ToxSci Advance Access published online on June 8, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl035
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1 Endocrinology Branch, Reproductive Toxicology Division, NHEERL, ORD, United States Environmental Protection Agency
* To whom correspondence should be addressed. Testis function in fetal and peripubertal male rats is disrupted by subchronic exposure to phthalate esters. In contrast to the male rat, it is generally held that reproduction in female rats is much less sensitive to phthalate-induced disruption. However, the current study demonstrates that oral administration of dibutyl phthalate (DBP) to female Long Evans Hooded (LE) rats from weaning, through puberty, mating and gestation disrupts pregnancy maintenance at dose levels similar to those that affect testis function in male rats. Administration of 500 and 1000 but not 250 mg DBP/kg/d to female LE rats induced mid-pregnancy abortions. The percentage of females delivering live pups was reduced by more than 50% at 500 mg/kg/d and by 90% at 1000 mg/kg/d in the absence of overt toxicity whereas the ages at vaginal opening and first estrus, estrous cyclicity, and mating indices (N mated/N paired or N pregnant/N mated) were not significantly affected. On gestational day 13, prior to the stage when litters were being aborted, ex vivo ovarian hormone production was significantly decreased by in vivo DBP-treatment at 500 and 1000 mg/kg/d. These results should be considered when evaluating mechanisms of reproductive toxicity for the phthalate esters because it is likely that these reproductive alterations in the female rat arise via a similar mode of action to that operative in male rats. DISCLAIMER: The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, ORD, 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 the mention of trade names or commercial products constitute endorsement or recommendation for use.
Received April 22, 2006
Accepted June 5, 2006
Reproductive and Developmental Toxicology
Chronic Di(n)butyl Phthalate Exposure Rats Reduces Fertility and Alters Ovarian Function During Pregnancy in Female Long Evans Hooded Rats
L. Earl Gray Jr. 1 *,
John Laskey 1,
and
Joseph Ostby 1
L. Earl Gray Jr., E-mail: gray.earl{at}epa.gov
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