TDMS Study 96007-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 09/30/03
EXPERIMENT: 96007 TEST: 03 TIME: 08:53:10
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G
PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6
------------------------------------------------------------------------------------------------------------------------------------
FINAL # 3 RATS CONTROL VS TREATED
REASONS FOR REMOVAL: 25018 Dosing Accident
25019 Moribund Sacrifice
25020 Natural Death
25021 Terminal Sacrifice
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE 001 0 NG/KG
INCLUDE 002 3 NG/KG
INCLUDE 003 10 NG/KG
INCLUDE 004 22 NG/KG
INCLUDE 005 46 NG/KG
INCLUDE 006 100 NG/KG
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 09/30/03
EXPERIMENT: 96007 TEST: 03 TIME: 08:53:10
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G
PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6
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
Hyperplasia
Hypertrophy
Vacuolization Cytoplasmic
Adrenal Medulla Hyperplasia
Bone Marrow Hyperplasia
Clitoral Gland Inflammation
Clitoral Gland: Duct Cyst
Harderian Gland Inflammation
Heart Cardiomyopathy
Intestine Large, Rectum Parasite Metazoan
Kidney Inflammation Chronic
Mineralization
Nephropathy
Kidney: Transitional Epithelium Hyperplasia
Liver Angiectasis
Cholangiofibrosis
Cytoplasmic Alteration
Degeneration Cystic
Eosinophilic Focus
Fatty Change Diffuse
Hyperplasia
Inflammation
Mixed Cell Focus
Necrosis
Pigmentation
Toxic Hepatopathy
Liver: Artery Inflammation Chronic
Liver: Bile Duct Cyst
Fibrosis
Hyperplasia
Liver: Centrilobular Degeneration
Liver: Hepatocyte Hypertrophy
Multinucleated
Liver: Oval Cell Hyperplasia
Liver: Portal Fibrosis
Lung Hemorrhage
Infiltration Cellular Histiocyte
Metaplasia
Lung: Alveolar Epithelium Hyperplasia
Metaplasia Bronchiolar
Lymph Node, Mandibular Ectasia
Hyperplasia
Lymph Node, Mesenteric Hyperplasia
Lymph Node: Lumbar Ectasia
Lymph Node: Mediastinal Ectasia
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 09/30/03
EXPERIMENT: 96007 TEST: 03 TIME: 08:53:10
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G
PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6
Hemorrhage
Mammary Gland Cyst
Hyperplasia
Mesentery: Artery Inflammation Chronic
Nose Inflammation
Nose: Nasolacrimal Duct Inflammation
Nose: Septum Inflammation
Oral Mucosa: Gingival Hyperplasia
Ovary Atrophy
Pancreas Inflammation Chronic
Pancreas: Acinus Atrophy
Vacuolization Cytoplasmic
Pancreas: Artery Inflammation Chronic
Pituitary Gland Angiectasis
Spleen Hematopoietic Cell Proliferation
Hyperplasia Lymphoid
Pigmentation
Spleen: Lymphoid Follicle Atrophy
Stomach, Forestomach Hyperkeratosis
Hyperplasia
Inflammation
Ulcer
Stomach, Glandular Mineralization
Ulcer
Thymus Atrophy
Thyroid Gland: Follicular Cell Hyperplasia
Hypertrophy
Tooth: Peridontal Tissue Inflammation
Urinary Bladder Inflammation
Uterus Metaplasia
Uterus: Endometrium Hyperplasia Cystic
===============================================================
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 1
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 11/53 (21%) 21/54 (39%) 18/53 (34%) 17/53 (32%) 17/53 (32%) 11/53 (21%) |
|POLY-3 RATE (b) | 11/40.84 21/37.32 18/40.08 17/35.48 17/40.70 11/45.07 |
|POLY-3 PERCENT (g) | 26.9% 56.3% 44.9% 47.9% 41.8% 24.4% |
|TERMINAL (d) | 6/25 (24%) 15/21 (71%) 12/23 (52%) 12/19 (63%) 12/22 (55%) 4/21 (19%) |
|FIRST INCIDENCE | 645 556 550 626 486 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.121N P=0.005 ** P=0.073 P=0.021 * P=0.087 P=0.518 |
|POLY 3 | P=0.021N* P=0.005 ** P=0.067 P=0.042 * P=0.113 P=0.492N |
|POLY 1.5 | P=0.036N* P=0.011 * P=0.069 P=0.071 P=0.122 P=0.510N |
|POLY 6 | P=0.017N* P=0.002 ** P=0.062 P=0.021 * P=0.096 P=0.509N |
|LOGISTIC REGRESSION| P=0.031N* P=0.004 ** P=0.074 P=0.024 * P=0.112 P=0.537N |
|COCH-ARM / FISHERS | P=0.121N P=0.033 * P=0.095 P=0.135 P=0.135 P=0.594N |
|ORDER RESTRICTED | P=0.035N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/54 (0%) 4/53 (8%) 5/53 (9%) 5/53 (9%) 27/53 (51%) |
|POLY-3 RATE (b) | 2/39.86 0/34.61 4/39.71 5/34.86 5/39.59 27/46.52 |
|POLY-3 PERCENT (g) | 5.0% 0.0% 10.1% 14.3% 12.6% 58.0% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 3/23 (13%) 3/19 (16%) 3/22 (14%) 12/21 (57%) |
|FIRST INCIDENCE | 646 --- 240 626 590 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.299N P=0.302 P=0.113 P=0.185 P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.269N P=0.334 P=0.162 P=0.211 P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.254N P=0.331 P=0.183 P=0.214 P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.287N P=0.333 P=0.140 P=0.205 P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.268N P=0.335 P=0.149 P=0.208 P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.243N P=0.339 P=0.219 P=0.219 P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 2
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Degeneration Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 11/53 (21%) 15/54 (28%) 21/53 (40%) 18/53 (34%) 17/53 (32%) 17/53 (32%) |
|POLY-3 RATE (b) | 11/41.19 15/37.14 21/40.29 18/37.16 17/42.13 17/46.12 |
|POLY-3 PERCENT (g) | 26.7% 40.4% 52.1% 48.4% 40.4% 36.9% |
|TERMINAL (d) | 4/25 (16%) 9/21 (43%) 13/23 (57%) 11/19 (58%) 8/22 (36%) 6/21 (29%) |
|FIRST INCIDENCE | 646 490 578 462 486 561 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.392 P=0.117 P=0.026 * P=0.020 * P=0.113 P=0.133 |
|POLY 3 | P=0.440N P=0.143 P=0.013 * P=0.034 * P=0.134 P=0.214 |
|POLY 1.5 | P=0.531N P=0.187 P=0.015 * P=0.052 P=0.134 P=0.194 |
|POLY 6 | P=0.387N P=0.104 P=0.011 * P=0.019 * P=0.126 P=0.213 |
|LOGISTIC REGRESSION| P=0.511N P=0.134 P=0.018 * P=0.031 * P=0.124 P=0.175 |
|COCH-ARM / FISHERS | P=0.328 P=0.267 P=0.028 * P=0.095 P=0.135 P=0.135 |
|ORDER RESTRICTED | P=0.059 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 16/53 (30%) 16/54 (30%) 18/53 (34%) 25/53 (47%) 29/53 (55%) 30/53 (57%) |
|POLY-3 RATE (b) | 16/41.46 16/37.20 18/41.07 25/40.57 29/44.68 30/47.52 |
|POLY-3 PERCENT (g) | 38.6% 43.0% 43.8% 61.6% 64.9% 63.1% |
|TERMINAL (d) | 10/25 (40%) 11/21 (52%) 12/23 (52%) 11/19 (58%) 14/22 (64%) 16/21 (76%) |
|FIRST INCIDENCE | 487 241 344 417 444 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002 ** P=0.354 P=0.332 P=0.009 ** P=0.008 ** P=0.004 ** |
|POLY 3 | P=0.004 ** P=0.431 P=0.396 P=0.024 * P=0.009 ** P=0.013 * |
|POLY 1.5 | P=0.002 ** P=0.512 P=0.386 P=0.031 * P=0.008 ** P=0.011 * |
|POLY 6 | P=0.005 ** P=0.338 P=0.392 P=0.019 * P=0.011 * P=0.012 * |
|LOGISTIC REGRESSION| P=0.002 ** P=0.410 P=0.385 P=0.018 * P=0.007 ** P=0.011 * |
|COCH-ARM / FISHERS | P<0.001 ** P=0.559N P=0.418 P=0.055 P=0.009 ** P=0.005 ** |
|ORDER RESTRICTED | P=0.007 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 3
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 41/53 (77%) 43/54 (80%) 46/53 (87%) 40/53 (75%) 45/53 (85%) 47/53 (89%) |
|POLY-3 RATE (b) | 41/44.21 43/45.74 46/46.99 40/46.09 45/48.42 47/51.08 |
|POLY-3 PERCENT (g) | 92.8% 94.0% 97.9% 86.8% 92.9% 92.0% |
|TERMINAL (d) | 25/25 (100%) 20/21 (95%) 23/23 (100%) 18/19 (95%) 22/22 (100%) 20/21 (95%) |
|FIRST INCIDENCE | 474 394 236 338 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.326 P=0.088 P=0.159 P=0.103 P=0.145 P=0.101 |
|POLY 3 | P=0.381N P=0.600 P=0.155 P=0.230N P=0.686 P=0.622N |
|POLY 1.5 | P=0.503 P=0.495 P=0.078 P=0.340N P=0.456 P=0.446 |
|POLY 6 | P=0.203N P=0.759N P=0.529 P=0.159N P=0.581N P=0.390N |
|LOGISTIC REGRESSION| P=0.552N P=0.071 P=0.025 * P=0.405 P=0.167 P=0.506 |
|COCH-ARM / FISHERS | P=0.082 P=0.480 P=0.156 P=0.500N P=0.229 P=0.098 |
|ORDER RESTRICTED | P=0.285N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/54 (2%) 2/53 (4%) 1/53 (2%) 3/53 (6%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/39.55 1/35.36 2/38.79 1/34.53 3/40.16 1/42.92 |
|POLY-3 PERCENT (g) | 0.0% 2.8% 5.2% 2.9% 7.5% 2.3% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 1/23 (4%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- 462 720 626 578 641 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.498 P=0.487 P=0.231 P=0.441 P=0.129 P=0.505 |
|POLY 3 | P=0.523 P=0.478 P=0.232 P=0.473 P=0.121 P=0.516 |
|POLY 1.5 | P=0.503 P=0.488 P=0.231 P=0.484 P=0.120 P=0.514 |
|POLY 6 | P=0.522 P=0.467 P=0.233 P=0.460 P=0.121 P=0.513 |
|LOGISTIC REGRESSION| P=0.440 P=0.539 P=0.232 P=0.497 P=0.121 P=0.492 |
|COCH-ARM / FISHERS | P=0.437 P=0.505 P=0.248 P=0.500 P=0.121 P=0.500 |
|ORDER RESTRICTED | P=0.188 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 4
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 11/53 (21%) 7/54 (13%) 12/53 (23%) 21/53 (40%) 18/53 (34%) 15/53 (28%) |
|POLY-3 RATE (b) | 11/40.73 7/35.24 12/40.94 21/38.47 18/41.90 15/45.44 |
|POLY-3 PERCENT (g) | 27.0% 19.9% 29.3% 54.6% 43.0% 33.0% |
|TERMINAL (d) | 9/25 (36%) 5/21 (24%) 6/23 (26%) 11/19 (58%) 9/22 (41%) 6/21 (29%) |
|FIRST INCIDENCE | 366 548 236 338 185 561 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.116 P=0.341N P=0.429 P=0.003 ** P=0.059 P=0.195 |
|POLY 3 | P=0.263 P=0.322N P=0.506 P=0.008 ** P=0.092 P=0.354 |
|POLY 1.5 | P=0.197 P=0.272N P=0.488 P=0.012 * P=0.093 P=0.326 |
|POLY 6 | P=0.309 P=0.377N P=0.528 P=0.005 ** P=0.093 P=0.366 |
|LOGISTIC REGRESSION| P=0.177 P=0.340N P=0.477 P=0.008 ** P=0.087 P=0.306 |
|COCH-ARM / FISHERS | P=0.084 P=0.207N P=0.500 P=0.028 * P=0.095 P=0.249 |
|ORDER RESTRICTED | P=0.031 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/54 (2%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/39.55 1/34.61 2/38.75 1/34.16 0/39.00 0/42.60 |
|POLY-3 PERCENT (g) | 0.0% 2.9% 5.2% 2.9% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 2/23 (9%) 1/19 (5%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- 731 (T) 731 (T) 731 (T) --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.256N P=0.465 P=0.219 P=0.445 (e) (e) |
|POLY 3 | P=0.225N P=0.473 P=0.232 P=0.471 (e) (e) |
|POLY 1.5 | P=0.229N P=0.486 P=0.231 P=0.483 (e) (e) |
|POLY 6 | P=0.226N P=0.461 P=0.232 P=0.456 (e) (e) |
|LOGISTIC REGRESSION| (e) P=0.465 P=0.219 P=0.445 (e) (e) |
|COCH-ARM / FISHERS | P=0.242N P=0.505 P=0.248 P=0.500 (e) (e) |
|ORDER RESTRICTED | P=0.295N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 5
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 19/53 (36%) 10/54 (19%) 18/53 (34%) 7/53 (13%) 10/53 (19%) 9/53 (17%) |
|POLY-3 RATE (b) | 19/41.29 10/36.14 18/40.63 7/35.79 10/39.76 9/44.75 |
|POLY-3 PERCENT (g) | 46.0% 27.7% 44.3% 19.6% 25.2% 20.1% |
|TERMINAL (d) | 11/25 (44%) 6/21 (29%) 11/23 (48%) 4/19 (21%) 7/22 (32%) 2/21 (10%) |
|FIRST INCIDENCE | 487 526 604 406 578 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.046N* P=0.137N P=0.565 P=0.051N P=0.086N P=0.057N |
|POLY 3 | P=0.007N** P=0.070N P=0.527N P=0.010N* P=0.036N* P=0.007N** |
|POLY 1.5 | P=0.012N* P=0.051N P=0.542N P=0.007N** P=0.036N* P=0.010N* |
|POLY 6 | P=0.005N** P=0.097N P=0.511N P=0.017N* P=0.041N* P=0.007N** |
|LOGISTIC REGRESSION| P=0.013N* P=0.097N P=0.528N P=0.017N* P=0.038N* P=0.012N* |
|COCH-ARM / FISHERS | P=0.044N* P=0.036N* P=0.500N P=0.006N** P=0.040N* P=0.023N* |
|ORDER RESTRICTED | P=0.003N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 36/53 (68%) 41/54 (76%) 32/53 (60%) 35/53 (66%) 37/53 (70%) 43/53 (81%) |
|POLY-3 RATE (b) | 36/52.64 41/51.71 32/51.50 35/51.56 37/49.92 43/50.67 |
|POLY-3 PERCENT (g) | 68.4% 79.3% 62.1% 67.9% 74.1% 84.9% |
|TERMINAL (d) | 9/25 (36%) 13/21 (62%) 7/23 (30%) 5/19 (26%) 12/22 (55%) 17/21 (81%) |
|FIRST INCIDENCE | 169 200 47 53 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.326 P=0.125 P=0.405N P=0.284 P=0.400 P=0.177 |
|POLY 3 | P=0.024 * P=0.144 P=0.321N P=0.561N P=0.335 P=0.036 * |
|POLY 1.5 | P=0.034 * P=0.181 P=0.298N P=0.541N P=0.387 P=0.055 |
|POLY 6 | P=0.015 * P=0.106 P=0.357N P=0.581N P=0.290 P=0.018 * |
|LOGISTIC REGRESSION| P=0.012 * P=0.492 P=0.209N P=0.130N P=0.521 P=0.057 |
|COCH-ARM / FISHERS | P=0.056 P=0.240 P=0.272N P=0.500N P=0.500 P=0.090 |
|ORDER RESTRICTED | P=0.038 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 6
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Brain |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/54 (2%) 1/53 (2%) 0/53 (0%) 2/53 (4%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 1/34.61 1/38.75 0/34.16 2/39.09 2/42.60 |
|POLY-3 PERCENT (g) | 0.0% 2.9% 2.6% 0.0% 5.1% 4.7% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 1/23 (4%) 0/19 (0%) 1/22 (5%) 2/21 (10%) |
|FIRST INCIDENCE | --- 731 (T) 731 (T) --- 708 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.113 P=0.465 P=0.483 (e) P=0.213 P=0.200 |
|POLY 3 | P=0.157 P=0.473 P=0.496 (e) P=0.234 P=0.254 |
|POLY 1.5 | P=0.150 P=0.486 P=0.495 (e) P=0.236 P=0.252 |
|POLY 6 | P=0.155 P=0.461 P=0.497 (e) P=0.230 P=0.247 |
|LOGISTIC REGRESSION| P=0.130 P=0.465 P=0.483 (e) P=0.223 P=0.200 |
|COCH-ARM / FISHERS | P=0.124 P=0.505 P=0.500 (e) P=0.248 P=0.248 |
|ORDER RESTRICTED | P=0.124 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 41/50 (82%) 40/52 (77%) 35/53 (66%) 34/52 (65%) 28/51 (55%) 26/53 (49%) |
|POLY-3 RATE (b) | 41/46.36 40/46.38 35/47.18 34/44.94 28/43.18 26/47.03 |
|POLY-3 PERCENT (g) | 88.4% 86.3% 74.2% 75.7% 64.8% 55.3% |
|TERMINAL (d) | 22/25 (88%) 18/21 (86%) 16/23 (70%) 13/19 (68%) 14/22 (64%) 12/21 (57%) |
|FIRST INCIDENCE | 169 264 177 53 185 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003N** P=0.258 P=0.323N P=0.471 P=0.075N P=0.039N* |
|POLY 3 | P<0.001N** P=0.498N P=0.054N P=0.074N P=0.004N** P<0.001N** |
|POLY 1.5 | P<0.001N** P=0.472N P=0.065N P=0.059N P=0.003N** P<0.001N** |
|POLY 6 | P<0.001N** P=0.513N P=0.050N P=0.103N P=0.006N** P<0.001N** |
|LOGISTIC REGRESSION| P<0.001N** P=0.453N P=0.063N P=0.063N P=0.003N** P<0.001N** |
|COCH-ARM / FISHERS | P<0.001N** P=0.349N P=0.052N P=0.046N* P=0.003N** P<0.001N** |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 7
