TDMS Study 92013-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Southern Research Inst 4-METHYLIMIDAZOLE DATE: 12/06/04
EXPERIMENT: 92013 TEST: 05 TIME: 08:37:02
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92013B
PATHOLOGIST: FARNELL, DANIEL R. CAS: 822-36-6
------------------------------------------------------------------------------------------------------------------------------------
FINAL #1 RATS
REASONS FOR REMOVAL: ALL
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE ALL
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Southern Research Inst 4-METHYLIMIDAZOLE DATE: 12/06/04
EXPERIMENT: 92013 TEST: 05 TIME: 08:37:02
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92013B
PATHOLOGIST: FARNELL, DANIEL R. CAS: 822-36-6
Rats(FISCHER 344)
-----------------------------
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
Brain
Clitoral/Preputial Gland
Heart
Islets, Pancreatic
Kidney
Liver
Lung
Nose
Ovary
Pancreas
Parathyroid Gland
Pituitary Gland
Salivary Glands
Spleen
Testes
Thyroid Gland
Urinary Bladder
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Southern Research Inst 4-METHYLIMIDAZOLE DATE: 12/06/04
EXPERIMENT: 92013 TEST: 05 TIME: 08:37:02
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92013B
PATHOLOGIST: FARNELL, DANIEL R. CAS: 822-36-6
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF 4-METHYLIMIDAZOLE
===============================================================
Male Rats
------------
Organ Morphology
----- ----------
Adrenal Medulla Pheochromocytoma Complex
Pheochromocytoma: Benign, Complex, Malignant, NOS
Brain Oligodendroglioma, Glioma, or Astrocytoma
Pituitary Gland: Pars Distalis or Unspecified Site
Adenoma
Carcinoma or Adenoma
Skin Fibroma
Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma
Thyroid Gland: C-Cell Adenoma
All Organs Benign Tumors
===============================================================
Female Rats
------------
Organ Morphology
----- ----------
Clitoral/Preputial Gland Adenoma
Carcinoma or Adenoma
Mammary Gland Fibroadenoma
Fibroma, Fibroadenoma, Carcinoma, or Adenoma
Pituitary Gland: Pars Distalis or Unspecified Site
Adenoma
Carcinoma or Adenoma
Uterus Polyp Stromal
Sarcoma Stromal or Polyp Stromal
All Organs Histiocytic Sarcoma
Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated
Benign Tumors
Malignant and Benign Tumors
===============================================================
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 1
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma Benign |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 5/50 (10%) 3/50 (6%) 3/50 (6%) |2/48 (4%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 8/45.33 5/43.44 3/44.41 3/44.07 |2/44.67 1/45.69 2/43.88 2/44.39 |
|POLY-3 PERCENT (g) | 17.7% 11.5% 6.8% 6.8% |4.5% 2.2% 4.6% 4.5% |
|TERMINAL (d) | 7/31 (23%) 2/34 (6%) 3/33 (9%) 2/32 (6%) |2/42 (5%) 1/39 (3%) 1/34 (3%) 2/35 (6%) |
|FIRST INCIDENCE | 700 700 729 (T) 607 |729 (T) 729 (T) 700 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.070N P=0.247N P=0.082N P=0.096N |P=0.453 P=0.526N P=0.619 P=0.628 |
|POLY 3 | P=0.066N P=0.303N P=0.104N P=0.106N |P=0.520 P=0.492N P=0.687 P=0.692 |
|POLY 1.5 | P=0.065N P=0.298N P=0.102N P=0.104N |P=0.530 P=0.486N P=0.689N P=0.686N |
|POLY 6 | P=0.068N P=0.298N P=0.105N P=0.109N |P=0.506 P=0.500N P=0.672 P=0.678 |
|LOGISTIC REGRESSION| P=0.074N P=0.299N P=0.096N P=0.115N |P=0.490 P=0.526N P=0.673 P=0.628 |
|COCH-ARM / FISHERS | P=0.066N P=0.277N P=0.100N P=0.100N |P=0.539 P=0.485N P=0.676N P=0.676N |
|ORDER RESTRICTED | P=0.070N (e) (e) (e) |P=0.600 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma Complex |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/48 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/45.39 0/43.15 0/44.41 0/43.64 |0/44.67 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 4.4% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |0/42 (0%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 685 --- --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.120N P=0.235N P=0.238N P=0.253N |(e) (e) (e) (e) |
|POLY 3 | P=0.109N P=0.249N P=0.242N P=0.246N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.110N P=0.246N P=0.240N P=0.243N |(e) (e) (e) (e) |
|POLY 6 | P=0.108N P=0.249N P=0.244N P=0.250N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.117N P=0.246N P=0.240N P=0.244N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.115N P=0.247N P=0.247N P=0.247N |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.032N* (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 2
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma Malignant |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |1/48 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 2/43.26 0/44.41 0/43.64 |1/44.67 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 4.6% 0.0% 0.0% |2.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 0/33 (0%) 0/32 (0%) |1/42 (2%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- 700 --- --- |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.419N P=0.244 (e) (e) |P=0.331N P=0.515N P=0.542N P=0.536N |
|POLY 3 | P=0.417N P=0.227 (e) (e) |P=0.298N P=0.495N P=0.504N P=0.501N |
|POLY 1.5 | P=0.414N P=0.229 (e) (e) |P=0.301N P=0.492N P=0.498N P=0.496N |
|POLY 6 | P=0.419N P=0.228 (e) (e) |P=0.296N P=0.500N P=0.513N P=0.509N |
|LOGISTIC REGRESSION| P=0.412N P=0.228 (e) (e) |P=0.331N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) |P=0.301N P=0.490N P=0.490N P=0.490N |
|ORDER RESTRICTED | P=0.245N (e) (e) (e) |P=0.121N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma: Benign, Complex, Malignant, NOS |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 10/50 (20%) 6/50 (12%) 3/50 (6%) 3/50 (6%) |3/48 (6%) 1/50 (2%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 10/45.50 6/43.44 3/44.41 3/44.07 |3/44.67 1/45.69 2/43.88 2/44.39 |
|POLY-3 PERCENT (g) | 22.0% 13.8% 6.8% 6.8% |6.7% 2.2% 4.6% 4.5% |
|TERMINAL (d) | 8/31 (26%) 3/34 (9%) 3/33 (9%) 2/32 (6%) |3/42 (7%) 1/39 (3%) 1/34 (3%) 2/35 (6%) |
|FIRST INCIDENCE | 685 700 729 (T) 607 |729 (T) 729 (T) 700 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.022N* P=0.182N P=0.030N* P=0.038N* |P=0.578N P=0.332N P=0.592N P=0.583N |
|POLY 3 | P=0.019N* P=0.234N P=0.037N* P=0.039N* |P=0.501N P=0.297N P=0.508N P=0.503N |
|POLY 1.5 | P=0.019N* P=0.229N P=0.037N* P=0.038N* |P=0.494N P=0.291N P=0.494N P=0.490N |
