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Effects of mixtures of phthalates and other toxicants on sexual differentiaion in rats: A risk assessment framework based upon disruption of common developing systems
Citation:
GRAY, L. E. Effects of mixtures of phthalates and other toxicants on sexual differentiaion in rats: A risk assessment framework based upon disruption of common developing systems. Presented at Chronic Hazard Advisory Panel meeting on Phthalates and Phthalates Substitutes, Durham, NC, July 26 - 28, 2010.
Impact/Purpose:
The author was invited to present this work in a Chronic Hazard Advisory Panel Society (CHAPS) CPSC meeting on cummulative effects of phthalates. They published these in the public docket of the meeting
Description:
PE are a large family of compounds used in a wide array of consumer, industrial and medical products. Studies have shown that in utero treatment with PE such as diethyl hexyl phthalate (DEHP) during the critical period of fetal reproductive development produced male reproductive malformations by reducing fetal T production and gene expression. It has been proposed that PE with straight side chains of C4 to C6 are likely reproductive toxicants but C3 or shorter and C7 or longer are not. The goal of this study was to test this by using a relatively rapid in vivo screen to evaluate a suite of PE for their potential reproductive toxicities. We investigated the effects of 12 PE on fetal testes T production and gene expression by exposing time pregnant Sprague-Dawley rats via oral gavage (750mg/kg/day) from gestational day (GD) 14-18. On GD 18, testes from three fetuses were collected and cultured for 3 hours. Medium was collected and T levels measured by RIA. The remaining testes were pooled by litter, mRNA extracted and gene expression for Ins13, STAR and Cyp11a was measured. Fetal testes T production was significantly reduced compared to control following treatment with BBP, DBP, DIBP, DPP, DiHP, DHeP(diheptyl-), DHP (dihexyl-), DCHP (dicyc1o-), and DINP. No effect on fetal T was seen with DEP, BrDEHP, DOTP or DiNCH. Gene expression of Ins13, STAR and Cyp11a was significantly reduced as compared to control by some of the above PE that also reduced T production. Some PE reduced reduce both fetal testes T production and gene expression with the reduction in T production being consistently the most robust response. Furthermore, some PE with straight chains less than C4 or longer than C6 disrupted fetal T synthesis. Disclaimer: This abstract does not reflect USEPA policy. Supported in part by NTPINIEHS IA# RW7592285501-1