1/9 (11%) 0/9 (0%) 0/11 (0%) 1/8 (13%) | |FIRST INCIDENCE | 275 (T) 275 (T) 275 (T) --- --- 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.495N P=0.465 P=0.720 P=0.540N P=0.500N P=0.693 | |POLY 3 | P=0.369N P=0.448 P=0.696 P=0.538N P=0.489N P=0.698 | |POLY 1.5 | P=0.389N P=0.441 P=0.701 P=0.529N P=0.497N P=0.711 | |POLY 6 | P=0.354N P=0.455 P=0.694 P=0.542N P=0.483N P=0.691 | |LOGISTIC REGRESSION| P=0.495N P=0.465 P=0.720 (e) (e) P=0.693 | |COCH-ARM / FISHERS | P=0.427N P=0.414 P=0.722 P=0.517N P=0.517N P=0.741 | |ORDER RESTRICTED | P=0.364N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Inflammation Acute Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 1/12.59 0/14.31 0/10.17 0/13.78 0/12.66 0/12.06 | |POLY-3 PERCENT (g) | 7.9% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/9 (11%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | 274 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.410N P=0.443N P=0.523N P=0.443N P=0.460N P=0.479N | |POLY 3 | P=0.403N P=0.474N P=0.542N P=0.482N P=0.499N P=0.509N | |POLY 1.5 | P=0.411N P=0.481N P=0.531N P=0.485N P=0.502N P=0.503N | |POLY 6 | P=0.398N P=0.470N P=0.551N P=0.481N P=0.497N P=0.513N | |LOGISTIC REGRESSION| P=0.410N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.416N P=0.500N P=0.517N P=0.500N P=0.517N P=0.500N | |ORDER RESTRICTED | P=0.069N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Inflammation Acute Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 1/14 (7%) 2/14 (14%) | |POLY-3 RATE (b) | 1/13.08 0/12.12 0/9.99 0/10.85 1/13.88 2/11.62 | |POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 7.2% 17.2% | |TERMINAL (d) | 1/11 (9%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | 275 (T) --- --- --- 267 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.066 P=0.519N P=0.540N P=0.540N P=0.743N P=0.436 | |POLY 3 | P=0.080 P=0.515N P=0.553N P=0.537N P=0.747N P=0.458 | |POLY 1.5 | P=0.076 P=0.510N P=0.545N P=0.526N P=0.756N P=0.461 | |POLY 6 | P=0.084 P=0.519N P=0.557N P=0.542N P=0.739N P=0.458 | |LOGISTIC REGRESSION| P=0.084 (e) (e) (e) P=0.763N P=0.677 | |COCH-ARM / FISHERS | P=0.068 P=0.500N P=0.517N P=0.500N P=0.741 P=0.473 | |ORDER RESTRICTED | P=0.079 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Inflammation Chronic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/12.59 0/14.31 0/10.17 0/13.78 0/12.66 0/12.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Inflammation Chronic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 1/14 (7%) 1/14 (7%) | |POLY-3 RATE (b) | 2/13.74 0/12.12 0/9.99 0/10.85 1/13.86 1/9.94 | |POLY-3 PERCENT (g) | 14.6% 0.0% 0.0% 0.0% 7.2% 10.1% | |TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 1/8 (13%) | |FIRST INCIDENCE | 200 --- --- --- 269 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.476 P=0.267N P=0.300N P=0.298N P=0.491N P=0.621N | |POLY 3 | P=0.500 P=0.260N P=0.309N P=0.288N P=0.497N P=0.613N | |POLY 1.5 | P=0.501 P=0.250N P=0.293N P=0.269N P=0.504N P=0.588N | |POLY 6 | P=0.503 P=0.272N P=0.321N P=0.301N P=0.493N P=0.630N | |LOGISTIC REGRESSION| P=0.500 P=0.215N P=0.228N P=0.209N P=0.636N P=0.543N | |COCH-ARM / FISHERS | P=0.507 P=0.241N P=0.259N P=0.241N P=0.527N P=0.527N | |ORDER RESTRICTED | P=0.233N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/12.59 0/14.31 0/10.17 0/13.78 0/12.66 2/12.