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Di-pentyl phthalate dosing during sexual differentiation disrupts fetal testis function and postnatal development of the male Sprague dawley rat with greater relative potency than other phthalates
Hannas, B., J. R. FURR, C. R. LAMBRIGHT, V. S. WILSON, P. M. Foster, AND L. E. GRAY. Di-pentyl phthalate dosing during sexual differentiation disrupts fetal testis function and postnatal development of the male Sprague dawley rat with greater relative potency than other phthalates. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 120(1):184-93, (2011).
This paper includes fetal and postnatal mammalian reproductive toxicity data for dipentyl phthalate, a phthalate ester which is included on both the NCEA IRIS and OCSPP agendas for risk assessment. Therefore, this paper may contribute to the protection of human health by providing dose response data for a targeted reproductive toxicant that would be useful in risk assessment.
Phthalate esters (PEs) constitute a large class of plasticizer compounds that are widely used for many consumer product applications. Ten or more members of the PE class of compounds have been shown to induce male fetal endocrine toxicity and postnatal reproductive malformations through disruption of androgen production during the sexual differentiation period of development. An early study conducted in the rat pubertal model suggested that dipentyl phthalate (DPeP) may be a more potent anti-androgen than some more extensively studied phthalates (Foster et al., 1980). Regulatory agencies require dose response and potency data to facilitate risk assessment; however, very little data are currently available for DPeP. The goal of this study was to establish a more comprehensive data set for DPeP, focusing on dose response and potency information for fetal and postnatal male reproductive endpoints. We dosed pregnant rats on GD 17 or GD 14-18 and subsequently evaluated fetal testicular testosterone (T) production on GD17.5 and GD 18, respectively. We also dosed pregnant rats on GD 8-18 and evaluated early postnatal endpoints in male offspring. Comparison of these data to data previously obtained under similar conditions for di (2-ethylhexyl) phthalate (DEHP, (Howdeshell et al. 2008)) indicate that DPeP is approximately 8-fold more potent in reducing fetal T production and 2-3-fold more potent in inducing development of early postnatal male reproductive malformations. Additionally, fetal testicular T production was more sensitive to inhibitory effects of DPeP exposure than was gene expression of target genes involved in male reproductive development, supporting the use of this endpoint as a critical effect in the risk assessment process. The research described in this article has been reviewed by the U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.