Target Organs and Levels of Evidence for TR-510
Toxicology and Carcinogenesis Studies of Urethane + Ethanol (CASRNs 51-79-6 & 64-17-5) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies)
Chemical (Study Title) CASRN |
Peer Review Date |
Route/Exposure Levels |
Study Laboratory |
Ethanol 64-17-5 |
09/05/2002 |
Dosed-Water 0, 10, 30, 0R 90 PPM |
National Center for Toxicological Research |
Levels of Evidence
Male Mice: Inadequate Study
Female Mice: Inadequate Study
Chemical (Study Title) CASRN |
Peer Review Date |
Route/Exposure Levels |
Study Laboratory |
Urethane 51-79-6 |
09/05/2002 |
Dosed-Water 0, 10, 30, OR 90 PPM |
National Center for Toxicological Research |
Levels of Evidence
Male Mice: Clear Evidence
Type |
Organ/Tissue (Lesion) |
Neoplastic Lesions |
- Liver: HEMANGIOSARCOMA 1/46 2/47 5/46 13/44 ADENOMA 7/46 13/47 17/46 17/44 ADENOMA OR CARCINOMA 12/46 18/47 24/46 23/44
- Lung: ALVEOLAR/BRONCHIOLAR ADENOMA 4/48 17/48 22/47 34/48 ALVEOLAR/BRONCHIOLAR CARCINOMA 1/48 1/48 9/47 9/48 COMBINED 5/48 18/48 29/47 37/48
- Harderian Gland: ADENOMA 3/47 11/47 25/47 28/47 CARCINOMA 0/47 1/47 7/47 16/47 COMBINED 3/47 12/47 30/47 38/47
- Heart: HEMANGIOSARCOMA 0/48 0/48 1/47 5/48
- Forestomach: SQUAMOUS CELL PAPILLOMA OR SQUAMOUS CELL CARCINOMA 0/46 2/47 3/44 5/45
- Skin: SQUAMOUS CELL PAPILLOMA OR SQUAMOUS CELL CARCINOMA (0/47, 1/48, 5/47, 8/48)
|
Non-Neoplastic Lesions |
- LIVER: EOSINOPHILIC FOCUS; ANGIECTASIS
- HEART: ENDOTHELIAL HYPERPLASIA; ANGIECTASIS
|
Female Mice: Clear Evidence
Type |
Organ/Tissue (Lesion) |
Neoplastic Lesions |
- Liver: HEMANGIOSARCOMA 0/48 0/47 1/47 7/47 ADENOMA 5/48 10/47 19/47 18/47 ADENOMA OR CARCINOMA 5/48 11/47 20/47 19/47
- Lung: ALVEOLAR/BRONCHIOLAR ADENOMA 4/48 6/48 17/48 29/47 ALVEOLAR/BRONCHIOLAR CARCINOMA 2/48 4/48 13/48 19/47 COMBINED 6/48 8/48 28/48 39/47
- Harderian Gland: ADENOMA 3/48 10/48 8/48 21/48 CARCINOMA 0/48 1/48 11/48 11/48 COMBINED 3/48 11/48 19/48 30/48
- Mammary Gland: ADENOACANTHOMA 0/47 1/46 1/46 11/48 ADENOCARCINOMA 4/47 3/46 3/46 11/48 COMBINED 4/47 4/46 4/46 22/48
- Ovary: BENIGN GRANULOSA CELL TUMOR 0/48 0/46 2/46 3/39 MALIGNANT GRANULOSA CELL TUMOR 0/48 0/46 0/46 3/39 COMBINED 0/48 0/46 2/46 5/39
- Spleen: HEMANGIOSARCOMA 0/48 0/45 1/47 4/46
- Uterus/Cervix: HEMANGIOSARCOMA 0/48 0/47 0/48 2/46
- Skin: HEMANGIOSARCOMA 0/48 0/48 0/46 2/48
|
Non-Neoplastic Lesions |
