TDMS Study 96007-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03
EXPERIMENT: 96007 TEST: 05 TIME: 11:40:09
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F
PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4
------------------------------------------------------------------------------------------------------------------------------------
FINAL #3/CONTROL VS. TREATED GROUPS
REASONS FOR REMOVAL: 25018 Dosing Accident
25019 Moribund Sacrifice
25020 Natural Death
25021 Terminal Sacrifice
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE 001 0 NG/KG
INCLUDE 002 6 NG/KG
INCLUDE 003 20 NG/KG
INCLUDE 004 44 NG/KG
INCLUDE 005 92 NG/KG
INCLUDE 006 200 NG/KG
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03
EXPERIMENT: 96007 TEST: 05 TIME: 11:40:09
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F
PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION(
===============================================================
Female Rats
------------
Organ Morphology
----- ----------
Adrenal Cortex Angiectasis
Atrophy
Degeneration Cystic
Hypertrophy
Necrosis
Vacuolization Cytoplasmic
Bone Marrow Hyperplasia
Clitoral Gland Inflammation
Harderian Gland Inflammation
Heart Cardiomyopathy
Hemorrhage
Heart: Artery Inflammation Chronic
Intestine Large, Cecum: Artery Inflammation Chronic
Intestine Large, Colon Parasite Metazoan
Intestine Large, Rectum Parasite Metazoan
Islets, Pancreatic Hyperplasia
Kidney Mineralization
Nephropathy
Pigmentation
Kidney: Transitional Epithelium Hyperplasia
Liver Angiectasis
Basophilic Focus
Cholangiofibrosis
Clear Cell Focus
Eosinophilic Focus
Fatty Change Diffuse
Hematopoietic Cell Proliferation
Hyperplasia
Necrosis
Pigmentation
Toxic Hepatopathy
Liver: Bile Duct Fibrosis
Hyperplasia
Liver: Hepatocyte Hypertrophy
Multinucleated
Liver: Oval Cell Hyperplasia
Lung Metaplasia
Lung: Alveolar Epithelium Hyperplasia
Metaplasia Bronchiolar
Lymph Node, Mandibular Hyperplasia
Lymph Node, Mesenteric Hyperplasia
Lymph Node: Lumbar Ectasia
Hemorrhage
Lymph Node: Mediastinal Ectasia
Mammary Gland Hyperplasia
Mesentery: Artery Inflammation Chronic
Nose: Respiratory Epithelium Hyperplasia
Oral Mucosa: Gingival Hyperplasia
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03
EXPERIMENT: 96007 TEST: 05 TIME: 11:40:09
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F
PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4
Ovary Cyst
Pancreas Cytoplasmic Alteration
Inflammation Chronic
Pancreas: Acinus Vacuolization Cytoplasmic
Pancreas: Artery Inflammation Chronic
Pituitary Gland Angiectasis
Pituitary Gland: Pars Distalis Hyperplasia
Salivary Glands Atrophy
Skin Inflammation
Ulcer
Spleen Pigmentation
Spleen: Red Pulp Atrophy
Stomach, Forestomach Hyperplasia
Stomach, Forestomach: Artery Inflammation Chronic
Stomach, Glandular Mineralization
Thymus Atrophy
Thyroid Gland: Follicular Cell Hypertrophy
Urinary Bladder: Transitional Epithelium
Hyperplasia
Uterus Hemorrhage
Inflammation Chronic
Metaplasia
Uterus: Endometrium Hyperplasia Cystic
===============================================================
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 1
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 31/53 (58%) 37/53 (70%) 30/53 (57%) 33/52 (63%) 27/53 (51%) 35/53 (66%) |
|POLY-3 RATE (b) | 31/44.10 37/44.05 30/41.40 33/43.41 27/38.23 35/43.16 |
|POLY-3 PERCENT (g) | 70.3% 84.0% 72.5% 76.0% 70.6% 81.1% |
|TERMINAL (d) | 20/25 (80%) 20/22 (91%) 20/24 (83%) 21/25 (84%) 17/20 (85%) 20/23 (87%) |
|FIRST INCIDENCE | 588 296 393 470 580 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.248 P=0.045 * P=0.444 P=0.295 P=0.417 P=0.108 |
|POLY 3 | P=0.310 P=0.074 P=0.507 P=0.345 P=0.590 P=0.152 |
|POLY 1.5 | P=0.352 P=0.103 P=0.527 P=0.369 P=0.506N P=0.182 |
|POLY 6 | P=0.300 P=0.059 P=0.498 P=0.313 P=0.542 P=0.141 |
|LOGISTIC REGRESSION| P=0.198 P=0.027 * P=0.326 P=0.150 P=0.510 P=0.039 * |
|COCH-ARM / FISHERS | P=0.467 P=0.156 P=0.500N P=0.374 P=0.279N P=0.274 |
|ORDER RESTRICTED | P=0.151 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 0/53 (0%) 4/53 (8%) |
|POLY-3 RATE (b) | 3/42.22 0/38.07 0/36.67 1/38.12 0/36.13 4/36.61 |
|POLY-3 PERCENT (g) | 7.1% 0.0% 0.0% 2.6% 0.0% 10.9% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 4/23 (17%) |
|FIRST INCIDENCE | 619 --- --- 675 --- 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.047 * P=0.155N P=0.150N P=0.361N P=0.160N P=0.431 |
|POLY 3 | P=0.054 P=0.138N P=0.145N P=0.342N P=0.149N P=0.422 |
|POLY 1.5 | P=0.055 P=0.130N P=0.138N P=0.328N P=0.140N P=0.451 |
|POLY 6 | P=0.055 P=0.147N P=0.152N P=0.359N P=0.155N P=0.393 |
|LOGISTIC REGRESSION| P=0.044 * P=0.135N P=0.141N P=0.336N P=0.144N P=0.400 |
|COCH-ARM / FISHERS | P=0.057 P=0.121N P=0.121N P=0.316N P=0.121N P=0.500 |
|ORDER RESTRICTED | P=0.019 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 2
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Degeneration Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 17/53 (32%) 14/53 (26%) 18/52 (35%) 12/53 (23%) 14/53 (26%) |
|POLY-3 RATE (b) | 4/42.40 17/41.16 14/38.67 18/40.53 12/37.63 14/38.15 |
|POLY-3 PERCENT (g) | 9.4% 41.3% 36.2% 44.4% 31.9% 36.7% |
|TERMINAL (d) | 2/25 (8%) 7/22 (32%) 7/24 (29%) 12/25 (48%) 6/20 (30%) 10/23 (44%) |
|FIRST INCIDENCE | 603 451 570 470 451 513 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.227 P<0.001 ** P=0.007 ** P<0.001 ** P=0.012 * P=0.005 ** |
|POLY 3 | P=0.173 P<0.001 ** P=0.003 ** P<0.001 ** P=0.011 * P=0.003 ** |
|POLY 1.5 | P=0.221 P<0.001 ** P=0.004 ** P<0.001 ** P=0.014 * P=0.004 ** |
|POLY 6 | P=0.137 P<0.001 ** P=0.003 ** P<0.001 ** P=0.010 * P=0.002 ** |
|LOGISTIC REGRESSION| P=0.216 P<0.001 ** P=0.004 ** P<0.001 ** P=0.013 * P=0.003 ** |
|COCH-ARM / FISHERS | P=0.318 P<0.001 ** P=0.009 ** P<0.001 ** P=0.028 * P=0.009 ** |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 8/53 (15%) 10/53 (19%) 10/53 (19%) 7/52 (13%) 10/53 (19%) 11/53 (21%) |
|POLY-3 RATE (b) | 8/42.51 10/39.47 10/38.48 7/39.37 10/38.01 11/39.44 |
|POLY-3 PERCENT (g) | 18.8% 25.3% 26.0% 17.8% 26.3% 27.9% |
|TERMINAL (d) | 6/25 (24%) 7/22 (32%) 6/24 (25%) 4/25 (16%) 5/20 (25%) 6/23 (26%) |
|FIRST INCIDENCE | 588 498 420 470 337 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.226 P=0.283 P=0.323 P=0.541N P=0.245 P=0.229 |
|POLY 3 | P=0.247 P=0.327 P=0.305 P=0.565N P=0.295 P=0.237 |
|POLY 1.5 | P=0.265 P=0.355 P=0.324 P=0.540N P=0.320 P=0.261 |
|POLY 6 | P=0.235 P=0.296 P=0.296 P=0.594N P=0.284 P=0.215 |
|LOGISTIC REGRESSION| P=0.243 P=0.309 P=0.297 P=0.570N P=0.295 P=0.251 |
|COCH-ARM / FISHERS | P=0.297 P=0.398 P=0.398 P=0.516N P=0.398 P=0.307 |
|ORDER RESTRICTED | P=0.285 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 3
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 42/53 (79%) 43/53 (81%) 43/53 (81%) 46/52 (88%) 44/53 (83%) 45/53 (85%) |
|POLY-3 RATE (b) | 42/48.81 43/46.73 43/44.51 46/48.81 44/46.44 45/47.92 |
|POLY-3 PERCENT (g) | 86.1% 92.0% 96.6% 94.2% 94.8% 93.9% |
|TERMINAL (d) | 23/25 (92%) 22/22 (100%) 24/24 (100%) 24/25 (96%) 20/20 (100%) 23/23 (100%) |
|FIRST INCIDENCE | 377 321 297 410 241 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.153 P=0.187 P=0.253 P=0.186 P=0.079 P=0.131 |
|POLY 3 | P=0.215 P=0.244 P=0.049 * P=0.127 P=0.110 P=0.142 |
|POLY 1.5 | P=0.231 P=0.358 P=0.116 P=0.142 P=0.168 P=0.185 |
|POLY 6 | P=0.204 P=0.133 P=0.030 * P=0.114 P=0.089 P=0.108 |
|LOGISTIC REGRESSION| P=0.118 P=0.316 P=0.109 P=0.103 P=0.108 P=0.122 |
|COCH-ARM / FISHERS | P=0.292 P=0.500 P=0.500 P=0.155 P=0.402 P=0.307 |
|ORDER RESTRICTED | P=0.026 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 0/53 (0%) 2/53 (4%) 0/52 (0%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 4/43.02 0/38.07 2/37.93 0/37.91 2/36.68 0/36.61 |
|POLY-3 PERCENT (g) | 9.3% 0.0% 5.3% 0.0% 5.5% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 1/20 (5%) 0/23 (0%) |
|FIRST INCIDENCE | 500 --- 301 --- 555 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.170N P=0.090N P=0.419N P=0.091N P=0.428N P=0.097N |
|POLY 3 | P=0.146N P=0.077N P=0.396N P=0.077N P=0.413N P=0.083N |
|POLY 1.5 | P=0.146N P=0.070N P=0.380N P=0.070N P=0.391N P=0.074N |
|POLY 6 | P=0.145N P=0.086N P=0.411N P=0.087N P=0.428N P=0.094N |
|LOGISTIC REGRESSION| P=0.137N P=0.060N P=0.274N P=0.063N P=0.342N P=0.060N |
|COCH-ARM / FISHERS | P=0.146N P=0.059N P=0.339N P=0.061N P=0.339N P=0.059N |
|ORDER RESTRICTED | P=0.013N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 4
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 9/53 (17%) 13/53 (25%) 14/53 (26%) 7/52 (13%) 17/53 (32%) 9/53 (17%) |
|POLY-3 RATE (b) | 9/42.91 13/41.59 14/41.26 7/39.98 17/38.33 9/38.25 |
|POLY-3 PERCENT (g) | 21.0% 31.3% 33.9% 17.5% 44.4% 23.5% |
|TERMINAL (d) | 5/25 (20%) 6/22 (27%) 5/24 (21%) 4/25 (16%) 9/20 (45%) 4/23 (17%) |
|FIRST INCIDENCE | 536 321 219 429 500 570 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.536 P=0.156 P=0.128 P=0.438N P=0.020 * P=0.472 |
|POLY 3 | P=0.499 P=0.201 P=0.135 P=0.452N P=0.018 * P=0.497 |
|POLY 1.5 | P=0.536N P=0.215 P=0.139 P=0.428N P=0.025 * P=0.534 |
|POLY 6 | P=0.461 P=0.186 P=0.137 P=0.484N P=0.016 * P=0.468 |
|LOGISTIC REGRESSION| P=0.481N P=0.213 P=0.161 P=0.428N P=0.019 * P=0.494 |
|COCH-ARM / FISHERS | P=0.436N P=0.237 P=0.173 P=0.410N P=0.057 P=0.602N |
|ORDER RESTRICTED | P=0.156 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 11/53 (21%) 12/53 (23%) 14/53 (26%) 14/52 (27%) 7/53 (13%) 10/53 (19%) |
|POLY-3 RATE (b) | 11/42.90 12/39.45 14/38.69 14/40.72 7/37.08 10/40.08 |
|POLY-3 PERCENT (g) | 25.6% 30.4% 36.2% 34.4% 18.9% 25.0% |
|TERMINAL (d) | 7/25 (28%) 7/22 (32%) 9/24 (38%) 9/25 (36%) 4/20 (20%) 3/23 (13%) |
|FIRST INCIDENCE | 500 498 451 470 561 412 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.277N P=0.361 P=0.255 P=0.289 P=0.383N P=0.575 |
|POLY 3 | P=0.222N P=0.405 P=0.211 P=0.260 P=0.325N P=0.572N |
|POLY 1.5 | P=0.215N P=0.442 P=0.234 P=0.282 P=0.295N P=0.549N |
|POLY 6 | P=0.221N P=0.370 P=0.201 P=0.239 P=0.336N P=0.587N |
|LOGISTIC REGRESSION| P=0.248N P=0.384 P=0.202 P=0.250 P=0.325N P=0.546N |
|COCH-ARM / FISHERS | P=0.193N P=0.500 P=0.324 P=0.304 P=0.219N P=0.500N |
|ORDER RESTRICTED | P=0.285N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 5
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Blood Vessel: Aorta |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 1/38.81 0/36.67 1/39.15 2/37.24 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 2.6% 5.4% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 467 --- 302 348 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.642N P=0.487 (e) P=0.504 P=0.216 (e) |
|POLY 3 | P=0.632 P=0.485 (e) P=0.487 P=0.212 (e) |
|POLY 1.5 | P=0.650N P=0.491 (e) P=0.494 P=0.218 (e) |
|POLY 6 | P=0.612 P=0.479 (e) P=0.479 P=0.210 (e) |
|LOGISTIC REGRESSION| P=0.574N P=0.539 (e) P=0.269 P=0.305 (e) |
|COCH-ARM / FISHERS | P=0.632N P=0.500 (e) P=0.500 P=0.248 (e) |
|ORDER RESTRICTED | P=0.320 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 2/36.67 0/38.22 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.5% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 2/24 (8%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- 728 (T) --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.406N (e) P=0.228 (e) (e) (e) |
|POLY 3 | P=0.425N (e) P=0.209 (e) (e) (e) |
|POLY 1.5 | P=0.419N (e) P=0.216 (e) (e) (e) |
|POLY 6 | P=0.426N (e) P=0.204 (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) P=0.228 (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.393N (e) P=0.248 (e) (e) (e) |
|ORDER RESTRICTED | P=0.369N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 6
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 38/53 (72%) 32/53 (60%) 37/53 (70%) 35/53 (66%) 42/53 (79%) 41/53 (77%) |
|POLY-3 RATE (b) | 38/52.51 32/50.34 37/51.22 35/48.91 42/52.39 41/50.42 |
|POLY-3 PERCENT (g) | 72.4% 63.6% 72.2% 71.6% 80.2% 81.3% |
|TERMINAL (d) | 12/25 (48%) 9/22 (41%) 11/24 (46%) 15/25 (60%) 13/20 (65%) 14/23 (61%) |
|FIRST INCIDENCE | 289 289 116 302 113 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.076 P=0.465N P=0.383 P=0.547N P=0.112 P=0.184 |
|POLY 3 | P=0.034 * P=0.225N P=0.581N P=0.553N P=0.237 P=0.198 |
|POLY 1.5 | P=0.033 * P=0.197N P=0.554N P=0.462N P=0.243 P=0.217 |
|POLY 6 | P=0.041 * P=0.265N P=0.575 P=0.524 P=0.228 P=0.197 |
|LOGISTIC REGRESSION| P=0.085 P=0.059N P=0.295N P=0.232N P=0.421 P=0.443 |
|COCH-ARM / FISHERS | P=0.054 P=0.153N P=0.500N P=0.338N P=0.249 P=0.328 |
|ORDER RESTRICTED | P=0.093 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 52/53 (98%) 47/51 (92%) 46/53 (87%) 51/53 (96%) 47/50 (94%) 47/53 (89%) |
|POLY-3 RATE (b) | 52/52.72 47/49.98 46/49.06 51/52.27 47/48.18 47/49.63 |
|POLY-3 PERCENT (g) | 98.6% 94.0% 93.8% 97.6% 97.6% 94.7% |
|TERMINAL (d) | 25/25 (100%) 21/22 (96%) 23/24 (96%) 24/25 (96%) 20/20 (100%) 22/23 (96%) |
