National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/9297

Abstract for TR-518 - Triethanolamine (CASRN 102-71-6)

Toxicology and Carcinogenesis Studies of Triethanolamine (CAS No. 102-71-6) in B6C3F1 Mice (Dermal Studies)

Link to the full study report in PDF. If you have difficulty accessing the document, please send email to the NTP Webmaster [ Send Email ] and identify documents/pages for which access is required.

 

 

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.

2-YEAR STUDY

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.

GENETIC TOXICOLOGY

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.

CONCLUSIONS

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
B6C3F1 Mice

Female
B6C3F1 Mice

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 exchanges
Cultured 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 with and without S9


Negative when administered in feed or by injection

Negative


Report Date: May 2004

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies

Target Organs & Incidences from 2-year Studies


Return to Long Term Abstracts

The NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.