In vivo metabolic fate of the xeno-estrogen 4-n-nonylphenol in Wistar rats

Drug Metab Dispos. 2003 Feb;31(2):168-78. doi: 10.1124/dmd.31.2.168.

Abstract

The distribution and the metabolic fate of 4-n-nonylphenol were investigated in male and female Wistar rats dosed orally with 1 microg/kg ("low-dose") or 10 mg/kg ("high-dose") labeled 4-n-nonylphenol. Following a 4-day metabolic balance study, neither the distribution pattern nor the residual levels of 4-n-nonylphenol were found to be different between groups, and no unexpected tissue-specific accumulation of 4-n-nonylphenol was detected. Most of the radioactivity was eliminated in urine, and consisted of hydrophilic metabolites very likely resulting from extensive beta-oxidation of the nonyl side chain and from the conjugation of the phenol to sulfate or to glucuronic acid. Traces of ring-hydroxylated nonylphenol were also characterized. Fecal excretion was mainly associated with unchanged 4-n-nonylphenol and with side chain hydroxylated 4-n-nonylphenol. Experiments carried out in pregnant rats exposed to a low-dose of 4-n-nonylphenol from day 3 to day 19 of gestation demonstrated similar metabolic pathways for this xeno-estrogen. Very limited amounts, if any, of non metabolized 4-n-nonylphenol did reach fetuses. The oxidative metabolism of 4-n-nonylphenol leads to the formation of both ring-hydroxylated and side chain hydroxylated metabolites. The latter metabolic pathway may be a major metabolic pathway for branched 4-nonyl-phenols and may be a clue to understand their biological activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estrogens / administration & dosage
  • Estrogens / metabolism*
  • Estrogens / urine
  • Female
  • Male
  • Phenols / administration & dosage
  • Phenols / metabolism*
  • Phenols / urine
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Tissue Distribution / drug effects
  • Tissue Distribution / physiology
  • Xenobiotics / administration & dosage
  • Xenobiotics / metabolism*
  • Xenobiotics / urine

Substances

  • Estrogens
  • Phenols
  • Xenobiotics
  • 4-nonylphenol