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 16.6% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 2/10 (20%) | |FIRST INCIDENCE | --- --- --- --- --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010 * (e) (e) (e) (e) P=0.257 | |POLY 3 | P=0.009 ** (e) (e) (e) (e) P=0.219 | |POLY 1.5 | P=0.009 ** (e) (e) (e) (e) P=0.226 | |POLY 6 | P=0.009 ** (e) (e) (e) (e) P=0.214 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.257 | |COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 4/14 (29%) | |POLY-3 RATE (b) | 1/13.08 0/12.12 0/9.99 0/10.85 0/13.80 4/10.90 | |POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 0.0% 36.7% | |TERMINAL (d) | 1/11 (9%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 3/8 (38%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- 92 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.519N P=0.540N P=0.540N P=0.500N P=0.095 | |POLY 3 | P<0.001 ** P=0.515N P=0.553N P=0.537N P=0.489N P=0.103 | |POLY 1.5 | P<0.001 ** P=0.510N P=0.545N P=0.526N P=0.497N P=0.113 | |POLY 6 | P<0.001 ** P=0.519N P=0.557N P=0.542N P=0.483N P=0.097 | |LOGISTIC REGRESSION| P=0.002 ** (e) (e) (e) (e) P=0.144 | |COCH-ARM / FISHERS | P=0.002 ** P=0.500N P=0.517N P=0.500N P=0.517N P=0.143 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/12.59 0/14.31 0/10.17 0/13.78 0/12.66 0/12.06 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 0/14 (0%) 4/15 (27%) 1/14 (7%) 0/14 (0%) | |POLY-3 RATE (b) | 0/13.08 1/12.12 0/9.99 4/11.68 1/13.80 0/9.94 | |POLY-3 PERCENT (g) | 0.0% 8.3% 0.0% 34.3% 7.3% 0.0% | |TERMINAL (d) | 0/11 (0%) 1/10 (10%) 0/9 (0%) 2/9 (22%) 1/11 (9%) 0/8 (0%) | |FIRST INCIDENCE | --- 275 (T) --- 165 275 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.502N P=0.481 (e) P=0.048 * P=0.500 (e) | |POLY 3 | P=0.488N P=0.485 (e) P=0.030 * P=0.511 (e) | |POLY 1.5 | P=0.483N P=0.490 (e) P=0.033 * P=0.503 (e) | |POLY 6 | P=0.486N P=0.480 (e) P=0.029 * P=0.517 (e) | |LOGISTIC REGRESSION| P=0.470N P=0.481 (e) P=0.048 * P=0.500 (e) | |COCH-ARM / FISHERS | P=0.460N P=0.500 (e) P=0.050 P=0.483 (e) | |ORDER RESTRICTED | P=0.191 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 3/15 (20%) 0/14 (0%) 0/15 (0%) 1/14 (7%) 0/14 (0%) | |POLY-3 RATE (b) | 0/12.30 3/14.94 0/10.17 0/13.78 1/12.79 0/11.92 | |POLY-3 PERCENT (g) | 0.0% 20.1% 0.0% 0.0% 7.8% 0.0% | |TERMINAL (d) | 0/9 (0%) 2/12 (17%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | --- 198 --- --- 261 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.303N P=0.171 (e) (e) P=0.500 (e) | |POLY 3 | P=0.258N P=0.144 (e) (e) P=0.508 (e) | |POLY 1.5 | P=0.267N P=0.138 (e) (e) P=0.507 (e) | |POLY 6 | P=0.253N P=0.150 (e) (e) P=0.508 (e) | |LOGISTIC REGRESSION| P=0.307N P=0.093 (e) (e) P=0.502 (e) | |COCH-ARM / FISHERS | P=0.305N P=0.125 (e) (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.192N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/14 (0%) 0/14 (0%) 0/15 (0%) 0/14 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 1/13.08 0/12.09 0/9.99 0/10.85 0/13.80 0/9.94 | |POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/11 (9%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.437N P=0.519N P=0.540N P=0.540N P=0.500N P=0.564N | |POLY 3 | P=0.332N P=0.516N P=0.553N P=0.537N P=0.489N P=0.554N | |POLY 1.5 | P=0.359N P=0.513N P=0.545N P=0.526N P=0.497N P=0.544N | |POLY 6 | P=0.314N P=0.520N P=0.557N P=0.542N P=0.483N P=0.560N | |LOGISTIC REGRESSION| P=0.437N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.420N P=0.517N P=0.517N P=0.500N P=0.517N P=0.517N | |ORDER RESTRICTED | P=0.112N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/12 (8%) 2/15 (13%) 0/13 (0%) 2/14 (14%) 0/14 (0%) 1/14 (7%) | |POLY-3 RATE (b) | 1/10.96 2/14.97 0/9.17 2/13.97 0/12.66 1/12.64 | |POLY-3 PERCENT (g) | 9.1% 13.4% 0.0% 14.3% 0.0% 7.9% | |TERMINAL (d) | 0/8 (0%) 0/12 (0%) 0/7 (0%) 1/12 (8%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | 271 198 --- 199 --- 180 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.477N P=0.562 P=0.557N P=0.581 P=0.517N P=0.759 | |POLY 3 | P=0.419N P=0.609 P=0.535N P=0.585 P=0.471N P=0.730N | |POLY 1.5 | P=0.424N P=0.604 P=0.514N P=0.581 P=0.467N P=0.724N | |POLY 6 | P=0.421N P=0.611 P=0.552N P=0.587 P=0.477N P=0.737N | |LOGISTIC REGRESSION| P=0.470N P=0.531 P=0.551N P=0.512 P=0.471N P=0.759N | |COCH-ARM / FISHERS | P=0.448N P=0.586 P=0.480N P=0.560 P=0.462N P=0.720N | |ORDER RESTRICTED | P=0.472N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 2/14 (14%) 0/12 (0%) 2/12 (17%) 2/14 (14%) 1/12 (8%) | |POLY-3 RATE (b) | 2/13.74 2/12.72 0/9.18 2/11.07 2/13.95 1/10.14 | |POLY-3 PERCENT (g) | 14.6% 15.7% 0.0% 18.1% 14.3% 9.9% | |TERMINAL (d) | 0/11 (0%) 1/10 (10%) 0/9 (0%) 1/9 (11%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | 200 198 --- 184 267 184 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.554N P=0.655 P=0.311N P=0.604 P=0.671N P=0.612N | |POLY 3 | P=0.522N P=0.671 P=0.329N P=0.619 P=0.694N P=0.607N | |POLY 1.5 | P=0.525N P=0.676 P=0.323N P=0.618 P=0.696 P=0.601N | |POLY 6 | P=0.518N P=0.664 P=0.328N P=0.622 P=0.688N P=0.608N | |LOGISTIC REGRESSION| P=0.533N P=0.658 P=0.261N P=0.627 P=0.605 P=0.518N | |COCH-ARM / FISHERS | P=0.541N P=0.674 P=0.299N P=0.611 P=0.674 P=0.586N | |ORDER RESTRICTED | P=0.639N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/12 (17%) 0/15 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 2/10.99 0/14.31 0/9.17 0/13.35 0/12.66 0/11.92 | |POLY-3 PERCENT (g) | 18.2% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/8 (0%) 0/12 (0%) 0/7 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | 271 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.217N P=0.202N P=0.300N P=0.217N P=0.254N P=0.254N | |POLY 3 | P=0.171N P=0.170N P=0.272N P=0.185N P=0.196N P=0.209N | |POLY 1.5 | P=0.180N P=0.169N P=0.245N P=0.184N P=0.192N P=0.198N | |POLY 6 | P=0.162N P=0.174N P=0.297N P=0.188N P=0.203N P=0.221N | |LOGISTIC REGRESSION| P=0.200N P=0.174N P=0.283N P=0.188N P=0.199N P=0.215N | |COCH-ARM / FISHERS | P=0.197N P=0.188N P=0.220N P=0.203N P=0.203N P=0.203N | |ORDER RESTRICTED | P=0.005N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/14 (0%) 0/12 (0%) 0/12 (0%) 0/14 (0%) 0/12 (0%) | |POLY-3 RATE (b) | 0/13.08 0/12.09 0/9.18 0/10.37 0/13.80 0/9.