Relationship between Urinary Phthalate and Bisphenol A Concentrations and Serum Thyroid Measures in U.S. Adults and Adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007–2008

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Abstract

Background: Limited animal, in vitro, and human studies have reported that exposure to phthalates or bisphenol A (BPA) may affect thyroid signaling.

Objective: We explored the cross-sectional relationship between urinary concentrations of metabolites of di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and BPA with a panel of serum thyroid measures among a representative sample of U.S. adults and adolescents.

Methods: We analyzed data on urinary biomarkers of exposure to phthalates and BPA, serum thyroid measures, and important covariates from 1,346 adults (ages ≥ 20 years) and 329 adolescents (ages 12–19 years) from the National Health and Nutrition Examination Survey (NHANES) 2007–2008 using multivariable linear regression.

Results: Among adults, we observed significant inverse relationships between urinary DEHP metabolites and total thyroxine (T ₄), free T ₄, total triiodothyronine (T ₃), and thyroglobulin, and positive relationships with thyroid-stimulating hormone (TSH). The strongest and most consistent relationships involved total T ₄, where adjusted regression coefficients for quintiles of oxidative DEHP metabolites displayed monotonic dose-dependent decreases in total T ₄ ( p-value for trend < 0.0001). Suggestive inverse relationships between urinary BPA and total T ₄ and TSH were also observed. Conversely, among adolescents, we observed significant positive relationships between DEHP metabolites and total T ₃. Mono(3-carboxypropyl) phthalate, a secondary metabolite of both DBP and di- n-octyl phthalate, was associated with several thyroid measures in both age groups, whereas other DBP metabolites were not associated with thyroid measures.

Conclusions: These results support previous reports of associations between phthalates—and possibly BPA—and altered thyroid hormones. More detailed studies are needed to determine the temporal relationships and potential clinical and public health implications of these associations.

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Most cited references 45

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Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004

Antonia M Calafat, Xiaoyun Ye, Lee-Yang Wong … (2007)

Background Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. Objectives We aimed to assess exposure to BPA and tOP in the U.S. general population. Methods We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry. Results BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p $45,000/year). Conclusions Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.

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In vitro molecular mechanisms of bisphenol A action.

Yelena B Wetherill, Benson T Akingbemi, Jun Kanno … (2007)

Bisphenol A (BPA, 2,2-bis (4-hydroxyphenyl) propane; CAS# 80-05-7) is a chemical used primarily in the manufacture of polycarbonate plastic, epoxy resins and as a non-polymer additive to other plastics. Recent evidence has demonstrated that human and wildlife populations are exposed to levels of BPA which cause adverse reproductive and developmental effects in a number of different wildlife species and laboratory animal models. However, there are major uncertainties surrounding the spectrum of BPA's mechanisms of action, the tissue-specific impacts of exposures, and the critical windows of susceptibility during which target tissues are sensitive to BPA exposures. As a foundation to address some of those uncertainties, this review was prepared by the "In vitro" expert sub-panel assembled during the "Bisphenol A: An Examination of the Relevance of Ecological, In vitro and Laboratory Animal Studies for Assessing Risks to Human Health" workshop held in Chapel Hill, NC, Nov 28-29, 2006. The specific charge of this expert panel was to review and assess the strength of the published literature pertaining to the mechanisms of BPA action. The resulting document is a detailed review of published studies that have focused on the mechanistic basis of BPA action in diverse experimental models and an assessment of the strength of the evidence regarding the published BPA research.

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Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.

Manori Silva, Dana Barr, John A. Reidy … (2004)

We measured the urinary monoester metabolites of seven commonly used phthalates in approximately 2,540 samples collected from participants of the National Health and Nutrition Examination Survey (NHANES), 1999-2000, who were greater than or equal to 6 years of age. We found detectable levels of metabolites monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP) in > 75% of the samples, suggesting widespread exposure in the United States to diethyl phthalate, dibutyl phthalate or diisobutylphthalate, benzylbutyl phthalate, and di-(2-ethylhexyl) phthalate, respectively. We infrequently detected monoisononyl phthalate, mono-cyclohexyl phthalate, and mono-n-octyl phthalate, suggesting that human exposures to di-isononyl phthalate, dioctylphthalate, and dicyclohexyl phthalate, respectively, are lower than those listed above, or the pathways, routes of exposure, or pharmacokinetic factors such as absorption, distribution, metabolism, and elimination are different. Non-Hispanic blacks had significantly higher concentrations of MEP than did Mexican Americans and non-Hispanic whites. Compared with adolescents and adults, children had significantly higher levels of MBP, MBzP, and MEHP but had significantly lower concentrations of MEP. Females had significantly higher concentrations of MEP and MBzP than did males, but similar MEHP levels. Of particular interest, females of all ages had significantly higher concentrations of the reproductive toxicant MBP than did males of all ages; however, women of reproductive age (i.e., 20-39 years of age) had concentrations similar to adolescent girls and women 40 years of age. These population data on exposure to phthalates will serve an important role in public health by helping to set research priorities and by establishing a nationally representative baseline of exposure with which population levels can be compared.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Journal ID (publisher-id): EHP

Title: Environmental Health Perspectives

Publisher: National Institute of Environmental Health Sciences

ISSN (Print): 0091-6765

ISSN (Electronic): 1552-9924

Publication date (Electronic): 11 July 2011

Publication date (Print): October 2011

Volume: 119

Issue: 10

Pages: 1396-1402

Affiliations

[1]Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA

Author notes

Address correspondence to J. Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S. Observatory St., Ann Arbor, MI 48109 USA. Telephone: (734) 764-7184. Fax: (734) 936-7283. E-mail: meekerj@ 123456umich.edu

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Publisher ID: ehp.1103582

DOI: 10.1289/ehp.1103582

PMC ID: 3230451

PubMed ID: 21749963

SO-VID: dfcd0ecf-2c92-4ae2-81c1-90abec1e7503

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Relationship between Urinary Phthalate and Bisphenol A Concentrations and Serum Thyroid Measures in U.S. Adults and Adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007–2008

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Most cited references 45

Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004

In vitro molecular mechanisms of bisphenol A action.

Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.

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