TDMS Study 91005-08 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Southern Research Inst METHYLENE BLUE TRIHYDRATE DATE: 04/26/05
EXPERIMENT: 91005 TEST: 08 TIME: 09:25:37
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: FARNELL, DANIEL CAS: 7220-79-3
------------------------------------------------------------------------------------------------------------------------------------
FINAL #1 MICE
REASONS FOR REMOVAL: ALL
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE ALL
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Southern Research Inst METHYLENE BLUE TRIHYDRATE DATE: 04/26/05
EXPERIMENT: 91005 TEST: 08 TIME: 09:25:37
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: FARNELL, DANIEL CAS: 7220-79-3
Mice(B6C3F1)
-----------------------------
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE
BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.
---------------
Adrenal Cortex
Adrenal Medulla
Bone Marrow
Islets, Pancreatic
Kidney
Liver
Lung
Ovary
Pancreas
Pituitary Gland
Spleen
Testes
Thyroid Gland
Urinary Bladder
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Southern Research Inst METHYLENE BLUE TRIHYDRATE DATE: 04/26/05
EXPERIMENT: 91005 TEST: 08 TIME: 09:25:37
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-05451 ROUTE: GAVAGE NTP C#: 91005C
PATHOLOGIST: FARNELL, DANIEL CAS: 7220-79-3
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF METHYLENE BLUE TRIHYDRATE
===============================================================
Male Mice
------------
Organ Morphology
----- ----------
Harderian Gland Adenoma
Carcinoma or Adenoma
Intestine Small: Site Unspecified Carcinoma
Carcinoma or Adenoma
Liver Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
Lung Alveolar/Bronchiolar Carcinoma
All Organs Hemangiosarcoma
Hemangiosarcoma or Hemangioma
===============================================================
Female Mice
------------
Organ Morphology
----- ----------
Liver Hepatocellular Carcinoma
Lung Alveolar/Bronchiolar Carcinoma
Pituitary Gland: Pars Distalis or Unspecified Site
Adenoma
All Organs Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type
Benign Tumors
Malignant Tumors
===============================================================
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 1
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 5/48 (10%) 5/50 (10%) 2/50 (4%) 5/48 (10%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 5/42.73 5/46.10 2/46.36 5/45.75 |0/44.58 0/45.81 1/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 11.7% 10.9% 4.3% 10.9% |0.0% 0.0% 2.1% 0.0% |
|TERMINAL (d) | 4/34 (12%) 5/38 (13%) 2/38 (5%) 5/40 (13%) |0/33 (0%) 0/40 (0%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 723 729 (T) 729 (T) 729 (T) |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.408N P=0.563N P=0.178N P=0.529N |P=0.676 (e) P=0.548 (e) |
|POLY 3 | P=0.469N P=0.582N P=0.184N P=0.587N |P=0.664 (e) P=0.513 (e) |
|POLY 1.5 | P=0.478N P=0.596N P=0.192N P=0.605N |P=0.659 (e) P=0.508 (e) |
|POLY 6 | P=0.457N P=0.565N P=0.175N P=0.565N |P=0.675 (e) P=0.522 (e) |
|LOGISTIC REGRESSION| P=0.421N P=0.561N P=0.175N P=0.541N |(e) (e) P=0.548 (e) |
|COCH-ARM / FISHERS | P=0.496N P=0.603N P=0.201N P=0.630N |P=0.649 (e) P=0.500 (e) |
|ORDER RESTRICTED | P=0.407N (e) (e) (e) |P=0.393 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma Benign |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/48 (0%) 0/50 (0%) 1/50 (2%) 2/48 (4%) |1/50 (2%) 1/50 (2%) 2/49 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/42.71 0/46.10 1/46.36 2/45.75 |1/44.58 1/45.81 2/46.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.4% |2.2% 2.2% 4.3% 0.0% |
|TERMINAL (d) | 0/34 (0%) 0/38 (0%) 1/38 (3%) 2/40 (5%) |1/33 (3%) 1/40 (3%) 2/41 (5%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- 729 (T) 729 (T) |729 (T) 729 (T) 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.073 (e) P=0.522 P=0.275 |P=0.319N P=0.718N P=0.576 P=0.447N |
|POLY 3 | P=0.064 (e) P=0.516 P=0.253 |P=0.359N P=0.755N P=0.516 P=0.489N |
|POLY 1.5 | P=0.062 (e) P=0.512 P=0.246 |P=0.365N P=0.758N P=0.506 P=0.493N |
|POLY 6 | P=0.066 (e) P=0.521 P=0.261 |P=0.348N P=0.748N P=0.531 P=0.481N |
|LOGISTIC REGRESSION| (e) (e) P=0.522 P=0.275 |P=0.319N P=0.718N P=0.576 (e) |
|COCH-ARM / FISHERS | P=0.058 (e) P=0.510 P=0.247 |P=0.375N P=0.753N P=0.492 P=0.500N |
|ORDER RESTRICTED | P=0.084 (e) (e) (e) |P=0.271N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 2
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Hemangiosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/44.11 2/46.35 0/46.36 0/47.59 |0/44.58 0/45.81 1/46.65 0/47.10 |
|POLY-3 PERCENT (g) | 2.3% 4.3% 0.0% 0.0% |0.0% 0.0% 2.1% 0.0% |
|TERMINAL (d) | 1/35 (3%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 1/41 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 676 --- --- |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.122N P=0.533 P=0.484N P=0.468N |P=0.675 (e) P=0.543 (e) |
|POLY 3 | P=0.126N P=0.517 P=0.490N P=0.485N |P=0.664 (e) P=0.509 (e) |
|POLY 1.5 | P=0.130N P=0.507 P=0.495N P=0.491N |P=0.658 (e) P=0.503 (e) |
|POLY 6 | P=0.123N P=0.530 P=0.485N P=0.478N |P=0.674 (e) P=0.518 (e) |
|LOGISTIC REGRESSION| P=0.130N P=0.507 (e) (e) |(e) (e) P=0.543 (e) |
|COCH-ARM / FISHERS | P=0.134N P=0.500 P=0.500N P=0.500N |P=0.648 (e) P=0.495 (e) |
|ORDER RESTRICTED | P=0.164N (e) (e) (e) |P=0.389 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Harderian Gland |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 1/50 (2%) 11/50 (22%) 5/50 (10%) |4/50 (8%) 2/50 (4%) 7/50 (14%) 3/50 (6%) |
|POLY-3 RATE (b) | 8/45.29 1/46.10 11/47.25 5/47.59 |4/45.16 2/45.99 7/48.01 3/47.10 |
|POLY-3 PERCENT (g) | 17.7% 2.2% 23.3% 10.5% |8.9% 4.4% 14.6% 6.4% |
|TERMINAL (d) | 5/35 (14%) 1/38 (3%) 8/38 (21%) 5/41 (12%) |2/33 (6%) 1/40 (3%) 6/42 (14%) 3/43 (7%) |
|FIRST INCIDENCE | 478 729 (T) 627 729 (T) |638 680 627 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.523 P=0.015N* P=0.384 P=0.196N |P=0.533N P=0.280N P=0.388 P=0.386N |
|POLY 3 | P=0.465 P=0.014N* P=0.341 P=0.244N |P=0.516 P=0.329N P=0.298 P=0.477N |
|POLY 1.5 | P=0.454 P=0.016N* P=0.323 P=0.257N |P=0.507 P=0.335N P=0.282 P=0.486N |
