Assessment of risk from exposure to acrylonitrile: the general approach used by a consultant

The concern from low-level exposure to acrylonitrile is primarily due to its potential for carcinogenicity. Several epidemiology studies provide suggestive evidence for an association of lung cancer in workers exposed to acrylonitrile; however, smoking may be a contributing factor and therefore the role of acrylonitrile as a causative factor is unclear. Seven animal bioassays, using three routes of exposure and two strains of rats, have provided consistent results. Tumors were induced in all studies, with the primary sites of tumor induction being the brain, ear canal, gastrointestinal tract and mammary glands. The linearized multistage model was used for extrapolation purposes. The risk based on brain tumors (astrocytomas) and stomach tumors following oral exposures ranged from 1 x 10(-1) to 4 x 10(-1)mg-1kg-1day-1. The risk of inhalation exposure is somewhat less, (2-3) x 10(-2). Support for carcinogenic potential is obtained from mutagenicity studies. Acrylonitrile has been found to be mutagenic and also binds with DNA. It has been speculated that acrylonitrile is metabolized to 2-cyanoethylene oxide, which is the proximate carcinogen.