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 1/13 (8%) 0/14 (0%) 0/14 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 2/13.45 0/12.12 1/10.45 0/10.63 0/13.80 0/9.94 | |POLY-3 PERCENT (g) | 14.9% 0.0% 9.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | 242 --- 200 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.268N P=0.602N P=0.290N P=0.232N P=0.328N | |POLY 3 | P=0.120N P=0.255N P=0.589N P=0.287N P=0.225N P=0.304N | |POLY 1.5 | P=0.132N P=0.246N P=0.586N P=0.274N P=0.230N P=0.287N | |POLY 6 | P=0.111N P=0.265N P=0.590N P=0.295N P=0.223N P=0.318N | |LOGISTIC REGRESSION| P=0.158N P=0.235N P=0.535N P=0.258N P=0.266N P=0.268N | |COCH-ARM / FISHERS | P=0.160N P=0.241N P=0.556N P=0.259N P=0.259N P=0.259N | |ORDER RESTRICTED | P=0.064N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/9 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/13 (0%) 0/9 (0%) | |POLY-3 RATE (b) | 0/8.90 0/12.35 0/4.80 0/10.39 0/11.66 0/8.25 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/6 (0%) 0/11 (0%) 0/4 (0%) 0/9 (0%) 0/10 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/13 (15%) 0/11 (0%) 0/12 (0%) 0/10 (0%) 0/11 (0%) 0/9 (0%) | |POLY-3 RATE (b) | 2/11.69 0/9.37 0/9.83 0/8.47 0/10.85 0/8.24 | |POLY-3 PERCENT (g) | 17.1% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/10 (20%) 0/9 (0%) 0/9 (0%) 0/7 (0%) 0/9 (0%) 0/7 (0%) | |FIRST INCIDENCE | 275 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.232N P=0.257N P=0.257N P=0.316N P=0.257N P=0.316N | |POLY 3 | P=0.200N P=0.281N P=0.270N P=0.306N P=0.245N P=0.312N | |POLY 1.5 | P=0.208N P=0.279N P=0.264N P=0.299N P=0.251N P=0.311N | |POLY 6 | P=0.195N P=0.281N P=0.276N P=0.312N P=0.241N P=0.313N | |LOGISTIC REGRESSION| P=0.232N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.233N P=0.283N P=0.260N P=0.308N P=0.283N P=0.338N | |ORDER RESTRICTED | P=0.026N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/14 (21%) 3/15 (20%) 8/13 (62%) 2/15 (13%) 8/14 (57%) 4/14 (29%) | |POLY-3 RATE (b) | 3/12.36 3/14.35 8/11.50 2/13.78 8/13.66 4/13.36 | |POLY-3 PERCENT (g) | 24.3% 20.9% 69.6% 14.5% 58.6% 30.0% | |TERMINAL (d) | 1/9 (11%) 2/12 (17%) 6/8 (75%) 2/12 (17%) 6/11 (55%) 2/10 (20%) | |FIRST INCIDENCE | 271 271 138 274 (T) 138 180 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407 P=0.558N P=0.046 * P=0.406N P=0.125 P=0.523 | |POLY 3 | P=0.422 P=0.598N P=0.026 * P=0.448N P=0.079 P=0.546 | |POLY 1.5 | P=0.414 P=0.605N P=0.030 * P=0.446N P=0.074 P=0.539 | |POLY 6 | P=0.426 P=0.596N P=0.022 * P=0.455N P=0.081 P=0.548 | |LOGISTIC REGRESSION| P=0.384 P=0.597N P=0.035 * P=0.449N P=0.062 P=0.494 | |COCH-ARM / FISHERS | P=0.383 P=0.639N P=0.041 * P=0.465N P=0.060 P=0.500 | |ORDER RESTRICTED | P=0.196 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/15 (67%) 4/14 (29%) 7/14 (50%) 6/12 (50%) 8/14 (57%) 5/14 (36%) | |POLY-3 RATE (b) | 10/14.06 4/12.09 7/10.98 6/12.00 8/14.00 5/10.00 | |POLY-3 PERCENT (g) | 71.1% 33.1% 63.8% 50.0% 57.1% 50.0% | |TERMINAL (d) | 7/11 (64%) 4/10 (40%) 6/9 (67%) 3/9 (33%) 5/11 (46%) 4/8 (50%) | |FIRST INCIDENCE | 200 275 (T) 67 165 267 269 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.440N P=0.071N P=0.470N P=0.335N P=0.367N P=0.296N | |POLY 3 | P=0.417N P=0.051N P=0.516N P=0.244N P=0.356N P=0.268N | |POLY 1.5 | P=0.390N P=0.041N* P=0.437N P=0.258N P=0.374N P=0.195N | |POLY 6 | P=0.422N P=0.072N P=0.593N P=0.240N P=0.351N P=0.335N | |LOGISTIC REGRESSION| P=0.320N P=0.042N* P=0.424N P=0.292N P=0.374N P=0.201N | |COCH-ARM / FISHERS | P=0.272N P=0.046N* P=0.297N P=0.315N P=0.442N P=0.097N | |ORDER RESTRICTED | P=0.282N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/14 (64%) 12/15 (80%) 8/13 (62%) 12/15 (80%) 13/14 (93%) 11/14 (79%) | |POLY-3 RATE (b) | 9/12.33 12/14.35 8/10.90 12/13.81 13/14.00 11/13.28 | |POLY-3 PERCENT (g) | 73.0% 83.7% 73.4% 86.9% 92.9% 82.8% | |TERMINAL (d) | 8/9 (89%) 11/12 (92%) 7/8 (88%) 11/12 (92%) 10/11 (91%) 8/10 (80%) | |FIRST INCIDENCE | 271 271 150 271 138 180 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.261 P=0.673 P=0.677 P=0.659 P=0.310 P=0.468 | |POLY 3 | P=0.328 P=0.422 P=0.676 P=0.338 P=0.193 P=0.451 | |POLY 1.5 | P=0.284 P=0.398 P=0.637N P=0.351 P=0.151 P=0.430 | |POLY 6 | P=0.383 P=0.434 P=0.633 P=0.310 P=0.234 P=0.471 | |LOGISTIC REGRESSION| P=0.163 (e) P=0.574 (e) P=0.093 P=0.316 | |COCH-ARM / FISHERS | P=0.202 P=0.298 P=0.598N P=0.298 P=0.082 P=0.339 | |ORDER RESTRICTED | P=0.270 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/15 (67%) 10/14 (71%) 11/14 (79%) 10/12 (83%) 11/14 (79%) 9/14 (64%) | |POLY-3 RATE (b) | 10/13.39 10/12.09 11/12.58 10/11.22 11/13.80 9/10.00 | |POLY-3 PERCENT (g) | 74.7% 82.7% 87.4% 89.2% 79.7% 90.0% | |TERMINAL (d) | 9/11 (82%) 10/10 (100%) 8/9 (89%) 8/9 (89%) 11/11 (100%) 8/8 (100%) | |FIRST INCIDENCE | 242 275 (T) 61 165 275 (T) 269 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.399 P=0.503 P=0.214 P=0.339 P=0.509 P=0.302 | |POLY 3 | P=0.355 P=0.495 P=0.367 P=0.341 P=0.557 P=0.333 | |POLY 1.5 | P=0.442 P=0.543 P=0.382 P=0.327 P=0.507 P=0.463 | |POLY 6 | P=0.309 P=0.414 P=0.352 P=0.358 P=0.583 P=0.239 | |LOGISTIC REGRESSION| P=0.572N P=0.466 P=0.271 P=0.214 P=0.675N P=0.271 | |COCH-ARM / FISHERS | P=0.410N P=0.550 P=0.383 P=0.298 P=0.383 P=0.600N | |ORDER RESTRICTED | P=0.277 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Bilateral, Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/14 (7%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/12.59 2/14.31 0/10.20 1/13.39 0/12.70 1/12.06 | |POLY-3 PERCENT (g) | 0.0% 14.0% 0.0% 7.5% 0.0% 8.3% | |TERMINAL (d) | 0/9 (0%) 2/12 (17%) 0/8 (0%) 1/12 (8%) 0/11 (0%) 1/10 (10%) | |FIRST INCIDENCE | --- 274 (T) --- 274 (T) --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.609 P=0.300 (e) P=0.557 (e) P=0.521 | |POLY 3 | P=0.623 P=0.261 (e) P=0.512 (e) P=0.491 | |POLY 1.5 | P=0.621 P=0.254 (e) P=0.506 (e) P=0.497 | |POLY 6 | P=0.622 P=0.267 (e) P=0.517 (e) P=0.487 | |LOGISTIC REGRESSION| (e) P=0.300 (e) P=0.557 (e) P=0.521 | |COCH-ARM / FISHERS | P=0.600 P=0.241 (e) P=0.483 (e) P=0.500 | |ORDER RESTRICTED | P=0.329 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Bilateral, Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/14 (7%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/12.59 2/14.31 0/10.20 1/13.39 0/12.70 1/12.06 | |POLY-3 PERCENT (g) | 0.0% 14.0% 0.0% 7.5% 0.0% 8.3% | |TERMINAL (d) | 0/9 (0%) 2/12 (17%) 0/8 (0%) 1/12 (8%) 0/11 (0%) 1/10 (10%) | |FIRST INCIDENCE | --- 274 (T) --- 274 (T) --- 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.609 P=0.300 (e) P=0.557 (e) P=0.521 | |POLY 3 | P=0.623 P=0.261 (e) P=0.512 (e) P=0.491 | |POLY 1.5 | P=0.621 P=0.254 (e) P=0.506 (e) P=0.497 | |POLY 6 | P=0.622 P=0.267 (e) P=0.517 (e) P=0.487 | |LOGISTIC REGRESSION| (e) P=0.300 (e) P=0.557 (e) P=0.521 | |COCH-ARM / FISHERS | P=0.600 P=0.241 (e) P=0.483 (e) P=0.500 | |ORDER RESTRICTED | P=0.329 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Unilateral | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 3/15 (20%) 2/14 (14%) 2/15 (13%) 1/15 (7%) | |POLY-3 RATE (b) | 1/12.63 2/14.31 3/11.17 2/13.43 2/12.70 1/12.06 | |POLY-3 PERCENT (g) | 7.9% 14.0% 26.9% 14.9% 15.8% 8.3% | |TERMINAL (d) | 0/9 (0%) 2/12 (17%) 2/8 (25%) 1/12 (8%) 2/11 (18%) 1/10 (10%) | |FIRST INCIDENCE | 271 274 (T) 78 271 274 (T) 274 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.386N P=0.585 P=0.266 P=0.552 P=0.537 P=0.758N | |POLY 3 | P=0.432N P=0.544 P=0.249 P=0.522 P=0.502 P=0.752 | |POLY 1.5 | P=0.413N P=0.533 P=0.268 P=0.510 P=0.501 P=0.758 | |POLY 6 | P=0.448N P=0.552 P=0.235 P=0.530 P=0.503 P=0.747 | |LOGISTIC REGRESSION| P=0.389N P=0.559 P=0.321 P=0.530 P=0.502 P=0.755 | |COCH-ARM / FISHERS | P=0.386N P=0.500 P=0.299 P=0.473 P=0.500 P=0.759N | |ORDER RESTRICTED | P=0.520 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Unilateral | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Unilateral, Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 4/15 (27%) 2/14 (14%) 3/15 (20%) 3/15 (20%) | |POLY-3 RATE (b) | 1/12.63 2/14.31 4/11.74 2/13.43 3/13.57 3/12.09 | |POLY-3 PERCENT (g) | 7.9% 14.0% 34.1% 14.9% 22.1% 24.8% | |TERMINAL (d) | 0/9 (0%) 2/12 (17%) 2/8 (25%) 1/12 (8%) 2/11 (18%) 2/10 (20%) | |FIRST INCIDENCE | 271 274 (T) 78 271 138 271 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.335 P=0.585 P=0.146 P=0.552 P=0.334 P=0.307 | |POLY 3 | P=0.282 P=0.544 P=0.133 P=0.522 P=0.323 P=0.278 | |POLY 1.5 | P=0.305 P=0.533 P=0.143 P=0.510 P=0.315 P=0.289 | |POLY 6 | P=0.265 P=0.552 P=0.129 P=0.530 P=0.329 P=0.269 | |LOGISTIC REGRESSION| P=0.338 P=0.559 P=0.188 P=0.530 P=0.294 P=0.267 | |COCH-ARM / FISHERS | P=0.335 P=0.500 P=0.165 P=0.473 P=0.299 P=0.299 | |ORDER RESTRICTED | P=0.271 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Testes: Unilateral, Germinal Epithelium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thymus | | Atrophy Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/12 (8%) 0/14 (0%) 1/12 (8%) 0/13 (0%) 4/14 (29%) 0/12 (0%) | |POLY-3 RATE (b) | 1/11.94 0/13.94 1/10.47 0/12.97 4/14.00 0/11.36 | |POLY-3 