Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys.
Bisphenol A (BPA) is a high-production volume industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of >90% of Americans aged 6-60 is controversial because of the potential for endocrine disruption, particularly during perinatal development, as suggested by in vitro, experimental animal, and epidemiological studies. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal rhesus monkeys by oral (PND 5, 35, 70) and intravenous injection (PND 77) routes using d6-BPA to avoid sample contamination. The concentration-time profiles observed in adult monkeys following oral administration of 100 μg/kg bw were remarkably similar to those previously reported in human volunteers given a similar dose; moreover, minimal pharmacokinetic differences were observed between neonatal and adult monkeys for the receptor-active aglycone form of BPA. Circulating concentrations of BPA aglycone were quite low following oral administration (< 1% of total), which reflects the redundancy of active UDP-glucuronosyl transferase isoforms in both gut and liver. No age-related changes were seen in internal exposure metrics for aglycone BPA in monkeys, a result clearly different from developing rats where significant inverse age-related changes, based on immaturity of Phase II metabolism and renal excretion, were recently reported. These observations imply that any toxicological effect observed in rats from early postnatal exposures to BPA could over-predict those possible in primates of the same age, based on significantly higher internal exposures and overall immaturity at birth.
Doerge
Daniel R
DR
Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. daniel.doerge@fda.hhs.gov
Twaddle
Nathan C
NC
Woodling
Kellie A
KA
Fisher
Jeffrey W
JW
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D041981:Gastrointestinal Tract / Q000201:enzymology; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology; D008253:Macaca mulatta; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D053719:Tandem Mass Spectrometry; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D014453:Glucuronosyltransferase; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds