TDMS Study 91005-08 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Southern Research Inst METHYLENE BLUE TRIHYDRATE DATE: 04/26/05
EXPERIMENT: 91005 TEST: 08 TIME: 08:51:26
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: FARNELL, DANIEL CAS: 7220-79-3
------------------------------------------------------------------------------------------------------------------------------------
FINAL #1 RATS
REASONS FOR REMOVAL: ALL
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE ALL
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Southern Research Inst METHYLENE BLUE TRIHYDRATE DATE: 04/26/05
EXPERIMENT: 91005 TEST: 08 TIME: 08:51:26
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: FARNELL, DANIEL CAS: 7220-79-3
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF METHYLENE BLUE TRIHYDRATE
===============================================================
Male Mice
------------
Organ Morphology
----- ----------
Bone Hyperostosis
Islets, Pancreatic Hyperplasia
Kidney Hydronephrosis
Liver Mixed Cell Focus
Liver: Hepatocyte Vacuolization Cytoplasmic
Mesentery: Fat Necrosis Focal
Nose Inflammation
Skin Ulcer
Spleen Hematopoietic Cell Proliferation
Hyperplasia Lymphoid
Thyroid Gland: Follicular Cell Hyperplasia Focal
===============================================================
Female Mice
------------
Organ Morphology
----- ----------
Bone Marrow Hyperplasia
Harderian Gland: Epithelium Hyperplasia
Liver Angiectasis Focal
Basophilic Focus
Liver: Hepatocyte Necrosis Focal
Lymph Node, Mandibular Hyperplasia Lymphoid
Mesentery: Fat Necrosis Focal
Nose Inflammation
Spleen Hematopoietic Cell Proliferation
Hyperplasia Lymphoid
Thyroid Gland: Follicle Degeneration Cystic Focal
Uterus: Endometrium Hyperplasia Cystic
===============================================================
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 1
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Accessory Adrenal Cortical Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/48 (2%) 0/50 (0%) 1/50 (2%) 0/48 (0%) |2/50 (4%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/42.71 0/46.10 1/46.52 0/45.75 |2/44.58 2/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 2.2% 0.0% |4.5% 4.4% 0.0% 0.0% |
|TERMINAL (d) | 1/34 (3%) 0/38 (0%) 0/38 (0%) 0/40 (0%) |2/33 (6%) 2/40 (5%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) --- 690 --- |729 (T) 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.437N P=0.478N P=0.737N P=0.468N |P=0.052N P=0.624N P=0.187N P=0.182N |
|POLY 3 | P=0.460N P=0.485N P=0.741N P=0.486N |P=0.066N P=0.684N P=0.223N P=0.225N |
|POLY 1.5 | P=0.461N P=0.489N P=0.746N P=0.492N |P=0.067N P=0.690N P=0.229N P=0.230N |
|POLY 6 | P=0.459N P=0.479N P=0.736N P=0.479N |P=0.064N P=0.674N P=0.213N P=0.217N |
|LOGISTIC REGRESSION| P=0.462N (e) P=0.749N (e) |P=0.052N P=0.624N (e) (e) |
|COCH-ARM / FISHERS | P=0.467N P=0.490N P=0.742N P=0.500N |P=0.070N P=0.691N P=0.247N P=0.247N |
|ORDER RESTRICTED | P=0.238N (e) (e) (e) |P=0.107N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Cytoplasmic Alteration Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/48 (8%) 0/50 (0%) 5/50 (10%) 5/48 (10%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 4/43.28 0/46.10 5/46.36 5/45.75 |1/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 9.2% 0.0% 10.8% 10.9% |2.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 3/34 (9%) 0/38 (0%) 5/38 (13%) 5/40 (13%) |1/33 (3%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 548 --- 729 (T) 729 (T) |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.163 P=0.053N P=0.566 P=0.594 |P=0.324N P=0.462N P=0.452N P=0.447N |
|POLY 3 | P=0.129 P=0.052N P=0.543 P=0.535 |P=0.355N P=0.495N P=0.487N P=0.489N |
|POLY 1.5 | P=0.126 P=0.055N P=0.534 P=0.520 |P=0.353N P=0.498N P=0.492N P=0.493N |
|POLY 6 | P=0.133 P=0.050N P=0.553 P=0.552 |P=0.359N P=0.489N P=0.478N P=0.481N |
|LOGISTIC REGRESSION| P=0.133 P=0.057N P=0.540 P=0.515 |P=0.324N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.117 P=0.054N P=0.526 P=0.500 |P=0.351N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.200 (e) (e) (e) |P=0.111N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 2
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/48 (4%) 1/50 (2%) 1/50 (2%) 1/48 (2%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/42.71 1/46.10 1/46.36 1/45.75 |0/44.58 0/45.81 1/46.65 0/47.10 |
|POLY-3 PERCENT (g) | 4.7% 2.2% 2.2% 2.2% |0.0% 0.0% 2.1% 0.0% |
|TERMINAL (d) | 2/34 (6%) 1/38 (3%) 1/38 (3%) 1/40 (3%) |0/33 (0%) 0/40 (0%) 1/41 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.390N P=0.461N P=0.461N P=0.443N |P=0.675 (e) P=0.543 (e) |
|POLY 3 | P=0.425N P=0.473N P=0.471N P=0.476N |P=0.664 (e) P=0.509 (e) |
|POLY 1.5 | P=0.428N P=0.481N P=0.478N P=0.486N |P=0.658 (e) P=0.503 (e) |
|POLY 6 | P=0.421N P=0.464N P=0.464N P=0.464N |P=0.674 (e) P=0.518 (e) |
|LOGISTIC REGRESSION| P=0.390N P=0.461N P=0.461N P=0.443N |(e) (e) P=0.543 (e) |
|COCH-ARM / FISHERS | P=0.436N P=0.485N P=0.485N P=0.500N |P=0.648 (e) P=0.495 (e) |
|ORDER RESTRICTED | P=0.381N (e) (e) (e) |P=0.389 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Bone |
| Hyperostosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |5/50 (10%) 5/50 (10%) 4/50 (8%) 5/50 (10%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 2/47.91 |5/44.94 5/46.28 4/48.17 5/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.2% |11.1% 10.8% 8.3% 10.6% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 1/41 (2%) |4/33 (12%) 4/40 (10%) 3/42 (7%) 5/43 (12%) |
|FIRST INCIDENCE | --- --- --- 641 |627 589 568 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.052 (e) (e) P=0.275 |P=0.417N P=0.534N P=0.380N P=0.472N |
|POLY 3 | P=0.045 * (e) (e) P=0.256 |P=0.508N P=0.612N P=0.457N P=0.600N |
|POLY 1.5 | P=0.044 * (e) (e) P=0.248 |P=0.517N P=0.622N P=0.475N P=0.612N |
|POLY 6 | P=0.047 * (e) (e) P=0.266 |P=0.491N P=0.594N P=0.429N P=0.579N |
|LOGISTIC REGRESSION| P=0.038 * (e) (e) P=0.202 |P=0.527N P=0.626N P=0.505N P=0.582N |
|COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.247 |P=0.537N P=0.630N P=0.500N P=0.630N |
|ORDER RESTRICTED | P=0.036 * (e) (e) (e) |P=0.616N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 3
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 3/50 (6%) 3/50 (6%) 2/50 (4%) |10/50 (20%) 4/50 (8%) 9/49 (18%) 4/50 (8%) |
|POLY-3 RATE (b) | 2/44.69 3/46.52 3/46.37 2/48.25 |10/45.69 4/45.84 9/48.02 4/47.29 |
|POLY-3 PERCENT (g) | 4.5% 6.5% 6.5% 4.1% |21.9% 8.7% 18.7% 8.5% |
|TERMINAL (d) | 1/35 (3%) 2/38 (5%) 2/38 (5%) 1/41 (2%) |6/33 (18%) 3/40 (8%) 5/41 (12%) 3/43 (7%) |
|FIRST INCIDENCE | 544 610 727 506 |568 720 283 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.463N P=0.538 P=0.536 P=0.658N |P=0.120N P=0.045N* P=0.338N P=0.035N* |
|POLY 3 | P=0.483N P=0.518 P=0.517 P=0.666N |P=0.168N P=0.070N P=0.452N P=0.062N |
|POLY 1.5 | P=0.495N P=0.507 P=0.509 P=0.677N |P=0.176N P=0.073N P=0.476N P=0.066N |
|POLY 6 | P=0.470N P=0.532 P=0.526 P=0.653N |P=0.155N P=0.067N P=0.418N P=0.056N |
|LOGISTIC REGRESSION| P=0.560N P=0.506 P=0.493 P=0.493 |P=0.207N P=0.072N P=0.569N P=0.072N |
|COCH-ARM / FISHERS | P=0.516N P=0.500 P=0.500 P=0.691N |P=0.195N P=0.074N P=0.520N P=0.074N |
|ORDER RESTRICTED | P=0.566N (e) (e) (e) |P=0.045N* (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Bone: Vertebra |
| Hypertrophy Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 0/47.59 |3/45.43 2/47.05 1/48.01 1/47.88 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |6.6% 4.3% 2.1% 2.1% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- --- --- |627 521 627 445 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.195N P=0.485N P=0.271N P=0.280N |
|POLY 3 | (e) (e) (e) (e) |P=0.195N P=0.484N P=0.286N P=0.287N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.198N P=0.492N P=0.294N P=0.294N |
|POLY 6 | (e) (e) (e) (e) |P=0.191N P=0.473N P=0.274N P=0.277N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.285N P=0.475N P=0.345N P=0.396N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.203N P=0.500N P=0.309N P=0.309N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.198N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 4
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Eye: Cornea |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/45 (4%) 0/49 (0%) 0/49 (0%) 1/47 (2%) |1/43 (2%) 1/48 (2%) 1/47 (2%) 1/47 (2%) |
|POLY-3 RATE (b) | 2/40.46 0/45.12 0/45.58 1/45.73 |1/38.84 1/45.00 1/46.13 1/45.13 |
|POLY-3 PERCENT (g) | 4.9% 0.0% 0.0% 2.2% |2.6% 2.2% 2.2% 2.2% |
|TERMINAL (d) | 2/35 (6%) 0/38 (0%) 0/38 (0%) 1/41 (2%) |0/32 (0%) 0/40 (0%) 1/42 (2%) 1/42 (2%) |
|FIRST INCIDENCE | 729 (T) --- --- 729 (T) |663 680 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.495N P=0.220N P=0.220N P=0.445N |P=0.577N P=0.730N P=0.711N P=0.714N |
