Chapter 40 - Animal/Human Concordance

Abstract

This chapter describes the degree of concordance between human and animal data. Evaluation is made of the biologic literature with respect to study outcomes as a measure of species sensitivity in ascertaining the extent to which animal models are predictors of potential human developmental toxicity or teratogenicity. The animal data are derived from experimental studies in which the agents that are designed to elicit toxicity either to the mother or the fetus, or to both are deliberately administered at dose levels during gestation. The rabbit and primate almost equally were most often unreactive, at a rate greater than 70%, followed by the rat, then the mouse and dog equally. When evaluated from the standpoint of concordance to human effects for the specific classes of developmental toxicity, the order changed somewhat to mouse, rat, primate, rabbit, and hamster. The use of the drug D-penicillamine in the treatment of Wilson's disease resulted in its identity as a human teratogen. A study in which the drug was fed at a concentration of 0.8% throughout gestation resulted in 21% of the fetuses being malformed, including the malformation cutis laxa and increased resorption. The concordance to some suspected human developmental neurotoxicants is also elaborated.