|POLY 6 | P=0.478 P=0.013N* P=0.364 P=0.230N |P=0.532 P=0.319N P=0.322 P=0.461N |
|LOGISTIC REGRESSION| P=0.430 P=0.018N* P=0.300 P=0.289N |P=0.500 P=0.337N P=0.265 P=0.491N |
|COCH-ARM / FISHERS | P=0.425 P=0.015N* P=0.306 P=0.277N |P=0.487 P=0.339N P=0.262 P=0.500N |
|ORDER RESTRICTED | P=0.241N (e) (e) (e) |P=0.398 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 3
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Harderian Gland |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 0/50 (0%) 4/50 (8%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 3/44.13 0/46.10 4/47.22 1/47.59 |0/44.58 1/46.20 2/47.66 2/47.37 |
|POLY-3 PERCENT (g) | 6.8% 0.0% 8.5% 2.1% |0.0% 2.2% 4.2% 4.2% |
|TERMINAL (d) | 2/35 (6%) 0/38 (0%) 2/38 (5%) 1/41 (2%) |0/33 (0%) 0/40 (0%) 1/42 (2%) 1/43 (2%) |
|FIRST INCIDENCE | 723 --- 605 729 (T) |--- 616 726 659 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.469N P=0.111N P=0.546 P=0.257N |P=0.202 P=0.496 P=0.297 P=0.285 |
|POLY 3 | P=0.494N P=0.111N P=0.537 P=0.279N |P=0.181 P=0.507 P=0.252 P=0.251 |
|POLY 1.5 | P=0.500N P=0.116N P=0.520 P=0.290N |P=0.175 P=0.503 P=0.246 P=0.245 |
|POLY 6 | P=0.487N P=0.106N P=0.557 P=0.267N |P=0.193 P=0.514 P=0.263 P=0.261 |
|LOGISTIC REGRESSION| P=0.527N P=0.104N P=0.493 P=0.255N |P=0.157 P=0.511 P=0.284 P=0.231 |
|COCH-ARM / FISHERS | P=0.518N P=0.121N P=0.500 P=0.309N |P=0.164 P=0.500 P=0.247 P=0.247 |
|ORDER RESTRICTED | P=0.211N (e) (e) (e) |P=0.167 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Harderian Gland |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 11/50 (22%) 1/50 (2%) 15/50 (30%) 6/50 (12%) |4/50 (8%) 3/50 (6%) 9/50 (18%) 5/50 (10%) |
|POLY-3 RATE (b) | 11/45.31 1/46.10 15/48.10 6/47.59 |4/45.16 3/46.39 9/48.02 5/47.37 |
|POLY-3 PERCENT (g) | 24.3% 2.2% 31.2% 12.6% |8.9% 6.5% 18.7% 10.6% |
|TERMINAL (d) | 7/35 (20%) 1/38 (3%) 10/38 (26%) 6/41 (15%) |2/33 (6%) 1/40 (3%) 7/42 (17%) 4/43 (9%) |
|FIRST INCIDENCE | 478 729 (T) 605 729 (T) |638 616 627 659 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.510N P=0.002N** P=0.343 P=0.088N |P=0.364 P=0.440N P=0.221 P=0.628 |
|POLY 3 | P=0.521 P=0.002N** P=0.304 P=0.117N |P=0.279 P=0.485N P=0.140 P=0.530 |
|POLY 1.5 | P=0.508 P=0.002N** P=0.276 P=0.127N |P=0.269 P=0.494N P=0.130 P=0.518 |
|POLY 6 | P=0.537 P<0.001N** P=0.342 P=0.106N |P=0.297 P=0.471N P=0.158 P=0.551 |
|LOGISTIC REGRESSION| P=0.471 P=0.003N** P=0.239 P=0.130N |P=0.254 P=0.500N P=0.124 P=0.504 |
|COCH-ARM / FISHERS | P=0.471 P=0.002N** P=0.247 P=0.143N |P=0.250 P=0.500N P=0.117 P=0.500 |
|ORDER RESTRICTED | P=0.097N (e) (e) (e) |P=0.225 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 4
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Intestine Small: Duodenum |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 1/46.36 2/47.91 |0/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.2% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 1/38 (3%) 1/41 (2%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- 729 (T) 641 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.074 (e) P=0.516 P=0.275 |(e) (e) (e) (e) |
|POLY 3 | P=0.068 (e) P=0.510 P=0.256 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.065 (e) P=0.505 P=0.248 |(e) (e) (e) (e) |
|POLY 6 | P=0.071 (e) P=0.515 P=0.266 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.058 (e) P=0.516 P=0.202 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.060 (e) P=0.500 P=0.247 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.087 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Intestine Small: Jejunum |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 2/46.36 2/47.59 |0/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 4.3% 4.2% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 2/38 (5%) 2/41 (5%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- 729 (T) 729 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.087 (e) P=0.257 P=0.274 |(e) (e) (e) (e) |
|POLY 3 | P=0.079 (e) P=0.248 P=0.255 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.076 (e) P=0.243 P=0.247 |(e) (e) (e) (e) |
|POLY 6 | P=0.083 (e) P=0.254 P=0.263 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) P=0.257 P=0.274 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.070 (e) P=0.247 P=0.247 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.126 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 5
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Intestine Small: Site Unspecified |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/44.11 1/46.10 2/46.36 2/47.91 |0/44.58 1/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 2.3% 2.2% 4.3% 4.2% |0.0% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 1/35 (3%) 1/38 (3%) 2/38 (5%) 1/41 (2%) |0/33 (0%) 1/40 (3%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 641 |--- 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.365 P=0.743N P=0.529 P=0.555 |P=0.419N P=0.538 (e) (e) |
|POLY 3 | P=0.347 P=0.751N P=0.517 P=0.529 |P=0.441N P=0.505 (e) (e) |
|POLY 1.5 | P=0.337 P=0.757N P=0.509 P=0.517 |P=0.445N P=0.502 (e) (e) |
|POLY 6 | P=0.360 P=0.744N P=0.526 P=0.543 |P=0.434N P=0.511 (e) (e) |
|LOGISTIC REGRESSION| P=0.335 P=0.743N P=0.529 P=0.490 |(e) P=0.538 (e) (e) |
|COCH-ARM / FISHERS | P=0.318 P=0.753N P=0.500 P=0.500 |P=0.449N P=0.500 (e) (e) |
|ORDER RESTRICTED | P=0.464 (e) (e) (e) |P=0.376N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Intestine Small: Site Unspecified |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 4/50 (8%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 1/46.10 2/46.36 4/47.68 |1/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 2.2% 4.3% 8.4% |2.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 2/38 (5%) 3/41 (7%) |1/33 (3%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- 729 (T) 729 (T) 705 |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.033 * P=0.516 P=0.257 P=0.087 |P=0.324N P=0.462N P=0.452N P=0.447N |
|POLY 3 | P=0.027 * P=0.509 P=0.248 P=0.071 |P=0.355N P=0.495N P=0.487N P=0.489N |
|POLY 1.5 | P=0.025 * P=0.504 P=0.243 P=0.067 |P=0.353N P=0.498N P=0.492N P=0.493N |
|POLY 6 | P=0.029 * P=0.515 P=0.254 P=0.077 |P=0.359N P=0.489N P=0.478N P=0.481N |