|POLY 6 | P=0.019N* P=0.231N P=0.038N* P=0.040N* |P=0.512N P=0.305N P=0.528N P=0.520N |
|LOGISTIC REGRESSION| P=0.022N* P=0.230N P=0.037N* P=0.044N* |P=0.542N P=0.332N P=0.538N P=0.583N |
|COCH-ARM / FISHERS | P=0.020N* P=0.207N P=0.036N* P=0.036N* |P=0.486N P=0.293N P=0.480N P=0.480N |
|ORDER RESTRICTED | P=0.017N* (e) (e) (e) |P=0.396N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 3
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Brain |
| Oligodendroglioma, Glioma, or Astrocytoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 1/44.84 2/45.37 |0/46.53 1/46.50 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.4% |0.0% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 605 369 |--- 421 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.075 (e) P=0.500 P=0.238 |P=0.569N P=0.508 (e) (e) |
|POLY 3 | P=0.073 (e) P=0.498 P=0.238 |P=0.574N P=0.500 (e) (e) |
|POLY 1.5 | P=0.072 (e) P=0.499 P=0.238 |P=0.569N P=0.502 (e) (e) |
|POLY 6 | P=0.072 (e) P=0.499 P=0.236 |P=0.581N P=0.497 (e) (e) |
|LOGISTIC REGRESSION| P=0.043 * (e) P=0.531 (e) |P=0.648N P=0.350 (e) (e) |
|COCH-ARM / FISHERS | P=0.070 (e) P=0.500 P=0.247 |P=0.567N P=0.500 (e) (e) |
|ORDER RESTRICTED | P=0.075 (e) (e) (e) |P=0.389N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Clitoral/Preputial Gland |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/49 (0%) |8/50 (16%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/45.22 1/43.26 0/44.41 0/42.87 |8/47.04 1/46.48 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 4.4% 2.3% 0.0% 0.0% |17.0% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 2/31 (7%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |6/43 (14%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) 700 --- --- |624 434 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.104N P=0.485N P=0.224N P=0.231N |P=0.002N** P=0.027N* P=0.012N* P=0.011N* |
|POLY 3 | P=0.102N P=0.515N P=0.241N P=0.249N |P<0.001N** P=0.017N* P=0.005N** P=0.005N** |
|POLY 1.5 | P=0.102N P=0.512N P=0.240N P=0.247N |P<0.001N** P=0.016N* P=0.004N** P=0.004N** |
|POLY 6 | P=0.102N P=0.514N P=0.242N P=0.252N |P<0.001N** P=0.018N* P=0.006N** P=0.006N** |
|LOGISTIC REGRESSION| P=0.106N P=0.514N (e) (e) |P<0.001N** P=0.019N* P=0.006N** P=0.005N** |
|COCH-ARM / FISHERS | P=0.102N P=0.500N P=0.247N P=0.253N |P<0.001N** P=0.015N* P=0.003N** P=0.003N** |
|ORDER RESTRICTED | P=0.082N (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 4
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Clitoral/Preputial Gland |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/49 (0%) |2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 1/45.01 0/42.87 |2/46.53 1/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 0.0% |4.3% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |2/43 (5%) 1/39 (3%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 538 --- |729 (T) 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.692 (e) P=0.492 (e) |P=0.127N P=0.534N P=0.291N P=0.285N |
|POLY 3 | P=0.682 (e) P=0.499 (e) |P=0.103N P=0.506N P=0.251N P=0.248N |
|POLY 1.5 | P=0.686 (e) P=0.499 (e) |P=0.102N P=0.500N P=0.244N P=0.242N |
|POLY 6 | P=0.676 (e) P=0.499 (e) |P=0.105N P=0.513N P=0.261N P=0.256N |
|LOGISTIC REGRESSION| P=0.702 (e) P=0.543 (e) |P=0.127N P=0.534N (e) (e) |
|COCH-ARM / FISHERS | P=0.692 (e) P=0.500 (e) |P=0.101N P=0.500N P=0.247N P=0.247N |
|ORDER RESTRICTED | P=0.380 (e) (e) (e) |P=0.081N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Clitoral/Preputial Gland |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 0/49 (0%) |10/50 (20%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/45.22 1/43.26 1/45.01 0/42.87 |10/47.04 2/46.48 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 4.4% 2.3% 2.2% 0.0% |21.3% 4.3% 0.0% 0.0% |
|TERMINAL (d) | 2/31 (7%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |8/43 (19%) 1/39 (3%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) 700 538 --- |624 434 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.159N P=0.485N P=0.490N P=0.231N |P<0.001N** P=0.025N* P=0.004N** P=0.004N** |
|POLY 3 | P=0.158N P=0.515N P=0.502N P=0.249N |P<0.001N** P=0.014N* P<0.001N** P<0.001N** |
|POLY 1.5 | P=0.157N P=0.512N P=0.501N P=0.247N |P<0.001N** P=0.013N* P<0.001N** P<0.001N** |
|POLY 6 | P=0.159N P=0.514N P=0.501N P=0.252N |P<0.001N** P=0.016N* P=0.002N** P<0.001N** |
|LOGISTIC REGRESSION| P=0.153N P=0.514N P=0.480N (e) |P<0.001N** P=0.016N* P=0.002N** P=0.002N** |
|COCH-ARM / FISHERS | P=0.156N P=0.500N P=0.500N P=0.253N |P<0.001N** P=0.014N* P<0.001N** P<0.001N** |
|ORDER RESTRICTED | P=0.128N (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 5
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Heart |
| Schwannoma Benign |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 4/48 (8%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 0/44.41 0/43.64 |1/46.53 1/45.69 4/42.10 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 2.2% 9.5% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |1/43 (2%) 1/39 (3%) 4/33 (12%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.522N P=0.740 P=0.109 P=0.541N |
|POLY 3 | (e) (e) (e) (e) |P=0.470N P=0.756 P=0.150 P=0.509N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.457N P=0.760 P=0.158 P=0.504N |
|POLY 6 | (e) (e) (e) (e) |P=0.488N P=0.752 P=0.138 P=0.517N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.522N P=0.740 P=0.109 (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.446N P=0.753N P=0.168 P=0.500N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.178N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 2/49 (4%) 1/49 (2%) 1/49 (2%) |0/49 (0%) 1/50 (2%) 0/48 (0%) 0/47 (0%) |
|POLY-3 RATE (b) | 3/45.50 2/42.28 1/43.75 1/43.07 |0/45.90 1/45.69 0/42.98 0/41.55 |
|POLY-3 PERCENT (g) | 6.6% 4.7% 2.3% 2.3% |0.0% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 2/31 (7%) 2/34 (6%) 1/33 (3%) 1/32 (3%) |0/43 (0%) 1/39 (3%) 0/34 (0%) 0/33 (0%) |
|FIRST INCIDENCE | 653 729 (T) 729 (T) 729 (T) |--- 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.199N P=0.475N P=0.298N P=0.309N |P=0.607N P=0.481 (e) (e) |
|POLY 3 | P=0.207N P=0.533N P=0.319N P=0.325N |P=0.583N P=0.499 (e) (e) |
|POLY 1.5 | P=0.206N P=0.528N P=0.317N P=0.321N |P=0.577N P=0.503 (e) (e) |
|POLY 6 | P=0.210N P=0.535N P=0.321N P=0.331N |P=0.591N P=0.494 (e) (e) |
|LOGISTIC REGRESSION| P=0.211N P=0.529N P=0.316N P=0.322N |(e) P=0.481 (e) (e) |
