TDMS Study 91005-07 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Southern Research Inst METHYLENE BLUE TRIHYDRATE DATE: 03/25/05
EXPERIMENT: 91005 TEST: 07 TIME: 10:12:59
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: HERSCHELL, GILES 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: 03/25/05
EXPERIMENT: 91005 TEST: 07 TIME: 10:12:59
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: HERSCHELL, GILES CAS: 7220-79-3
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF METHYLENE BLUE TRIHYDRATE
===============================================================
Male Rats
------------
Organ Morphology
----- ----------
Adrenal Medulla Hyperplasia
Esophagus Perforation
Heart Cardiomyopathy
Islets, Pancreatic Hyperplasia
Kidney Infarct
Liver Hepatodiaphragmatic Nodule
Liver: Bile Duct Hyperplasia
Lymph Node: Mediastinal Hyperplasia Lymphoid
Mesentery: Fat Necrosis
Nose Inflammation Chronic
Oral Mucosa: Pharyngeal Cyst
Inflammation
Pancreas Atrophy
Pancreas: Acinus Hyperplasia Focal
Pituitary Gland: Pars Distalis Angiectasis
Preputial Gland Cyst
Skin Inflammation Chronic
Spleen Hematopoietic Cell Proliferation
Hemorrhage
Necrosis
Spleen: Capsule Fibrosis
Stomach, Forestomach Edema
Erosion
Thyroid Gland: C-Cell Hyperplasia
===============================================================
Female Rats
------------
Organ Morphology
----- ----------
Islets, Pancreatic Metaplasia Hepatocyte
Liver Basophilic Focus
Eosinophilic Focus
Liver: Hepatocyte Vacuolization Cytoplasmic
Lymph Node: Mediastinal Hyperplasia Lymphoid
Mammary Gland Hyperplasia
Hyperplasia Atypical
Mesentery: Fat Necrosis
Ovary Cyst
Spleen Fibrosis
Spleen: Capsule Fibrosis
Stomach, Glandular Erosion
===============================================================
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 1
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Accessory Adrenal Cortical Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 23/50 (46%) 23/50 (46%) 28/50 (56%) 25/50 (50%) |9/50 (18%) 7/49 (14%) 8/50 (16%) 12/50 (24%) |
|POLY-3 RATE (b) | 23/44.67 23/45.27 28/48.30 25/43.85 |9/45.33 7/44.04 8/44.21 12/43.60 |
|POLY-3 PERCENT (g) | 51.5% 50.8% 58.0% 57.0% |19.9% 15.9% 18.1% 27.5% |
|TERMINAL (d) | 20/31 (65%) 17/33 (52%) 24/39 (62%) 18/31 (58%) |7/35 (20%) 5/32 (16%) 7/36 (19%) 9/35 (26%) |
|FIRST INCIDENCE | 641 561 489 465 |638 702 723 223 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.307 P=0.466N P=0.546N P=0.416 |P=0.192 P=0.457N P=0.486N P=0.299 |
|POLY 3 | P=0.262 P=0.559N P=0.335 P=0.376 |P=0.149 P=0.416N P=0.523N P=0.274 |
|POLY 1.5 | P=0.262 P=0.571N P=0.278 P=0.377 |P=0.152 P=0.412N P=0.512N P=0.278 |
|POLY 6 | P=0.282 P=0.528N P=0.423 P=0.401 |P=0.156 P=0.425N P=0.534N P=0.282 |
|LOGISTIC REGRESSION| P=0.226 P=0.535N P=0.373 P=0.327 |P=0.155 P=0.412N P=0.511N P=0.331 |
|COCH-ARM / FISHERS | P=0.301 P=0.579N P=0.212 P=0.421 |P=0.176 P=0.410N P=0.500N P=0.312 |
|ORDER RESTRICTED | P=0.430 (e) (e) (e) |P=0.202 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Degeneration Fatty |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 6/50 (12%) 7/50 (14%) 2/50 (4%) |11/50 (22%) 13/49 (27%) 13/50 (26%) 8/50 (16%) |
|POLY-3 RATE (b) | 7/44.39 6/44.50 7/47.25 2/41.96 |11/45.00 13/43.83 13/44.64 8/41.13 |
|POLY-3 PERCENT (g) | 15.8% 13.5% 14.8% 4.8% |24.5% 29.7% 29.1% 19.5% |
|TERMINAL (d) | 6/31 (19%) 5/33 (15%) 4/39 (10%) 2/31 (7%) |10/35 (29%) 13/32 (41%) 12/36 (33%) 7/35 (20%) |
|FIRST INCIDENCE | 544 652 690 729 (T) |652 729 (T) 596 725 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.074N P=0.457N P=0.442N P=0.083N |P=0.160N P=0.305 P=0.428 P=0.305N |
|POLY 3 | P=0.094N P=0.498N P=0.565N P=0.092N |P=0.270N P=0.376 P=0.397 P=0.383N |
|POLY 1.5 | P=0.091N P=0.501N P=0.587N P=0.089N |P=0.257N P=0.383 P=0.402 P=0.369N |
|POLY 6 | P=0.093N P=0.487N P=0.528N P=0.091N |P=0.257N P=0.363 P=0.395 P=0.376N |
|LOGISTIC REGRESSION| P=0.084N P=0.490N P=0.570N P=0.090N |P=0.206N P=0.354 P=0.393 P=0.331N |
|COCH-ARM / FISHERS | P=0.080N P=0.500N P=0.613N P=0.080N |P=0.193N P=0.385 P=0.408 P=0.306N |
|ORDER RESTRICTED | P=0.095N (e) (e) (e) |P=0.303N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 2
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 5/50 (10%) 5/50 (10%) 5/50 (10%) |5/50 (10%) 8/49 (16%) 8/50 (16%) 6/50 (12%) |
|POLY-3 RATE (b) | 6/44.06 5/44.50 5/47.41 5/42.38 |5/44.71 8/44.01 8/45.04 6/42.67 |
|POLY-3 PERCENT (g) | 13.6% 11.2% 10.6% 11.8% |11.2% 18.2% 17.8% 14.1% |
|TERMINAL (d) | 5/31 (16%) 4/33 (12%) 3/39 (8%) 3/31 (10%) |5/35 (14%) 6/32 (19%) 6/36 (17%) 4/35 (11%) |
|FIRST INCIDENCE | 662 652 619 626 |729 (T) 702 492 284 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.463N P=0.458N P=0.360N P=0.504N |P=0.526N P=0.225 P=0.296 P=0.490 |
|POLY 3 | P=0.482N P=0.493N P=0.449N P=0.527N |P=0.516 P=0.264 P=0.279 P=0.467 |
|POLY 1.5 | P=0.482N P=0.497N P=0.472N P=0.523N |P=0.517 P=0.265 P=0.279 P=0.469 |
|POLY 6 | P=0.475N P=0.482N P=0.415N P=0.523N |P=0.536 P=0.262 P=0.283 P=0.481 |
|LOGISTIC REGRESSION| P=0.488N P=0.480N P=0.454N P=0.527N |P=0.536 P=0.244 P=0.269 P=0.515 |
|COCH-ARM / FISHERS | P=0.465N P=0.500N P=0.500N P=0.500N |P=0.544N P=0.264 P=0.277 P=0.500 |
|ORDER RESTRICTED | P=0.568N (e) (e) (e) |P=0.379 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hypertrophy Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 5/50 (10%) 9/50 (18%) 8/50 (16%) |12/50 (24%) 11/49 (22%) 13/50 (26%) 7/50 (14%) |
|POLY-3 RATE (b) | 6/44.46 5/44.68 9/47.95 8/42.74 |12/45.00 11/43.83 13/44.64 7/41.13 |
|POLY-3 PERCENT (g) | 13.5% 11.2% 18.8% 18.7% |26.7% 25.1% 29.1% 17.0% |
|TERMINAL (d) | 3/31 (10%) 3/33 (9%) 5/39 (13%) 6/31 (19%) |11/35 (31%) 11/32 (34%) 12/36 (33%) 6/35 (17%) |
|FIRST INCIDENCE | 645 652 489 530 |652 729 (T) 596 725 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.214 P=0.463N P=0.449 P=0.381 |P=0.119N P=0.598 P=0.524 P=0.153N |
|POLY 3 | P=0.187 P=0.497N P=0.344 P=0.355 |P=0.209N P=0.529N P=0.491 P=0.206N |
|POLY 1.5 | P=0.192 P=0.499N P=0.320 P=0.362 |P=0.199N P=0.524N P=0.495 P=0.196N |
|POLY 6 | P=0.188 P=0.488N P=0.378 P=0.355 |P=0.197N P=0.541N P=0.490 P=0.200N |
|LOGISTIC REGRESSION| P=0.200 P=0.497N P=0.261 P=0.361 |P=0.156N P=0.548N P=0.488 P=0.167N |
|COCH-ARM / FISHERS | P=0.211 P=0.500N P=0.288 P=0.387 |P=0.146N P=0.522N P=0.500 P=0.154N |
|ORDER RESTRICTED | P=0.330 (e) (e) (e) |P=0.225N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 3
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |2/50 (4%) 1/49 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/44.19 0/44.21 0/46.96 1/41.96 |2/45.37 1/44.31 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 0.0% 2.4% |4.4% 2.3% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 1/31 (3%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 620 --- --- 729 (T) |563 585 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.533 P=0.509N P=0.491N P=0.752 |P=0.117N P=0.506N P=0.244N P=0.260N |
|POLY 3 | P=0.529 P=0.500N P=0.488N P=0.749 |P=0.107N P=0.508N P=0.243N P=0.260N |
|POLY 1.5 | P=0.530 P=0.500N P=0.493N P=0.752 |P=0.106N P=0.507N P=0.240N P=0.255N |
|POLY 6 | P=0.528 P=0.498N P=0.480N P=0.749 |P=0.107N P=0.511N P=0.245N P=0.259N |
|LOGISTIC REGRESSION| P=0.551 P=0.496N P=0.579N P=0.760N |P=0.055N P=0.535N P=0.243N P=0.194N |
|COCH-ARM / FISHERS | P=0.536 P=0.500N P=0.500N P=0.753N |P=0.104N P=0.508N P=0.247N P=0.247N |
|ORDER RESTRICTED | P=0.380 (e) (e) (e) |P=0.089N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 12/50 (24%) 8/50 (16%) 2/50 (4%) |1/50 (2%) 2/49 (4%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 7/44.47 12/44.46 8/46.97 2/42.07 |1/44.71 2/43.83 1/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 15.7% 27.0% 17.0% 4.8% |2.2% 4.6% 2.3% 0.0% |
|TERMINAL (d) | 4/31 (13%) 10/33 (30%) 7/39 (18%) 1/31 (3%) |1/35 (3%) 2/32 (6%) 1/36 (3%) 0/35 (0%) |
|FIRST INCIDENCE | 645 673 726 703 |729 (T) 729 (T) 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.015N* P=0.201 P=0.543N P=0.087N |P=0.192N P=0.469 P=0.756N P=0.500N |
|POLY 3 | P=0.020N* P=0.148 P=0.546 P=0.092N |P=0.217N P=0.493 P=0.758 P=0.517N |
|POLY 1.5 | P=0.019N* P=0.150 P=0.526 P=0.089N |P=0.215N P=0.494 P=0.759 P=0.514N |
|POLY 6 | P=0.019N* P=0.150 P=0.574 P=0.092N |P=0.215N P=0.491 P=0.758 P=0.515N |
|LOGISTIC REGRESSION| P=0.016N* P=0.166 P=0.592 P=0.090N |P=0.192N P=0.469 P=0.756N (e) |
|COCH-ARM / FISHERS | P=0.017N* P=0.154 P=0.500 P=0.080N |P=0.200N P=0.492 P=0.753N P=0.500N |
|ORDER RESTRICTED | P=0.024N* (e) (e) (e) |P=0.239N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 4
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Bone Marrow |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 7/50 (14%) 4/50 (8%) 9/50 (18%) |8/50 (16%) 8/49 (16%) 9/50 (18%) 6/50 (12%) |
|POLY-3 RATE (b) | 7/44.84 7/45.97 4/48.38 9/43.64 |8/47.40 8/45.23 9/46.82 6/43.82 |
|POLY-3 PERCENT (g) | 15.6% 15.2% 8.3% 20.6% |16.9% 17.7% 19.2% 13.7% |
|TERMINAL (d) | 3/31 (10%) 2/33 (6%) 1/39 (3%) 3/31 (10%) |2/35 (6%) 4/32 (13%) 3/36 (8%) 2/35 (6%) |
|FIRST INCIDENCE | 563 568 489 563 |344 395 492 284 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.359 P=0.573N P=0.194N P=0.391 |P=0.371N P=0.562 P=0.499 P=0.441N |
|POLY 3 | P=0.354 P=0.594N P=0.219N P=0.369 |P=0.388N P=0.568 P=0.489 P=0.448N |
|POLY 1.5 | P=0.353 P=0.604N P=0.237N P=0.370 |P=0.381N P=0.577 P=0.492 P=0.438N |
|POLY 6 | P=0.365 P=0.576N P=0.196N P=0.382 |P=0.375N P=0.554 P=0.492 P=0.443N |
|LOGISTIC REGRESSION| P=0.454 P=0.614N P=0.392N P=0.397 |P=0.100N P=0.581 P=0.605 P=0.169N |
|COCH-ARM / FISHERS | P=0.366 P=0.613N P=0.262N P=0.393 |P=0.328N P=0.590 P=0.500 P=0.387N |
|ORDER RESTRICTED | P=0.250 (e) (e) (e) |P=0.467N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Brain |
| Compression |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 10/50 (20%) 9/50 (18%) 6/50 (12%) |3/50 (6%) 8/49 (16%) 6/50 (12%) 5/50 (10%) |
|POLY-3 RATE (b) | 7/44.90 10/47.03 9/48.07 6/43.85 |3/45.12 8/44.68 6/44.75 5/41.31 |
|POLY-3 PERCENT (g) | 15.6% 21.3% 18.7% 13.7% |6.7% 17.9% 13.4% 12.1% |
|TERMINAL (d) | 2/31 (7%) 4/33 (12%) 4/39 (10%) 1/31 (3%) |1/35 (3%) 4/32 (13%) 4/36 (11%) 4/35 (11%) |
|FIRST INCIDENCE | 641 473 586 504 |652 628 593 677 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.326N P=0.338 P=0.547 P=0.517N |P=0.547N P=0.096 P=0.255 P=0.356 |
|POLY 3 | P=0.329N P=0.333 P=0.451 P=0.518N |P=0.488 P=0.094 P=0.237 P=0.309 |
|POLY 1.5 | P=0.326N P=0.318 P=0.425 P=0.517N |P=0.502 P=0.094 P=0.240 P=0.317 |
|POLY 6 | P=0.326N P=0.355 P=0.487 P=0.513N |P=0.493 P=0.094 P=0.236 P=0.312 |
|LOGISTIC REGRESSION| P=0.220N P=0.295 P=0.338 P=0.450N |P=0.515 P=0.094 P=0.241 P=0.315 |
|COCH-ARM / FISHERS | P=0.303N P=0.298 P=0.393 P=0.500N |P=0.549N P=0.094 P=0.243 P=0.357 |
|ORDER RESTRICTED | P=0.437N (e) (e) (e) |P=0.214 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 5
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Brain |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/49 (2%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/44.06 2/44.94 0/46.96 0/41.96 |1/45.01 1/44.12 1/44.78 0/41.11 |