|LOGISTIC REGRESSION| P=0.030 * P=0.516 P=0.257 P=0.079 |P=0.324N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.023 * P=0.500 P=0.247 P=0.059 |P=0.351N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.024 * (e) (e) (e) |P=0.111N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 6
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Intestine Small: Site Unspecified |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 6/50 (12%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/44.11 2/46.10 4/46.36 6/48.00 |1/44.58 1/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 2.3% 4.3% 8.6% 12.5% |2.2% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 1/35 (3%) 2/38 (5%) 4/38 (11%) 4/41 (10%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 641 |729 (T) 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.037 * P=0.529 P=0.204 P=0.091 |P=0.179N P=0.718N P=0.452N P=0.447N |
|POLY 3 | P=0.029 * P=0.515 P=0.194 P=0.071 |P=0.205N P=0.755N P=0.487N P=0.489N |
|POLY 1.5 | P=0.026 * P=0.506 P=0.187 P=0.065 |P=0.206N P=0.758N P=0.492N P=0.493N |
|POLY 6 | P=0.032 * P=0.526 P=0.202 P=0.080 |P=0.202N P=0.748N P=0.478N P=0.481N |
|LOGISTIC REGRESSION| P=0.030 * P=0.529 P=0.204 P=0.066 |P=0.179N P=0.718N (e) (e) |
|COCH-ARM / FISHERS | P=0.023 * P=0.500 P=0.181 P=0.056 |P=0.208N P=0.753N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.038 * (e) (e) (e) |P=0.241N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/49 (4%) 1/48 (2%) |1/46 (2%) 0/47 (0%) 0/49 (0%) 1/48 (2%) |
|POLY-3 RATE (b) | 0/44.11 2/46.10 2/45.58 1/46.16 |1/41.35 0/43.51 0/47.17 1/45.84 |
|POLY-3 PERCENT (g) | 0.0% 4.3% 4.4% 2.2% |2.4% 0.0% 0.0% 2.2% |
|TERMINAL (d) | 0/35 (0%) 2/38 (5%) 2/38 (5%) 1/41 (2%) |1/32 (3%) 0/40 (0%) 0/42 (0%) 1/42 (2%) |
|FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |729 (T) --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.567 P=0.257 P=0.257 P=0.532 |P=0.578 P=0.455N P=0.446N P=0.700N |
|POLY 3 | P=0.551 P=0.247 P=0.245 P=0.509 |P=0.552 P=0.490N P=0.474N P=0.737N |
|POLY 1.5 | P=0.533 P=0.241 P=0.239 P=0.502 |P=0.551 P=0.493N P=0.479N P=0.742N |
|POLY 6 | P=0.571 P=0.254 P=0.251 P=0.518 |P=0.553 P=0.484N P=0.465N P=0.729N |
|LOGISTIC REGRESSION| (e) P=0.257 P=0.257 P=0.532 |P=0.578 (e) (e) P=0.700N |
|COCH-ARM / FISHERS | P=0.508 P=0.247 P=0.242 P=0.490 |P=0.545 P=0.495N P=0.484N P=0.742N |
|ORDER RESTRICTED | P=0.235 (e) (e) (e) |P=0.367N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 7
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/49 (4%) 1/48 (2%) |1/46 (2%) 0/47 (0%) 0/49 (0%) 2/48 (4%) |
|POLY-3 RATE (b) | 0/44.11 2/46.10 2/45.58 1/46.16 |1/41.35 0/43.51 0/47.17 2/46.13 |
|POLY-3 PERCENT (g) | 0.0% 4.3% 4.4% 2.2% |2.4% 0.0% 0.0% 4.3% |
|TERMINAL (d) | 0/35 (0%) 2/38 (5%) 2/38 (5%) 1/41 (2%) |1/32 (3%) 0/40 (0%) 0/42 (0%) 1/42 (2%) |
|FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |729 (T) --- --- 649 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.567 P=0.257 P=0.257 P=0.532 |P=0.243 P=0.455N P=0.446N P=0.576 |
|POLY 3 | P=0.551 P=0.247 P=0.245 P=0.509 |P=0.223 P=0.490N P=0.474N P=0.538 |
|POLY 1.5 | P=0.533 P=0.241 P=0.239 P=0.502 |P=0.221 P=0.493N P=0.479N P=0.529 |
|POLY 6 | P=0.571 P=0.254 P=0.251 P=0.518 |P=0.226 P=0.484N P=0.465N P=0.552 |
|LOGISTIC REGRESSION| (e) P=0.257 P=0.257 P=0.532 |P=0.212 (e) (e) P=0.512 |
|COCH-ARM / FISHERS | P=0.508 P=0.247 P=0.242 P=0.490 |P=0.216 P=0.495N P=0.484N P=0.516 |
|ORDER RESTRICTED | P=0.235 (e) (e) (e) |P=0.154 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hemangiosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 5/50 (10%) 3/50 (6%) 1/49 (2%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/44.35 5/46.17 3/47.13 1/46.75 |0/44.58 0/45.81 2/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 4.5% 10.8% 6.4% 2.1% |0.0% 0.0% 4.2% 0.0% |
|TERMINAL (d) | 1/35 (3%) 3/38 (8%) 0/38 (0%) 1/41 (2%) |0/33 (0%) 0/40 (0%) 2/42 (5%) 0/43 (0%) |
|FIRST INCIDENCE | 665 717 605 729 (T) |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.152N P=0.258 P=0.543 P=0.447N |P=0.579 (e) P=0.293 (e) |
|POLY 3 | P=0.162N P=0.233 P=0.528 P=0.482N |P=0.558 (e) P=0.252 (e) |
|POLY 1.5 | P=0.172N P=0.223 P=0.515 P=0.492N |P=0.550 (e) P=0.246 (e) |
|POLY 6 | P=0.151N P=0.244 P=0.543 P=0.470N |P=0.572 (e) P=0.263 (e) |
|LOGISTIC REGRESSION| P=0.187N P=0.241 P=0.486 P=0.498N |(e) (e) P=0.293 (e) |
|COCH-ARM / FISHERS | P=0.189N P=0.218 P=0.500 P=0.508N |P=0.536 (e) P=0.247 (e) |
|ORDER RESTRICTED | P=0.206N (e) (e) (e) |P=0.260 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 8
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatoblastoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/44.11 2/46.33 2/46.52 0/46.75 |0/44.58 0/45.81 1/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 4.5% 4.3% 4.3% 0.0% |0.0% 0.0% 2.1% 0.0% |
|TERMINAL (d) | 2/35 (6%) 1/38 (3%) 1/38 (3%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 670 690 --- |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.135N P=0.660N P=0.662N P=0.204N |P=0.676 (e) P=0.548 (e) |
|POLY 3 | P=0.148N P=0.676N P=0.675N P=0.224N |P=0.664 (e) P=0.513 (e) |
|POLY 1.5 | P=0.154N P=0.686N P=0.684N P=0.232N |P=0.659 (e) P=0.508 (e) |
|POLY 6 | P=0.142N P=0.664N P=0.664N P=0.216N |P=0.675 (e) P=0.522 (e) |
|LOGISTIC REGRESSION| P=0.152N P=0.680N P=0.669N (e) |(e) (e) P=0.548 (e) |
|COCH-ARM / FISHERS | P=0.162N P=0.691N P=0.691N P=0.253N |P=0.649 (e) P=0.500 (e) |
|ORDER RESTRICTED | P=0.177N (e) (e) (e) |P=0.393 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 28/50 (56%) 33/50 (66%) 26/50 (52%) 27/49 (55%) |15/50 (30%) 19/50 (38%) 22/50 (44%) 13/50 (26%) |
|POLY-3 RATE (b) | 28/45.64 33/47.29 26/46.94 27/46.94 |15/45.71 19/46.42 22/48.11 13/47.10 |
|POLY-3 PERCENT (g) | 61.4% 69.8% 55.4% 57.5% |32.8% 40.9% 45.7% 27.6% |
|TERMINAL (d) | 25/35 (71%) 28/38 (74%) 24/38 (63%) 25/41 (61%) |11/33 (33%) 17/40 (43%) 20/42 (48%) 13/43 (30%) |
|FIRST INCIDENCE | 478 610 627 694 |617 616 627 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.057N P=0.377 P=0.244N P=0.188N |P=0.100N P=0.490 P=0.351 P=0.166N |
|POLY 3 | P=0.183N P=0.256 P=0.353N P=0.434N |P=0.243N P=0.276 P=0.141 P=0.374N |
|POLY 1.5 | P=0.210N P=0.213 P=0.390N P=0.483N |P=0.257N P=0.265 P=0.125 P=0.387N |
