TDMS Study 05187-09 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98
EXPERIMENT: 05187 TEST: 09 TIME: 08:46:20
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B
PATHOLOGIST: MISSING CAS: 93-15-2
------------------------------------------------------------------------------------------------------------------------------------
27 WEEK SSAC
REASONS FOR REMOVAL: 25017 Scheduled Sacrifice
REMOVAL DATE RANGE: 080994 081094
TREATMENT GROUPS: INCLUDE 001 0 MG/KG
INCLUDE 002 0 MG/KG
INCLUDE 009 300 MG/KG
INCLUDE 010 300 MG/KG
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus METHYLEUGENOL DATE: 07/20/98
EXPERIMENT: 05187 TEST: 09 TIME: 08:46:20
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-25337 ROUTE: GAVAGE NTP C#: 60991B
PATHOLOGIST: MISSING CAS: 93-15-2
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF METHYLEUGENOL
===============================================================
Male Rats
------------
Organ Morphology
----- ----------
Liver Basophilic Focus
Eosinophilic Focus
Mixed Cell Focus
Liver: Hepatocyte Hypertrophy
Liver: Oval Cell Hyperplasia
Salivary Glands: Submandibular Gland Cytoplasmic Alteration
Stomach, Glandular Atrophy
===============================================================
Female Rats
------------
Organ Morphology
----- ----------
Bone Marrow Hyperplasia
Liver Mixed Cell Focus
Liver: Hepatocyte Hypertrophy
Liver: Oval Cell Hyperplasia
Salivary Glands: Submandibular Gland Cytoplasmic Alteration
Stomach, Glandular Atrophy
===============================================================
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 1
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 1/5 (20%) | 0/5 (0%) 4/5 (80%) |
|POLY-3 ADJUSTED (b)| 0.0% 97.6% | 0.0% 99.8% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 1/5 (20%) | 0/5 (0%) 4/5 (80%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.500 | P=0.033 * |
|POLY 3 | P=0.160 | P<0.001 ** |
|POLY 1.5 | P=0.179 | P<0.001 ** |
|POLY 6 | P=0.159 | P<0.001 ** |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | P=0.500 | P=0.024 * |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Heart: Myocardium |
| Degeneration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/5 (60%) 2/5 (40%) | 0/5 (0%) 0/5 (0%) |
|POLY-3 ADJUSTED (b)| 99.6% 99.1% | 0.0% 0.0% |
|INT SACRIFICE 1 (c)| 3/5 (60%) 2/5 (40%) | 0/5 (0%) 0/5 (0%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 184 (I) 184 (I) | --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.500N | (e) |
|POLY 3 | P=0.409N | (e) |
|POLY 1.5 | P=0.416N | (e) |
|POLY 6 | P=0.409N | (e) |
|LOGISTIC REGRESSION| P=0.250N | (e) |
|COCH-ARM / FISHERS | P=0.500N | (e) |
|=================================================================================================================================|
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 2
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Nephropathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/5 (80%) 5/5 (100%) | 0/5 (0%) 0/5 (0%) |
|POLY-3 ADJUSTED (b)| 99.8% 100.0% | 0.0% 0.0% |
|INT SACRIFICE 1 (c)| 4/5 (80%) 5/5 (100%) | 0/5 (0%) 0/5 (0%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 184 (I) 184 (I) | --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.500 | (e) |
|POLY 3 | P=0.421 | (e) |
|POLY 1.5 | P=0.427 | (e) |
|POLY 6 | P=0.421 | (e) |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | P=0.500 | (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Basophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 3/5 (60%) | 0/5 (0%) 2/5 (40%) |
|POLY-3 ADJUSTED (b)| 0.0% 99.6% | 0.0% 99.1% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 3/5 (60%) | 0/5 (0%) 2/5 (40%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.095 | P=0.227 |
|POLY 3 | P=0.007 ** | P=0.052 |
|POLY 1.5 | P=0.009 ** | P=0.058 |
|POLY 6 | P=0.007 ** | P=0.051 |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | P=0.083 | P=0.222 |
|=================================================================================================================================|
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 3
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Clear Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 0/5 (0%) | 0/5 (0%) 2/5 (40%) |
|POLY-3 ADJUSTED (b)| 0.0% 0.0% | 0.0% 99.1% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 0/5 (0%) | 0/5 (0%) 2/5 (40%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) | P=0.227 |
|POLY 3 | (e) | P=0.052 |
|POLY 1.5 | (e) | P=0.058 |
|POLY 6 | (e) | P=0.051 |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | (e) | P=0.222 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Eosinophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 3/5 (60%) | 0/5 (0%) 0/5 (0%) |
|POLY-3 ADJUSTED (b)| 0.0% 99.6% | 0.0% 0.0% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 3/5 (60%) | 0/5 (0%) 0/5 (0%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.095 | (e) |