|COCH-ARM / FISHERS | P=0.204N P=0.510N P=0.316N P=0.316N |P=0.575N P=0.505 (e) (e) |
|ORDER RESTRICTED | P=0.240N (e) (e) (e) |P=0.397N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 6
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 2/49 (4%) 2/49 (4%) 1/49 (2%) |0/49 (0%) 1/50 (2%) 0/48 (0%) 0/47 (0%) |
|POLY-3 RATE (b) | 3/45.50 2/42.28 2/43.75 1/43.07 |0/45.90 1/45.69 0/42.98 0/41.55 |
|POLY-3 PERCENT (g) | 6.6% 4.7% 4.6% 2.3% |0.0% 2.2% 0.0% 0.0% |
|TERMINAL (d) | 2/31 (7%) 2/34 (6%) 2/33 (6%) 1/32 (3%) |0/43 (0%) 1/39 (3%) 0/34 (0%) 0/33 (0%) |
|FIRST INCIDENCE | 653 729 (T) 729 (T) 729 (T) |--- 729 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.232N P=0.475N P=0.486N P=0.309N |P=0.607N P=0.481 (e) (e) |
|POLY 3 | P=0.243N P=0.533N P=0.518N P=0.325N |P=0.583N P=0.499 (e) (e) |
|POLY 1.5 | P=0.241N P=0.528N P=0.515N P=0.321N |P=0.577N P=0.503 (e) (e) |
|POLY 6 | P=0.248N P=0.535N P=0.521N P=0.331N |P=0.591N P=0.494 (e) (e) |
|LOGISTIC REGRESSION| P=0.248N P=0.529N P=0.515N P=0.322N |(e) P=0.481 (e) (e) |
|COCH-ARM / FISHERS | P=0.238N P=0.510N P=0.510N P=0.316N |P=0.575N P=0.505 (e) (e) |
|ORDER RESTRICTED | P=0.267N (e) (e) (e) |P=0.397N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/48 (2%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 0/44.41 0/43.64 |0/46.53 0/45.69 1/43.90 2/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 2.3% 4.5% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 2/35 (6%) |
|FIRST INCIDENCE | --- --- --- --- |--- --- 653 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.058 (e) P=0.472 P=0.194 |
|POLY 3 | (e) (e) (e) (e) |P=0.066 (e) P=0.488 P=0.227 |
|POLY 1.5 | (e) (e) (e) (e) |P=0.068 (e) P=0.493 P=0.233 |
|POLY 6 | (e) (e) (e) (e) |P=0.063 (e) P=0.481 P=0.219 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.069 (e) P=0.474 P=0.194 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.071 (e) P=0.490 P=0.247 |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.067 (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 7
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 1/44.41 0/43.64 |0/46.53 2/46.30 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |0.0% 4.3% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 1/33 (3%) 0/32 (0%) |0/43 (0%) 1/39 (3%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 729 (T) --- |--- 536 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.697 (e) P=0.512 (e) |P=0.424N P=0.229 (e) (e) |
|POLY 3 | P=0.684 (e) P=0.496 (e) |P=0.418N P=0.236 (e) (e) |
|POLY 1.5 | P=0.688 (e) P=0.498 (e) |P=0.409N P=0.239 (e) (e) |
|POLY 6 | P=0.678 (e) P=0.495 (e) |P=0.429N P=0.233 (e) (e) |
|LOGISTIC REGRESSION| (e) (e) P=0.512 (e) |P=0.410N P=0.211 (e) (e) |
|COCH-ARM / FISHERS | P=0.694 (e) P=0.500 (e) |P=0.405N P=0.247 (e) (e) |
|ORDER RESTRICTED | P=0.377 (e) (e) (e) |P=0.255N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Lung |
| Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar |
| Adenoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 1/43.15 1/44.41 1/43.64 |0/46.53 2/46.30 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 2.3% 2.3% 2.3% |0.0% 4.3% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 1/33 (3%) 1/32 (3%) |0/43 (0%) 1/39 (3%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |--- 536 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.384 P=0.518 P=0.512 P=0.506 |P=0.424N P=0.229 (e) (e) |
|POLY 3 | P=0.373 P=0.491 P=0.496 P=0.493 |P=0.418N P=0.236 (e) (e) |
|POLY 1.5 | P=0.377 P=0.493 P=0.498 P=0.495 |P=0.409N P=0.239 (e) (e) |
|POLY 6 | P=0.366 P=0.491 P=0.495 P=0.490 |P=0.429N P=0.233 (e) (e) |
|LOGISTIC REGRESSION| (e) P=0.518 P=0.512 P=0.506 |P=0.410N P=0.211 (e) (e) |
|COCH-ARM / FISHERS | P=0.384 P=0.500 P=0.500 P=0.500 |P=0.405N P=0.247 (e) (e) |
|ORDER RESTRICTED | P=0.321 (e) (e) (e) |P=0.255N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 8
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|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%) 2/50 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 0/44.41 0/43.64 |2/46.67 1/45.79 2/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.3% 2.2% 4.6% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |1/43 (2%) 0/39 (0%) 2/34 (6%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- --- --- |694 705 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.249N P=0.525N P=0.610 P=0.282N |
|POLY 3 | (e) (e) (e) (e) |P=0.212N P=0.507N P=0.671 P=0.249N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.206N P=0.501N P=0.682 P=0.242N |
|POLY 6 | (e) (e) (e) (e) |P=0.222N P=0.514N P=0.653 P=0.258N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.214N P=0.500N P=0.663 P=0.242N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.200N P=0.500N P=0.691N P=0.247N |
|ORDER RESTRICTED | (e) (e) (e) (e) |P=0.165N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland |
| Fibroadenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |24/50 (48%) 6/50 (12%) 4/50 (8%) 1/50 (2%) |
|POLY-3 RATE (b) | 3/45.22 1/43.15 1/45.01 1/43.64 |24/47.04 6/45.69 4/43.76 1/44.39 |
|POLY-3 PERCENT (g) | 6.6% 2.3% 2.2% 2.3% |51.0% 13.1% 9.1% 2.3% |
|TERMINAL (d) | 3/31 (10%) 1/34 (3%) 0/33 (0%) 1/32 (3%) |22/43 (51%) 6/39 (15%) 4/34 (12%) 1/35 (3%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 538 729 (T) |624 729 (T) 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.239N P=0.272N P=0.293N P=0.293N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 3 | P=0.242N P=0.322N P=0.307N P=0.318N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 1.5 | P=0.241N P=0.319N P=0.307N P=0.314N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 6 | P=0.244N P=0.322N P=0.306N P=0.323N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|LOGISTIC REGRESSION| P=0.243N P=0.272N P=0.294N P=0.293N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|COCH-ARM / FISHERS | P=0.242N P=0.309N P=0.309N P=0.309N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|ORDER RESTRICTED | P=0.199N (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 9
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Mammary Gland |
| Fibroma, Fibroadenoma, Carcinoma, or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |25/50 (50%) 7/50 (14%) 6/50 (12%) 1/50 (2%) |
|POLY-3 RATE (b) | 3/45.22 1/43.15 1/45.01 1/43.64 |25/47.04 7/45.79 6/43.76 1/44.39 |