|POLY 6 | P=0.154N P=0.328 P=0.306N P=0.369N |P=0.220N P=0.296 P=0.169 P=0.349N |
|LOGISTIC REGRESSION| P=0.113N P=0.304 P=0.273N P=0.311N |P=0.207N P=0.295 P=0.156 P=0.329N |
|COCH-ARM / FISHERS | P=0.267N P=0.206 P=0.421N P=0.545N |P=0.292N P=0.263 P=0.107 P=0.412N |
|ORDER RESTRICTED | P=0.283N (e) (e) (e) |P=0.167N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 9
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 13/50 (26%) 10/50 (20%) 11/50 (22%) 14/49 (29%) |5/50 (10%) 4/50 (8%) 0/50 (0%) 3/50 (6%) |
|POLY-3 RATE (b) | 13/47.00 10/48.04 11/47.23 14/47.80 |5/44.87 4/45.84 0/47.65 3/47.29 |
|POLY-3 PERCENT (g) | 27.7% 20.8% 23.3% 29.3% |11.1% 8.7% 0.0% 6.3% |
|TERMINAL (d) | 5/35 (14%) 5/38 (13%) 7/38 (18%) 10/41 (24%) |4/33 (12%) 3/40 (8%) 0/42 (0%) 2/43 (5%) |
|FIRST INCIDENCE | 536 452 638 506 |650 720 --- 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.464 P=0.269N P=0.336N P=0.517N |P=0.133N P=0.393N P=0.019N* P=0.240N |
|POLY 3 | P=0.332 P=0.295N P=0.402N P=0.520 |P=0.178N P=0.487N P=0.026N* P=0.328N |
|POLY 1.5 | P=0.327 P=0.312N P=0.408N P=0.503 |P=0.182N P=0.495N P=0.028N* P=0.340N |
|POLY 6 | P=0.339 P=0.279N P=0.395N P=0.540 |P=0.171N P=0.472N P=0.023N* P=0.308N |
|LOGISTIC REGRESSION| P=0.244 P=0.327N P=0.446N P=0.308 |P=0.172N P=0.466N P=0.028N* P=0.332N |
|COCH-ARM / FISHERS | P=0.307 P=0.318N P=0.408N P=0.475 |P=0.192N P=0.500N P=0.028N* P=0.357N |
|ORDER RESTRICTED | P=0.433 (e) (e) (e) |P=0.090N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Carcinoma or Hepatoblastoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 15/50 (30%) 12/50 (24%) 13/50 (26%) 14/49 (29%) |5/50 (10%) 4/50 (8%) 1/50 (2%) 3/50 (6%) |
|POLY-3 RATE (b) | 15/47.00 12/48.27 13/47.38 14/47.80 |5/44.87 4/45.84 1/47.65 3/47.29 |
|POLY-3 PERCENT (g) | 31.9% 24.9% 27.4% 29.3% |11.1% 8.7% 2.1% 6.3% |
|TERMINAL (d) | 7/35 (20%) 6/38 (16%) 8/38 (21%) 10/41 (24%) |4/33 (12%) 3/40 (8%) 1/42 (2%) 2/43 (5%) |
|FIRST INCIDENCE | 536 452 638 506 |650 720 729 (T) 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.416N P=0.270N P=0.333N P=0.349N |P=0.154N P=0.393N P=0.063N P=0.240N |
|POLY 3 | P=0.528 P=0.297N P=0.401N P=0.478N |P=0.206N P=0.487N P=0.088N P=0.328N |
|POLY 1.5 | P=0.521 P=0.317N P=0.410N P=0.497N |P=0.211N P=0.495N P=0.094N P=0.340N |
|POLY 6 | P=0.535 P=0.275N P=0.391N P=0.458N |P=0.196N P=0.472N P=0.080N P=0.308N |
|LOGISTIC REGRESSION| P=0.433 P=0.337N P=0.442N P=0.503 |P=0.198N P=0.466N P=0.087N P=0.332N |
|COCH-ARM / FISHERS | P=0.498 P=0.326N P=0.412N P=0.526N |P=0.222N P=0.500N P=0.102N P=0.357N |
|ORDER RESTRICTED | P=0.483N (e) (e) (e) |P=0.150N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 10
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Carcinoma or Hepatocellular Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 37/50 (74%) 38/50 (76%) 33/50 (66%) 35/49 (71%) |19/50 (38%) 20/50 (40%) 22/50 (44%) 16/50 (32%) |
|POLY-3 RATE (b) | 37/47.72 38/48.71 33/47.59 35/47.85 |19/46.00 20/46.45 22/48.11 16/47.29 |
|POLY-3 PERCENT (g) | 77.5% 78.0% 69.3% 73.1% |41.3% 43.1% 45.7% 33.8% |
|TERMINAL (d) | 28/35 (80%) 30/38 (79%) 28/38 (74%) 30/41 (73%) |14/33 (42%) 17/40 (43%) 20/42 (48%) 15/43 (35%) |
|FIRST INCIDENCE | 478 452 627 506 |617 616 627 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.071N P=0.427N P=0.130N P=0.118N |P=0.090N P=0.400N P=0.459N P=0.103N |
|POLY 3 | P=0.264N P=0.576 P=0.244N P=0.395N |P=0.236N P=0.516 P=0.411 P=0.297N |
|POLY 1.5 | P=0.274N P=0.512 P=0.260N P=0.430N |P=0.249N P=0.503 P=0.382 P=0.311N |
|POLY 6 | P=0.253N P=0.541N P=0.220N P=0.349N |P=0.212N P=0.538 P=0.456 P=0.272N |
|LOGISTIC REGRESSION| P=0.218N P=0.511 P=0.191N P=0.373N |P=0.202N P=0.543 P=0.437 P=0.261N |
|COCH-ARM / FISHERS | P=0.312N P=0.500 P=0.257N P=0.475N |P=0.284N P=0.500 P=0.342 P=0.338N |
|ORDER RESTRICTED | P=0.363N (e) (e) (e) |P=0.276N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Carcinoma, Hepatocellular Adenoma, |
| or Hepatoblastoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 38/50 (76%) 39/50 (78%) 35/50 (70%) 35/49 (71%) |19/50 (38%) 20/50 (40%) 22/50 (44%) 16/50 (32%) |
|POLY-3 RATE (b) | 38/47.72 39/48.94 35/47.74 35/47.85 |19/46.00 20/46.45 22/48.11 16/47.29 |
|POLY-3 PERCENT (g) | 79.6% 79.7% 73.3% 73.1% |41.3% 43.1% 45.7% 33.8% |
|TERMINAL (d) | 29/35 (83%) 30/38 (79%) 29/38 (76%) 30/41 (73%) |14/33 (42%) 17/40 (43%) 20/42 (48%) 15/43 (35%) |
|FIRST INCIDENCE | 478 452 627 506 |617 616 627 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.049N* P=0.420N P=0.169N P=0.080N |P=0.090N P=0.400N P=0.459N P=0.103N |
|POLY 3 | P=0.198N P=0.598 P=0.308N P=0.302N |P=0.236N P=0.516 P=0.411 P=0.297N |
|POLY 1.5 | P=0.205N P=0.522 P=0.329N P=0.338N |P=0.249N P=0.503 P=0.382 P=0.311N |
|POLY 6 | P=0.190N P=0.504N P=0.272N P=0.256N |P=0.212N P=0.538 P=0.456 P=0.272N |
|LOGISTIC REGRESSION| P=0.158N P=0.510 P=0.244N P=0.280N |P=0.202N P=0.543 P=0.437 P=0.261N |
|COCH-ARM / FISHERS | P=0.241N P=0.500 P=0.326N P=0.387N |P=0.284N P=0.500 P=0.342 P=0.338N |
|ORDER RESTRICTED | P=0.355N (e) (e) (e) |P=0.276N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 11
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 11/50 (22%) 7/50 (14%) 8/50 (16%) 6/50 (12%) |1/50 (2%) 2/50 (4%) 3/50 (6%) 2/50 (4%) |
|POLY-3 RATE (b) | 11/44.75 7/46.10 8/46.36 6/48.16 |1/44.87 2/45.81 3/47.65 2/47.10 |
|POLY-3 PERCENT (g) | 24.6% 15.2% 17.3% 12.5% |2.2% 4.4% 6.3% 4.3% |
|TERMINAL (d) | 9/35 (26%) 7/38 (18%) 8/38 (21%) 4/41 (10%) |0/33 (0%) 2/40 (5%) 3/42 (7%) 2/43 (5%) |
|FIRST INCIDENCE | 605 729 (T) 729 (T) 610 |650 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.115N P=0.164N P=0.235N P=0.082N |P=0.491 P=0.550 P=0.381 P=0.571 |
|POLY 3 | P=0.146N P=0.194N P=0.273N P=0.106N |P=0.435 P=0.507 P=0.327 P=0.517 |
|POLY 1.5 | P=0.158N P=0.209N P=0.289N P=0.120N |P=0.426 P=0.502 P=0.318 P=0.510 |
|POLY 6 | P=0.133N P=0.180N P=0.260N P=0.091N |P=0.452 P=0.515 P=0.342 P=0.529 |
|LOGISTIC REGRESSION| P=0.140N P=0.169N P=0.241N P=0.123N |P=0.435 P=0.502 P=0.312 P=0.501 |
|COCH-ARM / FISHERS | P=0.182N P=0.218N P=0.306N P=0.143N |P=0.409 P=0.500 P=0.309 P=0.500 |