|POLY 3 | P=0.007 ** | (e) |
|POLY 1.5 | P=0.009 ** | (e) |
|POLY 6 | P=0.007 ** | (e) |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | P=0.083 | (e) |
|=================================================================================================================================|
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 4
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatodiaphragmatic Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/5 (20%) 0/5 (0%) | 1/5 (20%) 2/5 (40%) |
|POLY-3 ADJUSTED (b)| 97.6% 0.0% | 97.6% 99.1% |
|INT SACRIFICE 1 (c)| 1/5 (20%) 0/5 (0%) | 1/5 (20%) 2/5 (40%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 184 (I) --- | 184 (I) 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.500N | P=0.500 |
|POLY 3 | P=0.213N | P=0.308 |
|POLY 1.5 | P=0.231N | P=0.321 |
|POLY 6 | P=0.212N | P=0.306 |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | P=0.500N | P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Mixed Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 5/5 (100%) | 0/5 (0%) 3/5 (60%) |
|POLY-3 ADJUSTED (b)| 0.0% 100.0% | 0.0% 99.6% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 5/5 (100%) | 0/5 (0%) 3/5 (60%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.008 ** | P=0.095 |
|POLY 3 | P=1.000N | P=0.007 ** |
|POLY 1.5 | P=1.000N | P=0.009 ** |
|POLY 6 | P=1.000N | P=0.007 ** |
|LOGISTIC REGRESSION| P=0.006 ** | (e) |
|COCH-ARM / FISHERS | P=0.004 ** | P=0.083 |
|=================================================================================================================================|
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 5
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|POLY-3 ADJUSTED (b)| 0.0% 100.0% | 0.0% 100.0% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.008 ** | P=0.008 ** |
|POLY 3 | P=1.000N | P=1.000N |
|POLY 1.5 | P=1.000N | P=1.000N |
|POLY 6 | P=1.000N | P=1.000N |
|LOGISTIC REGRESSION| P=0.006 ** | P=0.006 ** |
|COCH-ARM / FISHERS | P=0.004 ** | P=0.004 ** |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver: Oval Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|POLY-3 ADJUSTED (b)| 0.0% 100.0% | 0.0% 100.0% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.008 ** | P=0.008 ** |
|POLY 3 | P=1.000N | P=1.000N |
|POLY 1.5 | P=1.000N | P=1.000N |
|POLY 6 | P=1.000N | P=1.000N |
|LOGISTIC REGRESSION| P=0.006 ** | P=0.006 ** |
|COCH-ARM / FISHERS | P=0.004 ** | P=0.004 ** |
|=================================================================================================================================|
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 6
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/5 (20%) 2/5 (40%) | 1/5 (20%) 1/5 (20%) |
|POLY-3 ADJUSTED (b)| 97.6% 99.1% | 97.6% 97.6% |
|INT SACRIFICE 1 (c)| 1/5 (20%) 2/5 (40%) | 1/5 (20%) 1/5 (20%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 184 (I) 184 (I) | 184 (I) 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.500 | P=0.773 |
|POLY 3 | P=0.308 | P=0.558 |
|POLY 1.5 | P=0.321 | P=0.574 |
|POLY 6 | P=0.306 | P=0.556 |
|LOGISTIC REGRESSION| (e) | (e) |
|COCH-ARM / FISHERS | P=0.500 | P=0.778N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Salivary Glands: Submandibular Gland |
| Cytoplasmic Alteration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|POLY-3 ADJUSTED (b)| 0.0% 100.0% | 0.0% 100.0% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.008 ** | P=0.008 ** |
|POLY 3 | P=1.000N | P=1.000N |
|POLY 1.5 | P=1.000N | P=1.000N |
|POLY 6 | P=1.000N | P=1.000N |
|LOGISTIC REGRESSION| P=0.006 ** | P=0.006 ** |
|COCH-ARM / FISHERS | P=0.004 ** | P=0.004 ** |
|=================================================================================================================================|
Date: 07/20/98 EXPERIMENT: 05187 TEST: 09 Page 7
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - METHYLEUGENOL
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 300 | 0 MG/KG 300 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|POLY-3 ADJUSTED (b)| 0.0% 100.0% | 0.0% 100.0% |
|INT SACRIFICE 1 (c)| 0/5 (0%) 5/5 (100%) | 0/5 (0%) 5/5 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) | 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 184 (I) | --- 184 (I) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.008 ** | P=0.008 ** |
|POLY 3 | P=1.000N | P=1.000N |
|POLY 1.5 | P=1.000N | P=1.000N |
|POLY 6 | P=1.000N | P=1.000N |
|LOGISTIC REGRESSION| P=0.006 ** | P=0.006 ** |
|COCH-ARM / FISHERS | P=0.004 ** | P=0.004 ** |
|=================================================================================================================================|
(a) Number of tumor-bearing animals / number of animals examined at site.
(b) Poly-3 adjusted lifetime tumor incidence.
(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.
(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).