Calafat, Antonia M

Goldman, Lynn R

Hauser, Russ

Koch, Holger M

Lanphear, Bruce P

Longnecker, Matthew P

Rudel, Ruthann A

Swan, Shanna H

Teitelbaum, Susan L

Whyatt, Robin M

Wolff, Mary S

Breast Cancer Research

Harvard University - DASH 

 Misuse of blood serum to assess exposure to bisphenol A andphthalates  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Calafat, A. M., H. M. Koch, S. H. Swan, R. Hauser, L. R.Goldman, B. P. Lanphear, M. P. Longnecker, et al. 2013.“Misuse of blood serum to assess exposure to bisphenol A andphthalates.” Breast Cancer Research : BCR 15 (5): 403.doi:10.1186/bcr3494. http://dx.doi.org/10.1186/bcr3494.Published Version doi:10.1186/bcr3494Accessed February 19, 2015 3:53:28 PM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152869Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACalafat et al. Breast Cancer Research 2013, 15:403http://breast-cancer-research.com/content/15/5/403LETTERMisuse of blood serum to assess exposure tobisphenol A and phthalatesAntonia M Calafat1, Holger M Koch2, Shanna H Swan3, Russ Hauser4, Lynn R Goldman5, Bruce P Lanphear6,Matthew P Longnecker7, Ruthann A Rudel8, Susan L Teitelbaum3, Robin M Whyatt9 and Mary S Wolff3*See related research by Sprague et al., http://breast-cancer-research.com/content/15/3/R45We noted serious methodologic issues in the measure-ment of bisphenol A (BPA), phthalate diesters, and theirmetabolites in blood serum and other tissues, asreported in the recent Breast Cancer Research article bySprague and colleagues [1]. Such measurements are ana-lytically possible. However, for the reasons that follow, itis seldom possible to verify that serum concentrations ofthese compounds are valid measures of exposure.BPA and phthalate diesters are non-persistent in thebody; they metabolize quickly and, as a result, the levels oftheir polar, hydrophilic metabolites in blood can be severalorders of magnitude lower than in urine (controlled hu-man studies suggest 30- to 100-fold higher levels in urinethan serum) [2-4]. Such low levels increase the possibilitythat contamination can obscure true exposures.Extraneous sources of phthalate diesters include plastics,personal care and consumer products, and building fur-nishings [2,5]. Phthalate diesters derived externally caneasily contaminate blood serum and other human matri-ces and overwhelm the very low levels in blood from dailyexposures [2,4]. Hydrolytic enzymes are ubiquitous inblood and most other matrices (but not urine). These en-zymes rapidly hydrolyze extraneous phthalate diesters to* Correspondence: mary.wolff@mssm.edu3Department of Preventive Medicine, Icahn School of Medicine at MountSinai, 1 Gustave L Levy Place, Box 1057, New York, NY 10029, USAFull list of author information is available at the end of the articleAuthors' responseBrian L Sprague, Amy Trentham-Dietz, Curtis J Hedman, Jue WanErin J Aiello Bowles and Elizabeth S BurnsideWe thank Calafat and colleagues for their discussion ofBPA and phthalate measurement. Their comments on thechallenges of exposure assessment for rapidly metabolizedchemicals echo the statements in our discussion. They© BioMed Central Ltd.2013their corresponding monoesters, beginning immediatelyafter sample collection, and this can artificially elevate theconcentrations of these hydrolytic monoesters, includingmonoethyl phthalate and mono-(2-ethylhexyl) phthalate.To the best of our knowledge, phthalate oxidative metabo-lites (such as mono-(2-ethyl-5-oxohexyl) phthalate) do notform as a result of recent external contamination. The oxi-dative metabolites were not measured in the study bySprague and colleagues [1]. Therefore, in blood, saliva, ortissues other than urine, only the phthalate oxidative me-tabolites (not the phthalate diesters or the hydrolyticmonoesters) are valid exposure biomarkers.BPA also has extraneous sources such as plastics [3,5].There are currently no comparable oxidative metabolitesthat can exclude recent contamination, but conjugatedBPA (not ‘free’ BPA) is the most valid exposure biomarkerand is not present to any significant degree in biologicalsamples other than urine. For these reasons, urine is thebest matrix for epidemiological assessment of exposure toBPA, phthalates, and other polar, non-persistent chemicalsto whose exposures can be episodic in nature.Moreover, because both BPA and the phthalate diestershave very short half-lives (regardless of the biomarker used),g, Jocelyn DC Hemming, John M Hampton, Diana SM Buist,further emphasize the susceptibility of blood serum mea-sures to contamination. We took several rigorous steps toavoid plasticizer contamination, including the use of