|ORDER RESTRICTED | P=0.093N (e) (e) (e) |P=0.379 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 4/50 (8%) 5/50 (10%) 7/50 (14%) |5/50 (10%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/44.11 4/46.10 5/46.49 7/47.68 |5/45.18 0/45.81 0/47.65 1/47.10 |
|POLY-3 PERCENT (g) | 2.3% 8.7% 10.8% 14.7% |11.1% 0.0% 0.0% 2.1% |
|TERMINAL (d) | 1/35 (3%) 4/38 (11%) 4/38 (11%) 6/41 (15%) |3/33 (9%) 0/40 (0%) 0/42 (0%) 1/43 (2%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 696 705 |638 --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.055 P=0.204 P=0.124 P=0.054 |P=0.088N P=0.025N* P=0.022N* P=0.066N |
|POLY 3 | P=0.043 * P=0.192 P=0.114 P=0.039 * |P=0.106N P=0.029N* P=0.026N* P=0.092N |
|POLY 1.5 | P=0.039 * P=0.184 P=0.108 P=0.035 * |P=0.106N P=0.030N* P=0.028N* P=0.096N |
|POLY 6 | P=0.048 * P=0.202 P=0.121 P=0.044 * |P=0.106N P=0.028N* P=0.024N* P=0.086N |
|LOGISTIC REGRESSION| P=0.049 * P=0.204 P=0.122 P=0.049 * |P=0.113N P=0.033N* P=0.034N* P=0.102N |
|COCH-ARM / FISHERS | P=0.033 * P=0.181 P=0.102 P=0.030 * |P=0.113N P=0.028N* P=0.028N* P=0.102N |
|ORDER RESTRICTED | P=0.027 * (e) (e) (e) |P=0.002N** (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 12
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar |
| Adenoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 12/50 (24%) 10/50 (20%) 13/50 (26%) 13/50 (26%) |6/50 (12%) 2/50 (4%) 3/50 (6%) 3/50 (6%) |
|POLY-3 RATE (b) | 12/44.75 10/46.10 13/46.49 13/48.26 |6/45.47 2/45.81 3/47.65 3/47.10 |
|POLY-3 PERCENT (g) | 26.8% 21.7% 28.0% 26.9% |13.2% 4.4% 6.3% 6.4% |
|TERMINAL (d) | 10/35 (29%) 10/38 (26%) 12/38 (32%) 10/41 (24%) |3/33 (9%) 2/40 (5%) 3/42 (7%) 3/43 (7%) |
|FIRST INCIDENCE | 605 729 (T) 696 610 |638 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.481 P=0.320N P=0.587N P=0.502N |P=0.239N P=0.101N P=0.164N P=0.158N |
|POLY 3 | P=0.406 P=0.373N P=0.545 P=0.587 |P=0.306N P=0.130N P=0.220N P=0.225N |
|POLY 1.5 | P=0.379 P=0.394N P=0.523 P=0.551 |P=0.311N P=0.133N P=0.229N P=0.232N |
|POLY 6 | P=0.441 P=0.352N P=0.566 P=0.556N |P=0.298N P=0.126N P=0.206N P=0.213N |
|LOGISTIC REGRESSION| P=0.426 P=0.324N P=0.592 P=0.582 |P=0.309N P=0.134N P=0.242N P=0.240N |
|COCH-ARM / FISHERS | P=0.329 P=0.405N P=0.500 P=0.500 |P=0.324N P=0.134N P=0.243N P=0.243N |
|ORDER RESTRICTED | P=0.565 (e) (e) (e) |P=0.134N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 0/47.59 |2/44.83 1/45.81 0/47.65 2/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.5% 2.2% 0.0% 4.3% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 2/43 (5%) |
|FIRST INCIDENCE | --- --- --- --- |663 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.597N P=0.445N P=0.199N P=0.609N |
|POLY 3 | (e) (e) (e) (e) |P=0.580 P=0.492N P=0.224N P=0.676N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.577 P=0.497N P=0.230N P=0.683N |
|POLY 6 | (e) (e) (e) (e) |P=0.586 P=0.484N P=0.215N P=0.663N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.583 P=0.496N P=0.240N P=0.682N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.569 P=0.500N P=0.247N P=0.691N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.390N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 13
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Mesentery |
| Hemangiosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 2/46.15 0/46.36 0/47.59 |0/44.58 0/45.81 0/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 4.3% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- 717 --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.249N P=0.258 (e) (e) |(e) (e) (e) (e) |
|POLY 3 | P=0.248N P=0.247 (e) (e) |(e) (e) (e) (e) |
|POLY 1.5 | P=0.255N P=0.241 (e) (e) |(e) (e) (e) (e) |
|POLY 6 | P=0.239N P=0.255 (e) (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.248N P=0.256 (e) (e) |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.264N P=0.247 (e) (e) |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.242N (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Cystadenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | |2/47 (4%) 3/48 (6%) 3/49 (6%) 2/48 (4%) |
|POLY-3 RATE (b) | |2/42.04 3/44.02 3/46.65 2/45.10 |
|POLY-3 PERCENT (g) | |4.8% 6.8% 6.4% 4.4% |
|TERMINAL (d) | |2/32 (6%) 3/39 (8%) 3/41 (7%) 2/41 (5%) |
|FIRST INCIDENCE | |729 (T) 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.426N P=0.590 P=0.613 P=0.603N |
|POLY 3 | |P=0.484N P=0.521 P=0.547 P=0.668N |
|POLY 1.5 | |P=0.492N P=0.514 P=0.535 P=0.675N |
|POLY 6 | |P=0.469N P=0.533 P=0.566 P=0.655N |
|LOGISTIC REGRESSION| |P=0.426N P=0.590 P=0.613 P=0.603N |
|COCH-ARM / FISHERS | |P=0.508N P=0.510 P=0.520 P=0.684N |
|ORDER RESTRICTED | |P=0.587N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 14
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis or Unspecified Site |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) |1/46 (2%) 7/49 (14%) 5/48 (10%) 3/47 (6%) |
|POLY-3 RATE (b) | 0/44.11 0/45.10 0/45.36 0/47.59 |1/41.35 7/45.60 5/46.17 3/44.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.4% 15.4% 10.8% 6.8% |
|TERMINAL (d) | 0/35 (0%) 0/37 (0%) 0/37 (0%) 0/41 (0%) |1/31 (3%) 6/40 (15%) 4/40 (10%) 3/40 (8%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) 680 568 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.419N P=0.067 P=0.162 P=0.400 |
|POLY 3 | (e) (e) (e) (e) |P=0.482N P=0.041 * P=0.129 P=0.329 |
|POLY 1.5 | (e) (e) (e) (e) |P=0.495N P=0.039 * P=0.121 P=0.323 |
|POLY 6 | (e) (e) (e) (e) |P=0.459N P=0.045 * P=0.141 P=0.340 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.498N P=0.048 * P=0.111 P=0.400 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.516N P=0.036 * P=0.112 P=0.317 |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.132 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skeletal Muscle |
| Rhabdomyosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 0/47.59 |0/44.58 2/45.81 2/47.70 0/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.4% 4.2% 0.0% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 2/40 (5%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- --- --- |--- 729 (T) 716 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.367N P=0.282 P=0.292 (e) |
|POLY 3 | (e) (e) (e) (e) |P=0.400N P=0.243 P=0.253 (e) |
|POLY 1.5 | (e) (e) (e) (e) |P=0.409N P=0.240 P=0.246 (e) |