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland: Duct |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 34/50 (68%) 37/52 (71%) 41/53 (77%) 42/52 (81%) 41/51 (80%) 48/53 (91%) |
|POLY-3 RATE (b) | 34/44.15 37/46.24 41/49.46 42/46.19 41/46.63 48/50.84 |
|POLY-3 PERCENT (g) | 77.0% 80.0% 82.9% 90.9% 87.9% 94.4% |
|TERMINAL (d) | 19/25 (76%) 14/21 (67%) 18/23 (78%) 18/19 (95%) 19/22 (86%) 21/21 (100%) |
|FIRST INCIDENCE | 169 264 54 53 141 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.075 P=0.129 P=0.124 P=0.008 ** P=0.091 P=0.011 * |
|POLY 3 | P=0.005 ** P=0.462 P=0.320 P=0.045 * P=0.120 P=0.008 ** |
|POLY 1.5 | P=0.005 ** P=0.448 P=0.249 P=0.067 P=0.118 P=0.006 ** |
|POLY 6 | P=0.004 ** P=0.481 P=0.397 P=0.025 * P=0.123 P=0.009 ** |
|LOGISTIC REGRESSION| P=0.010 * P=0.353 P=0.167 P=0.056 P=0.108 P=0.015 * |
|COCH-ARM / FISHERS | P=0.003 ** P=0.448 P=0.199 P=0.105 P=0.116 P=0.004 ** |
|ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus |
| Perforation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/52 (0%) 0/54 (0%) 2/53 (4%) 0/52 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/38.90 0/34.61 2/40.74 0/33.71 0/39.00 0/42.60 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 4.9% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 47 --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.394N (e) P=0.238 (e) (e) (e) |
|POLY 3 | P=0.355N (e) P=0.247 (e) (e) (e) |
|POLY 1.5 | P=0.369N (e) P=0.245 (e) (e) (e) |
|POLY 6 | P=0.346N (e) P=0.248 (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.392N (e) P=0.252 (e) (e) (e) |
|ORDER RESTRICTED | P=0.341N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 8
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus: Muscularis |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/52 (2%) 2/54 (4%) 1/53 (2%) 1/52 (2%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 1/39.60 2/35.11 1/38.75 1/33.71 2/39.90 0/42.60 |
|POLY-3 PERCENT (g) | 2.5% 5.7% 2.6% 3.0% 5.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 1/23 (4%) 1/19 (5%) 1/22 (5%) 0/21 (0%) |
|FIRST INCIDENCE | 492 578 731 (T) 731 (T) 341 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.272N P=0.450 P=0.751 P=0.719 P=0.480 P=0.475N |
|POLY 3 | P=0.239N P=0.458 P=0.756 P=0.724 P=0.503 P=0.485N |
|POLY 1.5 | P=0.244N P=0.480 P=0.757 P=0.740 P=0.506 P=0.485N |
|POLY 6 | P=0.246N P=0.435 P=0.755 P=0.704 P=0.494 P=0.493N |
|LOGISTIC REGRESSION| P=0.278N P=0.524 P=0.756N P=0.762N P=0.512 P=0.645N |
|COCH-ARM / FISHERS | P=0.275N P=0.514 P=0.748N P=0.752N P=0.507 P=0.495N |
|ORDER RESTRICTED | P=0.241N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Esophagus: Periesophageal Tissue |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/52 (0%) 0/54 (0%) 3/53 (6%) 0/52 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/38.90 0/34.61 3/41.71 0/33.71 0/39.00 0/42.60 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 7.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 47 --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.288N (e) P=0.122 (e) (e) (e) |
|POLY 3 | P=0.236N (e) P=0.131 (e) (e) (e) |
|POLY 1.5 | P=0.252N (e) P=0.128 (e) (e) (e) |
|POLY 6 | P=0.226N (e) P=0.132 (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.675N (e) P=0.365 (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.288N (e) P=0.125 (e) (e) (e) |
|ORDER RESTRICTED | P=0.246N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 9
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Eye: Retina |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 5/54 (9%) 5/53 (9%) 3/52 (6%) 4/53 (8%) 6/53 (11%) |
|POLY-3 RATE (b) | 5/39.55 5/35.79 5/38.75 3/34.14 4/39.20 6/42.60 |
|POLY-3 PERCENT (g) | 12.6% 14.0% 12.9% 8.8% 10.2% 14.1% |
|TERMINAL (d) | 5/25 (20%) 3/21 (14%) 5/23 (22%) 2/19 (11%) 3/22 (14%) 6/21 (29%) |
|FIRST INCIDENCE | 731 (T) 526 731 (T) 607 677 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.368 P=0.529 P=0.581 P=0.512N P=0.575N P=0.371 |
|POLY 3 | P=0.498 P=0.568 P=0.619 P=0.439N P=0.506N P=0.553 |
|POLY 1.5 | P=0.477 P=0.597 P=0.614 P=0.410N P=0.503N P=0.546 |
|POLY 6 | P=0.493 P=0.540 P=0.623 P=0.473N P=0.513N P=0.536 |
|LOGISTIC REGRESSION| P=0.502 P=0.529 P=0.581 P=0.509N P=0.556N P=0.371 |
|COCH-ARM / FISHERS | P=0.399 P=0.617N P=0.629N P=0.369N P=0.500N P=0.500 |
|ORDER RESTRICTED | P=0.658 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Harderian Gland |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 12/53 (23%) 3/54 (6%) 2/53 (4%) 2/52 (4%) 8/53 (15%) 6/53 (11%) |
|POLY-3 RATE (b) | 12/42.07 3/35.42 2/38.75 2/33.87 8/40.78 6/43.76 |
|POLY-3 PERCENT (g) | 28.5% 8.5% 5.2% 5.9% 19.6% 13.7% |
|TERMINAL (d) | 6/25 (24%) 1/21 (5%) 2/23 (9%) 1/19 (5%) 4/22 (18%) 2/21 (10%) |
|FIRST INCIDENCE | 366 578 731 (T) 690 317 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.478 P=0.040N* P=0.009N** P=0.023N* P=0.307N P=0.142N |
|POLY 3 | P=0.482N P=0.024N* P=0.005N** P=0.011N* P=0.242N P=0.074N |
|POLY 1.5 | P=0.530N P=0.017N* P=0.005N** P=0.007N** P=0.234N P=0.076N |
|POLY 6 | P=0.459N P=0.034N* P=0.006N** P=0.018N* P=0.265N P=0.083N |
|LOGISTIC REGRESSION| P=0.538 P=0.017N* P=0.005N** P=0.008N** P=0.230N P=0.087N |
|COCH-ARM / FISHERS | P=0.457 P=0.011N* P=0.004N** P=0.004N** P=0.229N P=0.098N |
|ORDER RESTRICTED | P=0.008N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 10
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Heart |
| Cardiomyopathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 10/53 (19%) 12/54 (22%) 22/53 (42%) 25/52 (48%) 32/53 (60%) 36/52 (69%) |
|POLY-3 RATE (b) | 10/41.81 12/36.26 22/41.99 25/38.88 32/43.24 36/47.96 |
|POLY-3 PERCENT (g) | 23.9% 33.1% 52.4% 64.3% 74.0% 75.1% |
|TERMINAL (d) | 6/25 (24%) 8/21 (38%) 10/23 (44%) 12/19 (63%) 19/22 (86%) 15/21 (71%) |
|FIRST INCIDENCE | 169 462 429 380 341 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.243 P=0.012 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.256 P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.316 P=0.004 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.201 P=0.006 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.325 P=0.007 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.425 P=0.010 * P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Colon |
| Parasite Metazoan |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/52 (2%) 2/53 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 2/51 (4%) |
|POLY-3 RATE (b) | 1/39.56 2/34.17 1/38.75 0/34.16 0/39.00 2/41.24 |
|POLY-3 PERCENT (g) | 2.5% 5.9% 2.6% 0.0% 0.0% 4.9% |
|TERMINAL (d) | 0/25 (0%) 2/21 (10%) 1/23 (4%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 701 731 (T) 731 (T) --- --- 648 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.458 P=0.437 P=0.751 P=0.557N P=0.515N P=0.479 |
|POLY 3 | P=0.476 P=0.449 P=0.757 P=0.529N P=0.503N P=0.515 |
|POLY 1.5 | P=0.472 P=0.471 P=0.756 P=0.516N P=0.500N P=0.513 |
|POLY 6 | P=0.474 P=0.427 P=0.757 P=0.545N P=0.507N P=0.507 |
|LOGISTIC REGRESSION| P=0.493 P=0.421 P=0.759 P=0.541N P=0.504N P=0.510 |
|COCH-ARM / FISHERS | P=0.452 P=0.507 P=0.748N P=0.495N P=0.495N P=0.493 |
|ORDER RESTRICTED | P=0.398 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 11
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Parasite Metazoan |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 6/52 (12%) 4/54 (7%) 0/53 (0%) 0/52 (0%) 2/53 (4%) 1/53 (2%) |
|POLY-3 RATE (b) | 6/39.78 4/34.61 0/38.75 0/33.80 2/39.77 1/42.60 |
|POLY-3 PERCENT (g) | 15.1% 11.6% 0.0% 0.0% 5.0% 2.4% |
|TERMINAL (d) | 2/25 (8%) 4/21 (19%) 0/23 (0%) 0/19 (0%) 1/22 (5%) 1/21 (5%) |
|FIRST INCIDENCE | 645 731 (T) --- --- 444 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.101N P=0.507N P=0.023N* P=0.048N* P=0.172N P=0.081N |
|POLY 3 | P=0.066N P=0.459N P=0.016N* P=0.025N* P=0.130N P=0.044N* |
|POLY 1.5 | P=0.071N P=0.410N P=0.016N* P=0.020N* P=0.128N P=0.045N* |
|POLY 6 | P=0.064N P=0.519N P=0.017N* P=0.033N* P=0.139N P=0.050N |
|LOGISTIC REGRESSION| P=0.073N P=0.495N P=0.018N* P=0.027N* P=0.131N P=0.047N* |
|COCH-ARM / FISHERS | P=0.094N P=0.347N P=0.013N* P=0.013N* P=0.129N P=0.053N |
|ORDER RESTRICTED | P=0.005N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Calculus Micro Observation Only |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/54 (2%) 1/53 (2%) 3/53 (6%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 1/39.58 1/34.61 1/39.25 3/35.01 2/39.47 0/42.60 |
|POLY-3 PERCENT (g) | 2.5% 2.9% 2.6% 8.6% 5.1% 0.0% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 0/23 (0%) 1/19 (5%) 1/22 (5%) 0/21 (0%) |
|FIRST INCIDENCE | 722 731 (T) 578 601 589 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.300N P=0.722 P=0.754N P=0.220 P=0.469 P=0.524N |
|POLY 3 | P=0.273N P=0.730 P=0.759 P=0.261 P=0.499 P=0.485N |
|POLY 1.5 | P=0.283N P=0.745 P=0.756 P=0.278 P=0.500 P=0.487N |
|POLY 6 | P=0.278N P=0.715 P=0.761N P=0.243 P=0.496 P=0.490N |
|LOGISTIC REGRESSION| P=0.301N P=0.717 P=0.760 P=0.267 P=0.496 P=0.507N |
|COCH-ARM / FISHERS | P=0.330N P=0.748N P=0.752N P=0.309 P=0.500 P=0.500N |
|ORDER RESTRICTED | P=0.243N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 12
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Casts Protein |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 5/54 (9%) 2/53 (4%) 0/53 (0%) 1/53 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 3/40.58 5/37.88 2/39.64 0/34.16 1/39.70 1/43.05 |
|POLY-3 PERCENT (g) | 7.4% 13.2% 5.1% 0.0% 2.5% 2.3% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 1/23 (4%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 512 341 348 --- 486 599 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.080N P=0.305 P=0.521N P=0.169N P=0.318N P=0.290N |
|POLY 3 | P=0.081N P=0.317 P=0.511N P=0.152N P=0.312N P=0.284N |
|POLY 1.5 | P=0.084N P=0.337 P=0.512N P=0.137N P=0.309N P=0.285N |
|POLY 6 | P=0.082N P=0.299 P=0.515N P=0.173N P=0.321N P=0.295N |
|LOGISTIC REGRESSION| P=0.134N P=0.427 P=0.486N P=0.121N P=0.302N P=0.343N |
|COCH-ARM / FISHERS | P=0.098N P=0.368 P=0.500N P=0.121N P=0.309N P=0.309N |
|ORDER RESTRICTED | P=0.050N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 1/53 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 2/39.90 0/34.61 0/38.75 0/34.16 1/39.47 1/43.05 |
|POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 0.0% 2.5% 2.3% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 631 --- --- --- 589 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.563 P=0.305N P=0.261N P=0.317N P=0.518N P=0.493N |
|POLY 3 | P=0.582 P=0.270N P=0.243N P=0.273N P=0.504N P=0.473N |
|POLY 1.5 | P=0.562 P=0.254N P=0.244N P=0.258N P=0.502N P=0.477N |
|POLY 6 | P=0.594 P=0.288N P=0.244N P=0.293N P=0.509N P=0.482N |
|LOGISTIC REGRESSION| P=0.516 P=0.263N P=0.242N P=0.267N P=0.501N P=0.501N |
|COCH-ARM / FISHERS | P=0.508 P=0.243N P=0.248N P=0.248N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.125N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 13
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 1/53 (2%) 1/53 (2%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 2/40.01 1/34.16 1/39.27 2/43.25 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 2.9% 2.6% 4.6% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 54 731 (T) 657 604 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.200 (e) P=0.234 P=0.445 P=0.512 P=0.251 |
|POLY 3 | P=0.222 (e) P=0.239 P=0.471 P=0.499 P=0.257 |
|POLY 1.5 | P=0.206 (e) P=0.237 P=0.483 P=0.499 P=0.254 |
|POLY 6 | P=0.229 (e) P=0.242 P=0.456 P=0.497 P=0.254 |
|LOGISTIC REGRESSION| P=0.118 (e) P=0.321 P=0.445 P=0.499 P=0.222 |
|COCH-ARM / FISHERS | P=0.170 (e) P=0.248 P=0.500 P=0.500 P=0.248 |
|ORDER RESTRICTED | P=0.144 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 1/54 (2%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 0/53 (0%) |
|POLY-3 RATE (b) | 5/40.43 1/35.11 0/38.75 1/34.57 1/39.21 0/42.60 |
|POLY-3 PERCENT (g) | 12.4% 2.9% 0.0% 2.9% 2.6% 0.0% |
|TERMINAL (d) | 4/25 (16%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 361 578 --- 615 675 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.069N P=0.143N P=0.041N* P=0.164N P=0.128N P=0.045N* |
|POLY 3 | P=0.047N* P=0.135N P=0.033N* P=0.140N P=0.107N P=0.026N* |
|POLY 1.5 | P=0.052N P=0.120N P=0.034N* P=0.124N P=0.105N P=0.026N* |
|POLY 6 | P=0.045N* P=0.152N P=0.033N* P=0.160N P=0.109N P=0.027N* |
|LOGISTIC REGRESSION| P=0.065N P=0.109N P=0.035N* P=0.116N P=0.105N P=0.031N* |
|COCH-ARM / FISHERS | P=0.071N P=0.098N P=0.028N* P=0.103N P=0.103N P=0.028N* |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 14
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 40/53 (75%) 39/54 (72%) 30/53 (57%) 32/53 (60%) 42/53 (79%) 42/53 (79%) |
|POLY-3 RATE (b) | 40/47.18 39/49.68 30/44.43 32/44.93 42/49.66 42/51.69 |
|POLY-3 PERCENT (g) | 84.8% 78.5% 67.5% 71.2% 84.6% 81.3% |
|TERMINAL (d) | 22/25 (88%) 14/21 (67%) 14/23 (61%) 12/19 (63%) 19/22 (86%) 15/21 (71%) |
|FIRST INCIDENCE | 169 241 47 338 185 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.242 P=0.290 P=0.136N P=0.559 P=0.277 P=0.309 |
|POLY 3 | P=0.257 P=0.282N P=0.032N* P=0.072N P=0.609N P=0.416N |
|POLY 1.5 | P=0.164 P=0.361N P=0.040N* P=0.080N P=0.511 P=0.557N |
|POLY 6 | P=0.372 P=0.205N P=0.024N* P=0.071N P=0.490N P=0.283N |
|LOGISTIC REGRESSION| P=0.091 P=0.479N P=0.039N* P=0.107N P=0.399 P=0.487 |
|COCH-ARM / FISHERS | P=0.053 P=0.436N P=0.032N* P=0.072N P=0.408 P=0.408 |
|ORDER RESTRICTED | P=0.250N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Nephropathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 34/53 (64%) 26/54 (48%) 32/53 (60%) 36/53 (68%) 39/53 (74%) 52/53 (98%) |
|POLY-3 RATE (b) | 34/45.60 26/39.85 32/41.81 36/42.25 39/47.46 52/52.55 |
|POLY-3 PERCENT (g) | 74.6% 65.3% 76.5% 85.2% 82.2% 99.0% |
|TERMINAL (d) | 21/25 (84%) 17/21 (81%) 21/23 (91%) 19/19 (100%) 21/22 (96%) 21/21 (100%) |
|FIRST INCIDENCE | 169 200 578 197 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.338N P=0.565N P=0.052 P=0.117 P=0.002 ** |
