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We noted serious methodologic issues in the measurement of bisphenol A (BPA), phthalate diesters, and their metabolites in blood serum and other tissues, as reported in the recent
BPA and phthalate diesters are non-persistent in the body; they metabolize quickly and, as a result, the levels of their polar, hydrophilic metabolites in blood can be several orders of magnitude lower than in urine (controlled human studies suggest 30- to 100-fold higher levels in urine than serum) [
Extraneous sources of phthalate diesters include plastics, personal care and consumer products, and building furnishings [
BPA also has extraneous sources such as plastics [
Moreover, because both BPA and the phthalate diesters have very short half-lives (regardless of the biomarker used), great care must be taken to ensure that measurements represent the daily habits of research subjects versus brief exposures from iatrogenic sources, such as collection devices, clinical apparatus, and tubing from medical procedures [
Brian L Sprague, Amy Trentham-Dietz, Curtis J Hedman, Jue Wang, Jocelyn DC Hemming, John M Hampton, Diana SM Buist, Erin J Aiello Bowles and Elizabeth S Burnside
We thank Calafat and colleagues for their discussion of BPA and phthalate measurement. Their comments on the challenges of exposure assessment for rapidly metabolized chemicals echo the statements in our discussion. They further emphasize the susceptibility of blood serum measures to contamination. We took several rigorous steps to avoid plasticizer contamination, including the use of glass labware, preparation steps to remove potential contaminants from labware, handling of labware and specimens in biosafety cabinets, and the assessment of method blanks as recommended in the literature [
Non-differential measurement error due to contamination would tend to attenuate the observed associations between the measured chemicals and mammographic breast density. However, for contamination to explain the observed positive associations of BPA and monoethyl phthalate with breast density, the samples from patients with high breast density would need to be more greatly contaminated. The conditions for introducing a positive bias by sample contamination are not readily apparent.
Nevertheless, we agree that accurate biomarker assessment is essential for elucidating the role of environmental chemicals in the etiology of breast cancer. Future studies that measure metabolites less susceptible to contamination, use a variety of specimen types (including urine), and assess exposure levels at multiple points in time are needed.
BPA: Bisphenol A.
The authors declare that they have no competing interests. The findings and conclusions in this letter are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.