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Author Doerge, Daniel R. ♦ Twaddle, Nathan C. ♦ Woodling, Kellie A. ♦ Fisher, Jeffrey W.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ DRUGS ♦ EXCRETION ♦ INTRAVENOUS INJECTION ♦ MACACUS ♦ ORAL ADMINISTRATION ♦ RATS ♦ URINE ♦ ANIMALS ♦ BIOLOGICAL MATERIALS ♦ BIOLOGICAL WASTES ♦ BODY FLUIDS ♦ CLEARANCE ♦ INJECTION ♦ INTAKE ♦ MAMMALS ♦ MATERIALS ♦ MONKEYS ♦ PRIMATES ♦ RODENTS ♦ VERTEBRATES ♦ WASTES
Abstract 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 {mu}g/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.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2010-10-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 248
Issue Number 1


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