TDMS Study 96021-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB 153) DATE: 10/09/03 EXPERIMENT: 96021 TEST: 01 TIME: 12:01:34 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: C96021 PATHOLOGIST: SELLS, DONALD CAS: 35065-27-1 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3 CONTROL VS. TREATED REASONS FOR REMOVAL: 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 UG/KG INCLUDE 002 10 UG/KG INCLUDE 003 100 UG/KG INCLUDE 004 300 UG/KG INCLUDE 005 1000 UG/KG INCLUDE 006 3000 UG/KG NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB 153) DATE: 10/09/03 EXPERIMENT: 96021 TEST: 01 TIME: 12:01:34 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: C96021 PATHOLOGIST: SELLS, DONALD CAS: 35065-27-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION ( =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Angiectasis Hematopoietic Cell Proliferation Hyperplasia Hypertrophy Bone Marrow Hyperplasia Clitoral Gland Inflammation Clitoral Gland: Duct Cyst Harderian Gland Inflammation Heart Cardiomyopathy Intestine Large, Rectum Parasite Metazoan Kidney Mineralization Nephropathy Liver Basophilic Focus Clear Cell Focus Eosinophilic Focus Fatty Change Diffuse Mixed Cell Focus Pigmentation Liver: Bile Duct Hyperplasia Liver: Centrilobular Degeneration Liver: Hepatocyte Hypertrophy Liver: Oval Cell Hyperplasia Lung Infiltration Cellular Histiocyte Lung: Alveolar Epithelium Hyperplasia Lymph Node, Mandibular Hyperplasia Lymph Node: Mediastinal Congestion Ectasia Hyperplasia Lymph Node: Renal Ectasia Mammary Gland Hyperplasia Nose Inflammation Nose: Turbinate Inflammation Oral Mucosa: Gingival Hyperplasia Ovary Atrophy Inflammation Chronic Oviduct Inflammation Chronic Pancreas: Acinus Hyperplasia Vacuolization Cytoplasmic Pituitary Gland Angiectasis Spleen Hematopoietic Cell Proliferation Spleen: Lymphoid Follicle Atrophy Stomach, Forestomach Hyperkeratosis Thyroid Gland: Follicular Cell Hypertrophy Tooth: Peridontal Tissue Inflammation Uterus Inflammation Inflammation Chronic Metaplasia Uterus: Endometrium Hyperplasia Cystic NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB 153) DATE: 10/09/03 EXPERIMENT: 96021 TEST: 01 TIME: 12:01:34 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: C96021 PATHOLOGIST: SELLS, DONALD CAS: 35065-27-1 =============================================================== Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/53 (40%) 23/54 (43%) 34/53 (64%) 25/53 (47%) 29/53 (55%) 21/51 (41%) | |POLY-3 RATE (b) | 21/42.96 23/34.81 34/45.38 25/39.94 29/42.63 21/35.81 | |POLY-3 PERCENT (g) | 48.9% 66.1% 74.9% 62.6% 68.0% 58.7% | |TERMINAL (d) | 12/24 (50%) 13/16 (81%) 24/28 (86%) 16/21 (76%) 15/20 (75%) 15/21 (71%) | |FIRST INCIDENCE | 502 360 429 443 514 452 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.376N P=0.050 P=0.058 P=0.152 P=0.051 P=0.314 | |POLY 3 | P=0.420N P=0.084 P=0.006 ** P=0.137 P=0.046 * P=0.251 | |POLY 1.5 | P=0.332N P=0.184 P=0.007 ** P=0.170 P=0.059 P=0.350 | |POLY 6 | P=0.541N P=0.033 * P=0.006 ** P=0.109 P=0.039 * P=0.164 | |LOGISTIC REGRESSION| P=0.388N P=0.095 P=0.012 * P=0.171 P=0.062 P=0.293 | |COCH-ARM / FISHERS | P=0.269N P=0.454 P=0.010 * P=0.278 P=0.086 P=0.515 | |ORDER RESTRICTED | P=0.061 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 1/36.33 2/38.40 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.8% 5.2% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 1/20 (5%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 731 (T) 715 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.679 (e) (e) P=0.473 P=0.215 (e) | |POLY 3 | P=0.639 (e) (e) P=0.486 P=0.233 (e) | |POLY 1.5 | P=0.655 (e) (e) P=0.488 P=0.235 (e) | |POLY 6 | P=0.624 (e) (e) P=0.485 P=0.230 (e) | |LOGISTIC REGRESSION| P=0.674 (e) (e) P=0.473 P=0.223 (e) | |COCH-ARM / FISHERS | P=0.681 (e) (e) P=0.500 P=0.248 (e) | |ORDER RESTRICTED | P=0.280 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/53 (17%) 12/54 (22%) 15/53 (28%) 13/53 (25%) 12/53 (23%) 13/51 (25%) | |POLY-3 RATE (b) | 9/40.67 12/33.09 15/41.93 13/38.58 12/40.17 13/36.59 | |POLY-3 PERCENT (g) | 22.1% 36.3% 35.8% 33.7% 29.9% 35.5% | |TERMINAL (d) | 5/24 (21%) 6/16 (38%) 13/28 (46%) 6/21 (29%) 5/20 (25%) 6/21 (29%) | |FIRST INCIDENCE | 437 527 591 530 617 479 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.318 P=0.088 P=0.212 P=0.179 P=0.250 P=0.136 | |POLY 3 | P=0.363 P=0.137 P=0.125 P=0.180 P=0.292 P=0.142 | |POLY 1.5 | P=0.372 P=0.191 P=0.124 P=0.187 P=0.301 P=0.158 | |POLY 6 | P=0.366 P=0.102 P=0.134 P=0.185 P=0.289 P=0.139 | |LOGISTIC REGRESSION| P=0.307 P=0.134 P=0.156 P=0.184 P=0.295 P=0.152 | |COCH-ARM / FISHERS | P=0.384 P=0.331 P=0.123 P=0.237 P=0.313 P=0.206 | |ORDER RESTRICTED | P=0.169 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/54 (2%) 0/53 (0%) 1/53 (2%) 0/53 (0%) 3/51 (6%) | |POLY-3 RATE (b) | 0/39.01 1/31.63 0/41.12 1/36.95 0/38.33 3/34.54 | |POLY-3 PERCENT (g) | 0.0% 3.2% 0.0% 2.7% 0.0% 8.7% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 527 --- 530 --- 442 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016 * P=0.450 (e) P=0.477 (e) P=0.097 | |POLY 3 | P=0.018 * P=0.458 (e) P=0.489 (e) P=0.097 | |POLY 1.5 | P=0.019 * P=0.473 (e) P=0.490 (e) P=0.101 | |POLY 6 | P=0.017 * P=0.447 (e) P=0.490 (e) P=0.096 | |LOGISTIC REGRESSION| P=0.026 * P=0.562 (e) P=0.540 (e) P=0.129 | |COCH-ARM / FISHERS | P=0.022 * P=0.505 (e) P=0.500 (e) P=0.114 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/53 (34%) 24/54 (44%) 27/53 (51%) 27/53 (51%) 28/53 (53%) 11/51 (22%) | |POLY-3 RATE (b) | 18/42.09 24/37.35 27/43.51 27/42.98 28/44.72 11/34.55 | |POLY-3 PERCENT (g) | 42.8% 64.3% 62.1% 62.8% 62.6% 31.8% | |TERMINAL (d) | 11/24 (46%) 11/16 (69%) 20/28 (71%) 13/21 (62%) 10/20 (50%) 8/21 (38%) | |FIRST INCIDENCE | 418 310 514 269 452 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016N* P=0.012 * P=0.159 P=0.035 * P=0.033 * P=0.207N | |POLY 3 | P=0.011N* P=0.035 * P=0.048 * P=0.042 * P=0.042 * P=0.222N | |POLY 1.5 | P=0.006N** P=0.064 P=0.051 P=0.039 * P=0.038 * P=0.175N | |POLY 6 | P=0.021N* P=0.023 * P=0.051 P=0.053 P=0.055 P=0.279N | |LOGISTIC REGRESSION| P=0.006N** P=0.039 * P=0.075 P=0.034 * P=0.033 * P=0.198N | |COCH-ARM / FISHERS | P=0.005N** P=0.181 P=0.058 P=0.058 P=0.039 * P=0.117N | |ORDER RESTRICTED | P=0.010N* (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 48/53 (91%) 35/54 (65%) 45/53 (85%) 35/53 (66%) 42/53 (79%) 41/51 (80%) | |POLY-3 RATE (b) | 48/49.83 35/42.29 45/48.98 35/43.86 42/46.92 41/44.17 | |POLY-3 PERCENT (g) | 96.3% 82.8% 91.9% 79.8% 89.5% 92.8% | |TERMINAL (d) | 24/24 (100%) 15/16 (94%) 28/28 (100%) 18/21 (86%) 20/20 (100%) 20/21 (95%) | |FIRST INCIDENCE | 211 250 418 443 341 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.265 P=0.547 P=0.121N P=0.116N P=0.465N P=0.538 | |POLY 3 | P=0.291 P=0.009N** P=0.250N P=0.004N** P=0.114N P=0.342N | |POLY 1.5 | P=0.316 P=0.003N** P=0.249N P=0.004N** P=0.095N P=0.237N | |POLY 6 | P=0.296 P=0.027N* P=0.299N P=0.005N** P=0.170N P=0.478N | |LOGISTIC REGRESSION| P=0.272 P=0.016N* P=0.181N P=0.005N** P=0.069N P=0.288N | |COCH-ARM / FISHERS | P=0.369 P<0.001N** P=0.278N P=0.002N** P=0.087N P=0.115N | |ORDER RESTRICTED | P=0.066N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 1/53 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 2/37.08 1/39.07 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% 2.6% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 568 467 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.619N (e) (e) P=0.232 P=0.508 (e) | |POLY 3 | P=0.615N (e) (e) P=0.225 P=0.500 (e) | |POLY 1.5 | P=0.608N (e) (e) P=0.226 P=0.501 (e) | |POLY 6 | P=0.621N (e) (e) P=0.227 P=0.499 (e) | |LOGISTIC REGRESSION| P=0.588N (e) (e) P=0.238 P=0.466 (e) | |COCH-ARM / FISHERS | P=0.596N (e) (e) P=0.248 P=0.500 (e) | |ORDER RESTRICTED | P=0.287 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/54 (4%) 1/53 (2%) 2/53 (4%) 3/53 (6%) 3/51 (6%) | |POLY-3 RATE (b) | 1/39.58 2/31.01 1/41.24 2/37.08 3/40.06 3/33.85 | |POLY-3 PERCENT (g) | 2.5% 6.5% 2.4% 5.4% 7.5% 8.9% | |TERMINAL (d) | 0/24 (0%) 2/16 (13%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 1/21 (5%) | |FIRST INCIDENCE | 551 731 (T) 700 568 467 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174 P=0.368 P=0.751N P=0.476 P=0.304 P=0.250 | |POLY 3 | P=0.162 P=0.416 P=0.752N P=0.477 P=0.309 P=0.250 | |POLY 1.5 | P=0.175 P=0.447 P=0.755N P=0.480 P=0.308 P=0.264 | |POLY 6 | P=0.150 P=0.388 P=0.746N P=0.478 P=0.308 P=0.240 | |LOGISTIC REGRESSION| P=0.192 P=0.426 P=0.756 P=0.517 P=0.289 P=0.289 | |COCH-ARM / FISHERS | P=0.194 P=0.507 P=0.752N P=0.500 P=0.309 P=0.294 | |ORDER RESTRICTED | P=0.204 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/53 (19%) 8/54 (15%) 14/53 (26%) 16/53 (30%) 12/53 (23%) 14/51 (27%) | |POLY-3 RATE (b) | 10/39.40 8/33.44 14/41.49 16/40.22 12/40.57 14/35.63 | |POLY-3 PERCENT (g) | 25.4% 23.9% 33.7% 39.8% 29.6% 39.3% | |TERMINAL (d) | 8/24 (33%) 2/16 (13%) 11/28 (39%) 6/21 (29%) 4/20 (20%) 9/21 (43%) | |FIRST INCIDENCE | 656 261 696 486 510 432 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.182 P=0.480 P=0.396 P=0.092 P=0.309 P=0.137 | |POLY 3 | P=0.191 P=0.552N P=0.277 P=0.123 P=0.432 P=0.141 | |POLY 1.5 | P=0.206 P=0.496N P=0.263 P=0.111 P=0.420 P=0.162 | |POLY 6 | P=0.176 P=0.589N P=0.308 P=0.156 P=0.456 P=0.131 | |LOGISTIC REGRESSION| P=0.160 P=0.603N P=0.369 P=0.087 P=0.375 P=0.105 | |COCH-ARM / FISHERS | P=0.221 P=0.382N P=0.243 P=0.129 P=0.406 P=0.210 | |ORDER RESTRICTED | P=0.144 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/53 (34%) 14/54 (26%) 19/53 (36%) 14/53 (26%) 20/53 (38%) 12/51 (24%) | |POLY-3 RATE (b) | 18/41.52 14/34.65 19/45.35 14/39.63 20/41.42 12/34.21 | |POLY-3 PERCENT (g) | 43.4% 40.4% 41.9% 35.3% 48.3% 35.1% | |TERMINAL (d) | 11/24 (46%) 7/16 (44%) 11/28 (39%) 6/21 (29%) 10/20 (50%) 9/21 (43%) | |FIRST INCIDENCE | 502 479 443 452 590 514 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.310N P=0.463 P=0.489N P=0.386N P=0.287 P=0.287N | |POLY 3 | P=0.373N P=0.489N P=0.533N P=0.300N P=0.406 P=0.305N | |POLY 1.5 | P=0.298N P=0.403N P=0.581N P=0.303N P=0.411 P=0.247N | |POLY 6 | P=0.463N P=0.555N P=0.471N P=0.283N P=0.415 P=0.365N | |LOGISTIC REGRESSION| P=0.278N P=0.530N P=0.543 P=0.330N P=0.384 P=0.302N | |COCH-ARM / FISHERS | P=0.228N P=0.243N P=0.500 P=0.263N P=0.420 P=0.169N | |ORDER RESTRICTED | P=0.424N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 1/54 (2%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 2/39.69 1/31.45 0/41.12 1/36.86 1/39.07 0/33.11 | |POLY-3 PERCENT (g) | 5.0% 3.2% 0.0% 2.7% 2.6% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 551 600 --- 568 467 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.314N P=0.615N P=0.240N P=0.532N P=0.513N P=0.302N | |POLY 3 | P=0.309N P=0.580N P=0.229N P=0.526N P=0.506N P=0.279N | |POLY 1.5 | P=0.300N P=0.548N P=0.230N P=0.518N P=0.499N P=0.265N | |POLY 6 | P=0.319N P=0.608N P=0.225N P=0.531N P=0.515N P=0.291N | |LOGISTIC REGRESSION| P=0.284N P=0.474N P=0.246N P=0.464N P=0.495N P=0.223N | |COCH-ARM / FISHERS | P=0.291N P=0.486N P=0.243N P=0.493N P=0.493N P=0.252N | |ORDER RESTRICTED | P=0.129N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/53 (64%) 41/54 (76%) 40/53 (75%) 38/53 (72%) 42/53 (79%) 46/51 (90%) | |POLY-3 RATE (b) | 34/49.96 41/52.65 40/52.69 38/50.69 42/51.29 46/51.00 | |POLY-3 PERCENT (g) | 68.1% 77.9% 75.9% 75.0% 81.9% 90.2% | |TERMINAL (d) | 11/24 (46%) 6/16 (38%) 17/28 (61%) 12/21 (57%) 13/20 (65%) 16/21 (76%) | |FIRST INCIDENCE | 399 250 418 59 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.033 * P=0.025 * P=0.427 P=0.213 P=0.114 P=0.013 * | |POLY 3 | P=0.006 ** P=0.180 P=0.250 P=0.288 P=0.077 P=0.004 ** | |POLY 1.5 | P=0.005 ** P=0.162 P=0.211 P=0.287 P=0.074 P=0.003 ** | |POLY 6 | P=0.009 ** P=0.210 P=0.299 P=0.289 P=0.084 P=0.008 ** | |LOGISTIC REGRESSION| P=0.004 ** P=0.397 P=0.097 P=0.339 P=0.067 P=0.004 ** | |COCH-ARM / FISHERS | P=0.003 ** P=0.132 P=0.145 P=0.266 P=0.065 