US EPA

Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. he methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. osimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. xtension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. redictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated (Overton and Miller 1988). odels that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. his paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. he ratio of these two values serves as a scaling factor that can be applied in the RfD methodology to account for the dosimetric differences in the inhaled deposited dose. his application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

Jarabek, A., M. Menache, J. Overton, Jr., M. Dourson, AND F. Miller. INHALATION REFERENCE DOSE (RFDI): AN APPLICATION OF INTERSPECIES DOSIMETRY MODELING FOR RISK ASSESSMENT OF INSOLUBLE PARTICLES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/408 (NTIS PB90245879).

Health Physics, 57(1):177-183, 1989