Abstract
BackgroundAssociations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies.MethodsWomen in the Nurses’ Health Study and Nurses’ Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid.ResultsOver 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results.ConclusionsSingle measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated.
Highlights
Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies
Bisphenol A (BPA)-containing plastics and epoxy resins are used in many items such as containers for foods and beverages, impact-resistant safety equipment and baby bottles, toys, coatings inside metal cans, dental composites and sealants, and in color developer used in certain types of receipt paper [1,2]
The first half of the extract was reconstituted in 125 μL 0.1% formic acid in methanol/water (1:1) for phthalates and analyzed by orbitrap liquid chromatography-mass spectrometry; 0.02 mL were injected onto a BETASIL Phenyl column (150 × 2.1 mm, 3 μm, Thermo, Waltham, Massachusetts) with mobile phase A (0.1% formic acid in water) and mobile phase B (0.1% formic acid in acetonitrile) at a flow rate of 0.35 mL per minute with the following gradient: 75% A/25% B at 0 minutes, increased to 60% A/40% B at 6 minutes, 40% A/60% B at 12 minutes and kept at the same ratio for 2 minutes, at 14.1 minutes changed back to initial condition and equilibrium for 4 minutes
Summary
Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. We assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies. Bisphenol A (BPA) is a man-made chemical used mainly in the manufacture of polycarbonate plastics and epoxy resins [1]. Phthalates, are a class of man-made chemicals used to produce plastics as well as other items. Human exposure to phthalates occurs through ingestion, inhalation, medical procedures, and dermal absorption [1,3]
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