chapter  51
12 Pages

Discussion and Summary

WithJames L. Schardein, Orest T. Macina

Relationships between agents considered developmental toxicants in humans and in laboratory animals used in nonclinical testing to demonstrate safety in humans show a number of interesting associations. The exception is misoprostol. While it is shown that the drug affects three classes of developmental toxicity in humans, no class has been replicated in laboratory species, even at very large dosage multiples. Another way of looking at these results is to evaluate those laboratory animals that showed complete concordance to the effects shown in humans. Physicochemical parameters characterize the steric, transport, and electronic properties of the respective compounds, as well as their ability to engage in intermolecular interactions. Investigation of the positive versus negative compound distribution with respect to each of the calculated parameters indicates that there are a limited number of parameters that can adequately distinguish between chemicals that can or cannot elicit human growth retardation, death, malformation, and functional deficit.