VOL.: 77 (2000) (p. 403)
CAS No.:
5. Summary of Data Reported and Evaluation
5.1 Exposure data
N-Nitrosodiethanolamine is a contaminant formed by the action of nitrites on ethanolamines in a wide range of products including metalworking fluids, pesticides, antifreeze and personal care products. Occupational exposure by inhalation and dermal contact may occur from water-diluted metalworking fluids contaminated with N-nitrosodiethanolamine. General population exposure is possible through contact with a variety of personal care products and the use of some tobacco products. Contamination levels in both metalworking fluids and personal care products have considerably decreased since the 1980s.
5.2 Human carcinogenicity data
Four studies showed inconsistent increases in cancer mortality or incidence at various sites among workers using metalworking fluids containing ethanolamines and sodium nitrite. Only one of them attempted indirectly to estimate exposure to nitrosamines, showing an increased risk for oesophageal cancer with increasing duration of exposure, but there was concomitant exposure to biocides, also associated with an increased risk for oesophageal cancer in this study.
5.3 Animal carcinogenicity data
N-Nitrosodiethanolamine was tested for carcinogenicity by addition to drinking-water in six studies in rats. It was also tested in hamsters by subcutaneous injection in three studies and in single studies by topical or buccal administration. In rats, it consistently produced liver tumours (principally hepatocellular carcinomas). It also produced adenocarcinomas and squamous-cell carcinomas of the nasal cavity. In hamsters, N-nitrosodiethanolamine consistently induced adenocarcinomas of the nasal cavity.
In a mouse lung screening assay, N-nitrosodiethanolamine increased the incidence and multiplicity of lung tumours.
5.4 Other relevant data
N-Nitrosodiethanolamine is metabolized in vivo slowly and only to a small extent, being principally eliminated unchanged in human and rodent urine. Bioactivation of N-nitrosodiethanolamine is associated with a- and b-hydroxylation pathways involving the enzymes CYP2E1 and alcohol dehydrogenase, resulting in DNA adduct formation.
Two studies have examined the potential genotoxic hazard of occupational exposure to N-nitrosodiethanolamine. The larger one, measuring DNA damage, indicated an association between single-strand breakage and the presence of N-nitrosodiethanolamine in the air of the workplace, but the effects of other exposures could not be excluded. The small study measuring chromosome damage in tool-room workers did not find any significant effect.
N-Nitrosodiethanolamine is mutagenic to bacteria. Studies using cultured cells in vitro found induction of DNA single-strand breakage after exposure to N-nitrosodiethanolamine in human buccal cells and in rat, hamster and pig hepatocytes. Chromosomal damage was detected in human lymphocytes without exogenous metabolic activity in one study; sister chromatid exchange frequency alone was increased and was detected at lower doses in another study with an exogenous metabolic system including alcohol dehydrogenase.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of N-nitrosodiethanolamine.
There is sufficient evidence in experimental animals for the carcinogenicity of N-nitrosodiethanolamine.
Overall evaluation
N-Nitrosodiethanolamine is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 17 (1978); Suppl. 7 (1987) (p. 67)
Synonyms
See Also:
Toxicological Abbreviations
Nitrosodiethanolamine, N- (IARC Summary & Evaluation, Volume 17, 1978)