|POLY-3 PERCENT (g) | 2.3% 4.5% 0.0% 0.0% |2.2% 2.3% 2.2% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/33 (3%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 662 473 --- --- |648 648 540 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.134N P=0.512 P=0.476N P=0.511N |P=0.328N P=0.746 P=0.750 P=0.524N |
|POLY 3 | P=0.131N P=0.507 P=0.487N P=0.510N |P=0.320N P=0.756 P=0.760 P=0.518N |
|POLY 1.5 | P=0.133N P=0.504 P=0.493N P=0.508N |P=0.317N P=0.756 P=0.760 P=0.515N |
|POLY 6 | P=0.128N P=0.513 P=0.479N P=0.510N |P=0.318N P=0.755 P=0.760 P=0.517N |
|LOGISTIC REGRESSION| P=0.084N P=0.510 P=0.542N P=0.487N |P=0.197N P=0.751 P=0.745 P=0.480N |
|COCH-ARM / FISHERS | P=0.134N P=0.500 P=0.500N P=0.500N |P=0.300N P=0.747 P=0.753N P=0.500N |
|ORDER RESTRICTED | P=0.181N (e) (e) (e) |P=0.342N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |4/50 (8%) 7/48 (15%) 4/50 (8%) 6/50 (12%) |
|POLY-3 RATE (b) | |4/44.71 7/44.91 4/44.74 6/41.73 |
|POLY-3 PERCENT (g) | |9.0% 15.6% 8.9% 14.4% |
|TERMINAL (d) | |4/35 (11%) 3/32 (9%) 3/36 (8%) 5/35 (14%) |
|FIRST INCIDENCE | |729 (T) 395 557 527 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.492 P=0.234 P=0.631N P=0.362 |
|POLY 3 | |P=0.445 P=0.263 P=0.643N P=0.326 |
|POLY 1.5 | |P=0.454 P=0.254 P=0.643N P=0.331 |
|POLY 6 | |P=0.453 P=0.273 P=0.641N P=0.336 |
|LOGISTIC REGRESSION| |P=0.517 P=0.228 P=0.639 P=0.323 |
|COCH-ARM / FISHERS | |P=0.503 P=0.239 P=0.643N P=0.370 |
|ORDER RESTRICTED | |P=0.352 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 6
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |1/50 (2%) 5/48 (10%) 2/50 (4%) 4/50 (8%) |
|POLY-3 RATE (b) | |1/44.71 5/43.14 2/44.88 4/41.11 |
|POLY-3 PERCENT (g) | |2.2% 11.6% 4.5% 9.7% |
|TERMINAL (d) | |1/35 (3%) 5/32 (16%) 1/36 (3%) 4/35 (11%) |
|FIRST INCIDENCE | |729 (T) 729 (T) 492 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.385 P=0.082 P=0.509 P=0.178 |
|POLY 3 | |P=0.337 P=0.093 P=0.501 P=0.154 |
|POLY 1.5 | |P=0.343 P=0.093 P=0.501 P=0.158 |
|POLY 6 | |P=0.342 P=0.092 P=0.503 P=0.156 |
|LOGISTIC REGRESSION| |P=0.336 P=0.082 P=0.496 P=0.178 |
|COCH-ARM / FISHERS | |P=0.377 P=0.093 P=0.500 P=0.181 |
|ORDER RESTRICTED | |P=0.135 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Esophagus |
| Perforation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 0/46.96 2/43.61 |0/44.71 0/43.83 1/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.6% |0.0% 0.0% 2.3% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 1/36 (3%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- --- 191 |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.042 * (e) (e) P=0.233 |P=0.655 (e) P=0.506 (e) |
|POLY 3 | P=0.043 * (e) (e) P=0.236 |P=0.609 (e) P=0.498 (e) |
|POLY 1.5 | P=0.042 * (e) (e) P=0.236 |P=0.615 (e) P=0.499 (e) |
|POLY 6 | P=0.043 * (e) (e) P=0.239 |P=0.615 (e) P=0.497 (e) |
|LOGISTIC REGRESSION| P=0.329 (e) (e) P=0.666 |(e) (e) P=0.506 (e) |
|COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.247 |P=0.650 (e) P=0.500 (e) |
|ORDER RESTRICTED | P=0.029 * (e) (e) (e) |P=0.379 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 7
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Eye |
| Cataract |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 3/49 (6%) 4/48 (8%) 3/48 (6%) |1/50 (2%) 2/49 (4%) 5/50 (10%) 3/50 (6%) |
|POLY-3 RATE (b) | 1/44.20 3/43.78 4/46.38 3/41.08 |1/44.71 2/43.83 5/44.68 3/41.11 |
|POLY-3 PERCENT (g) | 2.3% 6.9% 8.6% 7.3% |2.2% 4.6% 11.2% 7.3% |
|TERMINAL (d) | 0/31 (0%) 2/33 (6%) 3/39 (8%) 3/31 (10%) |1/35 (3%) 2/32 (6%) 2/36 (6%) 3/35 (9%) |
|FIRST INCIDENCE | 616 723 619 729 (T) |729 (T) 729 (T) 646 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.301 P=0.321 P=0.237 P=0.298 |P=0.219 P=0.469 P=0.113 P=0.305 |
|POLY 3 | P=0.270 P=0.302 P=0.194 P=0.279 |P=0.165 P=0.493 P=0.101 P=0.276 |
|POLY 1.5 | P=0.272 P=0.300 P=0.182 P=0.281 |P=0.171 P=0.494 P=0.101 P=0.281 |
|POLY 6 | P=0.275 P=0.307 P=0.211 P=0.281 |P=0.170 P=0.491 P=0.102 P=0.279 |
|LOGISTIC REGRESSION| P=0.278 P=0.299 P=0.104 P=0.284 |P=0.179 P=0.469 P=0.101 P=0.305 |
|COCH-ARM / FISHERS | P=0.287 P=0.301 P=0.168 P=0.293 |P=0.208 P=0.492 P=0.102 P=0.309 |
|ORDER RESTRICTED | P=0.223 (e) (e) (e) |P=0.140 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Eye |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/49 (0%) 1/48 (2%) 1/48 (2%) |0/50 (0%) 2/49 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/43.81 0/43.76 1/45.99 1/41.13 |0/44.71 2/44.33 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 2.2% 2.4% |0.0% 4.5% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 1/39 (3%) 0/31 (0%) |0/35 (0%) 1/32 (3%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) 715 |--- 576 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.474 P=0.488N P=0.710N P=0.753N |P=0.275N P=0.230 (e) (e) |
|POLY 3 | P=0.448 P=0.500N P=0.750N P=0.747 |P=0.265N P=0.235 (e) (e) |
|POLY 1.5 | P=0.450 P=0.502N P=0.758N P=0.746 |P=0.264N P=0.235 (e) (e) |
|POLY 6 | P=0.449 P=0.496N P=0.737N P=0.751 |P=0.264N P=0.235 (e) (e) |
|LOGISTIC REGRESSION| P=0.466 (e) P=0.710N P=0.759 |P=0.226N P=0.224 (e) (e) |
|COCH-ARM / FISHERS | P=0.461 P=0.505N P=0.742 P=0.742 |P=0.262N P=0.242 (e) (e) |
|ORDER RESTRICTED | P=0.515 (e) (e) (e) |P=0.262N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 8
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Eye: Cornea |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/48 (0%) 0/48 (0%) |1/50 (2%) 0/49 (0%) 1/50 (2%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/43.81 0/43.76 0/45.99 0/41.08 |1/45.25 0/43.83 1/44.49 2/41.11 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 0.0% 2.3% 4.9% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 2/35 (6%) |
|FIRST INCIDENCE | --- --- --- --- |563 --- 646 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.194 P=0.500N P=0.745 P=0.482 |
|POLY 3 | (e) (e) (e) (e) |P=0.185 P=0.506N P=0.757 P=0.467 |
|POLY 1.5 | (e) (e) (e) (e) |P=0.188 P=0.505N P=0.758 P=0.473 |
|POLY 6 | (e) (e) (e) (e) |P=0.187 P=0.509N P=0.756 P=0.468 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.223 P=0.541N P=0.749 P=0.504 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.205 P=0.505N P=0.753N P=0.500 |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.196 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Eye: Retina |
| Degeneration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/49 (4%) 4/48 (8%) 3/48 (6%) |2/50 (4%) 2/49 (4%) 4/50 (8%) 2/50 (4%) |
|POLY-3 RATE (b) | 1/44.20 2/43.78 4/46.38 3/41.08 |2/45.25 2/43.83 4/44.37 2/41.11 |
|POLY-3 PERCENT (g) | 2.3% 4.6% 8.6% 7.3% |4.4% 4.6% 9.0% 4.9% |
|TERMINAL (d) | 0/31 (0%) 1/33 (3%) 3/39 (8%) 3/31 (10%) |1/35 (3%) 2/32 (6%) 2/36 (6%) 2/35 (6%) |
|FIRST INCIDENCE | 616 723 619 729 (T) |563 729 (T) 687 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.212 P=0.510 P=0.237 P=0.298 |P=0.529 P=0.669 P=0.350 P=0.679 |
|POLY 3 | P=0.188 P=0.497 P=0.194 P=0.279 |P=0.460 P=0.683 P=0.328 P=0.659 |
|POLY 1.5 | P=0.190 P=0.495 P=0.182 P=0.281 |P=0.471 P=0.685 P=0.332 P=0.666 |
|POLY 6 | P=0.191 P=0.502 P=0.211 P=0.281 |P=0.466 P=0.679 P=0.326 P=0.661 |
|LOGISTIC REGRESSION| P=0.196 P=0.491 P=0.104 P=0.284 |P=0.485 P=0.687 P=0.337 P=0.686 |
|COCH-ARM / FISHERS | P=0.203 P=0.492 P=0.168 P=0.293 |P=0.521 P=0.684 P=0.339 P=0.691N |
|ORDER RESTRICTED | P=0.205 (e) (e) (e) |P=0.479 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 9
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Harderian Gland |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 3/50 (6%) 1/50 (2%) 4/50 (8%) |3/50 (6%) 3/49 (6%) 3/50 (6%) 4/50 (8%) |
|POLY-3 RATE (b) | 2/44.12 3/44.21 1/46.96 4/42.50 |3/45.32 3/44.53 3/44.64 4/42.19 |
|POLY-3 PERCENT (g) | 4.5% 6.8% 2.1% 9.4% |6.6% 6.7% 6.7% 9.5% |
|TERMINAL (d) | 1/31 (3%) 3/33 (9%) 1/39 (3%) 3/31 (10%) |1/35 (3%) 1/32 (3%) 2/36 (6%) 1/35 (3%) |
|FIRST INCIDENCE | 642 729 (T) 729 (T) 563 |640 576 596 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.319 P=0.523 P=0.439N P=0.327 |P=0.389 P=0.642 P=0.648 P=0.481 |
|POLY 3 | P=0.319 P=0.501 P=0.478N P=0.320 |P=0.364 P=0.654 P=0.655 P=0.461 |
|POLY 1.5 | P=0.319 P=0.500 P=0.488N P=0.323 |P=0.370 P=0.654 P=0.659 P=0.466 |
|POLY 6 | P=0.325 P=0.505 P=0.464N P=0.321 |P=0.372 P=0.653 P=0.653 P=0.468 |
|LOGISTIC REGRESSION| P=0.312 P=0.508 P=0.504N P=0.332 |P=0.469 P=0.646 P=0.661N P=0.537 |
|COCH-ARM / FISHERS | P=0.325 P=0.500 P=0.500N P=0.339 |P=0.405 P=0.651 P=0.661N P=0.500 |
|ORDER RESTRICTED | P=0.255 (e) (e) (e) |P=0.483 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Harderian Gland |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 3/50 (6%) |2/50 (4%) 2/49 (4%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 2/44.33 1/44.70 1/47.03 3/43.66 |2/45.30 2/44.61 1/44.88 1/42.08 |
|POLY-3 PERCENT (g) | 4.5% 2.2% 2.1% 6.9% |4.4% 4.5% 2.2% 2.4% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 641 582 710 504 |591 585 492 239 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.281 P=0.507N P=0.444N P=0.475 |P=0.351N P=0.677 P=0.502N P=0.527N |
|POLY 3 | P=0.294 P=0.497N P=0.479N P=0.493 |P=0.334N P=0.688 P=0.503N P=0.526N |
|POLY 1.5 | P=0.293 P=0.499N P=0.488N P=0.492 |P=0.330N P=0.688 P=0.501N P=0.521N |
|POLY 6 | P=0.298 P=0.493N P=0.466N P=0.499 |P=0.333N P=0.688 P=0.505N P=0.524N |
|LOGISTIC REGRESSION| P=0.472 P=0.493N P=0.552N P=0.653 |P=0.067N P=0.672 P=0.533N P=0.259N |
|COCH-ARM / FISHERS | P=0.295 P=0.500N P=0.500N P=0.500 |P=0.315N P=0.684 P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.276 (e) (e) (e) |P=0.461N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 10
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Heart |
| Cardiomyopathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 47/50 (94%) 46/50 (92%) 47/50 (94%) 45/50 (90%) |36/50 (72%) 41/49 (84%) 36/50 (72%) 32/50 (64%) |
|POLY-3 RATE (b) | 47/48.34 46/49.93 47/49.22 45/47.98 |36/48.22 41/46.72 36/46.58 32/41.90 |
|POLY-3 PERCENT (g) | 97.2% 92.1% 95.5% 93.8% |74.7% 87.8% 77.3% 76.4% |
|TERMINAL (d) | 31/31 (100%) 30/33 (91%) 38/39 (97%) 29/31 (94%) |27/35 (77%) 31/32 (97%) 29/36 (81%) 30/35 (86%) |
|FIRST INCIDENCE | 563 473 489 191 |344 576 540 544 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.422N P=0.350N P=0.045N* P=0.469N |P=0.058N P=0.093 P=0.538N P=0.291N |
|POLY 3 | P=0.478N P=0.236N P=0.537N P=0.354N |P=0.334N P=0.074 P=0.476 P=0.523 |
|POLY 1.5 | P=0.421N P=0.337N P=0.589N P=0.363N |P=0.225N P=0.090 P=0.521 P=0.552N |
|POLY 6 | P=0.524N P=0.145N P=0.492N P=0.320N |P=0.415N P=0.058 P=0.432 P=0.449 |
|LOGISTIC REGRESSION| P=0.502N P=0.506N P=0.422N P=0.587N |P=0.220N P=0.124 P=0.569 P=0.514N |
|COCH-ARM / FISHERS | P=0.329N P=0.500N P=0.661N P=0.357N |P=0.059N P=0.124 P=0.588N P=0.260N |
|ORDER RESTRICTED | P=0.332N (e) (e) (e) |P=0.372 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 13/50 (26%) 13/50 (26%) 17/50 (34%) 26/50 (52%) |13/49 (27%) 15/48 (31%) 15/48 (31%) 15/49 (31%) |
|POLY-3 RATE (b) | 13/45.38 13/45.80 17/47.66 26/44.35 |13/44.97 15/44.52 15/44.11 15/42.20 |
|POLY-3 PERCENT (g) | 28.7% 28.4% 35.7% 58.6% |28.9% 33.7% 34.0% 35.6% |
|TERMINAL (d) | 8/31 (26%) 8/33 (24%) 14/39 (36%) 19/31 (61%) |11/35 (31%) 11/32 (34%) 12/36 (33%) 11/35 (31%) |