|FIRST INCIDENCE | 289 289 196 302 113 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.417 P=0.485 P=0.488N P=0.416 P=0.331 P=0.499 |
|POLY 3 | P=0.471N P=0.212N P=0.184N P=0.637N P=0.645N P=0.251N |
|POLY 1.5 | P=0.366N P=0.191N P=0.116N P=0.590N P=0.533N P=0.163N |
|POLY 6 | P=0.567N P=0.241N P=0.264N P=0.650N P=0.673N P=0.382N |
|LOGISTIC REGRESSION| P=0.239N P=0.164N P=0.073N P=0.512N P=0.388N P=0.101N |
|COCH-ARM / FISHERS | P=0.188N P=0.170N P=0.030N* P=0.500N P=0.287N P=0.056N |
|ORDER RESTRICTED | P=0.208N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 7
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland: Duct |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 40/53 (75%) 37/51 (73%) 34/53 (64%) 41/53 (77%) 44/50 (88%) 40/53 (75%) |
|POLY-3 RATE (b) | 40/50.78 37/47.85 34/47.82 41/51.69 44/47.96 40/49.03 |
|POLY-3 PERCENT (g) | 78.8% 77.3% 71.1% 79.3% 91.7% 81.6% |
|TERMINAL (d) | 18/25 (72%) 14/22 (64%) 14/24 (58%) 17/25 (68%) 19/20 (95%) 17/23 (74%) |
|FIRST INCIDENCE | 289 296 196 302 113 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.150 P=0.448 P=0.439N P=0.348 P=0.071 P=0.294 |
|POLY 3 | P=0.129 P=0.528N P=0.251N P=0.571 P=0.055 P=0.458 |
|POLY 1.5 | P=0.149 P=0.506N P=0.220N P=0.546 P=0.055 P=0.500 |
|POLY 6 | P=0.125 P=0.540N P=0.284N P=0.600 P=0.065 P=0.437 |
|LOGISTIC REGRESSION| P=0.216 P=0.423N P=0.125N P=0.589 P=0.090 P=0.566N |
|COCH-ARM / FISHERS | P=0.198 P=0.454N P=0.145N P=0.500 P=0.082 P=0.589N |
|ORDER RESTRICTED | P=0.129 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/52 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.03 2/39.88 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- --- 302 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.590N (e) (e) P=0.244 (e) (e) |
|POLY 3 | P=0.608N (e) (e) P=0.226 (e) (e) |
|POLY 1.5 | P=0.600N (e) (e) P=0.233 (e) (e) |
|POLY 6 | P=0.615N (e) (e) P=0.219 (e) (e) |
|LOGISTIC REGRESSION| P=0.522N (e) (e) P=0.134 (e) (e) |
|COCH-ARM / FISHERS | P=0.585N (e) (e) P=0.248 (e) (e) |
|ORDER RESTRICTED | P=0.354 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 8
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus |
| Perforation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/52 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 1/39.00 2/37.89 1/38.94 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 5.3% 2.6% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 296 300 472 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.244N P=0.500 P=0.220 P=0.492 (e) (e) |
|POLY 3 | P=0.273N P=0.486 P=0.215 P=0.486 (e) (e) |
|POLY 1.5 | P=0.263N P=0.492 P=0.219 P=0.493 (e) (e) |
|POLY 6 | P=0.279N P=0.479 P=0.213 P=0.478 (e) (e) |
|LOGISTIC REGRESSION| P=0.152N P=0.551 P=0.501 P=0.487 (e) (e) |
|COCH-ARM / FISHERS | P=0.240N P=0.500 P=0.243 P=0.500 (e) (e) |
|ORDER RESTRICTED | P=0.349N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus: Muscularis |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/53 (4%) 1/52 (2%) 1/53 (2%) 1/53 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/41.78 2/38.44 1/36.87 1/38.22 1/36.89 1/37.11 |
|POLY-3 PERCENT (g) | 0.0% 5.2% 2.7% 2.6% 2.7% 2.7% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 0/24 (0%) 1/25 (4%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 624 393 728 (T) 451 577 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.584 P=0.220 P=0.487 P=0.500 P=0.474 P=0.460 |
|POLY 3 | P=0.575 P=0.219 P=0.475 P=0.482 P=0.475 P=0.476 |
|POLY 1.5 | P=0.589 P=0.226 P=0.479 P=0.491 P=0.481 P=0.485 |
|POLY 6 | P=0.562 P=0.211 P=0.473 P=0.473 P=0.473 P=0.469 |
|LOGISTIC REGRESSION| P=0.622N P=0.222 P=0.651 P=0.500 P=0.608 P=0.526 |
|COCH-ARM / FISHERS | P=0.614 P=0.248 P=0.495 P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.333 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 9
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus: Periesophageal Tissue |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/52 (4%) 2/53 (4%) 1/53 (2%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 1/39.00 2/37.89 2/39.62 1/36.44 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 5.3% 5.1% 2.7% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 296 300 472 642 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.330N P=0.500 P=0.220 P=0.226 P=0.473 (e) |
|POLY 3 | P=0.360N P=0.486 P=0.215 P=0.225 P=0.473 (e) |
|POLY 1.5 | P=0.344N P=0.492 P=0.219 P=0.231 P=0.480 (e) |
|POLY 6 | P=0.372N P=0.479 P=0.213 P=0.218 P=0.470 (e) |
|LOGISTIC REGRESSION| P=0.234N P=0.551 P=0.501 P=0.224 P=0.494 (e) |
|COCH-ARM / FISHERS | P=0.312N P=0.500 P=0.243 P=0.248 P=0.500 (e) |
|ORDER RESTRICTED | P=0.319 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Harderian Gland |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 16/53 (30%) 9/53 (17%) 10/53 (19%) 13/53 (25%) 8/52 (15%) 6/52 (12%) |
|POLY-3 RATE (b) | 16/42.80 9/39.12 10/38.44 13/40.12 8/36.30 6/38.13 |
|POLY-3 PERCENT (g) | 37.4% 23.0% 26.0% 32.4% 22.0% 15.7% |
|TERMINAL (d) | 11/25 (44%) 5/22 (23%) 5/24 (21%) 8/25 (32%) 6/20 (30%) 2/23 (9%) |
|FIRST INCIDENCE | 610 624 297 548 662 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.056N P=0.171N P=0.208N P=0.416N P=0.147N P=0.039N* |
|POLY 3 | P=0.036N* P=0.116N P=0.191N P=0.401N P=0.104N P=0.023N* |
|POLY 1.5 | P=0.035N* P=0.101N P=0.176N P=0.366N P=0.088N P=0.020N* |
|POLY 6 | P=0.035N* P=0.133N P=0.201N P=0.440N P=0.118N P=0.025N* |
|LOGISTIC REGRESSION| P=0.050N P=0.147N P=0.219N P=0.479N P=0.107N P=0.032N* |
|COCH-ARM / FISHERS | P=0.034N* P=0.085N P=0.129N P=0.332N P=0.057N P=0.017N* |
|ORDER RESTRICTED | P=0.014N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 10
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Heart |
| Cardiomyopathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 15/53 (28%) 12/53 (23%) 19/52 (37%) 13/53 (25%) 18/53 (34%) 24/52 (46%) |
|POLY-3 RATE (b) | 15/43.14 12/39.52 19/40.33 13/39.50 18/39.38 24/42.25 |
|POLY-3 PERCENT (g) | 34.8% 30.4% 47.1% 32.9% 45.7% 56.8% |
|TERMINAL (d) | 9/25 (36%) 8/22 (36%) 11/24 (46%) 9/25 (36%) 7/20 (35%) 11/23 (48%) |
|FIRST INCIDENCE | 500 526 246 548 113 443 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.006 ** P=0.492N P=0.189 P=0.485N P=0.157 P=0.029 * |
|POLY 3 | P=0.007 ** P=0.423N P=0.172 P=0.522N P=0.210 P=0.028 * |
|POLY 1.5 | P=0.006 ** P=0.383N P=0.178 P=0.470N P=0.239 P=0.030 * |
|POLY 6 | P=0.009 ** P=0.468N P=0.182 P=0.579N P=0.213 P=0.032 * |
|LOGISTIC REGRESSION| P=0.004 ** P=0.451N P=0.150 P=0.568N P=0.199 P=0.021 * |
|COCH-ARM / FISHERS | P=0.009 ** P=0.328N P=0.244 P=0.413N P=0.338 P=0.045 * |
|ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Heart |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/52 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) |
|POLY-3 RATE (b) | 2/43.24 0/38.07 0/36.03 0/38.22 0/36.13 0/36.44 |
|POLY-3 PERCENT (g) | 4.6% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 377 --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.257N P=0.255N P=0.262N P=0.248N P=0.273N P=0.258N |
|POLY 3 | P=0.222N P=0.266N P=0.280N P=0.265N P=0.279N P=0.277N |
|POLY 1.5 | P=0.232N P=0.255N P=0.269N P=0.253N P=0.267N P=0.263N |
|POLY 6 | P=0.211N P=0.279N P=0.287N P=0.280N P=0.288N P=0.290N |
|LOGISTIC REGRESSION| P=0.219N P=0.188N P=0.126N P=0.246N P=0.124N P=0.155N |
|COCH-ARM / FISHERS | P=0.249N P=0.248N P=0.252N P=0.248N P=0.248N P=0.252N |
|ORDER RESTRICTED | P=0.015N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 11
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Heart: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/52 (0%) 0/53 (0%) 1/53 (2%) 2/52 (4%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.03 0/38.22 1/36.33 2/36.89 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.8% 5.4% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | --- --- --- --- 675 597 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.013 * (e) (e) (e) P=0.462 P=0.205 |
|POLY 3 | P=0.014 * (e) (e) (e) P=0.472 P=0.210 |
|POLY 1.5 | P=0.015 * (e) (e) (e) P=0.479 P=0.218 |
|POLY 6 | P=0.014 * (e) (e) (e) P=0.469 P=0.203 |
|LOGISTIC REGRESSION| P=0.014 * (e) (e) (e) P=0.478 P=0.220 |
|COCH-ARM / FISHERS | P=0.015 * (e) (e) (e) P=0.500 P=0.243 |
|ORDER RESTRICTED | P=0.021 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Cecum: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 0/53 (0%) 0/52 (0%) 0/51 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/41.78 1/38.07 0/36.67 0/37.91 0/35.40 2/36.69 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 0.0% 0.0% 5.5% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | --- 728 (T) --- --- --- 706 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.073 P=0.475 (e) (e) (e) P=0.219 |
|POLY 3 | P=0.070 P=0.481 (e) (e) (e) P=0.209 |
|POLY 1.5 | P=0.073 P=0.489 (e) (e) (e) P=0.219 |
|POLY 6 | P=0.068 P=0.473 (e) (e) (e) P=0.200 |
|LOGISTIC REGRESSION| P=0.067 P=0.475 (e) (e) (e) P=0.197 |
|COCH-ARM / FISHERS | P=0.077 P=0.500 (e) (e) (e) P=0.248 |
|ORDER RESTRICTED | P=0.021 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 12
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Colon |
| Parasite Metazoan |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/51 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/42.66 0/38.07 0/36.67 0/38.22 0/35.40 0/36.61 |
|POLY-3 PERCENT (g) | 4.7% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 536 --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.266N P=0.274N P=0.282N P=0.286N P=0.280N P=0.292N |
|POLY 3 | P=0.222N P=0.263N P=0.272N P=0.262N P=0.280N P=0.273N |
|POLY 1.5 | P=0.232N P=0.252N P=0.262N P=0.250N P=0.270N P=0.259N |
|POLY 6 | P=0.210N P=0.276N P=0.281N P=0.277N P=0.288N P=0.287N |
|LOGISTIC REGRESSION| P=0.245N P=0.220N P=0.213N P=0.226N P=0.220N P=0.214N |
|COCH-ARM / FISHERS | P=0.250N P=0.248N P=0.248N P=0.248N P=0.257N P=0.248N |
|ORDER RESTRICTED | P=0.014N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Parasite Metazoan |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 5/53 (9%) 5/53 (9%) 1/53 (2%) 1/52 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 4/41.97 5/40.02 5/37.71 1/39.04 1/36.33 1/36.61 |
|POLY-3 PERCENT (g) | 9.5% 12.5% 13.3% 2.6% 2.8% 2.7% |
|TERMINAL (d) | 3/25 (12%) 0/22 (0%) 3/24 (13%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | 678 498 393 410 353 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.046N* P=0.417 P=0.445 P=0.195N P=0.248N P=0.215N |
|POLY 3 | P=0.044N* P=0.470 P=0.433 P=0.200N P=0.224N P=0.222N |
|POLY 1.5 | P=0.041N* P=0.480 P=0.448 P=0.189N P=0.214N P=0.205N |
|POLY 6 | P=0.047N* P=0.463 P=0.422 P=0.214N P=0.229N P=0.239N |
|LOGISTIC REGRESSION| P=0.036N* P=0.485 P=0.434 P=0.183N P=0.193N P=0.236N |
|COCH-ARM / FISHERS | P=0.036N* P=0.500 P=0.500 P=0.181N P=0.187N P=0.181N |
|ORDER RESTRICTED | P=0.097N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 13
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 0/52 (0%) 2/52 (4%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/37.91 0/35.44 2/36.53 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 5.5% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | --- --- --- --- --- 706 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.011 * (e) (e) (e) (e) P=0.219 |
|POLY 3 | P=0.009 ** (e) (e) (e) (e) P=0.208 |
|POLY 1.5 | P=0.009 ** (e) (e) (e) (e) P=0.217 |
|POLY 6 | P=0.009 ** (e) (e) (e) (e) P=0.200 |
|LOGISTIC REGRESSION| P=0.009 ** (e) (e) (e) (e) P=0.197 |
|COCH-ARM / FISHERS | P=0.010 * (e) (e) (e) (e) P=0.243 |
|ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Calculus Micro Observation Only |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 2/53 (4%) 4/53 (8%) 1/52 (2%) 2/53 (4%) 3/53 (6%) |
|POLY-3 RATE (b) | 5/41.89 2/38.07 4/36.67 1/38.22 2/36.21 3/37.37 |
|POLY-3 PERCENT (g) | 11.9% 5.3% 10.9% 2.6% 5.5% 8.0% |
|TERMINAL (d) | 4/25 (16%) 2/22 (9%) 4/24 (17%) 0/25 (0%) 1/20 (5%) 1/23 (4%) |
|FIRST INCIDENCE | 699 728 (T) 728 (T) 645 707 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.467N P=0.274N P=0.536N P=0.120N P=0.308N P=0.412N |
|POLY 3 | P=0.449N P=0.255N P=0.584N P=0.122N P=0.278N P=0.420N |
|POLY 1.5 | P=0.443N P=0.239N P=0.562N P=0.114N P=0.261N P=0.397N |
|POLY 6 | P=0.449N P=0.273N P=0.601N P=0.131N P=0.287N P=0.440N |
|LOGISTIC REGRESSION| P=0.483N P=0.294N P=0.599N P=0.136N P=0.287N P=0.436N |
|COCH-ARM / FISHERS | P=0.425N P=0.219N P=0.500N P=0.107N P=0.219N P=0.358N |
|ORDER RESTRICTED | P=0.224N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 14
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 2/53 (4%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 1/38.22 2/36.13 1/36.61 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.6% 5.5% 2.7% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 2/20 (10%) 1/23 (4%) |
