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Phthalates as developmental reproductive toxicants
Citation:
GRAY, L. E. Phthalates as developmental reproductive toxicants. Presented at Phthalates and Cummulative Risk Assessment, NCEA Workshop, Durham, NC, December 08 - 09, 2010.
Impact/Purpose:
The author was invited to present this work in a CPSC CHAPS meeting on cummulative effects of phthalates. They published these in the public docket of the meeting.
Description:
PE are a large family ofcompounds used in a wide array ofconsumer, industrial and medical products. Studies have shown that in utero treatment with PE such as diethyl hexyl phthalate (DEHP) during the critical period offetal reproductive development produced male reproductive malformations by reducing fetal T production and gene expression. It has been proposed that PE with straight side chains ofC4 to C6 are likely reproductive toxicants but C3 or shorter and C7 or longer are not. The goal ofthis study was to test this by using a relatively rapid in vivo screen to evaluate a suite ofPE 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 (750 mg/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 RlA. 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 (dicyclo-), and DINP. No effect on fetal Twas seen with DEP, BrDEHP, DOTP or DiNCR. Gene expression ofIns13, STAR and Cyp11a was significantly reduced as compared to control by some ofthe 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 doesn't reflect USEPA policy. Supported in part by NTPINIEHS IA# RW7592285501-