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ToxSci Advance Access published online on February 13, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj128
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received December 7, 2005
Accepted February 1, 2006

Reproductive and Developmental Toxicology

A Dose Response Study Following In Utero and Lactational Exposure to Di-(2-ethylhexyl) Phthalate (DEHP): Effects on Female Rat Reproductive Development

Simone Wichert Grande 1, Anderson J. M. Andrade 1, Chris E. Talsness 1, Konstanze Grote 1, and Ibrahim Chahoud 1 *

1 Charité University Medical School Berlin, Campus Benjamin Franklin, Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Garystrasse 5, 14195 Berlin, Germany

* To whom correspondence should be addressed.
Ibrahim Chahoud, E-mail: ibrahim.chahoud{at}charite.de


  Abstract

Phthalates, a class of chemicals used as plasticizers, are economically important due to several industrial applications. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate plasticizer, which has been described as a potent antiandrogen in males. We performed an extensive dose response study following developmental exposure to DEHP and evaluated the effects on female reproductive development. Two wide ranges of doses that included dose levels relevant for human exposure as well as high doses typically used in toxicological studies were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 22. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg bw/day and the high-doses were 5, 15, 45, 135 and 405 mg DEHP/kg bw/day. At the dose levels tested, no signs of maternal toxicity were observed. A significant delay in the age at vaginal opening (approximately 2 days) was observed at 15 mg DEHP/kg bw/day and above, as well as a trend for a delay in the age at first estrus at 135 and 405 mg DEHP/kg bw/day (approximately 2 days). Liver enlargement (characteristic of phthalate exposure in rats) was limited to the 135 and 405 mg DEHP/kg bw/day doses. Anogenital distance and nipple development were unaffected. Based on the results of delayed pubertal onset, the NOAEL for female reproductive development may be set at 5 mg DEHP/kg bw/day.

Keywords: DEHP; Female; Dose-response; Development; Endocrine Disruptors.
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[Abstract] [Full Text] [PDF]


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