A dose-response study following in utero and lactational exposure to Di(2-ethylhexyl)phthalate: Effects on female rat reproductive development

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

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

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, and it 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 body weight (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) 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), was observed. 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 no observed adverse effect level for female reproductive development may be set at 5 mg DEHP/kg bw/day.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalToxicological Sciences
Volume91
Issue number1
DOIs
StatePublished - May 2006
Externally publishedYes

Keywords

  • DEHP
  • Development
  • Dose-response
  • Endocrine disruptors
  • Female

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