|POLY 6 | (e) (e) (e) (e) |P=0.383N P=0.249 P=0.264 (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.385N P=0.282 P=0.264 (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.424N P=0.247 P=0.247 (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.272N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 15
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skin |
| Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, |
| or Fibrous Histiocytoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 1/44.53 1/46.10 0/46.36 0/47.59 |3/45.34 2/46.42 2/48.11 2/47.10 |
|POLY-3 PERCENT (g) | 2.3% 2.2% 0.0% 0.0% |6.6% 4.3% 4.2% 4.3% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 0/38 (0%) 0/41 (0%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 2/43 (5%) |
|FIRST INCIDENCE | 605 729 (T) --- --- |568 533 627 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.195N P=0.741N P=0.479N P=0.479N |P=0.394N P=0.459N P=0.435N P=0.418N |
|POLY 3 | P=0.206N P=0.753N P=0.492N P=0.487N |P=0.435N P=0.489N P=0.473N P=0.483N |
|POLY 1.5 | P=0.207N P=0.758N P=0.496N P=0.492N |P=0.439N P=0.496N P=0.485N P=0.489N |
|POLY 6 | P=0.205N P=0.748N P=0.488N P=0.481N |P=0.426N P=0.479N P=0.455N P=0.470N |
|LOGISTIC REGRESSION| P=0.220N P=0.760N P=0.484N P=0.644N |P=0.488N P=0.490N P=0.544N P=0.522N |
|COCH-ARM / FISHERS | P=0.208N P=0.753N P=0.500N P=0.500N |P=0.448N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.239N (e) (e) (e) |P=0.467N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skin |
| Fibrosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 0/47.59 |3/45.34 2/46.42 2/48.11 2/47.10 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |6.6% 4.3% 4.2% 4.3% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 2/43 (5%) |
|FIRST INCIDENCE | --- --- --- --- |568 533 627 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.394N P=0.459N P=0.435N P=0.418N |
|POLY 3 | (e) (e) (e) (e) |P=0.435N P=0.489N P=0.473N P=0.483N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.439N P=0.496N P=0.485N P=0.489N |
|POLY 6 | (e) (e) (e) (e) |P=0.426N P=0.479N P=0.455N P=0.470N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.488N P=0.490N P=0.544N P=0.522N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.448N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.467N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 16
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skin |
| Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 1/44.53 0/46.10 0/46.36 0/47.59 |3/45.34 2/46.42 2/48.11 2/47.10 |
|POLY-3 PERCENT (g) | 2.3% 0.0% 0.0% 0.0% |6.6% 4.3% 4.2% 4.3% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |1/33 (3%) 1/40 (3%) 0/42 (0%) 2/43 (5%) |
|FIRST INCIDENCE | 605 --- --- --- |568 533 627 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.340N P=0.483N P=0.479N P=0.479N |P=0.394N P=0.459N P=0.435N P=0.418N |
|POLY 3 | P=0.359N P=0.493N P=0.492N P=0.487N |P=0.435N P=0.489N P=0.473N P=0.483N |
|POLY 1.5 | P=0.355N P=0.498N P=0.496N P=0.492N |P=0.439N P=0.496N P=0.485N P=0.489N |
|POLY 6 | P=0.364N P=0.488N P=0.488N P=0.481N |P=0.426N P=0.479N P=0.455N P=0.470N |
|LOGISTIC REGRESSION| P=0.384N P=0.472N P=0.484N P=0.644N |P=0.488N P=0.490N P=0.544N P=0.522N |
|COCH-ARM / FISHERS | P=0.351N P=0.500N P=0.500N P=0.500N |P=0.448N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.108N (e) (e) (e) |P=0.467N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Skin |
| Hemangiosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/44.11 1/46.10 1/46.36 0/47.59 |1/44.61 1/45.81 2/47.65 0/47.10 |
|POLY-3 PERCENT (g) | 2.3% 2.2% 2.2% 0.0% |2.2% 2.2% 4.2% 0.0% |
|TERMINAL (d) | 1/35 (3%) 1/38 (3%) 1/38 (3%) 0/41 (0%) |0/33 (0%) 1/40 (3%) 2/42 (5%) 0/43 (0%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |721 729 (T) 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.275N P=0.743N P=0.743N P=0.468N |P=0.318N P=0.720N P=0.583 P=0.449N |
|POLY 3 | P=0.291N P=0.751N P=0.749N P=0.485N |P=0.358N P=0.755N P=0.523 P=0.489N |
|POLY 1.5 | P=0.295N P=0.757N P=0.755N P=0.491N |P=0.364N P=0.758N P=0.513 P=0.494N |
|POLY 6 | P=0.286N P=0.744N P=0.744N P=0.478N |P=0.348N P=0.749N P=0.538 P=0.481N |
|LOGISTIC REGRESSION| P=0.275N P=0.743N P=0.743N (e) |P=0.332N P=0.741N P=0.567 P=0.480N |
|COCH-ARM / FISHERS | P=0.303N P=0.753N P=0.753N P=0.500N |P=0.374N P=0.753N P=0.500 P=0.500N |
|ORDER RESTRICTED | P=0.314N (e) (e) (e) |P=0.274N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 17
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hemangiosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 2/49 (4%) 4/50 (8%) 1/49 (2%) 1/48 (2%) |0/47 (0%) 0/47 (0%) 1/49 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/43.27 4/46.37 1/45.73 1/46.16 |0/42.32 0/43.72 1/47.59 0/47.10 |
|POLY-3 PERCENT (g) | 4.6% 8.6% 2.2% 2.2% |0.0% 0.0% 2.1% 0.0% |
|TERMINAL (d) | 1/35 (3%) 1/38 (3%) 0/38 (0%) 1/41 (2%) |0/32 (0%) 0/40 (0%) 1/42 (2%) 0/43 (0%) |
|FIRST INCIDENCE | 723 676 690 729 (T) |--- --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.144N P=0.381 P=0.473N P=0.452N |P=0.679 (e) P=0.554 (e) |
|POLY 3 | P=0.156N P=0.370 P=0.481N P=0.477N |P=0.667 (e) P=0.523 (e) |
|POLY 1.5 | P=0.164N P=0.356 P=0.490N P=0.490N |P=0.664 (e) P=0.518 (e) |
|POLY 6 | P=0.147N P=0.385 P=0.470N P=0.463N |P=0.675 (e) P=0.531 (e) |
|LOGISTIC REGRESSION| P=0.159N P=0.371 P=0.482N P=0.450N |(e) (e) P=0.554 (e) |
|COCH-ARM / FISHERS | P=0.175N P=0.349 P=0.500N P=0.508N |P=0.658 (e) P=0.510 (e) |
|ORDER RESTRICTED | P=0.239N (e) (e) (e) |P=0.401 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Squamous Cell Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/44.11 1/46.10 2/46.36 2/47.59 |0/44.58 1/45.81 1/47.65 1/47.10 |
|POLY-3 PERCENT (g) | 0.0% 2.2% 4.3% 4.2% |0.0% 2.2% 2.1% 2.1% |
|TERMINAL (d) | 0/35 (0%) 1/38 (3%) 2/38 (5%) 2/41 (5%) |0/33 (0%) 1/40 (3%) 1/42 (2%) 1/43 (2%) |
|FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |--- 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.196 P=0.516 P=0.257 P=0.274 |P=0.465 P=0.538 P=0.548 P=0.553 |
|POLY 3 | P=0.185 P=0.509 P=0.248 P=0.255 |P=0.433 P=0.505 P=0.513 P=0.511 |
|POLY 1.5 | P=0.178 P=0.504 P=0.243 P=0.247 |P=0.425 P=0.502 P=0.508 P=0.507 |
|POLY 6 | P=0.195 P=0.515 P=0.254 P=0.263 |P=0.447 P=0.511 P=0.522 P=0.519 |