P<0.001 ** | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Brain | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 1/53 (2%) 1/53 (2%) 2/53 (4%) 0/51 (0%) | |POLY-3 RATE (b) | 1/39.53 0/31.01 1/41.24 1/36.64 2/38.74 0/33.11 | |POLY-3 PERCENT (g) | 2.5% 0.0% 2.4% 2.7% 5.2% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 571 --- 700 647 636 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.489N P=0.556N P=0.743N P=0.750 P=0.492 P=0.549N | |POLY 3 | P=0.478N P=0.548N P=0.752N P=0.744 P=0.493 P=0.535N | |POLY 1.5 | P=0.471N P=0.530N P=0.755N P=0.747 P=0.497 P=0.525N | |POLY 6 | P=0.485N P=0.564N P=0.745N P=0.743 P=0.488 P=0.543N | |LOGISTIC REGRESSION| P=0.475N P=0.471N P=0.759 P=0.758N P=0.500 P=0.485N | |COCH-ARM / FISHERS | P=0.467N P=0.495N P=0.752N P=0.752N P=0.500 P=0.510N | |ORDER RESTRICTED | P=0.414N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 1/53 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 2/37.11 1/38.71 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% 2.6% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 443 625 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.610N (e) (e) P=0.225 P=0.506 (e) | |POLY 3 | P=0.615N (e) (e) P=0.225 P=0.498 (e) | |POLY 1.5 | P=0.608N (e) (e) P=0.227 P=0.500 (e) | |POLY 6 | P=0.622N (e) (e) P=0.226 P=0.497 (e) | |LOGISTIC REGRESSION| P=0.593N (e) (e) P=0.250 P=0.500 (e) | |COCH-ARM / FISHERS | P=0.596N (e) (e) P=0.248 P=0.500 (e) | |ORDER RESTRICTED | P=0.286 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 52/53 (98%) 45/51 (88%) 41/52 (79%) 48/53 (91%) 48/51 (94%) 46/50 (92%) | |POLY-3 RATE (b) | 52/52.22 45/47.19 41/47.75 48/50.33 48/49.57 46/47.75 | |POLY-3 PERCENT (g) | 99.6% 95.4% 85.9% 95.4% 96.8% 96.3% | |TERMINAL (d) | 24/24 (100%) 14/14 (100%) 23/27 (85%) 21/21 (100%) 20/20 (100%) 21/21 (100%) | |FIRST INCIDENCE | 211 250 418 59 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.320 P=0.119 P=0.020N* P=0.513 P=0.524 P=0.439 | |POLY 3 | P=0.340 P=0.149N P=0.004N** P=0.190N P=0.353N P=0.270N | |POLY 1.5 | P=0.329 P=0.078N P=0.002N** P=0.161N P=0.303N P=0.195N | |POLY 6 | P=0.333 P=0.449N P=0.012N* P=0.241N P=0.487N P=0.516N | |LOGISTIC REGRESSION| P=0.283 P=0.122N P<0.001N** P=0.167N P=0.277N P=0.223N | |COCH-ARM / FISHERS | P=0.300 P=0.050N P=0.002N** P=0.103N P=0.294N P=0.164N | |ORDER RESTRICTED | P=0.077N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 49/53 (92%) 40/51 (78%) 36/52 (69%) 43/53 (81%) 45/51 (88%) 41/50 (82%) | |POLY-3 RATE (b) | 49/52.16 40/45.70 36/47.08 43/48.32 45/49.57 41/47.01 | |POLY-3 PERCENT (g) | 93.9% 87.5% 76.5% 89.0% 90.8% 87.2% | |TERMINAL (d) | 22/24 (92%) 11/14 (79%) 20/27 (74%) 20/21 (95%) 18/20 (90%) 17/21 (81%) | |FIRST INCIDENCE | 211 250 429 59 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.371 P=0.247 P=0.012N* P=0.467N P=0.550 P=0.522N | |POLY 3 | P=0.542 P=0.203N P=0.008N** P=0.275N P=0.403N P=0.193N | |POLY 1.5 | P=0.496 P=0.113N P=0.004N** P=0.182N P=0.375N P=0.149N | |POLY 6 | P=0.563N P=0.320N P=0.017N* P=0.424N P=0.453N P=0.239N | |LOGISTIC REGRESSION| P=0.409 P=0.049N* P=0.002N** P=0.094N P=0.343N P=0.091N | |COCH-ARM / FISHERS | P=0.417 P=0.039N* P=0.002N** P=0.075N P=0.346N P=0.096N | |ORDER RESTRICTED | P=0.150N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Esophagus: Muscularis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/54 (6%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 1/51 (2%) | |POLY-3 RATE (b) | 0/39.01 3/32.98 0/41.12 1/37.10 2/39.22 1/33.11 | |POLY-3 PERCENT (g) | 0.0% 9.1% 0.0% 2.7% 5.1% 3.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 1/21 (5%) | |FIRST INCIDENCE | --- 310 --- 452 579 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.577 P=0.097 (e) P=0.496 P=0.246 P=0.473 | |POLY 3 | P=0.518 P=0.091 (e) P=0.490 P=0.238 P=0.467 | |POLY 1.5 | P=0.548 P=0.100 (e) P=0.491 P=0.238 P=0.476 | |POLY 6 | P=0.491 P=0.084 (e) P=0.491 P=0.238 P=0.461 | |LOGISTIC REGRESSION| P=0.613 P=0.203 (e) P=0.583 P=0.237 P=0.473 | |COCH-ARM / FISHERS | P=0.600 P=0.125 (e) P=0.500 P=0.248 P=0.490 | |ORDER RESTRICTED | P=0.287 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/53 (2%) 0/53 (0%) 1/52 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 2/39.23 0/31.01 1/41.23 0/36.33 1/37.78 0/33.11 | |POLY-3 PERCENT (g) | 5.1% 0.0% 2.4% 0.0% 2.7% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 672 --- 701 --- 696 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.373N P=0.328N P=0.437N P=0.254N P=0.529N P=0.276N | |POLY 3 | P=0.341N P=0.293N P=0.483N P=0.254N P=0.513N P=0.276N | |POLY 1.5 | P=0.344N P=0.271N P=0.489N P=0.251N P=0.510N P=0.265N | |POLY 6 | P=0.341N P=0.313N P=0.471N P=0.256N P=0.518N P=0.284N | |LOGISTIC REGRESSION| P=0.371N P=0.306N P=0.474N P=0.254N P=0.516N P=0.278N | |COCH-ARM / FISHERS | P=0.357N P=0.243N P=0.500N P=0.248N P=0.507N P=0.257N | |ORDER RESTRICTED | P=0.088N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 20/53 (38%) 9/54 (17%) 13/53 (25%) 16/53 (30%) 16/53 (30%) 16/49 (33%) | |POLY-3 RATE (b) | 20/42.61 9/32.73 13/41.57 16/40.05 16/41.33 16/35.66 | |POLY-3 PERCENT (g) | 46.9% 27.5% 31.3% 40.0% 38.7% 44.9% | |TERMINAL (d) | 11/24 (46%) 5/16 (31%) 10/28 (36%) 9/21 (43%) 10/20 (50%) 10/21 (48%) | |FIRST INCIDENCE | 211 557 674 269 360 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.238 P=0.144N P=0.046N* P=0.410N P=0.423N P=0.478N | |POLY 3 | P=0.242 P=0.064N P=0.098N P=0.333N P=0.288N P=0.518N | |POLY 1.5 | P=0.248 P=0.037N* P=0.100N P=0.328N P=0.279N P=0.472N | |POLY 6 | P=0.236 P=0.097N P=0.093N P=0.331N P=0.309N P=0.552N | |LOGISTIC REGRESSION| P=0.195 P=0.050N P=0.071N P=0.323N P=0.276N P=0.475N | |COCH-ARM / FISHERS | P=0.243 P=0.012N* P=0.104N P=0.269N P=0.269N P=0.371N | |ORDER RESTRICTED | P=0.298N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/52 (42%) 18/54 (33%) 19/53 (36%) 19/53 (36%) 23/53 (43%) 24/51 (47%) | |POLY-3 RATE (b) | 22/42.16 18/37.44 19/43.18 19/40.93 23/43.20 24/36.80 | |POLY-3 PERCENT (g) | 52.2% 48.1% 44.0% 46.4% 53.2% 65.2% | |TERMINAL (d) | 14/24 (58%) 6/16 (38%) 12/28 (43%) 9/21 (43%) 9/20 (45%) 16/21 (76%) | |FIRST INCIDENCE | 399 250 522 263 452 442 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.073 P=0.381 P=0.184N P=0.490N P=0.350 P=0.180 | |POLY 3 | P=0.034 * P=0.441N P=0.288N P=0.375N P=0.549 P=0.157 | |POLY 1.5 | P=0.054 P=0.372N P=0.297N P=0.364N P=0.544 P=0.230 | |POLY 6 | P=0.022 * P=0.477N P=0.268N P=0.385N P=0.564 P=0.111 | |LOGISTIC REGRESSION| P=0.063 P=0.452N P=0.257N P=0.400N P=0.497 P=0.146 | |COCH-ARM / FISHERS | P=0.102 P=0.226N P=0.316N P=0.316N P=0.534 P=0.387 | |ORDER RESTRICTED | P=0.085 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Heart | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 2/54 (4%) 0/53 (0%) 1/53 (2%) 0/53 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 0/38.79 2/32.06 0/41.12 1/37.04 0/38.33 1/33.77 | |POLY-3 PERCENT (g) | 0.0% 6.2% 0.0% 2.7% 0.0% 3.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 393 --- 486 --- 509 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.590 P=0.186 (e) P=0.487 (e) P=0.461 | |POLY 3 | P=0.550 P=0.197 (e) P=0.491 (e) P=0.472 | |POLY 1.5 | P=0.570 P=0.212 (e) P=0.493 (e) P=0.480 | |POLY 6 | P=0.532 P=0.185 (e) P=0.491 (e) P=0.468 | |LOGISTIC REGRESSION| P=0.620 P=0.298 (e) P=0.572 (e) P=0.553 | |COCH-ARM / FISHERS | P=0.606 P=0.257 (e) P=0.505 (e) P=0.495 | |ORDER RESTRICTED | P=0.315 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Heart | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 2/54 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/38.79 2/32.06 0/41.12 0/36.33 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 6.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 393 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.399N P=0.186 (e) (e) (e) (e) | |POLY 3 | P=0.441N P=0.197 (e) (e) (e) (e) | |POLY 1.5 | P=0.422N P=0.212 (e) (e) (e) (e) | |POLY 6 | P=0.458N P=0.185 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.381N P=0.298 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.389N P=0.257 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.183N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/54 (2%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/39.01 1/31.56 1/41.91 0/36.33 1/38.93 2/33.80 | |POLY-3 PERCENT (g) | 0.0% 3.2% 2.4% 0.0% 2.6% 5.9% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 1/21 (5%) | |FIRST INCIDENCE | --- 557 429 --- 541 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.137 P=0.446 P=0.512 (e) P=0.486 P=0.219 | |POLY 3 | P=0.126 P=0.458 P=0.514 (e) P=0.500 P=0.205 | |POLY 1.5 | P=0.131 P=0.473 P=0.509 (e) P=0.500 P=0.212 | |POLY 6 | P=0.121 P=0.446 P=0.523 (e) P=0.499 P=0.201 | |LOGISTIC REGRESSION| P=0.147 P=0.539 P=0.365 (e) P=0.491 P=0.251 | |COCH-ARM / FISHERS | P=0.136 P=0.505 P=0.500 (e) P=0.500 P=0.233 | |ORDER RESTRICTED | P=0.074 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/54 (4%) 3/53 (6%) 7/53 (13%) 5/53 (9%) 5/50 (10%) | |POLY-3 RATE (b) | 1/39.01 2/32.35 3/41.75 7/38.34 5/40.49 5/34.16 | |POLY-3 PERCENT (g) | 2.6% 6.2% 7.2% 18.3% 12.4% 14.6% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 2/28 (7%) 4/21 (19%) 1/20 (5%) 2/21 (10%) | |FIRST INCIDENCE | 731 (T) 479 522 452 452 591 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.132 P=0.409 P=0.346 P=0.023 * P=0.094 P=0.068 | |POLY 3 | P=0.129 P=0.435 P=0.329 P=0.026 * P=0.108 P=0.071 | |POLY 1.5 | P=0.136 P=0.457 P=0.320 P=0.026 * P=0.106 P=0.076 | |POLY 6 | P=0.128 P=0.418 P=0.345 P=0.027 * P=0.111 P=0.070 | |LOGISTIC REGRESSION| P=0.147 P=0.540 P=0.318 P=0.030 * P=0.103 P=0.071 | |COCH-ARM / FISHERS | P=0.148 P=0.507 P=0.309 P=0.030 * P=0.103 P=0.090 | |ORDER RESTRICTED | P=0.061 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/54 (6%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 0/39.01 3/32.30 1/41.12 0/36.33 0/38.33 1/33.69 | |POLY-3 PERCENT (g) | 0.0% 9.3% 2.4% 0.0% 0.0% 3.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 1/28 (4%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 502 731 (T) --- --- 548 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.621N P=0.084 P=0.531 (e) (e) P=0.444 | |POLY 3 | P=0.633N P=0.088 P=0.511 (e) (e) P=0.471 | |POLY 1.5 | P=0.619N P=0.098 P=0.506 (e) (e) P=0.478 | |POLY 6 | P=0.645N P=0.081 P=0.518 (e) (e) P=0.467 | |LOGISTIC REGRESSION| P=0.590N P=0.120 P=0.531 (e) (e) P=0.526 | |COCH-ARM / FISHERS | P=0.591N P=0.125 P=0.500 (e) (e) P=0.490 | |ORDER RESTRICTED | P=0.314N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Calculus Micro Observation Only | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 5/54 (9%) 4/53 (8%) 7/53 (13%) 5/53 (9%) 1/51 (2%) | |POLY-3 RATE (b) | 3/39.32 5/32.34 4/42.05 7/37.97 5/39.56 1/33.87 | |POLY-3 PERCENT (g) | 7.6% 15.5% 9.5% 18.4% 12.6% 3.0% | |TERMINAL (d) | 2/24 (8%) 2/16 (13%) 2/28 (7%) 4/21 (19%) 3/20 (15%) 0/21 (0%) | |FIRST INCIDENCE | 644 479 418 263 383 452 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.119N P=0.198 P=0.578 P=0.133 P=0.296 P=0.364N | |POLY 3 | P=0.128N P=0.252 P=0.537 P=0.139 P=0.358 P=0.359N | |POLY 1.5 | P=0.117N P=0.287 P=0.523 P=0.141 P=0.360 P=0.346N | |POLY 6 | P=0.141N P=0.227 P=0.558 P=0.139 P=0.353 P=0.369N | |LOGISTIC REGRESSION| P=0.106N P=0.251 P=0.514 P=0.142 P=0.352 P=0.331N | |COCH-ARM / FISHERS | P=0.103N P=0.368 P=0.500 P=0.160 P=0.358 P=0.324N | |ORDER RESTRICTED | P=0.168N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 2/54 (4%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 3/39.60 2/32.20 2/42.40 1/36.90 0/38.33 1/33.32 | |POLY-3 PERCENT (g) | 7.6% 6.2% 4.7% 2.7% 0.0% 3.0% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 590 479 514 555 --- 675 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.296N P=0.625N P=0.471N P=0.352N P=0.139N P=0.380N | |POLY 3 | P=0.275N P=0.594N P=0.469N P=0.330N P=0.123N P=0.368N | |POLY 1.5 | P=0.269N P=0.560N P=0.481N P=0.326N P=0.121N P=0.351N | |POLY 6 | P=0.285N P=0.621N P=0.451N P=0.332N P=0.128N