|FIRST INCIDENCE | --- --- --- 645 728 (T) 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.150 (e) (e) P=0.454 P=0.190 P=0.483 |
|POLY 3 | P=0.149 (e) (e) P=0.482 P=0.206 P=0.474 |
|POLY 1.5 | P=0.158 (e) (e) P=0.489 P=0.214 P=0.483 |
|POLY 6 | P=0.140 (e) (e) P=0.475 P=0.201 P=0.465 |
|LOGISTIC REGRESSION| P=0.149 (e) (e) P=0.497 P=0.190 P=0.483 |
|COCH-ARM / FISHERS | P=0.169 (e) (e) P=0.495 P=0.248 P=0.500 |
|ORDER RESTRICTED | P=0.133 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/53 (2%) 1/53 (2%) 3/52 (6%) 2/53 (4%) 2/53 (4%) |
|POLY-3 RATE (b) | 2/42.16 1/38.07 1/36.82 3/38.64 2/36.47 2/36.61 |
|POLY-3 PERCENT (g) | 4.7% 2.6% 2.7% 7.8% 5.5% 5.5% |
|TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 2/25 (8%) 0/20 (0%) 2/23 (9%) |
|FIRST INCIDENCE | 619 728 (T) 689 470 642 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.417 P=0.542N P=0.543N P=0.480 P=0.634 P=0.646 |
|POLY 3 | P=0.419 P=0.536N P=0.547N P=0.460 P=0.641 P=0.643 |
|POLY 1.5 | P=0.435 P=0.521N P=0.535N P=0.476 P=0.655 P=0.662 |
|POLY 6 | P=0.404 P=0.552N P=0.556N P=0.441 P=0.634 P=0.623 |
|LOGISTIC REGRESSION| P=0.423 P=0.535N P=0.536N P=0.486 P=0.655 P=0.637 |
|COCH-ARM / FISHERS | P=0.458 P=0.500N P=0.500N P=0.491 P=0.691N P=0.691N |
|ORDER RESTRICTED | P=0.504 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 15
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 37/53 (70%) 45/53 (85%) 42/53 (79%) 43/52 (83%) 43/53 (81%) 31/53 (58%) |
|POLY-3 RATE (b) | 37/49.64 45/50.67 42/49.52 43/49.48 43/50.37 31/46.93 |
|POLY-3 PERCENT (g) | 74.5% 88.8% 84.8% 86.9% 85.4% 66.1% |
|TERMINAL (d) | 20/25 (80%) 20/22 (91%) 18/24 (75%) 20/25 (80%) 14/20 (70%) 11/23 (48%) |
|FIRST INCIDENCE | 289 289 219 302 241 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.165N P=0.041 * P=0.132 P=0.135 P=0.051 P=0.443N |
|POLY 3 | P=0.012N* P=0.044 * P=0.143 P=0.083 P=0.123 P=0.236N |
|POLY 1.5 | P=0.008N** P=0.045 * P=0.125 P=0.082 P=0.110 P=0.205N |
|POLY 6 | P=0.018N* P=0.047 * P=0.193 P=0.099 P=0.157 P=0.255N |
|LOGISTIC REGRESSION| P=0.005N** P=0.055 P=0.170 P=0.095 P=0.147 P=0.136N |
|COCH-ARM / FISHERS | P=0.006N** P=0.052 P=0.186 P=0.093 P=0.129 P=0.156N |
|ORDER RESTRICTED | P=0.011N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/37.91 2/37.24 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.4% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- --- --- 348 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.452 (e) (e) (e) P=0.216 (e) |
|POLY 3 | P=0.428 (e) (e) (e) P=0.212 (e) |
|POLY 1.5 | P=0.445 (e) (e) (e) P=0.218 (e) |
|POLY 6 | P=0.408 (e) (e) (e) P=0.210 (e) |
|LOGISTIC REGRESSION| P=0.490 (e) (e) (e) P=0.305 (e) |
|COCH-ARM / FISHERS | P=0.463 (e) (e) (e) P=0.248 (e) |
|ORDER RESTRICTED | P=0.163 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 16
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Nephropathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 34/53 (64%) 39/53 (74%) 35/53 (66%) 42/52 (81%) 36/53 (68%) 45/53 (85%) |
|POLY-3 RATE (b) | 34/45.99 39/47.20 35/43.05 42/47.43 36/42.52 45/48.53 |
|POLY-3 PERCENT (g) | 73.9% 82.6% 81.3% 88.6% 84.7% 92.7% |
|TERMINAL (d) | 20/25 (80%) 19/22 (86%) 23/24 (96%) 24/25 (96%) 19/20 (95%) 21/23 (91%) |
|FIRST INCIDENCE | 377 289 219 302 113 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.018 * P=0.084 P=0.297 P=0.064 P=0.092 P=0.013 * |
|POLY 3 | P=0.009 ** P=0.201 P=0.261 P=0.041 * P=0.138 P=0.007 ** |
|POLY 1.5 | P=0.010 * P=0.202 P=0.324 P=0.044 * P=0.212 P=0.006 ** |
|POLY 6 | P=0.015 * P=0.204 P=0.191 P=0.039 * P=0.103 P=0.011 * |
|LOGISTIC REGRESSION| P=0.005 ** P=0.110 P=0.222 P=0.020 * P=0.124 P=0.002 ** |
|COCH-ARM / FISHERS | P=0.024 * P=0.201 P=0.500 P=0.045 * P=0.419 P=0.012 * |
|ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/42.16 0/38.07 0/36.67 0/37.91 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 4.7% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 619 --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.266N P=0.265N P=0.265N P=0.267N P=0.283N P=0.280N |
|POLY 3 | P=0.225N P=0.260N P=0.269N P=0.261N P=0.273N P=0.270N |
|POLY 1.5 | P=0.234N P=0.251N P=0.261N P=0.252N P=0.263N P=0.257N |
|POLY 6 | P=0.214N P=0.271N P=0.276N P=0.273N P=0.280N P=0.282N |
|LOGISTIC REGRESSION| P=0.256N P=0.250N P=0.257N P=0.251N P=0.260N P=0.257N |
|COCH-ARM / FISHERS | P=0.248N P=0.248N P=0.248N P=0.252N P=0.248N P=0.248N |
|ORDER RESTRICTED | P=0.014N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 17
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney: Pelvis |
| Dilatation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 0/53 (0%) 0/52 (0%) 2/53 (4%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/41.78 1/38.81 0/36.67 0/37.91 2/37.24 1/36.98 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 0.0% 5.4% 2.7% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 467 --- --- 348 624 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.227 P=0.487 (e) (e) P=0.216 P=0.454 |
|POLY 3 | P=0.225 P=0.485 (e) (e) P=0.212 P=0.476 |
|POLY 1.5 | P=0.235 P=0.491 (e) (e) P=0.218 P=0.484 |
|POLY 6 | P=0.215 P=0.479 (e) (e) P=0.210 P=0.468 |
|LOGISTIC REGRESSION| P=0.273 P=0.539 (e) (e) P=0.305 P=0.505 |
|COCH-ARM / FISHERS | P=0.247 P=0.500 (e) (e) P=0.248 P=0.500 |
|ORDER RESTRICTED | P=0.139 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney: Pelvis |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/53 (2%) 0/53 (0%) 0/52 (0%) 5/53 (9%) 1/53 (2%) |
|POLY-3 RATE (b) | 1/41.78 1/38.75 0/36.67 0/37.91 5/36.20 1/36.61 |
|POLY-3 PERCENT (g) | 2.4% 2.6% 0.0% 0.0% 13.8% 2.7% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 3/20 (15%) 1/23 (4%) |
|FIRST INCIDENCE | 728 (T) 498 --- --- 717 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.232 P=0.737 P=0.508N P=0.500N P=0.067 P=0.744 |
|POLY 3 | P=0.221 P=0.744 P=0.526N P=0.519N P=0.071 P=0.731 |
|POLY 1.5 | P=0.236 P=0.751 P=0.520N P=0.512N P=0.078 P=0.742 |
|POLY 6 | P=0.205 P=0.737 P=0.531N P=0.528N P=0.066 P=0.720 |
|LOGISTIC REGRESSION| P=0.222 P=0.753N (e) (e) P=0.063 P=0.744 |
|COCH-ARM / FISHERS | P=0.254 P=0.752N P=0.500N P=0.505N P=0.103 P=0.752N |
|ORDER RESTRICTED | P=0.067 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 18
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney: Transitional Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 2/53 (4%) 1/53 (2%) 2/52 (4%) 6/53 (11%) 5/53 (9%) |
|POLY-3 RATE (b) | 2/41.78 2/38.75 1/36.82 2/37.91 6/36.20 5/36.69 |
|POLY-3 PERCENT (g) | 4.8% 5.2% 2.7% 5.3% 16.6% 13.6% |
|TERMINAL (d) | 2/25 (8%) 1/22 (5%) 0/24 (0%) 2/25 (8%) 4/20 (20%) 4/23 (17%) |
|FIRST INCIDENCE | 728 (T) 498 689 728 (T) 717 706 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.025 * P=0.652 P=0.526N P=0.697 P=0.080 P=0.180 |
|POLY 3 | P=0.022 * P=0.667 P=0.544N P=0.659 P=0.089 P=0.165 |
|POLY 1.5 | P=0.025 * P=0.678 P=0.534N P=0.673 P=0.101 P=0.183 |
|POLY 6 | P=0.019 * P=0.656 P=0.551N P=0.644 P=0.083 P=0.149 |
|LOGISTIC REGRESSION| P=0.020 * P=0.677 P=0.557N P=0.697 P=0.077 P=0.150 |
|COCH-ARM / FISHERS | P=0.032 * P=0.691N P=0.500N P=0.684 P=0.135 P=0.219 |
|ORDER RESTRICTED | P=0.052 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 6/53 (11%) 3/53 (6%) 4/53 (8%) 1/52 (2%) 0/53 (0%) 1/53 (2%) |
|POLY-3 RATE (b) | 6/42.92 3/38.07 4/36.67 1/37.91 0/36.13 1/36.61 |
|POLY-3 PERCENT (g) | 14.0% 7.9% 10.9% 2.6% 0.0% 2.7% |
|TERMINAL (d) | 1/25 (4%) 3/22 (14%) 4/24 (17%) 1/25 (4%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | 610 728 (T) 728 (T) 728 (T) --- 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.034N* P=0.340N P=0.456N P=0.095N P=0.036N* P=0.105N |
|POLY 3 | P=0.028N* P=0.303N P=0.471N P=0.077N P=0.026N* P=0.085N |
|POLY 1.5 | P=0.027N* P=0.276N P=0.441N P=0.068N P=0.023N* P=0.073N |
|POLY 6 | P=0.028N* P=0.339N P=0.503N P=0.091N P=0.030N* P=0.100N |
|LOGISTIC REGRESSION| P=0.033N* P=0.294N P=0.458N P=0.072N P=0.024N* P=0.078N |
|COCH-ARM / FISHERS | P=0.026N* P=0.244N P=0.371N P=0.059N P=0.013N* P=0.056N |
|ORDER RESTRICTED | P=0.013N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 19
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Basophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 22/53 (42%) 23/53 (43%) 20/53 (38%) 16/52 (31%) 15/53 (28%) 7/53 (13%) |
|POLY-3 RATE (b) | 22/44.73 23/42.87 20/40.67 16/39.96 15/39.21 7/37.90 |
|POLY-3 PERCENT (g) | 49.2% 53.7% 49.2% 40.0% 38.3% 18.5% |
|TERMINAL (d) | 10/25 (40%) 10/22 (46%) 11/24 (46%) 10/25 (40%) 8/20 (40%) 5/23 (22%) |
|FIRST INCIDENCE | 513 321 393 525 420 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001N** P=0.291 P=0.545 P=0.269N P=0.345N P=0.008N** |
|POLY 3 | P<0.001N** P=0.417 P=0.587N P=0.260N P=0.211N P=0.002N** |
|POLY 1.5 | P<0.001N** P=0.452 P=0.550N P=0.211N P=0.178N P<0.001N** |
|POLY 6 | P<0.001N** P=0.382 P=0.560 P=0.337N P=0.241N P=0.005N** |
|LOGISTIC REGRESSION| P<0.001N** P=0.392 P=0.573 P=0.255N P=0.206N P=0.003N** |
|COCH-ARM / FISHERS | P<0.001N** P=0.500 P=0.421N P=0.173N P=0.111N P<0.001N** |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Cholangiofibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 0/53 (0%) 3/52 (6%) 3/53 (6%) 5/53 (9%) |
|POLY-3 RATE (b) | 0/41.78 1/38.07 0/36.67 3/38.43 3/36.13 5/37.09 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 7.8% 8.3% 13.5% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 0/24 (0%) 2/25 (8%) 3/20 (15%) 4/23 (17%) |
|FIRST INCIDENCE | --- 728 (T) --- 570 728 (T) 586 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002 ** P=0.475 (e) P=0.115 P=0.083 P=0.024 * |
|POLY 3 | P=0.002 ** P=0.481 (e) P=0.104 P=0.094 P=0.021 * |
|POLY 1.5 | P=0.003 ** P=0.489 (e) P=0.109 P=0.101 P=0.024 * |
|POLY 6 | P=0.002 ** P=0.473 (e) P=0.098 P=0.090 P=0.019 * |
|LOGISTIC REGRESSION| P=0.002 ** P=0.475 (e) P=0.108 P=0.083 P=0.021 * |
|COCH-ARM / FISHERS | P=0.004 ** P=0.500 (e) P=0.118 P=0.121 P=0.028 * |
|ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 20
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Clear Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 13/53 (25%) 6/53 (11%) 10/53 (19%) 3/52 (6%) 6/53 (11%) 11/53 (21%) |
|POLY-3 RATE (b) | 13/43.13 6/38.07 10/36.67 3/38.49 6/36.41 11/36.61 |
|POLY-3 PERCENT (g) | 30.1% 15.8% 27.3% 7.8% 16.5% 30.1% |
|TERMINAL (d) | 9/25 (36%) 6/22 (27%) 10/24 (42%) 2/25 (8%) 4/20 (20%) 11/23 (48%) |
|FIRST INCIDENCE | 321 728 (T) 728 (T) 548 675 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.323 P=0.108N P=0.381N P=0.010N* P=0.152N P=0.515N |
|POLY 3 | P=0.330 P=0.099N P=0.486N P=0.010N* P=0.121N P=0.594N |
|POLY 1.5 | P=0.355 P=0.083N P=0.438N P=0.008N** P=0.102N P=0.524N |
|POLY 6 | P=0.310 P=0.121N P=0.531N P=0.012N* P=0.131N P=0.532 |
|LOGISTIC REGRESSION| P=0.292 P=0.102N P=0.475N P=0.011N* P=0.116N P=0.584 |
|COCH-ARM / FISHERS | P=0.406 P=0.064N P=0.319N P=0.007N** P=0.064N P=0.408N |
|ORDER RESTRICTED | P=0.140N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Eosinophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 15/53 (28%) 13/53 (25%) 18/53 (34%) 18/52 (35%) 23/53 (43%) 28/53 (53%) |
|POLY-3 RATE (b) | 15/45.03 13/41.26 18/40.23 18/40.45 23/44.28 28/46.89 |
|POLY-3 PERCENT (g) | 33.3% 31.5% 44.7% 44.5% 52.0% 59.7% |
|TERMINAL (d) | 6/25 (24%) 6/22 (27%) 7/24 (29%) 11/25 (44%) 5/20 (25%) 8/23 (35%) |
|FIRST INCIDENCE | 289 289 561 561 321 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.567N P=0.234 P=0.257 P=0.041 * P=0.009 ** |
|POLY 3 | P<0.001 ** P=0.521N P=0.192 P=0.196 P=0.054 P=0.007 ** |
|POLY 1.5 | P<0.001 ** P=0.476N P=0.215 P=0.242 P=0.052 P=0.007 ** |
|POLY 6 | P=0.002 ** P=0.570N P=0.194 P=0.158 P=0.066 P=0.010 * |
|LOGISTIC REGRESSION| P<0.001 ** P=0.422N P=0.246 P=0.262 P=0.083 P=0.012 * |
|COCH-ARM / FISHERS | P<0.001 ** P=0.413N P=0.338 P=0.313 P=0.078 P=0.009 ** |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 21
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Fatty Change Diffuse |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 4/53 (8%) 10/53 (19%) 12/52 (23%) 20/53 (38%) 26/53 (49%) |
|POLY-3 RATE (b) | 1/41.78 4/38.94 10/41.61 12/40.62 20/37.54 26/41.53 |
|POLY-3 PERCENT (g) | 2.4% 10.3% 24.0% 29.5% 53.3% 62.6% |
|TERMINAL (d) | 1/25 (4%) 1/22 (5%) 3/24 (13%) 6/25 (24%) 13/20 (65%) 16/23 (70%) |
|FIRST INCIDENCE | 728 (T) 526 246 472 580 412 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.146 P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.157 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.165 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.149 P=0.004 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.160 P=0.011 * P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.181 P=0.004 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Fatty Change Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 6/53 (11%) 5/53 (9%) 6/52 (12%) 6/53 (11%) 4/53 (8%) |
