National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/6407

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 Primary Uses Route/Exposure Levels Study Laboratory
Ethanol
64-17-5
09/05/2002 Solvent. In alcoholic beverages and manufacture of denatured alcohols. In gasohol. Anti-freeze agent. Chemical intermediate. In synthetic rubber, coatings, cosmetics, disinfectants, and pharmaceuticals. Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products. 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 Primary Uses Route/Exposure Levels Study Laboratory
Urethane
51-79-6
09/05/2002 Chemical intermediate; solubilizer for cosmetics and pesticides; byproduct of fermentation in foods and beverages. Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products. 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 Primary Uses Route/Exposure Levels Study Laboratory
Ethanol
64-17-5
09/05/2002 Solvent. In alcoholic beverages and manufacture of denatured alcohols. In gasohol. Anti-freeze agent. Chemical intermediate. In synthetic rubber, coatings, cosmetics, disinfectants, and pharmaceuticals. Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products. 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 Primary Uses Route/Exposure Levels Study Laboratory
Urethane + ethanol (combination)
URETHCOMB
09/05/2002 (Urethane) chemical intermediate; solubilizer for cosmetics and pesticides; (ethanol) solvent; in alcoholic beverages and manufacture of denatured alcohols; in gasohol; anti-freeze agent; chemical intermediate; in synthetic rubber, pharmaceuticals, disinfectants. Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products. 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


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