P=0.382N | |LOGISTIC REGRESSION| P=0.263N P=0.513N P=0.524N P=0.314N P=0.123N P=0.358N | |COCH-ARM / FISHERS | P=0.267N P=0.491N P=0.500N P=0.309N P=0.121N P=0.324N | |ORDER RESTRICTED | P=0.160N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 1/53 (2%) 2/53 (4%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 1/39.23 0/31.01 1/41.12 2/36.55 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 2.6% 0.0% 2.4% 5.5% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 1/28 (4%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 672 --- 731 (T) 675 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.302N P=0.574N P=0.719N P=0.489 P=0.507N P=0.538N | |POLY 3 | P=0.276N P=0.546N P=0.751N P=0.475 P=0.505N P=0.534N | |POLY 1.5 | P=0.279N P=0.529N P=0.754N P=0.480 P=0.502N P=0.525N | |POLY 6 | P=0.276N P=0.562N P=0.744N P=0.473 P=0.509N P=0.541N | |LOGISTIC REGRESSION| P=0.299N P=0.543N P=0.747N P=0.475 P=0.502N P=0.528N | |COCH-ARM / FISHERS | P=0.288N P=0.495N P=0.752N P=0.500 P=0.500N P=0.510N | |ORDER RESTRICTED | P=0.360N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/54 (4%) 3/53 (6%) 2/53 (4%) 2/53 (4%) 3/51 (6%) | |POLY-3 RATE (b) | 1/39.01 2/31.85 3/41.12 2/36.55 2/38.33 3/33.11 | |POLY-3 PERCENT (g) | 2.6% 6.3% 7.3% 5.5% 5.2% 9.1% | |TERMINAL (d) | 1/24 (4%) 1/16 (6%) 3/28 (11%) 1/21 (5%) 2/20 (10%) 3/21 (14%) | |FIRST INCIDENCE | 731 (T) 393 731 (T) 675 731 (T) 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.320 P=0.388 P=0.360 P=0.473 P=0.436 P=0.255 | |POLY 3 | P=0.303 P=0.430 P=0.323 P=0.477 P=0.494 P=0.247 | |POLY 1.5 | P=0.318 P=0.455 P=0.316 P=0.480 P=0.498 P=0.262 | |POLY 6 | P=0.289 P=0.408 P=0.336 P=0.478 P=0.489 P=0.237 | |LOGISTIC REGRESSION| P=0.298 P=0.490 P=0.360 P=0.472 P=0.436 P=0.255 | |COCH-ARM / FISHERS | P=0.336 P=0.507 P=0.309 P=0.500 P=0.500 P=0.294 | |ORDER RESTRICTED | P=0.218 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/54 (4%) 0/53 (0%) 0/53 (0%) 3/53 (6%) 1/51 (2%) | |POLY-3 RATE (b) | 0/39.01 2/32.01 0/41.12 0/36.33 3/38.34 1/34.11 | |POLY-3 PERCENT (g) | 0.0% 6.3% 0.0% 0.0% 7.8% 2.9% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 2/20 (10%) 0/21 (0%) | |FIRST INCIDENCE | --- 557 --- --- 729 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.375 P=0.183 (e) (e) P=0.095 P=0.492 | |POLY 3 | P=0.331 P=0.196 (e) (e) P=0.114 P=0.473 | |POLY 1.5 | P=0.356 P=0.209 (e) (e) P=0.117 P=0.481 | |POLY 6 | P=0.310 P=0.186 (e) (e) P=0.111 P=0.468 | |LOGISTIC REGRESSION| P=0.402 P=0.254 (e) (e) P=0.097 (e) | |COCH-ARM / FISHERS | P=0.391 P=0.252 (e) (e) P=0.121 P=0.490 | |ORDER RESTRICTED | P=0.122 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 40/53 (75%) 42/54 (78%) 41/53 (77%) 39/53 (74%) 40/53 (75%) 41/51 (80%) | |POLY-3 RATE (b) | 40/47.84 42/47.44 41/49.99 39/47.32 40/50.76 41/47.66 | |POLY-3 PERCENT (g) | 83.6% 88.5% 82.0% 82.4% 78.8% 86.0% | |TERMINAL (d) | 21/24 (88%) 15/16 (94%) 23/28 (82%) 17/21 (81%) 12/20 (60%) 17/21 (81%) | |FIRST INCIDENCE | 399 250 429 263 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263 P=0.025 * P=0.346N P=0.393 P=0.374 P=0.178 | |POLY 3 | P=0.494 P=0.327 P=0.525N P=0.551N P=0.355N P=0.482 | |POLY 1.5 | P=0.450 P=0.355 P=0.582N P=0.560N P=0.449N P=0.437 | |POLY 6 | P=0.539 P=0.345 P=0.450N P=0.529N P=0.243N P=0.548 | |LOGISTIC REGRESSION| P=0.306 P=0.260 P=0.547 P=0.576 P=0.588 P=0.311 | |COCH-ARM / FISHERS | P=0.323 P=0.479 P=0.500 P=0.500N P=0.589N P=0.357 | |ORDER RESTRICTED | P=0.539N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/53 (64%) 23/54 (43%) 24/53 (45%) 33/53 (62%) 28/53 (53%) 34/51 (67%) | |POLY-3 RATE (b) | 34/46.35 23/36.65 24/44.38 33/41.71 28/43.84 34/41.25 | |POLY-3 PERCENT (g) | 73.4% 62.8% 54.1% 79.1% 63.9% 82.4% | |TERMINAL (d) | 18/24 (75%) 12/16 (75%) 16/28 (57%) 18/21 (86%) 14/20 (70%) 19/21 (91%) | |FIRST INCIDENCE | 211 250 418 443 360 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.041 * P=0.463N P=0.019N* P=0.427 P=0.390N P=0.239 | |POLY 3 | P=0.028 * P=0.194N P=0.035N* P=0.337 P=0.212N P=0.196 | |POLY 1.5 | P=0.038 * P=0.091N P=0.034N* P=0.415 P=0.187N P=0.292 | |POLY 6 | P=0.019 * P=0.353N P=0.038N* P=0.293 P=0.252N P=0.117 | |LOGISTIC REGRESSION| P=0.023 * P=0.106N P=0.026N* P=0.494 P=0.163N P=0.290 | |COCH-ARM / FISHERS | P=0.053 P=0.020N* P=0.039N* P=0.500N P=0.162N P=0.475 | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/54 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 2/31.89 0/41.12 0/36.33 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 6.3% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 502 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.406N P=0.182 (e) (e) (e) (e) | |POLY 3 | P=0.441N P=0.195 (e) (e) (e) (e) | |POLY 1.5 | P=0.424N P=0.209 (e) (e) (e) (e) | |POLY 6 | P=0.458N P=0.184 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.387N P=0.247 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.390N P=0.252 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.182N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 4/54 (7%) 2/53 (4%) 4/53 (8%) 5/53 (9%) 4/51 (8%) | |POLY-3 RATE (b) | 1/39.13 4/32.69 2/41.12 4/36.70 5/39.13 4/35.08 | |POLY-3 PERCENT (g) | 2.6% 12.2% 4.9% 10.9% 12.8% 11.4% | |TERMINAL (d) | 0/24 (0%) 1/16 (6%) 2/28 (7%) 2/21 (10%) 3/20 (15%) 0/21 (0%) | |FIRST INCIDENCE | 701 250 731 (T) 675 613 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.219 P=0.116 P=0.556 P=0.160 P=0.089 P=0.137 | |POLY 3 | P=0.216 P=0.127 P=0.517 P=0.158 P=0.099 P=0.145 | |POLY 1.5 | P=0.228 P=0.145 P=0.511 P=0.161 P=0.101 P=0.151 | |POLY 6 | P=0.211 P=0.115 P=0.529 P=0.157 P=0.097 P=0.145 | |LOGISTIC REGRESSION| P=0.239 P=0.195 P=0.547 P=0.155 P=0.098 P=0.185 | |COCH-ARM / FISHERS | P=0.251 P=0.187 P=0.500 P=0.181 P=0.103 P=0.170 | |ORDER RESTRICTED | P=0.123 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 5/54 (9%) 2/53 (4%) 4/53 (8%) 6/53 (11%) 4/51 (8%) | |POLY-3 RATE (b) | 1/39.13 5/33.35 2/41.12 4/36.81 6/39.16 4/34.84 | |POLY-3 PERCENT (g) | 2.6% 15.0% 4.9% 10.9% 15.3% 11.5% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 2/28 (7%) 1/21 (5%) 3/20 (15%) 1/21 (5%) | |FIRST INCIDENCE | 701 250 731 (T) 675 621 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.256 P=0.062 P=0.556 P=0.166 P=0.051 P=0.137 | |POLY 3 | P=0.239 P=0.067 P=0.517 P=0.158 P=0.054 P=0.143 | |POLY 1.5 | P=0.257 P=0.078 P=0.511 P=0.162 P=0.055 P=0.150 | |POLY 6 | P=0.227 P=0.061 P=0.529 P=0.159 P=0.052 P=0.141 | |LOGISTIC REGRESSION| P=0.276 P=0.119 P=0.547 P=0.156 P=0.053 P=0.177 | |COCH-ARM / FISHERS | P=0.290 P=0.107 P=0.500 P=0.181 P=0.056 P=0.170 | |ORDER RESTRICTED | P=0.091 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 2/54 (4%) 2/53 (4%) 1/53 (2%) 8/53 (15%) 4/51 (8%) | |POLY-3 RATE (b) | 5/40.04 2/32.33 2/41.77 1/36.33 8/39.19 4/33.32 | |POLY-3 PERCENT (g) | 12.5% 6.2% 4.8% 2.8% 20.4% 12.0% | |TERMINAL (d) | 2/24 (8%) 0/16 (0%) 1/28 (4%) 1/21 (5%) 5/20 (25%) 3/21 (14%) | |FIRST INCIDENCE | 442 310 514 731 (T) 613 675 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.196 P=0.346N P=0.175N P=0.138N P=0.223 P=0.592N | |POLY 3 | P=0.166 P=0.310N P=0.197N P=0.123N P=0.256 P=0.615N | |POLY 1.5 | P=0.187 P=0.273N P=0.205N P=0.118N P=0.266 P=0.583N | |POLY 6 | P=0.147 P=0.343N P=0.185N P=0.127N P=0.247 P=0.640N | |LOGISTIC REGRESSION| P=0.194 P=0.201N P=0.216N P=0.116N P=0.262 P=0.604N | |COCH-ARM / FISHERS | P=0.219 P=0.211N P=0.219N P=0.103N P=0.278 P=0.525N | |ORDER RESTRICTED | P=0.130 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 16/53 (30%) 17/54 (31%) 25/53 (47%) 13/53 (25%) 10/53 (19%) 10/51 (20%) | |POLY-3 RATE (b) | 16/42.46 17/36.28 25/46.80 13/38.64 10/41.56 10/35.62 | |POLY-3 PERCENT (g) | 37.7% 46.9% 53.4% 33.6% 24.1% 28.1% | |TERMINAL (d) | 7/24 (29%) 6/16 (38%) 12/28 (43%) 6/21 (29%) 4/20 (20%) 5/21 (24%) | |FIRST INCIDENCE | 502 250 429 457 467 432 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.042N* P=0.154 P=0.169 P=0.455N P=0.215N P=0.281N | |POLY 3 | P=0.021N* P=0.271 P=0.094 P=0.441N P=0.127N P=0.252N | |POLY 1.5 | P=0.017N* P=0.349 P=0.077 P=0.412N P=0.124N P=0.211N | |POLY 6 | P=0.030N* P=0.225 P=0.123 P=0.470N P=0.138N P=0.300N | |LOGISTIC REGRESSION| P=0.021N* P=0.334 P=0.060 P=0.397N P=0.131N P=0.209N | |COCH-ARM / FISHERS | P=0.018N* P=0.526 P=0.055 P=0.332N P=0.129N P=0.154N | |ORDER RESTRICTED | P=0.044N* (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/53 (11%) 5/54 (9%) 5/53 (9%) 0/53 (0%) 0/53 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 6/39.13 5/32.17 5/41.12 0/36.33 0/38.33 2/33.11 | |POLY-3 PERCENT (g) | 15.3% 15.5% 12.2% 0.0% 0.0% 6.0% | |TERMINAL (d) | 5/24 (21%) 3/16 (19%) 5/28 (18%) 0/21 (0%) 0/20 (0%) 2/21 (10%) | |FIRST INCIDENCE | 701 438 731 (T) --- --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.112N P=0.504 P=0.389N P=0.025N* P=0.027N* P=0.177N | |POLY 3 | P=0.107N P=0.619 P=0.465N P=0.018N* P=0.015N* P=0.189N | |POLY 1.5 | P=0.104N P=0.589N P=0.478N P=0.018N* P=0.015N* P=0.174N | |POLY 6 | P=0.111N P=0.583 P=0.441N P=0.018N* P=0.016N* P=0.201N | |LOGISTIC REGRESSION| P=0.119N P=0.565 P=0.383N P=0.021N* P=0.019N* P=0.179N | |COCH-ARM / FISHERS | P=0.108N P=0.487N P=0.500N P=0.013N* P=0.013N* P=0.148N | |ORDER RESTRICTED | P=0.024N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 2/54 (4%) 16/53 (30%) 19/53 (36%) 23/53 (43%) 18/51 (35%) | |POLY-3 RATE (b) | 12/40.39 2/31.67 16/43.75 19/40.37 23/44.86 18/40.96 | |POLY-3 PERCENT (g) | 29.7% 6.3% 36.6% 47.1% 51.3% 44.0% | |TERMINAL (d) | 8/24 (33%) 1/16 (6%) 9/28 (32%) 7/21 (33%) 9/20 (45%) 5/21 (24%) | |FIRST INCIDENCE | 507 507 418 507 452 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.012 * P=0.031N* P=0.411 P=0.073 P=0.015 * P=0.074 | |POLY 3 | P=0.043 * P=0.012N* P=0.329 P=0.077 P=0.030 * P=0.129 | |POLY 1.5 | P=0.026 * P=0.008N** P=0.298 P=0.073 P=0.023 * P=0.114 | |POLY 6 | P=0.074 P=0.018N* P=0.381 P=0.097 P=0.046 * P=0.162 | |LOGISTIC REGRESSION| P=0.010 * P=0.015N* P=0.297 P=0.061 P=0.018 * P=0.107 | |COCH-ARM / FISHERS | P=0.014 * P=0.004N** P=0.255 P=0.100 P=0.019 * P=0.114 | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 7/54 (13%) 2/53 (4%) 11/53 (21%) 21/53 (40%) 17/51 (33%) | |POLY-3 RATE (b) | 3/39.88 7/34.47 2/41.30 11/38.71 21/44.01 17/37.33 | |POLY-3 PERCENT (g) | 7.5% 20.3% 4.8% 28.4% 47.7% 45.5% | |TERMINAL (d) | 0/24 (0%) 2/16 (13%) 1/28 (4%) 6/21 (29%) 8/20 (40%) 8/21 (38%) | |FIRST INCIDENCE | 608 393 683 457 452 432 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.082 P=0.442N P=0.017 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.100 P=0.484N P=0.014 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.119 P=0.489N P=0.015 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.086 P=0.475N P=0.014 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.195 P=0.487N P=0.017 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.168 P=0.500N P=0.021 * P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 0/54 (0%) 3/53 (6%) 5/53 (9%) 4/53 (8%) 1/51 (2%) | |POLY-3 RATE (b) | 4/39.26 0/31.01 3/41.36 5/37.11 4/39.10 1/33.11 | |POLY-3 PERCENT (g) | 10.2% 0.0% 7.3% 13.5% 10.2% 3.0% | |TERMINAL (d) | 2/24 (8%) 0/16 (0%) 1/28 (4%) 3/21 (14%) 2/20 (10%) 1/21 (5%) | |FIRST INCIDENCE | 696 --- 700 507 514 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.303N P=0.127N P=0.410N P=0.426 P=0.587 P=0.234N | |POLY 3 | P=0.290N P=0.096N P=0.471N P=0.464 P=0.643 P=0.232N | |POLY 1.5 | P=0.284N P=0.081N P=0.483N P=0.468 P=0.644N P=0.217N | |POLY 6 | P=0.300N P=0.111N P=0.452N P=0.464 P=0.639 P=0.245N | |LOGISTIC REGRESSION| P=0.311N P=0.111N P=0.443N P=0.454 P=0.632 P=0.235N | |COCH-ARM / FISHERS | P=0.284N P=0.057N P=0.500N P=0.500 P=0.642N P=0.194N | |ORDER RESTRICTED | P=0.226N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 20/53 (38%) 22/54 (41%) 13/53 (25%) 18/53 (34%) 16/53 (30%) 14/51 (27%) | |POLY-3 RATE (b) | 20/46.75 22/44.58 13/48.98 18/43.57 16/45.68 14/41.31 | |POLY-3 PERCENT (g) | 42.8% 49.4% 26.5% 41.3% 35.0% 33.9% | |TERMINAL (d) | 5/24 (21%) 2/16 (13%) 0/28 (0%) 3/21 (14%) 3/20 (15%) 1/21 (5%) | |FIRST INCIDENCE | 399 250 429 222 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283N P=0.175 P=0.112N P=0.530N P=0.351N P=0.349N | |POLY 3 | P=0.261N P=0.334 P=0.069N P=0.529N P=0.288N P=0.259N | |POLY 1.5 | P=0.223N P=0.375 P=0.081N P=0.501N P=0.274N P=0.227N | |POLY 6 | P=0.302N P=0.304 P=0.057N P=0.545N P=0.309N P=0.285N | |LOGISTIC REGRESSION| P=0.109N P=0.305N P=0.123N P=0.331N P=0.238N P=0.064N | |COCH-ARM / FISHERS | P=0.180N P=0.452 P=0.104N P=0.420N P=0.269N P=0.182N | |ORDER RESTRICTED | P=0.207N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 44/53 (83%) 39/54 (72%) 44/53 (83%) 47/53 (89%) 48/53 (91%) 45/51 (88%) | |POLY-3 RATE (b) | 44/49.23 39/47.02 44/49.13 47/49.54 48/51.05 45/47.50 | |POLY-3 PERCENT (g) | 89.4% 82.9% 89.6% 94.9% 94.0% 94.7% | |TERMINAL (d) | 20/24 (83%) 12/16 (75%) 25/28 (89%) 20/21 (95%) 20/20 (100%) 21/21 (100%) | |FIRST INCIDENCE | 399 250 429 59 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.135 P=0.188 P=0.286N P=0.199 P=0.171 P=0.146 | |POLY 3 | P=0.085 P=0.249N P=0.627 P=0.238 P=0.298 P=0.252 | |POLY 1.5 | P=0.087 P=0.184N P=0.609N P=0.255 P=0.277 P=0.287 | |POLY 6 | P=0.090 P=0.349N P=0.585 P=0.221 P=0.281 P=0.220 | |LOGISTIC REGRESSION| P=0.075 P=0.250N P=0.517N P=0.175 P=0.190 P=0.188 | |COCH-ARM / FISHERS | P=0.093 P=0.134N P=0.602N P=0.289 P=0.195 P=0.317 | |ORDER RESTRICTED | P=0.077 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/53 (55%) 19/54 (35%) 29/53 (55%) 25/53 (47%) 24/53 (45%) 15/51 (29%) | |POLY-3 RATE (b) | 29/42.75 19/33.52 29/44.08 25/39.82 24/41.75 15/37.02 | |POLY-3 PERCENT (g) | 67.8% 56.7% 65.8% 62.8% 57.5% 40.5% | |TERMINAL (d) | 20/24 (83%) 13/16 (81%) 23/28 (82%) 17/21 (81%) 15/20 (75%) 9/21 (43%) | |FIRST INCIDENCE | 418 479 429 452 452 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016N* P=0.472N P=0.272N P=0.502N P=0.440N P=0.029N* | |POLY 3 | P=0.003N** P=0.201N P=0.511N P=0.392N P=0.205N P=0.008N** | |POLY 1.5 | P=0.005N** P=0.109N P=0.532N P=0.375N P=0.207N P=0.007N** | |POLY 6 | P=0.002N** P=0.338N P=0.475N P=0.393N P=0.200N P=0.007N** | |LOGISTIC REGRESSION| P=0.016N* P=0.272N P=0.468N P=0.407N P=0.225N P=0.019N* | |COCH-ARM / FISHERS | P=0.013N* P=0.033N* P=0.577N P=0.280N P=0.219N P=0.008N** | |ORDER RESTRICTED | P=0.005N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 7/54 (13%) 7/53 (13%) 5/53 (9%) 12/53 (23%) 10/51 (20%) | |POLY-3 RATE (b) | 7/42.63 7/35.48 7/43.63 5/38.94 12/44.53 10/38.36 | |POLY-3 PERCENT (g) | 16.4% 19.7% 16.0% 12.8% 27.0% 26.1% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 1/20 (5%) 1/21 (5%) | |FIRST INCIDENCE | 442 261 429 263 341 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.085 P=0.437 P=0.561N P=0.443N P=0.160 P=0.192 | |POLY 3 | P=0.087 P=0.467 P=0.597N P=0.443N P=0.174 P=0.213 | |POLY 1.5 | P=0.090 P=0.522 P=0.602N P=0.424N P=0.170 P=0.229 | |POLY 6 | P=0.085 P=0.419 P=0.582N P=0.463N P=0.171 P=0.204 | |LOGISTIC REGRESSION| P=0.114 P=0.360N P=0.553 P=0.274N P=0.142 P=0.388 | |COCH-ARM / FISHERS | P=0.096 P=0.598N P=0.612N P=0.380N P=0.156 P=0.269 | |ORDER RESTRICTED | P=0.206 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 1/54 (2%) 2/53 (4%) 5/53 (9%) 5/53 (9%) 9/51 (18%) | |POLY-3 RATE (b) | 1/39.56 1/31.63 2/41.86 5/37.57 5/38.99 9/34.75 | |POLY-3 PERCENT (g) | 2.5% 3.2% 4.8% 13.3% 12.8% 25.9% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 2/21 (10%) 3/20 (15%) 4/21 (19%) | |FIRST INCIDENCE | 557 528 527 322 541 501 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.698 P=0.506 P=0.093 P=0.083 P=0.006 ** | |POLY 3 | P<0.001 ** P=0.709 P=0.520 P=0.088 P=0.096 P=0.003 ** | |POLY 1.5 | P<0.001 ** P=0.728 P=0.512 P=0.090 P=0.099 P=0.004 ** | |POLY 6 | P<0.001 ** P=0.691 P=0.533 P=0.086 P=0.091 P=0.003 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.717N P=0.472 P=0.104 P=0.101 P=0.005 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.748N P=0.500 P=0.103 P=0.103 P=0.007 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 2/54 (4%) 2/53 (4%) 3/53 (6%) 5/53 (9%) 2/51 (4%) | |POLY-3 RATE (b) | 3/39.38 2/31.56 2/41.12 3/36.49 5/39.40 2/33.11 | |POLY-3 PERCENT (g) | 7.6% 6.3% 4.9% 8.2% 12.7% 6.0% | |TERMINAL (d) | 1/24 (4%) 1/16 (6%) 2/28 (7%) 2/21 (10%) 3/20 (15%) 2/21 (10%) | |FIRST INCIDENCE | 664 557 731 (T) 691 452 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.577 P=0.663N P=0.426N P=0.612 P=0.308 P=0.568N | |POLY 3 | P=0.548 P=0.600N P=0.480N P=0.628 P=0.355 P=0.579N | |POLY 1.5 | P=0.572 P=0.564N P=0.487N P=0.635 P=0.358 P=0.557N | |POLY 6 | P=0.522 P=0.631N P=0.468N P=0.624 P=0.349 P=0.597N | |LOGISTIC REGRESSION| P=0.569 P=0.605N P=0.454N P=0.629 P=0.349 P=0.587N | |COCH-ARM / FISHERS | P=0.585N P=0.491N P=0.500N P=0.661N P=0.358 P=0.518N | |ORDER RESTRICTED | P=0.540 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/54 (2%) 2/53 (4%) 2/53 (4%) 2/53 (4%) 3/51 (6%) | |POLY-3 RATE (b) | 2/39.48 1/31.12 2/41.12 2/36.55 2/38.33 3/33.81 | |POLY-3 PERCENT (g) | 5.1% 3.2% 4.9% 5.5% 5.2% 8.9% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 2/28 (7%) 1/21 (5%) 2/20 (10%) 2/21 (10%) | |FIRST INCIDENCE | 590 701 731 (T) 675 731 (T) 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.251 P=0.617N P=0.655N P=0.662 P=0.642 P=0.424 | |POLY 3 | P=0.258 P=0.582N P=0.680N P=0.667 P=0.685 P=0.429 | |POLY 1.5 | P=0.266 P=0.552N P=0.685N P=0.672 P=0.690 P=0.447 | |POLY 6 | P=0.249 P=0.608N P=0.671N P=0.665 P=0.677 P=0.416 | |LOGISTIC REGRESSION| P=0.239 P=0.577N P=0.673N P=0.672 P=0.686 P=0.452 | |COCH-ARM / FISHERS | P=0.271 P=0.493N P=0.691N P=0.691N P=0.691N P=0.482 | |ORDER RESTRICTED | P=0.351 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 3/54 (6%) 2/53 (4%) 14/53 (26%) 10/53 (19%) 17/51 (33%) | |POLY-3 RATE (b) | 5/39.38 3/31.01 2/41.68 14/37.17 10/40.51 17/35.92 | |POLY-3 PERCENT (g) | 12.7% 9.7% 4.8% 37.7% 24.7% 47.3% | |TERMINAL (d) | 3/24 (13%) 3/16 (19%) 1/28 (4%) 12/21 (57%) 5/20 (25%) 12/21 (57%) | |FIRST INCIDENCE | 664 731 (T) 553 530 502 432 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.587N P=0.173N P=0.008 ** P=0.099 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.493N P=0.191N P=0.009 ** P=0.135 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.440N P=0.201N P=0.011 * P=0.134 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.543N P=0.177N P=0.007 ** P=0.138 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.565N P=0.193N P=0.009 ** P=0.123 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.347N P=0.219N P=0.020 * P=0.132 P=0.003 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Centrilobular | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 10/54 (19%) 4/53 (8%) 2/53 (4%) 2/53 (4%) 5/51 (10%) | |POLY-3 RATE (b) | 2/39.58 10/37.48 4/42.53 2/37.17 2/39.78 5/36.11 | |POLY-3 PERCENT (g) | 5.1% 26.7% 9.4% 5.4% 5.0% 13.9% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 1/28 (4%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 551 352 514 530 383 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.526 P=0.007 ** P=0.368 P=0.659 P=0.659 P=0.172 | |POLY 3 | P=0.528 P=0.009 ** P=0.370 P=0.672 P=0.693N P=0.177 | |POLY 1.5 | P=0.546 P=0.010 * P=0.357 P=0.675 P=0.692N P=0.186 | |POLY 6 | P=0.514 P=0.009 ** P=0.391 P=0.674 P=0.695 P=0.174 | |LOGISTIC REGRESSION| P=0.553N P=0.045 * P=0.322 P=0.694N P=0.688 P=0.299 | |COCH-ARM / FISHERS | P=0.567 P=0.015 * P=0.339 P=0.691N P=0.691N P=0.203 | |ORDER RESTRICTED | P=0.184 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 5/54 (9%) 5/53 (9%) 24/53 (45%) 39/53 (74%) 41/51 (80%) | |POLY-3 RATE (b) | 0/39.01 5/32.97 5/42.57 24/40.31 39/44.99 41/46.12 | |POLY-3 PERCENT (g) | 0.0% 15.2% 11.8% 59.5% 86.7% 88.9% | |TERMINAL (d) | 0/24 (0%) 2/16 (13%) 3/28 (11%) 15/21 (71%) 20/20 (100%) 19/21 (91%) | |FIRST INCIDENCE | --- 360 429 443 452 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.016 * P=0.046 * P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.018 * P=0.038 * P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.022 * P=0.035 * P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.015 * P=0.043 * P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.035 * P=0.030 * P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.030 * P=0.028 * P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 0/53 (0%) 4/51 (8%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 1/36.49 0/38.33 4/33.34 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.7% 0.0% 12.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 3/21 (14%) | |FIRST INCIDENCE | --- --- --- 691 --- 668 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.485 (e) P=0.047 * | |POLY 3 | P<0.001 ** (e) (e) P=0.487 (e) P=0.041 * | |POLY 1.5 | P<0.001 ** (e) (e) P=0.489 (e) P=0.046 * | |POLY 6 | P<0.001 ** (e) (e) P=0.487 (e) P=0.039 * | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.486 (e) P=0.040 * | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.500 (e) P=0.054 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Liver: Serosa | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 2/41.61 0/36.33 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- 656 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.461N (e) P=0.288 (e) (e) (e) | |POLY 3 | P=0.394N (e) P=0.251 (e) (e) (e) | |POLY 1.5 | P=0.407N (e) P=0.246 (e) (e) (e) | |POLY 6 | P=0.380N (e) P=0.262 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.443N (e) P=0.242 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.437N (e) P=0.248 (e) (e) (e) | |ORDER RESTRICTED | P=0.390N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/52 (87%) 40/54 (74%) 40/53 (75%) 40/53 (75%) 27/53 (51%) 28/51 (55%) | |POLY-3 RATE (b) | 45/48.19 40/46.36 40/48.58 40/44.56 27/44.57 28/38.75 | |POLY-3 PERCENT (g) | 93.4% 86.3% 82.4% 89.8% 60.6% 72.3% | |TERMINAL (d) | 23/24 (96%) 13/16 (81%) 23/28 (82%) 20/21 (95%) 12/20 (60%) 16/21 (76%) | |FIRST INCIDENCE | 410 250 418 360 341 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015N* P=0.151 P=0.087N P=0.505N P=0.021N* P=0.058N | |POLY 3 | P<0.001N** P=0.179N P=0.066N P=0.380N P<0.001N** P=0.002N** | |POLY 1.5 | P<0.001N** P=0.135N P=0.069N P=0.265N P<0.001N** P<0.001N** | |POLY 6 | P=0.006N** P=0.223N P=0.075N P=0.551N P<0.001N** P=0.014N* | |LOGISTIC REGRESSION| P<0.001N** P=0.316N P=0.078N P=0.293N P<0.001N** P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=0.085N P=0.116N P=0.116N P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lung | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/52 (12%) 7/54 (13%) 2/53 (4%) 6/53 (11%) 7/53 (13%) 9/51 (18%) | |POLY-3 RATE (b) | 6/40.63 7/34.41 2/41.12 6/37.04 7/40.36 9/35.33 | |POLY-3 PERCENT (g) | 14.8% 20.3% 4.9% 16.2% 17.4% 25.5% | |TERMINAL (d) | 3/24 (13%) 1/16 (6%) 2/28 (7%) 5/21 (24%) 0/20 (0%) 5/21 (24%) | |FIRST INCIDENCE | 410 360 731 (T) 486 467 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.069 P=0.297 P=0.113N P=0.534 P=0.459 P=0.186 | |POLY 3 | P=0.055 P=0.371 P=0.126N P=0.556 P=0.495 P=0.187 | |POLY 1.5 | P=0.064 P=0.418 P=0.127N P=0.576 P=0.503 P=0.215 | |POLY 6 | P=0.049 * P=0.343 P=0.123N P=0.538 P=0.491 P=0.173 | |LOGISTIC REGRESSION| P=0.076 P=0.567 P=0.128N P=0.600 P=0.517 P=0.247 | |COCH-ARM / FISHERS | P=0.082 P=0.529 P=0.129N P=0.606N P=0.515 P=0.275 | |ORDER RESTRICTED | P=0.109 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 20/52 (38%) 21/54 (39%) 16/53 (30%) 11/53 (21%) 9/53 (17%) 6/51 (12%) | |POLY-3 RATE (b) | 20/41.45 21/36.66 16/41.75 11/37.11 9/38.86 6/34.40 | |POLY-3 PERCENT (g) | 48.3% 57.3% 38.3% 29.6% 23.2% 17.4% | |TERMINAL (d) | 13/24 (54%) 10/16 (63%) 12/28 (43%) 8/21 (38%) 7/20 (35%) 4/21 (19%) | |FIRST INCIDENCE | 555 250 656 613 621 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.093 P=0.132N P=0.086N P=0.035N* P=0.007N** | |POLY 3 | P<0.001N** P=0.274 P=0.237N P=0.065N P=0.013N* P=0.003N** | |POLY 1.5 | P<0.001N** P=0.364 P=0.235N P=0.056N P=0.011N* P=0.002N** | |POLY 6 | P<0.001N** P=0.219 P=0.234N P=0.077N P=0.018N* P=0.005N** | |LOGISTIC