|POLY-3 RATE (b) | 5/42.06 6/40.20 5/36.67 6/40.20 6/37.85 4/38.38 |
|POLY-3 PERCENT (g) | 11.9% 14.9% 13.6% 14.9% 15.9% 10.4% |
|TERMINAL (d) | 4/25 (16%) 3/22 (14%) 5/24 (21%) 1/25 (4%) 2/20 (10%) 0/23 (0%) |
|FIRST INCIDENCE | 651 296 728 (T) 525 500 513 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.440N P=0.423 P=0.593 P=0.437 P=0.366 P=0.578N |
|POLY 3 | P=0.412N P=0.468 P=0.542 P=0.468 P=0.425 P=0.558N |
|POLY 1.5 | P=0.400N P=0.484 P=0.565 P=0.477 P=0.440 P=0.539N |
|POLY 6 | P=0.413N P=0.447 P=0.523 P=0.462 P=0.427 P=0.571N |
|LOGISTIC REGRESSION| P=0.383N P=0.506 P=0.526 P=0.475 P=0.428 P=0.534N |
|COCH-ARM / FISHERS | P=0.368N P=0.500 P=0.629N P=0.486 P=0.500 P=0.500N |
|ORDER RESTRICTED | P=0.559N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 22
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 24/53 (45%) 28/53 (53%) 27/53 (51%) 24/52 (46%) 39/53 (74%) 31/53 (58%) |
|POLY-3 RATE (b) | 24/48.52 28/47.78 27/46.71 24/42.21 39/47.23 31/46.44 |
|POLY-3 PERCENT (g) | 49.5% 58.6% 57.8% 56.9% 82.6% 66.8% |
|TERMINAL (d) | 10/25 (40%) 9/22 (41%) 9/24 (38%) 15/25 (60%) 17/20 (85%) 13/23 (57%) |
|FIRST INCIDENCE | 289 393 196 470 113 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.041 * P=0.179 P=0.238 P=0.463 P=0.002 ** P=0.080 |
|POLY 3 | P=0.016 * P=0.240 P=0.268 P=0.307 P<0.001 ** P=0.060 |
|POLY 1.5 | P=0.023 * P=0.248 P=0.279 P=0.403 P<0.001 ** P=0.075 |
|POLY 6 | P=0.012 * P=0.236 P=0.266 P=0.212 P<0.001 ** P=0.049 * |
|LOGISTIC REGRESSION| P=0.047 * P=0.344 P=0.451 P=0.531 P=0.004 ** P=0.150 |
|COCH-ARM / FISHERS | P=0.044 * P=0.280 P=0.349 P=0.542 P=0.003 ** P=0.122 |
|ORDER RESTRICTED | P=0.005 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatodiaphragmatic Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 3/53 (6%) 3/53 (6%) 1/52 (2%) 1/53 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 3/41.97 3/39.45 3/39.06 1/38.31 1/36.13 1/37.04 |
|POLY-3 PERCENT (g) | 7.2% 7.6% 7.7% 2.6% 2.8% 2.7% |
|TERMINAL (d) | 2/25 (8%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 1/20 (5%) 0/23 (0%) |
|FIRST INCIDENCE | 678 289 196 616 728 (T) 603 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.167N P=0.603 P=0.612 P=0.351N P=0.392N P=0.368N |
|POLY 3 | P=0.163N P=0.634 P=0.630 P=0.338N P=0.360N P=0.351N |
|POLY 1.5 | P=0.156N P=0.647 P=0.636 P=0.325N P=0.345N P=0.334N |
|POLY 6 | P=0.169N P=0.620 P=0.626 P=0.352N P=0.370N P=0.366N |
|LOGISTIC REGRESSION| P=0.120N P=0.651N P=0.551N P=0.338N P=0.366N P=0.348N |
|COCH-ARM / FISHERS | P=0.139N P=0.661N P=0.661N P=0.316N P=0.309N P=0.309N |
|ORDER RESTRICTED | P=0.300N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 23
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 3/52 (6%) 8/53 (15%) 12/53 (23%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 3/38.12 8/36.44 12/37.65 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.9% 22.0% 31.9% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 2/25 (8%) 5/20 (25%) 8/23 (35%) |
|FIRST INCIDENCE | --- --- --- 675 675 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) P=0.109 P=0.002 ** P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) P=0.102 P=0.002 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) P=0.108 P=0.002 ** P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) P=0.096 P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.095 P=0.002 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.118 P=0.003 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 47/53 (89%) 44/53 (83%) 47/53 (89%) 50/52 (96%) 48/53 (91%) 50/53 (94%) |
|POLY-3 RATE (b) | 47/51.32 44/50.12 47/49.49 50/51.75 48/50.99 50/51.75 |
|POLY-3 PERCENT (g) | 91.6% 87.8% 95.0% 96.6% 94.1% 96.6% |
|TERMINAL (d) | 23/25 (92%) 20/22 (91%) 23/24 (96%) 25/25 (100%) 18/20 (90%) 22/23 (96%) |
|FIRST INCIDENCE | 289 289 116 302 113 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.114 P=0.403 P=0.308 P=0.234 P=0.130 P=0.143 |
|POLY 3 | P=0.104 P=0.371N P=0.378 P=0.236 P=0.449 P=0.232 |
|POLY 1.5 | P=0.091 P=0.331N P=0.445 P=0.196 P=0.442 P=0.230 |
|POLY 6 | P=0.144 P=0.454N P=0.333 P=0.283 P=0.501 P=0.254 |
|LOGISTIC REGRESSION| P=0.075 P=0.308N P=0.494 P=0.141 P=0.444 P=0.217 |
|COCH-ARM / FISHERS | P=0.089 P=0.289N P=0.620N P=0.141 P=0.500 P=0.244 |
|ORDER RESTRICTED | P=0.086 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 24
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Mixed Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 33/53 (62%) 24/53 (45%) 24/53 (45%) 29/52 (56%) 27/53 (51%) 26/53 (49%) |
|POLY-3 RATE (b) | 33/45.39 24/39.87 24/37.89 29/39.73 27/39.18 26/38.39 |
|POLY-3 PERCENT (g) | 72.7% 60.2% 63.4% 73.0% 68.9% 67.7% |
|TERMINAL (d) | 21/25 (84%) 19/22 (86%) 20/24 (83%) 24/25 (96%) 19/20 (95%) 22/23 (96%) |
|FIRST INCIDENCE | 500 547 587 525 420 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.490 P=0.199N P=0.120N P=0.371N P=0.549 P=0.286N |
|POLY 3 | P=0.498 P=0.140N P=0.232N P=0.595 P=0.439N P=0.389N |
|POLY 1.5 | P=0.488N P=0.092N P=0.153N P=0.449N P=0.335N P=0.243N |
|POLY 6 | P=0.371 P=0.238N P=0.350N P=0.353 P=0.528N P=0.618N |
|LOGISTIC REGRESSION| P=0.379 P=0.141N P=0.190N P=0.546 P=0.464N P=0.428N |
|COCH-ARM / FISHERS | P=0.371N P=0.059N P=0.059N P=0.316N P=0.164N P=0.120N |
|ORDER RESTRICTED | P=0.460N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 10/53 (19%) 3/53 (6%) 3/52 (6%) 6/53 (11%) 18/53 (34%) |
|POLY-3 RATE (b) | 4/44.47 10/42.96 3/37.19 3/39.69 6/37.09 18/45.30 |
|POLY-3 PERCENT (g) | 9.0% 23.3% 8.1% 7.6% 16.2% 39.7% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 2/24 (8%) 0/25 (0%) 2/20 (10%) 2/23 (9%) |
|FIRST INCIDENCE | 377 289 570 410 555 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.065 P=0.547N P=0.547N P=0.279 P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.060 P=0.597N P=0.562N P=0.261 P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.066 P=0.570N P=0.539N P=0.290 P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.056 P=0.619N P=0.586N P=0.244 P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.115 P=0.418N P=0.496N P=0.406 P=0.002 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.075 P=0.500N P=0.511N P=0.371 P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 25
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 13/53 (25%) 11/53 (21%) 21/53 (40%) 44/52 (85%) 42/53 (79%) 48/53 (91%) |
|POLY-3 RATE (b) | 13/43.77 11/39.99 21/41.81 44/47.88 42/43.72 48/49.81 |
|POLY-3 PERCENT (g) | 29.7% 27.5% 50.2% 91.9% 96.1% 96.4% |
|TERMINAL (d) | 7/25 (28%) 6/22 (27%) 11/24 (46%) 24/25 (96%) 20/20 (100%) 22/23 (96%) |
|FIRST INCIDENCE | 321 503 246 410 267 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.559N P=0.053 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.508N P=0.037 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.471N P=0.041 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.544N P=0.039 * P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.471N P=0.048 * P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.408N P=0.072 P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Toxic Hepatopathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/53 (4%) 3/53 (6%) 8/52 (15%) 27/53 (51%) 44/53 (83%) |
|POLY-3 RATE (b) | 0/41.78 2/38.44 3/36.87 8/39.30 27/39.30 44/47.12 |
|POLY-3 PERCENT (g) | 0.0% 5.2% 8.1% 20.4% 68.7% 93.4% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 2/24 (8%) 5/25 (20%) 15/20 (75%) 22/23 (96%) |
|FIRST INCIDENCE | --- 624 677 470 420 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.220 P=0.105 P=0.004 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.219 P=0.097 P=0.002 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.226 P=0.102 P=0.003 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.211 P=0.094 P=0.002 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.222 P=0.093 P=0.004 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.248 P=0.121 P=0.003 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 26
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 7/53 (13%) 4/53 (8%) 2/53 (4%) 3/52 (6%) 2/53 (4%) 7/53 (13%) |
|POLY-3 RATE (b) | 7/42.31 4/38.30 2/36.67 3/37.91 2/36.15 7/37.91 |
|POLY-3 PERCENT (g) | 16.6% 10.4% 5.5% 7.9% 5.5% 18.5% |
|TERMINAL (d) | 4/25 (16%) 3/22 (14%) 2/24 (8%) 3/25 (12%) 1/20 (5%) 4/23 (17%) |
|FIRST INCIDENCE | 651 668 728 (T) 728 (T) 721 412 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.215 P=0.363N P=0.111N P=0.189N P=0.145N P=0.513 |
|POLY 3 | P=0.239 P=0.318N P=0.116N P=0.202N P=0.120N P=0.527 |
|POLY 1.5 | P=0.246 P=0.295N P=0.105N P=0.184N P=0.108N P=0.559 |
|POLY 6 | P=0.236 P=0.347N P=0.126N P=0.228N P=0.129N P=0.496 |
|LOGISTIC REGRESSION| P=0.199 P=0.347N P=0.121N P=0.221N P=0.123N P=0.515 |
|COCH-ARM / FISHERS | P=0.259 P=0.263N P=0.080N P=0.167N P=0.080N P=0.612N |
|ORDER RESTRICTED | P=0.152 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 4/53 (8%) 2/53 (4%) 2/52 (4%) 3/53 (6%) 6/53 (11%) |
|POLY-3 RATE (b) | 1/41.78 4/38.44 2/36.67 2/37.91 3/36.36 6/37.63 |
|POLY-3 PERCENT (g) | 2.4% 10.4% 5.5% 5.3% 8.3% 15.9% |
|TERMINAL (d) | 1/25 (4%) 3/22 (14%) 2/24 (8%) 2/25 (8%) 0/20 (0%) 3/23 (13%) |
|FIRST INCIDENCE | 728 (T) 624 728 (T) 728 (T) 675 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.035 * P=0.147 P=0.486 P=0.500 P=0.245 P=0.045 * |
|POLY 3 | P=0.033 * P=0.153 P=0.455 P=0.466 P=0.257 P=0.039 * |
|POLY 1.5 | P=0.037 * P=0.163 P=0.466 P=0.479 P=0.269 P=0.045 * |
|POLY 6 | P=0.031 * P=0.143 P=0.446 P=0.451 P=0.251 P=0.035 * |
|LOGISTIC REGRESSION| P=0.030 * P=0.138 P=0.486 P=0.500 P=0.245 P=0.041 * |
|COCH-ARM / FISHERS | P=0.045 * P=0.181 P=0.500 P=0.493 P=0.309 P=0.056 |
|ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 27
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 2/53 (4%) 2/53 (4%) 2/52 (4%) 1/53 (2%) 13/53 (25%) |
|POLY-3 RATE (b) | 3/42.17 2/38.74 2/36.67 2/38.28 1/36.41 13/40.14 |
|POLY-3 PERCENT (g) | 7.1% 5.2% 5.5% 5.2% 2.8% 32.4% |
|TERMINAL (d) | 1/25 (4%) 1/22 (5%) 2/24 (8%) 1/25 (4%) 0/20 (0%) 5/23 (22%) |
|FIRST INCIDENCE | 619 503 728 (T) 624 651 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.553N P=0.535N P=0.543N P=0.382N P=0.005 ** |
|POLY 3 | P<0.001 ** P=0.539N P=0.563N P=0.544N P=0.359N P=0.003 ** |
|POLY 1.5 | P<0.001 ** P=0.523N P=0.547N P=0.527N P=0.344N P=0.004 ** |
|POLY 6 | P<0.001 ** P=0.557N P=0.578N P=0.563N P=0.367N P=0.003 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.516N P=0.569N P=0.541N P=0.348N P=0.006 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.500N P=0.509N P=0.309N P=0.006 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Centrilobular |
| Degeneration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 2/53 (4%) 3/53 (6%) 4/52 (8%) 4/53 (8%) 5/53 (9%) |
|POLY-3 RATE (b) | 4/43.64 2/39.16 3/38.28 4/39.45 4/36.71 5/38.54 |
|POLY-3 PERCENT (g) | 9.2% 5.1% 7.8% 10.1% 10.9% 13.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 2/20 (10%) 0/23 (0%) |
|FIRST INCIDENCE | 310 420 451 589 555 443 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.189 P=0.404N P=0.580N P=0.553 P=0.551 P=0.417 |
|POLY 3 | P=0.195 P=0.388N P=0.571N P=0.587 P=0.546 P=0.422 |
|POLY 1.5 | P=0.207 P=0.368N P=0.555N P=0.606 P=0.573 P=0.448 |
|POLY 6 | P=0.187 P=0.409N P=0.581N P=0.571 P=0.528 P=0.401 |
|LOGISTIC REGRESSION| P=0.246 P=0.273N P=0.392N P=0.630N P=0.630N P=0.578 |
|COCH-ARM / FISHERS | P=0.229 P=0.339N P=0.500N P=0.631 P=0.642N P=0.500 |
|ORDER RESTRICTED | P=0.328 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 28
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 13/53 (25%) 17/53 (32%) 17/52 (33%) 24/53 (45%) 34/53 (64%) |
|POLY-3 RATE (b) | 2/42.11 13/41.41 17/40.93 17/43.29 24/43.66 34/45.17 |
|POLY-3 PERCENT (g) | 4.8% 31.4% 41.5% 39.3% 55.0% 75.3% |
|TERMINAL (d) | 0/25 (0%) 4/22 (18%) 7/24 (29%) 4/25 (16%) 10/20 (50%) 15/23 (65%) |
|FIRST INCIDENCE | 651 393 393 470 267 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Multinucleated |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 4/53 (8%) 13/52 (25%) 18/53 (34%) 35/53 (66%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 4/37.39 13/41.43 18/39.88 35/48.44 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 10.7% 31.4% 45.1% 72.3% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 2/24 (8%) 5/25 (20%) 7/20 (35%) 13/23 (57%) |
|FIRST INCIDENCE | --- --- 570 499 267 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) P=0.053 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** (e) P=0.047 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) P=0.050 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** (e) P=0.045 * P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) P=0.050 P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) P=0.059 P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 29