- LIVER: EOSINOPHILIC FOCUS; ANGIECTASIS; THROMBOSIS
- HEART: ENDOTHELIAL HYPERPLASIA
- UTERUS: ANGIECTASIS; THROMBOSIS
|
Chemical (Study Title) CASRN |
Peer Review Date |
Route/Exposure Levels |
Study Laboratory |
Ethanol 64-17-5 |
09/05/2002 |
Dosed-Water 0, 10, 30, 0R 90 PPM |
National Center for Toxicological Research |
Levels of Evidence
Male Mice: Inadequate Study
Female Mice: Inadequate Study
Chemical (Study Title) CASRN |
Peer Review Date |
Route/Exposure Levels |
Study Laboratory |
Urethane + ethanol (combination) URETHCOMB |
09/05/2002 |
Dosed-Water 0, 10, 30, OR 90 PPM |
National Center for Toxicological Research |
Levels of Evidence
Male Mice
Type |
Organ/Tissue (Lesion) |
Neoplastic Urethane & 2.5% ethanol |
- LIVER: HEMANGIOSARCOMA 3/47 4/48 3/46 11/48 ADENOMA 12/47 15/48 16/46 24/48 ADENOMA OR CARCINOMA 16/47 19/48 17/46 24/48
- LUNG: ALVEOLAR/BRONCHIOLAR ADENOMA 10/48 16/48 19/47 35/48 ALVEOLAR/BRONCHIOLAR CARCINOMA 2/48 3/48 8/47 24/48 COMBINED 11/48 19/48 24/47 43/48
- HARDERIAN GLAND: ADENOMA 6/48 14/48 21/47 27/48 CARCINOMA 0/48 0/48 1/47 16/48 COMBINED 6/48 14/48 21/47 38/48
- HEART: HEMANGIOSARCOMA 0/48 0/48 2/47 4/48
- SPLEEN: HEMANGIOSARCOMA 0/46 0/46 1/46 3/46
- SKIN: SQUAMOUS CELL PAPILLOMA OR SQUAMOUS CELL CARCINOMA 0/48 1/48 4/46 7/47
|
Neoplastic Urethane & 5% ethanol |
- LIVER: HEMANGIOSARCOMA 2/48 2/46 4/48 13/48
- LUNG: ALVEOLAR/BRONCHIOLAR ADEMONA 6/48 8/48 9/48 33/48 ALVEOLAR/BRONCHIOLAR CARCINOMA 5/48 4/48 5/48 17/48 COMBINED 11/48 11/48 14/48 40/48
- HARDERIAN GLAND: ADENOMA 5/47 12/48 15/48 26/45 CARCINOMA 0/47 2/48 2/48 10/45 COMBINED 5/47 14/48 17/48 35/45
- HEART: HEMANGIOSARCOMA 0/47 0/48 1/48 4/48
- SKIN: SQUAMOUS CELL PAPILLOMA OR SQUAMOUS CELL CARCINOMA 0/48 2/47 0/48 7/48
|
Non-Neoplastic Urethane & 2.5% ethanol |
- LIVER: EOSINOPHILIC FOCUS; ANGIECTASIS; REGENERATION
- HEART: ENDOTHELIAL HYPERPLASIA; ANGIECTASIS
|
Non-Neoplastic Urethane & 5% ethanol |
- LIVER: EOSINOPHILIC FOCUS; ANGIECTASIS; REGENERATION
- HEART: ENDOTHELIAL HYPERPLASIA; ANGIECTASIS
|
Other Considerations |
WEAK EVIDENCE OF INTERACTION: THE COADMINISTRATION OF URETHANE AND ETHANOL RESULTED IN MARGINAL CHANGES IN THE INCIDENCES OF SOME NEOPLASMS THAT WERE ATTRIBUTED TO URETHANE ALONE. IN MALES, INCREASING THE ETHANOL CONCENTRATION MAY HAVE DECREASED THE ALVEOLAR/BRONCHIOLAR AND HARDERIAN GLAND ADENOMA OR CARCINOMA RESPONSES TO URETHANE. OVERALL, THE FINDINGS WERE INSUFFICIENT TO ESTABLISH A DEFINITIVE EFFECT OF ETHANOL ON THE CARCINOGENICITY OF URETHANE IN B6C3F1 MICE. |