REGRESSION| P<0.001N** P=0.223 P=0.165N P=0.056N P=0.013N* P=0.005N** | |COCH-ARM / FISHERS | P<0.001N** P=0.561 P=0.246N P=0.038N* P=0.012N* P=0.002N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/51 (73%) 36/52 (69%) 30/53 (57%) 33/51 (65%) 37/53 (70%) 38/51 (75%) | |POLY-3 RATE (b) | 37/46.48 36/43.85 30/45.65 33/43.53 37/46.61 38/43.34 | |POLY-3 PERCENT (g) | 79.6% 82.1% 65.7% 75.8% 79.4% 87.7% | |TERMINAL (d) | 18/24 (75%) 14/16 (88%) 20/28 (71%) 16/21 (76%) 16/20 (80%) 19/21 (91%) | |FIRST INCIDENCE | 211 250 429 59 360 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.094 P=0.088 P=0.054N P=0.523N P=0.365 P=0.175 | |POLY 3 | P=0.049 * P=0.486 P=0.088N P=0.423N P=0.598N P=0.204 | |POLY 1.5 | P=0.069 P=0.565 P=0.073N P=0.362N P=0.543N P=0.288 | |POLY 6 | P=0.040 * P=0.405 P=0.120N P=0.507N P=0.568 P=0.147 | |LOGISTIC REGRESSION| P=0.113 P=0.579 P=0.053N P=0.325N P=0.485N P=0.310 | |COCH-ARM / FISHERS | P=0.147 P=0.439N P=0.067N P=0.261N P=0.464N P=0.500 | |ORDER RESTRICTED | P=0.104 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 1/52 (2%) 2/53 (4%) 1/51 (2%) 3/53 (6%) 1/51 (2%) | |POLY-3 RATE (b) | 1/38.11 1/31.26 2/41.12 1/35.02 3/38.75 1/33.11 | |POLY-3 PERCENT (g) | 2.6% 3.2% 4.9% 2.9% 7.7% 3.0% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 2/28 (7%) 1/21 (5%) 1/20 (5%) 1/21 (5%) | |FIRST INCIDENCE | 731 (T) 250 731 (T) 731 (T) 647 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.610 P=0.721 P=0.554 P=0.733 P=0.279 P=0.733 | |POLY 3 | P=0.590 P=0.715 P=0.527 P=0.742 P=0.310 P=0.729 | |POLY 1.5 | P=0.608 P=0.733 P=0.522 P=0.746 P=0.315 P=0.740 | |POLY 6 | P=0.573 P=0.699 P=0.536 P=0.742 P=0.305 P=0.720 | |LOGISTIC REGRESSION| P=0.617 P=0.668N P=0.554 P=0.733 P=0.298 P=0.733 | |COCH-ARM / FISHERS | P=0.617N P=0.748N P=0.515 P=0.752N P=0.324 P=0.752N | |ORDER RESTRICTED | P=0.493 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/3 (0%) 1/3 (33%) 2/3 (67%) 0/2 (0%) 0/5 (0%) 2/6 (33%) | |POLY-3 RATE (b) | 0/0.78 1/1.49 2/2.38 0/1.48 0/3.41 2/4.77 | |POLY-3 PERCENT (g) | 0.0% 67.2% 84.0% 0.0% 0.0% 41.9% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) 1/3 (33%) | |FIRST INCIDENCE | --- 507 501 --- --- 438 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.458 P=0.455 P=0.265 (e) (e) P=0.468 | |POLY 3 | P=0.637N P=0.669 P=0.509 (e) (e) P=0.641 | |POLY 1.5 | P=0.685 P=0.562 P=0.298 (e) (e) P=0.538 | |POLY 6 | P=0.576N P=0.932 P=0.931 (e) (e) P=0.734 | |LOGISTIC REGRESSION| P=0.554 P=0.521 P=0.469 (e) (e) P=0.436 | |COCH-ARM / FISHERS | P=0.538 P=0.500 P=0.200 (e) (e) P=0.417 | |ORDER RESTRICTED | P=0.569N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/2 (0%) 1/5 (20%) 2/6 (33%) | |POLY-3 RATE (b) | 0/0.78 0/0.82 0/1.59 0/1.48 1/4.31 2/3.98 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 23.2% 50.2% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) 2/3 (67%) | |FIRST INCIDENCE | --- --- --- --- 341 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.295 (e) (e) (e) P=0.504 P=1.000N | |POLY 3 | P=0.160 (e) (e) (e) P=0.741 P=0.626 | |POLY 1.5 | P=0.130 (e) (e) (e) P=0.691 P=0.513 | |POLY 6 | P=0.205 (e) (e) (e) P=0.778 P=0.758 | |LOGISTIC REGRESSION| P=0.095 (e) (e) (e) (e) P=1.000N | |COCH-ARM / FISHERS | P=0.083 (e) (e) (e) P=0.625 P=0.417 | |ORDER RESTRICTED | P=0.488 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/3 (100%) 0/3 (0%) 0/3 (0%) 0/2 (0%) 0/5 (0%) 0/6 (0%) | |POLY-3 RATE (b) | 3/3.00 0/0.82 0/1.59 0/1.48 0/3.41 0/3.98 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) 0/3 (0%) | |FIRST INCIDENCE | 399 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.268N P=0.170N P=0.112N P=0.131N P=0.126N P=0.151N | |POLY 3 | P<0.001N** P=0.096N P=0.002N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P=1.000N P=0.165N P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.206N P=0.051N P=0.162N (e) P=0.042N* P=0.062N | |COCH-ARM / FISHERS | P=0.126N P=0.050N P=0.050N P=0.100N P=0.018N* P=0.012N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/2 (0%) 0/5 (0%) 2/6 (33%) | |POLY-3 RATE (b) | 0/0.78 0/0.82 0/1.59 0/1.48 0/3.41 2/5.22 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 38.4% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) 0/3 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 514 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006 ** (e) (e) (e) (e) P=0.184 | |POLY 3 | P=0.106 (e) (e) (e) (e) P=0.646 | |POLY 1.5 | P=0.072 (e) (e) (e) (e) P=0.546 | |POLY 6 | P=0.168 (e) (e) (e) (e) P=0.724 | |LOGISTIC REGRESSION| P=0.026 * (e) (e) (e) (e) P=0.272 | |COCH-ARM / FISHERS | P=0.044 * (e) (e) (e) (e) P=0.417 | |ORDER RESTRICTED | P=0.516 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/3 (67%) 1/3 (33%) 0/3 (0%) 0/2 (0%) 0/5 (0%) 0/6 (0%) | |POLY-3 RATE (b) | 2/2.43 1/1.45 0/1.59 0/1.48 0/3.41 0/3.98 | |POLY-3 PERCENT (g) | 82.4% 69.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) 0/3 (0%) | |FIRST INCIDENCE | 399 528 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.269N P=0.572N P=0.233N P=0.253N P=0.240N P=0.261N | |POLY 3 | P=0.043N* P=0.854N P=0.229N P=0.241N P=0.050N P=0.027N* | |POLY 1.5 | P=0.060N P=0.682N P=0.186N P=0.255N P=0.052N P=0.027N* | |POLY 6 | P=0.024N* P=0.998N P=0.340N P=0.260N P=0.040N* P=0.029N* | |LOGISTIC REGRESSION| P=0.213N P=0.507N (e) (e) P=0.188N (e) | |COCH-ARM / FISHERS | P=0.127N P=0.500N P=0.200N P=0.300N P=0.107N P=0.083N | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Lymph Node: Renal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/2 (0%) 0/5 (0%) 2/6 (33%) | |POLY-3 RATE (b) | 0/0.78 0/0.82 0/1.59 0/1.48 0/3.41 2/3.98 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 50.2% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/2 (0%) 2/3 (67%) | |FIRST INCIDENCE | --- --- --- --- --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.309 (e) (e) (e) (e) P=1.000N | |POLY 3 | P=0.058 (e) (e) (e) (e) P=0.626 | |POLY 1.5 | P=0.052 (e) (e) (e) (e) P=0.513 | |POLY 6 | P=0.068 (e) (e) (e) (e) P=0.758 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=1.000N | |COCH-ARM / FISHERS | P=0.044 * (e) (e) (e) (e) P=0.417 | |ORDER RESTRICTED | P=0.397 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/54 (2%) 0/53 (0%) 2/53 (4%) 1/53 (2%) 3/51 (6%) | |POLY-3 RATE (b) | 2/39.84 1/31.85 0/41.12 2/36.33 1/38.43 3/33.11 | |POLY-3 PERCENT (g) | 5.0% 3.1% 0.0% 5.5% 2.6% 9.1% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 0/28 (0%) 2/21 (10%) 0/20 (0%) 3/21 (14%) | |FIRST INCIDENCE | 399 393 --- 731 (T) 706 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.155 P=0.587N P=0.221N P=0.649 P=0.525N P=0.440 | |POLY 3 | P=0.136 P=0.577N P=0.230N P=0.661 P=0.513N P=0.416 | |POLY 1.5 | P=0.145 P=0.549N P=0.233N P=0.668 P=0.507N P=0.439 | |POLY 6 | P=0.126 P=0.601N P=0.223N P=0.657 P=0.519N P=0.398 | |LOGISTIC REGRESSION| P=0.147 P=0.366N P=0.265N P=0.684 P=0.500N P=0.441 | |COCH-ARM / FISHERS | P=0.157 P=0.493N P=0.248N P=0.691N P=0.500N P=0.482 | |ORDER RESTRICTED | P=0.145 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/53 (42%) 23/54 (43%) 32/53 (60%) 27/53 (51%) 32/53 (60%) 22/51 (43%) | |POLY-3 RATE (b) | 22/43.38 23/37.94 32/46.73 27/43.99 32/45.28 22/36.86 | |POLY-3 PERCENT (g) | 50.7% 60.6% 68.5% 61.4% 70.7% 59.7% | |TERMINAL (d) | 12/24 (50%) 9/16 (56%) 19/28 (68%) 13/21 (62%) 12/20 (60%) 13/21 (62%) | |FIRST INCIDENCE | 211 250 429 59 467 432 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.507N P=0.105 P=0.168 P=0.142 P=0.038 * P=0.319 | |POLY 3 | P=0.467 P=0.239 P=0.056 P=0.204 P=0.034 * P=0.271 | |POLY 1.5 | P=0.526N P=0.320 P=0.045 * P=0.193 P=0.032 * P=0.348 | |POLY 6 | P=0.372 P=0.201 P=0.081 P=0.230 P=0.042 * P=0.220 | |LOGISTIC REGRESSION| P=0.435N P=0.299 P=0.049 * P=0.189 P=0.035 * P=0.331 | |COCH-ARM / FISHERS | P=0.376N P=0.533 P=0.040 * P=0.218 P=0.040 * P=0.512 | |ORDER RESTRICTED | P=0.126 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/54 (4%) 2/53 (4%) 3/53 (6%) 0/53 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 0/39.01 2/32.41 2/41.23 3/36.74 0/38.33 1/33.11 | |POLY-3 PERCENT (g) | 0.0% 6.2% 4.9% 8.2% 0.0% 3.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 1/28 (4%) 2/21 (10%) 0/20 (0%) 1/21 (5%) | |FIRST INCIDENCE | --- 393 701 613 --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.433N P=0.193 P=0.277 P=0.104 (e) P=0.473 | |POLY 3 | P=0.443N P=0.198 P=0.249 P=0.107 (e) P=0.467 | |POLY 1.5 | P=0.432N P=0.211 P=0.244 P=0.109 (e) P=0.476 | |POLY 6 | P=0.453N P=0.188 P=0.258 P=0.107 (e) P=0.461 | |LOGISTIC REGRESSION| P=0.424N P=0.342 P=0.262 P=0.108 (e) P=0.473 | |COCH-ARM / FISHERS | P=0.416N P=0.252 P=0.248 P=0.121 (e) P=0.490 | |ORDER RESTRICTED | P=0.291 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 6/54 (11%) 3/53 (6%) 6/53 (11%) 6/53 (11%) 3/51 (6%) | |POLY-3 RATE (b) | 1/39.01 6/33.97 3/41.75 6/38.92 6/38.96 3/33.11 | |POLY-3 PERCENT (g) | 2.6% 17.7% 7.2% 15.4% 15.4% 9.1% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 2/28 (7%) 2/21 (10%) 3/20 (15%) 3/21 (14%) | |FIRST INCIDENCE | 731 (T) 310 522 360 579 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.546N P=0.032 * P=0.346 P=0.049 * P=0.044 * P=0.255 | |POLY 3 | P=0.532 P=0.035 * P=0.329 P=0.053 P=0.053 P=0.247 | |POLY 1.5 | P=0.574 P=0.041 * P=0.320 P=0.052 P=0.055 P=0.262 | |POLY 6 | P=0.490 P=0.031 * P=0.345 P=0.057 P=0.051 P=0.237 | |LOGISTIC REGRESSION| P=0.523N P=0.075 P=0.318 P=0.064 P=0.051 P=0.255 | |COCH-ARM / FISHERS | P=0.516N P=0.059 P=0.309 P=0.056 P=0.056 P=0.294 | |ORDER RESTRICTED | P=0.121 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Nose: Goblet Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 1/53 (2%) 2/53 (4%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 2/41.73 1/36.33 2/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 2.8% 5.2% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 1/28 (4%) 1/21 (5%) 2/20 (10%) 0/21 (0%) | |FIRST INCIDENCE | --- --- 530 731 (T) 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.497N (e) P=0.249 P=0.473 P=0.198 (e) | |POLY 3 | P=0.489N (e) P=0.252 P=0.486 P=0.232 (e) | |POLY 1.5 | P=0.485N (e) P=0.246 P=0.488 P=0.235 (e) | |POLY 6 | P=0.491N (e) P=0.262 P=0.485 P=0.229 (e) | |LOGISTIC REGRESSION| P=0.503N (e) P=0.231 P=0.473 P=0.198 (e) | |COCH-ARM / FISHERS | P=0.484N (e) P=0.248 P=0.500 P=0.248 (e) | |ORDER RESTRICTED | P=0.313 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 2/39.01 0/31.01 0/41.12 0/36.33 0/38.33 2/33.11 | |POLY-3 PERCENT (g) | 5.1% 0.0% 0.0% 0.0% 0.0% 6.0% | |TERMINAL (d) | 2/24 (8%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 2/21 (10%) | |FIRST INCIDENCE | 731 (T) --- --- --- --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.151 P=0.330N P=0.204N P=0.267N P=0.278N P=0.648 | |POLY 3 | P=0.157 P=0.291N P=0.225N P=0.253N P=0.240N P=0.635 | |POLY 1.5 | P=0.158 P=0.271N P=0.230N P=0.250N P=0.238N P=0.650 | |POLY 6 | P=0.153 P=0.310N P=0.217N P=0.253N P=0.243N P=0.624 | |LOGISTIC REGRESSION| P=0.151 (e) (e) (e) (e) P=0.648 | |COCH-ARM / FISHERS | P=0.156 P=0.243N P=0.248N P=0.248N P=0.248N P=0.676 | |ORDER RESTRICTED | P=0.095 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 0/53 (0%) 1/53 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 2/42.71 0/36.33 1/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.7% 0.0% 2.6% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 1/20 (5%) 0/21 (0%) | |FIRST INCIDENCE | --- --- 429 --- 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.508N (e) P=0.252 (e) P=0.464 (e) | |POLY 3 | P=0.489N (e) P=0.258 (e) P=0.497 (e) | |POLY 1.5 | P=0.494N (e) P=0.250 (e) P=0.499 (e) | |POLY 6 | P=0.483N (e) P=0.269 (e) P=0.494 (e) | |LOGISTIC REGRESSION| P=0.497N (e) P=0.099 (e) P=0.464 (e) | |COCH-ARM / FISHERS | P=0.510N (e) P=0.248 (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.432 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Nose: Septum | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 3/54 (6%) 5/53 (9%) 3/53 (6%) 7/53 (13%) 6/51 (12%) | |POLY-3 RATE (b) | 