Interspecies extrapolation of pharmacokinetics.
The purpose of this paper is to use physiologically based pharmacokinetic models to demonstrate that if toxic response is a function of the time profile in physiological time of the concentration of the toxic moiety in the target tissue, then the appropriate interspecies scaling law for toxic compounds which are metabolically deactivated is mg kg-1 per unit of physiological time (mg kg-1 pt-1). At low dose rates this metric is approximately equivalent to mg kg-0.75 day-1. For reactive metabolites which are spontaneously deactivated, an approximate interspecies scaling law is mg kg-1 day-1.
Travis
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Health and Safety Research Division, Computing and Telecommunications Division Oak Ridge National Laboratory, TN 37831-6109.
White
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Ward
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D000818:Animals; D001835:Body Weight; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced; D010599:Pharmacokinetics; D012307:Risk Factors; D013045:Species Specificity