|POLY 3 | P=0.527N P=0.213N P=0.211N P=0.457N |P=0.598N P=0.727N P=0.721N P=0.726N |
|POLY 1.5 | P=0.525N P=0.217N P=0.215N P=0.469N |P=0.602N P=0.732N P=0.728N P=0.732N |
|POLY 6 | P=0.530N P=0.209N P=0.207N P=0.444N |P=0.593N P=0.721N P=0.712N P=0.719N |
|LOGISTIC REGRESSION| P=0.495N (e) (e) P=0.445N |P=0.623N P=0.739N P=0.770N P=0.754N |
|COCH-ARM / FISHERS | P=0.526N P=0.226N P=0.226N P=0.484N |P=0.612N P=0.725N P=0.730N P=0.730N |
|ORDER RESTRICTED | P=0.104N (e) (e) (e) |P=0.693N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Gallbladder |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/40 (0%) 0/44 (0%) 0/45 (0%) 0/44 (0%) |2/42 (5%) 0/45 (0%) 1/47 (2%) 2/44 (5%) |
|POLY-3 RATE (b) | 0/37.08 0/41.81 0/42.87 0/43.53 |2/38.36 0/42.33 1/46.13 2/43.04 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |5.2% 0.0% 2.2% 4.7% |
|TERMINAL (d) | 0/33 (0%) 0/38 (0%) 0/37 (0%) 0/41 (0%) |2/32 (6%) 0/39 (0%) 1/42 (2%) 2/42 (5%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.458 P=0.196N P=0.405N P=0.594N |
|POLY 3 | (e) (e) (e) (e) |P=0.411 P=0.215N P=0.436N P=0.652N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.408 P=0.219N P=0.444N P=0.661N |
|POLY 6 | (e) (e) (e) (e) |P=0.417 P=0.210N P=0.425N P=0.638N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.458 (e) P=0.405N P=0.594N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.396 P=0.230N P=0.457N P=0.674N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.356N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 5
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Harderian Gland: Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |1/49 (2%) 0/50 (0%) 0/50 (0%) 3/50 (6%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 1/46.36 0/47.59 |1/44.50 0/45.81 0/47.65 3/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |2.3% 0.0% 0.0% 6.4% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 1/38 (3%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 3/43 (7%) |
|FIRST INCIDENCE | --- --- 729 (T) --- |617 --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.665 (e) P=0.516 (e) |P=0.090 P=0.509N P=0.492N P=0.381 |
|POLY 3 | P=0.673 (e) P=0.510 (e) |P=0.073 P=0.494N P=0.486N P=0.326 |
|POLY 1.5 | P=0.664 (e) P=0.505 (e) |P=0.072 P=0.496N P=0.490N P=0.321 |
|POLY 6 | P=0.682 (e) P=0.515 (e) |P=0.075 P=0.491N P=0.480N P=0.336 |
|LOGISTIC REGRESSION| (e) (e) P=0.516 (e) |P=0.070 P=0.483N P=0.528N P=0.309 |
|COCH-ARM / FISHERS | P=0.649 (e) P=0.500 (e) |P=0.071 P=0.495N P=0.495N P=0.316 |
|ORDER RESTRICTED | P=0.390 (e) (e) (e) |P=0.044 * (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Harderian Gland: Epithelium |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |1/49 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/44.53 0/46.10 1/46.36 0/47.59 |1/44.10 1/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 4.5% 0.0% 2.2% 0.0% |2.3% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 1/35 (3%) 0/38 (0%) 1/38 (3%) 0/41 (0%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 605 --- 729 (T) --- |729 (T) 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.232N P=0.221N P=0.469N P=0.211N |P=0.179N P=0.718N P=0.452N P=0.447N |
|POLY 3 | P=0.249N P=0.229N P=0.486N P=0.223N |P=0.203N P=0.752N P=0.485N P=0.487N |
|POLY 1.5 | P=0.249N P=0.234N P=0.493N P=0.229N |P=0.205N P=0.755N P=0.489N P=0.490N |
|POLY 6 | P=0.249N P=0.224N P=0.479N P=0.216N |P=0.201N P=0.747N P=0.477N P=0.480N |
|LOGISTIC REGRESSION| P=0.261N P=0.233N P=0.507N P=0.286N |P=0.179N P=0.718N (e) (e) |
|COCH-ARM / FISHERS | P=0.253N P=0.247N P=0.500N P=0.247N |P=0.206N P=0.747N P=0.495N P=0.495N |
|ORDER RESTRICTED | P=0.066N (e) (e) (e) |P=0.239N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 6
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 17/50 (34%) 17/50 (34%) 7/49 (14%) 13/48 (27%) |0/46 (0%) 0/47 (0%) 0/49 (0%) 0/48 (0%) |
|POLY-3 RATE (b) | 17/45.75 17/46.89 7/45.58 13/46.63 |0/41.35 0/43.51 0/47.17 0/45.84 |
|POLY-3 PERCENT (g) | 37.2% 36.3% 15.4% 27.9% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 13/35 (37%) 13/38 (34%) 7/38 (18%) 11/41 (27%) |0/32 (0%) 0/40 (0%) 0/42 (0%) 0/42 (0%) |
|FIRST INCIDENCE | 530 638 729 (T) 610 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.053N P=0.470N P=0.011N* P=0.138N |(e) (e) (e) (e) |
|POLY 3 | P=0.096N P=0.550N P=0.014N* P=0.232N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.106N P=0.577N P=0.016N* P=0.260N |(e) (e) (e) (e) |
|POLY 6 | P=0.085N P=0.516N P=0.013N* P=0.200N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.096N P=0.557N P=0.016N* P=0.274N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.127N P=0.583N P=0.019N* P=0.301N |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.073N (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Hydronephrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/49 (4%) 0/49 (0%) 0/50 (0%) 0/48 (0%) |0/48 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/43.27 0/45.12 0/46.36 0/46.16 |0/42.61 0/45.81 0/47.59 0/47.10 |
|POLY-3 PERCENT (g) | 4.6% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/35 (3%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/32 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 723 --- --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.149N P=0.228N P=0.225N P=0.212N |(e) (e) (e) (e) |
|POLY 3 | P=0.165N P=0.228N P=0.222N P=0.223N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.161N P=0.234N P=0.227N P=0.231N |(e) (e) (e) (e) |
|POLY 6 | P=0.169N P=0.222N P=0.217N P=0.214N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.147N P=0.219N P=0.216N P=0.207N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.161N P=0.247N P=0.242N P=0.253N |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.025N* (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 7
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Infarct |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/49 (0%) 1/49 (2%) 0/50 (0%) 1/48 (2%) |0/48 (0%) 1/50 (2%) 2/49 (4%) 3/50 (6%) |
|POLY-3 RATE (b) | 0/43.24 1/45.12 0/46.36 1/46.16 |0/42.61 1/45.81 2/47.59 3/47.29 |
|POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 2.2% |0.0% 2.2% 4.2% 6.3% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 0/38 (0%) 1/41 (2%) |0/32 (0%) 1/40 (3%) 2/42 (5%) 2/43 (5%) |
|FIRST INCIDENCE | --- 729 (T) --- 729 (T) |--- 729 (T) 729 (T) 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.493 P=0.516 (e) P=0.532 |P=0.093 P=0.545 P=0.300 P=0.173 |
|POLY 3 | P=0.482 P=0.508 (e) P=0.513 |P=0.076 P=0.514 P=0.263 P=0.138 |
|POLY 1.5 | P=0.473 P=0.503 (e) P=0.506 |P=0.073 P=0.511 P=0.255 P=0.133 |
|POLY 6 | P=0.493 P=0.514 (e) P=0.521 |P=0.083 P=0.520 P=0.274 P=0.148 |
|LOGISTIC REGRESSION| (e) P=0.516 (e) P=0.532 |P=0.075 P=0.545 P=0.300 P=0.134 |
|COCH-ARM / FISHERS | P=0.460 P=0.500 (e) P=0.495 |P=0.067 P=0.510 P=0.253 P=0.129 |
|ORDER RESTRICTED | P=0.265 (e) (e) (e) |P=0.072 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Metaplasia Focal Osseous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/49 (6%) 0/49 (0%) 3/50 (6%) 4/48 (8%) |2/48 (4%) 1/50 (2%) 1/49 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 3/43.24 0/45.12 3/47.01 4/46.16 |2/42.61 1/45.81 1/47.59 0/47.10 |
|POLY-3 PERCENT (g) | 6.9% 0.0% 6.4% 8.7% |4.7% 2.2% 2.1% 0.0% |
|TERMINAL (d) | 3/35 (9%) 0/38 (0%) 1/38 (3%) 4/41 (10%) |2/32 (6%) 1/40 (3%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) --- 605 729 (T) |729 (T) 729 (T) 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.195 P=0.107N P=0.618N P=0.586 |P=0.129N P=0.422N P=0.405N P=0.176N |
|POLY 3 | P=0.162 P=0.111N P=0.623N P=0.536 |P=0.157N P=0.475N P=0.462N P=0.215N |
|POLY 1.5 | P=0.157 P=0.116N P=0.637N P=0.516 |P=0.159N P=0.481N P=0.473N P=0.221N |
|POLY 6 | P=0.170 P=0.106N P=0.607N P=0.559 |P=0.153N P=0.464N P=0.445N P=0.207N |
|LOGISTIC REGRESSION| P=0.155 (e) P=0.654N P=0.586 |P=0.129N P=0.422N P=0.405N (e) |
|COCH-ARM / FISHERS | P=0.145 P=0.121N P=0.651N P=0.488 |P=0.164N P=0.485N P=0.492N P=0.237N |
|ORDER RESTRICTED | P=0.219 (e) (e) (e) |P=0.102N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 8
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Nephropathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 40/49 (82%) 44/49 (90%) 44/50 (88%) 43/48 (90%) |6/48 (13%) 5/50 (10%) 9/49 (18%) 5/50 (10%) |
|POLY-3 RATE (b) | 40/46.05 44/46.77 44/48.41 43/46.92 |6/43.51 5/45.81 9/47.64 5/47.29 |
|POLY-3 PERCENT (g) | 86.9% 94.1% 90.9% 91.6% |13.8% 10.9% 18.9% 10.6% |
|TERMINAL (d) | 32/35 (91%) 37/38 (97%) 38/38 (100%) 38/41 (93%) |4/32 (13%) 5/40 (13%) 8/42 (19%) 4/43 (9%) |
|FIRST INCIDENCE | 536 610 605 641 |550 729 (T) 716 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.188N P=0.549 P=0.556 P=0.293N |P=0.394N P=0.378N P=0.474 P=0.343N |