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Oval Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 4/53 (8%) 2/53 (4%) 6/52 (12%) 15/53 (28%) 35/53 (66%) |
|POLY-3 RATE (b) | 1/41.78 4/38.73 2/37.15 6/38.93 15/37.58 35/44.51 |
|POLY-3 PERCENT (g) | 2.4% 10.3% 5.4% 15.4% 39.9% 78.6% |
|TERMINAL (d) | 1/25 (4%) 2/22 (9%) 1/24 (4%) 4/25 (16%) 8/20 (40%) 18/23 (78%) |
|FIRST INCIDENCE | 728 (T) 624 584 525 500 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.148 P=0.477 P=0.054 P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.155 P=0.459 P=0.044 * P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.164 P=0.468 P=0.048 * P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.147 P=0.454 P=0.040 * P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.149 P=0.463 P=0.045 * P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.181 P=0.500 P=0.053 P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 44/53 (83%) 44/53 (83%) 40/53 (75%) 40/53 (75%) 41/53 (77%) 36/52 (69%) |
|POLY-3 RATE (b) | 44/49.96 44/48.57 40/45.76 40/47.07 41/44.78 36/42.51 |
|POLY-3 PERCENT (g) | 88.1% 90.6% 87.4% 85.0% 91.6% 84.7% |
|TERMINAL (d) | 22/25 (88%) 18/22 (82%) 20/24 (83%) 21/25 (84%) 18/20 (90%) 21/23 (91%) |
|FIRST INCIDENCE | 310 432 219 429 348 451 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.309N P=0.250 P=0.539 P=0.507N P=0.276 P=0.390N |
|POLY 3 | P=0.350N P=0.466 P=0.590N P=0.436N P=0.406 P=0.424N |
|POLY 1.5 | P=0.166N P=0.487 P=0.502N P=0.334N P=0.536 P=0.234N |
|POLY 6 | P=0.505 P=0.509 P=0.631N P=0.545N P=0.366 P=0.633 |
|LOGISTIC REGRESSION| P=0.085N P=0.479 P=0.474N P=0.301N P=0.539 P=0.177N |
|COCH-ARM / FISHERS | P=0.055N P=0.602N P=0.237N P=0.237N P=0.313N P=0.076N |
|ORDER RESTRICTED | P=0.413N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 30
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 8/53 (15%) 7/53 (13%) 6/53 (11%) 7/53 (13%) 8/52 (15%) |
|POLY-3 RATE (b) | 5/43.26 8/38.96 7/37.70 6/40.97 7/38.10 8/40.24 |
|POLY-3 PERCENT (g) | 11.6% 20.5% 18.6% 14.6% 18.4% 19.9% |
|TERMINAL (d) | 1/25 (4%) 5/22 (23%) 5/24 (21%) 1/25 (4%) 3/20 (15%) 2/23 (9%) |
|FIRST INCIDENCE | 377 600 561 470 267 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.281 P=0.207 P=0.327 P=0.460 P=0.279 P=0.217 |
|POLY 3 | P=0.313 P=0.208 P=0.284 P=0.462 P=0.291 P=0.227 |
|POLY 1.5 | P=0.323 P=0.233 P=0.307 P=0.480 P=0.313 P=0.243 |
|POLY 6 | P=0.308 P=0.184 P=0.267 P=0.440 P=0.281 P=0.214 |
|LOGISTIC REGRESSION| P=0.330 P=0.244 P=0.335 P=0.538 P=0.391 P=0.363 |
|COCH-ARM / FISHERS | P=0.326 P=0.278 P=0.380 P=0.500 P=0.380 P=0.265 |
|ORDER RESTRICTED | P=0.266 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Metaplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 4/53 (8%) 3/52 (6%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 2/38.22 4/36.48 3/36.67 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.2% 11.0% 8.2% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 2/25 (8%) 0/20 (0%) 2/23 (9%) |
|FIRST INCIDENCE | --- --- --- 728 (T) 667 668 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.010 * (e) (e) P=0.237 P=0.049 * P=0.100 |
|POLY 3 | P=0.009 ** (e) (e) P=0.217 P=0.044 * P=0.096 |
|POLY 1.5 | P=0.010 * (e) (e) P=0.227 P=0.048 * P=0.103 |
|POLY 6 | P=0.008 ** (e) (e) P=0.207 P=0.043 * P=0.090 |
|LOGISTIC REGRESSION| P=0.009 ** (e) (e) P=0.237 P=0.044 * P=0.090 |
|COCH-ARM / FISHERS | P=0.012 * (e) (e) P=0.248 P=0.059 P=0.118 |
|ORDER RESTRICTED | P=0.017 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 31
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 14/53 (26%) 17/53 (32%) 12/53 (23%) 20/53 (38%) 8/53 (15%) 3/52 (6%) |
|POLY-3 RATE (b) | 14/42.58 17/40.17 12/37.26 20/40.24 8/36.84 3/37.09 |
|POLY-3 PERCENT (g) | 32.9% 42.3% 32.2% 49.7% 21.7% 8.1% |
|TERMINAL (d) | 11/25 (44%) 10/22 (46%) 9/24 (38%) 15/25 (60%) 4/20 (20%) 2/23 (9%) |
|FIRST INCIDENCE | 610 451 636 570 662 513 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001N** P=0.192 P=0.490N P=0.102 P=0.253N P=0.007N** |
|POLY 3 | P<0.001N** P=0.249 P=0.570N P=0.083 P=0.193N P=0.006N** |
|POLY 1.5 | P<0.001N** P=0.281 P=0.529N P=0.109 P=0.170N P=0.005N** |
|POLY 6 | P<0.001N** P=0.225 P=0.596 P=0.062 P=0.200N P=0.007N** |
|LOGISTIC REGRESSION| P<0.001N** P=0.192 P=0.585 P=0.048 * P=0.211N P=0.009N** |
|COCH-ARM / FISHERS | P<0.001N** P=0.335 P=0.411N P=0.149 P=0.115N P=0.004N** |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Metaplasia Bronchiolar |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 6/53 (11%) 5/53 (9%) 9/53 (17%) 23/53 (43%) 28/52 (54%) |
|POLY-3 RATE (b) | 5/41.78 6/38.76 5/37.19 9/38.79 23/37.87 28/39.89 |
|POLY-3 PERCENT (g) | 12.0% 15.5% 13.4% 23.2% 60.7% 70.2% |
|TERMINAL (d) | 5/25 (20%) 3/22 (14%) 4/24 (17%) 7/25 (28%) 16/20 (80%) 19/23 (83%) |
|FIRST INCIDENCE | 728 (T) 624 570 624 561 513 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.406 P=0.604 P=0.170 P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.447 P=0.556 P=0.148 P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.467 P=0.573 P=0.168 P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.430 P=0.547 P=0.128 P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.394 P=0.528 P=0.112 P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.629N P=0.195 P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 32
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mandibular |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/51 (4%) 1/53 (2%) 1/51 (2%) 1/51 (2%) |
|POLY-3 RATE (b) | 0/41.78 1/38.16 2/36.60 1/38.52 1/35.23 1/35.09 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 5.5% 2.6% 2.8% 2.9% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 0/25 (0%) 1/20 (5%) 1/23 (4%) |
|FIRST INCIDENCE | --- 706 301 645 728 (T) 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.559 P=0.462 P=0.224 P=0.454 P=0.455 P=0.483 |
|POLY 3 | P=0.519 P=0.482 P=0.208 P=0.484 P=0.466 P=0.465 |
|POLY 1.5 | P=0.536 P=0.489 P=0.212 P=0.491 P=0.473 P=0.475 |
|POLY 6 | P=0.506 P=0.474 P=0.206 P=0.476 P=0.462 P=0.457 |
|LOGISTIC REGRESSION| P=0.563 P=0.473 P=0.288 P=0.500 P=0.455 P=0.483 |
|COCH-ARM / FISHERS | P=0.569 P=0.500 P=0.238 P=0.500 P=0.490 P=0.490 |
|ORDER RESTRICTED | P=0.315 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mandibular |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 38/53 (72%) 41/53 (77%) 38/51 (75%) 31/53 (58%) 30/51 (59%) 29/51 (57%) |
|POLY-3 RATE (b) | 38/46.17 41/46.30 38/44.92 31/41.86 30/40.64 29/40.56 |
|POLY-3 PERCENT (g) | 82.3% 88.6% 84.6% 74.1% 73.8% 71.5% |
|TERMINAL (d) | 24/25 (96%) 21/22 (96%) 20/24 (83%) 22/25 (88%) 15/20 (75%) 19/23 (83%) |
|FIRST INCIDENCE | 321 321 196 470 353 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.056N P=0.110 P=0.335 P=0.215N P=0.484N P=0.223N |
|POLY 3 | P=0.016N* P=0.258 P=0.495 P=0.217N P=0.222N P=0.147N |
|POLY 1.5 | P=0.014N* P=0.284 P=0.442 P=0.146N P=0.200N P=0.120N |
|POLY 6 | P=0.020N* P=0.235 P=0.586 P=0.375N P=0.216N P=0.183N |
|LOGISTIC REGRESSION| P=0.023N* P=0.139 P=0.230 P=0.277N P=0.338N P=0.253N |
|COCH-ARM / FISHERS | P=0.011N* P=0.328 P=0.460 P=0.111N P=0.120N P=0.084N |
|ORDER RESTRICTED | P=0.052N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 33
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 0/53 (0%) 0/52 (0%) 0/52 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/41.78 1/38.83 0/36.67 0/37.91 0/35.44 2/36.98 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 0.0% 0.0% 5.4% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | --- 451 --- --- --- 624 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.067 P=0.492 (e) (e) (e) P=0.206 |
|POLY 3 | P=0.070 P=0.485 (e) (e) (e) P=0.211 |
|POLY 1.5 | P=0.073 P=0.491 (e) (e) (e) P=0.220 |
|POLY 6 | P=0.069 P=0.479 (e) (e) (e) P=0.203 |
|LOGISTIC REGRESSION| P=0.080 P=0.541 (e) (e) (e) P=0.214 |
|COCH-ARM / FISHERS | P=0.077 P=0.500 (e) (e) (e) P=0.248 |
|ORDER RESTRICTED | P=0.021 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Lumbar |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/5 (40%) 1/4 (25%) 0/4 (0%) 0/4 (0%) 1/3 (33%) 0/7 (0%) |
|POLY-3 RATE (b) | 2/4.62 1/2.09 0/1.82 0/2.06 1/2.97 0/4.67 |
|POLY-3 PERCENT (g) | 43.3% 48.0% 0.0% 0.0% 33.7% 0.0% |
|TERMINAL (d) | 1/3 (33%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/2 (0%) |
|FIRST INCIDENCE | 678 451 --- --- 675 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.240N P=0.729 P=0.531N P=0.515N P=0.662N P=0.302N |
|POLY 3 | P=0.116N P=0.728 P=0.459N P=0.426N P=0.669N P=0.197N |
|POLY 1.5 | P=0.134N P=0.711N P=0.388N P=0.346N P=0.678N P=0.171N |
|POLY 6 | P=0.097N P=0.657 P=0.559N P=0.552N P=0.656N P=0.225N |
|LOGISTIC REGRESSION| P=0.157N P=0.802N P=0.759N P=0.792N P=0.741N P=0.212N |
|COCH-ARM / FISHERS | P=0.176N P=0.595N P=0.278N P=0.278N P=0.714N P=0.152N |
|ORDER RESTRICTED | P=0.026N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 34
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Lumbar |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/5 (40%) 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/3 (0%) 0/7 (0%) |
|POLY-3 RATE (b) | 2/4.42 1/2.09 0/1.82 0/2.06 0/2.77 0/4.67 |
|POLY-3 PERCENT (g) | 45.2% 48.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 2/3 (67%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/2 (0%) |
|FIRST INCIDENCE | 728 (T) 451 --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.111N P=0.492 P=1.000N P=1.000N P=0.500N P=0.309N |
|POLY 3 | P=0.053N P=0.748 P=0.447N P=0.412N P=0.321N P=0.183N |
|POLY 1.5 | P=0.070N P=0.707N P=0.381N P=0.338N P=0.330N P=0.164N |
|POLY 6 | P=0.036N* P=0.697 P=0.545N P=0.537N P=0.308N P=0.196N |
|LOGISTIC REGRESSION| P=0.101N P=0.901N (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.114N P=0.595N P=0.278N P=0.278N P=0.357N P=0.152N |
|ORDER RESTRICTED | P=0.011N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Lumbar |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/5 (0%) 1/4 (25%) 1/4 (25%) 2/4 (50%) 1/3 (33%) 1/7 (14%) |
|POLY-3 RATE (b) | 0/4.42 1/2.06 1/2.14 2/2.80 1/2.97 1/4.90 |
|POLY-3 PERCENT (g) | 0.0% 48.6% 46.6% 71.4% 33.7% 20.4% |
|TERMINAL (d) | 0/3 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/2 (0%) |
|FIRST INCIDENCE | --- 467 638 599 675 668 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.481 P=0.487 P=0.454 P=0.200 P=0.454 P=0.455 |
|POLY 3 | P=0.620N P=0.345 P=0.352 P=0.064 P=0.415 P=0.521 |
|POLY 1.5 | P=0.594N P=0.387 P=0.382 P=0.092 P=0.404 P=0.534 |
|POLY 6 | P=0.623 P=0.306 P=0.320 P=0.040 * P=0.433 P=0.516 |
|LOGISTIC REGRESSION| P=0.544N P=0.983 P=0.387 P=0.157 P=0.315 P=0.541 |
|COCH-ARM / FISHERS | P=0.558N P=0.444 P=0.444 P=0.167 P=0.375 P=0.583 |
|ORDER RESTRICTED | P=0.080 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 35
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/5 (0%) 0/4 (0%) 0/4 (0%) 0/4 (0%) 2/3 (67%) 2/7 (29%) |
|POLY-3 RATE (b) | 0/4.42 0/1.32 0/1.82 0/2.06 2/2.80 2/4.72 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 71.5% 42.4% |
|TERMINAL (d) | 0/3 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 1/2 (50%) |
|FIRST INCIDENCE | --- --- --- --- 721 716 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.050 (e) (e) (e) P=0.115 P=0.188 |
|POLY 3 | P=0.030 * (e) (e) (e) P=0.047 * P=0.216 |
|POLY 1.5 | P=0.031 * (e) (e) (e) P=0.049 * P=0.244 |
|POLY 6 | P=0.029 * (e) (e) (e) P=0.045 * P=0.194 |
|LOGISTIC REGRESSION| P=0.105 (e) (e) (e) P=0.085 P=0.175 |
|COCH-ARM / FISHERS | P=0.052 (e) (e) (e) P=0.107 P=0.318 |
|ORDER RESTRICTED | P=0.007 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/5 (0%) 1/4 (25%) 0/4 (0%) 1/4 (25%) 1/3 (33%) 2/7 (29%) |
|POLY-3 RATE (b) | 0/4.42 1/2.09 0/1.82 1/2.78 1/2.80 2/5.58 |
|POLY-3 PERCENT (g) | 0.0% 48.0% 0.0% 35.9% 35.8% 35.9% |
|TERMINAL (d) | 0/3 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 1/2 (50%) |
|FIRST INCIDENCE | --- 451 --- 472 721 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.151 P=0.492 (e) P=0.486 P=0.465 P=0.200 |
|POLY 3 | P=0.246 P=0.347 (e) P=0.403 P=0.401 P=0.266 |
|POLY 1.5 | P=0.249 P=0.388 (e) P=0.428 P=0.397 P=0.279 |
|POLY 6 | P=0.240 P=0.307 (e) P=0.361 P=0.408 P=0.253 |
|LOGISTIC REGRESSION| P=0.190 P=0.997 (e) (e) P=0.399 P=0.503 |
|COCH-ARM / FISHERS | P=0.218 P=0.444 (e) P=0.444 P=0.375 P=0.318 |
|ORDER RESTRICTED | P=0.091 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 36
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 2/53 (4%) 0/53 (0%) 5/53 (9%) 4/53 (8%) 3/53 (6%) |
|POLY-3 RATE (b) | 1/41.81 2/38.38 0/36.67 5/39.84 4/37.01 3/37.13 |
|POLY-3 PERCENT (g) | 2.4% 5.2% 0.0% 12.6% 10.8% 8.1% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 0/24 (0%) 2/25 (8%) 3/20 (15%) 1/23 (4%) |
|FIRST INCIDENCE | 720 645 --- 429 353 624 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.153 P=0.449 P=0.523N P=0.095 P=0.132 P=0.259 |