|FIRST INCIDENCE | 586 561 586 401 |638 576 593 284 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.002 ** P=0.537N P=0.499 P=0.010 * |P=0.445 P=0.326 P=0.430 P=0.401 |
|POLY 3 | P<0.001 ** P=0.581N P=0.307 P=0.003 ** |P=0.328 P=0.397 P=0.386 P=0.332 |
|POLY 1.5 | P<0.001 ** P=0.586N P=0.285 P=0.003 ** |P=0.342 P=0.393 P=0.387 P=0.343 |
|POLY 6 | P<0.001 ** P=0.567N P=0.342 P=0.002 ** |P=0.343 P=0.403 P=0.392 P=0.348 |
|LOGISTIC REGRESSION| P<0.001 ** P=0.590N P=0.294 P=0.004 ** |P=0.336 P=0.380 P=0.381 P=0.341 |
|COCH-ARM / FISHERS | P<0.001 ** P=0.590N P=0.257 P=0.007 ** |P=0.423 P=0.386 P=0.386 P=0.412 |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.405 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 11
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Metaplasia Hepatocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/49 (4%) 0/48 (0%) 0/48 (0%) 0/49 (0%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 1/47.25 0/41.96 |2/44.36 0/43.14 0/43.32 0/40.27 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.1% 0.0% |4.5% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |2/35 (6%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 649 --- |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.647 (e) P=0.523 (e) |P=0.155N P=0.258N P=0.232N P=0.238N |
|POLY 3 | P=0.617 (e) P=0.515 (e) |P=0.156N P=0.243N P=0.242N P=0.259N |
|POLY 1.5 | P=0.626 (e) P=0.508 (e) |P=0.157N P=0.243N P=0.242N P=0.255N |
|POLY 6 | P=0.611 (e) P=0.525 (e) |P=0.155N P=0.244N P=0.241N P=0.257N |
|LOGISTIC REGRESSION| P=0.678 (e) P=0.446 (e) |P=0.155N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.649 (e) P=0.500 (e) |P=0.160N P=0.253N P=0.253N P=0.247N |
|ORDER RESTRICTED | P=0.394 (e) (e) (e) |P=0.037N* (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Kidney |
| Hydronephrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/43.81 1/44.39 0/46.96 2/43.07 |0/44.71 0/43.83 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 4.6% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- 682 --- 465 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.164 P=0.511 (e) P=0.232 |(e) (e) (e) (e) |
|POLY 3 | P=0.169 P=0.503 (e) P=0.233 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.167 P=0.501 (e) P=0.233 |(e) (e) (e) (e) |
|POLY 6 | P=0.173 P=0.507 (e) P=0.237 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.279 P=0.500 (e) P=0.343 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.168 P=0.500 (e) P=0.247 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.072 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 12
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Kidney |
| Infarct |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/49 (0%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 2/44.06 0/44.21 0/46.96 0/41.96 |1/45.01 0/43.83 2/44.18 2/41.11 |
|POLY-3 PERCENT (g) | 4.5% 0.0% 0.0% 0.0% |2.2% 0.0% 4.5% 4.9% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 2/36 (6%) 2/35 (6%) |
|FIRST INCIDENCE | 662 --- --- --- |648 --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.157N P=0.230N P=0.202N P=0.246N |P=0.199 P=0.514N P=0.495 P=0.486 |
|POLY 3 | P=0.154N P=0.236N P=0.223N P=0.248N |P=0.170 P=0.505N P=0.494 P=0.468 |
|POLY 1.5 | P=0.156N P=0.237N P=0.229N P=0.246N |P=0.175 P=0.504N P=0.497 P=0.474 |
|POLY 6 | P=0.152N P=0.234N P=0.214N P=0.248N |P=0.173 P=0.507N P=0.491 P=0.470 |
|LOGISTIC REGRESSION| P=0.160N P=0.237N P=0.243N P=0.243N |P=0.176 P=0.513N P=0.498 P=0.478 |
|COCH-ARM / FISHERS | P=0.160N P=0.247N P=0.247N P=0.247N |P=0.197 P=0.505N P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.033N* (e) (e) (e) |P=0.241 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Kidney |
| Nephropathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 35/50 (70%) 39/50 (78%) 33/50 (66%) 34/50 (68%) |14/50 (28%) 15/49 (31%) 21/50 (42%) 16/50 (32%) |
|POLY-3 RATE (b) | 35/46.58 39/47.42 33/48.34 34/46.20 |14/45.97 15/44.89 21/45.27 16/41.11 |
|POLY-3 PERCENT (g) | 75.1% 82.3% 68.3% 73.6% |30.5% 33.4% 46.4% 38.9% |
|TERMINAL (d) | 24/31 (77%) 28/33 (85%) 28/39 (72%) 22/31 (71%) |10/35 (29%) 10/32 (31%) 19/36 (53%) 16/35 (46%) |
|FIRST INCIDENCE | 586 540 586 465 |591 628 521 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.284N P=0.431 P=0.069N P=0.522N |P=0.340 P=0.419 P=0.118 P=0.398 |
|POLY 3 | P=0.245N P=0.267 P=0.298N P=0.527N |P=0.162 P=0.469 P=0.085 P=0.272 |
|POLY 1.5 | P=0.262N P=0.255 P=0.347N P=0.539N |P=0.195 P=0.473 P=0.093 P=0.306 |
|POLY 6 | P=0.216N P=0.297 P=0.241N P=0.495N |P=0.148 P=0.461 P=0.075 P=0.258 |
|LOGISTIC REGRESSION| P=0.339N P=0.233 P=0.237N P=0.555 |P=0.205 P=0.475 P=0.094 P=0.312 |
|COCH-ARM / FISHERS | P=0.245N P=0.247 P=0.415N P=0.500N |P=0.316 P=0.474 P=0.104 P=0.414 |
|ORDER RESTRICTED | P=0.293N (e) (e) (e) |P=0.180 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 13
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Basophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 6/50 (12%) 8/50 (16%) 6/50 (12%) |37/50 (74%) 34/49 (69%) 38/50 (76%) 40/50 (80%) |
|POLY-3 RATE (b) | 5/43.81 6/44.25 8/46.96 6/41.96 |37/46.42 34/45.40 38/45.78 40/44.09 |
|POLY-3 PERCENT (g) | 11.4% 13.6% 17.0% 14.3% |79.7% 74.9% 83.0% 90.7% |
|TERMINAL (d) | 5/31 (16%) 5/33 (15%) 8/39 (21%) 6/31 (19%) |30/35 (86%) 28/32 (88%) 32/36 (89%) 33/35 (94%) |
|FIRST INCIDENCE | 729 (T) 720 729 (T) 729 (T) |640 576 560 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.427 P=0.550 P=0.437 P=0.500 |P=0.223 P=0.568N P=0.563 P=0.298 |
|POLY 3 | P=0.389 P=0.507 P=0.322 P=0.470 |P=0.031 * P=0.374N P=0.440 P=0.101 |
|POLY 1.5 | P=0.395 P=0.503 P=0.301 P=0.476 |P=0.046 * P=0.372N P=0.474 P=0.125 |
|POLY 6 | P=0.391 P=0.519 P=0.354 P=0.472 |P=0.036 * P=0.398N P=0.398 P=0.124 |
|LOGISTIC REGRESSION| P=0.423 P=0.575 P=0.437 P=0.500 |P=0.008 ** P=0.374N P=0.349 P=0.042 * |
|COCH-ARM / FISHERS | P=0.425 P=0.500 P=0.277 P=0.500 |P=0.167 P=0.387N P=0.500 P=0.318 |
|ORDER RESTRICTED | P=0.452 (e) (e) (e) |P=0.051 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Clear Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 14/50 (28%) 13/50 (26%) 16/50 (32%) 12/50 (24%) |8/50 (16%) 5/49 (10%) 9/50 (18%) 8/50 (16%) |
|POLY-3 RATE (b) | 14/43.81 13/44.74 16/47.35 12/42.33 |8/45.00 5/43.83 9/45.22 8/41.11 |
|POLY-3 PERCENT (g) | 32.0% 29.1% 33.8% 28.4% |17.8% 11.4% 19.9% 19.5% |
|TERMINAL (d) | 14/31 (45%) 12/33 (36%) 15/39 (39%) 11/31 (36%) |7/35 (20%) 5/32 (16%) 6/36 (17%) 8/35 (23%) |
|FIRST INCIDENCE | 729 (T) 568 619 626 |652 729 (T) 557 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.411N P=0.422N P=0.466N P=0.404N |P=0.380 P=0.332N P=0.513 P=0.605 |
|POLY 3 | P=0.471N P=0.474N P=0.515 P=0.448N |P=0.285 P=0.292N P=0.504 P=0.531 |
|POLY 1.5 | P=0.467N P=0.488N P=0.469 P=0.444N |P=0.298 P=0.290N P=0.503 P=0.545 |
|POLY 6 | P=0.458N P=0.444N P=0.585 P=0.433N |P=0.294 P=0.297N P=0.511 P=0.536 |
|LOGISTIC REGRESSION| P=0.450N P=0.425N P=0.506N P=0.407N |P=0.296 P=0.296N P=0.492 P=0.574 |
|COCH-ARM / FISHERS | P=0.428N P=0.500N P=0.414 P=0.410N |P=0.362 P=0.290N P=0.500 P=0.607N |
|ORDER RESTRICTED | P=0.563N (e) (e) (e) |P=0.426 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 14
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Degeneration Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 3/50 (6%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 1/49 (2%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 5/44.59 3/44.21 2/46.96 1/41.96 |1/44.71 1/43.83 0/44.18 1/41.11 |
|POLY-3 PERCENT (g) | 11.2% 6.8% 4.3% 2.4% |2.2% 2.3% 0.0% 2.4% |
|TERMINAL (d) | 3/31 (10%) 3/33 (9%) 2/39 (5%) 1/31 (3%) |1/35 (3%) 1/32 (3%) 0/36 (0%) 1/35 (3%) |
|FIRST INCIDENCE | 616 729 (T) 729 (T) 729 (T) |729 (T) 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.067N P=0.340N P=0.154N P=0.113N |P=0.575N P=0.742 P=0.494N P=0.762 |
|POLY 3 | P=0.077N P=0.361N P=0.196N P=0.115N |P=0.589N P=0.756 P=0.502N P=0.742 |
|POLY 1.5 | P=0.076N P=0.360N P=0.205N P=0.112N |P=0.588N P=0.756 P=0.501N P=0.745 |
|POLY 6 | P=0.076N P=0.359N P=0.182N P=0.117N |P=0.589N P=0.755 P=0.503N P=0.744 |
|LOGISTIC REGRESSION| P=0.075N P=0.354N P=0.224N P=0.107N |P=0.575N P=0.742 (e) P=0.762 |
|COCH-ARM / FISHERS | P=0.072N P=0.357N P=0.218N P=0.102N |P=0.585N P=0.747 P=0.500N P=0.753N |
|ORDER RESTRICTED | P=0.068N (e) (e) (e) |P=0.552N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Eosinophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 1/50 (2%) 4/50 (8%) 3/50 (6%) |3/50 (6%) 2/49 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 5/43.81 1/44.21 4/47.41 3/42.58 |3/44.84 2/43.83 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 11.4% 2.3% 8.4% 7.1% |6.7% 4.6% 0.0% 0.0% |
|TERMINAL (d) | 5/31 (16%) 1/33 (3%) 2/39 (5%) 2/31 (7%) |2/35 (6%) 2/32 (6%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 619 530 |698 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.545N P=0.087N P=0.369N P=0.362N |P=0.035N* P=0.535N P=0.118N P=0.125N |
|POLY 3 | P=0.555N P=0.099N P=0.451N P=0.372N |P=0.038N* P=0.510N P=0.121N P=0.135N |
|POLY 1.5 | P=0.555N P=0.101N P=0.473N P=0.371N |P=0.038N* P=0.509N P=0.120N P=0.132N |
|POLY 6 | P=0.550N P=0.094N P=0.417N P=0.365N |P=0.038N* P=0.514N P=0.122N P=0.133N |
|LOGISTIC REGRESSION| P=0.558N P=0.087N P=0.442N P=0.377N |P=0.038N* P=0.516N P=0.122N P=0.132N |
|COCH-ARM / FISHERS | P=0.544N P=0.102N P=0.500N P=0.357N |P=0.037N* P=0.510N P=0.121N P=0.121N |
|ORDER RESTRICTED | P=0.268N (e) (e) (e) |P=0.045N* (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 15
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Hepatodiaphragmatic Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 9/50 (18%) 2/50 (4%) 3/50 (6%) 4/50 (8%) |7/50 (14%) 4/49 (8%) 7/50 (14%) 4/50 (8%) |
|POLY-3 RATE (b) | 9/43.98 2/44.94 3/46.96 4/42.01 |7/45.01 4/43.83 7/44.65 4/42.08 |
|POLY-3 PERCENT (g) | 20.5% 4.5% 6.4% 9.5% |15.6% 9.1% 15.7% 9.5% |
|TERMINAL (d) | 7/31 (23%) 1/33 (3%) 3/39 (8%) 3/31 (10%) |6/35 (17%) 4/32 (13%) 6/36 (17%) 3/35 (9%) |
|FIRST INCIDENCE | 702 473 729 (T) 717 |648 729 (T) 593 223 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.208N P=0.022N* P=0.025N* P=0.117N |P=0.333N P=0.312N P=0.602N P=0.269N |
|POLY 3 | P=0.228N P=0.022N* P=0.045N* P=0.131N |P=0.395N P=0.276N P=0.608 P=0.300N |
|POLY 1.5 | P=0.226N P=0.024N* P=0.051N P=0.129N |P=0.388N P=0.274N P=0.610 P=0.293N |
|POLY 6 | P=0.227N P=0.020N* P=0.037N* P=0.128N |P=0.384N P=0.280N P=0.608 P=0.295N |
|LOGISTIC REGRESSION| P=0.228N P=0.027N* P=0.025N* P=0.112N |P=0.376N P=0.278N P=0.604 P=0.256N |
|COCH-ARM / FISHERS | P=0.216N P=0.026N* P=0.061N P=0.117N |P=0.348N P=0.274N P=0.613N P=0.262N |
|ORDER RESTRICTED | P=0.024N* (e) (e) (e) |P=0.315N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |6/50 (12%) 4/49 (8%) 4/50 (8%) 5/50 (10%) |
|POLY-3 RATE (b) | 0/43.81 1/44.21 0/46.96 1/42.07 |6/45.00 4/44.19 4/44.18 5/41.83 |
|POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 2.4% |13.3% 9.1% 9.1% 12.0% |
|TERMINAL (d) | 0/31 (0%) 1/33 (3%) 0/39 (0%) 0/31 (0%) |5/35 (14%) 3/32 (9%) 4/36 (11%) 4/35 (11%) |
