Skip Navigation



ToxSci Advance Access published online on April 14, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn077
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
105/1/153    most recent
kfn077v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Howdeshell, K. L.
Right arrow Articles by Gray, L. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Howdeshell, K. L.
Right arrow Articles by Gray, L. E., Jr
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2008.

A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague Dawley rat in a cumulative, dose additive manner

Kembra L. Howdeshell*, Vickie S. Wilson*, Johnathan Furr*, Christy R. Lambright*, Cynthia V. Rider{dagger}, Chad R. Blystone{dagger}, Andrew K. Hotchkiss{dagger} and Leon Earl Gray, Jr*

* Reproductive Toxicology Division, NHEERL, ORD, United States Environmental Protection Agency (USEPA), Research Triangle Park, NC {dagger} Department of Molecular Biosciences, North Carolina State University/US EPA Cooperative Training Program (Grant CT82651210), Raleigh, NC

Correspondence and reprint requests: L Earl Gray Jr, US EPA, NHEERL, RTD (MD-72), Research Triangle Park, NC 27711, Fax: (919) 541-4017, Gray.earl{at}epa.gov

Received February 14, 2008; revision received April 2, 2008; accepted April 8, 2008


  Abstract

Phthalate diesters are chemicals to which humans are ubiquitously exposed. Exposure to certain phthalates during sexual differentiation causes reproductive tract malformations in male rats. In the fetal rat, exposure to the phthalates benzylbutyl (BBP), di(n)butyl (DBP), and diethylhexyl (DEHP) decreases testicular testosterone production and insulin-like 3 hormone mRNA levels. We characterized the dose response effects of six individual phthalates [BBP, DBP, DEHP, diethyl phthalate (DEP), diisobutyl phthalate (DiBP), and dipentyl phthalate (DPP)] on gestation day (GD) 18 testicular testosterone production following exposure of Sprague Dawley rats on GD8-18. BBP, DBP, DEHP, and DiBP were equipotent (ED50 of 440 ± 16 mg/kg/d), DPP was about 3-fold more potent (ED50 = 130 mg/kg/d) and DEP had no effect on fetal testosterone production. We hypothesized that coadministration of these five antiandrogenic phthalates would reduce testosterone production in a dose-additive fashion since they act via a common mode of toxicity. In a second study, dams were dosed at 100, 80, 60, 40, 20, 10, 5 or 0% of the mixture. The top dose contained 1300 mg of total phthalates/kg/d including BBP, DBP, DEHP, DiBP (300 mg/kg/d per chemical) and DPP (100 mg DPP/kg/d). This mixture ratio was selected such that each phthalate would contribute equally to the reduction in testosterone. As hypothesized, testosterone production was reduced in a dose-additive manner. Several of the individual phthalates and the mixture also induced fetal mortality, due to pregnancy loss. These data demonstrate that individual phthalates with a similar mechanism of action can elicit cumulative, dose additive effects on fetal testosterone production and pregnancy when administered as a mixture.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
A. J. Drake, S. van den Driesche, H. M. Scott, G. R. Hutchison, J. R. Seckl, and R. M. Sharpe
Glucocorticoids Amplify Dibutyl Phthalate-Induced Disruption of Testosterone Production and Male Reproductive Development
Endocrinology, November 1, 2009; 150(11): 5055 - 5064.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. R. Blystone, C. S. Lambright, M. C. Cardon, J. Furr, C. V. Rider, P. C. Hartig, V. S. Wilson, and L. E. Gray Jr
Cumulative and Antagonistic Effects of a Mixture of the Antiandrogens Vinclozolin and Iprodione in the Pubertal Male Rat
Toxicol. Sci., September 1, 2009; 111(1): 179 - 188.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
C. E. Talsness, A. J. M. Andrade, S. N. Kuriyama, J. A. Taylor, and F. S. vom Saal
Components of plastic: experimental studies in animals and relevance for human health
Phil Trans R Soc B, July 27, 2009; 364(1526): 2079 - 2096.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
C. V. Rider, V. S. Wilson, K. L. Howdeshell, A. K. Hotchkiss, J. R. Furr, C. R. Lambright, and L. E. Gray Jr
Cumulative Effects of In Utero Administration of Mixtures of "Antiandrogens" on Male Rat Reproductive Development
Toxicol Pathol, January 1, 2009; 37(1): 100 - 113.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.