Science Inventory

Fetal Phthalate Screen: Assessment of Several Phthalate Esters (PE) on Fetal Rodent Testosterone (T) Production and Gene Expressionfollowing In Utero Exposure

Citation:

LAMBRIGHT, C. R., J. R. FURR, M. C. CARDON, B. Hannas, D. Bermudez, N. WRENCH, P. Foster, L. E. GRAY, AND V. S. WILSON. Fetal Phthalate Screen: Assessment of Several Phthalate Esters (PE) on Fetal Rodent Testosterone (T) Production and Gene Expressionfollowing In Utero Exposure. Presented at Triangle Consortium for Reproductive Biology Meeting, Durham, NC, February 26, 2011.

Impact/Purpose:

PE are a large family of compounds used in a wide array of products from medical tubing to pharmaceuticals to cables. 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 testes T production and gene expression.

Description:

PE are a large family of compounds used in a wide array of products from medical tubing to pharmaceuticals to cables. 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 testes T production and gene expression. It has been proposed that di-n-alkyl 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 individual PE on fetal testes T production and gene expression by exposing timed 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 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 (dicyclo-), and DINP. No effect on fetal T was seenwithDEP,BrDEHP,DOTPorDiNCH. Gene expression of Ins13, STAR and Cyplla was significantly reduced as compared to control by some of the above PE that also reduced T production. We have shown that some PE are able to reduce both fetal testes T production and gene expression. Some PE with straight chains less than C4 or longer than C6 also can disrupt fetal T synthesis. Disclaimer: This abstract doesn't necessarily reflect USEPA policy.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 02/26/2011
Record Last Revised: 12/05/2012
OMB Category: Other
Record ID: 233271

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

TOXICOLOGY ASSESSMENT DIVISION

REPRODUCTIVE TOXICOLOGY BRANCH