Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys

Journal Article · Fri Oct 01 04:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.07.009· OSTI ID:21460213

Twaddle, Nathan C; Woodling, Kellie A ^[1]; Fisher, Jeffrey W ^[2]

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1. Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)
2. Department of Environmental Health Sciences, College of Public Health, University of Georgia, Athens, GA 30602 (United States)

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.

• OSTI ID: 21460213
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 248; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CLEARANCE
DRUGS
EXCRETION
INJECTION
INTAKE
INTRAVENOUS INJECTION
MACACUS
MAMMALS
MATERIALS
MONKEYS
ORAL ADMINISTRATION
PRIMATES
RATS
RODENTS
URINE
VERTEBRATES
WASTES