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ToxSci Advance Access originally published online on August 18, 2008
Toxicological Sciences 2008 106(2):376-383; doi:10.1093/toxsci/kfn171
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Higher Levels of Ethyl Paraben and Butyl Paraben in Rat Amniotic Fluid than in Maternal Plasma after Subcutaneous Administration

Hanne Frederiksen*,1, Camilla Taxvig{dagger}, Ulla Hass{dagger}, Anne M. Vinggaard{dagger} and Christine Nellemann{dagger}

* Department of Growth and Reproduction, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark {dagger} Department of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, DK-2860 Søborg, Denmark

1 To whom correspondence should be addressed at Department of Growth and Reproduction, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Fax: +45-3545-6054. E-mail: hanne.01.frederiksen{at}rh.regionh.dk.

Received May 30, 2008; accepted July 17, 2008


   Abstract

Parabens are a group of antimicrobial preservatives widely used in cosmetics, pharmaceuticals, and in foods. Previous in vitro and in vivo studies have shown weak estrogenic effects of some parabens. Thus, especially, exposure of fetus and infants via the mother is a matter of concern. In order to obtain more knowledge about the distribution of ethyl paraben and butyl paraben in pregnant rats and pups after perinatal exposure, the presented study was designed. The data show response and distribution of ethyl paraben and butyl paraben in maternal rat plasma, pools of amniotic fluids, placenta, whole-body fetuses, and in fetal liver after dosing of dams with 100, 200, and 400 mg/kg body weight (bw)/day from gestational day 7 to 21. After cesarean section of dams, the fluids and tissues were collected, deconjugated, and purified by solid-phase extraction, and ethyl paraben and butyl paraben were analyzed by liquid chromatography-tandem mass spectrometry. Markedly higher levels of ethyl paraben compared to butyl paraben were found in all fluids and tissues. Both ethyl paraben and butyl paraben in maternal plasma, livers, and whole-body tissues from fetus seemed to be saturated after dosing with ≥ 100 mg/kg bw/day, while both compounds were excreted into amniotic fluid in a dose-dependent manner. Significant difference was found between the level of ethyl paraben in maternal plasma and amniotic fluid after dosing with 200 mg/kg bw/day as well as between the levels of butyl paraben in maternal plasma and amniotic fluid after dosing with 100, 200, and 400 mg/kg bw/day.

Key Words: ethyl paraben; butyl paraben; distribution; pregnant rat; endocrine disruptor.


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