|POLY-3 PERCENT (g) | 6.6% 2.3% 2.2% 2.3% |53.1% 15.3% 13.7% 2.3% |
|TERMINAL (d) | 3/31 (10%) 1/34 (3%) 0/33 (0%) 1/32 (3%) |23/43 (54%) 6/39 (15%) 6/34 (18%) 1/35 (3%) |
|FIRST INCIDENCE | 729 (T) 729 (T) 538 729 (T) |624 705 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.239N P=0.272N P=0.293N P=0.293N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 3 | P=0.242N P=0.322N P=0.307N P=0.318N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 1.5 | P=0.241N P=0.319N P=0.307N P=0.314N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 6 | P=0.244N P=0.322N P=0.306N P=0.323N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|LOGISTIC REGRESSION| P=0.243N P=0.272N P=0.294N P=0.293N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|COCH-ARM / FISHERS | P=0.242N P=0.309N P=0.309N P=0.309N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|ORDER RESTRICTED | P=0.199N (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) |
| Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/45.22 2/43.72 0/44.41 0/43.64 |0/46.53 1/45.98 1/44.26 1/44.39 |
|POLY-3 PERCENT (g) | 0.0% 4.6% 0.0% 0.0% |0.0% 2.2% 2.3% 2.3% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 0/33 (0%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 1/35 (3%) |
|FIRST INCIDENCE | --- 547 --- --- |--- 653 581 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.406N P=0.243 (e) (e) |P=0.356 P=0.496 P=0.491 P=0.459 |
|POLY 3 | P=0.416N P=0.230 (e) (e) |P=0.367 P=0.498 P=0.490 P=0.491 |
|POLY 1.5 | P=0.413N P=0.231 (e) (e) |P=0.377 P=0.500 P=0.495 P=0.496 |
|POLY 6 | P=0.418N P=0.231 (e) (e) |P=0.353 P=0.495 P=0.483 P=0.483 |
|LOGISTIC REGRESSION| P=0.399N P=0.272 (e) (e) |P=0.383 P=0.488 P=0.498 P=0.459 |
|COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) |P=0.384 P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.247N (e) (e) (e) |P=0.318 (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 10
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Pancreas |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/48 (0%) 0/48 (0%) 2/49 (4%) |0/49 (0%) 0/49 (0%) 0/47 (0%) 0/47 (0%) |
|POLY-3 RATE (b) | 1/45.22 0/41.86 0/43.18 2/43.07 |0/45.90 0/45.30 0/42.54 0/41.55 |
|POLY-3 PERCENT (g) | 2.2% 0.0% 0.0% 4.6% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 0/33 (0%) 2/32 (6%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 0/33 (0%) |
|FIRST INCIDENCE | 729 (T) --- --- 729 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.245 P=0.482N P=0.488N P=0.511 |(e) (e) (e) (e) |
|POLY 3 | P=0.245 P=0.515N P=0.509N P=0.483 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.246 P=0.515N P=0.509N P=0.486 |(e) (e) (e) (e) |
|POLY 6 | P=0.242 P=0.513N P=0.508N P=0.479 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.245 (e) (e) P=0.511 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.244 P=0.510N P=0.510N P=0.492 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.122 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis or Unspecified Site |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 16/49 (33%) 13/49 (27%) 10/48 (21%) 7/48 (15%) |29/48 (60%) 19/50 (38%) 20/50 (40%) 9/50 (18%) |
|POLY-3 RATE (b) | 16/46.40 13/43.61 10/42.84 7/43.47 |29/46.70 19/46.68 20/44.79 9/44.91 |
|POLY-3 PERCENT (g) | 34.5% 29.8% 23.3% 16.1% |62.1% 40.7% 44.7% 20.0% |
|TERMINAL (d) | 10/31 (32%) 10/33 (30%) 10/32 (31%) 6/32 (19%) |25/42 (60%) 15/39 (39%) 17/34 (50%) 6/35 (17%) |
|FIRST INCIDENCE | 464 477 729 (T) 384 |498 636 555 642 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.018N* P=0.309N P=0.121N P=0.034N* |P<0.001N** P=0.084N P=0.266N P<0.001N** |
|POLY 3 | P=0.022N* P=0.402N P=0.176N P=0.037N* |P<0.001N** P=0.029N* P=0.068N P<0.001N** |
|POLY 1.5 | P=0.020N* P=0.382N P=0.160N P=0.033N* |P<0.001N** P=0.024N* P=0.052N P<0.001N** |
|POLY 6 | P=0.027N* P=0.413N P=0.197N P=0.044N* |P<0.001N** P=0.034N* P=0.099N P<0.001N** |
|LOGISTIC REGRESSION| P=0.020N* P=0.331N P=0.144N P=0.028N* |P<0.001N** P=0.027N* P=0.064N P<0.001N** |
|COCH-ARM / FISHERS | P=0.020N* P=0.329N P=0.139N P=0.031N* |P<0.001N** P=0.022N* P=0.034N* P<0.001N** |
|ORDER RESTRICTED | P=0.029N* (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 11
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis or Unspecified Site |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 16/49 (33%) 13/49 (27%) 10/48 (21%) 7/48 (15%) |29/48 (60%) 20/50 (40%) 20/50 (40%) 9/50 (18%) |
|POLY-3 RATE (b) | 16/46.40 13/43.61 10/42.84 7/43.47 |29/46.70 20/46.68 20/44.79 9/44.91 |
|POLY-3 PERCENT (g) | 34.5% 29.8% 23.3% 16.1% |62.1% 42.9% 44.7% 20.0% |
|TERMINAL (d) | 10/31 (32%) 10/33 (30%) 10/32 (31%) 6/32 (19%) |25/42 (60%) 16/39 (41%) 17/34 (50%) 6/35 (17%) |
|FIRST INCIDENCE | 464 477 729 (T) 384 |498 636 555 642 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.018N* P=0.309N P=0.121N P=0.034N* |P<0.001N** P=0.118N P=0.266N P<0.001N** |
|POLY 3 | P=0.022N* P=0.402N P=0.176N P=0.037N* |P<0.001N** P=0.046N* P=0.068N P<0.001N** |
|POLY 1.5 | P=0.020N* P=0.382N P=0.160N P=0.033N* |P<0.001N** P=0.039N* P=0.052N P<0.001N** |
|POLY 6 | P=0.027N* P=0.413N P=0.197N P=0.044N* |P<0.001N** P=0.054N P=0.099N P<0.001N** |
|LOGISTIC REGRESSION| P=0.020N* P=0.331N P=0.144N P=0.028N* |P<0.001N** P=0.042N* P=0.064N P<0.001N** |
|COCH-ARM / FISHERS | P=0.020N* P=0.329N P=0.139N P=0.031N* |P<0.001N** P=0.034N* P=0.034N* P<0.001N** |
|ORDER RESTRICTED | P=0.029N* (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Basal Cell Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/45.22 0/43.15 1/44.41 2/43.64 |0/46.53 0/45.69 0/43.76 1/44.39 |
|POLY-3 PERCENT (g) | 2.2% 0.0% 2.3% 4.6% |0.0% 0.0% 0.0% 2.3% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 1/33 (3%) 2/32 (6%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 1/35 (3%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) 729 (T) |--- --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.246 P=0.482N P=0.748N P=0.511 |P=0.178 (e) (e) P=0.459 |
|POLY 3 | P=0.246 P=0.509N P=0.757 P=0.488 |P=0.193 (e) (e) P=0.491 |
|POLY 1.5 | P=0.248 P=0.507N P=0.758 P=0.492 |P=0.196 (e) (e) P=0.496 |
|POLY 6 | P=0.241 P=0.509N P=0.756 P=0.482 |P=0.190 (e) (e) P=0.483 |
|LOGISTIC REGRESSION| P=0.246 (e) P=0.748N P=0.511 |(e) (e) (e) P=0.459 |
|COCH-ARM / FISHERS | P=0.247 P=0.500N P=0.753N P=0.500 |P=0.198 (e) (e) P=0.500 |
|ORDER RESTRICTED | P=0.215 (e) (e) (e) |P=0.112 (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 12