|POLY 3 | P=0.433 P=0.180 P=0.375 P=0.329 |P=0.494N P=0.464N P=0.355 P=0.442N |
|POLY 1.5 | P=0.368 P=0.148 P=0.310 P=0.267 |P=0.508N P=0.470N P=0.336 P=0.454N |
|POLY 6 | P=0.513 P=0.233 P=0.453 P=0.417 |P=0.469N P=0.452N P=0.384 P=0.419N |
|LOGISTIC REGRESSION| P=0.463N P=0.357 P=0.502 P=0.613 |P=0.499N P=0.465N P=0.318 P=0.473N |
|COCH-ARM / FISHERS | P=0.258 P=0.194 P=0.274 P=0.205 |P=0.535N P=0.471N P=0.303 P=0.471N |
|ORDER RESTRICTED | P=0.269 (e) (e) (e) |P=0.458N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney: Renal Tubule |
| Accumulation, Hyaline Droplet |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/49 (0%) 0/49 (0%) 1/50 (2%) 0/48 (0%) |2/48 (4%) 0/50 (0%) 0/49 (0%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/43.24 0/45.12 1/46.52 0/46.16 |2/42.71 0/45.81 0/47.59 2/47.13 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |4.7% 0.0% 0.0% 4.2% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |1/32 (3%) 0/40 (0%) 0/42 (0%) 1/43 (2%) |
|FIRST INCIDENCE | --- --- 690 --- |704 --- --- 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.666 (e) P=0.520 (e) |P=0.487 P=0.205N P=0.188N P=0.595N |
|POLY 3 | P=0.676 (e) P=0.515 (e) |P=0.439 P=0.222N P=0.214N P=0.658N |
|POLY 1.5 | P=0.665 (e) P=0.510 (e) |P=0.438 P=0.225N P=0.221N P=0.666N |
|POLY 6 | P=0.688 (e) P=0.520 (e) |P=0.442 P=0.216N P=0.204N P=0.643N |
|LOGISTIC REGRESSION| P=0.642 (e) P=0.501 (e) |P=0.455 P=0.217N P=0.210N P=0.643N |
|COCH-ARM / FISHERS | P=0.647 (e) P=0.505 (e) |P=0.431 P=0.237N P=0.242N P=0.676N |
|ORDER RESTRICTED | P=0.394 (e) (e) (e) |P=0.235N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 9
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney: Renal Tubule |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/49 (8%) 2/49 (4%) 3/50 (6%) 2/48 (4%) |1/48 (2%) 0/50 (0%) 3/49 (6%) 0/50 (0%) |
|POLY-3 RATE (b) | 4/43.86 2/45.12 3/46.36 2/46.16 |1/42.61 0/45.81 3/47.59 0/47.10 |
|POLY-3 PERCENT (g) | 9.1% 4.4% 6.5% 4.3% |2.4% 0.0% 6.3% 0.0% |
|TERMINAL (d) | 3/35 (9%) 2/38 (5%) 3/38 (8%) 2/41 (5%) |1/32 (3%) 0/40 (0%) 3/42 (7%) 0/43 (0%) |
|FIRST INCIDENCE | 530 729 (T) 729 (T) 729 (T) |729 (T) --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.307N P=0.309N P=0.462N P=0.280N |P=0.509N P=0.455N P=0.406 P=0.441N |
|POLY 3 | P=0.344N P=0.324N P=0.470N P=0.314N |P=0.551N P=0.486N P=0.346 P=0.480N |
|POLY 1.5 | P=0.352N P=0.333N P=0.479N P=0.328N |P=0.557N P=0.489N P=0.333 P=0.485N |
|POLY 6 | P=0.333N P=0.314N P=0.460N P=0.298N |P=0.540N P=0.480N P=0.364 P=0.472N |
|LOGISTIC REGRESSION| P=0.351N P=0.336N P=0.487N P=0.376N |P=0.509N (e) P=0.406 (e) |
|COCH-ARM / FISHERS | P=0.369N P=0.339N P=0.489N P=0.349N |P=0.569N P=0.490N P=0.316 P=0.490N |
|ORDER RESTRICTED | P=0.275N (e) (e) (e) |P=0.274N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Kidney: Renal Tubule |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/49 (6%) 1/49 (2%) 1/50 (2%) 1/48 (2%) |0/48 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 3/43.24 1/45.26 1/46.36 1/46.16 |0/42.61 0/45.81 0/47.59 0/47.10 |
|POLY-3 PERCENT (g) | 6.9% 2.2% 2.2% 2.2% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 3/35 (9%) 0/38 (0%) 1/38 (3%) 1/41 (2%) |0/32 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 694 729 (T) 729 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.244N P=0.274N P=0.276N P=0.250N |(e) (e) (e) (e) |
|POLY 3 | P=0.276N P=0.289N P=0.281N P=0.282N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.278N P=0.299N P=0.289N P=0.295N |(e) (e) (e) (e) |
|POLY 6 | P=0.273N P=0.278N P=0.272N P=0.268N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.251N P=0.280N P=0.276N P=0.250N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.286N P=0.309N P=0.301N P=0.316N |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.164N (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 10
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Angiectasis Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 0/46.75 |2/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.5% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |2/33 (6%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.136N P=0.197N P=0.187N P=0.182N |
|POLY 3 | (e) (e) (e) (e) |P=0.160N P=0.231N P=0.223N P=0.225N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.159N P=0.235N P=0.229N P=0.230N |
|POLY 6 | (e) (e) (e) (e) |P=0.163N P=0.225N P=0.213N P=0.217N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.136N (e) (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.160N P=0.247N P=0.247N P=0.247N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.025N* (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Basophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 3/50 (6%) |
|POLY-3 RATE (b) | 0/44.11 1/46.10 0/46.36 0/46.75 |0/44.58 1/45.81 0/47.65 3/47.10 |
|POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |0.0% 2.2% 0.0% 6.4% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 1/40 (3%) 0/42 (0%) 3/43 (7%) |
|FIRST INCIDENCE | --- 729 (T) --- --- |--- 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.430N P=0.516 (e) (e) |P=0.075 P=0.538 (e) P=0.172 |
|POLY 3 | P=0.443N P=0.509 (e) (e) |P=0.058 P=0.505 (e) P=0.129 |
|POLY 1.5 | P=0.449N P=0.504 (e) (e) |P=0.056 P=0.502 (e) P=0.125 |
|POLY 6 | P=0.438N P=0.515 (e) (e) |P=0.061 P=0.511 (e) P=0.137 |
|LOGISTIC REGRESSION| (e) P=0.516 (e) (e) |(e) P=0.538 (e) P=0.172 |
|COCH-ARM / FISHERS | P=0.452N P=0.500 (e) (e) |P=0.054 P=0.500 (e) P=0.121 |
|ORDER RESTRICTED | P=0.379N (e) (e) (e) |P=0.024 * (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 11
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Clear Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 20/50 (40%) 19/50 (38%) 22/50 (44%) 16/49 (33%) |3/50 (6%) 3/50 (6%) 4/50 (8%) 2/50 (4%) |
|POLY-3 RATE (b) | 20/44.53 19/46.20 22/46.36 16/47.16 |3/44.83 3/45.81 4/47.65 2/47.13 |
|POLY-3 PERCENT (g) | 44.9% 41.1% 47.5% 33.9% |6.7% 6.6% 8.4% 4.2% |
|TERMINAL (d) | 19/35 (54%) 18/38 (47%) 22/38 (58%) 15/41 (37%) |2/33 (6%) 3/40 (8%) 4/42 (10%) 1/43 (2%) |
|FIRST INCIDENCE | 605 704 729 (T) 610 |663 729 (T) 729 (T) 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.108N P=0.361N P=0.567 P=0.101N |P=0.326N P=0.579N P=0.622 P=0.393N |
|POLY 3 | P=0.199N P=0.439N P=0.487 P=0.192N |P=0.398N P=0.652N P=0.533 P=0.477N |
|POLY 1.5 | P=0.233N P=0.478N P=0.454 P=0.231N |P=0.408N P=0.659N P=0.519 P=0.486N |
|POLY 6 | P=0.161N P=0.395N P=0.522 P=0.151N |P=0.382N P=0.642N P=0.555 P=0.461N |
|LOGISTIC REGRESSION| P=0.142N P=0.345N P=0.571 P=0.144N |P=0.376N P=0.643N P=0.552 P=0.477N |
|COCH-ARM / FISHERS | P=0.299N P=0.500N P=0.420 P=0.291N |P=0.425N P=0.661N P=0.500 P=0.500N |
|ORDER RESTRICTED | P=0.223N (e) (e) (e) |P=0.446N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Congestion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/49 (2%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 1/46.89 |1/45.56 2/46.42 1/47.65 1/47.13 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.1% |2.2% 4.3% 2.1% 2.1% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 1/40 (3%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- --- 694 |185 533 729 (T) 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.201 (e) (e) P=0.529 |P=0.436N P=0.517 P=0.734N P=0.729N |
|POLY 3 | P=0.193 (e) (e) P=0.512 |P=0.466N P=0.506 P=0.751N P=0.753N |
|POLY 1.5 | P=0.190 (e) (e) P=0.505 |P=0.472N P=0.500 P=0.756N P=0.757N |
|POLY 6 | P=0.197 (e) (e) P=0.520 |P=0.455N P=0.517 P=0.741N P=0.744N |
|LOGISTIC REGRESSION| P=0.178 (e) (e) P=0.482 |P=0.589N P=0.566 P=0.705 P=0.624 |
|COCH-ARM / FISHERS | P=0.184 (e) (e) P=0.495 |P=0.477N P=0.500 P=0.753N P=0.753N |
|ORDER RESTRICTED | P=0.131 (e) (e) (e) |P=0.575N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 12
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Eosinophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/50 (4%) 2/49 (4%) |1/50 (2%) 1/50 (2%) 3/50 (6%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/44.11 2/46.10 2/46.36 2/46.75 |1/44.58 1/45.81 3/47.65 1/47.13 |
|POLY-3 PERCENT (g) | 0.0% 4.3% 4.3% 4.3% |2.2% 2.2% 6.3% 2.1% |
|TERMINAL (d) | 0/35 (0%) 2/38 (5%) 2/38 (5%) 2/41 (5%) |1/33 (3%) 1/40 (3%) 3/42 (7%) 0/43 (0%) |
|FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |729 (T) 729 (T) 729 (T) 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.326 P=0.257 P=0.257 P=0.274 |P=0.598 P=0.718N P=0.395 P=0.698N |
|POLY 3 | P=0.307 P=0.247 P=0.248 P=0.250 |P=0.547 P=0.755N P=0.330 P=0.748N |
|POLY 1.5 | P=0.294 P=0.241 P=0.243 P=0.243 |P=0.538 P=0.758N P=0.319 P=0.753N |
|POLY 6 | P=0.322 P=0.254 P=0.254 P=0.260 |P=0.564 P=0.748N P=0.347 P=0.739N |
|LOGISTIC REGRESSION| (e) P=0.257 P=0.257 P=0.274 |P=0.582 P=0.718N P=0.395 P=0.729N |