|LOGISTIC REGRESSION| (e) P=0.516 P=0.257 P=0.274 |(e) P=0.538 P=0.548 P=0.553 |
|COCH-ARM / FISHERS | P=0.164 P=0.500 P=0.247 P=0.247 |P=0.412 P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.165 (e) (e) (e) |P=0.337 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 18
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 3/49 (6%) 1/48 (2%) |1/46 (2%) 1/50 (2%) 0/49 (0%) 1/47 (2%) |
|POLY-3 RATE (b) | 3/44.11 1/46.10 3/45.58 1/46.16 |1/41.67 1/45.81 0/46.66 1/44.84 |
|POLY-3 PERCENT (g) | 6.8% 2.2% 6.6% 2.2% |2.4% 2.2% 0.0% 2.2% |
|TERMINAL (d) | 3/35 (9%) 1/38 (3%) 3/38 (8%) 1/41 (2%) |0/32 (0%) 1/40 (3%) 0/42 (0%) 1/41 (2%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |704 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.322N P=0.276N P=0.625N P=0.250N |P=0.544N P=0.724N P=0.457N P=0.713N |
|POLY 3 | P=0.366N P=0.290N P=0.647N P=0.289N |P=0.584N P=0.739N P=0.477N P=0.744N |
|POLY 1.5 | P=0.374N P=0.299N P=0.659N P=0.302N |P=0.586N P=0.741N P=0.482N P=0.748N |
|POLY 6 | P=0.355N P=0.279N P=0.634N P=0.274N |P=0.580N P=0.736N P=0.471N P=0.737N |
|LOGISTIC REGRESSION| P=0.322N P=0.276N P=0.625N P=0.250N |P=0.574N P=0.740N P=0.487N P=0.749N |
|COCH-ARM / FISHERS | P=0.392N P=0.309N P=0.651 P=0.324N |P=0.591N P=0.731N P=0.484N P=0.747N |
|ORDER RESTRICTED | P=0.226N (e) (e) (e) |P=0.507N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 3/49 (6%) 1/48 (2%) |1/46 (2%) 1/50 (2%) 0/49 (0%) 2/47 (4%) |
|POLY-3 RATE (b) | 3/44.11 1/46.10 3/45.58 1/46.16 |1/41.67 1/45.81 0/46.66 2/44.84 |
|POLY-3 PERCENT (g) | 6.8% 2.2% 6.6% 2.2% |2.4% 2.2% 0.0% 4.5% |
|TERMINAL (d) | 3/35 (9%) 1/38 (3%) 3/38 (8%) 1/41 (2%) |0/32 (0%) 1/40 (3%) 0/42 (0%) 2/41 (5%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |704 729 (T) --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.322N P=0.276N P=0.625N P=0.250N |P=0.424 P=0.724N P=0.457N P=0.577 |
|POLY 3 | P=0.366N P=0.290N P=0.647N P=0.289N |P=0.384 P=0.739N P=0.477N P=0.526 |
|POLY 1.5 | P=0.374N P=0.299N P=0.659N P=0.302N |P=0.379 P=0.741N P=0.482N P=0.519 |
|POLY 6 | P=0.355N P=0.279N P=0.634N P=0.274N |P=0.390 P=0.736N P=0.471N P=0.537 |
|LOGISTIC REGRESSION| P=0.322N P=0.276N P=0.625N P=0.250N |P=0.395 P=0.740N P=0.487N P=0.536 |
|COCH-ARM / FISHERS | P=0.392N P=0.309N P=0.651 P=0.324N |P=0.370 P=0.731N P=0.484N P=0.508 |
|ORDER RESTRICTED | P=0.226N (e) (e) (e) |P=0.286 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 19
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Polyp Stromal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | |0/50 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | |0/44.58 2/45.97 2/47.65 0/47.10 |
|POLY-3 PERCENT (g) | |0.0% 4.4% 4.2% 0.0% |
|TERMINAL (d) | |0/33 (0%) 1/40 (3%) 2/42 (5%) 0/43 (0%) |
|FIRST INCIDENCE | |--- 688 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.369N P=0.275 P=0.293 (e) |
|POLY 3 | |P=0.400N P=0.244 P=0.252 (e) |
|POLY 1.5 | |P=0.410N P=0.240 P=0.246 (e) |
|POLY 6 | |P=0.384N P=0.251 P=0.263 (e) |
|LOGISTIC REGRESSION| |P=0.406N P=0.240 P=0.293 (e) |
|COCH-ARM / FISHERS | |P=0.424N P=0.247 P=0.247 (e) |
|ORDER RESTRICTED | |P=0.273N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Hemangioma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 0/46.36 1/47.59 |1/45.01 1/45.81 0/47.65 2/47.13 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.1% |2.2% 2.2% 0.0% 4.2% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 1/41 (2%) |0/33 (0%) 1/40 (3%) 0/42 (0%) 1/43 (2%) |
|FIRST INCIDENCE | --- --- --- 729 (T) |604 729 (T) --- 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.203 (e) (e) P=0.532 |P=0.424 P=0.744N P=0.496N P=0.563 |
|POLY 3 | P=0.195 (e) (e) P=0.515 |P=0.386 P=0.757N P=0.489N P=0.516 |
|POLY 1.5 | P=0.192 (e) (e) P=0.509 |P=0.382 P=0.759N P=0.493N P=0.510 |
|POLY 6 | P=0.198 (e) (e) P=0.522 |P=0.394 P=0.752N P=0.481N P=0.528 |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.532 |P=0.368 P=0.761N P=0.539N P=0.484 |
|COCH-ARM / FISHERS | P=0.186 (e) (e) P=0.500 |P=0.374 P=0.753N P=0.500N P=0.500 |
|ORDER RESTRICTED | P=0.135 (e) (e) (e) |P=0.285 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 20
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Hemangiosarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 7/50 (14%) 5/50 (10%) 1/50 (2%) |3/50 (6%) 1/50 (2%) 3/50 (6%) 1/50 (2%) |
|POLY-3 RATE (b) | 6/44.37 7/46.37 5/47.29 1/47.59 |3/44.66 1/45.81 3/47.65 1/47.10 |
|POLY-3 PERCENT (g) | 13.5% 15.1% 10.6% 2.1% |6.7% 2.2% 6.3% 2.1% |
|TERMINAL (d) | 4/35 (11%) 4/38 (11%) 1/38 (3%) 1/41 (2%) |1/33 (3%) 1/40 (3%) 3/42 (7%) 1/43 (2%) |
|FIRST INCIDENCE | 665 676 605 729 (T) |716 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.020N* P=0.563 P=0.441N P=0.040N* |P=0.297N P=0.250N P=0.548N P=0.225N |
|POLY 3 | P=0.020N* P=0.534 P=0.456N P=0.045N* |P=0.356N P=0.296N P=0.632N P=0.287N |
|POLY 1.5 | P=0.022N* P=0.513 P=0.476N P=0.050N |P=0.362N P=0.302N P=0.645N P=0.294N |
|POLY 6 | P=0.018N* P=0.557 P=0.431N P=0.041N* |P=0.346N P=0.287N P=0.611N P=0.273N |
|LOGISTIC REGRESSION| P=0.024N* P=0.551 P=0.498N P=0.042N* |P=0.318N P=0.272N P=0.581N P=0.257N |
|COCH-ARM / FISHERS | P=0.027N* P=0.500 P=0.500N P=0.056N |P=0.374N P=0.309N P=0.661N P=0.309N |
|ORDER RESTRICTED | P=0.036N* (e) (e) (e) |P=0.223N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Hemangiosarcoma or Hemangioma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 7/50 (14%) 5/50 (10%) 2/50 (4%) |4/50 (8%) 2/50 (4%) 3/50 (6%) 3/50 (6%) |
|POLY-3 RATE (b) | 6/44.37 7/46.37 5/47.29 2/47.59 |4/45.09 2/45.81 3/47.65 3/47.13 |
|POLY-3 PERCENT (g) | 13.5% 15.1% 10.6% 4.2% |8.9% 4.4% 6.3% 6.4% |
|TERMINAL (d) | 4/35 (11%) 4/38 (11%) 1/38 (3%) 2/41 (5%) |1/33 (3%) 2/40 (5%) 3/42 (7%) 2/43 (5%) |
|FIRST INCIDENCE | 665 676 605 729 (T) |604 729 (T) 729 (T) 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.047N* P=0.563 P=0.441N P=0.096N |P=0.444N P=0.280N P=0.391N P=0.385N |
|POLY 3 | P=0.050N P=0.534 P=0.456N P=0.111N |P=0.524N P=0.330N P=0.470N P=0.476N |
|POLY 1.5 | P=0.055N P=0.513 P=0.476N P=0.120N |P=0.530N P=0.335N P=0.483N P=0.485N |
|POLY 6 | P=0.046N* P=0.557 P=0.431N P=0.102N |P=0.512N P=0.321N P=0.450N P=0.459N |
