Download - Bisphenol A

Polycarbonate/Bisphenol A group
15.7.2011
New FDA-study reconfirms very low internal human exposure to Bisphenol A through diet
as well as the validity of earlier studies used by regulators in BPA risk assessment
End of June 2011, the scientific journal Toxicological Science published online the results of a
new study by Teeguarden et.al.*. The study investigated actual internal human dietary exposure
to Bisphenol A (BPA) in 20 human volunteers. The study was conducted by researchers from the
US Food and Drug Administration (FDA) and the Center for Disease Control (CDC), executed at
a US government national laboratory, and funded by a grant from the US Environmental
Protection Agency (EPA).
The authors aimed to clarify a key question in the context of BPA safety discussion, namely
whether human blood/tissue concentrations of free, unmetabolised BPA are similar to, above, or
below blood/tissue concentrations claimed to cause adverse effects in animal models. The main
objective of their study was therefore to characterize internal exposure to BPA in humans via
realistic exposure routes and levels: “BPA exposures in this study can (…) be viewed as
representative of, or exceeding, the high end of the U.S. BPA exposure distribution.”
The results of the Teeguarden et.al. study reconfirm that BPA is efficiently metabolized and
rapidly excreted via urine: free BPA was below the limit of detection in all 320 blood samples
analyzed by the CDC laboratory, even for samples with detectable total BPA. These findings are
consistent with previous human and animal studies, and confirm the validity of earlier studies
(Voelkel et al., 2002 and 2005) that were used by regulators.
In particular, the authors note: “The consistency in the pharmacokinetics of BPA in humans in
these two independent reports confirms the importance of both studies for understanding human
oral-route pharmacokinetics of BPA and supports the direct use of the controlled human studies
for estimating plausible levels of BPA in human blood following dietary exposure.”
The study can be accessed via this link: at http://dx.doi.org/10.1093/toxsci/kfr160
For more information please contact:
Jasmin Bird
PC/BPA-Group PlasticsEurope
Tel: +32 2 676 17 38
Fax: +32 2 675 39 35
mail: jasmin.bird@plasticseurope.org
website: www.bisphenol-a-europe.org
*Justin G. Teeguarden; Antonia M. Calafat; Xiaoyum Ye; Daniel R. Doerge; Mona I.
Churchwell; Rudy Gunawan; Morgan Graham; 24-Hour Human Urine and Serum Profiles of Bisphenol
A During High Dietary Exposure in: Toxicological Science In-Press, published online 24.6.2011
ASSOCIATION OF PLASTICS MANUFACTURERS IN EUROPE AISBL
Avenue E. Van Nieuwenhuyse 4/3 - B -1160 Brussels - Belgium
Tel (32-2) 675 32 97 - Fax (32-2) 675 39 35
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Background information
Issue addressed in the study
Several large-scale urine biomonitoring studies have consistently demonstrated that human exposure
to BPA, from all sources, is extremely low with typical intake in the range of 25-50 nanograms/kg
bodyweight/day. These levels are more than 1,000 times below the safe intake limit (tolerable daily
intake, TDI) set by the European Food Safety Authority EFSA. Other studies, including several
controlled human volunteer studies, have shown that BPA is efficiently metabolized and rapidly
excreted in urine. Taken together, these studies provide a consistent and coherent understanding of
human exposure and metabolism.
In contrast, a number of smaller scale studies have reported significant levels of free (unmetabolized)
BPA in human blood. The levels reported are highly inconsistent with what is known about human
exposure and metabolism from the studies mentioned above. In addition, the validity of the data in
these blood biomonitoring studies is uncertain since other studies have suggested that sample
contamination may be a significant problem in trace level BPA analyses. Nevertheless, these studies
are used as evidence that people are exposed to high levels of BPA, with some claims that human
exposure is even higher than the TDI.
It was an objective of the Teeguarden-research team to contribute to understanding which of these
two sets of study data is valid.
What was done?
In the study, 20 human volunteers ate 3 meals in a day that were enriched in canned foods and
beverages to ensure that the participants were exposed to BPA. Based on how much total BPA was
found in urine, it was determined that the average exposure for all participants was 21% greater than
the 95 th percentile exposure determined by CDC’s population-scale urine biomonitoring data.
Blood and urine samples were collected from each participant hourly during the day of the study. The
blood samples were analyzed for both free BPA and total BPA, while urine samples were analyzed for
total BPA (previous data has shown that free BPA is not commonly found in urine), all with a sensitive
analytical method. This comprehensive set of data allows for a detailed analysis of the
pharmacokinetics of BPA.
Key Results
Total BPA was detected in only 14% of the 320 blood samples, only one of which was above 1 ppb.
Total BPA was below the sensitive limit of detection (0.3 ppb) for 86% of the samples.
Importantly, free BPA was below the limit of detection in all 320 blood samples analyzed by the CDC
lab, even for samples with detectable total BPA. Based on their results the authors note that reported
high levels of BPA in blood are unlikely to be valid: “Furthermore, the current results obtained using
analytical methodology 10-45 times more sensitive than the previous human study by Voelkel et al.
suggest that reported BPA concentrations in human blood of 1.4-19.2 nM [~0.3-4.4 ppb] (Vandenberg,
Chahoud et al. 2010) are highly unlikely in the general population exposed orally to amounts as much
as ~4 times greater than the 95 th upper percentile of aggregate exposure in the general U.S.
population.”
ASSOCIATION OF PLASTICS MANUFACTURERS IN EUROPE AISBL
Avenue E. Van Nieuwenhuyse 4/3 - B -1160 Brussels - Belgium
Tel (32-2) 675 32 97 - Fax (32-2) 675 39 35
VAT BE 416 155 338 - WWW.PLASTICSEUROPE.ORG
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Samples with detectable total BPA were further analyzed in the FDA lab to confirm the findings. Very
low but detectable levels of free BPA were found in 3 of these samples, but further analysis revealed
that contamination was most likely the source of the free BPA. The authors note, “the evidence
presented here and elsewhere for low-level contamination (Markham et al., 2010; Twaddle et al.,
2010), even in the face of extraordinary attention to this problem, suggests that these infrequent
positive determinations near the detection limit should be suspect” and “Thus, some attributions of
high blood BPA concentrations from oral exposure seem implausible.”
ASSOCIATION OF PLASTICS MANUFACTURERS IN EUROPE AISBL
Avenue E. Van Nieuwenhuyse 4/3 - B -1160 Brussels - Belgium
Tel (32-2) 675 32 97 - Fax (32-2) 675 39 35
VAT BE 416 155 338 - WWW.PLASTICSEUROPE.ORG
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