|POLY 3 | P<0.001 ** P=0.219N P=0.515 P=0.128 P=0.238 P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.137N P=0.539 P=0.232 P=0.232 P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.374N P=0.496 P=0.043 * P=0.219 P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.140N P=0.479N P=0.241 P=0.191 P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.070N P=0.421N P=0.419 P=0.201 P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 15
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney: Pelvis |
| Dilatation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/54 (2%) 1/53 (2%) 0/53 (0%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/40.16 1/34.62 1/39.54 0/34.16 2/39.72 0/42.60 |
|POLY-3 PERCENT (g) | 5.0% 2.9% 2.5% 0.0% 5.0% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 533 729 429 --- 599 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.261N P=0.540N P=0.507N P=0.275N P=0.685 P=0.237N |
|POLY 3 | P=0.234N P=0.552N P=0.505N P=0.274N P=0.691 P=0.224N |
|POLY 1.5 | P=0.245N P=0.528N P=0.508N P=0.258N P=0.692 P=0.225N |
|POLY 6 | P=0.231N P=0.577N P=0.505N P=0.295N P=0.688 P=0.230N |
|LOGISTIC REGRESSION| P=0.289N P=0.529N P=0.479N P=0.241N P=0.695N P=0.248N |
|COCH-ARM / FISHERS | P=0.283N P=0.493N P=0.500N P=0.248N P=0.691N P=0.248N |
|ORDER RESTRICTED | P=0.115N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney: Pelvis |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/54 (2%) 1/53 (2%) 1/53 (2%) 4/53 (8%) 2/53 (4%) |
|POLY-3 RATE (b) | 2/39.55 1/35.51 1/38.75 1/34.16 4/39.99 2/42.71 |
|POLY-3 PERCENT (g) | 5.1% 2.8% 2.6% 2.9% 10.0% 4.7% |
|TERMINAL (d) | 2/25 (8%) 0/21 (0%) 1/23 (4%) 1/19 (5%) 2/22 (9%) 1/21 (5%) |
|FIRST INCIDENCE | 731 (T) 341 731 (T) 731 (T) 444 701 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.290 P=0.543N P=0.529N P=0.596N P=0.302 P=0.643 |
|POLY 3 | P=0.383 P=0.538N P=0.507N P=0.551N P=0.341 P=0.667N |
|POLY 1.5 | P=0.362 P=0.519N P=0.510N P=0.530N P=0.340 P=0.670N |
|POLY 6 | P=0.384 P=0.557N P=0.506N P=0.577N P=0.339 P=0.675N |
|LOGISTIC REGRESSION| P=0.335 P=0.483N P=0.529N P=0.596N P=0.333 P=0.682 |
|COCH-ARM / FISHERS | P=0.295 P=0.493N P=0.500N P=0.500N P=0.339 P=0.691N |
|ORDER RESTRICTED | P=0.357 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 16
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Kidney: Transitional Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 6/54 (11%) 8/53 (15%) 8/53 (15%) 11/53 (21%) 11/53 (21%) |
|POLY-3 RATE (b) | 3/40.54 6/36.81 8/38.75 8/34.92 11/42.13 11/44.07 |
|POLY-3 PERCENT (g) | 7.4% 16.3% 20.7% 22.9% 26.1% 25.0% |
|TERMINAL (d) | 2/25 (8%) 3/21 (14%) 8/23 (35%) 7/19 (37%) 5/22 (23%) 6/21 (29%) |
|FIRST INCIDENCE | 169 341 731 (T) 453 185 599 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.024 * P=0.193 P=0.070 P=0.041 * P=0.020 * P=0.017 * |
|POLY 3 | P=0.052 P=0.193 P=0.081 P=0.055 P=0.021 * P=0.027 * |
|POLY 1.5 | P=0.043 * P=0.214 P=0.082 P=0.070 P=0.021 * P=0.026 * |
|POLY 6 | P=0.056 P=0.174 P=0.078 P=0.040 * P=0.022 * P=0.026 * |
|LOGISTIC REGRESSION| P=0.040 * P=0.285 P=0.094 P=0.078 P=0.022 * P=0.023 * |
|COCH-ARM / FISHERS | P=0.023 * P=0.254 P=0.101 P=0.101 P=0.021 * P=0.021 * |
|ORDER RESTRICTED | P=0.018 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/54 (2%) 1/53 (2%) 0/53 (0%) 3/53 (6%) 5/53 (9%) |
|POLY-3 RATE (b) | 2/39.55 1/35.17 1/38.75 0/34.16 3/39.00 5/43.18 |
|POLY-3 PERCENT (g) | 5.1% 2.8% 2.6% 0.0% 7.7% 11.6% |
|TERMINAL (d) | 2/25 (8%) 0/21 (0%) 1/23 (4%) 0/19 (0%) 3/22 (14%) 3/21 (14%) |
|FIRST INCIDENCE | 731 (T) 556 731 (T) --- 731 (T) 561 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.013 * P=0.543N P=0.529N P=0.300N P=0.441 P=0.175 |
|POLY 3 | P=0.021 * P=0.541N P=0.507N P=0.271N P=0.494 P=0.252 |
|POLY 1.5 | P=0.019 * P=0.522N P=0.510N P=0.256N P=0.497 P=0.247 |
|POLY 6 | P=0.022 * P=0.560N P=0.506N P=0.289N P=0.486 P=0.243 |
|LOGISTIC REGRESSION| P=0.023 * P=0.536N P=0.529N (e) P=0.441 P=0.234 |
|COCH-ARM / FISHERS | P=0.013 * P=0.493N P=0.500N P=0.248N P=0.500 P=0.219 |
|ORDER RESTRICTED | P=0.043 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 17
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Basophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 12/53 (23%) 9/54 (17%) 13/53 (25%) 8/53 (15%) 5/53 (9%) 8/53 (15%) |
|POLY-3 RATE (b) | 12/42.33 9/36.75 13/40.01 8/35.16 5/39.59 8/43.83 |
|POLY-3 PERCENT (g) | 28.4% 24.5% 32.5% 22.8% 12.6% 18.3% |
|TERMINAL (d) | 4/25 (16%) 4/21 (19%) 7/23 (30%) 5/19 (26%) 2/22 (9%) 3/21 (14%) |
|FIRST INCIDENCE | 492 485 429 592 642 610 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.126N P=0.505N P=0.449 P=0.485N P=0.091N P=0.283N |
|POLY 3 | P=0.065N P=0.447N P=0.432 P=0.382N P=0.066N P=0.194N |
|POLY 1.5 | P=0.077N P=0.383N P=0.446 P=0.311N P=0.060N P=0.191N |
|POLY 6 | P=0.067N P=0.520N P=0.402 P=0.478N P=0.079N P=0.224N |
|LOGISTIC REGRESSION| P=0.068N P=0.374N P=0.475 P=0.323N P=0.057N P=0.197N |
|COCH-ARM / FISHERS | P=0.130N P=0.297N P=0.500 P=0.229N P=0.055N P=0.229N |
|ORDER RESTRICTED | P=0.104N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Cholangiofibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/54 (2%) 2/53 (4%) 1/53 (2%) 11/53 (21%) 31/53 (58%) |
|POLY-3 RATE (b) | 1/39.86 1/35.19 2/38.75 1/34.16 11/40.33 31/47.12 |
|POLY-3 PERCENT (g) | 2.5% 2.8% 5.2% 2.9% 27.3% 65.8% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 2/23 (9%) 1/19 (5%) 6/22 (27%) 13/21 (62%) |
|FIRST INCIDENCE | 645 548 731 (T) 731 (T) 589 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.716 P=0.468 P=0.682 P=0.002 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.733 P=0.490 P=0.726 P=0.002 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.746 P=0.489 P=0.741 P=0.002 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.718 P=0.489 P=0.706 P=0.002 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.752N P=0.493 P=0.728 P=0.002 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.748N P=0.500 P=0.752N P=0.002 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 18
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Clear Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 1/54 (2%) 1/53 (2%) 4/53 (8%) 2/53 (4%) 2/53 (4%) |
|POLY-3 RATE (b) | 5/40.18 1/34.61 1/38.75 4/34.16 2/39.00 2/42.60 |
|POLY-3 PERCENT (g) | 12.4% 2.9% 2.6% 11.7% 5.1% 4.7% |
|TERMINAL (d) | 3/25 (12%) 1/21 (5%) 1/23 (4%) 4/19 (21%) 2/22 (9%) 2/21 (10%) |
|FIRST INCIDENCE | 548 731 (T) 731 (T) 731 (T) 731 (T) 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.433N P=0.142N P=0.113N P=0.617 P=0.263N P=0.262N |
|POLY 3 | P=0.318N P=0.138N P=0.108N P=0.602N P=0.226N P=0.191N |
|POLY 1.5 | P=0.338N P=0.120N P=0.109N P=0.559N P=0.222N P=0.193N |
|POLY 6 | P=0.315N P=0.159N P=0.108N P=0.624 P=0.236N P=0.203N |
|LOGISTIC REGRESSION| P=0.351N P=0.143N P=0.107N P=0.632 P=0.225N P=0.194N |
|COCH-ARM / FISHERS | P=0.406N P=0.098N P=0.103N P=0.500N P=0.219N P=0.219N |
|ORDER RESTRICTED | P=0.111N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Congestion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 2/39.85 0/34.61 0/38.75 0/34.16 0/39.00 2/43.86 |
|POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 0.0% 0.0% 4.6% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 648 --- --- --- --- 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.261 P=0.294N P=0.252N P=0.310N P=0.250N P=0.685N |
|POLY 3 | P=0.267 P=0.269N P=0.243N P=0.272N P=0.241N P=0.660N |
|POLY 1.5 | P=0.252 P=0.254N P=0.244N P=0.257N P=0.239N P=0.665N |
|POLY 6 | P=0.278 P=0.287N P=0.243N P=0.293N P=0.246N P=0.666N |
|LOGISTIC REGRESSION| P=0.197 P=0.269N P=0.242N P=0.273N P=0.241N P=0.627 |
|COCH-ARM / FISHERS | P=0.223 P=0.243N P=0.248N P=0.248N P=0.248N P=0.691N |
|ORDER RESTRICTED | P=0.121N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 19
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Cytoplasmic Alteration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 0/39.00 2/42.60 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.7% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 2/21 (10%) |
|FIRST INCIDENCE | --- --- --- --- --- 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.009 ** (e) (e) (e) (e) P=0.200 |
|POLY 3 | P=0.012 * (e) (e) (e) (e) P=0.254 |
|POLY 1.5 | P=0.012 * (e) (e) (e) (e) P=0.252 |
|POLY 6 | P=0.012 * (e) (e) (e) (e) P=0.247 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P=0.200 |
|COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.248 |
|ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Degeneration Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 4/53 (8%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 2/34.16 0/39.00 4/43.34 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.9% 0.0% 9.2% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 2/19 (11%) 0/22 (0%) 2/21 (10%) |
|FIRST INCIDENCE | --- --- --- 731 (T) --- 610 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003 ** (e) (e) P=0.179 (e) P=0.057 |
|POLY 3 | P=0.003 ** (e) (e) P=0.205 (e) P=0.072 |
|POLY 1.5 | P=0.003 ** (e) (e) P=0.218 (e) P=0.070 |
|POLY 6 | P=0.003 ** (e) (e) P=0.190 (e) P=0.070 |
|LOGISTIC REGRESSION| P=0.005 ** (e) (e) P=0.179 (e) P=0.069 |
|COCH-ARM / FISHERS | P=0.003 ** (e) (e) P=0.248 (e) P=0.059 |
|ORDER RESTRICTED | P=0.004 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 20
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Eosinophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 11/53 (21%) 14/54 (26%) 21/53 (40%) 27/53 (51%) 27/53 (51%) 44/53 (83%) |
|POLY-3 RATE (b) | 11/40.67 14/38.67 21/42.52 27/42.49 27/45.20 44/51.46 |
|POLY-3 PERCENT (g) | 27.1% 36.2% 49.4% 63.6% 59.7% 85.5% |
|TERMINAL (d) | 6/25 (24%) 7/21 (33%) 9/23 (39%) 10/19 (53%) 11/22 (50%) 18/21 (86%) |
|FIRST INCIDENCE | 645 449 550 380 341 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.181 P=0.032 * P<0.001 ** P=0.002 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.259 P=0.026 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.288 P=0.021 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.233 P=0.035 * P<0.001 ** P=0.002 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.236 P=0.021 * P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.344 P=0.028 * P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Fatty Change Diffuse |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/54 (4%) 12/53 (23%) 17/53 (32%) 30/53 (57%) 48/53 (91%) |
|POLY-3 RATE (b) | 0/39.55 2/36.25 12/41.24 17/38.36 30/44.14 48/51.82 |
|POLY-3 PERCENT (g) | 0.0% 5.5% 29.1% 44.3% 68.0% 92.6% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 6/23 (26%) 8/19 (42%) 17/22 (77%) 19/21 (91%) |
|FIRST INCIDENCE | --- 341 236 338 185 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.231 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.218 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.227 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.208 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.282 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.252 P<0.001 ** 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: 03 Page 21
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Fatty Change Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 6/54 (11%) 4/53 (8%) 4/53 (8%) 1/53 (2%) 2/53 (4%) |
|POLY-3 RATE (b) | 2/39.69 6/36.23 4/38.81 4/34.47 1/39.70 2/43.03 |
|POLY-3 PERCENT (g) | 5.0% 16.6% 10.3% 11.6% 2.5% 4.7% |
|TERMINAL (d) | 1/25 (4%) 3/21 (14%) 2/23 (9%) 3/19 (16%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 694 526 717 645 486 604 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.148N P=0.094 P=0.318 P=0.207 P=0.527N P=0.665 |
|POLY 3 | P=0.115N P=0.102 P=0.325 P=0.273 P=0.500N P=0.665N |
|POLY 1.5 | P=0.121N P=0.116 P=0.324 P=0.299 P=0.499N P=0.669N |
|POLY 6 | P=0.118N P=0.091 P=0.325 P=0.242 P=0.504N P=0.673N |
|LOGISTIC REGRESSION| P=0.114N P=0.109 P=0.325 P=0.228 P=0.500N P=0.673N |
|COCH-ARM / FISHERS | P=0.149N P=0.141 P=0.339 P=0.339 P=0.500N P=0.691N |
|ORDER RESTRICTED | P=0.191N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 2/54 (4%) 2/53 (4%) 4/53 (8%) 2/53 (4%) 2/53 (4%) |
|POLY-3 RATE (b) | 1/39.86 2/34.61 2/39.26 4/35.69 2/39.35 2/43.47 |
|POLY-3 PERCENT (g) | 2.5% 5.8% 5.1% 11.2% 5.1% 4.6% |
|TERMINAL (d) | 0/25 (0%) 2/21 (10%) 0/23 (0%) 1/19 (5%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 646 731 (T) 578 533 677 599 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.568N P=0.419 P=0.493 P=0.122 P=0.478 P=0.529 |
|POLY 3 | P=0.562N P=0.451 P=0.495 P=0.145 P=0.495 P=0.530 |
|POLY 1.5 | P=0.578N P=0.474 P=0.492 P=0.158 P=0.498 P=0.525 |
|POLY 6 | P=0.564N P=0.426 P=0.497 P=0.131 P=0.491 P=0.525 |
|LOGISTIC REGRESSION| P=0.570 P=0.435 P=0.495 P=0.176 P=0.497 P=0.457 |
|COCH-ARM / FISHERS | P=0.539 P=0.507 P=0.500 P=0.181 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.346 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 22
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatodiaphragmatic Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/54 (4%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/39.55 2/35.66 0/38.75 1/34.16 2/39.00 0/42.60 |
|POLY-3 PERCENT (g) | 0.0% 5.6% 0.0% 2.9% 5.1% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 2/22 (9%) 0/21 (0%) |
|FIRST INCIDENCE | --- 526 --- 731 (T) 731 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.467N P=0.200 (e) P=0.445 P=0.210 (e) |
|POLY 3 | P=0.450N P=0.214 (e) P=0.471 P=0.233 (e) |
|POLY 1.5 | P=0.451N P=0.224 (e) P=0.483 P=0.235 (e) |
|POLY 6 | P=0.463N P=0.205 (e) P=0.456 P=0.229 (e) |
|LOGISTIC REGRESSION| P=0.453N P=0.258 (e) P=0.445 P=0.210 (e) |
|COCH-ARM / FISHERS | P=0.482N P=0.252 (e) P=0.500 P=0.248 (e) |
