Pharmacokinetics of monobutylphthalate, the active metabolite of di-n-butylphthalate, in pregnant rats.
Di-n-butylphthalate (DBP) is a phthalic acid ester used as a plasticizer and solvent. DBP is a developmental toxicant in rats and mice, with adverse effects arising from the monoester metabolite monobutyl phthalate (MBP). The objective of this study was to evaluate the pharmacokinetics of MBP and monobutyl phthalate glucuronide (MBP-G) in pregnant rats following intravenous (i.v.) dosing with MBP. Pregnant dams were i.v. dosed with aqueous MBP (10, 30, or 50mg MBP/kg body weight) on gestation day (GD) 19. The pharmacokinetics of MBP and MBP-G were rapid: MBP was metabolized to MBP-G within 5 min, and MBP and MBP-G disappeared from maternal and fetal plasma within 24h of dosing. Results were consistent with two previous studies that utilized oral doses of DBP, suggesting that chemical (DBP versus MBP), vehicle (oil versus aqueous), dose level, and route (oral versus i.v.) have minimal effects on the maternal pharmacokinetics of MBP and MBP-G. This study provides direct pharmacokinetic analysis for MBP and MBP-G in pregnant rats during fetal male reproductive development, and indicates that future pharmacokinetic or toxicology studies can reliably utilize oral dosing with DBP.
CIIT Centers for Health Research, P.O. Box 12137, 6 Davis Drive, Research Triangle Park, NC 27709-2137, USA.
John J
JJ
Kremer
Carla C
CC
Williams
Horace D
HD
Parkinson
Susan J
SJ
Borghoff
D000818:Animals; D002853:Chromatography, Liquid; D003993:Dibutyl Phthalate / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D020719:Glucuronides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D008431:Maternal-Fetal Exchange; D010795:Phthalic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000378:metabolism*
D020719:Glucuronides; D010795:Phthalic Acids; D013723:Teratogens; D003993:Dibutyl Phthalate; C028577:monobutyl phthalate