|POLY 3 | P=0.148 P=0.470 P=0.526N P=0.089 P=0.143 P=0.263 |
|POLY 1.5 | P=0.160 P=0.482 P=0.520N P=0.095 P=0.152 P=0.278 |
|POLY 6 | P=0.139 P=0.458 P=0.531N P=0.083 P=0.137 P=0.252 |
|LOGISTIC REGRESSION| P=0.167 P=0.460 P=0.532N P=0.106 P=0.161 P=0.256 |
|COCH-ARM / FISHERS | P=0.180 P=0.500 P=0.500N P=0.103 P=0.181 P=0.309 |
|ORDER RESTRICTED | P=0.111 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 33/53 (62%) 29/53 (55%) 26/53 (49%) 20/53 (38%) 20/53 (38%) 17/53 (32%) |
|POLY-3 RATE (b) | 33/46.61 29/45.46 26/42.61 20/42.24 20/39.35 17/41.09 |
|POLY-3 PERCENT (g) | 70.8% 63.8% 61.0% 47.3% 50.8% 41.4% |
|TERMINAL (d) | 19/25 (76%) 13/22 (59%) 14/24 (58%) 12/25 (48%) 11/20 (55%) 8/23 (35%) |
|FIRST INCIDENCE | 289 296 219 410 113 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.011N* P=0.558 P=0.303N P=0.036N* P=0.117N P=0.023N* |
|POLY 3 | P=0.002N** P=0.300N P=0.213N P=0.014N* P=0.037N* P=0.003N** |
|POLY 1.5 | P<0.001N** P=0.294N P=0.189N P=0.011N* P=0.024N* P=0.002N** |
|POLY 6 | P=0.002N** P=0.298N P=0.230N P=0.021N* P=0.048N* P=0.004N** |
|LOGISTIC REGRESSION| P=0.002N** P=0.335N P=0.204N P=0.015N* P=0.028N* P=0.003N** |
|COCH-ARM / FISHERS | P<0.001N** P=0.277N P=0.120N P=0.010N* P=0.010N* P=0.002N** |
|ORDER RESTRICTED | P=0.002N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 37
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Inflammation Granulomatous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 4/53 (8%) 3/53 (6%) 4/53 (8%) 4/53 (8%) 3/53 (6%) |
|POLY-3 RATE (b) | 2/41.97 4/38.83 3/36.87 4/39.84 4/36.44 3/36.98 |
|POLY-3 PERCENT (g) | 4.8% 10.3% 8.1% 10.0% 11.0% 8.1% |
|TERMINAL (d) | 1/25 (4%) 1/22 (5%) 2/24 (8%) 1/25 (4%) 2/20 (10%) 2/23 (9%) |
|FIRST INCIDENCE | 678 645 675 429 667 624 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.483 P=0.278 P=0.448 P=0.298 P=0.253 P=0.436 |
|POLY 3 | P=0.478 P=0.301 P=0.441 P=0.312 P=0.273 P=0.442 |
|POLY 1.5 | P=0.503 P=0.315 P=0.455 P=0.325 P=0.290 P=0.463 |
|POLY 6 | P=0.455 P=0.288 P=0.431 P=0.299 P=0.265 P=0.423 |
|LOGISTIC REGRESSION| P=0.501 P=0.297 P=0.430 P=0.346 P=0.263 P=0.430 |
|COCH-ARM / FISHERS | P=0.543 P=0.339 P=0.500 P=0.339 P=0.339 P=0.500 |
|ORDER RESTRICTED | P=0.395 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mesentery: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/1 (0%) 1/2 (50%) 0/1 (0%) 2/3 (67%) 1/2 (50%) 4/4 (100%) |
|POLY-3 RATE (b) | 0/1.00 1/1.36 0/1.00 2/3.00 1/2.00 4/4.00 |
|POLY-3 PERCENT (g) | 0.0% 73.7% 0.0% 66.7% 50.0% 100.0% |
|TERMINAL (d) | 0/1 (0%) 1/1 (100%) 0/1 (0%) 1/2 (50%) 1/2 (50%) 2/2 (100%) |
|FIRST INCIDENCE | --- 728 (T) --- 548 728 (T) 624 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.013 * P=0.500 (e) P=0.292 P=0.638 P=0.075 |
|POLY 3 | P=0.051 P=0.570 (e) P=0.500 P=0.614 P=0.200 |
|POLY 1.5 | P=0.052 P=0.593 (e) P=0.500 P=0.614 P=0.200 |
|POLY 6 | P=0.048 * P=0.534 (e) P=0.500 P=0.614 P=0.200 |
|LOGISTIC REGRESSION| P=0.052 P=0.500 (e) (e) P=0.638 (e) |
|COCH-ARM / FISHERS | P=0.053 P=0.667 (e) P=0.500 P=0.667 P=0.200 |
|ORDER RESTRICTED | P=0.119 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 38
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 8/53 (15%) 3/53 (6%) 8/53 (15%) 11/53 (21%) 7/53 (13%) 6/53 (11%) |
|POLY-3 RATE (b) | 8/44.12 3/38.16 8/38.85 11/42.27 7/38.30 6/38.20 |
|POLY-3 PERCENT (g) | 18.1% 7.9% 20.6% 26.0% 18.3% 15.7% |
|TERMINAL (d) | 2/25 (8%) 2/22 (9%) 4/24 (17%) 4/25 (16%) 3/20 (15%) 2/23 (9%) |
|FIRST INCIDENCE | 321 706 517 302 321 443 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.540N P=0.168N P=0.509 P=0.250 P=0.567 P=0.494N |
|POLY 3 | P=0.537N P=0.148N P=0.498 P=0.264 P=0.606 P=0.501N |
|POLY 1.5 | P=0.512N P=0.127N P=0.522 P=0.286 P=0.586N P=0.459N |
|POLY 6 | P=0.542 P=0.177N P=0.482 P=0.241 P=0.584 P=0.545N |
|LOGISTIC REGRESSION| P=0.472N P=0.106N P=0.600 P=0.343 P=0.480N P=0.378N |
|COCH-ARM / FISHERS | P=0.468N P=0.101N P=0.607N P=0.307 P=0.500N P=0.388N |
|ORDER RESTRICTED | P=0.365 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Respiratory Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/53 (2%) 2/53 (4%) 1/53 (2%) 6/53 (11%) 3/53 (6%) |
|POLY-3 RATE (b) | 1/42.34 1/38.36 2/36.87 1/38.69 6/36.71 3/36.61 |
|POLY-3 PERCENT (g) | 2.4% 2.6% 5.4% 2.6% 16.3% 8.2% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 0/25 (0%) 4/20 (20%) 3/23 (13%) |
|FIRST INCIDENCE | 554 651 675 589 561 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.071 P=0.726 P=0.463 P=0.727 P=0.035 * P=0.269 |
|POLY 3 | P=0.063 P=0.739 P=0.452 P=0.741 P=0.035 * P=0.254 |
|POLY 1.5 | P=0.072 P=0.748 P=0.464 P=0.750 P=0.040 * P=0.273 |
|POLY 6 | P=0.054 P=0.729 P=0.443 P=0.730 P=0.032 * P=0.237 |
|LOGISTIC REGRESSION| P=0.071 P=0.750N P=0.483 P=0.752N P=0.041 * P=0.261 |
|COCH-ARM / FISHERS | P=0.089 P=0.752N P=0.500 P=0.752N P=0.056 P=0.309 |
|ORDER RESTRICTED | P=0.044 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 39
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Septum |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 2/53 (4%) 3/53 (6%) 2/53 (4%) 5/53 (9%) 3/53 (6%) |
|POLY-3 RATE (b) | 1/42.06 2/38.97 3/37.86 2/38.79 5/36.42 3/37.38 |
|POLY-3 PERCENT (g) | 2.4% 5.1% 7.9% 5.2% 13.7% 8.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 1/25 (4%) 3/20 (15%) 2/23 (9%) |
|FIRST INCIDENCE | 652 420 517 548 662 443 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.201 P=0.454 P=0.273 P=0.461 P=0.073 P=0.267 |
|POLY 3 | P=0.186 P=0.473 P=0.268 P=0.472 P=0.071 P=0.263 |
|POLY 1.5 | P=0.202 P=0.484 P=0.275 P=0.485 P=0.078 P=0.279 |
|POLY 6 | P=0.170 P=0.461 P=0.263 P=0.456 P=0.066 P=0.249 |
|LOGISTIC REGRESSION| P=0.218 P=0.527 P=0.315 P=0.501 P=0.070 P=0.301 |
|COCH-ARM / FISHERS | P=0.229 P=0.500 P=0.309 P=0.500 P=0.103 P=0.309 |
|ORDER RESTRICTED | P=0.106 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Oral Mucosa: Gingival |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 15/52 (29%) 11/53 (21%) 16/52 (31%) 20/53 (38%) 22/53 (42%) 20/53 (38%) |
|POLY-3 RATE (b) | 15/42.71 11/40.56 16/40.42 20/44.13 22/40.94 20/42.38 |
|POLY-3 PERCENT (g) | 35.1% 27.1% 39.6% 45.3% 53.7% 47.2% |
|TERMINAL (d) | 9/24 (38%) 4/22 (18%) 7/23 (30%) 9/25 (36%) 10/20 (50%) 10/23 (44%) |
|FIRST INCIDENCE | 500 498 219 410 321 451 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.036 * P=0.387N P=0.377 P=0.185 P=0.041 * P=0.131 |
|POLY 3 | P=0.042 * P=0.288N P=0.422 P=0.221 P=0.061 P=0.175 |
|POLY 1.5 | P=0.043 * P=0.266N P=0.432 P=0.227 P=0.071 P=0.185 |
|POLY 6 | P=0.044 * P=0.306N P=0.429 P=0.219 P=0.061 P=0.175 |
|LOGISTIC REGRESSION| P=0.043 * P=0.289N P=0.427 P=0.203 P=0.062 P=0.166 |
|COCH-ARM / FISHERS | P=0.055 P=0.232N P=0.500 P=0.224 P=0.124 P=0.224 |
|ORDER RESTRICTED | P=0.044 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 40
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 43/53 (81%) 40/53 (75%) 38/53 (72%) 43/52 (83%) 45/52 (87%) 45/53 (85%) |
|POLY-3 RATE (b) | 43/50.40 40/47.87 38/46.23 43/49.92 45/49.03 45/50.44 |
|POLY-3 PERCENT (g) | 85.3% 83.6% 82.2% 86.1% 91.8% 89.2% |
|TERMINAL (d) | 21/25 (84%) 18/22 (82%) 18/24 (75%) 20/25 (80%) 17/20 (85%) 18/23 (78%) |
|FIRST INCIDENCE | 310 289 300 302 267 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.096 P=0.417 P=0.509N P=0.394 P=0.113 P=0.194 |
|POLY 3 | P=0.147 P=0.516N P=0.442N P=0.570 P=0.233 P=0.382 |
|POLY 1.5 | P=0.103 P=0.442N P=0.385N P=0.560 P=0.219 P=0.350 |
|POLY 6 | P=0.224 P=0.581N P=0.465N P=0.581 P=0.276 P=0.447 |
|LOGISTIC REGRESSION| P=0.061 P=0.380N P=0.311N P=0.515 P=0.224 P=0.336 |
|COCH-ARM / FISHERS | P=0.088 P=0.319N P=0.180N P=0.518 P=0.314 P=0.398 |
|ORDER RESTRICTED | P=0.256 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 11/53 (21%) 18/53 (34%) 20/53 (38%) 17/52 (33%) 18/52 (35%) 13/53 (25%) |
|POLY-3 RATE (b) | 11/42.65 18/42.87 20/42.57 17/40.45 18/38.04 13/40.45 |
|POLY-3 PERCENT (g) | 25.8% 42.0% 47.0% 42.0% 47.3% 32.1% |
|TERMINAL (d) | 8/25 (32%) 7/22 (32%) 7/24 (29%) 11/25 (44%) 11/20 (55%) 6/23 (26%) |
|FIRST INCIDENCE | 554 451 393 499 337 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.442N P=0.055 P=0.034 * P=0.107 P=0.028 * P=0.302 |
|POLY 3 | P=0.413N P=0.082 P=0.031 * P=0.085 P=0.033 * P=0.344 |
|POLY 1.5 | P=0.372N P=0.085 P=0.028 * P=0.101 P=0.042 * P=0.365 |
|POLY 6 | P=0.453N P=0.085 P=0.041 * P=0.072 P=0.030 * P=0.332 |
|LOGISTIC REGRESSION| P=0.373N P=0.072 P=0.026 * P=0.070 P=0.031 * P=0.342 |
|COCH-ARM / FISHERS | P=0.311N P=0.095 P=0.043 * P=0.122 P=0.085 P=0.408 |
|ORDER RESTRICTED | P=0.091 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 41
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas |
| Cytoplasmic Alteration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 0/52 (0%) 3/52 (6%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/37.91 0/35.44 3/37.50 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 8.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- --- --- --- 603 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.086 |
|POLY 3 | P<0.001 ** (e) (e) (e) (e) P=0.100 |
|POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P=0.105 |
|POLY 6 | P<0.001 ** (e) (e) (e) (e) P=0.097 |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) (e) P=0.118 |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P=0.118 |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/53 (2%) 1/53 (2%) 1/52 (2%) 0/52 (0%) 4/52 (8%) |
|POLY-3 RATE (b) | 2/42.25 1/38.72 1/37.15 1/38.59 0/35.44 4/37.43 |
|POLY-3 PERCENT (g) | 4.7% 2.6% 2.7% 2.6% 0.0% 10.7% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | 588 516 587 499 --- 586 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.073 P=0.539N P=0.551N P=0.533N P=0.291N P=0.266 |
|POLY 3 | P=0.080 P=0.530N P=0.545N P=0.532N P=0.278N P=0.282 |
|POLY 1.5 | P=0.082 P=0.518N P=0.534N P=0.519N P=0.268N P=0.298 |
|POLY 6 | P=0.079 P=0.544N P=0.553N P=0.546N P=0.284N P=0.269 |
|LOGISTIC REGRESSION| P=0.089 P=0.482N P=0.503N P=0.494N P=0.255N P=0.308 |
|COCH-ARM / FISHERS | P=0.088 P=0.500N P=0.500N P=0.507N P=0.252N P=0.330 |
|ORDER RESTRICTED | P=0.042 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 42
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 1/53 (2%) 1/53 (2%) 1/52 (2%) 0/52 (0%) 3/52 (6%) |
|POLY-3 RATE (b) | 3/42.64 1/38.72 1/37.15 1/38.59 0/35.44 3/36.95 |
|POLY-3 PERCENT (g) | 7.0% 2.6% 2.7% 2.6% 0.0% 8.1% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | 588 516 587 499 --- 608 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.314 P=0.348N P=0.365N P=0.356N P=0.162N P=0.575 |
|POLY 3 | P=0.340 P=0.340N P=0.356N P=0.341N P=0.155N P=0.595 |
|POLY 1.5 | P=0.344 P=0.326N P=0.343N P=0.327N P=0.145N P=0.617 |
|POLY 6 | P=0.338 P=0.357N P=0.367N P=0.359N P=0.161N P=0.574 |
|LOGISTIC REGRESSION| P=0.355 P=0.287N P=0.303N P=0.299N P=0.128N P=0.629 |
|COCH-ARM / FISHERS | P=0.353 P=0.309N P=0.309N P=0.316N P=0.125N P=0.652 |
|ORDER RESTRICTED | P=0.211 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 2/52 (4%) 23/52 (44%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/37.91 2/35.47 23/41.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.6% 56.1% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 1/20 (5%) 13/23 (57%) |
|FIRST INCIDENCE | --- --- --- --- 721 451 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.203 P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) (e) P=0.202 P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.210 P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) (e) P=0.198 P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.197 P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.243 P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 43
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 2/53 (4%) 1/53 (2%) 2/52 (4%) 4/52 (8%) 11/52 (21%) |
|POLY-3 RATE (b) | 1/42.16 2/38.83 1/36.67 2/38.49 4/36.93 11/38.02 |
|POLY-3 PERCENT (g) | 2.4% 5.2% 2.7% 5.2% 10.8% 28.9% |
|TERMINAL (d) | 0/25 (0%) 1/22 (5%) 1/24 (4%) 1/25 (4%) 2/20 (10%) 5/23 (22%) |
|FIRST INCIDENCE | 619 451 728 (T) 548 113 586 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.469 P=0.735 P=0.461 P=0.139 P=0.002 ** |
|POLY 3 | P<0.001 ** P=0.471 P=0.729 P=0.468 P=0.140 P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.483 P=0.737 P=0.480 P=0.149 P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.457 P=0.722 P=0.454 P=0.136 P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.523 P=0.743 P=0.499 P=0.230 P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.752N P=0.493 P=0.176 P=0.002 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 20/53 (38%) 21/53 (40%) 20/53 (38%) 13/53 (25%) 12/53 (23%) 14/53 (26%) |
|POLY-3 RATE (b) | 20/42.80 21/40.48 20/40.83 13/40.08 12/37.55 14/39.27 |
|POLY-3 PERCENT (g) | 46.7% 51.9% 49.0% 32.4% 32.0% 35.7% |
