Quantitative Exposure-Response Assessment Approaches to Evaluate Acute Inhalation Toxicity of Phosgene

Abstract

Phosgene has been a long-term subject of toxicological research due to its widespread use, high toxicity, and status as a model of chemically induced lung injury. To take advantage of the abundant data set for the acute inhalation toxicity of phosgene, methods for exposure-response analysis that use more data than the traditional no-observed-adverse-effect level approach were used to perform an exposure-response assessment for phosgene. Categorical regression is particularly useful for acute exposures due to the ability to combine studies of various exposure durations, and thus provide estimates of effect severity for a range of both exposure concentrations and durations. Results from the categorical regression approach were compared to those from parametric curve fitting models (i.e., benchmark concentration models) that make use of information from an entire dose-response, but only for one exposure duration. While categorical regression analysis provided results that were comparable to benchmark concentration results, categorical regression provides an improvement over that technique by accounting for the effects of both exposure concentration and duration on response. The other major advantage afforded by categorical regression is the ability to combine studies, allowing the quantitative use of a larger data set, which increases confidence in the final result.