|COCH-ARM / FISHERS | P=0.274 P=0.247 P=0.247 P=0.242 |P=0.521 P=0.753N P=0.309 P=0.753N |
|ORDER RESTRICTED | P=0.198 (e) (e) (e) |P=0.466 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/49 (0%) |4/50 (8%) 1/50 (2%) 6/50 (12%) 2/50 (4%) |
|POLY-3 RATE (b) | 1/44.53 2/46.10 0/46.36 0/46.75 |4/45.25 1/45.99 6/47.70 2/47.10 |
|POLY-3 PERCENT (g) | 2.3% 4.3% 0.0% 0.0% |8.8% 2.2% 12.6% 4.3% |
|TERMINAL (d) | 0/35 (0%) 2/38 (5%) 0/38 (0%) 0/41 (0%) |2/33 (6%) 0/40 (0%) 5/42 (12%) 2/43 (5%) |
|FIRST INCIDENCE | 605 729 (T) --- --- |604 680 716 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.121N P=0.529 P=0.479N P=0.479N |P=0.445N P=0.150N P=0.506 P=0.253N |
|POLY 3 | P=0.130N P=0.512 P=0.492N P=0.490N |P=0.521N P=0.174N P=0.403 P=0.319N |
|POLY 1.5 | P=0.132N P=0.504 P=0.496N P=0.496N |P=0.527N P=0.177N P=0.389 P=0.326N |
|POLY 6 | P=0.127N P=0.520 P=0.488N P=0.484N |P=0.509N P=0.167N P=0.426 P=0.306N |
|LOGISTIC REGRESSION| P=0.140N P=0.500 P=0.484N P=0.647N |P=0.532N P=0.179N P=0.383 P=0.341N |
|COCH-ARM / FISHERS | P=0.136N P=0.500 P=0.500N P=0.505N |P=0.544N P=0.181N P=0.370 P=0.339N |
|ORDER RESTRICTED | P=0.166N (e) (e) (e) |P=0.306N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 13
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Infiltration Cellular Mixed Cell |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 2/50 (4%) 6/49 (12%) |11/50 (22%) 12/50 (24%) 12/50 (24%) 15/50 (30%) |
|POLY-3 RATE (b) | 3/44.53 1/46.10 2/46.36 6/46.75 |11/45.51 12/46.44 12/47.71 15/47.10 |
|POLY-3 PERCENT (g) | 6.7% 2.2% 4.3% 12.8% |24.2% 25.8% 25.2% 31.8% |
|TERMINAL (d) | 2/35 (6%) 1/38 (3%) 2/38 (5%) 6/41 (15%) |9/33 (27%) 11/40 (28%) 10/42 (24%) 15/43 (35%) |
|FIRST INCIDENCE | 605 729 (T) 729 (T) 729 (T) |550 521 716 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.086 P=0.278N P=0.460N P=0.323 |P=0.414 P=0.511N P=0.448N P=0.515 |
|POLY 3 | P=0.062 P=0.293N P=0.482N P=0.267 |P=0.237 P=0.522 P=0.552 P=0.277 |
|POLY 1.5 | P=0.060 P=0.301N P=0.490N P=0.253 |P=0.229 P=0.508 P=0.529 P=0.266 |
|POLY 6 | P=0.065 P=0.284N P=0.473N P=0.283 |P=0.257 P=0.545 P=0.589 P=0.304 |
|LOGISTIC REGRESSION| P=0.070 P=0.304N P=0.493N P=0.268 |P=0.261 P=0.512 P=0.567 P=0.313 |
|COCH-ARM / FISHERS | P=0.057 P=0.309N P=0.500N P=0.233 |P=0.209 P=0.500 P=0.500 P=0.247 |
|ORDER RESTRICTED | P=0.076 (e) (e) (e) |P=0.322 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Mixed Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 0/50 (0%) 0/49 (0%) |2/50 (4%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 3/44.11 1/46.10 0/46.36 0/46.75 |2/44.87 1/45.81 0/47.65 1/47.10 |
|POLY-3 PERCENT (g) | 6.8% 2.2% 0.0% 0.0% |4.5% 2.2% 0.0% 2.1% |
|TERMINAL (d) | 3/35 (9%) 1/38 (3%) 0/38 (0%) 0/41 (0%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 1/43 (2%) |
|FIRST INCIDENCE | 729 (T) 729 (T) --- --- |650 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.046N* P=0.276N P=0.107N P=0.095N |P=0.326N P=0.450N P=0.204N P=0.429N |
|POLY 3 | P=0.054N P=0.290N P=0.110N P=0.109N |P=0.368N P=0.493N P=0.224N P=0.483N |
|POLY 1.5 | P=0.054N P=0.299N P=0.114N P=0.114N |P=0.370N P=0.498N P=0.230N P=0.490N |
|POLY 6 | P=0.054N P=0.279N P=0.105N P=0.102N |P=0.365N P=0.485N P=0.216N P=0.471N |
|LOGISTIC REGRESSION| P=0.046N* P=0.276N (e) (e) |P=0.368N P=0.498N P=0.244N P=0.499N |
|COCH-ARM / FISHERS | P=0.056N P=0.309N P=0.121N P=0.125N |P=0.374N P=0.500N P=0.247N P=0.500N |
|ORDER RESTRICTED | P=0.017N* (e) (e) (e) |P=0.209N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 14
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Thrombosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 1/49 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 2/46.26 1/46.49 1/46.84 |0/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 4.3% 2.2% 2.1% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- 694 696 705 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.609 P=0.263 P=0.516 P=0.530 |(e) (e) (e) (e) |
|POLY 3 | P=0.603 P=0.248 P=0.511 P=0.512 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.590 P=0.242 P=0.506 P=0.505 |(e) (e) (e) (e) |
|POLY 6 | P=0.620 P=0.256 P=0.516 P=0.520 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.574 P=0.242 P=0.499 P=0.497 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.570 P=0.247 P=0.500 P=0.495 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.281 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Necrosis Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 4/49 (8%) |3/50 (6%) 3/50 (6%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/44.69 2/46.26 2/46.80 4/47.26 |3/44.61 3/46.02 1/47.74 0/47.10 |
|POLY-3 PERCENT (g) | 4.5% 4.3% 4.3% 8.5% |6.7% 6.5% 2.1% 0.0% |
|TERMINAL (d) | 1/35 (3%) 0/38 (0%) 0/38 (0%) 1/41 (2%) |2/33 (6%) 2/40 (5%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 544 694 645 641 |721 673 705 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.264 P=0.664N P=0.663N P=0.402 |P=0.030N* P=0.576N P=0.227N P=0.081N |
|POLY 3 | P=0.233 P=0.681N P=0.677N P=0.363 |P=0.039N* P=0.648N P=0.282N P=0.109N |
|POLY 1.5 | P=0.225 P=0.689N P=0.685N P=0.348 |P=0.041N* P=0.656N P=0.292N P=0.113N |
|POLY 6 | P=0.245 P=0.672N P=0.667N P=0.383 |P=0.037N* P=0.634N P=0.266N P=0.103N |
|LOGISTIC REGRESSION| P=0.180 P=0.693N P=0.687 P=0.233 |P=0.039N* P=0.642N P=0.263N P=0.090N |
|COCH-ARM / FISHERS | P=0.209 P=0.691N P=0.691N P=0.329 |P=0.044N* P=0.661N P=0.309N P=0.121N |
|ORDER RESTRICTED | P=0.307 (e) (e) (e) |P=0.068N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 15
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 29/50 (58%) 19/50 (38%) 32/50 (64%) 23/49 (47%) |12/50 (24%) 11/50 (22%) 8/50 (16%) 15/50 (30%) |
|POLY-3 RATE (b) | 29/45.11 19/46.10 32/47.46 23/47.16 |12/46.70 11/46.20 8/47.65 15/47.39 |
|POLY-3 PERCENT (g) | 64.3% 41.2% 67.4% 48.8% |25.7% 23.8% 16.8% 31.7% |
|TERMINAL (d) | 27/35 (77%) 19/38 (50%) 29/38 (76%) 22/41 (54%) |4/33 (12%) 10/40 (25%) 8/42 (19%) 13/43 (30%) |
|FIRST INCIDENCE | 548 729 (T) 605 610 |604 616 729 (T) 659 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.212N P=0.006N** P=0.553 P=0.023N* |P=0.465 P=0.369N P=0.124N P=0.569 |
|POLY 3 | P=0.392N P=0.019N* P=0.460 P=0.092N |P=0.288 P=0.512N P=0.210N P=0.341 |
|POLY 1.5 | P=0.443N P=0.026N* P=0.398 P=0.126N |P=0.284 P=0.510N P=0.216N P=0.338 |
|POLY 6 | P=0.328N P=0.012N* P=0.541 P=0.060N |P=0.298 P=0.514N P=0.202N P=0.351 |
|LOGISTIC REGRESSION| P=0.320N P=0.008N** P=0.541 P=0.054N |P=0.295 P=0.498N P=0.231N P=0.335 |
|COCH-ARM / FISHERS | P=0.534 P=0.036N* P=0.341 P=0.184N |P=0.268 P=0.500N P=0.227N P=0.326 |
|ORDER RESTRICTED | P=0.092N (e) (e) (e) |P=0.218 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 3/50 (6%) 2/50 (4%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/44.13 0/46.10 3/46.49 2/47.59 |1/44.58 0/45.81 0/47.65 1/47.10 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 6.5% 4.2% |2.2% 0.0% 0.0% 2.1% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 2/38 (5%) 2/41 (5%) |1/33 (3%) 0/40 (0%) 0/42 (0%) 1/43 (2%) |
|FIRST INCIDENCE | 723 --- 696 729 (T) |729 (T) --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.222 P=0.489N P=0.334 P=0.548 |P=0.579 P=0.462N P=0.452N P=0.702N |
|POLY 3 | P=0.205 P=0.491N P=0.324 P=0.526 |P=0.543 P=0.495N P=0.487N P=0.748N |
|POLY 1.5 | P=0.199 P=0.497N P=0.315 P=0.515 |P=0.541 P=0.498N P=0.492N P=0.753N |
|POLY 6 | P=0.213 P=0.485N P=0.334 P=0.539 |P=0.545 P=0.489N P=0.478N P=0.739N |
|LOGISTIC REGRESSION| P=0.211 P=0.483N P=0.331 P=0.550 |P=0.579 (e) (e) P=0.702N |
|COCH-ARM / FISHERS | P=0.185 P=0.500N P=0.309 P=0.500 |P=0.536 P=0.500N P=0.500N P=0.753N |
|ORDER RESTRICTED | P=0.203 (e) (e) (e) |P=0.383N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 16
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 3/50 (6%) 2/50 (4%) 3/50 (6%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 4/44.53 3/46.10 2/46.49 3/47.59 |2/44.97 0/45.81 1/47.65 1/47.10 |
|POLY-3 PERCENT (g) | 9.0% 6.5% 4.3% 6.3% |4.5% 0.0% 2.1% 2.1% |
|TERMINAL (d) | 3/35 (9%) 3/38 (8%) 1/38 (3%) 3/41 (7%) |0/33 (0%) 0/40 (0%) 1/42 (2%) 1/43 (2%) |
|FIRST INCIDENCE | 605 729 (T) 696 729 (T) |650 --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.361N P=0.455N P=0.301N P=0.418N |P=0.527N P=0.224N P=0.437N P=0.439N |
|POLY 3 | P=0.403N P=0.481N P=0.317N P=0.464N |P=0.568N P=0.233N P=0.480N P=0.484N |
|POLY 1.5 | P=0.410N P=0.493N P=0.327N P=0.479N |P=0.570N P=0.236N P=0.488N P=0.490N |
|POLY 6 | P=0.395N P=0.468N P=0.307N P=0.448N |P=0.565N P=0.229N P=0.467N P=0.473N |
|LOGISTIC REGRESSION| P=0.394N P=0.482N P=0.331N P=0.472N |P=0.576N P=0.237N P=0.508N P=0.507N |
|COCH-ARM / FISHERS | P=0.425N P=0.500N P=0.339N P=0.500N |P=0.576N P=0.247N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.381N (e) (e) (e) |P=0.255N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mandibular |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/43 (5%) 1/46 (2%) 0/48 (0%) 2/47 (4%) |9/48 (19%) 11/49 (22%) 12/48 (25%) 16/46 (35%) |