|TERMINAL (d) | 14/25 (56%) 11/22 (50%) 10/24 (42%) 9/25 (36%) 7/20 (35%) 7/23 (30%) |
|FIRST INCIDENCE | 651 600 301 470 580 513 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.102N P=0.281 P=0.431 P=0.144N P=0.220N P=0.284N |
|POLY 3 | P=0.057N P=0.398 P=0.505 P=0.127N P=0.125N P=0.207N |
|POLY 1.5 | P=0.052N P=0.434 P=0.503 P=0.111N P=0.109N P=0.187N |
|POLY 6 | P=0.059N P=0.381 P=0.536 P=0.150N P=0.127N P=0.219N |
|LOGISTIC REGRESSION| P=0.075N P=0.272 P=0.386 P=0.194N P=0.158N P=0.301N |
|COCH-ARM / FISHERS | P=0.045N* P=0.500 P=0.579N P=0.104N P=0.069N P=0.149N |
|ORDER RESTRICTED | P=0.102N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 44
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 2/41.83 0/38.07 0/36.67 1/38.52 1/36.36 1/37.29 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 2.6% 2.8% 2.7% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 715 --- --- 645 667 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.521 P=0.285N P=0.265N P=0.539N P=0.561N P=0.544N |
|POLY 3 | P=0.551 P=0.258N P=0.267N P=0.529N P=0.549N P=0.540N |
|POLY 1.5 | P=0.552 P=0.250N P=0.260N P=0.515N P=0.536N P=0.526N |
|POLY 6 | P=0.551 P=0.268N P=0.273N P=0.543N P=0.555N P=0.553N |
|LOGISTIC REGRESSION| P=0.541 P=0.277N P=0.272N P=0.539N P=0.556N P=0.510N |
|COCH-ARM / FISHERS | P=0.551 P=0.248N P=0.248N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.293N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/42.16 2/38.69 1/36.87 0/38.22 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 4.7% 5.2% 2.7% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/25 (4%) 1/22 (5%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 619 526 675 --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.094N P=0.652 P=0.548N P=0.267N P=0.283N P=0.280N |
|POLY 3 | P=0.085N P=0.663 P=0.547N P=0.259N P=0.273N P=0.270N |
|POLY 1.5 | P=0.084N P=0.676 P=0.535N P=0.249N P=0.263N P=0.257N |
|POLY 6 | P=0.085N P=0.649 P=0.555N P=0.272N P=0.280N P=0.282N |
|LOGISTIC REGRESSION| P=0.085N P=0.691 P=0.533N P=0.248N P=0.260N P=0.257N |
|COCH-ARM / FISHERS | P=0.081N P=0.691N P=0.500N P=0.248N P=0.248N P=0.248N |
|ORDER RESTRICTED | P=0.104N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 45
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 22/53 (42%) 16/53 (30%) 14/53 (26%) 11/53 (21%) 15/53 (28%) 19/53 (36%) |
|POLY-3 RATE (b) | 22/43.51 16/42.15 14/39.78 11/39.69 15/37.25 19/40.77 |
|POLY-3 PERCENT (g) | 50.6% 38.0% 35.2% 27.7% 40.3% 46.6% |
|TERMINAL (d) | 16/25 (64%) 7/22 (32%) 7/24 (29%) 8/25 (32%) 10/20 (50%) 11/23 (48%) |
|FIRST INCIDENCE | 610 467 301 472 513 412 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.289 P=0.316N P=0.142N P=0.025N* P=0.321N P=0.531N |
|POLY 3 | P=0.329 P=0.162N P=0.110N P=0.023N* P=0.235N P=0.440N |
|POLY 1.5 | P=0.357 P=0.159N P=0.104N P=0.018N* P=0.191N P=0.405N |
|POLY 6 | P=0.303 P=0.164N P=0.110N P=0.033N* P=0.272N P=0.478N |
|LOGISTIC REGRESSION| P=0.300 P=0.226N P=0.147N P=0.037N* P=0.253N P=0.532N |
|COCH-ARM / FISHERS | P=0.407 P=0.156N P=0.075N P=0.018N* P=0.111N P=0.345N |
|ORDER RESTRICTED | P=0.168N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Salivary Glands |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 0/53 (0%) 0/51 (0%) 0/53 (0%) 0/51 (0%) 2/51 (4%) |
|POLY-3 RATE (b) | 1/41.78 0/38.07 0/35.67 0/38.22 0/35.23 2/35.09 |
|POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 0.0% 0.0% 5.7% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 2/23 (9%) |
|FIRST INCIDENCE | 728 (T) --- --- --- --- 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.077 P=0.525N P=0.508N P=0.500N P=0.545N P=0.471 |
|POLY 3 | P=0.079 P=0.519N P=0.531N P=0.518N P=0.534N P=0.439 |
|POLY 1.5 | P=0.079 P=0.511N P=0.526N P=0.509N P=0.527N P=0.456 |
|POLY 6 | P=0.079 P=0.527N P=0.534N P=0.527N P=0.537N P=0.425 |
|LOGISTIC REGRESSION| P=0.077 (e) (e) (e) (e) P=0.471 |
|COCH-ARM / FISHERS | P=0.080 P=0.500N P=0.510N P=0.500N P=0.510N P=0.485 |
|ORDER RESTRICTED | P=0.034 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 46
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Skin |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/42.17 1/38.22 0/36.67 0/38.22 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 4.7% 2.6% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 619 689 --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.171N P=0.547N P=0.269N P=0.271N P=0.287N P=0.285N |
|POLY 3 | P=0.148N P=0.534N P=0.269N P=0.259N P=0.273N P=0.270N |
|POLY 1.5 | P=0.151N P=0.520N P=0.261N P=0.249N P=0.263N P=0.257N |
|POLY 6 | P=0.144N P=0.549N P=0.277N P=0.272N P=0.280N P=0.282N |
|LOGISTIC REGRESSION| P=0.165N P=0.524N P=0.257N P=0.248N P=0.259N P=0.256N |
|COCH-ARM / FISHERS | P=0.156N P=0.500N P=0.248N P=0.248N P=0.248N P=0.248N |
|ORDER RESTRICTED | P=0.044N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Skin |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/42.17 1/38.22 0/36.67 0/38.22 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 4.7% 2.6% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 619 689 --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.171N P=0.547N P=0.269N P=0.271N P=0.287N P=0.285N |
|POLY 3 | P=0.148N P=0.534N P=0.269N P=0.259N P=0.273N P=0.270N |
|POLY 1.5 | P=0.151N P=0.520N P=0.261N P=0.249N P=0.263N P=0.257N |
|POLY 6 | P=0.144N P=0.549N P=0.277N P=0.272N P=0.280N P=0.282N |
|LOGISTIC REGRESSION| P=0.165N P=0.524N P=0.257N P=0.248N P=0.259N P=0.256N |
|COCH-ARM / FISHERS | P=0.156N P=0.500N P=0.248N P=0.248N P=0.248N P=0.248N |
|ORDER RESTRICTED | P=0.044N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 47
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 49/53 (92%) 49/53 (92%) 48/53 (91%) 51/52 (98%) 46/52 (88%) 50/51 (98%) |
|POLY-3 RATE (b) | 49/51.40 49/51.66 48/50.39 51/51.53 46/48.46 50/50.58 |
|POLY-3 PERCENT (g) | 95.3% 94.8% 95.3% 99.0% 94.9% 98.9% |
|TERMINAL (d) | 25/25 (100%) 21/22 (96%) 23/24 (96%) 25/25 (100%) 20/20 (100%) 23/23 (100%) |
|FIRST INCIDENCE | 289 289 196 302 113 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.257 P=0.233 P=0.348 P=0.270 P=0.243 P=0.197 |
|POLY 3 | P=0.185 P=0.648N P=0.693N P=0.274 P=0.666N P=0.295 |
|POLY 1.5 | P=0.189 P=0.632N P=0.662N P=0.244 P=0.551N P=0.259 |
|POLY 6 | P=0.185 P=0.683N P=0.723N P=0.306 P=0.718 P=0.332 |
|LOGISTIC REGRESSION| P=0.154 P=0.606 P=0.617 P=0.170 P=0.539N P=0.158 |
|COCH-ARM / FISHERS | P=0.186 P=0.642N P=0.500N P=0.187 P=0.359N P=0.194 |
|ORDER RESTRICTED | P=0.206 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 52/53 (98%) 45/53 (85%) 50/53 (94%) 48/52 (92%) 49/52 (94%) 51/51 (100%) |
|POLY-3 RATE (b) | 52/53.00 45/49.65 50/51.50 48/50.73 49/50.30 51/51.00 |
|POLY-3 PERCENT (g) | 98.1% 90.6% 97.1% 94.6% 97.4% 100.0% |
|TERMINAL (d) | 24/25 (96%) 20/22 (91%) 24/24 (100%) 24/25 (96%) 20/20 (100%) 23/23 (100%) |
|FIRST INCIDENCE | 289 289 116 302 241 78 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.180 P=0.520N P=0.391 P=0.523N P=0.247 P=0.276 |
|POLY 3 | P=0.057 P=0.086N P=0.634N P=0.321N P=0.673N P=0.508 |
|POLY 1.5 | P=0.040 * P=0.042N* P=0.468N P=0.243N P=0.585N P=0.508 |
|POLY 6 | P=0.096 P=0.178N P=0.773 P=0.456N P=0.741N P=0.508 |
|LOGISTIC REGRESSION| P=0.033 * P=0.022N* P=0.318N P=0.171N P=0.410N (e) |
|COCH-ARM / FISHERS | P=0.039 * P=0.016N* P=0.309N P=0.176N P=0.302N P=0.510 |
|ORDER RESTRICTED | P=0.064 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 48
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen: Lymphoid Follicle |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 7/53 (13%) 8/53 (15%) 7/53 (13%) 6/52 (12%) 12/52 (23%) 4/51 (8%) |
|POLY-3 RATE (b) | 7/44.55 8/41.80 7/40.36 6/40.90 12/40.71 4/38.59 |
|POLY-3 PERCENT (g) | 15.7% 19.1% 17.3% 14.7% 29.5% 10.4% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 1/25 (4%) 2/20 (10%) 0/23 (0%) |
|FIRST INCIDENCE | 310 503 420 302 315 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.376N P=0.402 P=0.500 P=0.575N P=0.100 P=0.361N |
|POLY 3 | P=0.377N P=0.446 P=0.536 P=0.566N P=0.100 P=0.348N |
|POLY 1.5 | P=0.348N P=0.463 P=0.547 P=0.541N P=0.108 P=0.323N |
|POLY 6 | P=0.414N P=0.434 P=0.537 P=0.597N P=0.099 P=0.374N |
|LOGISTIC REGRESSION| P=0.274N P=0.575 P=0.506N P=0.467N P=0.229 P=0.208N |
|COCH-ARM / FISHERS | P=0.316N P=0.500 P=0.612N P=0.515N P=0.145 P=0.286N |
|ORDER RESTRICTED | P=0.255N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen: Red Pulp |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 0/52 (0%) 0/51 (0%) |
|POLY-3 RATE (b) | 2/42.70 0/38.07 0/36.67 0/37.91 0/35.44 0/36.35 |
|POLY-3 PERCENT (g) | 4.7% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | 310 --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.253N P=0.256N P=0.258N P=0.240N P=0.269N P=0.249N |
|POLY 3 | P=0.229N P=0.263N P=0.272N P=0.264N P=0.281N P=0.274N |
|POLY 1.5 | P=0.238N P=0.253N P=0.263N P=0.254N P=0.270N P=0.264N |
|POLY 6 | P=0.219N P=0.274N P=0.279N P=0.275N P=0.286N P=0.285N |
|LOGISTIC REGRESSION| P=0.237N P=0.201N P=0.165N P=0.237N P=0.167N P=0.195N |
|COCH-ARM / FISHERS | P=0.253N P=0.248N P=0.248N P=0.252N P=0.252N P=0.257N |
|ORDER RESTRICTED | P=0.014N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 49
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 1/53 (2%) 5/53 (9%) 6/53 (11%) 3/52 (6%) 10/53 (19%) |
|POLY-3 RATE (b) | 4/42.72 1/38.81 5/38.12 6/40.38 3/35.70 10/39.37 |
|POLY-3 PERCENT (g) | 9.4% 2.6% 13.1% 14.9% 8.4% 25.4% |
|TERMINAL (d) | 2/25 (8%) 0/22 (0%) 3/24 (13%) 2/25 (8%) 1/20 (5%) 5/23 (22%) |
|FIRST INCIDENCE | 289 467 219 429 668 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.007 ** P=0.215N P=0.463 P=0.348 P=0.596N P=0.059 |
|POLY 3 | P=0.006 ** P=0.208N P=0.428 P=0.333 P=0.597N P=0.048 * |
|POLY 1.5 | P=0.006 ** P=0.197N P=0.445 P=0.348 P=0.576N P=0.055 |
|POLY 6 | P=0.005 ** P=0.219N P=0.419 P=0.320 P=0.606N P=0.043 * |
|LOGISTIC REGRESSION| P=0.009 ** P=0.153N P=0.536 P=0.394 P=0.546N P=0.080 |
|COCH-ARM / FISHERS | P=0.009 ** P=0.181N P=0.500 P=0.371 P=0.511N P=0.075 |
|ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/53 (2%) 0/53 (0%) 2/53 (4%) 2/52 (4%) 2/53 (4%) |
|POLY-3 RATE (b) | 1/41.78 1/38.69 0/36.67 2/39.53 2/35.70 2/36.61 |
|POLY-3 PERCENT (g) | 2.4% 2.6% 0.0% 5.1% 5.6% 5.5% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 2/23 (9%) |
|FIRST INCIDENCE | 727 526 --- 429 668 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.212 P=0.732 P=0.516N P=0.486 P=0.438 P=0.466 |
|POLY 3 | P=0.206 P=0.744 P=0.526N P=0.481 P=0.445 P=0.454 |
|POLY 1.5 | P=0.218 P=0.750 P=0.520N P=0.490 P=0.457 P=0.471 |
|POLY 6 | P=0.195 P=0.737 P=0.531N P=0.470 P=0.442 P=0.438 |
|LOGISTIC REGRESSION| P=0.227 P=0.758N P=0.527N P=0.519 P=0.438 P=0.466 |
|COCH-ARM / FISHERS | P=0.232 P=0.752N P=0.500N P=0.500 P=0.493 P=0.500 |
|ORDER RESTRICTED | P=0.319 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 50
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/53 (4%) 2/53 (4%) 1/52 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/41.78 1/38.69 2/37.64 2/39.53 1/35.47 1/36.61 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 5.3% 5.1% 2.8% 2.7% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 0/25 (0%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | --- 526 219 429 721 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.585 P=0.482 P=0.231 P=0.231 P=0.476 P=0.483 |
|POLY 3 | P=0.553 P=0.485 P=0.214 P=0.225 P=0.467 P=0.474 |
|POLY 1.5 | P=0.572 P=0.491 P=0.220 P=0.231 P=0.475 P=0.483 |
|POLY 6 | P=0.536 P=0.478 P=0.210 P=0.218 P=0.464 P=0.465 |
|LOGISTIC REGRESSION| P=0.599N P=0.530 P=0.326 P=0.231 P=0.464 P=0.483 |
|COCH-ARM / FISHERS | P=0.607 P=0.500 P=0.248 P=0.248 P=0.495 P=0.500 |
|ORDER RESTRICTED | P=0.266 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 3/53 (6%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/38.22 1/35.44 3/36.76 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.8% 8.2% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 1/20 (5%) 2/23 (9%) |
|FIRST INCIDENCE | --- --- --- --- 728 (T) 689 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002 ** (e) (e) (e) P=0.455 P=0.107 |
|POLY 3 | P=0.002 ** (e) (e) (e) P=0.467 P=0.097 |
|POLY 1.5 | P=0.002 ** (e) (e) (e) P=0.475 P=0.104 |
|POLY 6 | P=0.002 ** (e) (e) (e) P=0.464 P=0.090 |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.455 P=0.089 |
|COCH-ARM / FISHERS | P=0.002 ** (e) (e) (e) P=0.495 P=0.121 |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 51
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Erosion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 1/52 (2%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 1/37.19 2/39.83 1/35.48 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.7% 5.0% 2.8% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- 570 410 717 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.549N (e) P=0.481 P=0.251 P=0.477 (e) |