4/40.77 3/32.94 5/41.91 3/38.34 7/39.64 6/34.73 | |POLY-3 PERCENT (g) | 9.8% 9.1% 11.9% 7.8% 17.7% 17.3% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 3/28 (11%) 0/21 (0%) 3/20 (15%) 2/21 (10%) | |FIRST INCIDENCE | 211 310 501 360 579 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.147 P=0.618N P=0.562 P=0.534N P=0.231 P=0.283 | |POLY 3 | P=0.129 P=0.615N P=0.517 P=0.534N P=0.241 P=0.270 | |POLY 1.5 | P=0.141 P=0.574N P=0.509 P=0.530N P=0.248 P=0.293 | |POLY 6 | P=0.121 P=0.652N P=0.535 P=0.533N P=0.235 P=0.257 | |LOGISTIC REGRESSION| P=0.165 P=0.289N P=0.474 P=0.380N P=0.263 P=0.376 | |COCH-ARM / FISHERS | P=0.160 P=0.489N P=0.500 P=0.500N P=0.263 P=0.346 | |ORDER RESTRICTED | P=0.261 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Nose: Turbinate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/53 (15%) 3/54 (6%) 5/53 (9%) 9/53 (17%) 10/53 (19%) 10/51 (20%) | |POLY-3 RATE (b) | 8/42.11 3/33.77 5/41.91 9/39.90 10/40.29 10/36.05 | |POLY-3 PERCENT (g) | 19.0% 8.9% 11.9% 22.6% 24.8% 27.7% | |TERMINAL (d) | 2/24 (8%) 0/16 (0%) 4/28 (14%) 3/21 (14%) 4/20 (20%) 4/21 (19%) | |FIRST INCIDENCE | 211 261 429 360 360 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.065 P=0.197N P=0.224N P=0.424 P=0.345 P=0.293 | |POLY 3 | P=0.049 * P=0.181N P=0.275N P=0.450 P=0.353 P=0.258 | |POLY 1.5 | P=0.055 P=0.146N P=0.277N P=0.452 P=0.372 P=0.291 | |POLY 6 | P=0.044 * P=0.221N P=0.270N P=0.458 P=0.332 P=0.234 | |LOGISTIC REGRESSION| P=0.070 P=0.017N* P=0.306N P=0.560 P=0.399 P=0.402 | |COCH-ARM / FISHERS | P=0.066 P=0.095N P=0.278N P=0.500 P=0.398 P=0.364 | |ORDER RESTRICTED | P=0.087 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/21 (100%) 10/12 (83%) 16/16 (100%) 11/12 (92%) 16/16 (100%) 25/25 (100%) | |POLY-3 RATE (b) | 21/21.00 10/11.60 16/16.00 11/12.00 16/16.00 25/25.00 | |POLY-3 PERCENT (g) | 100.0% 86.2% 100.0% 91.7% 100.0% 100.0% | |TERMINAL (d) | 10/10 (100%) 2/3 (67%) 10/10 (100%) 7/8 (88%) 8/8 (100%) 12/12 (100%) | |FIRST INCIDENCE | 211 310 418 528 383 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.024 * P=0.405N (e) P=0.056N (e) (e) | |POLY 3 | P=0.270 P=0.161N (e) P=0.387N (e) (e) | |POLY 1.5 | P=0.248 P=0.135N (e) P=0.387N (e) (e) | |POLY 6 | P=0.306 P=0.220N (e) P=0.387N (e) (e) | |LOGISTIC REGRESSION| P=0.241 P=0.073N (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.233 P=0.125N (e) P=0.364N (e) (e) | |ORDER RESTRICTED | P=0.171 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 47/53 (89%) 43/53 (81%) 42/53 (79%) 38/53 (72%) 44/53 (83%) 39/50 (78%) | |POLY-3 RATE (b) | 47/51.19 43/47.35 42/49.67 38/45.27 44/48.54 39/46.48 | |POLY-3 PERCENT (g) | 91.8% 90.8% 84.6% 83.9% 90.7% 83.9% | |TERMINAL (d) | 22/24 (92%) 14/16 (88%) 22/28 (79%) 18/21 (86%) 18/20 (90%) 15/21 (71%) | |FIRST INCIDENCE | 211 250 418 263 383 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.526 P=0.122 P=0.102N P=0.288N P=0.498 P=0.502N | |POLY 3 | P=0.254N P=0.578N P=0.188N P=0.164N P=0.567N P=0.171N | |POLY 1.5 | P=0.297N P=0.480N P=0.170N P=0.101N P=0.461N P=0.166N | |POLY 6 | P=0.221N P=0.598N P=0.198N P=0.242N P=0.649N P=0.166N | |LOGISTIC REGRESSION| P=0.400N P=0.364N P=0.132N P=0.046N* P=0.285N P=0.128N | |COCH-ARM / FISHERS | P=0.370N P=0.208N P=0.145N P=0.025N* P=0.289N P=0.116N | |ORDER RESTRICTED | P=0.164N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/53 (26%) 7/53 (13%) 17/53 (32%) 17/53 (32%) 16/53 (30%) 17/50 (34%) | |POLY-3 RATE (b) | 14/41.40 7/32.97 17/43.79 17/39.33 16/40.30 17/36.24 | |POLY-3 PERCENT (g) | 33.8% 21.2% 38.8% 43.2% 39.7% 46.9% | |TERMINAL (d) | 6/24 (25%) 3/16 (19%) 11/28 (39%) 9/21 (43%) 9/20 (45%) 12/21 (57%) | |FIRST INCIDENCE | 557 261 443 360 479 443 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.097 P=0.288N P=0.502 P=0.240 P=0.299 P=0.175 | |POLY 3 | P=0.090 P=0.171N P=0.398 P=0.256 P=0.370 P=0.165 | |POLY 1.5 | P=0.102 P=0.127N P=0.376 P=0.270 P=0.396 P=0.199 | |POLY 6 | P=0.073 P=0.228N P=0.425 P=0.248 P=0.327 P=0.133 | |LOGISTIC REGRESSION| P=0.080 P=0.146N P=0.380 P=0.255 P=0.386 P=0.166 | |COCH-ARM / FISHERS | P=0.114 P=0.071N P=0.335 P=0.335 P=0.415 P=0.266 | |ORDER RESTRICTED | P=0.062 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Ovary | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 2/53 (4%) 1/53 (2%) 5/53 (9%) 7/50 (14%) | |POLY-3 RATE (b) | 0/39.01 0/30.84 2/41.12 1/36.55 5/38.97 7/33.89 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.9% 2.7% 12.8% 20.7% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 2/28 (7%) 0/21 (0%) 2/20 (10%) 4/21 (19%) | |FIRST INCIDENCE | --- --- 731 (T) 675 617 501 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.272 P=0.507 P=0.031 * P=0.006 ** | |POLY 3 | P<0.001 ** (e) P=0.249 P=0.487 P=0.029 * P=0.004 ** | |POLY 1.5 | P<0.001 ** (e) P=0.244 P=0.489 P=0.030 * P=0.004 ** | |POLY 6 | P<0.001 ** (e) P=0.256 P=0.487 P=0.029 * P=0.003 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.272 P=0.488 P=0.030 * P=0.004 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.248 P=0.500 P=0.028 * P=0.005 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Oviduct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/38 (3%) 2/44 (5%) 1/35 (3%) 1/39 (3%) 0/45 (0%) | |POLY-3 RATE (b) | 0/37.44 1/22.64 2/34.18 1/23.85 1/28.49 0/29.26 | |POLY-3 PERCENT (g) | 0.0% 4.4% 5.9% 4.2% 3.5% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/13 (0%) 2/22 (9%) 1/12 (8%) 1/16 (6%) 0/19 (0%) | |FIRST INCIDENCE | --- 557 731 (T) 731 (T) 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.315N P=0.446 P=0.218 P=0.362 P=0.419 (e) | |POLY 3 | P=0.328N P=0.402 P=0.216 P=0.410 P=0.445 (e) | |POLY 1.5 | P=0.318N P=0.414 P=0.214 P=0.415 P=0.448 (e) | |POLY 6 | P=0.337N P=0.396 P=0.220 P=0.404 P=0.441 (e) | |LOGISTIC REGRESSION| P=0.322N P=0.486 P=0.218 P=0.362 P=0.419 (e) | |COCH-ARM / FISHERS | P=0.303N P=0.432 P=0.216 P=0.412 P=0.438 (e) | |ORDER RESTRICTED | P=0.319 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Oviduct | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/38 (0%) 2/44 (5%) 1/35 (3%) 5/39 (13%) 7/45 (16%) | |POLY-3 RATE (b) | 1/37.44 0/22.08 2/34.18 1/24.06 5/29.02 7/30.90 | |POLY-3 PERCENT (g) | 2.7% 0.0% 5.9% 4.2% 17.2% 22.7% | |TERMINAL (d) | 1/24 (4%) 0/13 (0%) 2/22 (9%) 0/12 (0%) 3/16 (19%) 3/19 (16%) | |FIRST INCIDENCE | 731 (T) --- 731 (T) 675 617 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.622N P=0.469 P=0.686 P=0.053 P=0.019 * | |POLY 3 | P<0.001 ** P=0.602N P=0.468 P=0.659 P=0.049 * P=0.012 * | |POLY 1.5 | P<0.001 ** P=0.588N P=0.464 P=0.664 P=0.051 P=0.014 * | |POLY 6 | P<0.001 ** P=0.611N P=0.475 P=0.652 P=0.047 * P=0.012 * | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.469 P=0.651 P=0.047 * P=0.015 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.568N P=0.452 P=0.657 P=0.055 P=0.020 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/53 (2%) 1/53 (2%) 0/53 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 2/39.01 0/31.01 1/41.12 1/36.33 0/38.33 2/33.11 | |POLY-3 PERCENT (g) | 5.1% 0.0% 2.4% 2.8% 0.0% 6.0% | |TERMINAL (d) | 2/24 (8%) 0/16 (0%) 1/28 (4%) 1/21 (5%) 0/20 (0%) 2/21 (10%) | |FIRST INCIDENCE | 731 (T) --- 731 (T) 731 (T) --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.327 P=0.330N P=0.446N P=0.547N P=0.278N P=0.648 | |POLY 3 | P=0.343 P=0.291N P=0.482N P=0.525N P=0.240N P=0.635 | |POLY 1.5 | P=0.343 P=0.271N P=0.489N P=0.520N P=0.238N P=0.650 | |POLY 6 | P=0.340 P=0.310N P=0.469N P=0.527N P=0.243N P=0.624 | |LOGISTIC REGRESSION| P=0.327 (e) P=0.446N P=0.547N (e) P=0.648 | |COCH-ARM / FISHERS | P=0.335 P=0.243N P=0.500N P=0.500N P=0.248N P=0.676 | |ORDER RESTRICTED | P=0.285 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 1/53 (2%) 1/53 (2%) 0/53 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 1/39.01 0/31.01 1/41.12 1/36.33 0/38.33 2/33.11 | |POLY-3 PERCENT (g) | 2.6% 0.0% 2.4% 2.8% 0.0% 6.0% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 1/28 (4%) 1/21 (5%) 0/20 (0%) 2/21 (10%) | |FIRST INCIDENCE | 731 (T) --- 731 (T) 731 (T) --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.213 P=0.581N P=0.728N P=0.733 P=0.536N P=0.453 | |POLY 3 | P=0.222 P=0.545N P=0.749N P=0.746 P=0.503N P=0.443 | |POLY 1.5 | P=0.224 P=0.529N P=0.754N P=0.748 P=0.501N P=0.458 | |POLY 6 | P=0.220 P=0.560N P=0.742N P=0.745 P=0.506N P=0.432 | |LOGISTIC REGRESSION| P=0.213 (e) P=0.728N P=0.733 (e) P=0.453 | |COCH-ARM / FISHERS | P=0.220 P=0.495N P=0.752N P=0.752N P=0.500N P=0.485 | |ORDER RESTRICTED | P=0.169 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 3/39.01 0/31.01 0/41.12 0/36.33 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 7.7% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/24 (13%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.267N P=0.199N P=0.094N P=0.143N P=0.153N P=0.143N | |POLY 3 | P=0.235N P=0.164N P=0.109N P=0.131N P=0.121N P=0.149N | |POLY 1.5 | P=0.241N P=0.146N P=0.113N P=0.129N P=0.120N P=0.141N | |POLY 6 | P=0.234N P=0.181N P=0.102N P=0.131N P=0.122N P=0.155N | |LOGISTIC REGRESSION| P=0.267N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.263N P=0.118N P=0.121N P=0.121N P=0.121N P=0.129N | |ORDER RESTRICTED | P=0.004N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 2/51 (4%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 1/36.55 1/38.95 2/34.31 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.7% 2.6% 5.8% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 675 529 438 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.041 * (e) (e) P=0.507 P=0.491 P=0.206 | |POLY 3 | P=0.047 * (e) (e) P=0.487 P=0.500 P=0.209 | |POLY 1.5 | P=0.049 * (e) (e) P=0.489 P=0.500 P=0.215 | |POLY 6 | P=0.046 * (e) (e) P=0.487 P=0.499 P=0.206 | |LOGISTIC REGRESSION| P=0.057 (e) (e) P=0.488 P=0.488 P=0.273 | |COCH-ARM / FISHERS | P=0.051 (e) (e) P=0.500 P=0.500 P=0.238 | |ORDER RESTRICTED | P=0.046 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/49 (4%) 0/46 (0%) 0/50 (0%) 1/47 (2%) 0/46 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 2/36.68 0/27.75 0/38.12 1/32.21 0/32.50 1/31.77 | |POLY-3 PERCENT (g) | 5.5% 0.0% 0.0% 3.1% 0.0% 3.2% | |TERMINAL (d) | 2/23 (9%) 0/15 (0%) 0/25 (0%) 1/18 (6%) 0/16 (0%) 0/20 (0%) | |FIRST INCIDENCE | 731 (T) --- --- 731 (T) --- 432 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.608 P=0.336N P=0.219N P=0.586N P=0.320N P=0.537N | |POLY 3 | P=0.615 P=0.303N P=0.228N P=0.545N P=0.264N P=0.550N | |POLY 1.5 | P=0.617 P=0.284N P=0.229N P=0.538N P=0.258N P=0.536N | |POLY 6 | P=0.612 P=0.319N P=0.224N P=0.552N P=0.273N P=0.560N | |LOGISTIC REGRESSION| P=0.606 (e) (e) P=0.586N (e) P=0.514N | |COCH-ARM / FISHERS | P=0.616 P=0.263N P=0.242N P=0.516N P=0.263N P=0.508N | |ORDER RESTRICTED | P=0.180N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 16/54 (30%) 20/53 (38%) 26/53 (49%) 28/53 (53%) 14/50 (28%) | |POLY-3 RATE (b) | 15/41.30 16/33.39 20/43.37 26/40.45 28/42.22 14/34.86 | |POLY-3 PERCENT (g) | 36.3% 47.9% 46.1% 64.3% 66.3% 40.2% | |TERMINAL (d) | 8/24 (33%) 9/16 (56%) 13/28 (46%) 14/21 (67%) 14/20 (70%) 8/21 (38%) | |FIRST INCIDENCE | 211 506 429 443 497 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.404N P=0.125 P=0.396 P=0.016 * P=0.006 ** P=0.484 | |POLY 3 | P=0.448N P=0.212 P=0.237 P=0.006 ** P=0.003 ** P=0.456 | |POLY 1.5 | P=0.396N P=0.303 P=0.220 P=0.008 ** P=0.004 ** P=0.502 | |POLY 6 | P=0.505N P=0.153 P=0.275 P=0.007 ** P=0.003 ** P=0.427 | |LOGISTIC REGRESSION| P=0.418N P=0.197 P=0.247 P=0.009 ** P=0.005 ** P=0.463 | |COCH-ARM / FISHERS | P=0.342N P=0.525 P=0.204 P=0.023 * P=0.009 ** P=0.574N | |ORDER RESTRICTED | P=0.035 * (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/39.01 0/31.01 1/41.23 0/36.33 1/38.47 0/32.96 | |POLY-3 PERCENT (g) | 5.1% 0.0% 2.4% 0.0% 2.6% 0.0% | |TERMINAL (d) | 2/24 (8%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) --- 701 --- 696 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.369N P=0.330N P=0.444N P=0.267N P=0.546N P=0.267N | |POLY 3 | P=0.342N P=0.291N P=0.481N P=0.253N P=0.505N P=0.275N | |POLY 1.5 | P=0.345N P=0.271N P=0.488N P=0.250N P=0.502N P=0.267N | |POLY 6 | P=0.341N P=0.310N P=0.467N P=0.253N P=0.509N P=0.281N | |LOGISTIC REGRESSION| P=0.371N (e) P=0.453N (e) P=0.518N (e) | |COCH-ARM / FISHERS | P=0.361N P=0.243N P=0.500N P=0.248N P=0.500N P=0.262N | |ORDER RESTRICTED | P=0.088N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/53 (43%) 18/54 (33%) 22/53 (42%) 16/53 (30%) 23/53 (43%) 25/50 (50%) | |POLY-3 RATE (b) | 23/43.52 18/37.90 22/46.11 16/38.87 23/43.74 25/39.73 | |POLY-3 PERCENT (g) | 52.9% 47.5% 47.7% 41.2% 52.6% 62.9% | |TERMINAL (d) | 13/24 (54%) 4/16 (25%) 12/28 (43%) 10/21 (48%) 10/20 (50%) 12/21 (57%) | |FIRST INCIDENCE | 507 438 443 452 497 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.060 P=0.458 P=0.340N P=0.218N P=0.410 P=0.180 | |POLY 3 | P=0.054 P=0.394N P=0.389N P=0.192N P=0.578N P=0.230 | |POLY 1.5 | P=0.058 P=0.331N P=0.425N P=0.166N P=0.574N P=0.249 | |POLY 6 | P=0.057 P=0.420N P=0.348N P=0.223N P=0.579N P=0.240 | |LOGISTIC REGRESSION| P=0.051 P=0.369N P=0.467N P=0.158N P=0.567 P=0.210 | |COCH-ARM / FISHERS | P=0.065 P=0.192N P=0.500N P=0.113N P=0.578N P=0.318 | |ORDER RESTRICTED | P=0.117 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 46/53 (87%) 48/54 (89%) 52/53 (98%) 48/53 (91%) 46/53 (87%) 47/51 (92%) | |POLY-3 RATE (b) | 46/50.02 48/51.77 52/52.78 48/50.29 46/51.38 47/48.75 | |POLY-3 PERCENT (g) | 92.0% 92.7% 98.5% 95.5% 89.5% 96.4% | |TERMINAL (d) | 23/24 (96%) 14/16 (88%) 28/28 (100%) 20/21 (95%) 19/20 (95%) 21/21 (100%) | |FIRST INCIDENCE | 399 250 418 222 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.349 P=0.026 * P=0.521 P=0.224 P=0.330 P=0.143 | |POLY 3 | P=0.460 P=0.601 P=0.097 P=0.360 P=0.465N P=0.269 | |POLY 1.5 | P=0.494 P=0.561 P=0.064 P=0.332 P=0.509N P=0.279 | |POLY 6 | P=0.433 P=0.683 P=0.171 P=0.446 P=0.410N P=0.291 | |LOGISTIC REGRESSION| P=0.489 P=0.436 P=0.041 * P=0.258 P=0.612 P=0.199 | |COCH-ARM / FISHERS | P=0.508 P=0.485 P=0.030 * P=0.380 P=0.612N P=0.286 | |ORDER RESTRICTED | P=0.258 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 47/53 (89%) 42/54 (78%) 47/53 (89%) 49/53 (92%) 49/53 (92%) 46/51 (90%) | |POLY-3 RATE (b) | 47/51.94 42/45.63 47/49.60 49/51.60 49/50.56 46/47.77 | |POLY-3 PERCENT (g) | 90.5% 92.0% 94.8% 95.0% 96.9% 96.3% | |TERMINAL (d) | 22/24 (92%) 15/16 (94%) 28/28 (100%) 20/21 (95%) 19/20 (95%) 20/21 (95%) | |FIRST INCIDENCE | 211 250 418 59 360 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.220 P=0.145 P=0.263N P=0.237 P=0.250 P=0.217 | |POLY 3 | P=0.175 P=0.539 P=0.308 P=0.296 P=0.155 P=0.203 | |POLY 1.5 | P=0.165 P=0.517N P=0.438 P=0.311 P=0.202 P=0.268 | |POLY 6 | P=0.214 P=0.410 P=0.196 P=0.302 P=0.158 P=0.187 | |LOGISTIC REGRESSION| P=0.182 P=0.286N P=0.585N P=0.391 P=0.369 P=0.446 | |COCH-ARM / FISHERS | P=0.220 P=0.105N P=0.620N P=0.371 P=0.371 P=0.527 | |ORDER RESTRICTED | P=0.102 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 6/54 (11%) 2/53 (4%) 3/53 (6%) 3/53 (6%) 3/51 (6%) | |POLY-3 RATE (b) | 1/39.45 6/33.78 2/41.67 3/37.82 3/39.41 3/34.51 | |POLY-3 PERCENT (g) | 2.5% 17.8% 4.8% 7.9% 7.6% 8.7% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 603 479 636 443 617 501 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.511 P=0.031 * P=0.542 P=0.284 P=0.310 P=0.234 | |POLY 3 | P=0.500 P=0.033 * P=0.519 P=0.289 P=0.304 P=0.257 | |POLY 1.5 | P=0.525 P=0.040 * P=0.512 P=0.290 P=0.305 P=0.268 | |POLY 6 | P=0.483 P=0.030 * P=0.533 P=0.290 P=0.303 P=0.254 | |LOGISTIC REGRESSION| P=0.579 P=0.064 P=0.495 P=0.343 P=0.306 P=0.315 | |COCH-ARM / FISHERS | P=0.570 P=0.059 P=0.500 P=0.309 P=0.309 P=0.294 | |ORDER RESTRICTED | P=0.269 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Spleen: Red Pulp | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 2/37.11 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 443 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.547N (e) (e) P=0.225 (e) (e) | |POLY 3 | P=0.547N (e) (e) P=0.225 (e) (e) | |POLY 1.5 | P=0.546N (e) (e) P=0.227 (e) (e) | |POLY 6 | P=0.550N (e) (e) P=0.226 (e) (e) | |LOGISTIC REGRESSION| P=0.539N (e) (e) P=0.250 (e) (e) | |COCH-ARM / FISHERS | P=0.544N (e) (e) P=0.248 (e) (e) | |ORDER RESTRICTED | P=0.376 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/54 (2%) 0/53 (0%) 0/53 (0%) 1/53 (2%) 2/51 (4%) | |POLY-3 RATE (b) | 0/39.01 1/31.97 0/41.12 0/36.33 1/38.34 2/33.98 | |POLY-3 PERCENT (g) | 0.0% 3.1% 0.0% 0.0% 2.6% 5.9% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 250 --- --- 729 586 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.058 P=0.508 (e) (e) P=0.473 P=0.188 | |POLY 3 | P=0.055 P=0.461 (e) (e) P=0.497 P=0.207 | |POLY 1.5 | P=0.060 P=0.475 (e) (e) P=0.499 P=0.213 | |POLY 6 | P=0.053 P=0.448 (e) (e) P=0.494 P=0.204 | |LOGISTIC REGRESSION| P=0.076 P=0.665 (e) (e) P=0.482 P=0.236 | |COCH-ARM / FISHERS | P=0.068 P=0.505 (e) (e) P=0.500 P=0.238 | |ORDER RESTRICTED | P=0.045 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 4/54 (7%) 2/53 (4%) 6/53 (11%) 4/53 (8%) 4/51 (8%) | |POLY-3 RATE (b) | 3/39.67 4/32.27 2/41.61 6/37.17 4/38.59 4/35.48 | |POLY-3 PERCENT (g) | 7.6% 12.4% 4.8% 16.1% 10.4% 11.3% | |TERMINAL (d) | 2/24 (8%) 2/16 (13%) 0/28 (0%) 4/21 (19%) 1/20 (5%) 0/21 (0%) | |FIRST INCIDENCE | 507 250 656 526 696 442 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.419 P=0.337 P=0.432N P=0.197 P=0.447 P=0.410 | |POLY 3 | P=0.425 P=0.388 P=0.478N P=0.207 P=0.485 P=0.438 | |POLY 1.5 | P=0.437 P=0.430 P=0.487N P=0.213 P=0.493 P=0.449 | |POLY 6 | P=0.418 P=0.353 P=0.461N P=0.205 P=0.476 P=0.439 | |LOGISTIC REGRESSION| P=0.446 P=0.484 P=0.494N P=0.212 P=0.488 P=0.524 | |COCH-ARM / FISHERS | P=0.458 P=0.511 P=0.500N P=0.244 P=0.500 P=0.478 | |ORDER RESTRICTED | P=0.431 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 3/53 (6%) 3/53 (6%) 2/51 (4%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 3/36.86 3/39.24 2/34.27 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 8.1% 7.6% 5.8% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 2/21 (10%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 568 579 442 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.127 (e) (e) P=0.101 P=0.121 P=0.206 | |POLY 3 | P=0.126 (e) (e) P=0.108 P=0.119 P=0.208 | |POLY 1.5 | P=0.131 (e) (e) P=0.109 P=0.119 P=0.215 | |POLY 6 | P=0.123 (e) (e) P=0.108 P=0.119 P=0.206 | |LOGISTIC REGRESSION| P=0.141 (e) (e) P=0.110 P=0.121 P=0.269 | |COCH-ARM / FISHERS | P=0.143 (e) (e) P=0.121 P=0.121 P=0.238 | |ORDER RESTRICTED | P=0.076 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/54 (2%) 0/53 (0%) 2/53 (4%) 2/53 (4%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 1/31.72 0/41.12 2/36.69 2/38.81 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 3.2% 0.0% 5.5% 5.2% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 479 --- 675 636 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.535N P=0.473 (e) P=0.227 P=0.236 (e) | |POLY 3 | P=0.555N P=0.459 (e) P=0.223 P=0.235 (e) | |POLY 1.5 | P=0.535N P=0.474 (e) P=0.225 P=0.237 (e) | |POLY 6 | P=0.572N P=0.447 (e) P=0.224 P=0.234 (e) | |LOGISTIC REGRESSION| P=0.507N P=0.599 (e) P=0.223 P=0.236 (e) | |COCH-ARM / FISHERS | P=0.503N P=0.505 (e) P=0.248 P=0.248 (e) | |ORDER RESTRICTED | P=0.268 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 3/53 (6%) 1/51 (2%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 2/36.86 3/39.24 1/33.59 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% 7.6% 3.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 568 579 586 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283 (e) (e) P=0.214 P=0.121 P=0.449 | |POLY 3 | P=0.270 (e) (e) P=0.224 P=0.119 P=0.470 | |POLY 1.5 | P=0.283 (e) (e) P=0.226 P=0.119 P=0.477 | |POLY 6 | P=0.261 (e) (e) P=0.225 P=0.119 P=0.467 | |LOGISTIC REGRESSION| P=0.303 (e) (e) P=0.230 P=0.121 P=0.509 | |COCH-ARM / FISHERS | P=0.307 (e) (e) P=0.248 P=0.121 P=0.490 | |ORDER RESTRICTED | P=0.126 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 1/53 (2%) 2/53 (4%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 1/39.23 0/31.01 1/41.46 2/36.48 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 2.6% 0.0% 2.4% 5.5% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | 672 --- 636 693 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.306N P=0.574N P=0.720N P=0.467 P=0.507N P=0.538N | |POLY 3 | P=0.277N P=0.546N P=0.749N P=0.475 P=0.505N P=0.534N | |POLY 1.5 | P=0.279N P=0.529N P=0.753N P=0.479 P=0.502N P=0.525N | |POLY 6 | P=0.278N P=0.562N P=0.741N P=0.472 P=0.509N P=0.541N | |LOGISTIC REGRESSION| P=0.296N P=0.543N P=0.761N P=0.474 P=0.502N P=0.528N | |COCH-ARM / FISHERS | P=0.288N P=0.495N P=0.752N P=0.500 P=0.500N P=0.510N | |ORDER RESTRICTED | P=0.361N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 2/36.48 0/38.33 0/33.11 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.5% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 693 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.558N (e) (e) P=0.209 (e) (e) | |POLY 3 | P=0.549N (e) (e) P=0.222 (e) (e) | |POLY 1.5 | P=0.548N (e) (e) P=0.224 (e) (e) | |POLY 6 | P=0.553N (e) (e) P=0.221 (e) (e) | |LOGISTIC REGRESSION| P=0.559N (e) (e) P=0.219 (e) (e) | |COCH-ARM / FISHERS | P=0.544N (e) (e) P=0.248 (e) (e) | |ORDER RESTRICTED | P=0.374 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 8/54 (15%) 8/53 (15%) 10/53 (19%) 10/53 (19%) 2/51 (4%) | |POLY-3 RATE (b) | 5/40.87 8/35.58 8/44.05 10/38.79 10/40.92 2/33.11 | |POLY-3 PERCENT (g) | 12.2% 22.5% 18.2% 25.8% 24.4% 6.0% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 2/28 (7%) 4/21 (19%) 5/20 (25%) 2/21 (10%) | |FIRST INCIDENCE | 551 250 429 452 467 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.086N P=0.163 P=0.326 P=0.109 P=0.113 P=0.318N | |POLY 3 | P=0.115N P=0.187 P=0.324 P=0.101 P=0.124 P=0.308N | |POLY 1.5 | P=0.087N P=0.217 P=0.307 P=0.106 P=0.129 P=0.278N | |POLY 6 | P=0.154N P=0.167 P=0.348 P=0.098 P=0.115 P=0.339N | |LOGISTIC REGRESSION| P=0.059N P=0.410 P=0.243 P=0.121 P=0.133 P=0.257N | |COCH-ARM / FISHERS | P=0.060N P=0.290 P=0.278 P=0.132 P=0.132 P=0.235N | |ORDER RESTRICTED | P=0.094N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 38/48 (79%) 38/53 (72%) 37/52 (71%) 35/53 (66%) 41/53 (77%) 30/47 (64%) | |POLY-3 RATE (b) | 38/45.92 38/44.44 37/47.29 35/45.23 41/48.12 30/40.74 | |POLY-3 PERCENT (g) | 82.8% 85.5% 78.3% 77.4% 85.2% 73.6% | |TERMINAL (d) | 19/23 (83%) 13/16 (81%) 21/27 (78%) 16/21 (76%) 17/20 (85%) 11/18 (61%) | |FIRST INCIDENCE | 211 352 429 263 341 79 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.434N P=0.074 P=0.264N P=0.547N P=0.241 P=0.515N | |POLY 3 | P=0.182N P=0.470 P=0.381N P=0.344N P=0.481 P=0.208N | |POLY 1.5 | P=0.148N P=0.582 P=0.329N P=0.273N P=0.563 P=0.147N | |POLY 6 | P=0.232N P=0.444 P=0.409N P=0.385N P=0.398 P=0.262N | |LOGISTIC REGRESSION| P=0.211N P=0.461N P=0.235N P=0.147N P=0.515N P=0.070N | |COCH-ARM / FISHERS | P=0.172N P=0.263N P=0.245N P=0.105N P=0.509N P=0.076N | |ORDER RESTRICTED | P=0.169N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Thymus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 3/53 (6%) 0/52 (0%) 0/53 (0%) 0/53 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 0/35.93 3/32.64 0/40.12 0/36.33 0/38.33 0/29.69 | |POLY-3 PERCENT (g) | 0.0% 9.