In vivo metabolic fate of the xeno-estrogen 4-n-nonylphenol in Wistar rats.
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.
Zalko
Daniel
D
Institut National de la Recherche Agronomique, Unité Mixte Recherche Xénobiotiques, 180 Chemin de Tournefeuille, BP3, 31931 Toulouse cédex 9, France. dzalko@toulouse.inra.fr
Costagliola
Rémi
R
Dorio
Céline
C
Rathahao
Estelle
E
Cravedi
Jean-Pierre
JP
D000818:Animals; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D005260:Female; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D015262:Xenobiotics / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine
D004967:Estrogens; D010636:Phenols; D015262:Xenobiotics; C041594:4-nonylphenol