Lack of human relevance for procymidone’s developmental toxicity attributable to species difference in its kinetics and metabolism

Abstract

The agricultural fungicide procymidone can cause external genitalia abnormalities in rats but not monkeys or rabbits. To investigate the relevance of developmental findings in rats to humans, we conducted in vitro plasma protein binding studies, in vitro metabolism (biotransformation) studies using liver S9 fractions and hepatocytes, and in vivo metabolism and excretion studies using chimeric mice with humanized hepatocytes. On the basis of these results, we concluded that the metabolic and excretion profiles of procymidone in humans are similar to those in monkeys and rabbits but differ from those in rats. From the findings of this and previous studies, we judge the developmental toxicity potential of procymidone to be very low in humans.