INHALATION RFC METHODOLOGY - DOSIMETRIC ADJUSTMENTS AND DOSE-RESPONSEESTIMATION OF NONCANCER TOXICITY IN THE UPPER RESPIRATORY-TRACT

Evaluation of noncancer toxicity involves the evaluation of an array o f different adverse end points across various target tissues. The U.S. Environmental Protection Agency (EPA) inhalation reference concentrat ion (RfC) methodology represents an approach for derivation of dose-re sponse estimates for noncancer toxicity. The RfC methodology differs f rom other methodologies described at this symposium in that it incorpo rates dosimetric adjustments to account for species-specific relations hips of exposure concentration to deposited/delivered dose in order to extrapolate across species. The physicochemical characteristics of th e inhaled chemical are considered as key determinants to its interacti on with respiratory tract components and ultimate deposition. This art icle 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 controversia l interpretation or those requiring additional research are highlighte d.