Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5855816 | Regulatory Toxicology and Pharmacology | 2016 | 12 Pages |
Abstract
To help develop a comprehensive, quantitative understanding of the hazards of 1,2-dichloroethane (ethylene dichloride, EDC, CAS No. 107-06-2) exposure by the inhalation route, the results of existing subchronic studies and an extended one-generation reproductive toxicity (EOGRT) study recently conducted by the oral route in rats were extrapolated using a physiologically based pharmacokinetic (PBPK) model. The no observed adverse effects levels (NOAELs) for the endpoints of neurotoxicity and reproductive/developmental toxicity were the highest tested doses of 169 and 155Â mg/kg-day, respectively. These NOAELs were equivalent to continuous exposure of rats to minimums of 76Â ppm and 62Â ppm EDC, respectively, using total metabolism of EDC as the dose metric that is equivalent in the oral and inhalation scenarios. In contrast, the subchronic study NOAEL of 37.5Â mg/kg-day corresponded to continuous inhalation of 4.4Â ppm EDC, based on equivalent extrahepatic metabolism. The selection of the internal metric which serves to establish route-to-route equivalency was found to profoundly influence the NOAEL-equivalent inhalation exposure concentration and thus will be a key determinant of inhalation toxicity reference criteria developed on the basis of EDC studies conducted by the oral route.
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Authors
Lisa M. Sweeney, Michael L. Gargas,