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Cummulative effects of a 9 phthalate mixture using DEHP, DiHP, DiBP, DBP, BBP, DCHP, D(hexyl)P,D(heptyl)P and DPeP on Charles River-Sprague Dawley (CR-SD) fetal rat testis testosterone(T) production and gene expression
Citation:
Wilson, V., J. Furr, C. Lambright, B. Hannas, AND E. Gray. Cummulative effects of a 9 phthalate mixture using DEHP, DiHP, DiBP, DBP, BBP, DCHP, D(hexyl)P,D(heptyl)P and DPeP on Charles River-Sprague Dawley (CR-SD) fetal rat testis testosterone(T) production and gene expression. Presented at Society of Toxicology meeting, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX
Description:
In utero exposure to mixtures of 2 to 5 phthalate esters (PE) with similar modes of action have been shown to inhibit male reproductive development in a dose-additive fashion. Further when PE were administered to pregnant dams during the period of sexual differentiation, when reproductive malformations were observed in male offspring they correlated to significant reductions in fetal T levels. We have observed that a mixture of 9 PE administered on gestation day (GD> 14-18 to Harlan SD rats (dilutions ala fixed ratio mixture; top dose of 80mg DEHP, D1HP, DIBP, DBP, BBP, DCHP, D(hexyl)P, D(heptyl)P, and 10mg DPeP/kgfd) reduced fetal T production in a dose additive manner (Hannas et al, 2011). The current study compared the sensitivity of the fetal testis of CR-SD to the Harlan SD rat for disruption of testis T production and gene expression of the 9 PE mixture. A pilot postnatal study with Harlan SD rats (administered at the top dose and 67, 33, 17, and 8% of the top dose) the high dose group produced a high incidence of phthalate syndrome malformations accurately predicted by dose addition modeling, but far in excess of that predicted by response addition. The CR-SD rat (EDSO = 38% of top dose) was slightly less sensitive to disruption than the Harlan SD rat (E050 = 26%) for fetal T production. Results demonstrate that mixtures 019 PE behave in a manner accurately predicted by dose addition modeling. Thus considering PE hazard Identification on an individual basis, without inclusion of other PE, could underestimate the risk posed by a mixture of PE5. Future postnatal 9 PE studies are planned in the CR-SD rats to determine the point of departure correlation between reduced fetal T levels and the resultant postnatal male reproductive malformations. Disclaimer: This abstract does not necessarily reflect USEPA policy. Supported in part by NTP/NIEHS Interagency Agreement# RW-75-92285501.