|ORDER RESTRICTED | P=0.352N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 3/53 (6%) 7/53 (13%) 36/53 (68%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 3/34.16 7/39.45 36/49.45 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 8.8% 17.7% 72.8% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 3/19 (16%) 4/22 (18%) 14/21 (67%) |
|FIRST INCIDENCE | --- --- --- 731 (T) 673 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) P=0.075 P=0.007 ** P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) P=0.094 P=0.007 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) P=0.104 P=0.007 ** P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) P=0.082 P=0.006 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.075 P=0.007 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.121 P=0.006 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 23
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 33/53 (62%) 46/54 (85%) 47/53 (89%) 50/53 (94%) 52/53 (98%) 49/53 (92%) |
|POLY-3 RATE (b) | 33/47.21 46/52.59 47/50.65 50/51.86 52/52.36 49/52.42 |
|POLY-3 PERCENT (g) | 69.9% 87.5% 92.8% 96.4% 99.3% 93.5% |
|TERMINAL (d) | 17/25 (68%) 16/21 (76%) 23/23 (100%) 19/19 (100%) 22/22 (100%) 18/21 (86%) |
|FIRST INCIDENCE | 351 200 47 53 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.176 P=0.008 ** P=0.014 * P<0.001 ** P=0.002 ** P=0.010 * |
|POLY 3 | P=0.005 ** P=0.022 * P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P=0.002 ** P=0.014 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P=0.010 * P=0.038 * P=0.002 ** P<0.001 ** P<0.001 ** P=0.003 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.008 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.006 ** 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 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Mixed Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 30/53 (57%) 19/54 (35%) 29/53 (55%) 23/53 (43%) 30/53 (57%) 21/53 (40%) |
|POLY-3 RATE (b) | 30/41.81 19/37.69 29/41.41 23/37.31 30/43.75 21/45.03 |
|POLY-3 PERCENT (g) | 71.8% 50.4% 70.0% 61.6% 68.6% 46.6% |
|TERMINAL (d) | 22/25 (88%) 13/21 (62%) 20/23 (87%) 16/19 (84%) 20/22 (91%) 14/21 (67%) |
|FIRST INCIDENCE | 492 394 578 485 396 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.249N P=0.109N P=0.524 P=0.582 P=0.334 P=0.156N |
|POLY 3 | P=0.019N* P=0.029N* P=0.530N P=0.213N P=0.463N P=0.009N** |
|POLY 1.5 | P=0.047N* P=0.023N* P=0.562N P=0.164N P=0.508N P=0.016N* |
|POLY 6 | P=0.010N* P=0.038N* P=0.491N P=0.297N P=0.446N P=0.007N** |
|LOGISTIC REGRESSION| P=0.033N* P=0.088N P=0.539N P=0.422N P=0.567 P=0.016N* |
|COCH-ARM / FISHERS | P=0.247N P=0.021N* P=0.500N P=0.122N P=0.578N P=0.060N |
|ORDER RESTRICTED | P=0.005N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 24
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 4/54 (7%) 4/53 (8%) 8/53 (15%) 10/53 (19%) 17/53 (32%) |
|POLY-3 RATE (b) | 1/39.67 4/36.95 4/40.33 8/38.63 10/42.48 17/46.77 |
|POLY-3 PERCENT (g) | 2.5% 10.8% 9.9% 20.7% 23.5% 36.4% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 1/23 (4%) 1/19 (5%) 2/22 (9%) 2/21 (10%) |
|FIRST INCIDENCE | 701 341 47 373 185 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.160 P=0.185 P=0.013 * P=0.006 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.156 P=0.182 P=0.013 * P=0.005 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.168 P=0.179 P=0.014 * P=0.005 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.143 P=0.185 P=0.011 * P=0.005 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.220 P=0.200 P=0.024 * P=0.005 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.187 P=0.181 P=0.016 * P=0.004 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 9/54 (17%) 34/53 (64%) 48/53 (91%) 52/53 (98%) 53/53 (100%) |
|POLY-3 RATE (b) | 4/40.41 9/36.83 34/43.56 48/50.11 52/52.01 53/53.00 |
|POLY-3 PERCENT (g) | 9.9% 24.4% 78.1% 95.8% 100.0% 100.0% |
|TERMINAL (d) | 1/25 (4%) 4/21 (19%) 18/23 (78%) 18/19 (95%) 22/22 (100%) 21/21 (100%) |
|FIRST INCIDENCE | 533 556 429 197 185 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.069 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.078 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.093 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.067 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.090 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.125 P<0.001 ** 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: 03 Page 25
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Toxic Hepatopathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/54 (4%) 8/53 (15%) 30/53 (57%) 45/53 (85%) 53/53 (100%) |
|POLY-3 RATE (b) | 0/39.55 2/35.11 8/39.47 30/40.91 45/48.20 53/53.00 |
|POLY-3 PERCENT (g) | 0.0% 5.7% 20.3% 73.3% 93.4% 100.0% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 5/23 (22%) 13/19 (68%) 22/22 (100%) 21/21 (100%) |
|FIRST INCIDENCE | --- 578 578 462 185 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.200 P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.211 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.223 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.200 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.223 P=0.004 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.252 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 0/39.00 2/43.31 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.6% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- --- --- --- 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.018 * (e) (e) (e) (e) P=0.258 |
|POLY 3 | P=0.012 * (e) (e) (e) (e) P=0.258 |
|POLY 1.5 | P=0.012 * (e) (e) (e) (e) P=0.254 |
|POLY 6 | P=0.013 * (e) (e) (e) (e) P=0.255 |
|LOGISTIC REGRESSION| P=0.010 * (e) (e) (e) (e) P=0.212 |
|COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.248 |
|ORDER RESTRICTED | P=0.012 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 26
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 1/54 (2%) 2/53 (4%) 2/53 (4%) 0/53 (0%) 21/53 (40%) |
|POLY-3 RATE (b) | 3/39.85 1/34.61 2/38.76 2/34.72 0/39.00 21/44.46 |
|POLY-3 PERCENT (g) | 7.5% 2.9% 5.2% 5.8% 0.0% 47.2% |
|TERMINAL (d) | 2/25 (8%) 1/21 (5%) 1/23 (4%) 1/19 (5%) 0/22 (0%) 14/21 (67%) |
|FIRST INCIDENCE | 648 731 (T) 728 557 --- 612 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.382N P=0.529N P=0.609N P=0.136N P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.357N P=0.513N P=0.563N P=0.122N P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.332N P=0.514N P=0.537N P=0.120N P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.384N P=0.514N P=0.595N P=0.125N P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.379N P=0.509N P=0.563N P=0.124N P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.302N P=0.500N P=0.500N P=0.121N P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/54 (4%) 0/53 (0%) 1/53 (2%) 3/53 (6%) 4/53 (8%) |
|POLY-3 RATE (b) | 0/39.55 2/35.02 0/38.75 1/34.67 3/40.18 4/43.38 |
|POLY-3 PERCENT (g) | 0.0% 5.7% 0.0% 2.9% 7.5% 9.2% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 0/23 (0%) 0/19 (0%) 1/22 (5%) 2/21 (10%) |
|FIRST INCIDENCE | --- 613 --- 578 486 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.025 * P=0.186 (e) P=0.479 P=0.117 P=0.062 |
|POLY 3 | P=0.020 * P=0.210 (e) P=0.474 P=0.121 P=0.072 |
|POLY 1.5 | P=0.019 * P=0.222 (e) P=0.484 P=0.120 P=0.070 |
|POLY 6 | P=0.020 * P=0.199 (e) P=0.461 P=0.120 P=0.070 |
|LOGISTIC REGRESSION| P=0.016 * P=0.214 (e) P=0.513 P=0.121 P=0.068 |
|COCH-ARM / FISHERS | P=0.014 * P=0.252 (e) P=0.500 P=0.121 P=0.059 |
|ORDER RESTRICTED | P=0.021 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 27
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 5/53 (9%) 4/54 (7%) 7/53 (13%) 22/53 (42%) 40/53 (75%) 53/53 (100%) |
|POLY-3 RATE (b) | 5/40.16 4/35.12 7/39.03 22/38.54 40/45.67 53/53.00 |
|POLY-3 PERCENT (g) | 12.5% 11.4% 17.9% 57.1% 87.6% 100.0% |
|TERMINAL (d) | 4/25 (16%) 2/21 (10%) 4/23 (17%) 11/19 (58%) 21/22 (96%) 21/21 (100%) |
|FIRST INCIDENCE | 533 578 676 406 317 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.597N P=0.346 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.584N P=0.356 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.546N P=0.355 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.623N P=0.356 P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.597N P=0.364 P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.488N P=0.380 P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Centrilobular |
| Degeneration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 2/54 (4%) 0/53 (0%) 4/53 (8%) 3/53 (6%) 5/53 (9%) |
|POLY-3 RATE (b) | 2/39.97 2/36.33 0/38.75 4/34.98 3/40.40 5/43.88 |
|POLY-3 PERCENT (g) | 5.0% 5.5% 0.0% 11.4% 7.4% 11.4% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 648 264 --- 592 518 610 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.085 P=0.646 P=0.243N P=0.225 P=0.501 P=0.224 |
|POLY 3 | P=0.076 P=0.660 P=0.244N P=0.276 P=0.505 P=0.254 |
|POLY 1.5 | P=0.069 P=0.678 P=0.244N P=0.300 P=0.503 P=0.248 |
|POLY 6 | P=0.077 P=0.638 P=0.245N P=0.249 P=0.503 P=0.250 |
|LOGISTIC REGRESSION| P=0.041 * P=0.638N P=0.242N P=0.281 P=0.501 P=0.225 |
|COCH-ARM / FISHERS | P=0.049 * P=0.684N P=0.248N P=0.339 P=0.500 P=0.219 |
|ORDER RESTRICTED | P=0.110 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 28
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 19/54 (35%) 19/53 (36%) 42/53 (79%) 41/53 (77%) 52/53 (98%) |
|POLY-3 RATE (b) | 0/39.55 19/40.44 19/42.70 42/47.70 41/49.86 52/52.59 |
|POLY-3 PERCENT (g) | 0.0% 47.0% 44.5% 88.0% 82.2% 98.9% |
|TERMINAL (d) | 0/25 (0%) 9/21 (43%) 9/23 (39%) 16/19 (84%) 18/22 (82%) 21/21 (100%) |
|FIRST INCIDENCE | --- 361 54 197 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P<0.001 ** 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<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** 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 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Multinucleated |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 16/53 (30%) 26/53 (49%) 36/53 (68%) 51/53 (96%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 16/41.40 26/41.16 36/46.14 51/52.67 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 38.7% 63.2% 78.0% 96.8% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 7/23 (30%) 11/19 (58%) 17/22 (77%) 20/21 (95%) |
|FIRST INCIDENCE | --- --- 550 373 317 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) P<0.001 ** 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: 03 Page 29
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Oval Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 4/54 (7%) 3/53 (6%) 20/53 (38%) 38/53 (72%) 53/53 (100%) |
|POLY-3 RATE (b) | 0/39.55 4/35.11 3/39.46 20/37.65 38/44.76 53/53.00 |
|POLY-3 PERCENT (g) | 0.0% 11.4% 7.6% 53.1% 84.9% 100.0% |
|TERMINAL (d) | 0/25 (0%) 3/21 (14%) 1/23 (4%) 11/19 (58%) 21/22 (96%) 21/21 (100%) |
|FIRST INCIDENCE | --- 578 578 380 444 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.043 * P=0.125 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.046 * P=0.117 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.052 P=0.115 P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.040 * P=0.120 P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.043 * P=0.117 P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.061 P=0.121 P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Portal |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 5/53 (9%) 27/53 (51%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 5/39.43 27/47.36 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 12.7% 57.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 2/22 (9%) 11/21 (52%) |
|FIRST INCIDENCE | --- --- --- --- 657 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.030 * P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) (e) P=0.029 * P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.030 * P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) (e) P=0.028 * P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.030 * P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.028 * P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 30
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Congestion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 0/52 (0%) 0/53 (0%) 0/52 (0%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 2/40.74 0/33.71 0/39.00 0/41.64 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 4.9% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 47 --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.394N (e) P=0.238 (e) (e) (e) |
|POLY 3 | P=0.360N (e) P=0.243 (e) (e) (e) |
|POLY 1.5 | P=0.374N (e) P=0.241 (e) (e) (e) |
|POLY 6 | P=0.350N (e) P=0.245 (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.397N (e) P=0.248 (e) (e) (e) |
|ORDER RESTRICTED | P=0.344N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Edema |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 0/52 (0%) 1/53 (2%) 0/52 (0%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 2/39.68 0/33.71 1/39.47 0/41.64 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% 2.5% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 429 --- 589 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.481N (e) P=0.235 (e) P=0.505 (e) |
|POLY 3 | P=0.470N (e) P=0.237 (e) P=0.500 (e) |
|POLY 1.5 | P=0.487N (e) P=0.234 (e) P=0.500 (e) |
|POLY 6 | P=0.461N (e) P=0.240 (e) P=0.498 (e) |
|LOGISTIC REGRESSION| P=0.562N (e) P=0.249 (e) P=0.501 (e) |
|COCH-ARM / FISHERS | P=0.522N (e) P=0.248 (e) P=0.500 (e) |
|ORDER RESTRICTED | P=0.389 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 31
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 1/54 (2%) 0/53 (0%) 0/52 (0%) 0/53 (0%) 2/52 (4%) |
|POLY-3 RATE (b) | 0/39.55 1/35.31 0/38.75 0/33.71 0/39.00 2/42.48 |
|POLY-3 PERCENT (g) | 0.0% 2.8% 0.0% 0.0% 0.0% 4.7% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- 490 --- --- --- 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.096 P=0.491 (e) (e) (e) P=0.247 |
