Metabolism and Kinetics of Bisphenol A in Humans at Low Doses Following Oral Administration

Citations Over TimeTop 10% of 2002 papers

Abstract

Bisphenol A is a widely used industrial chemical with many potential sources of human exposure. Bisphenol A is a weak estrogen and has been implicated as an "endocrine disruptor". This term is used for a variety of chemicals encountered in the environment which have estrogenic activity. It has been postulated that human exposure to these chemicals may elicit unwanted estrogenic effects in humans such as reduced fertility, altered development and cancer. Up to now the body burden of bisphenol A in humans is unknown. Therefore, we investigated the metabolism and toxicokinetics of bisphenol A in humans exposed to low doses since systemic bioavailability has a major influence on possible estrogenic effects in vivo. Human subjects (three males and three females, and four males for detailed description of blood kinetics) were administered d(16)-bisphenol A (5 mg). Blood and urine samples were taken in intervals (up to 96 h), metabolites formed were identified by GC/MS and LC-MS/MS and quantified by GC/MS-NCI and LC-MS/MS. d(16)-Bisphenol A glucuronide was the only metabolite of d(16)-bisphenol A detected in urine and blood samples, and concentrations of free d(16)-bisphenol A were below the limit of detection both in urine (6 nM) and blood samples (10 nM). d(16)-Bisphenol A glucuronide was cleared from human blood and excreted with urine with terminal half-lives of less than 6 h; the applied doses were completely recovered in urine as d(16)-bisphenol A glucuronide. Maximum blood levels of d(16)-bisphenol A glucuronide (approximately 800 nM) were measured 80 min after oral administration of d(16)-bisphenol A (5 mg). The obtained data indicate major species differences in the disposition of bisphenol A. Enterohepatic circulation of bisphenol A glucuronide in rats results in a slow rate of excretion, whereas bisphenol A is rapidly conjugated and excreted by humans due to the absence of enterohepatic circulation. The efficient glucuronidation of bisphenol A and the rapid excretion of the formed glucuronide result in a low body burden of the estrogenic bisphenol A in humans following oral absorption of low doses.

Related Papers

• → Urinary Concentrations of Bisphenol A and Three Other Bisphenols in Convenience Samples of U.S. Adults during 2000–2014(2015)386 cited
• → Human exposure of bisphenol A and its analogues: understandings from human urinary excretion data and wastewater-based epidemiology(2019)116 cited
• → Bisphenol A and its alternatives in Austrian thermal paper receipts, and the migration from reusable plastic drinking bottles into water and artificial saliva using UHPLC-MS/MS(2021)84 cited
• → Exposure to New Emerging Bisphenols Among Young Children in Switzerland(2020)77 cited
• → Detection of Endocrine Disruptor Bisphenol A and Bisphenol S in Bangladeshi Thermal Paper Receipts(2022)3 cited