An Approach for Extrapolating Dose Rate Information from Animals to Humans. P. S. Price and R. E. Keenan, ChemRisk7 - A Division of McLaren/Hart Environmental Engineering, 1685, Congress St., Portland, ME 04102
Dose-response information for noncarcinogenic effects in animals are routinely generated in toxicological studies and can be used to produce a dose response curve for the effect. However, such curves are not believed to be directly applicable for predicting human responses to the same chemicals because of differences between the test animals and humans. The reasons for this are; one, humans as a species are believed to have different sensitivity from test species, and two, that the distribution of tolerances in individual humans is believed to be broader than in test animals because of the greater inter-individual variation in humans. This paper presents a model that allows a simple means of predicting the dose causing a specified level of response R in humans (EDRh) based on information in the animal dose response model. The model can be expressed as:
Where the doses causing a response of R% and 50% in animals and in human populations are defined as EDRa, EDRh, ED50a, and ED50h, respectively, UFH and UFA are the uncertainty factors for intra- and inter- species uncertainty, and NOAEL is a high quality NOAEL or benchmark dose for the effect in the test system. Application of this equation using different values of R gives the dose-response curve for the effect in humans. When the uncertainty in the estimates of the terms of the equation are expressed as distributions, the result is a prediction of a dose response in humans with confidence limits.