ACRYLONITRILE: HAZARD CHARACTERIZATION AND EXPOSURE-RESPONSE ANALYSIS

Abstract

Acrylonitrile was assessed as a Priority Substance under the Canadian Environmental Protection Act. Based on studies in animals, cancer is considered the critical endpoint for effects of acrylonitrile on human health. A range of tumours in rats – including those of the central nervous system (brain and/or spinal cord), ear canal, gastrointestinal tract and mammary glands – has been consistently observed following both ingestion and inhalation. While increases in cancer have not been observed in available epidemiological studies, their power is insufficient to rule out increases in rare tumours. Available data are insufficient to support a consensus view on a plausible mode of action for induction of tumours by acrylonitrile by other than direct interaction with genetic material. Tumorigenic Concentrations₀₅ (TC₀₅) have been derived, based upon a 5% increase in tumours of the central nervous system in rats. Quantitative estimates of carcinogenic potency derived on the basis of an inhalation bioassay in rats ranged from 6 to 8.9 mg/m³ (human equivalent values). Estimates from drinking water bioassays (TD₀₅) ranged from 0.56 to 2.3 mg/kg body weight per day (human equivalent values).

ACKNOWLEDGMENTS

To ensure transparency and defensibility of the health assessments, a cut-off date for consideration of new data is specified so as not to compromise the integrity of several stages of internal and external review. Data obtained after November 1998 were not considered for inclusion in this assessment.

Sections of the Assessment Report and supporting documentation were reviewed by R. Liteplo and D. Blakey of Health Canada. D. Moir of Health Canada reviewed data relevant to physiologically based pharmacokinetic modelling for this assessment. M. Walker of Health Canada provided statistical support. The health-related sections of the supporting documentation and the Assessment Report were based in part upon a review of the epidemiological data, prepared under contract by J. Siemiatycki of the Institut Armand-Frappier.

In order to address primarily adequacy of coverage, sections of the supporting documentation pertaining to human health were reviewed externally by J.J. Collins, Solutia Inc., St. Louis, Missouri; B. Ghanayem, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; G.L. Kedderis, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina; N. Krivanek, E.I. du Pont de Nemours & Co., Newark, Delaware; D. Strother, BP Chemicals Inc., Cleveland, Ohio; and J. Whysner, American Health Foundation, Valhalla, New York.

Accuracy of reporting, adequacy of coverage and defensibility of conclusions with respect to hazard characterization and exposure–response analyses were considered in written review by staff of the Information Department of BIBRA International and at a panel meeting of the following members, convened by Toxicology Excellence for Risk Assessment (TERA) on November 17, 1998, in Cincinnati, Ohio: M.J. Aardema, The Procter & Gamble Co.; M.L. Dourson, TERA; S. Felter, The Procter & Gamble Co.; M.A. Friedman, private consultant; M.L. Gargas, ChemRisk Division, McLaren/Hart; R.G. Tardiff, The Sapphire Group, Inc.; V.T. Vu, Environmental Protection Agency; and V. Walker, New York State Department of Health.