Pharmacokinetics of DBP in utero to Assess Human Risk

The Hamner Institutes, Research Triangle Park NC

Investigators

Abstract

DESCRIPTION (provided by applicant): Di-n-butyl phthalate (DBP) is a phthalic acid ester and a widespread environmental contaminant. DBP is a known reproductive toxicant in rats and mice, with adverse effects arising from the monoester metabolite - monobutyl phthalate (MBP). One principal uncertainty is the concentration of MBP required to impair human male reproductive development in utero. Mechanistic studies in rats have shown that in utero exposure to DBP decreases testosterone concentration in the fetal testes, possibly due to MBP-induced disruption in testosterone biosynthesis. The goal of this project is to develop a quantitative understanding of the relationship between DBP exposure and the concentration of MBP and testosterone in the fetal testes required to elicit an adverse response in rats. To accomplish this goal, a physiologically based pharmacokinetic (PBPK) model will be developed for rats to quantitatively understand the relationship between DBP exposure and the metabolism and distribution of its physiologically-active metabolite MBP. By understanding this dose-response relationship in rats, this model can be extrapolated to provide information on the real-world dangers of DBP to human health.