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Correspondence Volume 124 | 2016

Environ Health Perspect; DOI:10.1289/ehp.1611282

Response to “Comment on ‘Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology’”

Antonia M. Calafat,1 Matthew P. Longnecker,2 Holger M. Koch,3 Shanna H. Swan,4 Russ Hauser,5 Lynn R. Goldman,6 Bruce P. Lanphear,7 Ruthann A. Rudel,8 Stephanie M. Engel,9 Susan L. Teitelbaum,4 Robin M. Whyatt,10 and Mary S. Wolff4

1Centers for Disease Control and Prevention, Atlanta, Georgia, USA; 2National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, North Carolina, USA; 3Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Ruhr-Universität Bochum, Bochum, Germany; 4Icahn School of Medicine at Mount Sinai, New York, New York, USA; 5Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA; 6Milken Institute School of Public Health, George Washington University, Washington, DC, USA; 7British Columbia Children’s Hospital, Vancouver, British Columbia, Canada; 8Silent Spring Institute, Boston, Massachusetts, USA; 9University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 10Mailman School of Public Health, Columbia University, New York, New York, USA

About This Article open

Citation: Calafat AM, Longnecker MP, Koch HM, Swan SH, Hauser R, Goldman LR, Lanphear BP, Rudel RA, Engel SM, Teitelbaum SL, Whyatt RM, Wolff MS. 2016. Response to “Comment on ‘Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology.’” Environ Health Perspect 124:A66–A67;

Address correspondence to M. Wolff, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1057, New York, NY 10029 USA. E-mail:

R.A.R. is employed at the Silent Spring Institute, a 501(c)(3) public charity funded by federal grants and contracts, foundation grants, and private donations, including from breast cancer organizations. When this reply was written, M.P.L. was working part-time at Ramboll with support from 3M; however, the work on the reply was done solely with support by the National Institute of Environmental Health Sciences, where M.P.L. works as a government contractor. The authors certify that their freedom to design, conduct, interpret, and publish research was not compromised by any sponsor.

Final Publication: 1 April 2016

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Related EHP Articles

Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology

Antonia M. Calafat, Matthew P. Longnecker, Holger M. Koch, Shanna H. Swan, Russ Hauser, Lynn R. Goldman, Bruce P. Lanphear, Ruthann A. Rudel, Stephanie M. Engel, Susan L. Teitelbaum, Robin M. Whyatt, and Mary S. Wolff

Comment on “Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology”

Richard W. Stahlhut, Richard B. van Breemen, Roy R. Gerona, Julia A. Taylor, Wade V. Welshons, and Frederick S. vom Saal

We appreciate the opportunity to respond to the letter from Stahlhut et al. regarding our Brief Communication. We stressed the importance of biospecimen integrity and the potential danger of unrecognized contamination of convenience samples, particularly with ubiquitous environmental chemicals such as bisphenol A (BPA) and phthalates.

We did not discuss the important area of experimental research and specifically pharmacokinetic studies, although we based our argument partly on knowledge of concentration changes in various compartments postexposure. We agree that information from pharmacokinetic models is quite valuable and note that experimental studies that use isotope-labeled materials are not susceptible to extraneous contamination. Such experimental studies do not support using polar metabolites, such as unmetabolized BPA, as biomarkers in epidemiologic studies (Thayer et al. 2015). For example, even in situations that may result in exposures higher than background levels, such as handling cash register receipts, BPA serum concentrations are below or near the detection limit and much lower than urinary concentrations (Thayer et al. 2016).

The figure in our Brief Communication revealed the sharp increase in the number of publications using blood-based polar biomarkers over the past 15 years, especially etiologic studies. Our main point was that urine is the most dependable biomonitoring matrix for population research, a position that Stahlhut et al. also support in their letter.

Target-organ dose may inform biological models, but measuring this dose is not always possible, although it can be inferred from pharmacokinetic studies. For environmental epidemiology, reliable measurements in urine can be used to quantify exposures.

A suitable exposure biomarker involves more than detecting the analyte with precise and accurate methods. For pervasive chemicals and particularly for archived samples, specimen integrity must be confirmed. This is true for any matrix, including urine (Guidry et al. 2015; Koch et al. 2012), to ensure valid results.


Guidry VT, Longnecker MP, Aase H, Eggesbo M, Zeiner P, Reichborn-Kjennerud T, et al. 2015. Measurement of total and free urinary phenol and paraben concentrations over the course of pregnancy: assessing reliability and contamination of specimens in the Norwegian Mother and Child Cohort Study. Environ Health Perspect 123(7):705–711, doi: 10.1289/ehp.1408325.

Koch HM, Kolossa-Gehring M, Schroter-Kermani C, Angerer J, Bruning T. 2012. Bisphenol A in 24 h urine and plasma samples of the German Environmental Specimen Bank from 1995 to 2009: a retrospective exposure evaluation. J Expos Sci Environ Epidemiol 22(6):610–616, doi: 10.1038/jes.2012.39.

Thayer KA, Doerge DR, Hunt D, Schurman SH, Twaddle NC, Churchwell MI, et al. 2015. Pharmacokinetics of bisphenol A in humans following a single oral administration. Environ Int 83:107–115, doi: 10.1016/j.envint.2015.06.008.

Thayer KA, Taylor KW, Garantziotis S, Schurman S, Kissling GE, Hunt D, et al. 2016. Bisphenol A, bisphenol S, and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP) in urine and blood of cashiers. Environ Health Perspect 124(4):437–444, doi: 10.1289/ehp.1409427.

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