|LOGISTIC REGRESSION| P=0.057N P=0.551 P=0.498N P=0.101N |P=0.521N P=0.333N P=0.489N P=0.490N |
|COCH-ARM / FISHERS | P=0.063N P=0.500 P=0.500N P=0.134N |P=0.545N P=0.339N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.091N (e) (e) (e) |P=0.426N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 21
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Histiocytic Sarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/44.11 0/46.10 3/46.96 0/47.59 |2/44.72 0/45.81 0/47.65 1/47.13 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 6.4% 0.0% |4.5% 0.0% 0.0% 2.1% |
|TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/38 (0%) 0/41 (0%) |0/33 (0%) 0/40 (0%) 0/42 (0%) 0/43 (0%) |
|FIRST INCIDENCE | --- --- 645 --- |704 --- --- 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.501 (e) P=0.144 (e) |P=0.480N P=0.212N P=0.195N P=0.421N |
|POLY 3 | P=0.507 (e) P=0.130 (e) |P=0.528N P=0.232N P=0.223N P=0.482N |
|POLY 1.5 | P=0.494 (e) P=0.125 (e) |P=0.527N P=0.235N P=0.229N P=0.489N |
|POLY 6 | P=0.521 (e) P=0.137 (e) |P=0.530N P=0.226N P=0.215N P=0.469N |
|LOGISTIC REGRESSION| P=0.447 (e) P=0.115 (e) |P=0.519N P=0.233N P=0.228N P=0.482N |
|COCH-ARM / FISHERS | P=0.471 (e) P=0.121 (e) |P=0.529N P=0.247N P=0.247N P=0.500N |
|ORDER RESTRICTED | P=0.174 (e) (e) (e) |P=0.119N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, |
| NOS, or Undifferentiated Cell Type |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 5/50 (10%) |6/50 (12%) 4/50 (8%) 9/50 (18%) 12/50 (24%) |
|POLY-3 RATE (b) | 2/44.11 2/46.15 2/46.36 5/47.75 |6/45.54 4/46.21 9/48.48 12/48.93 |
|POLY-3 PERCENT (g) | 4.5% 4.3% 4.3% 10.5% |13.2% 8.7% 18.6% 24.5% |
|TERMINAL (d) | 2/35 (6%) 1/38 (3%) 2/38 (5%) 4/41 (10%) |4/33 (12%) 2/40 (5%) 7/42 (17%) 8/43 (19%) |
|FIRST INCIDENCE | 729 (T) 717 729 (T) 687 |568 673 568 445 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.150 P=0.664N P=0.665N P=0.288 |P=0.048 * P=0.292N P=0.436 P=0.211 |
|POLY 3 | P=0.126 P=0.678N P=0.676N P=0.250 |P=0.025 * P=0.360N P=0.334 P=0.126 |
|POLY 1.5 | P=0.121 P=0.687N P=0.684N P=0.236 |P=0.022 * P=0.368N P=0.314 P=0.114 |
|POLY 6 | P=0.133 P=0.666N P=0.666N P=0.267 |P=0.030 * P=0.346N P=0.367 P=0.147 |
|LOGISTIC REGRESSION| P=0.139 P=0.663N P=0.665N P=0.268 |P=0.013 * P=0.370N P=0.268 P=0.070 |
|COCH-ARM / FISHERS | P=0.111 P=0.691N P=0.691N P=0.218 |P=0.017 * P=0.370N P=0.288 P=0.096 |
|ORDER RESTRICTED | P=0.171 (e) (e) (e) |P=0.052 (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 22
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 37/50 (74%) 38/50 (76%) 39/50 (78%) 35/50 (70%) |25/50 (50%) 29/50 (58%) 32/50 (64%) 22/50 (44%) |
|POLY-3 RATE (b) | 37/46.55 38/47.29 39/47.60 35/48.67 |25/46.86 29/46.76 32/48.63 22/47.13 |
|POLY-3 PERCENT (g) | 79.5% 80.4% 81.9% 71.9% |53.4% 62.0% 65.8% 46.7% |
|TERMINAL (d) | 30/35 (86%) 33/38 (87%) 33/38 (87%) 30/41 (73%) |17/33 (52%) 25/40 (63%) 29/42 (69%) 21/43 (49%) |
|FIRST INCIDENCE | 478 610 627 610 |604 616 568 722 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.070N P=0.406N P=0.487N P=0.096N |P=0.041N* P=0.543N P=0.509 P=0.077N |
|POLY 3 | P=0.180N P=0.563 P=0.483 P=0.260N |P=0.197N P=0.259 P=0.149 P=0.329N |
|POLY 1.5 | P=0.229N P=0.501 P=0.434 P=0.324N |P=0.200N P=0.257 P=0.133 P=0.330N |
|POLY 6 | P=0.128N P=0.583N P=0.550 P=0.190N |P=0.189N P=0.267 P=0.175 P=0.322N |
|LOGISTIC REGRESSION| P=0.123N P=0.509N P=0.560N P=0.196N |P=0.149N P=0.302 P=0.152 P=0.259N |
|COCH-ARM / FISHERS | P=0.333N P=0.500 P=0.408 P=0.412N |P=0.230N P=0.274 P=0.113 P=0.344N |
|ORDER RESTRICTED | P=0.224N (e) (e) (e) |P=0.133N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 26/50 (52%) 23/50 (46%) 25/50 (50%) 26/50 (52%) |26/50 (52%) 15/50 (30%) 18/50 (36%) 24/50 (48%) |
|POLY-3 RATE (b) | 26/48.10 23/48.86 25/48.67 26/48.85 |26/47.15 15/47.72 18/49.01 24/49.38 |
|POLY-3 PERCENT (g) | 54.1% 47.1% 51.4% 53.2% |55.2% 31.4% 36.7% 48.6% |
|TERMINAL (d) | 15/35 (43%) 13/38 (34%) 16/38 (42%) 20/41 (49%) |15/33 (46%) 9/40 (23%) 12/42 (29%) 18/43 (42%) |
|FIRST INCIDENCE | 536 452 605 506 |568 533 568 445 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.414N P=0.258N P=0.362N P=0.326N |P=0.432N P=0.012N* P=0.025N* P=0.141N |
|POLY 3 | P=0.440 P=0.315N P=0.476N P=0.548N |P=0.422 P=0.015N* P=0.052N P=0.330N |
|POLY 1.5 | P=0.443 P=0.340N P=0.493N P=0.558N |P=0.403 P=0.017N* P=0.061N P=0.359N |
|POLY 6 | P=0.431 P=0.289N P=0.453N P=0.544N |P=0.448 P=0.012N* P=0.041N* P=0.294N |
|LOGISTIC REGRESSION| P=0.390 P=0.355N P=0.532N P=0.507 |P=0.338 P=0.021N* P=0.075N P=0.431N |
|COCH-ARM / FISHERS | P=0.422 P=0.345N P=0.500N P=0.579N |P=0.351 P=0.021N* P=0.079N P=0.421N |
|ORDER RESTRICTED | P=0.573N (e) (e) (e) |P=0.079N (e) (e) (e) |
|=================================================================================================================================|
Date: 04/26/05 EXPERIMENT: 91005 TEST: 08 Page 23
Statistical Analysis of Primary Tumors in Mice(B6C3F1) - METHYLENE BLUE TRIHYDRATE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 2.5 12.5 25 |0 MG/KG 2.5 12.5 25 |
| | MG/KG MG/KG MG/KG | MG/KG MG/KG MG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 46/50 (92%) 47/50 (94%) 46/50 (92%) 47/50 (94%) |39/50 (78%) 36/50 (72%) 40/50 (80%) 37/50 (74%) |
|POLY-3 RATE (b) | 46/48.96 47/49.00 46/49.05 47/49.59 |39/48.08 36/47.88 40/49.01 37/49.38 |
|POLY-3 PERCENT (g) | 94.0% 95.9% 93.8% 94.8% |81.1% 75.2% 81.6% 74.9% |
|TERMINAL (d) | 33/35 (94%) 36/38 (95%) 35/38 (92%) 39/41 (95%) |25/33 (76%) 29/40 (73%) 34/42 (81%) 31/43 (72%) |
|FIRST INCIDENCE | 478 452 605 506 |568 533 568 445 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.153N P=0.368N P=0.297N P=0.164N |P=0.095N P=0.091N P=0.129N P=0.052N |
|POLY 3 | P=0.565N P=0.508 P=0.655N P=0.608 |P=0.381N P=0.323N P=0.578 P=0.310N |
|POLY 1.5 | P=0.577N P=0.436 P=0.638 P=0.563 |P=0.405N P=0.329N P=0.553 P=0.331N |
|POLY 6 | P=0.553N P=0.599 P=0.589N P=0.658 |P=0.354N P=0.320N P=0.597N P=0.290N |
|LOGISTIC REGRESSION| P=0.490N P=0.452 P=0.603N P=0.647 |P=0.427N P=0.302N P=0.598 P=0.359N |
|COCH-ARM / FISHERS | P=0.486 P=0.500 P=0.643N P=0.500 |P=0.508N P=0.322N P=0.500 P=0.408N |
|ORDER RESTRICTED | P=0.652 (e) (e) (e) |P=0.363N (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).