|FIRST INCIDENCE | --- 729 (T) --- 703 |652 628 729 (T) 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.468 P=0.512 (e) P=0.512 |P=0.495N P=0.422N P=0.358N P=0.510N |
|POLY 3 | P=0.458 P=0.502 (e) P=0.492 |P=0.551N P=0.381N P=0.381N P=0.551N |
|POLY 1.5 | P=0.458 P=0.501 (e) P=0.493 |P=0.544N P=0.381N P=0.376N P=0.544N |
|POLY 6 | P=0.462 P=0.505 (e) P=0.493 |P=0.544N P=0.382N P=0.385N P=0.543N |
|LOGISTIC REGRESSION| P=0.457 P=0.512 (e) P=0.493 |P=0.556N P=0.382N P=0.372N P=0.542N |
|COCH-ARM / FISHERS | P=0.464 P=0.500 (e) P=0.500 |P=0.505N P=0.383N P=0.370N P=0.500N |
|ORDER RESTRICTED | P=0.243 (e) (e) (e) |P=0.488N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 16
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 41/50 (82%) 35/50 (70%) 38/50 (76%) 37/50 (74%) |7/50 (14%) 5/49 (10%) 6/50 (12%) 2/50 (4%) |
|POLY-3 RATE (b) | 41/47.46 35/47.66 38/47.71 37/44.29 |7/45.04 5/44.59 6/45.23 2/41.13 |
|POLY-3 PERCENT (g) | 86.4% 73.4% 79.6% 83.5% |15.5% 11.2% 13.3% 4.9% |
|TERMINAL (d) | 28/31 (90%) 25/33 (76%) 32/39 (82%) 28/31 (90%) |6/35 (17%) 2/32 (6%) 4/36 (11%) 1/35 (3%) |
|FIRST INCIDENCE | 563 473 649 530 |638 628 540 725 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.406N P=0.110N P=0.025N* P=0.307N |P=0.093N P=0.434N P=0.494N P=0.087N |
|POLY 3 | P=0.420 P=0.081N P=0.261N P=0.461N |P=0.116N P=0.386N P=0.497N P=0.102N |
|POLY 1.5 | P=0.508 P=0.094N P=0.280N P=0.374N |P=0.110N P=0.389N P=0.498N P=0.098N |
|POLY 6 | P=0.342 P=0.070N P=0.241N P=0.558N |P=0.114N P=0.383N P=0.492N P=0.099N |
|LOGISTIC REGRESSION| P=0.536 P=0.114N P=0.094N P=0.424N |P=0.098N P=0.393N P=0.501N P=0.097N |
|COCH-ARM / FISHERS | P=0.393N P=0.121N P=0.312N P=0.235N |P=0.086N P=0.394N P=0.500N P=0.080N |
|ORDER RESTRICTED | P=0.261N (e) (e) (e) |P=0.093N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver: Centrilobular |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |2/50 (4%) 0/49 (0%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/43.98 0/44.21 1/47.35 2/42.37 |2/44.71 0/43.83 1/44.82 0/41.11 |
|POLY-3 PERCENT (g) | 4.6% 0.0% 2.1% 4.7% |4.5% 0.0% 2.2% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |2/35 (6%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 685 --- 619 658 |729 (T) --- 521 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.385 P=0.230N P=0.441N P=0.689 |P=0.253N P=0.258N P=0.491N P=0.238N |
|POLY 3 | P=0.378 P=0.236N P=0.474N P=0.681 |P=0.264N P=0.241N P=0.499N P=0.256N |
|POLY 1.5 | P=0.379 P=0.237N P=0.486N P=0.682 |P=0.262N P=0.241N P=0.499N P=0.253N |
|POLY 6 | P=0.380 P=0.233N P=0.457N P=0.685 |P=0.261N P=0.242N P=0.497N P=0.254N |
|LOGISTIC REGRESSION| P=0.408 P=0.235N P=0.547N P=0.689 |P=0.218N (e) P=0.501N (e) |
|COCH-ARM / FISHERS | P=0.387 P=0.247N P=0.500N P=0.691N |P=0.251N P=0.253N P=0.500N P=0.247N |
|ORDER RESTRICTED | P=0.389 (e) (e) (e) |P=0.087N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 17
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 1/50 (2%) 2/50 (4%) 3/50 (6%) |4/50 (8%) 4/49 (8%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 5/44.99 1/44.50 2/47.59 3/43.47 |4/45.81 4/44.94 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 11.1% 2.3% 4.2% 6.9% |8.7% 8.9% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 1/31 (3%) |1/35 (3%) 1/32 (3%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 544 652 586 401 |591 395 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.497N P=0.103N P=0.173N P=0.380N |P=0.012N* P=0.616 P=0.075N P=0.083N |
|POLY 3 | P=0.484N P=0.103N P=0.194N P=0.375N |P=0.011N* P=0.633 P=0.065N P=0.075N |
|POLY 1.5 | P=0.486N P=0.103N P=0.204N P=0.371N |P=0.010N* P=0.634 P=0.063N P=0.072N |
|POLY 6 | P=0.480N P=0.102N P=0.180N P=0.377N |P=0.011N* P=0.627 P=0.067N P=0.076N |
|LOGISTIC REGRESSION| P=0.317N P=0.100N P=0.318N P=0.235N |P=0.003N** P=0.616 P=0.062N P=0.048N* |
|COCH-ARM / FISHERS | P=0.484N P=0.102N P=0.218N P=0.357N |P=0.009N** P=0.631 P=0.059N P=0.059N |
|ORDER RESTRICTED | P=0.149N (e) (e) (e) |P=0.033N* (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lung |
| Congestion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 4/50 (8%) 3/50 (6%) 7/50 (14%) |5/50 (10%) 2/49 (4%) 5/50 (10%) 8/50 (16%) |
|POLY-3 RATE (b) | 3/44.88 4/46.57 3/47.52 7/44.86 |5/45.01 2/44.52 5/45.65 8/44.94 |
|POLY-3 PERCENT (g) | 6.7% 8.6% 6.3% 15.6% |11.1% 4.5% 11.0% 17.8% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 1/31 (3%) |4/35 (11%) 0/32 (0%) 2/36 (6%) 2/35 (6%) |
|FIRST INCIDENCE | 453 473 637 191 |648 621 560 312 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.112 P=0.500 P=0.592N P=0.159 |P=0.067 P=0.251N P=0.622 P=0.258 |
|POLY 3 | P=0.115 P=0.520 P=0.636N P=0.156 |P=0.071 P=0.220N P=0.622N P=0.274 |
|POLY 1.5 | P=0.114 P=0.511 P=0.648N P=0.155 |P=0.068 P=0.222N P=0.625N P=0.266 |
|POLY 6 | P=0.119 P=0.536 P=0.615N P=0.164 |P=0.079 P=0.219N P=0.614N P=0.295 |
|LOGISTIC REGRESSION| P=0.305 P=0.605 P=0.523 P=0.310 |P=0.202 P=0.226N P=0.627N P=0.427 |
|COCH-ARM / FISHERS | P=0.117 P=0.500 P=0.661N P=0.159 |P=0.074 P=0.226N P=0.630N P=0.277 |
|ORDER RESTRICTED | P=0.114 (e) (e) (e) |P=0.099 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 18
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lung |
| Foreign Body |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 1/47.66 2/43.61 |0/44.71 0/43.83 0/44.18 1/41.83 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.1% 4.6% |0.0% 0.0% 0.0% 2.4% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 489 191 |--- --- --- 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.058 (e) P=0.504 P=0.233 |P=0.176 (e) (e) P=0.483 |
|POLY 3 | P=0.060 (e) P=0.517 P=0.236 |P=0.179 (e) (e) P=0.487 |
|POLY 1.5 | P=0.060 (e) P=0.509 P=0.236 |P=0.180 (e) (e) P=0.488 |
|POLY 6 | P=0.060 (e) P=0.527 P=0.239 |P=0.182 (e) (e) P=0.490 |
|LOGISTIC REGRESSION| P=0.423 (e) P=0.307 P=0.666 |P=0.353 (e) (e) P=0.677 |
|COCH-ARM / FISHERS | P=0.060 (e) P=0.500 P=0.247 |P=0.188 (e) (e) P=0.500 |
|ORDER RESTRICTED | P=0.074 (e) (e) (e) |P=0.108 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lung |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 28/50 (56%) 29/50 (58%) 36/50 (72%) 26/50 (52%) |41/50 (82%) 37/49 (76%) 39/50 (78%) 38/50 (76%) |
|POLY-3 RATE (b) | 28/45.50 29/46.20 36/48.15 26/43.80 |41/48.29 37/47.25 39/46.77 38/44.10 |
|POLY-3 PERCENT (g) | 61.5% 62.8% 74.8% 59.4% |84.9% 78.3% 83.4% 86.2% |
|TERMINAL (d) | 21/31 (68%) 22/33 (67%) 31/39 (80%) 19/31 (61%) |30/35 (86%) 27/32 (84%) 32/36 (89%) 30/35 (86%) |
|FIRST INCIDENCE | 563 576 586 576 |344 395 557 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.430N P=0.532N P=0.484 P=0.438N |P=0.358N P=0.489N P=0.381N P=0.398N |
|POLY 3 | P=0.536 P=0.538 P=0.115 P=0.503N |P=0.318 P=0.276N P=0.533N P=0.552 |
|POLY 1.5 | P=0.524N P=0.518 P=0.092 P=0.490N |P=0.401 P=0.278N P=0.474N P=0.608N |
|POLY 6 | P=0.524N P=0.580 P=0.159 P=0.483N |P=0.314 P=0.293N P=0.607N P=0.557 |
|LOGISTIC REGRESSION| P=0.534N P=0.519 P=0.187 P=0.526N |P=0.367 P=0.286N P=0.437N P=0.577 |
|COCH-ARM / FISHERS | P=0.435N P=0.500 P=0.072 P=0.421N |P=0.367N P=0.294N P=0.402N P=0.312N |
|ORDER RESTRICTED | P=0.373N (e) (e) (e) |P=0.429 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 19
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lung |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 29/50 (58%) 23/50 (46%) 36/50 (72%) 30/50 (60%) |29/50 (58%) 33/49 (67%) 29/50 (58%) 33/50 (66%) |
|POLY-3 RATE (b) | 29/46.82 23/46.20 36/48.47 30/45.45 |29/46.26 33/46.39 29/45.72 33/44.76 |
|POLY-3 PERCENT (g) | 62.0% 49.8% 74.3% 66.0% |62.7% 71.1% 63.4% 73.7% |
|TERMINAL (d) | 19/31 (61%) 18/33 (55%) 31/39 (80%) 22/31 (71%) |23/35 (66%) 25/32 (78%) 26/36 (72%) 27/35 (77%) |
|FIRST INCIDENCE | 544 473 586 191 |640 568 560 223 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.166 P=0.128N P=0.544 P=0.481 |P=0.431 P=0.156 P=0.548N P=0.258 |
|POLY 3 | P=0.101 P=0.160N P=0.135 P=0.423 |P=0.254 P=0.254 P=0.558 P=0.175 |
|POLY 1.5 | P=0.116 P=0.158N P=0.119 P=0.453 |P=0.285 P=0.244 P=0.573 P=0.192 |
|POLY 6 | P=0.091 P=0.162N P=0.163 P=0.396 |P=0.247 P=0.262 P=0.535 P=0.178 |
|LOGISTIC REGRESSION| P=0.112 P=0.154N P=0.162 P=0.449 |P=0.197 P=0.219 P=0.534 P=0.145 |
|COCH-ARM / FISHERS | P=0.149 P=0.158N P=0.104 P=0.500 |P=0.389 P=0.226 P=0.580N P=0.268 |
|ORDER RESTRICTED | P=0.106 (e) (e) (e) |P=0.191 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 9/50 (18%) 4/50 (8%) 6/50 (12%) |1/50 (2%) 4/49 (8%) 3/50 (6%) 2/50 (4%) |
|POLY-3 RATE (b) | 7/44.83 9/44.92 4/46.96 6/42.41 |1/44.71 4/44.60 3/44.18 2/41.31 |
|POLY-3 PERCENT (g) | 15.6% 20.0% 8.5% 14.2% |2.2% 9.0% 6.8% 4.8% |
|TERMINAL (d) | 4/31 (13%) 6/33 (18%) 4/39 (10%) 4/31 (13%) |1/35 (3%) 2/32 (6%) 3/36 (8%) 1/35 (3%) |
|FIRST INCIDENCE | 620 590 729 (T) 652 |729 (T) 568 729 (T) 677 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.252N P=0.431 P=0.173N P=0.512N |P=0.539N P=0.170 P=0.315 P=0.506 |
|POLY 3 | P=0.271N P=0.393 P=0.235N P=0.543N |P=0.568 P=0.178 P=0.301 P=0.472 |
|POLY 1.5 | P=0.268N P=0.392 P=0.246N P=0.532N |P=0.576 P=0.176 P=0.303 P=0.476 |
|POLY 6 | P=0.268N P=0.400 P=0.218N P=0.547N |P=0.577 P=0.179 P=0.300 P=0.478 |
|LOGISTIC REGRESSION| P=0.268N P=0.394 P=0.254N P=0.524N |P=0.573N P=0.171 P=0.315 P=0.474 |
|COCH-ARM / FISHERS | P=0.252N P=0.393 P=0.262N P=0.500N |P=0.544N P=0.175 P=0.309 P=0.500 |
|ORDER RESTRICTED | P=0.304N (e) (e) (e) |P=0.282 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 20
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 3/50 (6%) 4/50 (8%) 9/50 (18%) |0/49 (0%) 1/49 (2%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 7/43.91 3/44.81 4/46.96 9/43.37 |0/44.36 1/43.83 1/44.82 0/41.11 |
|POLY-3 PERCENT (g) | 15.9% 6.7% 8.5% 20.8% |0.0% 2.3% 2.2% 0.0% |
|TERMINAL (d) | 6/31 (19%) 2/33 (6%) 4/39 (10%) 7/31 (23%) |0/35 (0%) 1/32 (3%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 702 540 729 (T) 465 |--- 729 (T) 521 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.143 P=0.136N P=0.146N P=0.391 |P=0.542N P=0.482 P=0.504 (e) |
|POLY 3 | P=0.142 P=0.148N P=0.223N P=0.381 |P=0.553N P=0.498 P=0.502 (e) |
|POLY 1.5 | P=0.142 P=0.153N P=0.240N P=0.379 |P=0.549N P=0.499 P=0.503 (e) |
|POLY 6 | P=0.144 P=0.139N P=0.199N P=0.392 |P=0.552N P=0.496 P=0.502 (e) |
|LOGISTIC REGRESSION| P=0.140 P=0.153N P=0.149N P=0.367 |P=0.447N P=0.482 P=0.424 (e) |
|COCH-ARM / FISHERS | P=0.149 P=0.159N P=0.262N P=0.393 |P=0.531N P=0.500 P=0.505 (e) |
|ORDER RESTRICTED | P=0.112 (e) (e) (e) |P=0.404 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lymph Node: Mediastinal |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 9/21 (43%) 9/17 (53%) 10/10 (100%) 15/18 (83%) |5/15 (33%) 7/8 (88%) 8/11 (73%) 2/3 (67%) |
|POLY-3 RATE (b) | 9/18.01 9/16.69 10/10.00 15/17.05 |5/13.78 7/7.70 8/10.37 2/2.06 |
|POLY-3 PERCENT (g) | 50.0% 53.9% 100.0% 88.0% |36.3% 90.9% 77.2% 97.1% |
|TERMINAL (d) | 7/11 (64%) 5/10 (50%) 9/9 (100%) 12/13 (92%) |4/10 (40%) 4/4 (100%) 6/8 (75%) 2/2 (100%) |
|FIRST INCIDENCE | 649 540 637 508 |652 395 492 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.067 P=0.557 P=0.288 P=0.119 |P=0.548 P=0.045 * P=0.129 P=0.494 |
