Mass spectrometric determination of p-nonylphenol metabolism and disposition following oral administration to Sprague-Dawley rats.
Isomers of 4-nonylphenol (NP), which are important industrial compounds and environmental breakdown products from widely used surfactants, have estrogenic activity in vitro and in vivo that has prompted interest in its potential for modulation of endocrine function in humans and wildlife. Mass spectrometry was used to quantify NP and metabolites in serum and endocrine-responsive tissues from dietary exposure in Sprague-Dawley rats. Tissue accumulation of NP aglycone was observed despite the predominance of glucuronidation in blood. Serum toxicokinetics of total NP, measured following gavage administration, showed rapid absorption and elimination (average half-times 0.8 and 3.5 h, respectively). NP was similarly administered by gavage to pregnant dams and total and aglycone NP were measured in dam serum and fetuses to show placental transfer into serum and brain. These data provide a basis for future correlations of biologic effects observed following dietary exposure in rats with those predicted from environmental exposures to humans.
Doerge
Daniel R
DR
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. ddoerge@nctr.fda.gov
Twaddle
Nathan C
NC
Churchwell
Mona I
MI
Chang
Hebron C
HC
Newbold
Retha R
RR
Delclos
K Barry
KB
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006207:Half-Life; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008431:Maternal-Fetal Exchange; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D021241:Spectrometry, Mass, Electrospray Ionization; D014018:Tissue Distribution
D020847:Estrogen Receptor Modulators; D010636:Phenols; C041594:4-nonylphenol