|POLY-3 RATE (b) | 2/38.60 1/43.19 0/44.77 2/45.00 |9/43.10 11/45.28 12/46.01 16/43.91 |
|POLY-3 PERCENT (g) | 5.2% 2.3% 0.0% 4.4% |20.9% 24.3% 26.1% 36.4% |
|TERMINAL (d) | 1/31 (3%) 0/35 (0%) 0/38 (0%) 2/39 (5%) |8/31 (26%) 10/39 (26%) 11/40 (28%) 14/39 (36%) |
|FIRST INCIDENCE | 478 452 --- 729 (T) |568 589 627 528 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.609 P=0.493N P=0.220N P=0.631N |P=0.128 P=0.597N P=0.545 P=0.211 |
|POLY 3 | P=0.600 P=0.461N P=0.205N P=0.638N |P=0.058 P=0.449 P=0.372 P=0.084 |
|POLY 1.5 | P=0.599 P=0.470N P=0.209N P=0.648N |P=0.052 P=0.432 P=0.345 P=0.074 |
|POLY 6 | P=0.603 P=0.450N P=0.199N P=0.625N |P=0.071 P=0.478 P=0.417 P=0.104 |
|LOGISTIC REGRESSION| P=0.510 P=0.390N P=0.195N P=0.629 |P=0.054 P=0.452 P=0.376 P=0.078 |
|COCH-ARM / FISHERS | P=0.593 P=0.474N P=0.221N P=0.657N |P=0.043 * P=0.421 P=0.311 P=0.063 |
|ORDER RESTRICTED | P=0.344N (e) (e) (e) |P=0.078 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 17
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/47 (0%) 0/50 (0%) 0/48 (0%) 0/48 (0%) |0/46 (0%) 1/49 (2%) 2/49 (4%) 0/48 (0%) |
|POLY-3 RATE (b) | 0/41.29 0/46.10 0/44.58 0/46.15 |0/40.91 1/44.84 2/46.66 0/45.73 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 2.2% 4.3% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/37 (0%) 0/41 (0%) |0/30 (0%) 1/40 (3%) 2/42 (5%) 0/42 (0%) |
|FIRST INCIDENCE | --- --- --- --- |--- 729 (T) 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.526N P=0.557 P=0.315 (e) |
|POLY 3 | (e) (e) (e) (e) |P=0.558N P=0.518 P=0.267 (e) |
|POLY 1.5 | (e) (e) (e) (e) |P=0.567N P=0.515 P=0.261 (e) |
|POLY 6 | (e) (e) (e) (e) |P=0.542N P=0.524 P=0.278 (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.557 P=0.315 (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.583N P=0.516 P=0.263 (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.334N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/47 (0%) 0/50 (0%) 3/48 (6%) 0/48 (0%) |1/46 (2%) 2/49 (4%) 2/49 (4%) 1/48 (2%) |
|POLY-3 RATE (b) | 0/41.29 0/46.10 3/45.08 0/46.15 |1/40.91 2/45.00 2/46.66 1/45.73 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 0.0% |2.4% 4.4% 4.3% 2.2% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/37 (0%) 0/41 (0%) |1/30 (3%) 1/40 (3%) 2/42 (5%) 1/42 (2%) |
|FIRST INCIDENCE | --- --- 645 --- |729 (T) 688 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.505 (e) P=0.146 (e) |P=0.439N P=0.581 P=0.617 P=0.685N |
|POLY 3 | P=0.513 (e) P=0.135 (e) |P=0.487N P=0.533 P=0.546 P=0.735N |
|POLY 1.5 | P=0.497 (e) P=0.129 (e) |P=0.497N P=0.527 P=0.536 P=0.742N |
|POLY 6 | P=0.533 (e) P=0.142 (e) |P=0.472N P=0.544 P=0.561 P=0.725N |
|LOGISTIC REGRESSION| P=0.449 (e) P=0.119 (e) |P=0.476N P=0.535 P=0.617 P=0.685N |
|COCH-ARM / FISHERS | P=0.469 (e) P=0.125 (e) |P=0.513N P=0.524 P=0.524 P=0.742N |
|ORDER RESTRICTED | P=0.180 (e) (e) (e) |P=0.541N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 18
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/47 (4%) 2/50 (4%) 2/48 (4%) 0/48 (0%) |6/46 (13%) 7/49 (14%) 10/49 (20%) 8/48 (17%) |
|POLY-3 RATE (b) | 2/41.29 2/46.10 2/44.58 0/46.15 |6/41.27 7/44.84 10/46.71 8/45.73 |
|POLY-3 PERCENT (g) | 4.8% 4.3% 4.5% 0.0% |14.5% 15.6% 21.4% 17.5% |
|TERMINAL (d) | 2/35 (6%) 2/38 (5%) 2/37 (5%) 0/41 (0%) |5/30 (17%) 7/40 (18%) 9/42 (21%) 8/42 (19%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |627 729 (T) 716 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.134N P=0.665N P=0.675N P=0.204N |P=0.500 P=0.536N P=0.443 P=0.595N |
|POLY 3 | P=0.143N P=0.654N P=0.666N P=0.213N |P=0.372 P=0.564 P=0.290 P=0.467 |
|POLY 1.5 | P=0.149N P=0.664N P=0.676N P=0.221N |P=0.353 P=0.554 P=0.272 P=0.449 |
|POLY 6 | P=0.136N P=0.642N P=0.656N P=0.204N |P=0.403 P=0.581 P=0.320 P=0.498 |
|LOGISTIC REGRESSION| P=0.134N P=0.665N P=0.675N (e) |P=0.433 P=0.601 P=0.332 P=0.514 |
|COCH-ARM / FISHERS | P=0.160N P=0.668N P=0.684N P=0.242N |P=0.317 P=0.549 P=0.248 P=0.420 |
|ORDER RESTRICTED | P=0.168N (e) (e) (e) |P=0.437 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Iliac |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 1/3 (33%) 0/3 (0%) 0/6 (0%) |1/7 (14%) 0/5 (0%) 2/10 (20%) 2/10 (20%) |
|POLY-3 RATE (b) | 0/5.00 1/2.95 0/2.56 0/5.69 |1/6.69 0/3.99 2/9.42 2/8.17 |
|POLY-3 PERCENT (g) | 0.0% 33.9% 0.0% 0.0% |15.0% 0.0% 21.2% 24.5% |
|TERMINAL (d) | 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/4 (0%) |0/3 (0%) 0/2 (0%) 2/8 (25%) 1/5 (20%) |
|FIRST INCIDENCE | --- 676 --- --- |655 --- 729 (T) 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.428N P=0.525 (e) (e) |P=0.320 P=0.481N P=0.735 P=0.597 |
|POLY 3 | P=0.407N P=0.389 (e) (e) |P=0.319 P=0.600N P=0.623 P=0.574 |
|POLY 1.5 | P=0.400N P=0.390 (e) (e) |P=0.328 P=0.585N P=0.624 P=0.593 |
|POLY 6 | P=0.421N P=0.385 (e) (e) |P=0.322 P=0.619N P=0.626 P=0.561 |
|LOGISTIC REGRESSION| P=0.310N (e) (e) (e) |P=0.315 P=0.467N P=0.631 P=0.619 |
|COCH-ARM / FISHERS | P=0.398N P=0.375 (e) (e) |P=0.344 P=0.583N P=0.640 P=0.640 |
|ORDER RESTRICTED | P=0.261N (e) (e) (e) |P=0.363 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 19
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 0/3 (0%) 0/3 (0%) 1/6 (17%) |2/7 (29%) 0/5 (0%) 0/10 (0%) 1/10 (10%) |
|POLY-3 RATE (b) | 0/5.00 0/2.75 0/2.56 1/5.69 |2/6.41 0/3.99 0/9.42 1/7.99 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 17.6% |31.2% 0.0% 0.0% 12.5% |
|TERMINAL (d) | 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/4 (25%) |2/3 (67%) 0/2 (0%) 0/8 (0%) 1/5 (20%) |
|FIRST INCIDENCE | --- --- --- 729 (T) |729 (T) --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.236 (e) (e) P=0.455 |P=0.314N P=0.309N P=0.055N P=0.298N |
|POLY 3 | P=0.255 (e) (e) P=0.526 |P=0.347N P=0.337N P=0.132N P=0.417N |
|POLY 1.5 | P=0.258 (e) (e) P=0.531 |P=0.361N P=0.322N P=0.136N P=0.401N |
|POLY 6 | P=0.251 (e) (e) P=0.516 |P=0.329N P=0.356N P=0.123N P=0.426N |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.455 |P=0.314N (e) (e) P=0.298N |
|COCH-ARM / FISHERS | P=0.245 (e) (e) P=0.545 |P=0.378N P=0.318N P=0.154N P=0.360N |
|ORDER RESTRICTED | P=0.146 (e) (e) (e) |P=0.075N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Mesentery: Fat |
| Necrosis Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/5 (60%) 7/11 (64%) 4/5 (80%) 0/4 (0%) |16/18 (89%) 12/14 (86%) 13/15 (87%) 4/13 (31%) |
|POLY-3 RATE (b) | 3/4.79 7/9.91 4/4.87 0/3.80 |16/17.96 12/13.30 13/14.69 4/11.17 |
|POLY-3 PERCENT (g) | 62.7% 70.7% 82.2% 0.0% |89.1% 90.2% 88.5% 35.8% |
|TERMINAL (d) | 2/3 (67%) 6/8 (75%) 3/3 (100%) 0/2 (0%) |11/12 (92%) 10/10 (100%) 9/10 (90%) 2/7 (29%) |
|FIRST INCIDENCE | 665 717 645 --- |550 533 568 659 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.087N P=0.644 P=0.525 P=0.142N |P=0.007N** P=0.325N P=0.397N P=0.008N** |
|POLY 3 | P=0.030N* P=0.613 P=0.516 P=0.083N |P<0.001N** P=0.695 P=0.692N P<0.001N** |
|POLY 1.5 | P=0.037N* P=0.626 P=0.508 P=0.085N |P<0.001N** P=0.691N P=0.663N P<0.001N** |
|POLY 6 | P=0.025N* P=0.613 P=0.529 P=0.079N |P<0.001N** P=0.614 P=0.706 P=0.003N** |
|LOGISTIC REGRESSION| P=0.045N* P=0.719 P=0.500 P=0.119N |P<0.001N** P=0.633N P=0.633N P=0.002N** |
|COCH-ARM / FISHERS | P=0.066N P=0.654 P=0.500 P=0.119N |P<0.001N** P=0.597N P=0.626N P<0.001N** |
|ORDER RESTRICTED | P=0.041N* (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 20
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Nose |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 3/50 (6%) 3/50 (6%) 6/50 (12%) |0/50 (0%) 3/50 (6%) 7/50 (14%) 11/50 (22%) |
|POLY-3 RATE (b) | 1/44.11 3/46.43 3/47.81 6/48.32 |0/44.58 3/45.81 7/47.71 11/47.91 |
|POLY-3 PERCENT (g) | 2.3% 6.5% 6.3% 12.4% |0.0% 6.6% 14.7% 23.0% |
|TERMINAL (d) | 1/35 (3%) 2/38 (5%) 0/38 (0%) 3/41 (7%) |0/33 (0%) 3/40 (8%) 5/42 (12%) 9/43 (21%) |
|FIRST INCIDENCE | 729 (T) 638 261 610 |--- 729 (T) 716 445 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.068 P=0.339 P=0.337 P=0.095 |P<0.001 ** P=0.157 P=0.023 * P=0.003 ** |
|POLY 3 | P=0.055 P=0.324 P=0.335 P=0.072 |P<0.001 ** P=0.124 P=0.010 * P<0.001 ** |
|POLY 1.5 | P=0.051 P=0.313 P=0.323 P=0.065 |P<0.001 ** P=0.121 P=0.009 ** P<0.001 ** |
|POLY 6 | P=0.062 P=0.337 P=0.348 P=0.082 |P<0.001 ** P=0.129 P=0.012 * P<0.001 ** |
|LOGISTIC REGRESSION| P=0.025 * P=0.310 P=0.287 P=0.051 |P<0.001 ** P=0.157 P=0.017 * P<0.001 ** |
|COCH-ARM / FISHERS | P=0.043 * P=0.309 P=0.309 P=0.056 |P<0.001 ** P=0.121 P=0.006 ** P<0.001 ** |