|POLY 3 | P=0.079 P=0.477 (e) (e) (e) P=0.253 |
|POLY 1.5 | P=0.079 P=0.488 (e) (e) (e) P=0.250 |
|POLY 6 | P=0.077 P=0.467 (e) (e) (e) P=0.249 |
|LOGISTIC REGRESSION| P=0.046 * P=0.536 (e) (e) (e) P=0.171 |
|COCH-ARM / FISHERS | P=0.074 P=0.505 (e) (e) (e) P=0.243 |
|ORDER RESTRICTED | P=0.037 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 41/53 (77%) 46/54 (85%) 43/53 (81%) 43/52 (83%) 49/53 (92%) 50/52 (96%) |
|POLY-3 RATE (b) | 41/48.55 46/49.22 43/46.24 43/44.24 49/50.17 50/51.42 |
|POLY-3 PERCENT (g) | 84.5% 93.5% 93.0% 97.2% 97.7% 97.2% |
|TERMINAL (d) | 19/25 (76%) 19/21 (91%) 22/23 (96%) 19/19 (100%) 22/22 (100%) 20/21 (95%) |
|FIRST INCIDENCE | 351 241 344 380 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.202 P=0.068 P=0.330 P=0.058 P=0.081 P=0.083 |
|POLY 3 | P=0.018 * P=0.121 P=0.146 P=0.026 * P=0.016 * P=0.022 * |
|POLY 1.5 | P=0.009 ** P=0.143 P=0.178 P=0.074 P=0.018 * P=0.015 * |
|POLY 6 | P=0.027 * P=0.109 P=0.118 P=0.014 * P=0.012 * P=0.027 * |
|LOGISTIC REGRESSION| P=0.025 * P=0.106 P=0.276 P=0.119 P=0.020 * P=0.015 * |
|COCH-ARM / FISHERS | P=0.002 ** P=0.215 P=0.406 P=0.331 P=0.028 * P=0.004 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 32
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 0/54 (0%) 0/53 (0%) 2/52 (4%) 0/53 (0%) 0/52 (0%) |
|POLY-3 RATE (b) | 1/40.25 0/34.61 0/38.75 2/34.74 0/39.00 0/41.64 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 5.8% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 487 --- --- 373 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.355N P=0.513N P=0.504N P=0.456 P=0.509N P=0.479N |
|POLY 3 | P=0.347N P=0.530N P=0.508N P=0.449 P=0.506N P=0.493N |
|POLY 1.5 | P=0.353N P=0.516N P=0.508N P=0.467 P=0.504N P=0.493N |
|POLY 6 | P=0.347N P=0.544N P=0.509N P=0.427 P=0.511N P=0.500N |
|LOGISTIC REGRESSION| P=0.442N P=0.464N P=0.466N P=0.543 P=0.495N P=0.655N |
|COCH-ARM / FISHERS | P=0.377N P=0.495N P=0.500N P=0.493 P=0.500N P=0.505N |
|ORDER RESTRICTED | P=0.271N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Inflammation Granulomatous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/54 (2%) 2/53 (4%) 2/52 (4%) 0/53 (0%) 0/52 (0%) |
|POLY-3 RATE (b) | 2/39.90 1/34.61 2/38.88 2/34.84 0/39.00 0/41.64 |
|POLY-3 PERCENT (g) | 5.0% 2.9% 5.1% 5.7% 0.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 1/23 (4%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 645 731 (T) 697 485 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.098N P=0.583N P=0.671 P=0.593 P=0.264N P=0.259N |
|POLY 3 | P=0.082N P=0.550N P=0.686 P=0.645 P=0.242N P=0.227N |
|POLY 1.5 | P=0.087N P=0.527N P=0.684 P=0.662 P=0.239N P=0.228N |
|POLY 6 | P=0.082N P=0.575N P=0.686 P=0.624 P=0.247N P=0.234N |
|LOGISTIC REGRESSION| P=0.092N P=0.562N P=0.689 P=0.692 P=0.240N P=0.229N |
|COCH-ARM / FISHERS | P=0.102N P=0.493N P=0.691N P=0.684 P=0.248N P=0.252N |
|ORDER RESTRICTED | P=0.146N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 33
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Metaplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 0/54 (0%) 0/53 (0%) 0/52 (0%) 5/53 (9%) 6/52 (12%) |
|POLY-3 RATE (b) | 1/39.55 0/34.61 0/38.75 0/33.71 5/39.04 6/43.19 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% 12.8% 13.9% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 4/22 (18%) 2/21 (10%) |
|FIRST INCIDENCE | 731 (T) --- --- --- 720 561 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.535N P=0.517N P=0.555N P=0.076 P=0.060 |
|POLY 3 | P<0.001 ** P=0.527N P=0.504N P=0.532N P=0.096 P=0.070 |
|POLY 1.5 | P<0.001 ** P=0.514N P=0.505N P=0.520N P=0.099 P=0.067 |
|POLY 6 | P<0.001 ** P=0.539N P=0.503N P=0.545N P=0.091 P=0.069 |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.072 P=0.059 |
|COCH-ARM / FISHERS | P<0.001 ** P=0.495N P=0.500N P=0.505N P=0.103 P=0.053 |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 12/53 (23%) 0/54 (0%) 0/53 (0%) 0/52 (0%) 0/53 (0%) 0/52 (0%) |
|POLY-3 RATE (b) | 12/40.71 0/34.61 0/38.75 0/33.71 0/39.00 0/41.64 |
|POLY-3 PERCENT (g) | 29.5% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 6/25 (24%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 645 --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003N** P=0.002N** P<0.001N** P=0.003N** P<0.001N** P<0.001N** |
|POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|LOGISTIC REGRESSION| P=0.002N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|COCH-ARM / FISHERS | P=0.002N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 34
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Metaplasia Bronchiolar |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 19/54 (35%) 33/53 (62%) 35/52 (67%) 45/53 (85%) 46/52 (88%) |
|POLY-3 RATE (b) | 2/39.55 19/38.13 33/43.14 35/42.04 45/47.86 46/50.05 |
|POLY-3 PERCENT (g) | 5.1% 49.8% 76.5% 83.3% 94.0% 91.9% |
|TERMINAL (d) | 2/25 (8%) 11/21 (52%) 19/23 (83%) 17/19 (90%) 22/22 (100%) 19/21 (91%) |
|FIRST INCIDENCE | 731 (T) 449 578 380 341 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P<0.001 ** 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<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** 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 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mandibular |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 0/54 (0%) 0/52 (0%) 0/50 (0%) 1/51 (2%) 6/52 (12%) |
|POLY-3 RATE (b) | 0/38.56 0/34.61 0/37.95 0/33.43 1/38.33 6/41.66 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.6% 14.4% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 6/21 (29%) |
|FIRST INCIDENCE | --- --- --- --- 590 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.500 P=0.008 ** |
|POLY 3 | P<0.001 ** (e) (e) (e) P=0.499 P=0.019 * |
|POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.499 P=0.020 * |
|POLY 6 | P<0.001 ** (e) (e) (e) P=0.497 P=0.016 * |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.502 P=0.008 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.500 P=0.014 * |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 35
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mandibular |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 25/51 (49%) 31/54 (57%) 23/52 (44%) 22/50 (44%) 15/51 (29%) 16/52 (31%) |
|POLY-3 RATE (b) | 25/42.13 31/44.45 23/41.82 22/38.78 15/39.61 16/44.39 |
|POLY-3 PERCENT (g) | 59.3% 69.7% 55.0% 56.7% 37.9% 36.0% |
|TERMINAL (d) | 16/25 (64%) 14/21 (67%) 12/23 (52%) 10/19 (53%) 8/22 (36%) 10/21 (48%) |
|FIRST INCIDENCE | 366 241 177 406 590 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.005N** P=0.054 P=0.525N P=0.372 P=0.085N P=0.123N |
|POLY 3 | P<0.001N** P=0.203 P=0.426N P=0.495N P=0.036N* P=0.020N* |
|POLY 1.5 | P<0.001N** P=0.224 P=0.433N P=0.447N P=0.033N* P=0.021N* |
|POLY 6 | P<0.001N** P=0.195 P=0.415N P=0.557N P=0.040N* P=0.026N* |
|LOGISTIC REGRESSION| P<0.001N** P=0.159 P=0.440N P=0.514N P=0.032N* P=0.027N* |
|COCH-ARM / FISHERS | P=0.003N** P=0.253 P=0.386N P=0.380N P=0.034N* P=0.045N* |
|ORDER RESTRICTED | P=0.003N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mandibular |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 3/54 (6%) 3/52 (6%) 0/50 (0%) 0/51 (0%) 2/52 (4%) |
|POLY-3 RATE (b) | 0/38.56 3/37.03 3/40.81 0/33.43 0/37.86 2/42.56 |
|POLY-3 PERCENT (g) | 0.0% 8.1% 7.4% 0.0% 0.0% 4.7% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- 200 47 --- --- 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.549N P=0.125 P=0.118 (e) (e) P=0.271 |
|POLY 3 | P=0.587N P=0.110 P=0.128 (e) (e) P=0.259 |
|POLY 1.5 | P=0.590N P=0.119 P=0.126 (e) (e) P=0.257 |
|POLY 6 | P=0.590N P=0.102 P=0.129 (e) (e) P=0.254 |
|LOGISTIC REGRESSION| P=0.284 P=0.156 P=0.254 (e) (e) P=0.189 |
|COCH-ARM / FISHERS | P=0.602N P=0.132 P=0.125 (e) (e) P=0.252 |
|ORDER RESTRICTED | P=0.202 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 36
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/52 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 2/51 (4%) |
|POLY-3 RATE (b) | 1/40.17 0/34.17 0/38.75 0/34.16 2/39.85 2/41.63 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% 5.0% 4.8% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 469 --- --- --- 518 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.099 P=0.517N P=0.513N P=0.527N P=0.496 P=0.527 |
|POLY 3 | P=0.093 P=0.532N P=0.507N P=0.532N P=0.497 P=0.512 |
|POLY 1.5 | P=0.085 P=0.518N P=0.506N P=0.518N P=0.500 P=0.511 |
|POLY 6 | P=0.096 P=0.546N P=0.509N P=0.549N P=0.493 P=0.506 |
|LOGISTIC REGRESSION| P=0.047 * P=0.453N P=0.449N P=0.449N P=0.519 P=0.398 |
|COCH-ARM / FISHERS | P=0.065 P=0.495N P=0.495N P=0.495N P=0.507 P=0.493 |
|ORDER RESTRICTED | P=0.147 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Lumbar |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/2 (50%) 2/6 (33%) 1/3 (33%) 2/5 (40%) 0/6 (0%) 0/9 (0%) |
|POLY-3 RATE (b) | 1/2.00 2/2.88 1/2.62 2/4.38 0/3.39 0/6.57 |
|POLY-3 PERCENT (g) | 50.0% 69.4% 38.2% 45.7% 0.0% 0.0% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/3 (0%) |
|FIRST INCIDENCE | 717 341 578 578 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.113N P=0.455 P=0.751 P=0.410 P=0.533N P=0.543N |
|POLY 3 | P=0.015N* P=0.706 P=0.712N P=0.750N P=0.363N P=0.192N |
|POLY 1.5 | P=0.015N* P=0.796 P=0.693N P=0.724N P=0.297N P=0.169N |
|POLY 6 | P=0.020N* P=0.574 P=0.740N P=0.784 P=0.491N P=0.234N |
|LOGISTIC REGRESSION| P=0.028N* P=0.922 P=0.520N P=0.456N P=0.830N P=0.315N |
|COCH-ARM / FISHERS | P=0.024N* P=0.643N P=0.700N P=0.714N P=0.250N P=0.182N |
|ORDER RESTRICTED | P=0.112N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 37
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Lumbar |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/2 (0%) 2/6 (33%) 0/3 (0%) 1/5 (20%) 0/6 (0%) 0/9 (0%) |
|POLY-3 RATE (b) | 0/1.94 2/2.76 0/2.11 1/4.07 0/3.39 0/6.57 |
|POLY-3 PERCENT (g) | 0.0% 72.6% 0.0% 24.6% 0.0% 0.0% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/3 (0%) |
|FIRST INCIDENCE | --- 448 --- 578 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.241N P=0.211 (e) P=0.468 (e) (e) |
|POLY 3 | P=0.185N P=0.211 (e) P=0.649 (e) (e) |
|POLY 1.5 | P=0.158N P=0.333 (e) P=0.661 (e) (e) |
|POLY 6 | P=0.212N P=0.109 (e) P=0.625 (e) (e) |
|LOGISTIC REGRESSION| P=0.183N P=0.468 (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.126N P=0.536 (e) P=0.714 (e) (e) |
|ORDER RESTRICTED | P=0.169N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/2 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/6 (17%) 3/9 (33%) |
|POLY-3 RATE (b) | 0/1.94 0/1.48 0/2.11 0/3.56 1/3.87 3/7.60 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 25.9% 39.5% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/3 (0%) |
|FIRST INCIDENCE | --- --- --- --- 590 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.005 ** (e) (e) (e) P=0.500 P=0.137 |
|POLY 3 | P=0.044 * (e) (e) (e) P=0.649 P=0.422 |
|POLY 1.5 | P=0.036 * (e) (e) (e) P=0.680 P=0.442 |
|POLY 6 | P=0.073 (e) (e) (e) P=0.591 P=0.401 |
|LOGISTIC REGRESSION| P=0.024 * (e) (e) (e) P=0.980 P=0.588 |
|COCH-ARM / FISHERS | P=0.023 * (e) (e) (e) P=0.750 P=0.509 |
|ORDER RESTRICTED | P=0.263 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 38
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/2 (0%) 1/6 (17%) 0/3 (0%) 1/5 (20%) 0/6 (0%) 5/9 (56%) |
|POLY-3 RATE (b) | 0/1.94 1/2.43 0/2.11 1/3.65 0/3.39 5/8.27 |
|POLY-3 PERCENT (g) | 0.0% 41.1% 0.0% 27.4% 0.0% 60.5% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/3 (33%) |
|FIRST INCIDENCE | --- 264 --- 708 --- 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.009 ** P=0.500 (e) P=0.440 (e) P=0.059 |
|POLY 3 | P=0.015 * P=0.553 (e) P=0.632 (e) P=0.221 |
|POLY 1.5 | P=0.013 * P=0.633 (e) P=0.653 (e) P=0.236 |
|POLY 6 | P=0.022 * P=0.443 (e) P=0.589 (e) P=0.206 |
|LOGISTIC REGRESSION| P=0.007 ** (e) (e) P=0.425 (e) P=0.428 |
|COCH-ARM / FISHERS | P=0.016 * P=0.750 (e) P=0.714 (e) P=0.273 |
|ORDER RESTRICTED | P=0.130 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/2 (0%) 0/6 (0%) 1/3 (33%) 1/5 (20%) 2/6 (33%) 1/9 (11%) |
|POLY-3 RATE (b) | 0/1.94 0/1.48 1/2.12 1/3.72 2/4.29 1/7.02 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 47.1% 26.9% 46.7% 14.3% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/3 (0%) |
|FIRST INCIDENCE | --- --- 728 690 578 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.324 (e) P=0.492 P=0.438 P=0.242 P=0.515 |
|POLY 3 | P=0.515N (e) P=0.519 P=0.635 P=0.403 P=0.764 |
|POLY 1.5 | P=0.547N (e) P=0.548 P=0.654 P=0.451 P=0.774 |
|POLY 6 | P=0.568N (e) P=0.467 P=0.597 P=0.327 P=0.749 |
|LOGISTIC REGRESSION| P=0.575N (e) P=0.381 P=0.608 P=0.814 P=0.945 |
|COCH-ARM / FISHERS | P=0.589 (e) P=0.600 P=0.714 P=0.536 P=0.818 |
|ORDER RESTRICTED | P=0.446 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 39
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/53 (8%) 3/54 (6%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 1/53 (2%) |
|POLY-3 RATE (b) | 4/41.40 3/35.67 0/38.75 1/34.87 1/39.04 1/42.92 |
|POLY-3 PERCENT (g) | 9.7% 8.4% 0.0% 2.9% 2.6% 2.3% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 366 556 --- 485 720 641 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.155N P=0.609N P=0.078N P=0.268N P=0.200N P=0.176N |
|POLY 3 | P=0.155N P=0.581N P=0.068N P=0.234N P=0.196N P=0.167N |
|POLY 1.5 | P=0.161N P=0.545N P=0.067N P=0.210N P=0.188N P=0.166N |
|POLY 6 | P=0.156N P=0.618N P=0.071N P=0.267N P=0.208N P=0.179N |
|LOGISTIC REGRESSION| P=0.200N P=0.467N P=0.055N P=0.150N P=0.178N P=0.245N |
|COCH-ARM / FISHERS | P=0.185N P=0.489N P=0.059N P=0.181N P=0.181N P=0.181N |
|ORDER RESTRICTED | P=0.049N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 25/53 (47%) 21/54 (39%) 24/53 (45%) 22/53 (42%) 18/53 (34%) 16/53 (30%) |
|POLY-3 RATE (b) | 25/44.58 21/38.80 24/42.10 22/37.99 18/43.24 16/44.03 |
|POLY-3 PERCENT (g) | 56.1% 54.1% 57.0% 57.9% 41.6% 36.3% |