glasslabware, preparation steps to remove potential contami-nants from labware, handling of labware and specimens inbiosafety cabinets, and the assessment of method blanksas recommended in the literature [6]. Assessment ofmethod blanks showed that iatrogenic contamination waslower than the limits of detection for BPA and phthalates.Calafat et al. Breast Cancer Research Page 2 of 22013, 15:403http://breast-cancer-research.com/content/15/5/403great care must be taken to ensure that measurements rep-resent the daily habits of research subjects versus brief expo-sures from iatrogenic sources, such as collection devices,clinical apparatus, and tubing from medical procedures [2,5].Non-differential measurement error due to contamin-ation would tend to attenuate the observed associationsbetween the measured chemicals and mammographicbreast density. However, for contamination to explainthe observed positive associations of BPA and monoethylphthalate with breast density, the samples from patientswith high breast density would need to be more greatlycontaminated. The conditions for introducing a positivebias by sample contamination are not readily apparent.Nevertheless, we agree that accurate biomarker assess-ment is essential for elucidating the role of environmen-tal chemicals in the etiology of breast cancer. Futurestudies that measure metabolites less susceptible to con-tamination, use a variety of specimen types (includingurine), and assess exposure levels at multiple points intime are needed.AbbreviationBPA: Bisphenol A.Competing interestsThe authors declare that they have no competing interests. The findings andconclusions in this letter are those of the authors and do not necessarilyrepresent the official position of the Centers for Disease Control andPrevention.Author details1Centers for Disease Control and Prevention, 4770 Buford Hwy, MS-F17,Atlanta, GA 30341, USA. 2Institute for Prevention and Occupational Medicineof the German Social Accident Insurance, Institute of the Ruhr-Universität-Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.3Department of Preventive Medicine, Icahn School of Medicine at MountSinai, 1 Gustave L Levy Place, Box 1057, New York, NY 10029, USA.4Department of Environmental Health, Harvard School of Public Health,Building I room 1409, 665 Huntington Avenue, Boston, MA 02115, USA.5George Washington University, School of Public Health and Health Services,2175 K Street, NW, 5th Floor, Washington, DC 20037, USA. 6British ColumbiaChildren’s Hospital, 3415 Ash Street, Vancouver, BC V5Z 3E5, Canada.7National Institute of Environmental Health Sciences, PO Box 12233 MD A3-05, Durham, NC 27709, USA. 8Silent Spring Institute, 29 Crafts Street, Newton,MA 02458, USA. 9Columbia University Mailman School of Public Health, 60Haven Avenue B-109, New York, NY 10032, USA.Published:References1. Sprague BL, Trentham-Dietz A, Hedman CJ, Wang J, Hemming JD, HamptonJM, Buist DS, Bowles EJ, Sisney GS, Burnside ES: Circulating serumxenoestrogens and mammographic breast density. Breast Cancer Res2013, 15:R45.2. Calafat AM, Needham LL: What additional factors beyond state-of-the-artanalytical methods are needed for optimal generation andinterpretation of biomonitoring data? Environ Health Perspect 2009,117:1481–1485.3. Koch HM, Kolossa-Gehring M, Schröter-Kermani C, Angerer J, Brüning T:Bisphenol A in 24 h urine and plasma samples of the GermanEnvironmental Specimen Bank from 1995 to 2009: a retrospectiveexposure evaluation. J Expo Sci Environ Epidemiol 2012, 22:610–616.01 Oct 20134. Wolff MS, Swan S: Phthalate biomarkers in pediatric research, eletter.Pediatrics 2010 [http://pediatrics.aappublications.org/cgi/eletters/125/1/e122], [http://pediatrics.aappublications.org/content/125/1/e122.short/reply#pediatrics_el_50433]5. Longnecker MP, Harbak K, Kissling GE, Hoppin JA, Eggesbo M, Jusko TA,Eide J, Koch HM: The concentration of bisphenol A in urine is affected byspecimen collection, a preservative, and handling. Environ Res. in press.6. Ye X, Zhou X, Hennings R, Kramer J, Calafat AM: Potential externalcontamination with bisphenol A and other ubiquitous organicenvironmental chemicals during biomonitoring analysis: an elusivelaboratory challenge. Environ Health Perspect 2013, 121:283–286.Cite this article as: Calafat et al.: Misuse of blood serum to assessexposure to bisphenol A and phthalates. Breast Cancer Research10.1186/bcr34942013, 15:403

Misuse of blood serum to assess exposure to bisphenol A and phthalates

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Misuse of blood serum to assess exposure to bisphenol A and phthalates

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