Estimating equivalent human concentrations of no observed adverse effect levels: a comparison of several methods.

Four methods for intra- and inter-species dose extrapolation for inhalation reference doses are discussed. Dichloromethane is used as an example to illustrate quantitative differences in the methods. The methods include a procedure recommended by the U.S. EPA in 1980, 2 approaches to using physiologically-based pharmacokinetic (PB-PK) models that depend on the extent of knowledge of the values of physiological parameters, and a proposed method based on the concepts inherent to PB-PK models but requiring significantly less data on physiological parameters.