|TERMINAL (d) | 13/25 (52%) 12/21 (57%) 13/23 (57%) 13/19 (68%) 9/22 (41%) 10/21 (48%) |
|FIRST INCIDENCE | 487 462 54 53 141 614 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.041N* P=0.565 P=0.549 P=0.359 P=0.224N P=0.126N |
|POLY 3 | P=0.006N** P=0.518N P=0.553 P=0.523 P=0.119N P=0.042N* |
|POLY 1.5 | P=0.008N** P=0.396N P=0.584 P=0.510N P=0.105N P=0.037N* |
|POLY 6 | P=0.008N** P=0.539 P=0.507 P=0.353 P=0.153N P=0.069N |
|LOGISTIC REGRESSION| P=0.008N** P=0.415N P=0.543N P=0.513N P=0.119N P=0.028N* |
|COCH-ARM / FISHERS | P=0.035N* P=0.252N P=0.500N P=0.348N P=0.118N P=0.055N |
|ORDER RESTRICTED | P=0.029N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 40
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mesentery: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/2 (0%) 1/2 (50%) 0/0 (0%) 0/1 (0%) 4/6 (67%) 7/8 (88%) |
|POLY-3 RATE (b) | 0/0.71 1/1.61 0/0.00 0/0.84 4/5.52 7/7.72 |
|POLY-3 PERCENT (g) | 0.0% 62.1% 0.0% 0.0% 72.4% 90.7% |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/4 (75%) 3/3 (100%) |
|FIRST INCIDENCE | --- 200 --- --- 642 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.004 ** P=0.455 (e) (e) P=0.511 P=0.075 |
|POLY 3 | (e) P=0.659 (e) (e) P=0.533 P=0.408 |
|POLY 1.5 | (e) P=0.620 (e) (e) P=0.453 P=0.274 |
|POLY 6 | (e) P=0.728 (e) (e) P=0.624 P=0.602 |
|LOGISTIC REGRESSION| P=0.032 * P=0.465 (e) (e) P=0.602 P=0.249 |
|COCH-ARM / FISHERS | P=0.024 * P=0.500 (e) (e) P=0.214 P=0.067 |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/53 (0%) 3/53 (6%) 5/53 (9%) 4/53 (8%) |
|POLY-3 RATE (b) | 2/40.42 0/34.61 0/38.75 3/35.64 5/41.65 4/42.93 |
|POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 8.4% 12.0% 9.3% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 0/22 (0%) 3/21 (14%) |
|FIRST INCIDENCE | 474 --- --- 373 341 638 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.039 * P=0.277N P=0.248N P=0.433 P=0.216 P=0.306 |
|POLY 3 | P=0.046 * P=0.273N P=0.246N P=0.443 P=0.227 P=0.365 |
|POLY 1.5 | P=0.041 * P=0.256N P=0.246N P=0.466 P=0.224 P=0.364 |
|POLY 6 | P=0.046 * P=0.292N P=0.248N P=0.412 P=0.227 P=0.350 |
|LOGISTIC REGRESSION| P=0.016 * P=0.220N P=0.228N P=0.540 P=0.219 P=0.350 |
|COCH-ARM / FISHERS | P=0.026 * P=0.243N P=0.248N P=0.500 P=0.219 P=0.339 |
|ORDER RESTRICTED | P=0.056 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 41
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Nasolacrimal Duct |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) |
|POLY-3 RATE (b) | 2/40.42 0/34.61 0/38.75 0/34.16 0/39.00 0/42.60 |
|POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 366 --- --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.249N P=0.261N P=0.256N P=0.267N P=0.254N P=0.250N |
|POLY 3 | P=0.219N P=0.273N P=0.246N P=0.276N P=0.245N P=0.225N |
|POLY 1.5 | P=0.230N P=0.257N P=0.246N P=0.260N P=0.242N P=0.226N |
|POLY 6 | P=0.209N P=0.290N P=0.246N P=0.296N P=0.249N P=0.231N |
|LOGISTIC REGRESSION| P=0.268N P=0.209N P=0.218N P=0.213N P=0.234N P=0.314N |
|COCH-ARM / FISHERS | P=0.249N P=0.243N P=0.248N P=0.248N P=0.248N P=0.248N |
|ORDER RESTRICTED | P=0.008N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Respiratory Epithelium |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 2/40.05 0/42.60 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- --- --- 474 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.495 (e) (e) (e) P=0.237 (e) |
|POLY 3 | P=0.540 (e) (e) (e) P=0.239 (e) |
|POLY 1.5 | P=0.524 (e) (e) (e) P=0.239 (e) |
|POLY 6 | P=0.535 (e) (e) (e) P=0.239 (e) |
|LOGISTIC REGRESSION| P=0.418 (e) (e) (e) P=0.240 (e) |
|COCH-ARM / FISHERS | P=0.461 (e) (e) (e) P=0.248 (e) |
|ORDER RESTRICTED | P=0.190 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 42
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Respiratory Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/53 (0%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 1/35.03 2/39.91 0/42.60 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.9% 5.0% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- --- 373 518 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.556 (e) (e) P=0.508 P=0.246 (e) |
|POLY 3 | P=0.599 (e) (e) P=0.476 P=0.239 (e) |
|POLY 1.5 | P=0.585 (e) (e) P=0.486 P=0.238 (e) |
|POLY 6 | P=0.592 (e) (e) P=0.463 P=0.238 (e) |
|LOGISTIC REGRESSION| P=0.441 (e) (e) P=0.562 P=0.239 (e) |
|COCH-ARM / FISHERS | P=0.522 (e) (e) P=0.500 P=0.248 (e) |
|ORDER RESTRICTED | P=0.257 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Septum |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 0/39.00 2/42.93 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.7% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | --- --- --- --- --- 638 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.015 * (e) (e) (e) (e) P=0.229 |
|POLY 3 | P=0.012 * (e) (e) (e) (e) P=0.256 |
|POLY 1.5 | P=0.012 * (e) (e) (e) (e) P=0.253 |
|POLY 6 | P=0.012 * (e) (e) (e) (e) P=0.251 |
|LOGISTIC REGRESSION| P=0.015 * (e) (e) (e) (e) P=0.251 |
|COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.248 |
|ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 43
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Nose: Turbinate, Septum |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 1/53 (2%) 1/53 (2%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 1/38.88 1/34.16 0/39.00 2/43.48 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.6% 2.9% 0.0% 4.6% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 697 731 (T) --- 561 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.139 (e) P=0.500 P=0.445 (e) P=0.273 |
|POLY 3 | P=0.135 (e) P=0.497 P=0.471 (e) P=0.259 |
|POLY 1.5 | P=0.128 (e) P=0.495 P=0.483 (e) P=0.255 |
|POLY 6 | P=0.138 (e) P=0.498 P=0.456 (e) P=0.256 |
|LOGISTIC REGRESSION| P=0.124 (e) P=0.496 P=0.445 (e) P=0.185 |
|COCH-ARM / FISHERS | P=0.110 (e) P=0.500 P=0.500 (e) P=0.248 |
|ORDER RESTRICTED | P=0.075 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Oral Mucosa: Gingival |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/2 (50%) 7/9 (78%) 14/16 (88%) 13/16 (81%) 15/22 (68%) 16/29 (55%) |
|POLY-3 RATE (b) | 1/1.13 7/8.69 14/14.70 13/14.96 15/20.33 16/24.97 |
|POLY-3 PERCENT (g) | 88.9% 80.5% 95.3% 86.9% 73.8% 64.1% |
|TERMINAL (d) | 1/1 (100%) 4/5 (80%) 6/6 (100%) 2/3 (67%) 6/8 (75%) 6/9 (67%) |
|FIRST INCIDENCE | 731 (T) 448 240 533 317 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.128 P=0.172 P=0.006 ** P<0.001 ** P=0.007 ** P=0.007 ** |
|POLY 3 | P=0.011N* P=0.804N P=0.990 P=0.878N P=0.732N P=0.659N |
|POLY 1.5 | P=0.010N* P=0.797 P=0.820 P=0.788 P=0.789N P=0.698N |
|POLY 6 | P=0.022N* P=0.787N P=1.000N P=0.860N P=0.715N P=0.670N |
|LOGISTIC REGRESSION| P=0.009N** P=0.606 P=0.587 P=0.703 P=0.682 P=0.723N |
|COCH-ARM / FISHERS | P=0.016N* P=0.491 P=0.314 P=0.405 P=0.565 P=0.708 |
|ORDER RESTRICTED | P=0.729N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 44
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 49/51 (96%) 46/53 (87%) 50/53 (94%) 44/53 (83%) 50/53 (94%) 31/53 (58%) |
|POLY-3 RATE (b) | 49/50.31 46/50.52 50/51.00 44/49.02 50/51.02 31/49.18 |
|POLY-3 PERCENT (g) | 97.4% 91.1% 98.0% 89.8% 98.0% 63.0% |
|TERMINAL (d) | 24/25 (96%) 20/21 (95%) 22/23 (96%) 17/19 (90%) 21/22 (96%) 11/21 (52%) |
|FIRST INCIDENCE | 169 200 177 197 317 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003N** P=0.320 P=0.373 P=0.285 P=0.320 P=0.020N* |
|POLY 3 | P<0.001N** P=0.145N P=0.681 P=0.098N P=0.686 P<0.001N** |
|POLY 1.5 | P<0.001N** P=0.110N P=0.622 P=0.069N P=0.663 P<0.001N** |
|POLY 6 | P<0.001N** P=0.230N P=0.735 P=0.163N P=0.735 P<0.001N** |
|LOGISTIC REGRESSION| P<0.001N** P=0.091N P=0.668N P=0.046N* P=0.551N P<0.001N** |
|COCH-ARM / FISHERS | P<0.001N** P=0.090N P=0.518N P=0.030N* P=0.518N P<0.001N** |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 14/51 (27%) 16/53 (30%) 13/53 (25%) 15/53 (28%) 14/53 (26%) 13/53 (25%) |
|POLY-3 RATE (b) | 14/40.42 16/37.06 13/41.36 15/38.19 14/41.59 13/45.33 |
|POLY-3 PERCENT (g) | 34.6% 43.2% 31.4% 39.3% 33.7% 28.7% |
|TERMINAL (d) | 10/25 (40%) 9/21 (43%) 7/23 (30%) 8/19 (42%) 6/22 (27%) 7/21 (33%) |
|FIRST INCIDENCE | 533 490 429 406 486 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.341N P=0.215 P=0.556N P=0.233 P=0.494 P=0.582N |
|POLY 3 | P=0.178N P=0.291 P=0.471N P=0.422 P=0.557N P=0.358N |
|POLY 1.5 | P=0.212N P=0.352 P=0.484N P=0.472 P=0.553N P=0.373N |
|POLY 6 | P=0.179N P=0.245 P=0.457N P=0.362 P=0.560N P=0.374N |
|LOGISTIC REGRESSION| P=0.223N P=0.256 P=0.497N P=0.406 P=0.577N P=0.400N |
|COCH-ARM / FISHERS | P=0.356N P=0.464 P=0.454N P=0.549 P=0.540N P=0.454N |
|ORDER RESTRICTED | P=0.275N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 45
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Oviduct |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/2 (100%) 1/1 (100%) 1/2 (50%) 0/0 (0%) 0/1 (0%) 1/1 (100%) |
|POLY-3 RATE (b) | 2/2.00 1/1.00 1/2.00 0/0.00 0/0.61 1/1.00 |
|POLY-3 PERCENT (g) | 100.0% 100.0% 50.0% 0.0% 0.0% 100.0% |
|TERMINAL (d) | 1/1 (100%) 0/0 (0%) 1/2 (50%) 0/0 (0%) 0/0 (0%) 1/1 (100%) |
|FIRST INCIDENCE | 717 729 731 (T) --- --- 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.451N (e) P=0.330N (e) P=0.533N (e) |
|POLY 3 | (e) (e) P=0.500N (e) P=0.333N (e) |
|POLY 1.5 | (e) (e) P=0.500N (e) P=0.333N (e) |
|POLY 6 | (e) (e) P=0.500N (e) P=0.333N (e) |
|LOGISTIC REGRESSION| P=0.729 (e) P=0.330N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.681N (e) P=0.500N (e) P=0.333N (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 0/54 (0%) 2/52 (4%) 2/53 (4%) 3/52 (6%) 6/51 (12%) |
|POLY-3 RATE (b) | 0/38.86 0/34.61 2/38.64 2/35.09 3/39.79 6/42.58 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.2% 5.7% 7.5% 14.1% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 2/23 (9%) 0/19 (0%) 1/22 (5%) 2/21 (10%) |
|FIRST INCIDENCE | --- --- 731 (T) 578 396 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002 ** (e) P=0.219 P=0.201 P=0.121 P=0.022 * |
|POLY 3 | P=0.002 ** (e) P=0.235 P=0.215 P=0.122 P=0.020 * |
|POLY 1.5 | P<0.001 ** (e) P=0.235 P=0.226 P=0.122 P=0.019 * |
|POLY 6 | P=0.002 ** (e) P=0.234 P=0.202 P=0.121 P=0.019 * |
|LOGISTIC REGRESSION| P<0.001 ** (e) P=0.219 P=0.256 P=0.128 P=0.015 * |
|COCH-ARM / FISHERS | P<0.001 ** (e) P=0.252 P=0.257 P=0.125 P=0.013 * |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 46
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/51 (2%) 2/54 (4%) 4/52 (8%) 4/53 (8%) 4/52 (8%) 9/51 (18%) |
|POLY-3 RATE (b) | 1/38.86 2/34.80 4/38.91 4/35.09 4/39.60 9/43.33 |
|POLY-3 PERCENT (g) | 2.6% 5.8% 10.3% 11.4% 10.1% 20.8% |
|TERMINAL (d) | 1/25 (4%) 1/21 (5%) 3/23 (13%) 2/19 (11%) 2/22 (9%) 3/21 (14%) |
|FIRST INCIDENCE | 731 (T) 681 659 578 518 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.005 ** P=0.434 P=0.158 P=0.118 P=0.164 P=0.012 * |
|POLY 3 | P=0.004 ** P=0.461 P=0.177 P=0.147 P=0.183 P=0.013 * |
|POLY 1.5 | P=0.003 ** P=0.485 P=0.176 P=0.164 P=0.183 P=0.011 * |
|POLY 6 | P=0.005 ** P=0.439 P=0.177 P=0.130 P=0.181 P=0.013 * |
|LOGISTIC REGRESSION| P=0.003 ** P=0.428 P=0.173 P=0.147 P=0.183 P=0.010 * |
|COCH-ARM / FISHERS | P=0.002 ** P=0.522 P=0.187 P=0.194 P=0.187 P=0.008 ** |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/51 (4%) 0/54 (0%) 0/52 (0%) 1/53 (2%) 2/52 (4%) 0/51 (0%) |
|POLY-3 RATE (b) | 2/39.17 0/34.61 0/38.64 1/34.16 2/38.45 0/40.86 |
|POLY-3 PERCENT (g) | 5.1% 0.0% 0.0% 2.9% 5.2% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 2/22 (9%) 0/21 (0%) |
|FIRST INCIDENCE | 646 --- --- 731 (T) 731 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.459N P=0.299N P=0.262N P=0.613N P=0.655 P=0.262N |
|POLY 3 | P=0.389N P=0.265N P=0.240N P=0.548N P=0.688 P=0.227N |
|POLY 1.5 | P=0.405N P=0.248N P=0.240N P=0.522N P=0.693 P=0.227N |
|POLY 6 | P=0.385N P=0.285N P=0.241N P=0.579N P=0.679 P=0.236N |
|LOGISTIC REGRESSION| P=0.427N P=0.263N P=0.238N P=0.571N P=0.685 P=0.228N |
|COCH-ARM / FISHERS | P=0.457N P=0.234N P=0.243N P=0.485N P=0.684N P=0.248N |
|ORDER RESTRICTED | P=0.086N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 47
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/51 (2%) 0/54 (0%) 0/52 (0%) 1/53 (2%) 15/52 (29%) 42/51 (82%) |
|POLY-3 RATE (b) | 1/39.16 0/34.61 0/38.64 1/34.16 15/39.85 42/47.15 |
|POLY-3 PERCENT (g) | 2.6% 0.0% 0.0% 2.9% 37.7% 89.1% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 11/22 (50%) 21/21 (100%) |
|FIRST INCIDENCE | 648 --- --- 731 (T) 486 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.561N P=0.506N P=0.690 P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.525N P=0.503N P=0.730 P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.510N P=0.503N P=0.746 P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.540N P=0.504N P=0.708 P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.502N P=0.498N P=0.732 P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.486N P=0.495N P=0.743N P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Artery |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 1/54 (2%) 1/52 (2%) 2/53 (4%) 2/52 (4%) 7/51 (14%) |
|POLY-3 RATE (b) | 0/38.86 1/35.59 1/38.64 2/34.16 2/38.45 7/42.11 |
|POLY-3 PERCENT (g) | 0.0% 2.8% 2.6% 5.9% 5.2% 16.6% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 1/23 (4%) 2/19 (11%) 2/22 (9%) 4/21 (19%) |
|FIRST INCIDENCE | --- 200 731 (T) 731 (T) 731 (T) 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.511 P=0.483 P=0.179 P=0.210 P=0.009 ** |
|POLY 3 | P<0.001 ** P=0.482 P=0.499 P=0.209 P=0.234 P=0.010 * |
|POLY 1.5 | P<0.001 ** P=0.495 P=0.498 P=0.224 P=0.237 P=0.010 * |
|POLY 6 | P<0.001 ** P=0.469 P=0.498 P=0.193 P=0.229 P=0.009 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.380 P=0.483 P=0.179 P=0.210 P=0.011 * |
|COCH-ARM / FISHERS | P<0.001 ** P=0.514 P=0.505 P=0.257 P=0.252 P=0.006 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 48
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 25/53 (47%) 18/54 (33%) 25/52 (48%) 20/53 (38%) 21/53 (40%) 9/52 (17%) |
