Sunday, August 23, 2009

BPA extrapolation

BrooklynDodger(s) comments: The highlighted sentence appears to contradict itself. Were the reviewers asleep? Still, a mechanism for greater sensitivity of younger organisms.

Toxicology Letters
Bisphenol A levels in blood depend on age and exposure
Pages 32-40
Hans Mielke, Ursula Gundert-Remy

Federal Institute for Risk Assessment/Bundesinstitut für Risikobewertung (BfR), Thielallee 88-92, D-14195 Berlin, Germany

Received 24 April 2009;
revised 17 June 2009;
accepted 19 June 2009.
Available online 26 June 2009.


We present two approaches to estimate blood concentrations of Bisphenol A (BPA). Simple kinetic principles were applied to calculate steady state plasma concentrations. A physiologically based model was used to simulate the blood concentration time profile in several age groups exploring the influence of not yet fully developed metabolic capacity on the blood concentrations in the newborn.

Both approaches gave concordant results and are in excellent agreement with experimental results [Völkel, W., Colnot, T., Csanady, G.A., Filser, J.G., Dekant, W., 2002. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem. Res. Toxicol. 15, 1281–1287]. The predictions also agree with published results obtained with a different physiologically based model.

According to model simulations, BPA is present in the blood of the normal population at concentrations several orders of magnitude lower than most measurements reported in the literature. At the same external exposure level, the newborn is predicted to have 3 times greater blood concentration than the adult. This is due to the not yet fully developed glucuronidation activity in the newborn, not fully compensated by the unimpaired sulfation pathway. For the highest measured external BPA exposure, the predicted blood concentrations of 2.6 pg/ml (steady state concentration) and 8.2 pg/ml (peak concentration) in the adult are lower than the in vitro concentrations at which inhibiting adiponectin release from human adipocytes and stimulation of β-cell production and secretion were observed.

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