Effect of in utero exposure to di-(2-ethylhexyl)phthalate: Distribution in the rat fetus and testosterone production by rat fetal testis in culture

DEHP is known to cause reproductive toxicity in rats, particularly during the neonatal period. Pregnant and brood rats were treated by gavage with 750 mg/kg b.w./day DEHP starting on GD14 within PND4. Two hours after 14C-DEHP administration on GD15, GD18, GD21 and PND4, the radioactivity content was measured in the dams blood and in the liver, gonads and carcass of the offspring. The radioactivity concentration recovered in the fetuses was one or two order of magnitude lower than the concentration found in the dam plasma. A low proportion of radioactivity was present in fetal gonads, ca. 2%, 5% and 3.6% on GD18, GD21 and PND4, respectively. The effect on testosterone production of DEHP and its metabolites (MEHP, metabolites VI and IX) was assessed in fetal testis cultures using a dose-range which included the maximal exposure observed in vivo. None of the compounds affected testosterone production. Thus, DEHP and/or its metabolites appear to cross the placental barrier, reach the fetal gonads. In vitro, neither DEHP nor its main metabolites decreased the testosterone production.