Female Mice
Type |
Organ/Tissue (Lesion) |
Neoplastic Urethane & 2.5% ethanol |
- LIVER: HEMANGIOSARCOMA 1/47 2/47 0/47 7/46 ADENOMA 6/47 5/47 15/47 23/46 ADENOMA OR CARCINOMA 7/47 5/47 16/47 23/46
- LUNG: ALVEOLAR/BRONCHIOLAR ADENOMA 5/47 10/47 16/48 28/48 ALVEOLAR/BRONCHIOLAR CARCINOMA 0/47 2/47 6/48 23/48 COMBINED 5/47 11/47 21/48 38/48
- HARDERIAN GLAND: ADENOMA 2/47 3/47 9/46 19/47 CARCINOMA 1/47 3/47 6/46 16/47 COMBINED 3/47 5/47 15/46 35/47
- MAMMARY GLAND: ADENOACANTHOMA 0/47 0/45 2/48 3/47 ADENOCARCINOMA 4/47 3/45 11/48 14/47 COMBINED 4/47 3/45 12/48 16/47
- HEART: HEMANGIOSARCOMA 0/47 0/47 0/48 3/48
- SPLEEN: HEMANGIOSARCOMA 0/47 0/46 0/46 3/46
- SKIN: HEMANGIOSARCOMA 0/47 0/47 0/48 2/47
|
Neoplastic Urethane & 5% ethanol |
- LIVER: HEMANGIOSARCOMA 0/48 0/47 0/48 6/48 ADENOMA 3/48 6/47 16/48 16/48 ADENOMA OR CARCINOMA 3/48 7/47 16/48 17/48
- LUNG: ALVEOLAR/BRONCHIOLAR ADEMONA 5/48 10/48 18/48 30/48 ALVEOLAR/BRONCHIOLAR CARCINOMA 1/48 7/48 9/48 23/48 COMBINED 5/48 17/48 24/48 37/48
- HARDERIAN GLAND: ADENOMA 4/48 7/48 6/46 20/46 CARCINOMA 1/48 11/48 7/46 10/46 COMBINED 5/48 18/48 13/46 29/46
- MAMMARY GLAND: ADENOACANTHOMA 0/47 0/48 1/48 9/45 ADENOCARCINOMA 3/47 4/48 6/48 15/45 COMBINED 3/47 4/48 7/48 23/45
- HEART: HEMANGIOSARCOMA 0/47 0/48 0/48 6/47
- OVARY: BENIGN GRANULOSA CELL TUMOR 0/46 0/47 5/46 3/45 BENIGN OR MALIGNANT GRANULOSA CELL TUMOR 0/46 0/47 6/46 3/45
|
Non-Neoplastic Urethane & 2.5% ethanol |
- LIVER: EOSINOPHILIC FOCUS; ANGIECTASIS; THROMBOSIS; REGENERATION
- HEART: ENDOTHELIAL HYPERPLASIA; ANGIECTASIS
- UTERUS: ANGIECTASIS; THROMBOSIS
|
Non-Neoplastic Urethane & 5% ethanol |
- LIVER: EOSINOPHILIC FOCUS; ANGIECTASIS; THROMBOSIS; REGENERATION
- HEART: ENDOTHELIAL HYPERPLASIA; ANGIECTASIS
|
Other Considerations |
WEAK EVIDENCE OF INTERACTION: THE COADMINISTRATION OF URETHANE AND ETHANOL RESULTED IN MARGINAL CHANGES IN THE INCIDENCES OF SOME NEOPLASMS THAT WERE ATTRIBUTED TO URETHANE ALONE. IN FEMALES, INCREASING THE ETHANOL CONCENTRATION MAY HAVE INCREASED THE HEMANGIOSARCOMA OF THE HEART AND ALVEOLAR/BRONCHIOLAR ADENOMA OR CARCINOM A RESPONSES TO URETHANE. OVERALL, THE FINDINGS WERE INSUFFICIENT TO ESTABLISH A DEFINITIVE EFFECT OF ETHANOL ON THE CARCINOGENICITY OF URETHANE IN B6C3F1 MICE |