Details

Autor(en) / Beteiligte

• Thayer, Kristina A.
• Doerge, Daniel R.
• Hunt, Dawn
• Schurman, Shepherd H.
• Twaddle, Nathan C.
• Churchwell, Mona I.
• Garantziotis, Stavros
• Kissling, Grace E.
• Easterling, Michael R.
• Bucher, John R.
• Birnbaum, Linda S.

Titel

Pharmacokinetics of bisphenol A in humans following a single oral administration

Ist Teil von

• Environment international, 2015-10, Vol.83, p.107-115

Ort / Verlag

Netherlands: Elsevier Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA. To reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration. We exposed six men and eight women to 100μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates. Mean serum total (unconjugated and conjugated) d6-BPA Cmax of 1711nM (390ng/ml) was observed at Tmax of 1.1±0.50h. Unconjugated d6-BPA appeared in serum within 5–20min of dosing with a mean Cmax of 6.5nM (1.5ng/ml) observed at Tmax of 1.3±0.52h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48h in some subjects at concentrations near the LOD (0.001–0.002ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4±2.0h and 6.2±2.6h, respectively. Recovery of total administered d6-BPA in urine was 84–109%. Most subjects (10 of 14) excreted >90% as metabolites within 24h. Using more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24h. [Display omitted] •Findings are consistent with data from animal and other human studies.•Maximum total serum levels are 3.9ng/ml for each μg ingested per kg.•Maximum unconjugated serum levels are 0.015ng/ml for each μg ingested per kg.•Unconjugated BPA in blood following oral administration is <1% of the total.•Most subjects excreted >90% as conjugated metabolites within 24h.