ACETALDEHYDE: HAZARD CHARACTERIZATION AND EXPOSURE–RESPONSE ANALYSIS

Abstract

Acetaldehyde has been assessed as a Priority Substance under the Canadian Environmental Protection Act. Based on short-term and long-term inhalation studies conducted in experimental animals, the target tissue has consistently been the site of entry, with non-neoplastic and neoplastic effects occurring principally in the upper respiratory tract at lowest concentrations. It is likely that both the genotoxicity and irritancy of acetaldehyde play a role in its carcinogenicity. A tolerable concentration of 390 μg/m³ has been derived based upon the benchmark dose associated with a 5% adverse effect for non-neoplastic lesions in the nasal cavities of rats in a short-term inhalation assay. Also, a tumorigenic concentration of 28 mg/m³ has been derived, based on the concentration associated with a 5% increase in the incidence of nasal adenocarcinomas and squamous cell carcinomas (combined) in rats exposed by inhalation.

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 April 1998 were not considered for inclusion in this assessment.

Sections of the supporting documentation on genotoxicity were reviewed by D. Blakey of the Environmental and Occupational Toxicology Division of Health Canada. Sections of the supporting documentation pertaining to human health were reviewed externally by R. Keefe (Imperial Oil) and C. Chopra (Bio-Tox Research Limited), primarily to address adequacy of coverage. Accuracy of reporting, adequacy of coverage and defensibility of conclusions with respect to hazard characterization and dose-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 in Risk Assessment (TERA) on September 30, 1997, in Cincinnati, Ohio: K. Blackburn, Procter & Gamble; M. Bogdanffy, DuPont; M. Dourson, TERA; R. Keenan, ChemRisk Division of McLaren/Hart; G. Leikauf, University of Cincinnati; R. Manning, Georgia Department of Natural Resources; E. Ohanian, U.S. Environmental Protection Agency; K. Poirier, Procter & Gamble; A. Renwick, University of Southampton; L. Rosato, Millennium Petrochemical; and L. Sirinek, Ohio Environmental Protection Agency. Helpful written comments were also received from A. Jarabek of the U.S. Environmental Protection Agency.