VOL.: 77 (2000) (p. 349)
CAS No.:
5. Summary of Data Reported and Evaluation
5.1 Exposure data
Diethanolamine is a viscous liquid widely used as a chemical intermediate and as a corrosion inhibitor and surface-active agent in various products including metalworking fluids, oils, fuels, paints, inks, cosmetic formulations and agricultural products. Occupational exposure may occur by inhalation and dermal contact, particularly in metal-machining occupations. No data were available on environmental exposure to this substance. The general population may be exposed through contact with a variety of personal care products.
5.2 Human carcinogenicity data
Two cohort studies and two nested case–control studies looked at cancer mortality or incidence among workers using metalworking fluids with ethanolamines as additives, with or without sodium nitrite. Small excesses were observed for cancers at various sites, in particular the stomach, oesophagus and larynx. In most of these studies, only associations with use of soluble oils or synthetic fluids were presented and no results were given specifically in relation to diethanolamine exposure. It is difficult to draw conclusions regarding diethanolamine using data from studies of exposures to these complex mixtures.
5.3 Animal carcinogenicity data
Diethanolamine was tested for carcinogenicity by dermal application in one study in mice and in one study in rats. In the mouse study, there was a treatment-related increase in the incidences of both hepatocellular adenomas and carcinomas in both males and females, as well as an increase in the incidence of hepatoblastomas in males. There was also a marginal increase of renal tubule adenomas in males. In rats, no treatment-related increase in the incidence of tumours was seen in either males or females.
In a Tg.AC transgenic mouse model using similar doses to the first mouse study, there was no treatment-related increase in the incidence of skin tumours after skin application.
5.4 Other relevant data
Diethanolamine is metabolized by biosynthetic routes common to endogenous alkanolamines (ethanolamine and choline) and incorporated into phospholipids. It is excreted predominantly unchanged with a half-life of approximately one week in urine. In the absence of sodium nitrite, no conversion to N-nitrosodiethanolamine is observed. Diethanolamine competitively inhibits the cellular uptake of choline in vitro and hepatic changes in choline homeostasis, consistent with choline deficiency, are observed in vivo.
No data on reproductive and developmental effects in humans were available.
Oral or dermal exposure of rats to diethanolamine during organogenesis was not associated with any sign of developmental toxicity, while inhalation exposure to diethanolamine aerosols caused signs of developmental toxicity. Dermal exposure of rabbits during organogenesis caused no sign of developmental toxicity.
Testicular effects have been found after exposure of rats to diethanolamine in the drinking water.
No data on genetic and related effects of diethanolamine in humans were available to the Working Group.
Diethanolamine induced cell transformation in Syrian hamster embryo cells in vitro in two studies but not in another. It did not induce gene mutations, sister chromatid exchanges or chromosomal aberrations. Diethanolamine did not induce micronucleus formation in larval newt blood cells in either the absence or presence of sodium nitrite or nitrate. It was without effect on gene conversion in yeast and was not mutagenic in bacteria.
The limited data available to the Working Group do not indicate that diethanolamine is genotoxic.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of diethanolamine.
There is limited evidence in experimental animals for the carcinogenicity of diethanolamine.
Overall evaluation
Diethanolamine is not classifiable as to its carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
Synonyms
See Also:
Toxicological Abbreviations
Diethanolamine (ICSC)