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Basal Cell Adenoma, Basosquamous Tumor Benign, or |
| Trichoepithelioma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/45.22 0/43.15 1/44.41 2/43.64 |1/46.53 0/45.69 0/43.76 1/44.39 |
|POLY-3 PERCENT (g) | 2.2% 0.0% 2.3% 4.6% |2.2% 0.0% 0.0% 2.3% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 1/33 (3%) 2/32 (6%) |1/43 (2%) 0/39 (0%) 0/34 (0%) 1/35 (3%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) 729 (T) |729 (T) --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.246 P=0.482N P=0.748N P=0.511 |P=0.552 P=0.519N P=0.547N P=0.715 |
|POLY 3 | P=0.246 P=0.509N P=0.757 P=0.488 |P=0.588 P=0.504N P=0.512N P=0.750 |
|POLY 1.5 | P=0.248 P=0.507N P=0.758 P=0.492 |P=0.591 P=0.500N P=0.506N P=0.756 |
|POLY 6 | P=0.241 P=0.509N P=0.756 P=0.482 |P=0.584 P=0.508N P=0.521N P=0.742 |
|LOGISTIC REGRESSION| P=0.246 (e) P=0.748N P=0.511 |P=0.552 (e) (e) P=0.715 |
|COCH-ARM / FISHERS | P=0.247 P=0.500N P=0.753N P=0.500 |P=0.595 P=0.500N P=0.500N P=0.753N |
|ORDER RESTRICTED | P=0.215 (e) (e) (e) |P=0.390 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous |
| Tumor (benign, malignant or NOS), or Trichoepithelioma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 2/50 (4%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/45.22 0/43.15 2/44.46 2/43.64 |1/46.53 0/45.69 0/43.76 1/44.39 |
|POLY-3 PERCENT (g) | 2.2% 0.0% 4.5% 4.6% |2.2% 0.0% 0.0% 2.3% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 1/33 (3%) 2/32 (6%) |1/43 (2%) 0/39 (0%) 0/34 (0%) 1/35 (3%) |
|FIRST INCIDENCE | 729 (T) --- 717 729 (T) |729 (T) --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.243 P=0.482N P=0.518 P=0.511 |P=0.552 P=0.519N P=0.547N P=0.715 |
|POLY 3 | P=0.241 P=0.509N P=0.494 P=0.488 |P=0.588 P=0.504N P=0.512N P=0.750 |
|POLY 1.5 | P=0.244 P=0.507N P=0.496 P=0.492 |P=0.591 P=0.500N P=0.506N P=0.756 |
|POLY 6 | P=0.236 P=0.509N P=0.493 P=0.482 |P=0.584 P=0.508N P=0.521N P=0.742 |
|LOGISTIC REGRESSION| P=0.224 (e) P=0.497 P=0.511 |P=0.552 (e) (e) P=0.715 |
|COCH-ARM / FISHERS | P=0.245 P=0.500N P=0.500 P=0.500 |P=0.595 P=0.500N P=0.500N P=0.753N |
|ORDER RESTRICTED | P=0.259 (e) (e) (e) |P=0.390 (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 13
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor |
| (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 0/50 (0%) 5/50 (10%) 2/50 (4%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 3/45.22 0/43.15 5/44.46 2/43.64 |2/46.53 0/45.69 0/43.76 1/44.39 |
|POLY-3 PERCENT (g) | 6.6% 0.0% 11.3% 4.6% |4.3% 0.0% 0.0% 2.3% |
|TERMINAL (d) | 3/31 (10%) 0/34 (0%) 4/33 (12%) 2/32 (6%) |2/43 (5%) 0/39 (0%) 0/34 (0%) 1/35 (3%) |
|FIRST INCIDENCE | 729 (T) --- 717 729 (T) |729 (T) --- --- 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.546 P=0.105N P=0.389 P=0.485N |P=0.515N P=0.260N P=0.291N P=0.572N |
|POLY 3 | P=0.536 P=0.127N P=0.347 P=0.516N |P=0.462N P=0.241N P=0.251N P=0.516N |
|POLY 1.5 | P=0.541 P=0.126N P=0.351 P=0.510N |P=0.463N P=0.238N P=0.244N P=0.507N |
|POLY 6 | P=0.525 P=0.127N P=0.344 P=0.523N |P=0.462N P=0.246N P=0.261N P=0.529N |
|LOGISTIC REGRESSION| P=0.517 (e) P=0.362 P=0.485N |P=0.515N (e) (e) P=0.572N |
|COCH-ARM / FISHERS | P=0.544 P=0.121N P=0.357 P=0.500N |P=0.461N P=0.247N P=0.247N P=0.500N |
|ORDER RESTRICTED | P=0.277 (e) (e) (e) |P=0.143N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Fibroma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 2/50 (4%) 4/50 (8%) 3/50 (6%) |1/50 (2%) 1/50 (2%) 5/50 (10%) 0/50 (0%) |
|POLY-3 RATE (b) | 8/46.10 2/44.09 4/44.91 3/44.29 |1/46.53 1/45.81 5/44.09 0/44.39 |
|POLY-3 PERCENT (g) | 17.4% 4.5% 8.9% 6.8% |2.2% 2.2% 11.3% 0.0% |
|TERMINAL (d) | 5/31 (16%) 1/34 (3%) 1/33 (3%) 1/32 (3%) |1/43 (2%) 0/39 (0%) 4/34 (12%) 0/35 (0%) |
|FIRST INCIDENCE | 589 275 635 628 |729 (T) 700 638 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.140N P=0.047N* P=0.181N P=0.117N |P=0.545N P=0.744 P=0.063 P=0.541N |
|POLY 3 | P=0.124N P=0.052N P=0.189N P=0.111N |P=0.502N P=0.757 P=0.089 P=0.509N |
|POLY 1.5 | P=0.123N P=0.050N P=0.185N P=0.107N |P=0.486N P=0.760 P=0.096 P=0.504N |
|POLY 6 | P=0.127N P=0.054N P=0.193N P=0.116N |P=0.522N P=0.753 P=0.081 P=0.517N |
|LOGISTIC REGRESSION| P=0.117N P=0.029N* P=0.177N P=0.096N |P=0.489N P=0.761 P=0.090 (e) |
|COCH-ARM / FISHERS | P=0.124N P=0.046N* P=0.178N P=0.100N |P=0.474N P=0.753N P=0.102 P=0.500N |
|ORDER RESTRICTED | P=0.060N (e) (e) (e) |P=0.152N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 14
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, |
| or Fibrous Histiocytoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 2/50 (4%) 5/50 (10%) 3/50 (6%) |1/50 (2%) 1/50 (2%) 5/50 (10%) 0/50 (0%) |
|POLY-3 RATE (b) | 8/46.10 2/44.09 5/45.05 3/44.29 |1/46.53 1/45.81 5/44.09 0/44.39 |
|POLY-3 PERCENT (g) | 17.4% 4.5% 11.1% 6.8% |2.2% 2.2% 11.3% 0.0% |
|TERMINAL (d) | 5/31 (16%) 1/34 (3%) 1/33 (3%) 1/32 (3%) |1/43 (2%) 0/39 (0%) 4/34 (12%) 0/35 (0%) |
|FIRST INCIDENCE | 589 275 635 628 |729 (T) 700 638 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.160N P=0.047N* P=0.277N P=0.117N |P=0.545N P=0.744 P=0.063 P=0.541N |
|POLY 3 | P=0.141N P=0.052N P=0.290N P=0.111N |P=0.502N P=0.757 P=0.089 P=0.509N |
|POLY 1.5 | P=0.139N P=0.050N P=0.285N P=0.107N |P=0.486N P=0.760 P=0.096 P=0.504N |
|POLY 6 | P=0.144N P=0.054N P=0.294N P=0.116N |P=0.522N P=0.753 P=0.081 P=0.517N |
|LOGISTIC REGRESSION| P=0.132N P=0.029N* P=0.275N P=0.096N |P=0.489N P=0.761 P=0.090 (e) |
|COCH-ARM / FISHERS | P=0.139N P=0.046N* P=0.277N P=0.100N |P=0.474N P=0.753N P=0.102 P=0.500N |
|ORDER RESTRICTED | P=0.067N (e) (e) (e) |P=0.152N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Keratoacanthoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/45.22 0/43.15 3/44.41 0/43.64 |0/46.53 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 2.2% 0.0% 6.8% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 3/33 (9%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.498N P=0.482N P=0.327 P=0.494N |(e) (e) (e) (e) |
|POLY 3 | P=0.507N P=0.509N P=0.299 P=0.507N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.503N P=0.507N P=0.301 P=0.505N |(e) (e) (e) (e) |
|POLY 6 | P=0.514N P=0.509N P=0.296 P=0.510N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.498N (e) P=0.327 (e) |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.500N P=0.500N P=0.309 P=0.500N |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.266N (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 15
