Di(2-ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre- and postnatally exposed Wistar rats

Reprod Toxicol. 2003 Mar-Apr;17(2):163-70. doi: 10.1016/s0890-6238(02)00149-1.

Abstract

Di(2-ethylhexyl) adipate (DEHA) has replaced the phthalates in thin plasticized polyvinyl chloride films used for food packaging, mainly because some phthalates induce testis toxicity and antiandrogenic effects. A dose-range finding study followed by a dose-response/effect study in Wistar rats investigated whether pre- and postnatal DEHA doses of 0, 800, or 1200mg/kg/day body weight and doses of 0, 200, 400, or 800mg/kg/day (main study) elicited developmental toxicity including antiandrogenic effects. In the main study, DEHA induced a prolonged gestation period (800mg/kg/day) and a dose-related increase in postnatal death (400 and 800mg/kg/day). DEHA also induced a permanent decrease in offspring body weight (800mg/kg/day). No antiandrogenic endpoints were affected. We conclude that DEHA induced developmental toxicity and the NOAEL is 200mg/kg. DEHA did not induce antiandrogenic effects similar to those of di(2-ethylhexyl) phthalate even though the chemical structures have similarities and the two chemicals have a common metabolite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / toxicity*
  • Androgens / biosynthesis*
  • Animals
  • Birth Weight / drug effects
  • Diethylhexyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Female
  • Fetal Death / chemically induced
  • Genitalia, Male / drug effects
  • Genitalia, Male / growth & development
  • Growth / drug effects
  • Litter Size / drug effects
  • Male
  • Organ Size / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects
  • Teratogens*
  • Testosterone / biosynthesis
  • Weight Gain / drug effects

Substances

  • Androgen Antagonists
  • Androgens
  • Teratogens
  • Testosterone
  • Diethylhexyl Phthalate