|ORDER RESTRICTED | P=0.039 * (e) (e) (e) |P<0.001 ** (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Nose: Nasolacrimal Duct |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 3/44.24 0/46.10 1/46.36 1/47.59 |0/44.58 1/46.42 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 6.8% 0.0% 2.2% 2.1% |0.0% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 2/35 (6%) 0/38 (0%) 1/38 (3%) 1/41 (2%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 694 --- 729 (T) 729 (T) |--- 533 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.348N P=0.108N P=0.279N P=0.253N |P=0.454N P=0.496 (e) (e) |
|POLY 3 | P=0.383N P=0.111N P=0.289N P=0.280N |P=0.439N P=0.508 (e) (e) |
|POLY 1.5 | P=0.382N P=0.116N P=0.297N P=0.290N |P=0.444N P=0.504 (e) (e) |
|POLY 6 | P=0.384N P=0.107N P=0.280N P=0.268N |P=0.431N P=0.515 (e) (e) |
|LOGISTIC REGRESSION| P=0.358N P=0.109N P=0.277N P=0.266N |P=0.519N P=0.535 (e) (e) |
|COCH-ARM / FISHERS | P=0.387N P=0.121N P=0.309N P=0.309N |P=0.449N P=0.500 (e) (e) |
|ORDER RESTRICTED | P=0.087N (e) (e) (e) |P=0.378N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 21
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |3/47 (6%) 2/48 (4%) 0/49 (0%) 2/48 (4%) |
|POLY-3 RATE (b) | |3/42.25 2/44.02 0/46.65 2/45.10 |
|POLY-3 PERCENT (g) | |7.1% 4.5% 0.0% 4.4% |
|TERMINAL (d) | |2/32 (6%) 2/39 (5%) 0/41 (0%) 2/41 (5%) |
|FIRST INCIDENCE | |673 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.301N P=0.417N P=0.086N P=0.396N |
|POLY 3 | |P=0.349N P=0.481N P=0.102N P=0.470N |
|POLY 1.5 | |P=0.352N P=0.487N P=0.106N P=0.478N |
|POLY 6 | |P=0.344N P=0.471N P=0.096N P=0.456N |
|LOGISTIC REGRESSION| |P=0.334N P=0.472N P=0.107N P=0.462N |
|COCH-ARM / FISHERS | |P=0.359N P=0.490N P=0.113N P=0.490N |
|ORDER RESTRICTED | |P=0.189N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |12/47 (26%) 12/48 (25%) 16/49 (33%) 13/48 (27%) |
|POLY-3 RATE (b) | |12/43.21 12/45.11 16/47.47 13/45.91 |
|POLY-3 PERCENT (g) | |27.8% 26.6% 33.7% 28.3% |
|TERMINAL (d) | |9/32 (28%) 10/39 (26%) 12/41 (29%) 11/41 (27%) |
|FIRST INCIDENCE | |550 533 627 528 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.497N P=0.419N P=0.502 P=0.444N |
|POLY 3 | |P=0.449 P=0.546N P=0.351 P=0.571 |
|POLY 1.5 | |P=0.435 P=0.561N P=0.326 P=0.553 |
|POLY 6 | |P=0.478 P=0.522N P=0.395 P=0.585N |
|LOGISTIC REGRESSION| |P=0.415 P=0.568N P=0.313 P=0.537 |
|COCH-ARM / FISHERS | |P=0.401 P=0.570N P=0.294 P=0.525 |
|ORDER RESTRICTED | |P=0.542 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 22
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Thrombosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |3/47 (6%) 0/48 (0%) 0/49 (0%) 3/48 (6%) |
|POLY-3 RATE (b) | |3/42.04 0/44.02 0/46.65 3/45.91 |
|POLY-3 PERCENT (g) | |7.1% 0.0% 0.0% 6.5% |
|TERMINAL (d) | |3/32 (9%) 0/39 (0%) 0/41 (0%) 1/41 (2%) |
|FIRST INCIDENCE | |729 (T) --- --- 528 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.410 P=0.088N P=0.081N P=0.569N |
|POLY 3 | |P=0.371 P=0.110N P=0.101N P=0.621N |
|POLY 1.5 | |P=0.369 P=0.113N P=0.105N P=0.634N |
|POLY 6 | |P=0.374 P=0.105N P=0.094N P=0.600N |
|LOGISTIC REGRESSION| |P=0.348 (e) (e) P=0.658 |
|COCH-ARM / FISHERS | |P=0.362 P=0.117N P=0.113N P=0.651N |
|ORDER RESTRICTED | |P=0.154N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Pancreas: Duct |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/48 (0%) 0/50 (0%) 1/49 (2%) 0/48 (0%) |2/46 (4%) 0/46 (0%) 2/49 (4%) 2/49 (4%) |
|POLY-3 RATE (b) | 0/42.16 0/46.10 1/45.58 0/46.16 |2/41.68 0/42.91 2/47.17 2/46.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |4.8% 0.0% 4.2% 4.3% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 1/38 (3%) 0/41 (0%) |1/32 (3%) 0/40 (0%) 2/42 (5%) 2/42 (5%) |
|FIRST INCIDENCE | --- --- 729 (T) --- |638 --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.665 (e) P=0.516 (e) |P=0.421 P=0.215N P=0.612N P=0.612N |
|POLY 3 | P=0.676 (e) P=0.516 (e) |P=0.391 P=0.231N P=0.649N P=0.657N |
|POLY 1.5 | P=0.666 (e) P=0.510 (e) |P=0.391 P=0.235N P=0.658N P=0.662N |
|POLY 6 | P=0.689 (e) P=0.522 (e) |P=0.393 P=0.224N P=0.634N P=0.647N |
|LOGISTIC REGRESSION| (e) (e) P=0.516 (e) |P=0.390 P=0.238N P=0.672N P=0.669N |
|COCH-ARM / FISHERS | P=0.647 (e) P=0.505 (e) |P=0.383 P=0.247N P=0.667N P=0.667N |
|ORDER RESTRICTED | P=0.395 (e) (e) (e) |P=0.484 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 23
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Parathyroid Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/46 (0%) 3/50 (6%) 3/48 (6%) 2/46 (4%) |1/48 (2%) 1/48 (2%) 1/46 (2%) 1/49 (2%) |
|POLY-3 RATE (b) | 0/40.69 3/46.10 3/44.79 2/44.32 |1/42.94 1/43.81 1/43.65 1/46.10 |
|POLY-3 PERCENT (g) | 0.0% 6.5% 6.7% 4.5% |2.3% 2.3% 2.3% 2.2% |
|TERMINAL (d) | 0/32 (0%) 3/38 (8%) 2/36 (6%) 2/40 (5%) |0/32 (0%) 1/38 (3%) 1/38 (3%) 1/42 (2%) |
|FIRST INCIDENCE | --- 729 (T) 605 729 (T) |638 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.437 P=0.153 P=0.144 P=0.289 |P=0.571N P=0.741N P=0.734N P=0.723N |
|POLY 3 | P=0.405 P=0.142 P=0.136 P=0.257 |P=0.607N P=0.756N P=0.757N P=0.745N |
|POLY 1.5 | P=0.386 P=0.137 P=0.132 P=0.248 |P=0.611N P=0.759N P=0.759 P=0.749N |
|POLY 6 | P=0.430 P=0.148 P=0.142 P=0.267 |P=0.600N P=0.751N P=0.748N P=0.736N |
|LOGISTIC REGRESSION| P=0.378 P=0.153 P=0.125 P=0.289 |P=0.617N P=0.763N P=0.745 P=0.759 |
|COCH-ARM / FISHERS | P=0.358 P=0.137 P=0.129 P=0.247 |P=0.621N P=0.753N P=0.742 P=0.747N |
|ORDER RESTRICTED | P=0.154 (e) (e) (e) |P=0.725N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) |2/46 (4%) 1/49 (2%) 0/48 (0%) 0/47 (0%) |
|POLY-3 RATE (b) | 0/44.11 0/45.10 0/45.36 0/47.59 |2/41.35 1/45.42 0/45.65 0/44.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.8% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/37 (0%) 0/37 (0%) 0/41 (0%) |2/31 (7%) 1/40 (3%) 0/40 (0%) 0/40 (0%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.086N P=0.411N P=0.184N P=0.184N |
|POLY 3 | (e) (e) (e) (e) |P=0.102N P=0.467N P=0.216N P=0.223N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.102N P=0.473N P=0.221N P=0.227N |
|POLY 6 | (e) (e) (e) (e) |P=0.102N P=0.458N P=0.208N P=0.216N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.086N P=0.411N (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.104N P=0.476N P=0.237N P=0.242N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.066N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 24
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/49 (2%) 1/49 (2%) 3/50 (6%) |0/46 (0%) 0/49 (0%) 1/48 (2%) 1/47 (2%) |
|POLY-3 RATE (b) | 3/44.11 1/45.10 1/45.36 3/47.59 |0/41.35 0/45.42 1/45.65 1/44.10 |
|POLY-3 PERCENT (g) | 6.8% 2.2% 2.2% 6.3% |0.0% 0.0% 2.2% 2.3% |
|TERMINAL (d) | 3/35 (9%) 1/37 (3%) 1/37 (3%) 3/41 (7%) |0/31 (0%) 0/40 (0%) 1/40 (3%) 1/40 (3%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |--- --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.507 P=0.285N P=0.285N P=0.588N |P=0.234 (e) P=0.551 P=0.551 |
|POLY 3 | P=0.467 P=0.297N P=0.295N P=0.627N |P=0.215 (e) P=0.520 P=0.513 |
|POLY 1.5 | P=0.462 P=0.307N P=0.304N P=0.641N |P=0.213 (e) P=0.515 P=0.510 |
|POLY 6 | P=0.472 P=0.287N P=0.286N P=0.609N |P=0.220 (e) P=0.527 P=0.519 |
|LOGISTIC REGRESSION| P=0.507 P=0.285N P=0.285N P=0.588N |(e) (e) P=0.551 P=0.551 |
|COCH-ARM / FISHERS | P=0.448 P=0.316N P=0.316N P=0.661N |P=0.207 (e) P=0.511 P=0.505 |
|ORDER RESTRICTED | P=0.364N (e) (e) (e) |P=0.264 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Cytoplasmic Alteration Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) |1/46 (2%) 4/49 (8%) 1/48 (2%) 2/47 (4%) |
|POLY-3 RATE (b) | 0/44.11 0/45.10 0/45.36 0/47.59 |1/41.35 4/45.81 1/45.65 2/44.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.4% 8.7% 2.2% 4.5% |
|TERMINAL (d) | 0/35 (0%) 0/37 (0%) 0/37 (0%) 0/41 (0%) |1/31 (3%) 3/40 (8%) 1/40 (3%) 2/40 (5%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) 616 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.419N P=0.245 P=0.704N P=0.589 |
|POLY 3 | (e) (e) (e) (e) |P=0.464N P=0.211 P=0.738N P=0.522 |
|POLY 1.5 | (e) (e) (e) (e) |P=0.471N P=0.204 P=0.744N P=0.517 |
|POLY 6 | (e) (e) (e) (e) |P=0.450N P=0.222 P=0.729N P=0.534 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.472N P=0.201 P=0.704N P=0.589 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.483N P=0.201 P=0.742N P=0.508 |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.435 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 25
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Preputial Gland |
| Degeneration Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 11/50 (22%) 11/50 (22%) 16/50 (32%) 11/48 (23%) | |
|POLY-3 RATE (b) | 11/45.32 11/46.52 16/47.29 11/46.04 | |
|POLY-3 PERCENT (g) | 24.3% 23.7% 33.8% 23.9% | |
|TERMINAL (d) | 8/35 (23%) 10/38 (26%) 13/38 (34%) 9/39 (23%) | |
|FIRST INCIDENCE | 559 610 605 641 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.521N P=0.506N P=0.270 P=0.478N | |
|POLY 3 | P=0.476 P=0.569N P=0.216 P=0.580N | |
|POLY 1.5 | P=0.454 P=0.588N P=0.200 P=0.588 | |