|POLY 3 | P<0.001 ** P=0.543 P=0.002 ** P=0.009 ** |P=0.042 * P=0.010 * P=0.044 * P=0.206 |
|POLY 1.5 | P<0.001 ** P=0.475 P<0.001 ** P=0.008 ** |P=0.051 P=0.011 * P=0.044 * P=0.227 |
|POLY 6 | P<0.001 ** P=0.634 P=0.005 ** P=0.014 * |P=0.048 * P=0.010 * P=0.050 P=0.209 |
|LOGISTIC REGRESSION| P=0.002 ** P=0.399 P=0.017 * P=0.010 * |P=0.103 P=0.021 * P=0.047 * P=0.214 |
|COCH-ARM / FISHERS | P=0.002 ** P=0.385 P=0.002 ** P=0.011 * |P=0.158 P=0.019 * P=0.055 P=0.326 |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.252 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 21
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Lymph Node: Pancreatic |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/21 (10%) 4/17 (24%) 1/10 (10%) 1/18 (6%) |1/15 (7%) 0/8 (0%) 1/11 (9%) 1/3 (33%) |
|POLY-3 RATE (b) | 2/17.51 4/14.82 1/9.67 1/16.24 |1/13.50 0/6.25 1/9.37 1/3.00 |
|POLY-3 PERCENT (g) | 11.4% 27.0% 10.3% 6.2% |7.4% 0.0% 10.7% 33.3% |
|TERMINAL (d) | 2/11 (18%) 4/10 (40%) 1/9 (11%) 0/13 (0%) |1/10 (10%) 0/4 (0%) 1/8 (13%) 0/2 (0%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 504 |729 (T) --- 729 (T) 284 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.124N P=0.272 P=0.573N P=0.466N |P=0.288 P=0.682N P=0.716 P=0.596 |
|POLY 3 | P=0.188N P=0.247 P=0.709N P=0.527N |P=0.188 P=0.649N P=0.678 P=0.392 |
|POLY 1.5 | P=0.203N P=0.241 P=0.727N P=0.539N |P=0.179 P=0.640N P=0.681 P=0.381 |
|POLY 6 | P=0.166N P=0.259 P=0.681N P=0.507N |P=0.204 P=0.656N P=0.679 P=0.410 |
|LOGISTIC REGRESSION| P=0.213N P=0.272 P=0.573N P=0.567N |P=0.324 (e) P=0.716 P=0.924 |
|COCH-ARM / FISHERS | P=0.222N P=0.233 P=0.704 P=0.559N |P=0.165 P=0.652N P=0.677 P=0.314 |
|ORDER RESTRICTED | P=0.204N (e) (e) (e) |P=0.257 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 23/50 (46%) 18/50 (36%) 20/50 (40%) 20/50 (40%) |0/50 (0%) 0/49 (0%) 2/50 (4%) 1/50 (2%) |
|POLY-3 RATE (b) | 23/45.74 18/48.14 20/48.62 20/44.79 |0/44.71 0/43.83 2/44.18 1/41.11 |
|POLY-3 PERCENT (g) | 50.3% 37.4% 41.1% 44.7% |0.0% 0.0% 4.5% 2.4% |
|TERMINAL (d) | 14/31 (45%) 7/33 (21%) 12/39 (31%) 12/31 (39%) |0/35 (0%) 0/32 (0%) 2/36 (6%) 1/35 (3%) |
|FIRST INCIDENCE | 641 473 586 504 |--- --- 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.464N P=0.193N P=0.135N P=0.377N |P=0.218 (e) P=0.244 P=0.500 |
|POLY 3 | P=0.515N P=0.144N P=0.245N P=0.371N |P=0.179 (e) P=0.234 P=0.483 |
|POLY 1.5 | P=0.501N P=0.169N P=0.286N P=0.372N |P=0.184 (e) P=0.236 P=0.486 |
|POLY 6 | P=0.524N P=0.116N P=0.197N P=0.359N |P=0.184 (e) P=0.234 P=0.485 |
|LOGISTIC REGRESSION| P=0.442N P=0.209N P=0.296N P=0.394N |(e) (e) P=0.244 P=0.500 |
|COCH-ARM / FISHERS | P=0.449N P=0.208N P=0.343N P=0.343N |P=0.210 (e) P=0.247 P=0.500 |
|ORDER RESTRICTED | P=0.298N (e) (e) (e) |P=0.166 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 22
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |18/50 (36%) 19/49 (39%) 9/50 (18%) 7/50 (14%) |
|POLY-3 RATE (b) | 1/43.81 0/44.21 1/46.96 0/41.96 |18/45.56 19/45.87 9/44.64 7/41.11 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 2.1% 0.0% |39.5% 41.4% 20.2% 17.0% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 1/39 (3%) 0/31 (0%) |15/35 (43%) 13/32 (41%) 8/36 (22%) 7/35 (20%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) --- |563 568 596 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.461N P=0.488N P=0.710N P=0.500N |P<0.001N** P=0.396 P=0.031N* P=0.010N* |
|POLY 3 | P=0.471N P=0.498N P=0.745N P=0.509N |P=0.002N** P=0.511 P=0.035N* P=0.017N* |
|POLY 1.5 | P=0.470N P=0.499N P=0.752N P=0.507N |P=0.002N** P=0.494 P=0.034N* P=0.015N* |
|POLY 6 | P=0.472N P=0.495N P=0.734N P=0.508N |P=0.002N** P=0.533 P=0.035N* P=0.016N* |
|LOGISTIC REGRESSION| P=0.461N (e) P=0.710N (e) |P=0.002N** P=0.471 P=0.037N* P=0.015N* |
|COCH-ARM / FISHERS | P=0.464N P=0.500N P=0.753N P=0.500N |P<0.001N** P=0.469 P=0.035N* P=0.010N* |
|ORDER RESTRICTED | P=0.259N (e) (e) (e) |P=0.010N* (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland |
| Hyperplasia Atypical |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 3/49 (6%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 0/46.96 0/41.96 |3/44.71 3/43.83 1/44.35 0/41.11 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |6.7% 6.9% 2.3% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |3/35 (9%) 3/32 (9%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 687 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.040N* P=0.622 P=0.295N P=0.121N |
|POLY 3 | (e) (e) (e) (e) |P=0.048N* P=0.653 P=0.308N P=0.134N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.048N* P=0.654 P=0.307N P=0.132N |
|POLY 6 | (e) (e) (e) (e) |P=0.047N* P=0.652 P=0.307N P=0.132N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.044N* P=0.622 P=0.308N (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.043N* P=0.651 P=0.309N P=0.121N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.086N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 23
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland: Duct |
| Dilatation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |31/50 (62%) 28/49 (57%) 29/50 (58%) 24/50 (48%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 0/46.96 0/41.96 |31/46.75 28/46.68 29/46.26 24/41.99 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |66.3% 60.0% 62.7% 57.2% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |25/35 (71%) 18/32 (56%) 25/36 (69%) 21/35 (60%) |
|FIRST INCIDENCE | --- --- --- --- |563 395 492 573 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.105N P=0.504N P=0.383N P=0.132N |
|POLY 3 | (e) (e) (e) (e) |P=0.281N P=0.335N P=0.440N P=0.248N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.231N P=0.351N P=0.425N P=0.210N |
|POLY 6 | (e) (e) (e) (e) |P=0.297N P=0.317N P=0.461N P=0.252N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.226N P=0.382N P=0.449N P=0.224N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.108N P=0.387N P=0.419N P=0.114N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.296N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland: Duct |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/49 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 0/46.96 0/41.96 |2/44.92 0/43.83 0/44.18 1/41.11 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.5% 0.0% 0.0% 2.4% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |1/35 (3%) 0/32 (0%) 0/36 (0%) 1/35 (3%) |
|FIRST INCIDENCE | --- --- --- --- |674 --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.519N P=0.247N P=0.234N P=0.497N |
|POLY 3 | (e) (e) (e) (e) |P=0.528N P=0.243N P=0.241N P=0.531N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.528N P=0.242N P=0.239N P=0.525N |
|POLY 6 | (e) (e) (e) (e) |P=0.527N P=0.244N P=0.242N P=0.529N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.547N P=0.242N P=0.238N P=0.526N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.527N P=0.253N P=0.247N P=0.500N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.150N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 24
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Mesentery: Fat |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 14/16 (88%) 9/11 (82%) 8/9 (89%) 7/12 (58%) |17/17 (100%) 14/14 (100%) 11/12 (92%) 8/8 (100%) |
|POLY-3 RATE (b) | 14/15.69 9/10.53 8/8.61 7/11.21 |17/17.00 14/14.00 11/12.00 8/8.00 |
|POLY-3 PERCENT (g) | 89.2% 85.5% 92.9% 62.5% |100.0% 100.0% 91.7% 100.0% |
|TERMINAL (d) | 9/10 (90%) 8/9 (89%) 5/5 (100%) 4/6 (67%) |10/10 (100%) 11/11 (100%) 9/10 (90%) 7/7 (100%) |
|FIRST INCIDENCE | 544 652 637 530 |344 621 557 677 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.311N P=0.140N P=0.398N P=0.216N |P=0.034N* (e) P=0.064N (e) |
|POLY 3 | P=0.058N P=0.629N P=0.674 P=0.103N |P=0.558N (e) P=0.430N (e) |
|POLY 1.5 | P=0.057N P=0.597N P=0.686 P=0.095N |P=0.558N (e) P=0.430N (e) |
|POLY 6 | P=0.069N P=0.668N P=0.653 P=0.124N |P=0.558N (e) P=0.430N (e) |
|LOGISTIC REGRESSION| P=0.058N P=0.490N P=0.741N P=0.093N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.059N P=0.545N P=0.757N P=0.093N |P=0.558N (e) P=0.414N (e) |
|ORDER RESTRICTED | P=0.028N* (e) (e) (e) |P=0.371N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Nose |
| Foreign Body |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/50 (14%) 4/50 (8%) 12/50 (24%) 7/50 (14%) |4/50 (8%) 3/49 (6%) 1/50 (2%) 3/50 (6%) |
|POLY-3 RATE (b) | 7/44.37 4/44.24 12/47.40 7/42.47 |4/44.71 3/43.93 1/44.35 3/41.73 |
|POLY-3 PERCENT (g) | 15.8% 9.0% 25.3% 16.5% |9.0% 6.8% 2.3% 7.2% |
|TERMINAL (d) | 5/31 (16%) 3/33 (9%) 10/39 (26%) 6/31 (19%) |4/35 (11%) 2/32 (6%) 0/36 (0%) 2/35 (6%) |
|FIRST INCIDENCE | 642 723 649 576 |729 (T) 702 687 527 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.278 P=0.234N P=0.306 P=0.601 |P=0.379N P=0.542N P=0.172N P=0.509N |
|POLY 3 | P=0.242 P=0.262N P=0.192 P=0.580 |P=0.408N P=0.510N P=0.181N P=0.538N |
|POLY 1.5 | P=0.250 P=0.263N P=0.174 P=0.586 |P=0.406N P=0.509N P=0.180N P=0.533N |
|POLY 6 | P=0.242 P=0.257N P=0.221 P=0.581 |P=0.402N P=0.511N P=0.180N P=0.528N |
|LOGISTIC REGRESSION| P=0.253 P=0.246N P=0.206 P=0.583 |P=0.419N P=0.524N P=0.180N P=0.533N |
|COCH-ARM / FISHERS | P=0.281 P=0.262N P=0.154 P=0.613N |P=0.386N P=0.511N P=0.181N P=0.500N |
|ORDER RESTRICTED | P=0.220 (e) (e) (e) |P=0.329N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 25
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Nose |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 12/50 (24%) 3/50 (6%) 20/50 (40%) 15/50 (30%) |8/50 (16%) 7/49 (14%) 9/50 (18%) 6/50 (12%) |
|POLY-3 RATE (b) | 12/45.22 3/44.24 20/48.11 15/45.51 |8/45.30 7/44.62 9/45.74 6/41.73 |
|POLY-3 PERCENT (g) | 26.5% 6.8% 41.6% 33.0% |17.7% 15.7% 19.7% 14.4% |
|TERMINAL (d) | 8/31 (26%) 2/33 (6%) 15/39 (39%) 7/31 (23%) |6/35 (17%) 4/32 (13%) 4/36 (11%) 5/35 (14%) |
|FIRST INCIDENCE | 563 723 586 401 |648 628 492 527 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.021 * P=0.012N* P=0.222 P=0.323 |P=0.391N P=0.558N P=0.506 P=0.405N |
|POLY 3 | P=0.017 * P=0.011N* P=0.092 P=0.330 |P=0.457N P=0.513N P=0.509 P=0.451N |
|POLY 1.5 | P=0.015 * P=0.011N* P=0.079 P=0.320 |P=0.446N P=0.513N P=0.506 P=0.440N |
|POLY 6 | P=0.022 * P=0.011N* P=0.117 P=0.352 |P=0.449N P=0.514N P=0.518 P=0.445N |
|LOGISTIC REGRESSION| P=0.019 * P=0.012N* P=0.077 P=0.362 |P=0.412N P=0.516N P=0.501 P=0.439N |
|COCH-ARM / FISHERS | P=0.018 * P=0.011N* P=0.066 P=0.326 |P=0.382N P=0.517N P=0.500 P=0.387N |
|ORDER RESTRICTED | P=0.014 * (e) (e) (e) |P=0.537N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Oral Mucosa: Pharyngeal |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 2/4 (50%) |1/2 (50%) 0/0 (0%) 0/0 (0%) 1/1 (100%) |
|POLY-3 RATE (b) | 0/1.00 0/0.00 0/0.00 2/3.66 |1/1.53 0/0.00 0/0.00 1/1.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 54.7% |65.2% 0.0% 0.0% 100.0% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |1/1 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- 576 |729 (T) --- --- 544 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.043 * (e) (e) P=0.253 |P=0.168 P=1.000N P=1.000N P=0.468 |
|POLY 3 | (e) (e) (e) P=0.559 |(e) (e) (e) P=0.785 |
|POLY 1.5 | (e) (e) (e) P=0.568 |(e) (e) (e) P=0.692 |