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Squamous Cell Papilloma, Papilloma, Squamous Cell |
| Carcinoma or Keratoacanthoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/45.22 0/43.15 3/44.41 0/43.64 |1/46.53 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 4.4% 0.0% 6.8% 0.0% |2.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 2/31 (7%) 0/34 (0%) 3/33 (9%) 0/32 (0%) |1/43 (2%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) --- |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.291N P=0.218N P=0.529 P=0.231N |P=0.334N P=0.519N P=0.547N P=0.541N |
|POLY 3 | P=0.298N P=0.248N P=0.492 P=0.245N |P=0.303N P=0.504N P=0.512N P=0.509N |
|POLY 1.5 | P=0.296N P=0.246N P=0.495 P=0.242N |P=0.306N P=0.500N P=0.506N P=0.504N |
|POLY 6 | P=0.304N P=0.247N P=0.489 P=0.248N |P=0.301N P=0.508N P=0.521N P=0.517N |
|LOGISTIC REGRESSION| P=0.291N (e) P=0.529 (e) |P=0.334N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.296N P=0.247N P=0.500 P=0.247N |P=0.306N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.158N (e) (e) (e) |P=0.130N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Skin |
| Squamous Cell Papilloma, Papilloma, or Keratoacanthoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/45.22 0/43.15 3/44.41 0/43.64 |1/46.53 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 2.2% 0.0% 6.8% 0.0% |2.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/31 (3%) 0/34 (0%) 3/33 (9%) 0/32 (0%) |1/43 (2%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 729 (T) --- 729 (T) --- |729 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.498N P=0.482N P=0.327 P=0.494N |P=0.334N P=0.519N P=0.547N P=0.541N |
|POLY 3 | P=0.507N P=0.509N P=0.299 P=0.507N |P=0.303N P=0.504N P=0.512N P=0.509N |
|POLY 1.5 | P=0.503N P=0.507N P=0.301 P=0.505N |P=0.306N P=0.500N P=0.506N P=0.504N |
|POLY 6 | P=0.514N P=0.509N P=0.296 P=0.510N |P=0.301N P=0.508N P=0.521N P=0.517N |
|LOGISTIC REGRESSION| P=0.498N (e) P=0.327 (e) |P=0.334N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.500N P=0.500N P=0.309 P=0.500N |P=0.306N P=0.500N P=0.500N P=0.500N |
|ORDER RESTRICTED | P=0.266N (e) (e) (e) |P=0.130N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 16
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Testes |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 46/50 (92%) 44/50 (88%) 47/50 (94%) 45/50 (90%) | |
|POLY-3 RATE (b) | 46/48.36 44/46.88 47/49.24 45/47.41 | |
|POLY-3 PERCENT (g) | 95.1% 93.9% 95.5% 94.9% | |
|TERMINAL (d) | 30/31 (97%) 32/34 (94%) 32/33 (97%) 31/32 (97%) | |
|FIRST INCIDENCE | 582 516 498 607 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.498 P=0.281N P=0.533N P=0.524N | |
|POLY 3 | P=0.571 P=0.579N P=0.670 P=0.689N | |
|POLY 1.5 | P=0.584 P=0.535N P=0.595 P=0.625N | |
|POLY 6 | P=0.563 P=0.571N P=0.677N P=0.735N | |
|LOGISTIC REGRESSION| P=0.560 P=0.597 P=0.405 P=0.653N | |
|COCH-ARM / FISHERS | P=0.533N P=0.370N P=0.500 P=0.500N | |
|ORDER RESTRICTED | P=0.664 (e) (e) (e) | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 11/47 (23%) 7/46 (15%) 3/48 (6%) 10/44 (23%) |10/47 (21%) 8/44 (18%) 6/40 (15%) 8/45 (18%) |
|POLY-3 RATE (b) | 11/43.77 7/40.94 3/43.27 10/39.55 |10/44.16 8/42.14 6/38.47 8/40.99 |
|POLY-3 PERCENT (g) | 25.1% 17.1% 6.9% 25.3% |22.7% 19.0% 15.6% 19.5% |
|TERMINAL (d) | 9/31 (29%) 7/34 (21%) 2/33 (6%) 10/32 (31%) |9/42 (21%) 8/38 (21%) 5/34 (15%) 7/34 (21%) |
|FIRST INCIDENCE | 667 729 (T) 706 729 (T) |700 729 (T) 700 642 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.489N P=0.162N P=0.018N* P=0.480N |P=0.528N P=0.487N P=0.356N P=0.581N |
|POLY 3 | P=0.552N P=0.262N P=0.019N* P=0.593 |P=0.411N P=0.439N P=0.299N P=0.465N |
|POLY 1.5 | P=0.547N P=0.254N P=0.019N* P=0.594N |P=0.393N P=0.435N P=0.296N P=0.442N |
|POLY 6 | P=0.552 P=0.262N P=0.020N* P=0.588 |P=0.437N P=0.451N P=0.309N P=0.498N |
|LOGISTIC REGRESSION| P=0.551 P=0.224N P=0.021N* P=0.587N |P=0.459N P=0.459N P=0.308N P=0.495N |
|COCH-ARM / FISHERS | P=0.538N P=0.231N P=0.018N* P=0.569N |P=0.384N P=0.458N P=0.319N P=0.437N |
|ORDER RESTRICTED | P=0.207N (e) (e) (e) |P=0.439N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 17
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/47 (0%) 0/46 (0%) 2/48 (4%) 0/44 (0%) |1/47 (2%) 0/44 (0%) 2/40 (5%) 0/45 (0%) |
|POLY-3 RATE (b) | 0/43.51 0/40.94 2/43.18 0/39.55 |1/44.04 0/42.14 2/38.35 0/40.67 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 4.6% 0.0% |2.3% 0.0% 5.2% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 2/33 (6%) 0/32 (0%) |1/42 (2%) 0/38 (0%) 2/34 (6%) 0/34 (0%) |
|FIRST INCIDENCE | --- --- 729 (T) --- |729 (T) --- 729 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.597 (e) P=0.252 (e) |P=0.515N P=0.520N P=0.426 P=0.542N |
|POLY 3 | P=0.575 (e) P=0.235 (e) |P=0.488N P=0.509N P=0.452 P=0.516N |
|POLY 1.5 | P=0.578 (e) P=0.238 (e) |P=0.480N P=0.508N P=0.453 P=0.510N |
|POLY 6 | P=0.575 (e) P=0.234 (e) |P=0.499N P=0.511N P=0.447 P=0.523N |
|LOGISTIC REGRESSION| (e) (e) P=0.252 (e) |P=0.515N (e) P=0.426 (e) |
|COCH-ARM / FISHERS | P=0.584 (e) P=0.253 (e) |P=0.472N P=0.516N P=0.439 P=0.511N |
|ORDER RESTRICTED | P=0.247 (e) (e) (e) |P=0.318N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 11/47 (23%) 7/46 (15%) 5/48 (10%) 10/44 (23%) |11/47 (23%) 8/44 (18%) 8/40 (20%) 8/45 (18%) |
|POLY-3 RATE (b) | 11/43.77 7/40.94 5/43.27 10/39.55 |11/44.16 8/42.14 8/38.47 8/40.99 |
|POLY-3 PERCENT (g) | 25.1% 17.1% 11.6% 25.3% |24.9% 19.0% 20.8% 19.5% |
|TERMINAL (d) | 9/31 (29%) 7/34 (21%) 4/33 (12%) 10/32 (31%) |10/42 (24%) 8/38 (21%) 7/34 (21%) 7/34 (21%) |
|FIRST INCIDENCE | 667 729 (T) 706 729 (T) |700 729 (T) 700 642 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.515N P=0.162N P=0.071N P=0.480N |P=0.481N P=0.391N P=0.496N P=0.488N |
|POLY 3 | P=0.523 P=0.262N P=0.085N P=0.593 |P=0.363N P=0.344N P=0.429N P=0.369N |
|POLY 1.5 | P=0.528 P=0.254N P=0.082N P=0.594N |P=0.343N P=0.340N P=0.424N P=0.347N |
|POLY 6 | P=0.517 P=0.262N P=0.087N P=0.588 |P=0.391N P=0.355N P=0.442N P=0.401N |
|LOGISTIC REGRESSION| P=0.519 P=0.224N P=0.083N P=0.587N |P=0.412N P=0.363N P=0.446N P=0.400N |
|COCH-ARM / FISHERS | P=0.538 P=0.231N P=0.078N P=0.569N |P=0.332N P=0.362N P=0.453N P=0.342N |
|ORDER RESTRICTED | P=0.316N (e) (e) (e) |P=0.427N (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 18