|POLY-3 RATE (b) | 25/42.71 18/37.45 25/40.65 20/37.33 21/41.42 9/43.32 |
|POLY-3 PERCENT (g) | 58.5% 48.1% 61.5% 53.6% 50.7% 20.8% |
|TERMINAL (d) | 14/25 (56%) 11/21 (52%) 13/23 (57%) 12/19 (63%) 11/22 (50%) 4/21 (19%) |
|FIRST INCIDENCE | 474 557 550 453 578 647 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.002N** P=0.385N P=0.478 P=0.489 P=0.435N P=0.005N** |
|POLY 3 | P<0.001N** P=0.228N P=0.478 P=0.408N P=0.300N P<0.001N** |
|POLY 1.5 | P<0.001N** P=0.164N P=0.470 P=0.315N P=0.288N P<0.001N** |
|POLY 6 | P<0.001N** P=0.307N P=0.487 P=0.540N P=0.325N P<0.001N** |
|LOGISTIC REGRESSION| P<0.001N** P=0.266N P=0.507 P=0.455N P=0.282N P<0.001N** |
|COCH-ARM / FISHERS | P<0.001N** P=0.103N P=0.541 P=0.216N P=0.278N P<0.001N** |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Cytoplasmic Alteration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 0/54 (0%) 1/52 (2%) 4/53 (8%) 3/53 (6%) 0/52 (0%) |
|POLY-3 RATE (b) | 1/39.55 0/34.61 1/38.01 4/34.87 3/39.38 0/42.44 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 2.6% 11.5% 7.6% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 1/23 (4%) 3/19 (16%) 2/22 (9%) 0/21 (0%) |
|FIRST INCIDENCE | 731 (T) --- 731 (T) 485 621 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.476N P=0.535N P=0.744 P=0.115 P=0.270 P=0.535N |
|POLY 3 | P=0.373N P=0.527N P=0.753 P=0.141 P=0.303 P=0.486N |
|POLY 1.5 | P=0.395N P=0.514N P=0.750 P=0.156 P=0.304 P=0.489N |
|POLY 6 | P=0.374N P=0.539N P=0.754 P=0.123 P=0.299 P=0.490N |
|LOGISTIC REGRESSION| P=0.412N (e) P=0.744 P=0.136 P=0.294 (e) |
|COCH-ARM / FISHERS | P=0.475N P=0.495N P=0.748 P=0.181 P=0.309 P=0.505N |
|ORDER RESTRICTED | P=0.207N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 49
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 3/54 (6%) 1/52 (2%) 2/53 (4%) 2/53 (4%) 0/52 (0%) |
|POLY-3 RATE (b) | 0/39.55 3/34.91 1/38.01 2/34.57 2/39.47 0/42.44 |
|POLY-3 PERCENT (g) | 0.0% 8.6% 2.6% 5.8% 5.1% 0.0% |
|TERMINAL (d) | 0/25 (0%) 2/21 (10%) 1/23 (4%) 0/19 (0%) 1/22 (5%) 0/21 (0%) |
|FIRST INCIDENCE | --- 647 731 (T) 645 589 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.262N P=0.087 P=0.483 P=0.170 P=0.228 (e) |
|POLY 3 | P=0.239N P=0.097 P=0.492 P=0.208 P=0.236 (e) |
|POLY 1.5 | P=0.243N P=0.107 P=0.491 P=0.219 P=0.237 (e) |
|POLY 6 | P=0.249N P=0.088 P=0.493 P=0.195 P=0.234 (e) |
|LOGISTIC REGRESSION| P=0.235N P=0.088 P=0.483 P=0.208 P=0.237 (e) |
|COCH-ARM / FISHERS | P=0.276N P=0.125 P=0.495 P=0.248 P=0.248 (e) |
|ORDER RESTRICTED | P=0.239N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 19/53 (36%) 19/54 (35%) 16/52 (31%) 21/53 (40%) 26/53 (49%) 19/52 (37%) |
|POLY-3 RATE (b) | 19/43.37 19/41.40 16/40.26 21/39.02 26/42.48 19/46.73 |
|POLY-3 PERCENT (g) | 43.8% 45.9% 39.7% 53.8% 61.2% 40.7% |
|TERMINAL (d) | 11/25 (44%) 5/21 (24%) 10/23 (44%) 10/19 (53%) 15/22 (68%) 8/21 (38%) |
|FIRST INCIDENCE | 487 264 578 453 486 581 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.442 P=0.370 P=0.411N P=0.152 P=0.076 P=0.515 |
|POLY 3 | P=0.478N P=0.510 P=0.437N P=0.239 P=0.072 P=0.464N |
|POLY 1.5 | P=0.530 P=0.547 P=0.431N P=0.303 P=0.087 P=0.494N |
|POLY 6 | P=0.455N P=0.492 P=0.443N P=0.186 P=0.058 P=0.460N |
|LOGISTIC REGRESSION| P=0.503 P=0.548 P=0.393N P=0.283 P=0.103 P=0.566N |
|COCH-ARM / FISHERS | P=0.300 P=0.552N P=0.365N P=0.421 P=0.119 P=0.551 |
|ORDER RESTRICTED | P=0.362 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 50
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Intermedia |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/52 (0%) 0/53 (0%) 1/53 (2%) 1/52 (2%) |
|POLY-3 RATE (b) | 2/40.18 0/34.61 0/38.01 0/34.16 1/39.55 1/42.44 |
|POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 0.0% 2.5% 2.4% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 526 --- --- --- 557 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.529 P=0.264N P=0.244N P=0.278N P=0.506N P=0.521N |
|POLY 3 | P=0.581 P=0.271N P=0.249N P=0.274N P=0.505N P=0.481N |
|POLY 1.5 | P=0.560 P=0.255N P=0.250N P=0.259N P=0.503N P=0.483N |
|POLY 6 | P=0.590 P=0.289N P=0.249N P=0.295N P=0.511N P=0.491N |
|LOGISTIC REGRESSION| P=0.512 P=0.236N P=0.242N P=0.240N P=0.498N P=0.501N |
|COCH-ARM / FISHERS | P=0.504 P=0.243N P=0.252N P=0.248N P=0.500N P=0.507N |
|ORDER RESTRICTED | P=0.130N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Salivary Glands |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 0/54 (0%) 0/52 (0%) 2/50 (4%) 1/51 (2%) 0/52 (0%) |
|POLY-3 RATE (b) | 0/38.56 0/34.61 0/37.95 2/33.80 1/37.86 0/41.66 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.9% 2.6% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 1/22 (5%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- --- 626 731 (T) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.662N (e) (e) P=0.182 P=0.475 (e) |
|POLY 3 | P=0.633N (e) (e) P=0.208 P=0.496 (e) |
|POLY 1.5 | P=0.639N (e) (e) P=0.218 P=0.498 (e) |
|POLY 6 | P=0.641N (e) (e) P=0.195 P=0.493 (e) |
|LOGISTIC REGRESSION| P=0.638N (e) (e) P=0.209 P=0.475 (e) |
|COCH-ARM / FISHERS | P=0.672N (e) (e) P=0.243 P=0.500 (e) |
|ORDER RESTRICTED | P=0.251 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 51
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Salivary Glands |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 0/54 (0%) 2/52 (4%) 3/50 (6%) 0/51 (0%) 1/52 (2%) |
|POLY-3 RATE (b) | 0/38.56 0/34.61 2/38.95 3/33.80 0/37.86 1/42.11 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.1% 8.9% 0.0% 2.4% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 1/23 (4%) 2/19 (11%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 54 626 --- 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.618 (e) P=0.229 P=0.079 (e) P=0.536 |
|POLY 3 | P=0.604N (e) P=0.239 P=0.095 (e) P=0.518 |
|POLY 1.5 | P=0.616N (e) P=0.238 P=0.103 (e) P=0.516 |
|POLY 6 | P=0.604N (e) P=0.238 P=0.086 (e) P=0.512 |
|LOGISTIC REGRESSION| P=0.558 (e) P=0.311 P=0.089 (e) P=0.465 |
|COCH-ARM / FISHERS | P=0.600 (e) P=0.252 P=0.118 (e) P=0.505 |
|ORDER RESTRICTED | P=0.221 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Skin |
| Cyst Epithelial Inclusion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 1/39.55 0/34.61 0/38.75 0/34.16 0/39.00 2/42.83 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% 0.0% 4.7% |
|TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 731 (T) --- --- --- --- 668 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.085 P=0.535N P=0.517N P=0.555N P=0.525N P=0.456 |
|POLY 3 | P=0.100 P=0.527N P=0.504N P=0.529N P=0.503N P=0.528 |
|POLY 1.5 | P=0.095 P=0.514N P=0.505N P=0.517N P=0.501N P=0.524 |
|POLY 6 | P=0.103 P=0.539N P=0.503N P=0.544N P=0.506N P=0.521 |
|LOGISTIC REGRESSION| P=0.104 (e) (e) (e) (e) P=0.511 |
|COCH-ARM / FISHERS | P=0.083 P=0.495N P=0.500N P=0.500N P=0.500N P=0.500 |
|ORDER RESTRICTED | P=0.067 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 52
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Skin |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 2/39.74 0/34.16 0/39.00 1/42.66 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% 0.0% 2.3% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 1/23 (4%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- 54 --- --- 716 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.478 (e) P=0.229 (e) (e) P=0.492 |
|POLY 3 | P=0.536 (e) P=0.238 (e) (e) P=0.515 |
|POLY 1.5 | P=0.519 (e) P=0.236 (e) (e) P=0.513 |
|POLY 6 | P=0.545 (e) P=0.239 (e) (e) P=0.511 |
|LOGISTIC REGRESSION| P=0.383 (e) P=0.305 (e) (e) P=0.501 |
|COCH-ARM / FISHERS | P=0.482 (e) P=0.248 (e) (e) P=0.500 |
|ORDER RESTRICTED | P=0.297 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 46/51 (90%) 50/54 (93%) 38/53 (72%) 42/53 (79%) 44/52 (85%) 43/52 (83%) |
|POLY-3 RATE (b) | 46/47.32 50/52.86 38/45.09 42/46.12 44/49.47 43/50.03 |
|POLY-3 PERCENT (g) | 97.2% 94.6% 84.3% 91.1% 88.9% 86.0% |
|TERMINAL (d) | 25/25 (100%) 20/21 (95%) 21/23 (91%) 18/19 (95%) 20/22 (91%) 20/21 (95%) |
|FIRST INCIDENCE | 185 200 47 338 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.269N P=0.069 P=0.222N P=0.205 P=0.479 P=0.555 |
|POLY 3 | P=0.053N P=0.429N P=0.017N* P=0.149N P=0.087N P=0.032N* |
|POLY 1.5 | P=0.093N P=0.559N P=0.017N* P=0.129N P=0.134N P=0.059N |
|POLY 6 | P=0.041N* P=0.323N P=0.017N* P=0.185N P=0.058N P=0.023N* |
|LOGISTIC REGRESSION| P=0.127N P=0.347 P=0.024N* P=0.231N P=0.317N P=0.085N |
|COCH-ARM / FISHERS | P=0.355N P=0.463 P=0.015N* P=0.100N P=0.290N P=0.206N |
|ORDER RESTRICTED | P=0.023N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 53
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/51 (2%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 4/52 (8%) |
|POLY-3 RATE (b) | 1/39.45 0/34.61 0/38.75 0/34.16 0/38.45 4/42.29 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% 0.0% 9.5% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 2/21 (10%) |
|FIRST INCIDENCE | 645 --- --- --- --- 641 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003 ** P=0.576N P=0.522N P=0.584N P=0.511N P=0.161 |
|POLY 3 | P=0.002 ** P=0.526N P=0.504N P=0.529N P=0.505N P=0.199 |
|POLY 1.5 | P=0.002 ** P=0.511N P=0.502N P=0.514N P=0.502N P=0.200 |
|POLY 6 | P=0.002 ** P=0.542N P=0.506N P=0.546N P=0.510N P=0.189 |
|LOGISTIC REGRESSION| P=0.003 ** P=0.500N P=0.495N P=0.503N P=0.497N P=0.195 |
|COCH-ARM / FISHERS | P=0.002 ** P=0.486N P=0.490N P=0.490N P=0.495N P=0.187 |
|ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 45/51 (88%) 49/54 (91%) 49/53 (92%) 51/53 (96%) 49/52 (94%) 47/52 (90%) |
|POLY-3 RATE (b) | 45/49.73 49/50.86 49/50.96 51/52.36 49/50.80 47/50.25 |
|POLY-3 PERCENT (g) | 90.5% 96.3% 96.2% 97.4% 96.5% 93.5% |
|TERMINAL (d) | 23/25 (92%) 20/21 (95%) 23/23 (100%) 18/19 (95%) 21/22 (96%) 21/21 (100%) |
|FIRST INCIDENCE | 169 241 47 53 141 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.360N P=0.076 P=0.226 P=0.021 * P=0.192 P=0.287 |
|POLY 3 | P=0.552N P=0.193 P=0.203 P=0.125 P=0.193 P=0.415 |
|POLY 1.5 | P=0.532N P=0.246 P=0.238 P=0.118 P=0.175 P=0.454 |
|POLY 6 | P=0.552 P=0.191 P=0.171 P=0.158 P=0.243 P=0.335 |
|LOGISTIC REGRESSION| P=0.503N P=0.395 P=0.333 P=0.148 P=0.228 P=0.496 |
|COCH-ARM / FISHERS | P=0.534 P=0.459 P=0.346 P=0.123 P=0.234 P=0.486 |
|ORDER RESTRICTED | P=0.125 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 54
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen: Lymphoid Follicle |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 4/51 (8%) 0/54 (0%) 1/53 (2%) 0/53 (0%) 1/52 (2%) 1/52 (2%) |
|POLY-3 RATE (b) | 4/42.10 0/34.61 1/39.74 0/34.16 1/38.63 1/41.88 |
|POLY-3 PERCENT (g) | 9.5% 0.0% 2.5% 0.0% 2.6% 2.4% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 169 --- 47 --- 683 667 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.348N P=0.083N P=0.202N P=0.085N P=0.195N P=0.173N |
|POLY 3 | P=0.300N P=0.089N P=0.196N P=0.092N P=0.205N P=0.179N |
|POLY 1.5 | P=0.325N P=0.074N P=0.189N P=0.076N P=0.194N P=0.173N |
|POLY 6 | P=0.282N P=0.107N P=0.203N P=0.112N P=0.216N P=0.194N |
|LOGISTIC REGRESSION| P=0.592N P=0.022N* P=0.042N* P=0.022N* P=0.138N P=0.441N |
|COCH-ARM / FISHERS | P=0.383N P=0.052N P=0.170N P=0.054N P=0.175N P=0.175N |
|ORDER RESTRICTED | P=0.017N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Hyperkeratosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/54 (2%) 1/53 (2%) 1/53 (2%) 2/53 (4%) 3/53 (6%) |
|POLY-3 RATE (b) | 1/40.16 1/35.30 1/39.74 1/34.87 2/39.36 3/43.51 |
|POLY-3 PERCENT (g) | 2.5% 2.8% 2.5% 2.9% 5.1% 6.9% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 533 492 54 485 659 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.140 P=0.747 P=0.755N P=0.745 P=0.493 P=0.331 |
|POLY 3 | P=0.140 P=0.732 P=0.759 P=0.729 P=0.493 P=0.334 |
|POLY 1.5 | P=0.131 P=0.745 P=0.758 P=0.742 P=0.496 P=0.330 |
|POLY 6 | P=0.141 P=0.717 P=0.759 P=0.711 P=0.487 P=0.327 |
|LOGISTIC REGRESSION| P=0.048 * P=0.728N P=0.644N P=0.731N P=0.500 P=0.249 |
|COCH-ARM / FISHERS | P=0.104 P=0.748N P=0.752N P=0.752N P=0.500 P=0.309 |
|ORDER RESTRICTED | P=0.247 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 55
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 4/54 (7%) 4/53 (8%) 2/53 (4%) 7/53 (13%) 11/53 (21%) |
|POLY-3 RATE (b) | 3/39.67 4/35.31 4/39.80 2/34.96 7/40.91 11/45.30 |
|POLY-3 PERCENT (g) | 7.6% 11.3% 10.1% 5.7% 17.1% 24.3% |
|TERMINAL (d) | 2/25 (8%) 2/21 (10%) 2/23 (9%) 0/19 (0%) 2/22 (9%) 3/21 (14%) |
|FIRST INCIDENCE | 701 492 54 485 486 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003 ** P=0.417 P=0.476 P=0.605N P=0.138 P=0.025 * |
|POLY 3 | P=0.003 ** P=0.436 P=0.502 P=0.558N P=0.167 P=0.035 * |
|POLY 1.5 | P=0.002 ** P=0.466 P=0.497 P=0.534N P=0.163 P=0.031 * |
|POLY 6 | P=0.004 ** P=0.405 P=0.505 P=0.587N P=0.168 P=0.037 * |
|LOGISTIC REGRESSION| P=0.002 ** P=0.415 P=0.500 P=0.552N P=0.156 P=0.027 * |
|COCH-ARM / FISHERS | P<0.001 ** P=0.511 P=0.500 P=0.500N P=0.160 P=0.021 * |
|ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/53 (2%) 1/54 (2%) 2/53 (4%) 0/53 (0%) 2/53 (4%) 5/53 (9%) |
|POLY-3 RATE (b) | 1/40.42 1/34.62 2/39.31 0/34.16 2/39.91 5/44.24 |
|POLY-3 PERCENT (g) | 2.5% 2.9% 5.1% 0.0% 5.0% 11.3% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 366 729 578 --- 486 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.021 * P=0.744 P=0.508 P=0.496N P=0.496 P=0.128 |
|POLY 3 | P=0.019 * P=0.725 P=0.490 P=0.533N P=0.496 P=0.122 |
|POLY 1.5 | P=0.016 * P=0.741 P=0.488 P=0.520N P=0.497 P=0.119 |
|POLY 6 | P=0.020 * P=0.708 P=0.493 P=0.549N P=0.493 P=0.120 |
|LOGISTIC REGRESSION| P=0.009 ** P=0.736N P=0.526 P=0.436N P=0.507 P=0.048 * |
|COCH-ARM / FISHERS | P=0.012 * P=0.748N P=0.500 P=0.500N P=0.500 P=0.103 |
|ORDER RESTRICTED | P=0.032 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 56
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/54 (2%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 4/53 (8%) |