|POLY 6 | (e) (e) (e) P=0.540 |(e) (e) (e) P=0.956 |
|LOGISTIC REGRESSION| P=0.675 (e) (e) P=0.915 |P=0.220 (e) (e) P=0.546 |
|COCH-ARM / FISHERS | P=0.366 (e) (e) P=0.600 |P=0.414 P=1.000 P=1.000 P=0.667 |
|ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 26
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Oral Mucosa: Pharyngeal |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 2/4 (50%) |0/2 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) |
|POLY-3 RATE (b) | 0/1.00 0/0.00 0/0.00 2/3.66 |0/1.53 0/0.00 0/0.00 0/0.42 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 54.7% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- 576 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.043 * (e) (e) P=0.253 |(e) (e) (e) (e) |
|POLY 3 | (e) (e) (e) P=0.559 |(e) (e) (e) (e) |
|POLY 1.5 | (e) (e) (e) P=0.568 |(e) (e) (e) (e) |
|POLY 6 | (e) (e) (e) P=0.540 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.675 (e) (e) P=0.915 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.366 (e) (e) P=0.600 |(e) (e) (e) (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Ovary |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |11/50 (22%) 4/49 (8%) 9/50 (18%) 10/50 (20%) |
|POLY-3 RATE (b) | |11/44.71 4/44.15 9/44.64 10/41.90 |
|POLY-3 PERCENT (g) | |24.6% 9.1% 20.2% 23.9% |
|TERMINAL (d) | |11/35 (31%) 3/32 (9%) 8/36 (22%) 8/35 (23%) |
|FIRST INCIDENCE | |729 (T) 641 596 527 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.333 P=0.063N P=0.375N P=0.505N |
|POLY 3 | |P=0.255 P=0.045N* P=0.401N P=0.568N |
|POLY 1.5 | |P=0.262 P=0.046N* P=0.401N P=0.562N |
|POLY 6 | |P=0.270 P=0.043N* P=0.396N P=0.546N |
|LOGISTIC REGRESSION| |P=0.248 P=0.050N P=0.404N P=0.579N |
|COCH-ARM / FISHERS | |P=0.317 P=0.049N* P=0.402N P=0.500N |
|ORDER RESTRICTED | |P=0.325N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 27
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Pancreas |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 43/50 (86%) 31/50 (62%) 35/50 (70%) 32/50 (64%) |26/49 (53%) 20/48 (42%) 23/48 (48%) 23/49 (47%) |
|POLY-3 RATE (b) | 43/48.10 31/48.72 35/49.06 32/44.80 |26/45.89 20/44.32 23/44.53 23/42.60 |
|POLY-3 PERCENT (g) | 89.4% 63.6% 71.3% 71.4% |56.7% 45.1% 51.7% 54.0% |
|TERMINAL (d) | 30/31 (97%) 18/33 (55%) 28/39 (72%) 22/31 (71%) |20/35 (57%) 15/32 (47%) 19/36 (53%) 18/35 (51%) |
|FIRST INCIDENCE | 544 540 586 563 |638 585 596 223 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.138N P=0.020N* P=0.004N** P=0.045N* |P=0.446N P=0.266N P=0.329N P=0.376N |
|POLY 3 | P=0.184N P=0.002N** P=0.019N* P=0.019N* |P=0.457 P=0.184N P=0.393N P=0.485N |
|POLY 1.5 | P=0.146N P=0.003N** P=0.027N* P=0.015N* |P=0.482 P=0.179N P=0.386N P=0.453N |
|POLY 6 | P=0.218N P<0.001N** P=0.011N* P=0.020N* |P=0.470 P=0.195N P=0.397N P=0.483N |
|LOGISTIC REGRESSION| P=0.115N P=0.006N** P=0.026N* P=0.020N* |P=0.425 P=0.184N P=0.390N P=0.486N |
|COCH-ARM / FISHERS | P=0.081N P=0.006N** P=0.045N* P=0.010N* |P=0.479N P=0.179N P=0.381N P=0.343N |
|ORDER RESTRICTED | P=0.013N* (e) (e) (e) |P=0.427N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 6/50 (12%) 15/50 (30%) 12/50 (24%) |3/49 (6%) 1/48 (2%) 2/48 (4%) 1/49 (2%) |
|POLY-3 RATE (b) | 4/44.20 6/44.74 15/47.64 12/42.78 |3/44.78 1/43.14 2/43.32 1/40.47 |
|POLY-3 PERCENT (g) | 9.1% 13.4% 31.5% 28.1% |6.7% 2.3% 4.6% 2.5% |
|TERMINAL (d) | 3/31 (10%) 5/33 (15%) 13/39 (33%) 9/31 (29%) |1/35 (3%) 1/32 (3%) 2/36 (6%) 0/35 (0%) |
|FIRST INCIDENCE | 616 568 619 626 |648 729 (T) 729 (T) 677 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.009 ** P=0.396 P=0.020 * P=0.029 * |P=0.326N P=0.333N P=0.499N P=0.317N |
|POLY 3 | P=0.006 ** P=0.377 P=0.007 ** P=0.020 * |P=0.358N P=0.319N P=0.515N P=0.342N |
|POLY 1.5 | P=0.006 ** P=0.373 P=0.005 ** P=0.021 * |P=0.353N P=0.316N P=0.512N P=0.335N |
|POLY 6 | P=0.006 ** P=0.386 P=0.009 ** P=0.020 * |P=0.353N P=0.323N P=0.517N P=0.340N |
|LOGISTIC REGRESSION| P=0.007 ** P=0.372 P=0.008 ** P=0.022 * |P=0.352N P=0.312N P=0.510N P=0.314N |
|COCH-ARM / FISHERS | P=0.010 * P=0.370 P=0.005 ** P=0.027 * |P=0.328N P=0.316N P=0.510N P=0.309N |
|ORDER RESTRICTED | P=0.010 * (e) (e) (e) |P=0.261N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 28
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 14/50 (28%) 30/50 (60%) 16/50 (32%) 15/50 (30%) |28/50 (56%) 27/49 (55%) 29/50 (58%) 21/50 (42%) |
|POLY-3 RATE (b) | 14/45.17 30/48.23 16/47.92 15/44.82 |28/45.76 27/46.10 29/46.83 21/41.83 |
|POLY-3 PERCENT (g) | 31.0% 62.2% 33.4% 33.5% |61.2% 58.6% 61.9% 50.2% |
|TERMINAL (d) | 8/31 (26%) 19/33 (58%) 12/39 (31%) 8/31 (26%) |24/35 (69%) 19/32 (59%) 21/36 (58%) 19/35 (54%) |
|FIRST INCIDENCE | 641 473 586 508 |638 568 492 573 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.105N P=0.008 ** P=0.499N P=0.481 |P=0.090N P=0.496 P=0.535 P=0.115N |
|POLY 3 | P=0.078N P<0.001 ** P=0.490 P=0.490 |P=0.203N P=0.482N P=0.557 P=0.201N |
|POLY 1.5 | P=0.082N P<0.001 ** P=0.457 P=0.483 |P=0.176N P=0.508N P=0.534 P=0.184N |
|POLY 6 | P=0.068N P=0.002 ** P=0.535 P=0.512 |P=0.198N P=0.447N P=0.581N P=0.189N |
|LOGISTIC REGRESSION| P=0.081N P<0.001 ** P=0.462 P=0.490 |P=0.190N P=0.546N P=0.463 P=0.191N |
|COCH-ARM / FISHERS | P=0.082N P<0.001 ** P=0.414 P=0.500 |P=0.091N P=0.545N P=0.500 P=0.115N |
|ORDER RESTRICTED | P=0.136N (e) (e) (e) |P=0.235N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 3/50 (6%) 6/50 (12%) 5/50 (10%) |21/50 (42%) 19/49 (39%) 16/50 (32%) 23/50 (46%) |
|POLY-3 RATE (b) | 6/44.01 3/44.21 6/47.11 5/42.01 |21/46.12 19/46.06 16/45.87 23/43.23 |
|POLY-3 PERCENT (g) | 13.6% 6.8% 12.7% 11.9% |45.5% 41.3% 34.9% 53.2% |
|TERMINAL (d) | 5/31 (16%) 3/33 (9%) 5/39 (13%) 4/31 (13%) |16/35 (46%) 13/32 (41%) 13/36 (36%) 19/35 (54%) |
|FIRST INCIDENCE | 675 729 (T) 690 717 |591 395 540 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.494 P=0.213N P=0.458N P=0.500N |P=0.383 P=0.536N P=0.201N P=0.396 |
|POLY 3 | P=0.457 P=0.239N P=0.572N P=0.533N |P=0.252 P=0.418N P=0.201N P=0.302 |
|POLY 1.5 | P=0.463 P=0.241N P=0.594N P=0.526N |P=0.270 P=0.427N P=0.200N P=0.318 |
|POLY 6 | P=0.458 P=0.232N P=0.539N P=0.532N |P=0.260 P=0.418N P=0.204N P=0.316 |
|LOGISTIC REGRESSION| P=0.478 P=0.210N P=0.513N P=0.509N |P=0.274 P=0.450N P=0.210N P=0.292 |
|COCH-ARM / FISHERS | P=0.488 P=0.243N P=0.620N P=0.500N |P=0.366 P=0.452N P=0.204N P=0.420 |
|ORDER RESTRICTED | P=0.513N (e) (e) (e) |P=0.174 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 29
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 9/50 (18%) 9/50 (18%) 9/50 (18%) 13/50 (26%) |5/50 (10%) 8/49 (16%) 6/50 (12%) 6/50 (12%) |
|POLY-3 RATE (b) | 9/45.31 9/44.21 9/46.96 13/42.67 |5/45.55 8/44.33 6/44.78 6/42.22 |
|POLY-3 PERCENT (g) | 19.9% 20.4% 19.2% 30.5% |11.0% 18.1% 13.4% 14.2% |
|TERMINAL (d) | 6/31 (19%) 9/33 (27%) 9/39 (23%) 11/31 (36%) |3/35 (9%) 7/32 (22%) 5/36 (14%) 4/35 (11%) |
|FIRST INCIDENCE | 544 729 (T) 729 (T) 563 |563 576 540 544 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.159 P=0.562N P=0.423N P=0.225 |P=0.509N P=0.233 P=0.504 P=0.466 |
|POLY 3 | P=0.140 P=0.581 P=0.571N P=0.182 |P=0.542 P=0.257 P=0.488 P=0.447 |
|POLY 1.5 | P=0.145 P=0.589 P=0.585N P=0.196 |P=0.550 P=0.261 P=0.494 P=0.454 |
|POLY 6 | P=0.140 P=0.578 P=0.546N P=0.175 |P=0.551N P=0.250 P=0.483 P=0.456 |
|LOGISTIC REGRESSION| P=0.140 P=0.598N P=0.595N P=0.207 |P=0.522N P=0.263 P=0.502 P=0.504 |
|COCH-ARM / FISHERS | P=0.167 P=0.602N P=0.602N P=0.235 |P=0.503N P=0.264 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.179 (e) (e) (e) |P=0.451 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Preputial Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 0/50 (0%) 0/50 (0%) 3/50 (6%) | |
|POLY-3 RATE (b) | 4/44.19 0/44.21 0/46.96 3/42.13 | |
|POLY-3 PERCENT (g) | 9.1% 0.0% 0.0% 7.1% | |
|TERMINAL (d) | 3/31 (10%) 0/33 (0%) 0/39 (0%) 2/31 (7%) | |
|FIRST INCIDENCE | 620 --- --- 687 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.523 P=0.060N P=0.044N* P=0.503N | |
|POLY 3 | P=0.518 P=0.060N P=0.053N P=0.526N | |
|POLY 1.5 | P=0.517 P=0.060N P=0.056N P=0.520N | |
|POLY 6 | P=0.521 P=0.058N P=0.048N* P=0.526N | |
|LOGISTIC REGRESSION| P=0.508 P=0.062N P=0.060N P=0.522N | |
|COCH-ARM / FISHERS | P=0.519 P=0.059N P=0.059N P=0.500N | |
|ORDER RESTRICTED | P=0.079N (e) (e) (e) | |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 30
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Preputial Gland |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 5/50 (10%) 4/50 (8%) 4/50 (8%) | |
|POLY-3 RATE (b) | 5/43.81 5/44.31 4/46.96 4/41.96 | |
|POLY-3 PERCENT (g) | 11.4% 11.3% 8.5% 9.5% | |
|TERMINAL (d) | 5/31 (16%) 3/33 (9%) 4/39 (10%) 4/31 (13%) | |
|FIRST INCIDENCE | 729 (T) 712 729 (T) 729 (T) | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.379N P=0.581N P=0.357N P=0.500N | |
|POLY 3 | P=0.406N P=0.624N P=0.457N P=0.527N | |
|POLY 1.5 | P=0.405N P=0.627N P=0.476N P=0.522N | |
|POLY 6 | P=0.400N P=0.613N P=0.427N P=0.525N | |
|LOGISTIC REGRESSION| P=0.382N P=0.574N P=0.357N P=0.500N | |
|COCH-ARM / FISHERS | P=0.389N P=0.630N P=0.500N P=0.500N | |
|ORDER RESTRICTED | P=0.561N (e) (e) (e) | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Prostate |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 31/50 (62%) 28/50 (56%) 27/50 (54%) 26/50 (52%) | |
|POLY-3 RATE (b) | 31/47.65 28/48.13 27/49.55 26/46.86 | |
|POLY-3 PERCENT (g) | 65.1% 58.2% 54.5% 55.5% | |
|TERMINAL (d) | 18/31 (58%) 17/33 (52%) 18/39 (46%) 16/31 (52%) | |
|FIRST INCIDENCE | 563 473 489 401 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.262N P=0.298N P=0.088N P=0.288N | |
|POLY 3 | P=0.225N P=0.313N P=0.195N P=0.226N | |
|POLY 1.5 | P=0.226N P=0.323N P=0.223N P=0.226N | |
|POLY 6 | P=0.225N P=0.303N P=0.165N P=0.229N | |
|LOGISTIC REGRESSION| P=0.181N P=0.344N P=0.332N P=0.204N | |
|COCH-ARM / FISHERS | P=0.208N P=0.342N P=0.272N P=0.210N | |
|ORDER RESTRICTED | P=0.254N (e) (e) (e) | |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 31
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 5/50 (10%) 1/50 (2%) |0/50 (0%) 3/49 (6%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 5/47.29 1/41.96 |0/44.71 3/44.12 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 10.6% 2.4% |0.0% 6.8% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 4/39 (10%) 1/31 (3%) |0/35 (0%) 2/32 (6%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 637 729 (T) |--- 648 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.178 (e) P=0.054 P=0.500 |P=0.170N P=0.109 (e) (e) |
|POLY 3 | P=0.150 (e) P=0.038 * P=0.491 |P=0.170N P=0.116 (e) (e) |
|POLY 1.5 | P=0.158 (e) P=0.034 * P=0.493 |P=0.169N P=0.116 (e) (e) |
|POLY 6 | P=0.146 (e) P=0.043 * P=0.492 |P=0.169N P=0.116 (e) (e) |
|LOGISTIC REGRESSION| P=0.173 (e) P=0.037 * P=0.500 |P=0.174N P=0.117 (e) (e) |
|COCH-ARM / FISHERS | P=0.185 (e) P=0.028 * P=0.500 |P=0.167N P=0.117 (e) (e) |
|ORDER RESTRICTED | P=0.061 (e) (e) (e) |P=0.176N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Spleen |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |2/49 (4%) 0/48 (0%) 0/49 (0%) 0/49 (0%) |
|POLY-3 RATE (b) | 1/43.94 2/44.21 2/47.03 2/42.11 |2/44.36 0/43.14 0/43.73 0/40.27 |
