Does rapid metabolism ensure negligible risk from bisphenol A?

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Date: Nov. 2009
From: Environmental Health Perspectives(Vol. 117, Issue 11)
Publisher: National Institute of Environmental Health Sciences
Document Type: Report
Length: 4,591 words
Lexile Measure: 1500L

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BACKGROUND: Bisphenol A (BPA) risks are being evaluated by many regulatory bodies because exposure is widespread and the potential exists for toxicity at low doses.

OBJECTIVE: We evaluated evidence that BPA is cleared more rapidly in humans than in rats in relation to BPA risk assessment.

DISCUSSION: The European Food Safety Authority (EFSA) relied on pharmacokinetic evidence to conclude that rodent toxicity data are not directly relevant to human risk assessment. Further, the EFSA argues that rapid metabolism will result in negligible exposure during the perinatal period because of BPA glucuronidation in pregnant women or sulfation in newborns. These arguments fail to consider the deconjugation of BPA glucuronide in utero by [beta]-glucuronidase, an enzyme that is present in high concentrations in placenta and various other tissues. Further, arylsulfatase C, which reactivates endogenous sulfated estrogens, develops early in life and so may deconjugate BPA sulfate in newborns. Biomonitoring studies and laboratory experiments document free BPA in rat and human maternal, placental, and fetal tissues, indicating that human BPA exposure is not negligible. The pattern of these detections is consistent with deconjugation in the placenta, resulting in fetal exposure. The tolerable daily intake set by the EFSA (0.05 mg/kg/day) is well above effect levels reported in some animal studies.

CONCLUSION: This potential risk should not be dismissed on the basis of an uncertain pharmacokinetic argument. Rather, risk assessors need to decipher the BPA dose response and apply it to humans with comprehensive pharmacokinetic models that account for metabolite deconjugation.

KEY WORDS: [beta]-glucuronidase, bisphenol A, endocrine disruption, fetus, glucuronidation, metabolism, neonate. Environ Health Perspect 117:1639-1643 (2009). doi: 10.1289/ehp.0901010 available via [Online 14 July 2009]


Few current or past risk assessment issues are as challenging as those raised by bisphenol A (BPA). There is widespread BPA exposure to the general public, including pregnant women and infants, and the chemical is in the class of environmental hormones for which risk assessment approaches are still developing. Given that BPA is one of a large number of estrogenic chemicals to which humans are frequently exposed, this chemical represents something of a test case. Increasing the stakes is evidence for low-dose effects within the range of human exposure for end points that have implications for reproductive health and cancer. However, this evidence is in dispute, with major scientific and regulatory bodies disagreeing over BPA's low-dose risks. Health Canada (2008) calls it a hazardous substance and has banned it from baby bottles. In contrast, the U.S. Food and Drug Administration and the European Food Safety Authority (EFSA) have found no immediate cause for concern and are not taking action to limit exposure.

Other recent reviews and commentaries have focused on the evidence of harm from low-dose exposure (Bucher 2009; Myers et al. 2009; Tyl 2008); we do not address those data here. Rather, we focus on an element that has not received critical attention: the claim raised by the EFSA that rapid metabolic clearance of BPA via first-pass glucuronide metabolism minimizes internal exposure to free BPA (EFSA 2008)....

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Gale Document Number: GALE|A212769449