PERCENT (g) | 8.4% 0.0% 9.6% 0.0% 28.6% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 1/11 (9%) 0/10 (0%) | |FIRST INCIDENCE | 271 --- 150 --- 138 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.510 P=0.469N P=0.719 P=0.484N P=0.197 P=0.517N | |POLY 3 | P=0.490 P=0.469N P=0.731 P=0.483N P=0.213 P=0.510N | |POLY 1.5 | P=0.504 P=0.469N P=0.741 P=0.484N P=0.212 P=0.506N | |POLY 6 | P=0.474 P=0.469N P=0.724 P=0.483N P=0.215 P=0.514N | |LOGISTIC REGRESSION| P=0.526 (e) P=0.538N (e) (e) P=0.503N | |COCH-ARM / FISHERS | P=0.522 P=0.462N P=0.761N P=0.480N P=0.213 P=0.500N | |ORDER RESTRICTED | P=0.252 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thymus | | Atrophy Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 1/13 (8%) 1/12 (8%) 2/12 (17%) 2/13 (15%) 2/11 (18%) | |POLY-3 RATE (b) | 3/14.39 1/12.38 1/10.44 2/11.96 2/13.00 2/10.02 | |POLY-3 PERCENT (g) | 20.9% 8.1% 9.6% 16.7% 15.4% 20.0% | |TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 0/8 (0%) | |FIRST INCIDENCE | 109 192 67 165 269 184 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.472 P=0.344N P=0.403N P=0.587N P=0.499N P=0.641N | |POLY 3 | P=0.445 P=0.355N P=0.423N P=0.588N P=0.548N P=0.669N | |POLY 1.5 | P=0.439 P=0.353N P=0.417N P=0.595N P=0.556N P=0.670N | |POLY 6 | P=0.455 P=0.357N P=0.426N P=0.582N P=0.540N P=0.663N | |LOGISTIC REGRESSION| P=0.445 P=0.410N P=0.167N P=0.585N P=0.574 P=0.598N | |COCH-ARM / FISHERS | P=0.447 P=0.356N P=0.389N P=0.612N P=0.572N P=0.654N | |ORDER RESTRICTED | P=0.589N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thymus | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/12 (0%) 0/14 (0%) 0/12 (0%) 1/13 (8%) 2/14 (14%) 2/12 (17%) | |POLY-3 RATE (b) | 0/11.90 0/13.94 0/9.63 1/12.97 2/12.66 2/11.39 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.7% 15.8% 17.6% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 1/12 (8%) 2/11 (18%) 1/10 (10%) | |FIRST INCIDENCE | --- --- --- 274 (T) 274 (T) 271 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.031 * (e) (e) P=0.557 P=0.280 P=0.242 | |POLY 3 | P=0.027 * (e) (e) P=0.517 P=0.243 P=0.218 | |POLY 1.5 | P=0.027 * (e) (e) P=0.517 P=0.251 P=0.222 | |POLY 6 | P=0.026 * (e) (e) P=0.518 P=0.236 P=0.215 | |LOGISTIC REGRESSION| P=0.025 * (e) (e) P=0.557 P=0.280 P=0.217 | |COCH-ARM / FISHERS | P=0.027 * (e) (e) P=0.520 P=0.280 P=0.239 | |ORDER RESTRICTED | P=0.078 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thymus | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 1/13 (8%) 1/12 (8%) 0/12 (0%) 0/13 (0%) 1/11 (9%) | |POLY-3 RATE (b) | 2/13.08 1/11.72 1/10.03 0/10.47 0/12.88 1/9.26 | |POLY-3 PERCENT (g) | 15.3% 8.5% 10.0% 0.0% 0.0% 10.8% | |TERMINAL (d) | 2/11 (18%) 1/10 (10%) 0/9 (0%) 0/9 (0%) 0/11 (0%) 1/8 (13%) | |FIRST INCIDENCE | 275 (T) 275 (T) 207 --- --- 275 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.459N P=0.535N P=0.577N P=0.280N P=0.234N P=0.616N | |POLY 3 | P=0.430N P=0.539N P=0.594N P=0.282N P=0.233N P=0.622N | |POLY 1.5 | P=0.440N P=0.540N P=0.602N P=0.281N P=0.243N P=0.622N | |POLY 6 | P=0.424N P=0.539N P=0.580N P=0.281N P=0.225N P=0.618N | |LOGISTIC REGRESSION| P=0.464N P=0.535N P=0.594N (e) (e) P=0.616N | |COCH-ARM / FISHERS | P=0.465N P=0.556N P=0.586N P=0.299N P=0.278N P=0.619N | |ORDER RESTRICTED | P=0.265N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/13 (15%) 0/15 (0%) 0/13 (0%) 0/14 (0%) 0/14 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 2/12.94 0/14.31 0/10.06 0/13.39 0/12.66 0/11.92 | |POLY-3 PERCENT (g) | 15.5% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/9 (0%) 0/12 (0%) 0/8 (0%) 0/12 (0%) 0/11 (0%) 0/10 (0%) | |FIRST INCIDENCE | 197 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.217N P=0.208N P=0.291N P=0.216N P=0.249N P=0.258N | |POLY 3 | P=0.166N P=0.207N P=0.292N P=0.222N P=0.235N P=0.249N | |POLY 1.5 | P=0.175N P=0.203N P=0.269N P=0.218N P=0.227N P=0.235N | |POLY 6 | P=0.158N P=0.210N P=0.311N P=0.226N P=0.242N P=0.263N | |LOGISTIC REGRESSION| P=0.183N P=0.188N P=0.133N P=0.216N P=0.142N P=0.114N | |COCH-ARM / FISHERS | P=0.201N P=0.206N P=0.240N P=0.222N P=0.222N P=0.222N | |ORDER RESTRICTED | P=0.010N* (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/13 (0%) 0/12 (0%) 0/15 (0%) 0/14 (0%) 0/11 (0%) | |POLY-3 RATE (b) | 1/13.39 0/11.67 0/8.84 0/10.85 0/13.80 0/8.74 | |POLY-3 PERCENT (g) | 7.5% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/11 (0%) 0/10 (0%) 0/8 (0%) 0/9 (0%) 0/11 (0%) 0/7 (0%) | |FIRST INCIDENCE | 242 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.430N P=0.533N P=0.573N P=0.552N P=0.485N P=0.573N | |POLY 3 | P=0.373N P=0.527N P=0.581N P=0.542N P=0.494N P=0.584N | |POLY 1.5 | P=0.392N P=0.526N P=0.574N P=0.528N P=0.499N P=0.577N | |POLY 6 | P=0.355N P=0.531N P=0.587N P=0.550N P=0.492N P=0.591N | |LOGISTIC REGRESSION| P=0.438N P=0.550N P=0.544N P=0.496N P=0.591N P=0.555N | |COCH-ARM / FISHERS | P=0.437N P=0.536N P=0.556N P=0.500N P=0.517N P=0.577N | |ORDER RESTRICTED | P=0.152N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/05/03 EXPERIMENT: 99033 TEST: 01 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(TG.AC HETEROZYGOUS TRANSGENIC) - TRANSGENIC MODEL EVALUATION II (ASPA Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | VEHICLE 3125 PPM 6250 PPM 12500 25000 50000 | | | CONTROL PPM PPM PPM | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/15 (67%) 8/13 (62%) 9/13 (69%) 10/12 (83%) 10/14 (71%) 10/14 (71%) | |POLY-3 RATE (b) | 10/14.06 8/11.67 9/9.84 10/10.33 10/13.85 10/10.84 | |POLY-3 PERCENT (g) | 71.1% 68.6% 91.5% 96.8% 72.2% 92.3% | |TERMINAL (d) | 7/11 (64%) 8/10 (80%) 9/9 (100%) 9/9 (100%) 9/11 (82%) 8/8 (100%) | |FIRST INCIDENCE | 200 275 (T) 275 (T) 184 270 92 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.090 P=0.494N P=0.493 P=0.341 P=0.630N P=0.231 | |POLY 3 | P=0.201 P=0.613N P=0.237 P=0.126 P=0.636 P=0.201 | |POLY 1.5 | P=0.256 P=0.568N P=0.332 P=0.177 P=0.622 P=0.300 | |POLY 6 | P=0.162 P=0.663 P=0.161 P=0.099 P=0.628 P=0.133 | |LOGISTIC REGRESSION| P=0.171 P=0.507N P=0.361 P=0.173 P=0.664N P=0.283 | |COCH-ARM / FISHERS | P=0.425 P=0.544N P=0.604 P=0.298 P=0.550 P=0.550 | |ORDER RESTRICTED | P=0.104 (e) (e) (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).