Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile

Acrylonitrile (AN) is an important intermediary for the synthesis of a vari ety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to A N, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such in dustries and the world-wide population using products containing and possib ly liberating AN. An understanding of the effect of acrylonitrile must be b ased on a characterization of its metabolism as well as of the resulting pr oducts and their genotoxic properties. Tests for mutagenicity in bacteria h ave in general been positive, those in plants and on unscheduled DNA synthe sis doubtful, and those on chromosome aberrations in vivo negative. Whereve r positive results had been obtained, metabolic activation of AN appeared t o be a prerequisite. The extent to which such mutagenic effects are signifi cant in man depends, however, also on the conditions of exposure. It appear s from the limited data that the ultimate mutagenic factor(s), such as 2-cy anoethylene oxide, may have little opportunity to act under conditions wher e people are exposed because it is formed only in small amounts and is rapi dly degraded. The carcinogenic action of AN has been evaluated by various a gencies and ranged from 'reasonably be anticipated to be a human carcinogen ' to 'cannot be excluded', the most recent evaluation bring 'possibly carci nogenic to humans. Animal data that confirm the carcinogenic potential of A N have certain limitations with respect to the choice of species, type of r umors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN shoul d continue to be carefully monitored, but AN would not have to be considere d a cancer risk to the population provided limitations on releases from con sumer products and guidelines on AN in water and air,re enforced. AN is ter atogenic in laboratory animals (rat, hamster) at high doses when foetal/emb ryonic (and maternal) toxicity already is manifest. Pregnant workers should not be exposed to AN. In view of the small concentrations generally encoun tered outside plants, women nor professionally exposed would appear not to be at risk of teratogenic effects due to AN. Future research should concent rate on the elucidation of the different degradation pathways in man and on epidemiological studies in workers including pregnant women, assessing als o, if possible, individual exposure by bio-monitoring. (C) 1999 Elsevier Sc ience B.V. All rights reserved.