Inhalation RfC Methodology: Dosimetric Adjustments and Dose-Response Estimation of Noncancer Toxicity in The Upper Respiratory Tract

Abstract

Evaluation of noncancer toxicity involves the evaluation of an array of different adverse end points across various target tissues. The U.S. Environmental Protection Agency (EPA) inhalation reference concentration (RfC) methodology represents an approach for derivation of dose-response estimates for noncancer toxicity. The RfC methodology differs from other methodologies described at this symposium in that it incorporates dosimetric adjustments to account for species-specific relationships of exposure concentration to deposited/delivered dose in order to extrapolate across species. The physicochemical characteristics of the inhaled chemical are considered as key determinants to its interaction with respiratory tract components and ultimate deposition. This article discusses the RfC approach to noncancer toxicity with emphasis on the evaluation of toxicity in the upper respiratory tract (URT). The derivation of default dosimetric adjustments for extrapolation of URT delivered dose across species is also presented. Areas of controversial interpretation or those requiring additional research are highlighted.