|POLY 6 | P=0.503 P=0.550N P=0.235 P=0.553N | |
|LOGISTIC REGRESSION| P=0.452 P=0.577N P=0.200 P=0.580 | |
|COCH-ARM / FISHERS | P=0.409 P=0.595N P=0.184 P=0.553 | |
|ORDER RESTRICTED | P=0.467 (e) (e) (e) | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Preputial Gland |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 3/48 (6%) | |
|POLY-3 RATE (b) | 2/44.16 1/46.10 2/46.58 3/45.64 | |
|POLY-3 PERCENT (g) | 4.5% 2.2% 4.3% 6.6% | |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 1/38 (3%) 2/39 (5%) | |
|FIRST INCIDENCE | 723 729 (T) 673 716 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.313 P=0.478N P=0.665N P=0.549 | |
|POLY 3 | P=0.281 P=0.485N P=0.675N P=0.515 | |
|POLY 1.5 | P=0.274 P=0.494N P=0.684N P=0.501 | |
|POLY 6 | P=0.288 P=0.475N P=0.664N P=0.531 | |
|LOGISTIC REGRESSION| P=0.286 P=0.469N P=0.680N P=0.539 | |
|COCH-ARM / FISHERS | P=0.260 P=0.500N P=0.691N P=0.480 | |
|ORDER RESTRICTED | P=0.364 (e) (e) (e) | |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 26
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Seminal Vesicle |
| Dilatation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/49 (4%) 2/50 (4%) 0/50 (0%) 0/49 (0%) | |
|POLY-3 RATE (b) | 2/43.13 2/46.10 0/46.36 0/46.75 | |
|POLY-3 PERCENT (g) | 4.6% 4.3% 0.0% 0.0% | |
|TERMINAL (d) | 2/35 (6%) 2/38 (5%) 0/38 (0%) 0/41 (0%) | |
|FIRST INCIDENCE | 729 (T) 729 (T) --- --- | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.060N P=0.665N P=0.220N P=0.204N | |
|POLY 3 | P=0.066N P=0.670N P=0.221N P=0.220N | |
|POLY 1.5 | P=0.067N P=0.680N P=0.227N P=0.227N | |
|POLY 6 | P=0.065N P=0.658N P=0.215N P=0.211N | |
|LOGISTIC REGRESSION| P=0.060N P=0.665N (e) (e) | |
|COCH-ARM / FISHERS | P=0.070N P=0.684N P=0.242N P=0.247N | |
|ORDER RESTRICTED | P=0.104N (e) (e) (e) | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skin |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 2/47.91 |0/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.2% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 1/41 (2%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- --- 641 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.052 (e) (e) P=0.275 |(e) (e) (e) (e) |
|POLY 3 | P=0.045 * (e) (e) P=0.256 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.044 * (e) (e) P=0.248 |(e) (e) (e) (e) |
|POLY 6 | P=0.047 * (e) (e) P=0.266 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.038 * (e) (e) P=0.202 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.247 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.036 * (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 27
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skin: Subcutaneous Tissue |
| Edema |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/44.35 1/46.10 2/47.10 1/47.75 |0/44.58 0/45.81 0/47.65 1/47.40 |
|POLY-3 PERCENT (g) | 2.3% 2.2% 4.3% 2.1% |0.0% 0.0% 0.0% 2.1% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 665 729 (T) 605 687 |--- --- --- 649 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.605 P=0.741N P=0.537 P=0.723N |P=0.199 (e) (e) P=0.522 |
|POLY 3 | P=0.596 P=0.752N P=0.521 P=0.744N |P=0.194 (e) (e) P=0.512 |
|POLY 1.5 | P=0.586 P=0.757N P=0.511 P=0.751N |P=0.191 (e) (e) P=0.507 |
|POLY 6 | P=0.608 P=0.746N P=0.532 P=0.736N |P=0.199 (e) (e) P=0.521 |
|LOGISTIC REGRESSION| P=0.530 P=0.762N P=0.497 P=0.728 |P=0.166 (e) (e) P=0.470 |
|COCH-ARM / FISHERS | P=0.569 P=0.753N P=0.500 P=0.753N |P=0.186 (e) (e) P=0.500 |
|ORDER RESTRICTED | P=0.608 (e) (e) (e) |P=0.132 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Spinal Cord |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/4 (0%) 2/4 (50%) 0/1 (0%) 0/2 (0%) |0/1 (0%) 0/2 (0%) 0/1 (0%) 0/1 (0%) |
|POLY-3 RATE (b) | 0/3.57 2/3.78 0/0.81 0/1.85 |0/0.43 0/1.37 0/0.69 0/0.81 |
|POLY-3 PERCENT (g) | 0.0% 53.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/3 (0%) 0/1 (0%) 0/0 (0%) 0/1 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 15 --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.247N P=0.265 (e) (e) |(e) (e) (e) (e) |
|POLY 3 | P=0.441N P=0.201 (e) (e) |(e) (e) (e) (e) |
|POLY 1.5 | P=0.436N P=0.198 (e) (e) |(e) (e) (e) (e) |
|POLY 6 | P=0.459N P=0.204 (e) (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.627N P=0.429 (e) (e) |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.436N P=0.214 (e) (e) |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.301 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 28
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Congestion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/48 (0%) |0/47 (0%) 2/47 (4%) 0/49 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/43.24 0/46.10 0/45.58 0/46.16 |0/42.32 2/43.72 0/47.59 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.6% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/32 (0%) 2/40 (5%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- --- --- |--- 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.227N P=0.289 (e) (e) |
|POLY 3 | (e) (e) (e) (e) |P=0.238N P=0.244 (e) (e) |
|POLY 1.5 | (e) (e) (e) (e) |P=0.244N P=0.240 (e) (e) |
|POLY 6 | (e) (e) (e) (e) |P=0.230N P=0.251 (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.289 (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.253N P=0.247 (e) (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.234N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 14/49 (29%) 16/50 (32%) 25/49 (51%) 29/48 (60%) |23/47 (49%) 21/47 (45%) 31/49 (63%) 40/50 (80%) |
|POLY-3 RATE (b) | 14/45.74 16/48.28 25/47.71 29/47.72 |23/44.12 21/44.52 31/48.11 40/47.94 |
|POLY-3 PERCENT (g) | 30.6% 33.1% 52.4% 60.8% |52.1% 47.2% 64.4% 83.4% |
|TERMINAL (d) | 7/35 (20%) 10/38 (26%) 17/38 (45%) 25/41 (61%) |15/32 (47%) 19/40 (48%) 27/42 (64%) 37/43 (86%) |
|FIRST INCIDENCE | 478 452 605 506 |550 533 627 528 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.006 ** P=0.517 P=0.068 P=0.023 * |P=0.004 ** P=0.163N P=0.476 P=0.070 |
|POLY 3 | P<0.001 ** P=0.483 P=0.025 * P=0.002 ** |P<0.001 ** P=0.400N P=0.160 P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.456 P=0.020 * P=0.002 ** |P<0.001 ** P=0.414N P=0.145 P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.513 P=0.032 * P=0.003 ** |P<0.001 ** P=0.380N P=0.182 P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.432 P=0.017 * P<0.001 ** |P<0.001 ** P=0.393N P=0.180 P=0.002 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.440 P=0.019 * P<0.001 ** |P<0.001 ** P=0.418N P=0.113 P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 29
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/49 (14%) 6/50 (12%) 2/49 (4%) 3/48 (6%) |17/47 (36%) 15/47 (32%) 17/49 (35%) 11/50 (22%) |
|POLY-3 RATE (b) | 7/43.24 6/46.10 2/45.58 3/46.16 |17/43.64 15/44.20 17/47.64 11/47.10 |
|POLY-3 PERCENT (g) | 16.2% 13.0% 4.4% 6.5% |39.0% 33.9% 35.7% 23.4% |
|TERMINAL (d) | 7/35 (20%) 6/38 (16%) 2/38 (5%) 3/41 (7%) |13/32 (41%) 14/40 (35%) 16/42 (38%) 11/43 (26%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |617 589 716 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.045N* P=0.435N P=0.061N P=0.100N |P=0.035N* P=0.195N P=0.251N P=0.027N* |
|POLY 3 | P=0.063N P=0.451N P=0.066N P=0.132N |P=0.081N P=0.395N P=0.458N P=0.082N |
|POLY 1.5 | P=0.067N P=0.471N P=0.072N P=0.146N |P=0.082N P=0.409N P=0.478N P=0.085N |
|POLY 6 | P=0.057N P=0.428N P=0.060N P=0.116N |P=0.077N P=0.374N P=0.431N P=0.075N |
|LOGISTIC REGRESSION| P=0.045N* P=0.435N P=0.061N P=0.100N |P=0.067N P=0.388N P=0.426N P=0.072N |
|COCH-ARM / FISHERS | P=0.076N P=0.484N P=0.080N P=0.167N |P=0.093N P=0.414N P=0.525N P=0.094N |
|ORDER RESTRICTED | P=0.067N (e) (e) (e) |P=0.086N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Diverticulum |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/48 (0%) |1/50 (2%) 0/50 (0%) 1/50 (2%) 3/49 (6%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 0/46.16 |1/44.62 0/45.81 1/47.65 3/46.84 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 0.0% 2.1% 6.4% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 1/42 (2%) 3/43 (7%) |
|FIRST INCIDENCE | --- --- --- --- |718 --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.104 P=0.468N P=0.710N P=0.401 |
|POLY 3 | (e) (e) (e) (e) |P=0.079 P=0.495N P=0.746N P=0.323 |
|POLY 1.5 | (e) (e) (e) (e) |P=0.077 P=0.498N P=0.752N P=0.313 |
|POLY 6 | (e) (e) (e) (e) |P=0.082 P=0.489N P=0.736N P=0.339 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.093 P=0.491N P=0.733N P=0.366 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.072 P=0.500N P=0.753N P=0.301 |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.091 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 30
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 1/48 (2%) |2/50 (4%) 0/50 (0%) 3/50 (6%) 1/49 (2%) |