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | | |
|----------- | | |
|OVERALL (a) | 0/47 (0%) 1/46 (2%) 0/48 (0%) 0/44 (0%) |2/47 (4%) 3/44 (7%) 0/40 (0%) 0/45 (0%) |
|POLY-3 RATE (b) | 0/43.51 1/40.94 0/43.18 0/39.55 |2/44.04 3/42.48 0/38.35 0/40.67 |
|POLY-3 PERCENT (g) | 0.0% 2.4% 0.0% 0.0% |4.5% 7.1% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 0/33 (0%) 0/32 (0%) |2/42 (5%) 2/38 (5%) 0/34 (0%) 0/34 (0%) |
|FIRST INCIDENCE | --- 729 (T) --- --- |729 (T) 636 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.567N P=0.518 (e) (e) |P=0.097N P=0.464 P=0.286N P=0.286N |
|POLY 3 | P=0.583N P=0.488 (e) (e) |P=0.082N P=0.484 P=0.268N P=0.255N |
|POLY 1.5 | P=0.581N P=0.490 (e) (e) |P=0.080N P=0.484 P=0.267N P=0.249N |
|POLY 6 | P=0.584N P=0.488 (e) (e) |P=0.086N P=0.482 P=0.271N P=0.264N |
|LOGISTIC REGRESSION| (e) P=0.518 (e) (e) |P=0.081N P=0.473 (e) (e) |
|COCH-ARM / FISHERS | P=0.576N P=0.495 (e) (e) |P=0.081N P=0.468 P=0.289N P=0.258N |
|ORDER RESTRICTED | P=0.388N (e) (e) (e) |P=0.087N (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Tongue |
| Squamous Cell Carcinoma or Papilloma Squamous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/45.22 2/43.72 0/44.41 0/43.64 |0/46.53 1/45.98 1/44.26 1/44.39 |
|POLY-3 PERCENT (g) | 0.0% 4.6% 0.0% 0.0% |0.0% 2.2% 2.3% 2.3% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 0/33 (0%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 1/35 (3%) |
|FIRST INCIDENCE | --- 547 --- --- |--- 653 581 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.406N P=0.243 (e) (e) |P=0.356 P=0.496 P=0.491 P=0.459 |
|POLY 3 | P=0.416N P=0.230 (e) (e) |P=0.367 P=0.498 P=0.490 P=0.491 |
|POLY 1.5 | P=0.413N P=0.231 (e) (e) |P=0.377 P=0.500 P=0.495 P=0.496 |
|POLY 6 | P=0.418N P=0.231 (e) (e) |P=0.353 P=0.495 P=0.483 P=0.483 |
|LOGISTIC REGRESSION| P=0.399N P=0.272 (e) (e) |P=0.383 P=0.488 P=0.498 P=0.459 |
|COCH-ARM / FISHERS | P=0.405N P=0.247 (e) (e) |P=0.384 P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.247N (e) (e) (e) |P=0.318 (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 19
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Uterus |
| Polyp Stromal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | |16/50 (32%) 5/50 (10%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | |16/47.69 5/45.89 2/43.76 2/44.39 |
|POLY-3 PERCENT (g) | |33.6% 10.9% 4.6% 4.5% |
|TERMINAL (d) | |14/43 (33%) 4/39 (10%) 2/34 (6%) 2/35 (6%) |
|FIRST INCIDENCE | |302 677 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P<0.001N** P=0.014N* P=0.002N** P=0.002N** |
|POLY 3 | |P<0.001N** P=0.007N** P<0.001N** P<0.001N** |
|POLY 1.5 | |P<0.001N** P=0.006N** P<0.001N** P<0.001N** |
|POLY 6 | |P<0.001N** P=0.008N** P<0.001N** P<0.001N** |
|LOGISTIC REGRESSION| |P<0.001N** P=0.007N** P<0.001N** P<0.001N** |
|COCH-ARM / FISHERS | |P<0.001N** P=0.006N** P<0.001N** P<0.001N** |
|ORDER RESTRICTED | |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Uterus |
| Sarcoma Stromal or Polyp Stromal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | |17/50 (34%) 5/50 (10%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | |17/47.69 5/45.89 2/43.76 2/44.39 |
|POLY-3 PERCENT (g) | |35.6% 10.9% 4.6% 4.5% |
|TERMINAL (d) | |15/43 (35%) 4/39 (10%) 2/34 (6%) 2/35 (6%) |
|FIRST INCIDENCE | |302 677 729 (T) 729 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P<0.001N** P=0.009N** P<0.001N** P<0.001N** |
|POLY 3 | |P<0.001N** P=0.004N** P<0.001N** P<0.001N** |
|POLY 1.5 | |P<0.001N** P=0.003N** P<0.001N** P<0.001N** |
|POLY 6 | |P<0.001N** P=0.004N** P<0.001N** P<0.001N** |
|LOGISTIC REGRESSION| |P<0.001N** P=0.004N** P<0.001N** P<0.001N** |
|COCH-ARM / FISHERS | |P<0.001N** P=0.004N** P<0.001N** P<0.001N** |
|ORDER RESTRICTED | |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 20
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|Zymbal's Gland |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 3/46.20 1/43.15 2/45.02 0/43.64 |0/46.53 2/45.69 1/43.88 0/44.39 |
|POLY-3 PERCENT (g) | 6.5% 2.3% 4.4% 0.0% |0.0% 4.4% 2.3% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 1/33 (3%) 0/32 (0%) |0/43 (0%) 2/39 (5%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | 547 729 (T) 531 --- |--- 729 (T) 700 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.114N P=0.319N P=0.515N P=0.146N |P=0.510N P=0.217 P=0.465 (e) |
|POLY 3 | P=0.107N P=0.330N P=0.512N P=0.129N |P=0.480N P=0.233 P=0.488 (e) |
|POLY 1.5 | P=0.105N P=0.323N P=0.507N P=0.125N |P=0.468N P=0.237 P=0.494 (e) |
|POLY 6 | P=0.110N P=0.335N P=0.518N P=0.135N |P=0.495N P=0.229 P=0.480 (e) |
|LOGISTIC REGRESSION| P=0.097N P=0.258N P=0.443N P=0.080N |P=0.480N P=0.217 P=0.498 (e) |
|COCH-ARM / FISHERS | P=0.104N P=0.309N P=0.500N P=0.121N |P=0.461N P=0.247 P=0.500 (e) |
|ORDER RESTRICTED | P=0.064N (e) (e) (e) |P=0.319 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Histiocytic Sarcoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 0/43.15 1/44.48 1/44.02 |2/47.21 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 2.3% |4.2% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 0/34 (0%) 0/33 (0%) 0/32 (0%) |1/43 (2%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- --- 712 622 |498 --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.235 (e) P=0.506 P=0.504 |P=0.127N P=0.253N P=0.265N P=0.262N |
|POLY 3 | P=0.233 (e) P=0.497 P=0.495 |P=0.112N P=0.245N P=0.255N P=0.251N |
|POLY 1.5 | P=0.235 (e) P=0.498 P=0.496 |P=0.113N P=0.240N P=0.246N P=0.244N |
|POLY 6 | P=0.230 (e) P=0.496 P=0.493 |P=0.111N P=0.250N P=0.266N P=0.261N |
|LOGISTIC REGRESSION| P=0.237 (e) P=0.496 P=0.552 |P=0.118N P=0.261N P=0.234N P=0.249N |
|COCH-ARM / FISHERS | P=0.236 (e) P=0.500 P=0.500 |P=0.115N P=0.247N P=0.247N P=0.247N |
|ORDER RESTRICTED | P=0.246 (e) (e) (e) |P=0.035N* (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 21
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Leukemia: Lymphocytic, Monocytic, Mononuclear, or |
| Undifferentiated |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 15/50 (30%) 18/50 (36%) 22/50 (44%) 20/50 (40%) |9/50 (18%) 7/50 (14%) 16/50 (32%) 20/50 (40%) |
|POLY-3 RATE (b) | 15/47.00 18/45.55 22/47.58 20/47.38 |9/47.04 7/47.43 16/46.44 20/47.92 |
|POLY-3 PERCENT (g) | 31.9% 39.5% 46.2% 42.2% |19.1% 14.8% 34.5% 41.7% |
|TERMINAL (d) | 5/31 (16%) 9/34 (27%) 12/33 (36%) 7/32 (22%) |7/43 (16%) 4/39 (10%) 7/34 (21%) 11/35 (31%) |