|POLY 3 | P=0.576N (e) P=0.477 P=0.226 P=0.468 (e) |
|POLY 1.5 | P=0.563N (e) P=0.482 P=0.232 P=0.475 (e) |
|POLY 6 | P=0.587N (e) P=0.474 P=0.219 P=0.464 (e) |
|LOGISTIC REGRESSION| P=0.507N (e) P=0.531 P=0.174 P=0.464 (e) |
|COCH-ARM / FISHERS | P=0.538N (e) P=0.500 P=0.248 P=0.495 (e) |
|ORDER RESTRICTED | P=0.325 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 9/53 (17%) 1/53 (2%) 3/53 (6%) 2/52 (4%) 4/53 (8%) |
|POLY-3 RATE (b) | 2/41.98 9/41.30 1/36.67 3/39.77 2/36.56 4/38.05 |
|POLY-3 PERCENT (g) | 4.8% 21.8% 2.7% 7.5% 5.5% 10.5% |
|TERMINAL (d) | 1/25 (4%) 2/22 (9%) 1/24 (4%) 1/25 (4%) 0/20 (0%) 1/23 (4%) |
|FIRST INCIDENCE | 675 393 728 (T) 302 348 498 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.526N P=0.021 * P=0.531N P=0.478 P=0.635 P=0.286 |
|POLY 3 | P=0.502N P=0.022 * P=0.547N P=0.475 P=0.644 P=0.292 |
|POLY 1.5 | P=0.492N P=0.023 * P=0.535N P=0.489 P=0.654 P=0.307 |
|POLY 6 | P=0.507N P=0.021 * P=0.557N P=0.458 P=0.640 P=0.278 |
|LOGISTIC REGRESSION| P=0.456N P=0.030 * P=0.555N P=0.524 P=0.683N P=0.332 |
|COCH-ARM / FISHERS | P=0.473N P=0.026 * P=0.500N P=0.500 P=0.684 P=0.339 |
|ORDER RESTRICTED | P=0.256N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 52
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thymus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 43/53 (81%) 36/49 (73%) 36/50 (72%) 44/52 (85%) 39/49 (80%) 48/51 (94%) |
|POLY-3 RATE (b) | 43/48.07 36/45.02 36/45.09 44/49.53 39/43.28 48/50.00 |
|POLY-3 PERCENT (g) | 89.5% 80.0% 79.8% 88.8% 90.1% 96.0% |
|TERMINAL (d) | 23/25 (92%) 16/21 (76%) 17/23 (74%) 22/25 (88%) 17/20 (85%) 21/23 (91%) |
|FIRST INCIDENCE | 377 296 219 302 267 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.031 * P=0.516N P=0.424N P=0.339 P=0.330 P=0.089 |
|POLY 3 | P=0.010 * P=0.140N P=0.139N P=0.600N P=0.605 P=0.173 |
|POLY 1.5 | P=0.005 ** P=0.164N P=0.168N P=0.610 P=0.578 P=0.082 |
|POLY 6 | P=0.027 * P=0.134N P=0.116N P=0.598N P=0.623N P=0.324 |
|LOGISTIC REGRESSION| P=0.003 ** P=0.325N P=0.348N P=0.346 P=0.323 P=0.011 * |
|COCH-ARM / FISHERS | P=0.006 ** P=0.246N P=0.194N P=0.416 P=0.521N P=0.042 * |
|ORDER RESTRICTED | P=0.022 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 15/53 (28%) 16/53 (30%) 9/51 (18%) 13/53 (25%) 9/51 (18%) 11/51 (22%) |
|POLY-3 RATE (b) | 15/43.91 16/42.27 9/37.05 13/39.17 9/37.41 11/37.65 |
|POLY-3 PERCENT (g) | 34.2% 37.9% 24.3% 33.2% 24.1% 29.2% |
|TERMINAL (d) | 10/25 (40%) 4/22 (18%) 6/24 (25%) 10/25 (40%) 3/20 (15%) 5/23 (22%) |
|FIRST INCIDENCE | 513 432 570 570 420 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.280N P=0.348 P=0.179N P=0.475N P=0.279N P=0.385N |
|POLY 3 | P=0.271N P=0.447 P=0.233N P=0.556N P=0.224N P=0.405N |
|POLY 1.5 | P=0.247N P=0.463 P=0.211N P=0.488N P=0.201N P=0.362N |
|POLY 6 | P=0.288N P=0.445 P=0.245N P=0.556 P=0.237N P=0.434N |
|LOGISTIC REGRESSION| P=0.272N P=0.445 P=0.215N P=0.549N P=0.203N P=0.381N |
|COCH-ARM / FISHERS | P=0.212N P=0.500 P=0.145N P=0.413N P=0.145N P=0.286N |
|ORDER RESTRICTED | P=0.314N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 53
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 7/53 (13%) 13/53 (25%) 24/51 (47%) 24/53 (45%) 24/51 (47%) 22/51 (43%) |
|POLY-3 RATE (b) | 7/42.51 13/40.89 24/41.21 24/41.67 24/41.85 22/41.33 |
|POLY-3 PERCENT (g) | 16.5% 31.8% 58.2% 57.6% 57.4% 53.2% |
|TERMINAL (d) | 3/25 (12%) 6/22 (27%) 11/24 (46%) 15/25 (60%) 8/20 (40%) 10/23 (44%) |
|FIRST INCIDENCE | 651 498 196 472 113 442 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.011 * P=0.066 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P=0.005 ** P=0.079 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P=0.005 ** P=0.088 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P=0.008 ** P=0.072 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P=0.005 ** P=0.079 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P=0.009 ** P=0.107 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Tooth: Peridontal Tissue |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 33/33 (100%) 25/25 (100%) 22/22 (100%) 30/30 (100%) 29/29 (100%) 29/29 (100%) |
|POLY-3 RATE (b) | 33/33.00 25/25.00 22/22.00 30/30.00 29/29.00 29/29.00 |
|POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% |
|TERMINAL (d) | 19/19 (100%) 11/11 (100%) 10/10 (100%) 15/15 (100%) 13/13 (100%) 17/17 (100%) |
|FIRST INCIDENCE | 289 498 300 410 321 443 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | (e) (e) (e) (e) (e) (e) |
|POLY 3 | (e) (e) (e) (e) (e) (e) |
|POLY 1.5 | (e) (e) (e) (e) (e) (e) |
|POLY 6 | (e) (e) (e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 54
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Trachea: Peritracheal Tissue |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/53 (2%) 2/52 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/41.78 1/39.00 2/37.89 1/38.94 0/36.13 0/36.61 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 5.3% 2.6% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 296 300 472 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.244N P=0.500 P=0.220 P=0.492 (e) (e) |
|POLY 3 | P=0.273N P=0.486 P=0.215 P=0.486 (e) (e) |
|POLY 1.5 | P=0.263N P=0.492 P=0.219 P=0.493 (e) (e) |
|POLY 6 | P=0.279N P=0.479 P=0.213 P=0.478 (e) (e) |
|LOGISTIC REGRESSION| P=0.152N P=0.551 P=0.501 P=0.487 (e) (e) |
|COCH-ARM / FISHERS | P=0.240N P=0.500 P=0.243 P=0.500 (e) (e) |
|ORDER RESTRICTED | P=0.349N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Urinary Bladder |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 3/52 (6%) 1/53 (2%) 1/53 (2%) 6/51 (12%) 1/53 (2%) |
|POLY-3 RATE (b) | 2/41.83 3/39.95 1/36.82 1/38.79 6/35.70 1/36.61 |
|POLY-3 PERCENT (g) | 4.8% 7.5% 2.7% 2.6% 16.8% 2.7% |
|TERMINAL (d) | 1/25 (4%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 3/20 (15%) 1/23 (4%) |
|FIRST INCIDENCE | 715 432 689 548 668 728 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.565 P=0.449 P=0.543N P=0.523N P=0.089 P=0.541N |
|POLY 3 | P=0.539 P=0.479 P=0.544N P=0.526N P=0.085 P=0.546N |
|POLY 1.5 | P=0.567 P=0.484 P=0.534N P=0.514N P=0.094 P=0.529N |
|POLY 6 | P=0.508 P=0.474 P=0.552N P=0.540N P=0.082 P=0.563N |
|LOGISTIC REGRESSION| P=0.584N P=0.538 P=0.555N P=0.512N P=0.080 P=0.560N |
|COCH-ARM / FISHERS | P=0.568N P=0.491 P=0.500N P=0.500N P=0.123 P=0.500N |
|ORDER RESTRICTED | P=0.290 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 55
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Urinary Bladder: Transitional Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/52 (2%) 0/53 (0%) 0/53 (0%) 4/51 (8%) 4/53 (8%) |
|POLY-3 RATE (b) | 0/41.78 1/38.42 0/36.67 0/38.22 4/36.78 4/36.69 |
|POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 0.0% 10.9% 10.9% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 3/23 (13%) |
|FIRST INCIDENCE | --- 498 --- --- 321 706 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002 ** P=0.483 (e) (e) P=0.053 P=0.053 |
|POLY 3 | P=0.002 ** P=0.483 (e) (e) P=0.045 * P=0.045 * |
|POLY 1.5 | P=0.002 ** P=0.488 (e) (e) P=0.047 * P=0.050 |
|POLY 6 | P<0.001 ** P=0.478 (e) (e) P=0.044 * P=0.040 * |
|LOGISTIC REGRESSION| P=0.002 ** P=0.529 (e) (e) P=0.066 P=0.041 * |
|COCH-ARM / FISHERS | P=0.003 ** P=0.495 (e) (e) P=0.054 P=0.059 |
|ORDER RESTRICTED | P=0.008 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 1/52 (2%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 0/37.91 1/36.00 2/38.08 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.8% 5.3% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 0/25 (0%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- --- --- 555 412 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.014 * (e) (e) (e) P=0.471 P=0.225 |
|POLY 3 | P=0.015 * (e) (e) (e) P=0.470 P=0.217 |
|POLY 1.5 | P=0.016 * (e) (e) (e) P=0.476 P=0.224 |
|POLY 6 | P=0.015 * (e) (e) (e) P=0.469 P=0.210 |
|LOGISTIC REGRESSION| P=0.020 * (e) (e) (e) P=0.537 P=0.316 |
|COCH-ARM / FISHERS | P=0.016 * (e) (e) (e) P=0.495 P=0.248 |
|ORDER RESTRICTED | P=0.023 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 56
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 6/53 (11%) 1/53 (2%) 7/52 (13%) 3/52 (6%) 4/53 (8%) |
|POLY-3 RATE (b) | 3/42.38 6/38.78 1/36.67 7/40.07 3/37.09 4/37.67 |
|POLY-3 PERCENT (g) | 7.1% 15.5% 2.7% 17.5% 8.1% 10.6% |
|TERMINAL (d) | 2/25 (8%) 4/22 (18%) 1/24 (4%) 3/25 (12%) 0/20 (0%) 2/23 (9%) |
|FIRST INCIDENCE | 536 526 728 (T) 470 348 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.522 P=0.184 P=0.327N P=0.143 P=0.579 P=0.457 |
|POLY 3 | P=0.529 P=0.197 P=0.358N P=0.132 P=0.600 P=0.436 |
|POLY 1.5 | P=0.549 P=0.215 P=0.344N P=0.142 P=0.612 P=0.460 |
|POLY 6 | P=0.512 P=0.179 P=0.370N P=0.124 P=0.599 P=0.412 |
|LOGISTIC REGRESSION| P=0.563 P=0.205 P=0.343N P=0.155 P=0.634N P=0.497 |
|COCH-ARM / FISHERS | P=0.557N P=0.244 P=0.309N P=0.152 P=0.652 P=0.500 |
|ORDER RESTRICTED | P=0.405 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 5/53 (9%) 3/53 (6%) 3/52 (6%) 4/52 (8%) 3/53 (6%) |
|POLY-3 RATE (b) | 0/41.78 5/41.13 3/37.89 3/38.22 4/38.22 3/38.42 |
|POLY-3 PERCENT (g) | 0.0% 12.2% 7.9% 7.9% 10.5% 7.8% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 1/24 (4%) 2/25 (8%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- 451 497 645 353 412 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.378 P=0.031 * P=0.110 P=0.109 P=0.048 * P=0.106 |
|POLY 3 | P=0.383 P=0.029 * P=0.101 P=0.103 P=0.049 * P=0.104 |
|POLY 1.5 | P=0.400 P=0.029 * P=0.105 P=0.109 P=0.050 P=0.109 |
|POLY 6 | P=0.370 P=0.028 * P=0.100 P=0.097 P=0.050 P=0.099 |
|LOGISTIC REGRESSION| P=0.480 P=0.044 * P=0.130 P=0.098 P=0.111 P=0.164 |
|COCH-ARM / FISHERS | P=0.430 P=0.028 * P=0.121 P=0.118 P=0.057 P=0.121 |
|ORDER RESTRICTED | P=0.090 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 57
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Metaplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 17/53 (32%) 25/53 (47%) 21/53 (40%) 36/52 (69%) 31/52 (60%) 35/53 (66%) |
|POLY-3 RATE (b) | 17/45.44 25/45.80 21/42.51 36/48.18 31/45.06 35/46.29 |
|POLY-3 PERCENT (g) | 37.4% 54.6% 49.4% 74.7% 68.8% 75.6% |
|TERMINAL (d) | 8/25 (32%) 7/22 (32%) 10/24 (42%) 16/25 (64%) 11/20 (55%) 19/23 (83%) |
|FIRST INCIDENCE | 321 289 300 302 267 329 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002 ** P=0.055 P=0.193 P<0.001 ** P=0.003 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.070 P=0.174 P<0.001 ** P=0.002 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.071 P=0.192 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.074 P=0.161 P<0.001 ** P=0.002 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.086 P=0.243 P<0.001 ** P=0.004 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.082 P=0.272 P<0.001 ** P=0.004 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 3/52 (6%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/41.78 0/38.07 0/36.67 1/37.91 3/37.42 1/37.26 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.6% 8.0% 2.7% |
|TERMINAL (d) | 0/25 (0%) 0/22 (0%) 0/24 (0%) 1/25 (4%) 0/20 (0%) 0/23 (0%) |
|FIRST INCIDENCE | --- --- --- 728 (T) 353 513 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.131 (e) (e) P=0.500 P=0.101 P=0.473 |
|POLY 3 | P=0.125 (e) (e) P=0.481 P=0.099 P=0.477 |
|POLY 1.5 | P=0.133 (e) (e) P=0.488 P=0.102 P=0.485 |
|POLY 6 | P=0.116 (e) (e) P=0.472 P=0.100 P=0.470 |
|LOGISTIC REGRESSION| P=0.161 (e) (e) P=0.500 P=0.180 P=0.555 |
|COCH-ARM / FISHERS | P=0.144 (e) (e) P=0.495 P=0.118 P=0.500 |
|ORDER RESTRICTED | P=0.076 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 58
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION(
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 6 NG/KG 20 NG/KG 44 NG/KG 92 NG/KG 200 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus: Endometrium |
| Hyperplasia Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 31/53 (58%) 29/53 (55%) 29/53 (55%) 33/52 (63%) 39/52 (75%) 37/53 (70%) |
|POLY-3 RATE (b) | 31/47.62 29/44.39 29/43.19 33/43.55 39/45.13 37/45.40 |
|POLY-3 PERCENT (g) | 65.1% 65.3% 67.2% 75.8% 86.4% 81.5% |
|TERMINAL (d) | 16/25 (64%) 14/22 (64%) 14/24 (58%) 21/25 (84%) 19/20 (95%) 19/23 (83%) |
|FIRST INCIDENCE | 310 289 300 302 321 326 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.019 * P=0.434 P=0.491 P=0.307 P=0.019 * P=0.078 |
|POLY 3 | P=0.006 ** P=0.581 P=0.506 P=0.173 P=0.010 * P=0.049 * |
|POLY 1.5 | P=0.009 ** P=0.522N P=0.556 P=0.265 P=0.015 * P=0.074 |
|POLY 6 | P=0.004 ** P=0.498 P=0.476 P=0.088 P=0.008 ** P=0.032 * |
|LOGISTIC REGRESSION| P=0.009 ** P=0.496N P=0.580 P=0.293 P=0.020 * P=0.081 |
|COCH-ARM / FISHERS | P=0.022 * P=0.422N P=0.422N P=0.374 P=0.056 P=0.156 |
|ORDER RESTRICTED | P=0.014 * (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).