|POLY-3 RATE (b) | 0/44.11 3/46.57 0/46.36 1/46.26 |2/44.91 0/45.81 3/48.27 1/47.13 |
|POLY-3 PERCENT (g) | 0.0% 6.4% 0.0% 2.2% |4.5% 0.0% 6.2% 2.1% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 0/38 (0%) 0/41 (0%) |1/33 (3%) 0/40 (0%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | --- 638 --- 705 |638 --- 568 649 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.441N P=0.142 (e) P=0.530 |P=0.597N P=0.219N P=0.572 P=0.449N |
|POLY 3 | P=0.460N P=0.129 (e) P=0.509 |P=0.586 P=0.233N P=0.533 P=0.483N |
|POLY 1.5 | P=0.473N P=0.123 (e) P=0.502 |P=0.576 P=0.236N P=0.519 P=0.493N |
|POLY 6 | P=0.445N P=0.136 (e) P=0.519 |P=0.602 P=0.228N P=0.554 P=0.468N |
|LOGISTIC REGRESSION| P=0.500N P=0.120 (e) P=0.492 |P=0.516 P=0.237N P=0.468 P=0.549N |
|COCH-ARM / FISHERS | P=0.487N P=0.121 (e) P=0.490 |P=0.555 P=0.247N P=0.500 P=0.508N |
|ORDER RESTRICTED | P=0.279 (e) (e) (e) |P=0.419N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach: Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 2/50 (4%) 3/50 (6%) 2/48 (4%) |2/50 (4%) 2/50 (4%) 2/50 (4%) 1/49 (2%) |
|POLY-3 RATE (b) | 3/44.93 2/46.43 3/46.79 2/46.40 |2/44.58 2/45.97 2/47.74 1/47.13 |
|POLY-3 PERCENT (g) | 6.7% 4.3% 6.4% 4.3% |4.5% 4.4% 4.2% 2.1% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 2/38 (5%) 0/41 (0%) |2/33 (6%) 1/40 (3%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 544 638 605 694 |729 (T) 688 705 649 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.434N P=0.467N P=0.622N P=0.446N |P=0.303N P=0.629N P=0.604N P=0.426N |
|POLY 3 | P=0.475N P=0.485N P=0.643N P=0.485N |P=0.348N P=0.683N P=0.669N P=0.481N |
|POLY 1.5 | P=0.485N P=0.495N P=0.652N P=0.499N |P=0.358N P=0.689N P=0.680N P=0.491N |
|POLY 6 | P=0.463N P=0.474N P=0.634N P=0.468N |P=0.334N P=0.672N P=0.651N P=0.464N |
|LOGISTIC REGRESSION| P=0.550N P=0.490N P=0.648 P=0.651N |P=0.366N P=0.678N P=0.647N P=0.509N |
|COCH-ARM / FISHERS | P=0.504N P=0.500N P=0.661N P=0.520N |P=0.374N P=0.691N P=0.691N P=0.508N |
|ORDER RESTRICTED | P=0.491N (e) (e) (e) |P=0.442N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 31
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Erosion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/47 (4%) 1/47 (2%) 2/47 (4%) 1/48 (2%) |0/45 (0%) 0/47 (0%) 0/50 (0%) 0/46 (0%) |
|POLY-3 RATE (b) | 2/42.52 1/43.53 2/44.39 1/46.30 |0/40.83 0/44.30 0/47.65 0/44.39 |
|POLY-3 PERCENT (g) | 4.7% 2.3% 4.5% 2.2% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/42 (0%) |
|FIRST INCIDENCE | 544 670 627 610 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.444N P=0.473N P=0.656N P=0.459N |(e) (e) (e) (e) |
|POLY 3 | P=0.451N P=0.492N P=0.678N P=0.470N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.457N P=0.498N P=0.686N P=0.479N |(e) (e) (e) (e) |
|POLY 6 | P=0.444N P=0.485N P=0.670N P=0.460N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.559N P=0.468N P=0.702 P=0.737N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.471N P=0.500N P=0.692N P=0.492N |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.405N (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Thymus |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/38 (0%) 1/47 (2%) 0/40 (0%) 0/44 (0%) |8/43 (19%) 13/47 (28%) 11/44 (25%) 14/49 (29%) |
|POLY-3 RATE (b) | 0/33.04 1/43.24 0/37.11 0/42.16 |8/38.48 13/42.97 11/42.65 14/46.29 |
|POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 0.0% |20.8% 30.3% 25.8% 30.2% |
|TERMINAL (d) | 0/28 (0%) 1/36 (3%) 0/31 (0%) 0/37 (0%) |8/30 (27%) 13/38 (34%) 11/39 (28%) 13/42 (31%) |
|FIRST INCIDENCE | --- 729 (T) --- --- |729 (T) 729 (T) 729 (T) 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.426N P=0.550 (e) (e) |P=0.430 P=0.344 P=0.551 P=0.363 |
|POLY 3 | P=0.433N P=0.553 (e) (e) |P=0.315 P=0.235 P=0.395 P=0.230 |
|POLY 1.5 | P=0.438N P=0.547 (e) (e) |P=0.296 P=0.226 P=0.369 P=0.215 |
|POLY 6 | P=0.426N P=0.560 (e) (e) |P=0.349 P=0.250 P=0.431 P=0.258 |
|LOGISTIC REGRESSION| (e) P=0.550 (e) (e) |P=0.388 P=0.344 P=0.551 P=0.295 |
|COCH-ARM / FISHERS | P=0.443N P=0.553 (e) (e) |P=0.258 P=0.223 P=0.322 P=0.192 |
|ORDER RESTRICTED | P=0.393N (e) (e) (e) |P=0.266 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 32
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicle |
| Degeneration Cystic Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 12/50 (24%) 11/49 (22%) 7/48 (15%) |17/46 (37%) 15/50 (30%) 28/49 (57%) 23/47 (49%) |
|POLY-3 RATE (b) | 6/44.78 12/46.15 11/45.71 7/46.22 |17/42.38 15/47.10 28/47.53 23/45.58 |
|POLY-3 PERCENT (g) | 13.4% 26.0% 24.1% 15.2% |40.1% 31.9% 58.9% 50.5% |
|TERMINAL (d) | 4/35 (11%) 11/38 (29%) 10/38 (26%) 6/41 (15%) |14/32 (44%) 12/40 (30%) 23/42 (55%) 20/41 (49%) |
|FIRST INCIDENCE | 605 717 696 716 |638 521 627 649 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.301N P=0.137 P=0.194 P=0.612 |P=0.142 P=0.196N P=0.197 P=0.466 |
|POLY 3 | P=0.384N P=0.105 P=0.151 P=0.524 |P=0.038 * P=0.276N P=0.055 P=0.223 |
|POLY 1.5 | P=0.413N P=0.098 P=0.142 P=0.502 |P=0.034 * P=0.293N P=0.046 * P=0.202 |
|POLY 6 | P=0.351N P=0.113 P=0.161 P=0.551 |P=0.050 P=0.253N P=0.075 P=0.263 |
|LOGISTIC REGRESSION| P=0.352N P=0.121 P=0.164 P=0.520 |P=0.039 * P=0.301N P=0.059 P=0.229 |
|COCH-ARM / FISHERS | P=0.460N P=0.096 P=0.133 P=0.468 |P=0.027 * P=0.306N P=0.039 * P=0.169 |
|ORDER RESTRICTED | P=0.252 (e) (e) (e) |P=0.052 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 14/50 (28%) 5/50 (10%) 10/49 (20%) 11/48 (23%) |5/46 (11%) 2/50 (4%) 3/49 (6%) 5/47 (11%) |
|POLY-3 RATE (b) | 14/44.13 5/46.10 10/45.58 11/46.30 |5/41.57 2/45.81 3/46.66 5/44.84 |
|POLY-3 PERCENT (g) | 31.7% 10.9% 21.9% 23.8% |12.0% 4.4% 6.4% 11.2% |
|TERMINAL (d) | 13/35 (37%) 5/38 (13%) 10/38 (26%) 10/41 (24%) |5/32 (16%) 2/40 (5%) 3/42 (7%) 5/41 (12%) |
|FIRST INCIDENCE | 723 729 (T) 729 (T) 694 |729 (T) 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.495N P=0.011N* P=0.167N P=0.177N |P=0.483 P=0.135N P=0.217N P=0.468N |
|POLY 3 | P=0.473 P=0.013N* P=0.209N P=0.270N |P=0.400 P=0.178N P=0.295N P=0.582N |
|POLY 1.5 | P=0.452 P=0.016N* P=0.232N P=0.309N |P=0.392 P=0.182N P=0.306N P=0.595N |
|POLY 6 | P=0.502 P=0.010N* P=0.183N P=0.225N |P=0.413 P=0.171N P=0.276N P=0.560N |
|LOGISTIC REGRESSION| P=0.521N P=0.010N* P=0.171N P=0.188N |P=0.483 P=0.135N P=0.217N P=0.468N |
|COCH-ARM / FISHERS | P=0.408 P=0.020N* P=0.259N P=0.365N |P=0.372 P=0.185N P=0.322N P=0.616N |
|ORDER RESTRICTED | P=0.104N (e) (e) (e) |P=0.346N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 33
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Tissue NOS: Abdominal |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/1 (0%) 2/2 (100%) 0/0 (0%) 0/1 (0%) |0/3 (0%) 0/0 (0%) 0/0 (0%) 0/3 (0%) |
|POLY-3 RATE (b) | 0/0.98 2/2.00 0/0.00 0/0.59 |0/2.39 0/0.00 0/0.00 0/1.47 |
|POLY-3 PERCENT (g) | 0.0% 100.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/0 (0%) 1/1 (100%) 0/0 (0%) 0/0 (0%) |0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 717 --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.439N P=0.516 (e) (e) |(e) (e) (e) (e) |
|POLY 3 | (e) P=0.333 (e) (e) |(e) (e) (e) (e) |
|POLY 1.5 | (e) P=0.333 (e) (e) |(e) (e) (e) (e) |
|POLY 6 | (e) P=0.333 (e) (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) P=0.333 (e) (e) |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.356N P=0.333 (e) (e) |(e) (e) (e) (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Tooth |
| Dysplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 43/43 (100%) 37/37 (100%) 33/33 (100%) 35/35 (100%)|2/2 (100%) 10/10 (100%) 3/3 (100%) 3/3 (100%) |
|POLY-3 RATE (b) | 43/43.00 37/37.00 33/33.00 35/35.00 |2/2.00 10/10.00 3/3.00 3/3.00 |
|POLY-3 PERCENT (g) | 100.0% 100.0% 100.0% 100.0% |100.0% 100.0% 100.0% 100.0% |
|TERMINAL (d) | 34/34 (100%) 33/33 (100%) 27/27 (100%) 29/29 (100%)|2/2 (100%) 9/9 (100%) 3/3 (100%) 2/2 (100%) |
|FIRST INCIDENCE | 530 638 605 610 |729 (T) 673 729 (T) 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 34
Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Uterus: Endometrium |
| Hyperplasia Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |48/50 (96%) 45/50 (90%) 49/50 (98%) 48/50 (96%) |
|POLY-3 RATE (b) | |48/48.45 45/48.39 49/49.06 48/48.50 |
|POLY-3 PERCENT (g) | |99.1% 93.0% 99.9% 99.0% |
|TERMINAL (d) | |33/33 (100%) 37/40 (93%) 42/42 (100%) 43/43 (100%) |
|FIRST INCIDENCE | |568 521 568 528 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.049N* P=0.031N* P=0.034N* P=0.011N* |
|POLY 3 | |P=0.185 P=0.138N P=0.918 P=0.954N |
|POLY 1.5 | |P=0.256 P=0.168N P=0.737 P=0.790N |
|POLY 6 | |P=0.150 P=0.125N P=1.000 P=1.000 |
|LOGISTIC REGRESSION| |P=0.280 P=0.172N (e) P=0.486 |
|COCH-ARM / FISHERS | |P=0.268 P=0.218N P=0.500 P=0.691N |
|ORDER RESTRICTED | |P=0.156 (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).