|FIRST INCIDENCE | 582 567 493 584 |624 434 578 368 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.181 P=0.375 P=0.160 P=0.211 |P<0.001 ** P=0.458N P=0.041 * P=0.007 ** |
|POLY 3 | P=0.184 P=0.292 P=0.110 P=0.205 |P<0.001 ** P=0.386N P=0.073 P=0.013 * |
|POLY 1.5 | P=0.175 P=0.297 P=0.108 P=0.198 |P<0.001 ** P=0.379N P=0.078 P=0.014 * |
|POLY 6 | P=0.200 P=0.303 P=0.113 P=0.221 |P<0.001 ** P=0.398N P=0.068 P=0.012 * |
|LOGISTIC REGRESSION| P=0.172 P=0.325 P=0.115 P=0.226 |P=0.002 ** P=0.402N P=0.081 P=0.014 * |
|COCH-ARM / FISHERS | P=0.168 P=0.335 P=0.107 P=0.201 |P=0.002 ** P=0.393N P=0.083 P=0.013 * |
|ORDER RESTRICTED | P=0.169 (e) (e) (e) |P=0.003 ** (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Mesothelioma: Benign, Malignant, NOS |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 2/43.68 3/44.87 1/43.94 |0/46.53 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 4.6% 6.7% 2.3% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 2/33 (6%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- 567 594 650 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.449 P=0.243 P=0.130 P=0.491 |(e) (e) (e) (e) |
|POLY 3 | P=0.428 P=0.229 P=0.117 P=0.494 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.434 P=0.231 P=0.118 P=0.496 |(e) (e) (e) (e) |
|POLY 6 | P=0.421 P=0.231 P=0.117 P=0.492 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.450 P=0.264 P=0.124 P=0.529 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.444 P=0.247 P=0.121 P=0.500 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.183 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 22
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Mesothelioma: Malignant |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/45.22 2/43.68 3/44.87 1/43.94 |0/46.53 0/45.69 0/43.76 0/44.39 |
|POLY-3 PERCENT (g) | 0.0% 4.6% 6.7% 2.3% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/31 (0%) 1/34 (3%) 2/33 (6%) 0/32 (0%) |0/43 (0%) 0/39 (0%) 0/34 (0%) 0/35 (0%) |
|FIRST INCIDENCE | --- 567 594 650 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.449 P=0.243 P=0.130 P=0.491 |(e) (e) (e) (e) |
|POLY 3 | P=0.428 P=0.229 P=0.117 P=0.494 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.434 P=0.231 P=0.118 P=0.496 |(e) (e) (e) (e) |
|POLY 6 | P=0.421 P=0.231 P=0.117 P=0.492 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.450 P=0.264 P=0.124 P=0.529 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.444 P=0.247 P=0.121 P=0.500 |(e) (e) (e) (e) |
|ORDER RESTRICTED | P=0.183 (e) (e) (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 50/50 (100%) 49/50 (98%) 48/50 (96%) 47/50 (94%) |48/50 (96%) 32/50 (64%) 29/50 (58%) 20/50 (40%) |
|POLY-3 RATE (b) | 50/50.00 49/49.05 48/49.24 47/48.27 |48/49.00 32/47.78 29/45.80 20/45.23 |
|POLY-3 PERCENT (g) | 100.0% 99.9% 97.5% 97.4% |98.0% 67.0% 63.3% 44.2% |
|TERMINAL (d) | 31/31 (100%) 34/34 (100%) 33/33 (100%) 32/32 (100%)|42/43 (98%) 25/39 (64%) 22/34 (65%) 16/35 (46%) |
|FIRST INCIDENCE | 464 275 498 384 |302 434 555 642 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.369N P=0.354N P=0.331N P=0.390N |P<0.001N** P=0.011N* P=0.022N* P<0.001N** |
|POLY 3 | P=0.123N P=1.000N P=0.399N P=0.362N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 1.5 | P=0.071N P=0.999N P=0.317N P=0.213N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|POLY 6 | P=0.289N P=1.000N P=0.512N P=0.750N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|LOGISTIC REGRESSION| P=0.046N* (e) P=0.267N P=0.215N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|COCH-ARM / FISHERS | P=0.062N P=0.500N P=0.247N P=0.121N |P<0.001N** P<0.001N** P<0.001N** P<0.001N** |
|ORDER RESTRICTED | P=0.116N (e) (e) (e) |P<0.001N** (e) (e) (e) |
|=================================================================================================================================|
Date: 12/06/04 EXPERIMENT: 92013 TEST: 05 Page 23
Statistical Analysis of Primary Tumors in Rats(FISCHER 344) - 4-METHYLIMIDAZOLE
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 22/50 (44%) 21/50 (42%) 30/50 (60%) 24/50 (48%) |19/50 (38%) 15/50 (30%) 25/50 (50%) 21/50 (42%) |
|POLY-3 RATE (b) | 22/48.23 21/46.12 30/49.89 24/49.35 |19/47.72 15/49.00 25/46.69 21/47.92 |
|POLY-3 PERCENT (g) | 45.6% 45.5% 60.1% 48.6% |39.8% 30.6% 53.5% 43.8% |
|TERMINAL (d) | 7/31 (23%) 11/34 (32%) 14/33 (42%) 8/32 (25%) |16/43 (37%) 8/39 (21%) 14/34 (41%) 12/35 (34%) |
|FIRST INCIDENCE | 547 547 493 369 |498 421 578 368 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.281 P=0.482N P=0.159 P=0.384 |P=0.102 P=0.371N P=0.051 P=0.220 |
|POLY 3 | P=0.354 P=0.579N P=0.106 P=0.462 |P=0.201 P=0.232N P=0.128 P=0.425 |
|POLY 1.5 | P=0.328 P=0.562N P=0.095 P=0.446 |P=0.214 P=0.231N P=0.141 P=0.438 |
|POLY 6 | P=0.376 P=0.582 P=0.121 P=0.478 |P=0.187 P=0.240N P=0.117 P=0.405 |
|LOGISTIC REGRESSION| P=0.302 P=0.492N P=0.090 P=0.533 |P=0.226 P=0.269N P=0.142 P=0.422 |
|COCH-ARM / FISHERS | P=0.275 P=0.500N P=0.080 P=0.421 |P=0.217 P=0.263N P=0.157 P=0.419 |
|ORDER RESTRICTED | P=0.300 (e) (e) (e) |P=0.138 (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 PPM 625 PPM 1250 PPM 2500 PPM |0 PPM 1250 PPM 2500 PPM 5000 PPM |
| | | |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # # # |# # # # |
|----------- | | |
|OVERALL (a) | 50/50 (100%) 49/50 (98%) 50/50 (100%) 50/50 (100%)|48/50 (96%) 39/50 (78%) 42/50 (84%) 36/50 (72%) |
|POLY-3 RATE (b) | 50/50.00 49/49.05 50/50.00 50/50.00 |48/49.00 39/50.00 42/47.58 36/48.81 |
|POLY-3 PERCENT (g) | 100.0% 99.9% 100.0% 100.0% |98.0% 78.0% 88.3% 73.8% |
|TERMINAL (d) | 31/31 (100%) 34/34 (100%) 33/33 (100%) 32/32 (100%)|42/43 (98%) 28/39 (72%) 29/34 (85%) 23/35 (66%) |
|FIRST INCIDENCE | 464 275 493 369 |302 421 555 368 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.457 P=0.354N (e) (e) |P=0.343N P=0.201N P=0.320 P=0.252N |
|POLY 3 | P=1.000 P=1.000N (e) (e) |P=0.004N** P=0.002N** P=0.062N P<0.001N** |
|POLY 1.5 | P=0.992 P=0.999N (e) (e) |P=0.003N** P=0.002N** P=0.045N* P<0.001N** |
|POLY 6 | P=1.000 P=1.000N (e) (e) |P=0.005N** P=0.002N** P=0.080N P<0.001N** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.005N** P=0.007N** P=0.039N* P<0.001N** |
|COCH-ARM / FISHERS | P=0.567 P=0.500N (e) (e) |P=0.005N** P=0.007N** P=0.046N* P<0.001N** |
|ORDER RESTRICTED | P=0.379 (e) (e) (e) |P<0.001N** (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).