|POLY-3 RATE (b) | 2/40.54 1/34.62 0/38.75 1/34.87 1/39.20 4/43.49 |
|POLY-3 PERCENT (g) | 4.9% 2.9% 0.0% 2.9% 2.6% 9.2% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) |
|FIRST INCIDENCE | 366 729 --- 485 677 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.063 P=0.540N P=0.247N P=0.541N P=0.512N P=0.342 |
|POLY 3 | P=0.062 P=0.555N P=0.247N P=0.552N P=0.512N P=0.369 |
|POLY 1.5 | P=0.058 P=0.531N P=0.247N P=0.531N P=0.507N P=0.365 |
|POLY 6 | P=0.063 P=0.580N P=0.248N P=0.578N P=0.519N P=0.361 |
|LOGISTIC REGRESSION| P=0.044 * P=0.482N P=0.213N P=0.450N P=0.497N P=0.286 |
|COCH-ARM / FISHERS | P=0.046 * P=0.493N P=0.248N P=0.500N P=0.500N P=0.339 |
|ORDER RESTRICTED | P=0.081 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 3/53 (6%) 0/53 (0%) |
|POLY-3 RATE (b) | 3/41.09 0/34.61 0/38.75 1/34.37 3/40.69 0/42.60 |
|POLY-3 PERCENT (g) | 7.3% 0.0% 0.0% 2.9% 7.4% 0.0% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 169 --- --- 675 141 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.361N P=0.166N P=0.139N P=0.400N P=0.657 P=0.129N |
|POLY 3 | P=0.309N P=0.152N P=0.129N P=0.371N P=0.659 P=0.112N |
|POLY 1.5 | P=0.330N P=0.137N P=0.128N P=0.345N P=0.661 P=0.112N |
|POLY 6 | P=0.303N P=0.170N P=0.131N P=0.404N P=0.653 P=0.118N |
|LOGISTIC REGRESSION| P=0.522N P=0.088N P=0.089N P=0.262N P=0.658N P=0.229N |
|COCH-ARM / FISHERS | P=0.398N P=0.118N P=0.121N P=0.309N P=0.661N P=0.121N |
|ORDER RESTRICTED | P=0.028N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 57
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) |
|POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 0/39.00 2/43.18 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.6% |
|TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | --- --- --- --- --- 604 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.017 * (e) (e) (e) (e) P=0.247 |
|POLY 3 | P=0.012 * (e) (e) (e) (e) P=0.257 |
|POLY 1.5 | P=0.012 * (e) (e) (e) (e) P=0.254 |
|POLY 6 | P=0.013 * (e) (e) (e) (e) P=0.254 |
|LOGISTIC REGRESSION| P=0.012 * (e) (e) (e) (e) P=0.230 |
|COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.248 |
|ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thymus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 36/51 (71%) 41/52 (79%) 44/52 (85%) 41/49 (84%) 44/46 (96%) 42/42 (100%) |
|POLY-3 RATE (b) | 36/45.37 41/45.88 44/48.28 41/43.55 44/44.09 42/42.00 |
|POLY-3 PERCENT (g) | 79.3% 89.4% 91.1% 94.2% 99.8% 100.0% |
|TERMINAL (d) | 20/25 (80%) 17/20 (85%) 21/23 (91%) 18/18 (100%) 20/20 (100%) 18/18 (100%) |
|FIRST INCIDENCE | 169 264 47 338 185 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.279 P=0.056 P=0.092 P=0.018 * P=0.038 * P=0.055 |
|POLY 3 | P<0.001 ** P=0.128 P=0.073 P=0.024 * P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.148 P=0.058 P=0.032 * P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.144 P=0.105 P=0.021 * P=0.002 ** P=0.002 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.136 P=0.050 P=0.041 * P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.231 P=0.070 P=0.094 P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 58
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/52 (0%) 1/54 (2%) 1/53 (2%) 1/51 (2%) 4/53 (8%) 1/52 (2%) |
|POLY-3 RATE (b) | 0/38.90 1/34.61 1/38.75 1/33.58 4/39.18 1/41.66 |
|POLY-3 PERCENT (g) | 0.0% 2.9% 2.6% 3.0% 10.2% 2.4% |
|TERMINAL (d) | 0/25 (0%) 1/21 (5%) 1/23 (4%) 1/19 (5%) 3/22 (14%) 1/21 (5%) |
|FIRST INCIDENCE | --- 731 (T) 731 (T) 731 (T) 683 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.277 P=0.465 P=0.483 P=0.445 P=0.050 P=0.465 |
|POLY 3 | P=0.375 P=0.477 P=0.499 P=0.471 P=0.060 P=0.514 |
|POLY 1.5 | P=0.360 P=0.489 P=0.498 P=0.481 P=0.062 P=0.513 |
|POLY 6 | P=0.365 P=0.463 P=0.499 P=0.457 P=0.057 P=0.508 |
|LOGISTIC REGRESSION| P=0.310 P=0.465 P=0.483 P=0.445 P=0.054 P=0.465 |
|COCH-ARM / FISHERS | P=0.296 P=0.509 P=0.505 P=0.495 P=0.061 P=0.500 |
|ORDER RESTRICTED | P=0.095 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 19/52 (37%) 17/54 (31%) 22/53 (42%) 19/51 (37%) 16/53 (30%) 23/52 (44%) |
|POLY-3 RATE (b) | 19/40.39 17/38.91 22/41.52 19/37.61 16/42.50 23/45.63 |
|POLY-3 PERCENT (g) | 47.0% 43.7% 53.0% 50.5% 37.7% 50.4% |
|TERMINAL (d) | 12/25 (48%) 9/21 (43%) 15/23 (65%) 9/19 (47%) 7/22 (32%) 11/21 (52%) |
|FIRST INCIDENCE | 646 241 177 380 341 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.300 P=0.475 P=0.249 P=0.220 P=0.465N P=0.185 |
|POLY 3 | P=0.504 P=0.470N P=0.371 P=0.467 P=0.255N P=0.461 |
|POLY 1.5 | P=0.421 P=0.420N P=0.360 P=0.502 P=0.273N P=0.415 |
|POLY 6 | P=0.544 P=0.531N P=0.358 P=0.419 P=0.253N P=0.461 |
|LOGISTIC REGRESSION| P=0.426 P=0.558N P=0.331 P=0.345 P=0.325N P=0.375 |
|COCH-ARM / FISHERS | P=0.232 P=0.365N P=0.374 P=0.551 P=0.315N P=0.275 |
|ORDER RESTRICTED | P=0.565 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 59
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/52 (4%) 2/54 (4%) 0/53 (0%) 0/51 (0%) 0/53 (0%) 0/52 (0%) |
|POLY-3 RATE (b) | 2/38.90 2/35.51 0/38.75 0/33.58 0/39.00 0/41.66 |
|POLY-3 PERCENT (g) | 5.1% 5.6% 0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 2/25 (8%) 1/21 (5%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) |
|FIRST INCIDENCE | 731 (T) 341 --- --- --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.108N P=0.645 P=0.256N P=0.300N P=0.266N P=0.277N |
|POLY 3 | P=0.100N P=0.662 P=0.237N P=0.271N P=0.236N P=0.222N |
|POLY 1.5 | P=0.099N P=0.681 P=0.239N P=0.258N P=0.234N P=0.223N |
|POLY 6 | P=0.101N P=0.639 P=0.237N P=0.288N P=0.240N P=0.228N |
|LOGISTIC REGRESSION| P=0.100N P=0.694N (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.103N P=0.677N P=0.243N P=0.252N P=0.243N P=0.248N |
|ORDER RESTRICTED | P=0.042N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/52 (6%) 4/54 (7%) 4/53 (8%) 7/51 (14%) 10/53 (19%) 17/52 (33%) |
|POLY-3 RATE (b) | 3/39.78 4/35.62 4/40.05 7/35.23 10/40.94 17/45.27 |
|POLY-3 PERCENT (g) | 7.5% 11.2% 10.0% 19.9% 24.4% 37.6% |
|TERMINAL (d) | 2/25 (8%) 2/21 (10%) 2/23 (9%) 3/19 (16%) 6/22 (27%) 9/21 (43%) |
|FIRST INCIDENCE | 361 485 429 578 444 396 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.418 P=0.472 P=0.085 P=0.027 * P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.439 P=0.504 P=0.108 P=0.036 * P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.471 P=0.498 P=0.122 P=0.037 * P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.409 P=0.508 P=0.094 P=0.034 * P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.506 P=0.517 P=0.134 P=0.040 * P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.521 P=0.511 P=0.151 P=0.039 * P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 60
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Tooth: Peridontal Tissue |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 15/16 (94%) 16/16 (100%) 12/12 (100%) 13/13 (100%) 14/14 (100%) 18/18 (100%) |
|POLY-3 RATE (b) | 15/15.64 16/16.00 12/12.00 13/13.00 14/14.00 18/18.00 |
|POLY-3 PERCENT (g) | 95.9% 100.0% 100.0% 100.0% 100.0% 100.0% |
|TERMINAL (d) | 9/9 (100%) 9/9 (100%) 5/5 (100%) 4/4 (100%) 6/6 (100%) 8/8 (100%) |
|FIRST INCIDENCE | 185 449 429 53 317 599 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.315 P=0.337 P=0.479 P=0.186 P=0.376 P=0.232 |
|POLY 3 | P=0.605 P=0.705 P=0.752 P=0.739 P=0.727 P=0.685 |
|POLY 1.5 | P=0.515 P=0.595 P=0.649 P=0.634 P=0.620 P=0.572 |
|POLY 6 | P=0.815 P=0.915 P=0.935 P=0.930 P=0.925 P=0.907 |
|LOGISTIC REGRESSION| P=0.445 P=0.501 P=0.554 P=0.546 P=0.523 P=0.500 |
|COCH-ARM / FISHERS | P=0.440 P=0.500 P=0.571 P=0.552 P=0.533 P=0.471 |
|ORDER RESTRICTED | P=0.048 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Urinary Bladder |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 6/52 (12%) 10/53 (19%) 4/53 (8%) 0/52 (0%) 8/53 (15%) 3/53 (6%) |
|POLY-3 RATE (b) | 6/39.16 10/37.73 4/39.66 0/33.80 8/42.02 3/42.71 |
|POLY-3 PERCENT (g) | 15.3% 26.5% 10.1% 0.0% 19.0% 7.0% |
|TERMINAL (d) | 4/25 (16%) 5/21 (24%) 2/23 (9%) 0/19 (0%) 4/22 (18%) 2/21 (10%) |
|FIRST INCIDENCE | 697 341 578 --- 141 701 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.180N P=0.141 P=0.398N P=0.041N* P=0.325 P=0.315N |
|POLY 3 | P=0.109N P=0.174 P=0.359N P=0.024N* P=0.441 P=0.198N |
|POLY 1.5 | P=0.119N P=0.192 P=0.368N P=0.020N* P=0.435 P=0.202N |
|POLY 6 | P=0.115N P=0.157 P=0.352N P=0.030N* P=0.435 P=0.210N |
|LOGISTIC REGRESSION| P=0.168N P=0.184 P=0.372N P=0.036N* P=0.404 P=0.251N |
|COCH-ARM / FISHERS | P=0.172N P=0.220 P=0.359N P=0.013N* P=0.402 P=0.235N |
|ORDER RESTRICTED | P=0.039N* (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 61
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Urinary Bladder: Transitional Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/52 (2%) 2/53 (4%) 1/53 (2%) 0/52 (0%) 6/53 (11%) 2/53 (4%) |
|POLY-3 RATE (b) | 1/38.97 2/35.07 1/38.75 0/33.80 6/40.81 2/42.71 |
|POLY-3 PERCENT (g) | 2.6% 5.7% 2.6% 0.0% 14.7% 4.7% |
|TERMINAL (d) | 1/25 (4%) 1/21 (5%) 1/23 (4%) 0/19 (0%) 3/22 (14%) 1/21 (5%) |
|FIRST INCIDENCE | 731 (T) 341 731 (T) --- 185 701 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.194 P=0.457 P=0.744 P=0.555N P=0.053 P=0.455 |
|POLY 3 | P=0.266 P=0.463 P=0.760 P=0.528N P=0.062 P=0.532 |
|POLY 1.5 | P=0.251 P=0.481 P=0.759 P=0.517N P=0.062 P=0.529 |
|POLY 6 | P=0.260 P=0.444 P=0.760 P=0.543N P=0.060 P=0.523 |
|LOGISTIC REGRESSION| P=0.196 P=0.517 P=0.744 (e) P=0.062 P=0.492 |
|COCH-ARM / FISHERS | P=0.195 P=0.507 P=0.748N P=0.500N P=0.059 P=0.507 |
|ORDER RESTRICTED | P=0.113 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 7/52 (13%) 6/53 (11%) 12/53 (23%) 9/53 (17%) 11/53 (21%) 5/53 (9%) |
|POLY-3 RATE (b) | 7/40.38 6/35.29 12/42.83 9/36.87 11/43.62 5/43.72 |
|POLY-3 PERCENT (g) | 17.3% 17.0% 28.0% 24.4% 25.2% 11.4% |
|TERMINAL (d) | 4/25 (16%) 3/21 (14%) 4/23 (17%) 3/19 (16%) 2/22 (9%) 1/21 (5%) |
|FIRST INCIDENCE | 185 556 348 416 141 604 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.227N P=0.613N P=0.152 P=0.223 P=0.204 P=0.430N |
|POLY 3 | P=0.138N P=0.605N P=0.182 P=0.313 P=0.269 P=0.322N |
|POLY 1.5 | P=0.162N P=0.562N P=0.163 P=0.346 P=0.255 P=0.329N |
|POLY 6 | P=0.137N P=0.594 P=0.204 P=0.278 P=0.282 P=0.334N |
|LOGISTIC REGRESSION| P=0.268N P=0.539N P=0.168 P=0.381 P=0.235 P=0.375N |
|COCH-ARM / FISHERS | P=0.262N P=0.485N P=0.167 P=0.410 P=0.232 P=0.367N |
|ORDER RESTRICTED | P=0.163N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 62
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/52 (0%) 2/53 (4%) 3/53 (6%) 0/53 (0%) 3/53 (6%) 1/53 (2%) |
|POLY-3 RATE (b) | 0/38.97 2/34.17 3/39.25 0/34.16 3/39.00 1/43.05 |
|POLY-3 PERCENT (g) | 0.0% 5.9% 7.6% 0.0% 7.7% 2.3% |
|TERMINAL (d) | 0/25 (0%) 2/21 (10%) 2/23 (9%) 0/19 (0%) 3/22 (14%) 0/21 (0%) |
|FIRST INCIDENCE | --- 731 (T) 578 --- 731 (T) 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.594 P=0.200 P=0.118 (e) P=0.097 P=0.536 |
|POLY 3 | P=0.543N P=0.208 P=0.119 (e) P=0.118 P=0.520 |
|POLY 1.5 | P=0.560N P=0.221 P=0.118 (e) P=0.120 P=0.518 |
|POLY 6 | P=0.544N P=0.196 P=0.120 (e) P=0.113 P=0.516 |
|LOGISTIC REGRESSION| P=0.550N P=0.200 P=0.120 (e) P=0.097 P=0.463 |
|COCH-ARM / FISHERS | P=0.597 P=0.252 P=0.125 (e) P=0.125 P=0.505 |
|ORDER RESTRICTED | P=0.206 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Metaplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 29/52 (56%) 31/53 (58%) 28/53 (53%) 23/53 (43%) 32/53 (60%) 17/53 (32%) |
|POLY-3 RATE (b) | 29/45.30 31/45.05 28/46.99 23/43.47 32/47.83 17/46.13 |
|POLY-3 PERCENT (g) | 64.0% 68.8% 59.6% 52.9% 66.9% 36.9% |
|TERMINAL (d) | 15/25 (60%) 14/21 (67%) 11/23 (48%) 8/19 (42%) 14/22 (64%) 7/21 (33%) |
|FIRST INCIDENCE | 351 241 177 197 317 546 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.017N* P=0.199 P=0.552 P=0.529N P=0.258 P=0.053N |
|POLY 3 | P=0.002N** P=0.393 P=0.409N P=0.189N P=0.469 P=0.006N** |
|POLY 1.5 | P=0.002N** P=0.427 P=0.445N P=0.162N P=0.441 P=0.006N** |
|POLY 6 | P=0.002N** P=0.367 P=0.374N P=0.231N P=0.485 P=0.007N** |
|LOGISTIC REGRESSION| P=0.007N** P=0.427 P=0.471N P=0.149N P=0.386 P=0.010N* |
|COCH-ARM / FISHERS | P=0.007N** P=0.466 P=0.458N P=0.142N P=0.390 P=0.012N* |
|ORDER RESTRICTED | P=0.002N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 63
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus: Endometrium |
| Hyperplasia Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 30/52 (58%) 33/53 (62%) 35/53 (66%) 27/53 (51%) 31/53 (58%) 19/53 (36%) |
|POLY-3 RATE (b) | 30/44.70 33/43.20 35/44.03 27/41.69 31/46.95 19/44.95 |
|POLY-3 PERCENT (g) | 67.1% 76.4% 79.5% 64.8% 66.0% 42.3% |
|TERMINAL (d) | 15/25 (60%) 17/21 (81%) 19/23 (83%) 14/19 (74%) 14/22 (64%) 10/21 (48%) |
|FIRST INCIDENCE | 361 361 348 197 141 474 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.007N** P=0.121 P=0.186 P=0.326 P=0.366 P=0.091N |
|POLY 3 | P<0.001N** P=0.221 P=0.127 P=0.499N P=0.546N P=0.011N* |
|POLY 1.5 | P<0.001N** P=0.276 P=0.137 P=0.398N P=0.543N P=0.010N* |
|POLY 6 | P<0.001N** P=0.179 P=0.118 P=0.553 P=0.592N P=0.021N* |
|LOGISTIC REGRESSION| P<0.001N** P=0.234 P=0.180 P=0.426N P=0.540 P=0.009N** |
|COCH-ARM / FISHERS | P=0.002N** P=0.390 P=0.249 P=0.309N P=0.546 P=0.020N* |
|ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Vagina |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/0 (0%) 0/1 (0%) 0/1 (0%) 2/3 (67%) 0/3 (0%) 0/1 (0%) |
|POLY-3 RATE (b) | 0/0.00 0/0.31 0/0.97 2/2.24 0/2.18 0/0.56 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 89.4% 0.0% 0.0% |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/1 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- 690 --- --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.591N (e) (e) P=0.455 (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| P=0.719N (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.506N (e) (e) P=1.000 (e) (e) |
|ORDER RESTRICTED | (e) (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).