|POLY-3 PERCENT (g) | 2.3% 4.5% 4.3% 4.8% |4.5% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 2/33 (6%) 1/39 (3%) 1/31 (3%) |2/35 (6%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 694 729 (T) 712 692 |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.442 P=0.521 P=0.576 P=0.497 |P=0.155N P=0.258N P=0.232N P=0.238N |
|POLY 3 | P=0.424 P=0.502 P=0.524 P=0.485 |P=0.156N P=0.243N P=0.240N P=0.259N |
|POLY 1.5 | P=0.427 P=0.501 P=0.513 P=0.488 |P=0.157N P=0.243N P=0.239N P=0.255N |
|POLY 6 | P=0.427 P=0.507 P=0.539 P=0.487 |P=0.155N P=0.244N P=0.240N P=0.257N |
|LOGISTIC REGRESSION| P=0.429 P=0.512 P=0.524 P=0.487 |P=0.155N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.442 P=0.500 P=0.500 P=0.500 |P=0.159N P=0.253N P=0.247N P=0.247N |
|ORDER RESTRICTED | P=0.446 (e) (e) (e) |P=0.037N* (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 32
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Spleen |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 11/50 (22%) 12/50 (24%) 17/50 (34%) 20/50 (40%) |3/49 (6%) 5/48 (10%) 7/49 (14%) 8/49 (16%) |
|POLY-3 RATE (b) | 11/45.05 12/46.56 17/48.19 20/45.44 |3/45.11 5/44.22 7/46.31 8/40.86 |
|POLY-3 PERCENT (g) | 24.4% 25.8% 35.3% 44.0% |6.7% 11.3% 15.1% 19.6% |
|TERMINAL (d) | 6/31 (19%) 5/33 (15%) 13/39 (33%) 9/31 (29%) |1/35 (3%) 2/32 (6%) 2/36 (6%) 7/35 (20%) |
|FIRST INCIDENCE | 563 540 586 504 |563 395 492 544 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.023 * P=0.552 P=0.321 P=0.060 |P=0.078 P=0.341 P=0.171 P=0.098 |
|POLY 3 | P=0.014 * P=0.536 P=0.179 P=0.037 * |P=0.052 P=0.345 P=0.168 P=0.069 |
|POLY 1.5 | P=0.013 * P=0.519 P=0.157 P=0.035 * |P=0.056 P=0.347 P=0.164 P=0.075 |
|POLY 6 | P=0.017 * P=0.567 P=0.214 P=0.046 * |P=0.053 P=0.341 P=0.174 P=0.070 |
|LOGISTIC REGRESSION| P=0.018 * P=0.498 P=0.138 P=0.040 * |P=0.130 P=0.340 P=0.177 P=0.085 |
|COCH-ARM / FISHERS | P=0.016 * P=0.500 P=0.133 P=0.041 * |P=0.078 P=0.346 P=0.159 P=0.100 |
|ORDER RESTRICTED | P=0.031 * (e) (e) (e) |P=0.057 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Spleen |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/49 (0%) 0/48 (0%) 0/49 (0%) 0/49 (0%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 0/46.96 2/42.11 |0/44.36 0/43.14 0/43.73 0/40.27 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.8% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 1/31 (3%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- --- 692 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.040 * (e) (e) P=0.240 |(e) (e) (e) (e) |
|POLY 3 | P=0.041 * (e) (e) P=0.228 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.041 * (e) (e) P=0.230 |(e) (e) (e) (e) |
|POLY 6 | P=0.042 * (e) (e) P=0.230 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.039 * (e) (e) P=0.229 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.247 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.026 * (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 33
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Spleen |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/49 (2%) 0/48 (0%) 0/49 (0%) 0/49 (0%) |
|POLY-3 RATE (b) | 2/44.36 0/44.21 0/46.96 0/41.96 |1/44.83 0/43.14 0/43.73 0/40.27 |
|POLY-3 PERCENT (g) | 4.5% 0.0% 0.0% 0.0% |2.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 620 --- --- --- |591 --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.158N P=0.242N P=0.213N P=0.248N |P=0.373N P=0.509N P=0.513N P=0.537N |
|POLY 3 | P=0.153N P=0.238N P=0.225N P=0.250N |P=0.340N P=0.508N P=0.505N P=0.521N |
|POLY 1.5 | P=0.156N P=0.238N P=0.230N P=0.246N |P=0.342N P=0.506N P=0.503N P=0.517N |
|POLY 6 | P=0.151N P=0.236N P=0.217N P=0.251N |P=0.339N P=0.510N P=0.506N P=0.521N |
|LOGISTIC REGRESSION| P=0.137N P=0.235N P=0.289N P=0.212N |P=0.254N P=0.521N P=0.530N P=0.429N |
|COCH-ARM / FISHERS | P=0.160N P=0.247N P=0.247N P=0.247N |P=0.350N P=0.505N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.034N* (e) (e) (e) |P=0.140N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Spleen: Capsule |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 7/50 (14%) 12/50 (24%) 30/50 (60%) |8/49 (16%) 17/48 (35%) 12/49 (24%) 20/49 (41%) |
|POLY-3 RATE (b) | 1/44.13 7/44.21 12/47.51 30/45.11 |8/44.73 17/44.46 12/45.18 20/41.90 |
|POLY-3 PERCENT (g) | 2.3% 15.8% 25.3% 66.5% |17.9% 38.2% 26.6% 47.7% |
|TERMINAL (d) | 0/31 (0%) 7/33 (21%) 10/39 (26%) 22/31 (71%) |6/35 (17%) 12/32 (38%) 9/36 (25%) 17/35 (49%) |
|FIRST INCIDENCE | 641 729 (T) 586 504 |648 621 492 544 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P<0.001 ** P=0.038 * P=0.005 ** P<0.001 ** |P=0.040 * P=0.024 * P=0.242 P=0.007 ** |
|POLY 3 | P<0.001 ** P=0.030 * P<0.001 ** P<0.001 ** |P=0.016 * P=0.026 * P=0.231 P=0.002 ** |
|POLY 1.5 | P<0.001 ** P=0.030 * P<0.001 ** P<0.001 ** |P=0.018 * P=0.026 * P=0.230 P=0.002 ** |
|POLY 6 | P<0.001 ** P=0.030 * P=0.002 ** P<0.001 ** |P=0.018 * P=0.026 * P=0.236 P=0.002 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.035 * P=0.002 ** P<0.001 ** |P=0.017 * P=0.026 * P=0.224 P=0.003 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.030 * P<0.001 ** P<0.001 ** |P=0.034 * P=0.027 * P=0.226 P=0.007 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 34
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Edema |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |2/50 (4%) 3/49 (6%) 1/49 (2%) 0/49 (0%) |
|POLY-3 RATE (b) | 6/45.33 0/44.21 1/47.44 2/43.47 |2/45.25 3/44.45 1/44.18 0/40.27 |
|POLY-3 PERCENT (g) | 13.2% 0.0% 2.1% 4.6% |4.4% 6.8% 2.3% 0.0% |
|TERMINAL (d) | 2/31 (7%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |1/35 (3%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 544 --- 586 401 |563 641 596 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.243N P=0.020N* P=0.046N* P=0.159N |P=0.089N P=0.492 P=0.512N P=0.257N |
|POLY 3 | P=0.219N P=0.016N* P=0.049N* P=0.146N |P=0.090N P=0.492 P=0.508N P=0.264N |
|POLY 1.5 | P=0.224N P=0.016N* P=0.052N P=0.143N |P=0.088N P=0.492 P=0.508N P=0.260N |
|POLY 6 | P=0.213N P=0.017N* P=0.044N* P=0.148N |P=0.089N P=0.492 P=0.507N P=0.262N |
|LOGISTIC REGRESSION| P=0.094N P=0.016N* P=0.104N P=0.055N |P=0.052N P=0.480 P=0.531N P=0.212N |
|COCH-ARM / FISHERS | P=0.231N P=0.013N* P=0.056N P=0.134N |P=0.079N P=0.490 P=0.508N P=0.253N |
|ORDER RESTRICTED | P=0.011N* (e) (e) (e) |P=0.126N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Erosion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 1/49 (2%) |
|POLY-3 RATE (b) | 3/44.05 0/44.21 0/46.96 1/41.96 |0/44.71 0/43.83 0/43.73 1/40.27 |
|POLY-3 PERCENT (g) | 6.8% 0.0% 0.0% 2.4% |0.0% 0.0% 0.0% 2.5% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 1/31 (3%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 1/35 (3%) |
|FIRST INCIDENCE | 694 --- --- 729 (T) |--- --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.322N P=0.111N P=0.088N P=0.308N |P=0.192 (e) (e) P=0.500 |
|POLY 3 | P=0.319N P=0.118N P=0.108N P=0.323N |P=0.174 (e) (e) P=0.479 |
|POLY 1.5 | P=0.322N P=0.119N P=0.113N P=0.319N |P=0.176 (e) (e) P=0.482 |
|POLY 6 | P=0.316N P=0.116N P=0.101N P=0.323N |P=0.176 (e) (e) P=0.482 |
|LOGISTIC REGRESSION| P=0.332N P=0.118N P=0.110N P=0.318N |(e) (e) (e) P=0.500 |
|COCH-ARM / FISHERS | P=0.327N P=0.121N P=0.121N P=0.309N |P=0.185 (e) (e) P=0.495 |
|ORDER RESTRICTED | P=0.042N* (e) (e) (e) |P=0.104 (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 35
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/49 (0%) 0/49 (0%) 2/49 (4%) |
|POLY-3 RATE (b) | 0/43.81 0/44.21 0/46.96 0/41.96 |1/45.25 0/43.83 0/43.73 2/40.27 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 0.0% 0.0% 5.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 2/35 (6%) |
|FIRST INCIDENCE | --- --- --- --- |563 --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.204 P=0.500N P=0.513N P=0.482 |
|POLY 3 | (e) (e) (e) (e) |P=0.195 P=0.506N P=0.507N P=0.459 |
|POLY 1.5 | (e) (e) (e) (e) |P=0.196 P=0.505N P=0.506N P=0.466 |
|POLY 6 | (e) (e) (e) (e) |P=0.197 P=0.509N P=0.507N P=0.462 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.215 P=0.541N P=0.566N P=0.496 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.206 P=0.505N P=0.505N P=0.492 |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.106 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |4/50 (8%) 3/49 (6%) 1/49 (2%) 1/49 (2%) |
|POLY-3 RATE (b) | 4/44.97 1/44.39 2/47.50 2/43.37 |4/45.69 3/44.45 1/44.18 1/40.29 |
|POLY-3 PERCENT (g) | 8.9% 2.3% 4.2% 4.6% |8.8% 6.8% 2.3% 2.5% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |2/35 (6%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 586 682 619 465 |516 641 596 725 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.424N P=0.187N P=0.283N P=0.365N |P=0.102N P=0.520N P=0.192N P=0.201N |
|POLY 3 | P=0.416N P=0.182N P=0.312N P=0.354N |P=0.105N P=0.515N P=0.189N P=0.219N |
|POLY 1.5 | P=0.418N P=0.181N P=0.324N P=0.351N |P=0.103N P=0.513N P=0.187N P=0.212N |
|POLY 6 | P=0.412N P=0.181N P=0.296N P=0.354N |P=0.105N P=0.517N P=0.189N P=0.218N |
|LOGISTIC REGRESSION| P=0.246N P=0.174N P=0.468N P=0.187N |P=0.065N P=0.523N P=0.192N P=0.172N |
|COCH-ARM / FISHERS | P=0.414N P=0.181N P=0.339N P=0.339N |P=0.092N P=0.511N P=0.187N P=0.187N |
|ORDER RESTRICTED | P=0.211N (e) (e) (e) |P=0.145N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 36
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Forestomach: Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 0/50 (0%) 3/50 (6%) 3/50 (6%) |2/50 (4%) 2/49 (4%) 2/49 (4%) 3/49 (6%) |
|POLY-3 RATE (b) | 4/44.64 0/44.21 3/47.59 3/43.47 |2/45.90 2/44.28 2/45.02 3/41.24 |
|POLY-3 PERCENT (g) | 9.0% 0.0% 6.3% 6.9% |4.4% 4.5% 4.4% 7.3% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 1/39 (3%) 1/31 (3%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 2/35 (6%) |
|FIRST INCIDENCE | 544 --- 586 401 |516 641 492 239 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.410 P=0.061N P=0.414N P=0.513N |P=0.355 P=0.688 P=0.688 P=0.472 |
|POLY 3 | P=0.413 P=0.061N P=0.465N P=0.514N |P=0.341 P=0.681 P=0.687 P=0.451 |
|POLY 1.5 | P=0.412 P=0.061N P=0.481N P=0.512N |P=0.348 P=0.683 P=0.687 P=0.460 |
|POLY 6 | P=0.416 P=0.060N P=0.442N P=0.513N |P=0.344 P=0.678 P=0.688 P=0.452 |
|LOGISTIC REGRESSION| P=0.566 P=0.062N P=0.603N P=0.373N |P=0.461N P=0.666 P=0.712 P=0.689N |
|COCH-ARM / FISHERS | P=0.418 P=0.059N P=0.500N P=0.500N |P=0.375 P=0.684 P=0.684 P=0.490 |
|ORDER RESTRICTED | P=0.284N (e) (e) (e) |P=0.429 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Edema |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |2/50 (4%) 1/49 (2%) 1/48 (2%) 0/49 (0%) |
|POLY-3 RATE (b) | 1/44.06 0/44.21 0/46.96 2/42.70 |2/45.25 1/43.99 1/43.78 0/40.27 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 0.0% 4.7% |4.4% 2.3% 2.3% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 1/31 (3%) |1/35 (3%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 662 --- --- 465 |563 687 596 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.201 P=0.495N P=0.476N P=0.492 |P=0.183N P=0.507N P=0.512N P=0.257N |
|POLY 3 | P=0.207 P=0.499N P=0.487N P=0.489 |P=0.186N P=0.510N P=0.512N P=0.264N |