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/16 (0%) 0/27 (0%) 0/21 (0%) 0/20 (0%) 0/18 (0%) | |FIRST INCIDENCE | --- 261 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.275N P=0.112 (e) (e) (e) (e) | |POLY 3 | P=0.318N P=0.101 (e) (e) (e) (e) | |POLY 1.5 | P=0.300N P=0.113 (e) (e) (e) (e) | |POLY 6 | P=0.335N P=0.092 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.243N P=0.310 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.272N P=0.141 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.121N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 19/51 (37%) 17/52 (33%) 23/53 (43%) 17/53 (32%) 19/53 (36%) 16/51 (31%) | |POLY-3 RATE (b) | 19/40.16 17/33.23 23/42.07 17/38.74 19/40.97 16/35.74 | |POLY-3 PERCENT (g) | 47.3% 51.2% 54.7% 43.9% 46.4% 44.8% | |TERMINAL (d) | 12/24 (50%) 9/16 (56%) 20/28 (71%) 9/21 (43%) 11/20 (55%) 11/21 (52%) | |FIRST INCIDENCE | 555 528 530 526 479 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.395N P=0.237 P=0.503 P=0.564N P=0.407 P=0.551N | |POLY 3 | P=0.323N P=0.461 P=0.320 P=0.467N P=0.557N P=0.504N | |POLY 1.5 | P=0.289N P=0.566 P=0.331 P=0.448N P=0.536N P=0.434N | |POLY 6 | P=0.386N P=0.389 P=0.308 P=0.475N P=0.589N P=0.585N | |LOGISTIC REGRESSION| P=0.406N P=0.335 P=0.421 P=0.494N P=0.582 P=0.554N | |COCH-ARM / FISHERS | P=0.282N P=0.390N P=0.331 P=0.364N P=0.522N P=0.338N | |ORDER RESTRICTED | P=0.517N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 0/52 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 2/51 (4%) | |POLY-3 RATE (b) | 1/38.95 0/30.30 0/41.12 0/36.33 2/38.75 2/33.81 | |POLY-3 PERCENT (g) | 2.6% 0.0% 0.0% 0.0% 5.2% 5.9% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 1/21 (5%) | |FIRST INCIDENCE | 399 --- --- --- 647 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.067 P=0.538N P=0.496N P=0.520N P=0.500 P=0.452 | |POLY 3 | P=0.068 P=0.549N P=0.489N P=0.514N P=0.498 P=0.451 | |POLY 1.5 | P=0.072 P=0.531N P=0.490N P=0.509N P=0.505 P=0.467 | |POLY 6 | P=0.065 P=0.565N P=0.485N P=0.518N P=0.492 P=0.439 | |LOGISTIC REGRESSION| P=0.081 P=0.340N P=0.661N P=0.371N P=0.516 P=0.573 | |COCH-ARM / FISHERS | P=0.076 P=0.495N P=0.490N P=0.490N P=0.515 P=0.500 | |ORDER RESTRICTED | P=0.112 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 9/52 (17%) 9/53 (17%) 12/53 (23%) 10/53 (19%) 17/51 (33%) | |POLY-3 RATE (b) | 5/39.16 9/34.89 9/43.62 12/38.19 10/41.39 17/39.62 | |POLY-3 PERCENT (g) | 12.8% 25.8% 20.6% 31.4% 24.2% 42.9% | |TERMINAL (d) | 3/24 (13%) 3/16 (19%) 5/28 (18%) 8/21 (38%) 3/20 (15%) 6/21 (29%) | |FIRST INCIDENCE | 507 261 418 452 360 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** P=0.087 P=0.275 P=0.035 * P=0.118 P=0.002 ** | |POLY 3 | P=0.004 ** P=0.126 P=0.254 P=0.040 * P=0.149 P=0.002 ** | |POLY 1.5 | P=0.004 ** P=0.150 P=0.241 P=0.045 * P=0.151 P=0.002 ** | |POLY 6 | P=0.004 ** P=0.107 P=0.273 P=0.037 * P=0.146 P=0.002 ** | |LOGISTIC REGRESSION| P=0.005 ** P=0.279 P=0.210 P=0.045 * P=0.151 P=0.005 ** | |COCH-ARM / FISHERS | P=0.005 ** P=0.206 P=0.217 P=0.065 P=0.150 P=0.004 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 53 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/34 (97%) 13/13 (100%) 19/19 (100%) 21/22 (95%) 23/23 (100%) 35/35 (100%) | |POLY-3 RATE (b) | 33/33.44 13/13.00 19/19.00 21/22.00 23/23.00 35/35.00 | |POLY-3 PERCENT (g) | 98.7% 100.0% 100.0% 95.5% 100.0% 100.0% | |TERMINAL (d) | 14/14 (100%) 4/4 (100%) 12/12 (100%) 9/10 (90%) 10/10 (100%) 17/17 (100%) | |FIRST INCIDENCE | 211 261 418 222 383 360 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.030 * P=0.161N P=0.011N* P=0.136N P=0.210N P=0.384 | |POLY 3 | P=0.484 P=0.969 P=0.943 P=0.554N P=0.927 P=0.890 | |POLY 1.5 | P=0.429 P=0.852 P=0.790 P=0.606N P=0.758 P=0.685 | |POLY 6 | P=0.556 P=1.000 P=1.000 P=0.481N P=1.000 P=1.000 | |LOGISTIC REGRESSION| P=0.368 P=0.645 P=0.657 P=0.662N P=0.585 P=0.490 | |COCH-ARM / FISHERS | P=0.368 P=0.723 P=0.642 P=0.636N P=0.596 P=0.493 | |ORDER RESTRICTED | P=0.335 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/53 (15%) 11/53 (21%) 6/53 (11%) 8/53 (15%) 13/53 (25%) 9/50 (18%) | |POLY-3 RATE (b) | 8/41.11 11/35.14 6/42.66 8/37.88 13/42.45 9/36.88 | |POLY-3 PERCENT (g) | 19.5% 31.3% 14.1% 21.1% 30.6% 24.4% | |TERMINAL (d) | 3/24 (13%) 4/16 (25%) 3/28 (11%) 3/21 (14%) 6/20 (30%) 3/21 (14%) | |FIRST INCIDENCE | 442 261 443 555 383 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.309 P=0.131 P=0.312N P=0.543 P=0.137 P=0.359 | |POLY 3 | P=0.313 P=0.174 P=0.356N P=0.539 P=0.174 P=0.399 | |POLY 1.5 | P=0.325 P=0.212 P=0.366N P=0.552 P=0.173 P=0.413 | |POLY 6 | P=0.303 P=0.147 P=0.341N P=0.535 P=0.172 P=0.394 | |LOGISTIC REGRESSION| P=0.343 P=0.288 P=0.390N P=0.567 P=0.165 P=0.474 | |COCH-ARM / FISHERS | P=0.343 P=0.307 P=0.388N P=0.607N P=0.165 P=0.447 | |ORDER RESTRICTED | P=0.346 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 54 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/53 (6%) 2/53 (4%) 3/53 (6%) 2/53 (4%) 3/50 (6%) | |POLY-3 RATE (b) | 0/39.01 3/31.56 2/41.12 3/36.70 2/38.40 3/34.22 | |POLY-3 PERCENT (g) | 0.0% 9.5% 4.9% 8.2% 5.2% 8.8% | |TERMINAL (d) | 0/24 (0%) 1/16 (6%) 2/28 (7%) 1/21 (5%) 1/20 (5%) 1/21 (5%) | |FIRST INCIDENCE | --- 622 731 (T) 675 715 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.291 P=0.073 P=0.272 P=0.114 P=0.215 P=0.099 | |POLY 3 | P=0.277 P=0.084 P=0.249 P=0.107 P=0.233 P=0.095 | |POLY 1.5 | P=0.289 P=0.094 P=0.244 P=0.109 P=0.235 P=0.099 | |POLY 6 | P=0.268 P=0.077 P=0.256 P=0.107 P=0.230 P=0.094 | |LOGISTIC REGRESSION| P=0.290 P=0.086 P=0.272 P=0.107 P=0.223 P=0.124 | |COCH-ARM / FISHERS | P=0.309 P=0.121 P=0.248 P=0.121 P=0.248 P=0.111 | |ORDER RESTRICTED | P=0.090 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus | | Adenomyosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/54 (2%) 0/53 (0%) 1/53 (2%) 0/53 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 2/39.39 1/31.01 0/41.12 1/36.33 0/38.33 1/32.95 | |POLY-3 PERCENT (g) | 5.1% 3.2% 0.0% 2.8% 0.0% 3.0% | |TERMINAL (d) | 1/24 (4%) 1/16 (6%) 0/28 (0%) 1/21 (5%) 0/20 (0%) 1/21 (5%) | |FIRST INCIDENCE | 621 731 (T) --- 731 (T) --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.635N P=0.620N P=0.211N P=0.531N P=0.253N P=0.558N | |POLY 3 | P=0.634N P=0.582N P=0.227N P=0.528N P=0.243N P=0.562N | |POLY 1.5 | P=0.629N P=0.552N P=0.231N P=0.522N P=0.240N P=0.547N | |POLY 6 | P=0.643N P=0.610N P=0.221N P=0.533N P=0.247N P=0.574N | |LOGISTIC REGRESSION| P=0.646N P=0.600N P=0.230N P=0.525N P=0.240N P=0.563N | |COCH-ARM / FISHERS | P=0.627N P=0.493N P=0.248N P=0.500N P=0.248N P=0.522N | |ORDER RESTRICTED | P=0.263N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 55 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/54 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/39.01 2/32.05 0/41.12 0/36.33 0/38.33 0/32.95 | |POLY-3 PERCENT (g) | 0.0% 6.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 0/20 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 506 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.410N P=0.191 (e) (e) (e) (e) | |POLY 3 | P=0.444N P=0.196 (e) (e) (e) (e) | |POLY 1.5 | P=0.426N P=0.210 (e) (e) (e) (e) | |POLY 6 | P=0.459N P=0.186 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.390N P=0.265 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.393N P=0.252 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.184N (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 6/54 (11%) 6/53 (11%) 2/53 (4%) 16/53 (30%) 8/50 (16%) | |POLY-3 RATE (b) | 5/40.20 6/34.19 6/42.45 2/36.33 16/41.62 8/36.27 | |POLY-3 PERCENT (g) | 12.4% 17.6% 14.1% 5.5% 38.5% 22.1% | |TERMINAL (d) | 3/24 (13%) 0/16 (0%) 4/28 (14%) 2/21 (10%) 7/20 (35%) 3/21 (14%) | |FIRST INCIDENCE | 442 250 501 731 (T) 452 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.064 P=0.332 P=0.577 P=0.262N P=0.006 ** P=0.196 | |POLY 3 | P=0.054 P=0.386 P=0.539 P=0.257N P=0.005 ** P=0.206 | |POLY 1.5 | P=0.057 P=0.424 P=0.523 P=0.247N P=0.006 ** P=0.215 | |POLY 6 | P=0.053 P=0.363 P=0.563 P=0.265N P=0.005 ** P=0.206 | |LOGISTIC REGRESSION| P=0.063 P=0.558 P=0.504 P=0.240N P=0.007 ** P=0.259 | |COCH-ARM / FISHERS | P=0.065 P=0.513 P=0.500 P=0.219N P=0.007 ** P=0.240 | |ORDER RESTRICTED | P=0.023 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 56 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/54 (2%) 5/53 (9%) 4/53 (8%) 2/53 (4%) 8/50 (16%) | |POLY-3 RATE (b) | 2/39.39 1/31.67 5/41.33 4/38.05 2/39.57 8/35.02 | |POLY-3 PERCENT (g) | 5.1% 3.2% 12.1% 10.5% 5.1% 22.8% | |TERMINAL (d) | 1/24 (4%) 0/16 (0%) 4/28 (14%) 1/21 (5%) 0/20 (0%) 3/21 (14%) | |FIRST INCIDENCE | 621 506 674 322 502 486 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** P=0.598N P=0.288 P=0.315 P=0.672 P=0.031 * | |POLY 3 | P=0.010 * P=0.575N P=0.234 P=0.319 P=0.693N P=0.026 * | |POLY 1.5 | P=0.010 * P=0.548N P=0.228 P=0.320 P=0.692N P=0.029 * | |POLY 6 | P=0.010 * P=0.599N P=0.246 P=0.323 P=0.696N P=0.025 * | |LOGISTIC REGRESSION| P=0.009 ** P=0.512N P=0.251 P=0.351 P=0.695 P=0.031 * | |COCH-ARM / FISHERS | P=0.010 * P=0.493N P=0.219 P=0.339 P=0.691N P=0.037 * | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/53 (43%) 29/54 (54%) 27/53 (51%) 17/53 (32%) 27/53 (51%) 32/50 (64%) | |POLY-3 RATE (b) | 23/45.42 29/42.63 27/46.84 17/40.45 27/43.75 32/41.90 | |POLY-3 PERCENT (g) | 50.6% 68.0% 57.6% 42.0% 61.7% 76.4% | |TERMINAL (d) | 11/24 (46%) 9/16 (56%) 15/28 (54%) 8/21 (38%) 12/20 (60%) 16/21 (76%) | |FIRST INCIDENCE | 399 250 418 452 452 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.025 * P=0.024 * P=0.473 P=0.293N P=0.201 P=0.021 * | |POLY 3 | P=0.007 ** P=0.065 P=0.316 P=0.275N P=0.190 P=0.007 ** | |POLY 1.5 | P=0.009 ** P=0.087 P=0.303 P=0.243N P=0.223 P=0.010 * | |POLY 6 | P=0.006 ** P=0.061 P=0.346 P=0.296N P=0.171 P=0.006 ** | |LOGISTIC REGRESSION| P=0.014 * P=0.159 P=0.282 P=0.185N P=0.273 P=0.020 * | |COCH-ARM / FISHERS | P=0.017 * P=0.191 P=0.280 P=0.158N P=0.280 P=0.029 * | |ORDER RESTRICTED | P=0.007 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 57 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/39.01 0/31.01 0/41.12 1/36.33 2/38.33 0/32.95 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.8% 5.2% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 1/21 (5%) 2/20 (10%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- 731 (T) 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.676 (e) (e) P=0.473 P=0.198 (e) | |POLY 3 | P=0.644 (e) (e) P=0.486 P=0.232 (e) | |POLY 1.5 | P=0.657 (e) (e) P=0.488 P=0.235 (e) | |POLY 6 | P=0.632 (e) (e) P=0.485 P=0.229 (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.473 P=0.198 (e) | |COCH-ARM / FISHERS | P=0.677 (e) (e) P=0.500 P=0.248 (e) | |ORDER RESTRICTED | P=0.279 (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus: Cervix | | Hyperplasia Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/39.28 0/31.01 0/41.12 0/36.33 2/39.10 0/32.95 | |POLY-3 PERCENT (g) | 2.6% 0.0% 0.0% 0.0% 5.1% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/16 (0%) 0/28 (0%) 0/21 (0%) 1/20 (5%) 0/21 (0%) | |FIRST INCIDENCE | 656 --- --- --- 452 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.693N P=0.578N P=0.465N P=0.507N P=0.474 P=0.543N | |POLY 3 | P=0.695N P=0.547N P=0.491N P=0.516N P=0.498 P=0.535N | |POLY 1.5 | P=0.689N P=0.529N P=0.494N P=0.512N P=0.500 P=0.527N | |POLY 6 | P=0.702 P=0.562N P=0.485N P=0.518N P=0.494 P=0.542N | |LOGISTIC REGRESSION| P=0.683N P=0.532N P=0.498N P=0.508N P=0.500 P=0.524N | |COCH-ARM / FISHERS | P=0.684N P=0.495N P=0.500N P=0.500N P=0.500 P=0.515N | |ORDER RESTRICTED | P=0.323N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/09/03 EXPERIMENT: 96021 TEST: 01 Page 58 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 UG/KG 10 UG/KG 100 300 1000 3000 | | | UG/KG UG/KG UG/KG UG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/53 (70%) 29/54 (54%) 32/53 (60%) 28/53 (53%) 25/53 (47%) 21/50 (42%) | |POLY-3 RATE (b) | 37/47.57 29/39.48 32/47.80 28/41.68 25/43.18 21/39.37 | |POLY-3 PERCENT (g) | 77.8% 73.5% 66.9% 67.2% 57.9% 53.4% | |TERMINAL (d) | 18/24 (75%) 12/16 (75%) 18/28 (64%) 15/21 (71%) 13/20 (65%) 10/21 (48%) | |FIRST INCIDENCE | 410 250 418 322 479 387 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040N* P=0.397 P=0.117N P=0.233N P=0.103N P=0.057N | |POLY 3 | P=0.007N** P=0.406N P=0.156N P=0.170N P=0.025N* P=0.009N** | |POLY 1.5 | P=0.007N** P=0.229N P=0.166N P=0.122N P=0.017N* P=0.006N** | |POLY 6 | P=0.009N** P=0.589N P=0.147N P=0.228N P=0.039N* P=0.015N* | |LOGISTIC REGRESSION| P=0.011N* P=0.246N P=0.182N P=0.092N P=0.014N* P=0.007N** | |COCH-ARM / FISHERS | P=0.011N* P=0.065N P=0.208N P=0.055N P=0.015N* P=0.004N** | |ORDER RESTRICTED | P=0.007N** (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).