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Home » Study Results & Research Projects » NTP Study Reports » All Long-Term Reports » Abstract for TR-518 - Triethanolamine
Chemical Formula: C6H15NO3
Triethanolamine is widely used in the manufacturing of household detergents and polishes, textiles, agricultural herbicides, mineral and vegetable oils, paraffin and waxes, pharmaceutical ointments, petroleum demulsifiers, synthetic resins, plasticizers, adhesives, and sealants. It is used as a chemical intermediate for anionic and nonionic surfactants, a vulcanization accelerator, a humectant and softening agent and in many other industrial applications. The National Cancer Institute nominated triethanolamine for study because of its widespread use in cosmetics and other consumer products, its high potential for worker exposure due to its many industrial uses, and its potential for conversion to the carcinogen N-nitrosodiethanolamine. Previous 3-month and 2-year studies of triethanolamine were conducted by the National Toxicology Program in F344/N rats and B6C3F1 mice; results from the 2-year rat study indicated equivocal evidence of carcinogenic activity based on a marginal increase in the incidence of renal tubule adenoma (NTP, 1991). Interpretation of the results from the 2-year study in mice was complicated by Helicobacter hepaticus infection, prompting a repeat 2-year study in mice. Male and female B6C3F1 mice received triethanolamine (greater than 99% pure) by dermal application for 2 years; a study of absorption, distribution, metabolism, and excretion was performed in additional mice. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse peripheral blood erythrocytes.
Groups of 50 male and 50 female mice received dermal applications of 0, 200, 630, or 2,000 mg/kg (males) and 0, 100, 300, or 1,000 mg/kg (females) triethanolamine in acetone, 5 days per week, for 104 (males) or 104 to 105 (females) weeks.
Survival of all dosed groups was similar to that of the vehicle control groups. Body weights of 2,000 mg/kg males were less than those of the vehicle controls from weeks 17 to 37 and at the end of the study; body weights of dosed groups of females were similar to those of the vehicle controls throughout the study. Treatment-related clinical findings included skin irritation at the site of application, which increased with increasing dose and was more severe in males than in females.
Gross lesions observed at necropsy included nodules and masses of the liver in dosed females. The incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined) were significantly increased in all dosed groups of females. The incidence of hemangiosarcoma of the liver in 630 mg/kg males was marginally increased. The incidences of eosinophilic focus in all dosed groups of mice were greater than those in the vehicle controls.
Gross lesions observed at necropsy included visible crusts at the site of application in all dosed groups of mice. Treatment-related epidermal hyperplasia, suppurative inflammation, ulceration, and dermal chronic inflammation occurred at the site of application in most dosed groups of mice, and the incidences and severities of these lesions generally increased with increasing dose.
Triethanolamine was not mutagenic in any of the in vitro or in vivo tests. It did not induce mutations in Salmonella typhimurium, and no induction of sister chromatid exchanges or chromosomal aberrations was noted in cultured Chinese hamster ovary cells exposed to triethanolamine. These in vitro tests were all conducted with and without S9 metabolic activation. Triethanolamine did not induce sex-linked recessive lethal mutations in germ cells of adult male Drosophila melanogaster exposed by feeding or injection. No increase in the frequency of micronucleated erythrocytes was observed in peripheral blood samples of male or female mice that received dermal applications of triethanolamine for 13 weeks.
Under the conditions of this 2-year dermal study, there was equivocal evidence of carcinogenic activity of triethanolamine in male B6C3F1 mice based on the occurrence of liver hemangiosarcoma. There was some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular adenoma.
Exposure to triethanolamine by dermal application resulted in increased incidences of eosinophilic focus of the liver in males and females. Dosed mice developed treatment-related nonneoplastic lesions at the site of application.
Synonyms: Nitrilo-2,2N,2NN-triethanol; 2,2N,2NN-nitrilotriethanol; 2,2N,2NN-nitrilotrisethanol; TEA; triaethanolamin-NG; triethanolamin; triethylolamine; tri(hydroxyethyl)amine; 2,2N,2NN-trihydroxytriethylamine; trihydroxytriethylamine; tris(hydroxyethyl)amine; tris(2--hydroxyethyl)amine; trolamine
Trade names: Daltogen, Sterolamide, Thiofaco T-35
Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Triethanolamine
Male |
Female |
|
---|---|---|
Doses in acetone by dermal application |
Vehicle control, 200, 630, or 2,000 mg/kg |
Vehicle control, 100, 300, or 1,000 mg/kg |
Survival rates |
37/50, 43/50, 34/50, 40/50 |
35/50, 34/50, 41/50, 32/50 |
Body weights |
2,000 mg/kg group less than the vehicle control group |
Dosed groups similar to the vehicle control group |
Nonneoplastic effects |
Liver: eosinophilic focus (9/50, 20/50, 31/50, 30/50) Skin (site of application): epidermis, hyperplasia (5/50, 44/50, 45/50, 49/50); epidermis, inflammation, suppurative (1/50, 11/50, 33/50, 42/50); epidermis, ulcer (0/50, 3/50, 20/50, 47/50); dermis, inflammation, chronic (1/50, 15/50, 40/50, 49/50) |
Skin (site of application): epidermis, hyperplasia (14/50, 50/50, 46/50, 50/50); epidermis, inflammation, suppurative (1/50, 2/50, 20/50, 32/50); epidermis, ulcer (1/50, 1/50, 6/50, 17/50); dermis, inflammation, chronic (4/50, 27/50, 31/50, 44/50) |
Neoplastic effects |
None |
Liver: hepatocellular adenoma (9/50, 18/50, 20/50, 33/50); hepatocellular adenoma or carcinoma (12/50, 23/50, 24/50, 34/50) |
Equivocal Findings |
Liver: hemangiosarcoma (1/50, 0/50, 6/50, 1/50) |
|
Level of evidence of carcinogenic activity |
Eqivocal evidence |
Some evidence |
Genetic Toxicology |
|
Salmonella typhimurium gene mutations: Sister chromatid exchangesCultured Chinese hamster ovary cells in vitro: Chromosomal aberrations Cultured Chinese hamster ovary cells in vitro: Sex-linked recessive lethal mutations Drosophila melanogaster:
Micronucleated erythrocytes
Mouse peripheral blood in vivo:
|
Negative in strains TA98, TA100, TA1535, and TA1537 with and without S9 Negative with and without S9
Negative |
Report Date: May 2004
Pathology Tables, Survival and Growth Curves from NTP 2-year Studies
Target Organs & Incidences from 2-year Studies
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Web page last updated on January 11, 2008
The National Institute of Environmental Health Sciences is one of the National Institutes of Health within the U.S. Department of Health and Human Services. The National Toxicology Program is headquartered on the NIEHS campus in Research Triangle Park, NC.