|POLY 1.5 | P=0.206 P=0.500N P=0.493N P=0.491 |P=0.184N P=0.508N P=0.513N P=0.260N |
|POLY 6 | P=0.208 P=0.497N P=0.479N P=0.491 |P=0.183N P=0.513N P=0.508N P=0.262N |
|LOGISTIC REGRESSION| P=0.290 P=0.499N P=0.542N P=0.579 |P=0.122N P=0.517N P=0.554N P=0.212N |
|COCH-ARM / FISHERS | P=0.208 P=0.500N P=0.500N P=0.500 |P=0.172N P=0.508N P=0.515N P=0.253N |
|ORDER RESTRICTED | P=0.122 (e) (e) (e) |P=0.140N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 37
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Erosion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |2/50 (4%) 2/49 (4%) 0/48 (0%) 0/49 (0%) |
|POLY-3 RATE (b) | 4/44.81 2/44.53 1/47.35 1/42.25 |2/45.51 2/45.15 0/43.32 0/40.27 |
|POLY-3 PERCENT (g) | 8.9% 4.5% 2.1% 2.4% |4.4% 4.4% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 544 652 619 652 |591 395 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.130N P=0.319N P=0.149N P=0.195N |P=0.085N P=0.680 P=0.260N P=0.279N |
|POLY 3 | P=0.129N P=0.340N P=0.162N P=0.197N |P=0.077N P=0.691 P=0.248N P=0.265N |
|POLY 1.5 | P=0.129N P=0.340N P=0.170N P=0.192N |P=0.076N P=0.690 P=0.247N P=0.260N |
|POLY 6 | P=0.127N P=0.336N P=0.152N P=0.198N |P=0.076N P=0.689 P=0.249N P=0.265N |
|LOGISTIC REGRESSION| P=0.094N P=0.335N P=0.261N P=0.149N |P=0.011N* P=0.667 P=0.275N P=0.182N |
|COCH-ARM / FISHERS | P=0.126N P=0.339N P=0.181N P=0.181N |P=0.072N P=0.684 P=0.258N P=0.253N |
|ORDER RESTRICTED | P=0.104N (e) (e) (e) |P=0.138N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |2/50 (4%) 1/49 (2%) 1/48 (2%) 0/49 (0%) |
|POLY-3 RATE (b) | 2/44.54 1/44.21 2/47.59 1/41.96 |2/45.36 1/43.99 1/43.78 0/40.27 |
|POLY-3 PERCENT (g) | 4.5% 2.3% 4.2% 2.4% |4.4% 2.3% 2.3% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/33 (3%) 0/39 (0%) 1/31 (3%) |1/35 (3%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 586 729 (T) 586 729 (T) |516 687 596 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.487N P=0.500N P=0.653N P=0.519N |P=0.180N P=0.510N P=0.505N P=0.254N |
|POLY 3 | P=0.493N P=0.503N P=0.670N P=0.521N |P=0.186N P=0.511N P=0.512N P=0.264N |
|POLY 1.5 | P=0.491N P=0.502N P=0.680N P=0.515N |P=0.184N P=0.509N P=0.513N P=0.260N |
|POLY 6 | P=0.492N P=0.501N P=0.654N P=0.524N |P=0.183N P=0.513N P=0.509N P=0.263N |
|LOGISTIC REGRESSION| P=0.432N P=0.498N P=0.570 P=0.474N |P=0.109N P=0.523N P=0.567N P=0.190N |
|COCH-ARM / FISHERS | P=0.479N P=0.500N P=0.691N P=0.500N |P=0.172N P=0.508N P=0.515N P=0.253N |
|ORDER RESTRICTED | P=0.469N (e) (e) (e) |P=0.140N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 38
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Testes: Bilateral, Germinal Epithelium |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |
|POLY-3 RATE (b) | 1/43.94 0/44.21 2/47.44 0/41.96 | |
|POLY-3 PERCENT (g) | 2.3% 0.0% 4.2% 0.0% | |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 1/39 (3%) 0/31 (0%) | |
|FIRST INCIDENCE | 694 --- 586 --- | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.536N P=0.489N P=0.552 P=0.506N | |
|POLY 3 | P=0.547N P=0.499N P=0.527 P=0.509N | |
|POLY 1.5 | P=0.543N P=0.500N P=0.515 P=0.507N | |
|POLY 6 | P=0.550N P=0.496N P=0.544 P=0.509N | |
|LOGISTIC REGRESSION| P=0.504N P=0.500N P=0.439 P=0.505N | |
|COCH-ARM / FISHERS | P=0.529N P=0.500N P=0.500 P=0.500N | |
|ORDER RESTRICTED | P=0.334N (e) (e) (e) | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Testes: Germinal Epithelium |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | |
|POLY-3 RATE (b) | 2/43.94 0/44.21 2/47.44 1/41.96 | |
|POLY-3 PERCENT (g) | 4.6% 0.0% 4.2% 2.4% | |
|TERMINAL (d) | 1/31 (3%) 0/33 (0%) 1/39 (3%) 1/31 (3%) | |
|FIRST INCIDENCE | 694 --- 586 729 (T) | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.612 P=0.227N P=0.630N P=0.503N | |
|POLY 3 | P=0.590 P=0.236N P=0.666N P=0.516N | |
|POLY 1.5 | P=0.595 P=0.237N P=0.678N P=0.513N | |
|POLY 6 | P=0.586 P=0.233N P=0.648N P=0.516N | |
|LOGISTIC REGRESSION| P=0.613 P=0.233N P=0.662 P=0.511N | |
|COCH-ARM / FISHERS | P=0.613 P=0.247N P=0.691N P=0.500N | |
|ORDER RESTRICTED | P=0.417N (e) (e) (e) | |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 39
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland |
| Ultimobranchial Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |2/50 (4%) 0/49 (0%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 3/43.91 1/44.21 0/46.96 2/42.07 |2/44.71 0/43.83 1/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 6.8% 2.3% 0.0% 4.8% |4.5% 0.0% 2.3% 0.0% |
|TERMINAL (d) | 2/31 (7%) 1/33 (3%) 0/39 (0%) 1/31 (3%) |2/35 (6%) 0/32 (0%) 1/36 (3%) 0/35 (0%) |
|FIRST INCIDENCE | 702 729 (T) --- 703 |729 (T) --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.473N P=0.280N P=0.085N P=0.492N |P=0.243N P=0.258N P=0.490N P=0.238N |
|POLY 3 | P=0.473N P=0.303N P=0.107N P=0.520N |P=0.265N P=0.241N P=0.504N P=0.256N |
|POLY 1.5 | P=0.477N P=0.305N P=0.112N P=0.516N |P=0.263N P=0.241N P=0.502N P=0.253N |
|POLY 6 | P=0.468N P=0.297N P=0.100N P=0.518N |P=0.262N P=0.242N P=0.505N P=0.254N |
|LOGISTIC REGRESSION| P=0.487N P=0.283N P=0.095N P=0.513N |P=0.243N (e) P=0.490N (e) |
|COCH-ARM / FISHERS | P=0.479N P=0.309N P=0.121N P=0.500N |P=0.251N P=0.253N P=0.500N P=0.247N |
|ORDER RESTRICTED | P=0.192N (e) (e) (e) |P=0.087N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 2/50 (4%) 9/50 (18%) 4/50 (8%) |10/50 (20%) 11/49 (22%) 7/50 (14%) 5/50 (10%) |
|POLY-3 RATE (b) | 8/43.91 2/44.21 9/46.96 4/42.76 |10/45.83 11/44.91 7/44.18 5/41.83 |
|POLY-3 PERCENT (g) | 18.2% 4.5% 19.2% 9.4% |21.8% 24.5% 15.8% 12.0% |
|TERMINAL (d) | 7/31 (23%) 2/33 (6%) 9/39 (23%) 2/31 (7%) |6/35 (17%) 7/32 (22%) 7/36 (19%) 4/35 (11%) |
|FIRST INCIDENCE | 702 729 (T) 729 (T) 576 |591 576 729 (T) 480 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.437N P=0.036N* P=0.506N P=0.183N |P=0.052N P=0.431 P=0.293N P=0.153N |
|POLY 3 | P=0.466N P=0.043N* P=0.561 P=0.188N |P=0.074N P=0.479 P=0.325N P=0.173N |
|POLY 1.5 | P=0.465N P=0.044N* P=0.533 P=0.189N |P=0.069N P=0.481 P=0.312N P=0.164N |
|POLY 6 | P=0.458N P=0.040N* P=0.601 P=0.179N |P=0.074N P=0.473 P=0.340N P=0.173N |
|LOGISTIC REGRESSION| P=0.464N P=0.032N* P=0.507N P=0.196N |P=0.065N P=0.480 P=0.305N P=0.149N |
|COCH-ARM / FISHERS | P=0.444N P=0.046N* P=0.500 P=0.178N |P=0.050N P=0.479 P=0.298N P=0.131N |
|ORDER RESTRICTED | P=0.170N (e) (e) (e) |P=0.140N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 40
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicle |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |2/50 (4%) 1/49 (2%) 2/50 (4%) 4/50 (8%) |
|POLY-3 RATE (b) | 1/43.81 2/44.21 4/47.35 1/41.96 |2/44.92 1/43.83 2/44.18 4/41.11 |
|POLY-3 PERCENT (g) | 2.3% 4.5% 8.5% 2.4% |4.5% 2.3% 4.5% 9.7% |
|TERMINAL (d) | 1/31 (3%) 2/33 (6%) 3/39 (8%) 1/31 (3%) |1/35 (3%) 1/32 (3%) 2/36 (6%) 4/35 (11%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 619 729 (T) |674 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.591N P=0.522 P=0.246 P=0.762 |P=0.152 P=0.518N P=0.684N P=0.340 |
|POLY 3 | P=0.557 P=0.503 P=0.203 P=0.751 |P=0.121 P=0.509N P=0.688 P=0.297 |
|POLY 1.5 | P=0.565 P=0.501 P=0.192 P=0.753 |P=0.125 P=0.507N P=0.691 P=0.304 |
|POLY 6 | P=0.557 P=0.509 P=0.221 P=0.752 |P=0.123 P=0.512N P=0.686 P=0.299 |
|LOGISTIC REGRESSION| P=0.580 P=0.522 P=0.186 P=0.762 |P=0.129 P=0.507N P=0.691 P=0.306 |
|COCH-ARM / FISHERS | P=0.591 P=0.500 P=0.181 P=0.753N |P=0.142 P=0.508N P=0.691N P=0.339 |
|ORDER RESTRICTED | P=0.371 (e) (e) (e) |P=0.146 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Urinary Bladder |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/49 (2%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/43.81 2/44.42 0/46.96 1/41.94 |0/44.71 0/43.83 0/44.18 0/41.11 |
|POLY-3 PERCENT (g) | 0.0% 4.5% 0.0% 2.4% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/33 (0%) 0/39 (0%) 0/31 (0%) |0/35 (0%) 0/32 (0%) 0/36 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- 682 --- 465 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.644 P=0.259 (e) P=0.496 |(e) (e) (e) (e) |
|POLY 3 | P=0.639 P=0.240 (e) P=0.491 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.637 P=0.238 (e) P=0.491 |(e) (e) (e) (e) |
|POLY 6 | P=0.632N P=0.245 (e) P=0.494 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.555N P=0.239 (e) P=0.702 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.640 P=0.247 (e) P=0.495 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.317 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 41
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Uterus |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |1/50 (2%) 3/49 (6%) 2/50 (4%) 3/50 (6%) |
|POLY-3 RATE (b) | |1/44.71 3/43.83 2/44.21 3/41.11 |
|POLY-3 PERCENT (g) | |2.2% 6.9% 4.5% 7.3% |
|TERMINAL (d) | |1/35 (3%) 3/32 (9%) 1/36 (3%) 3/35 (9%) |
|FIRST INCIDENCE | |729 (T) 729 (T) 723 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.371 P=0.273 P=0.513 P=0.305 |
|POLY 3 | |P=0.315 P=0.298 P=0.496 P=0.276 |
|POLY 1.5 | |P=0.321 P=0.299 P=0.498 P=0.281 |
|POLY 6 | |P=0.319 P=0.296 P=0.496 P=0.279 |
|LOGISTIC REGRESSION| |P=0.368 P=0.273 P=0.508 P=0.305 |
|COCH-ARM / FISHERS | |P=0.353 P=0.301 P=0.500 P=0.309 |
|ORDER RESTRICTED | |P=0.236 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Uterus |
| Hydrometra |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |1/50 (2%) 4/49 (8%) 2/50 (4%) 1/50 (2%) |
|POLY-3 RATE (b) | |1/45.00 4/43.83 2/44.29 1/42.05 |
|POLY-3 PERCENT (g) | |2.2% 9.1% 4.5% 2.4% |
|TERMINAL (d) | |0/35 (0%) 4/32 (13%) 1/36 (3%) 0/35 (0%) |
|FIRST INCIDENCE | |652 729 (T) 702 284 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.301N P=0.158 P=0.501 P=0.748 |
|POLY 3 | |P=0.330N P=0.170 P=0.494 P=0.745 |
|POLY 1.5 | |P=0.325N P=0.172 P=0.497 P=0.748 |
|POLY 6 | |P=0.327N P=0.167 P=0.493 P=0.748 |
|LOGISTIC REGRESSION| |P=0.249N P=0.172 P=0.500 P=0.574N |
|COCH-ARM / FISHERS | |P=0.303N P=0.175 P=0.500 P=0.753N |
|ORDER RESTRICTED | |P=0.373N (e) (e) (e) |
|=================================================================================================================================|
Date: 03/25/05 EXPERIMENT: 91005 TEST: 07 Page 42
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |0 MG/KG 5 MG/KG 25 MG/KG 50 MG/KG |
| | | |
|=================================================================================================================================|
| |
|Uterus: Endometrium |
| Hyperplasia Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |4/50 (8%) 1/49 (2%) 0/50 (0%) 2/50 (4%) |
|POLY-3 RATE (b) | |4/45.01 1/43.93 0/44.18 2/41.11 |
|POLY-3 PERCENT (g) | |8.9% 2.3% 0.0% 4.9% |
|TERMINAL (d) | |3/35 (9%) 0/32 (0%) 0/36 (0%) 2/35 (6%) |
|FIRST INCIDENCE | |648 702 --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.323N P=0.204N P=0.065N P=0.347N |
|POLY 3 | |P=0.336N P=0.186N P=0.062N P=0.380N |
|POLY 1.5 | |P=0.335N P=0.185N P=0.062N P=0.372N |
|POLY 6 | |P=0.335N P=0.188N P=0.063N P=0.377N |
|LOGISTIC REGRESSION| |P=0.353N P=0.185N P=0.064N P=0.371N |
|COCH-ARM / FISHERS | |P=0.326N P=0.187N P=0.059N P=0.339N |
|ORDER RESTRICTED | |P=0.093N (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).