Effects of Gender on the Association of Urinary Phthalate Metabolites with Thyroid Hormones in Children: A Prospective Cohort Study in Taiwan

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Abstract

Phthalates are considered endocrine disruptors. Our study assessed the gender-specific effects of phthalate exposure on thyroid function in children. In total, 189 Taiwanese children were enrolled in the study. One-spot urine and blood samples were collected for analyzing 12 phthalate metabolites in urine and thyroid hormones. The association between urinary phthalate metabolites and serum thyroid hormones was determined using a generalized linear model with a log link function; the children were categorized into groups for analysis according to the 33rd and 66th percentiles. The data were stratified according to gender and adjusted for a priori defined covariates. In girls, a positive association existed between urinary di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-hydroxyhexyl) phthalate) and free thyroxine (T4). In boys, urinary dibutyl phthalate (DBP) metabolites (mono-i-butyl phthalate and mono-n-butyl phthalate) were positively associated with free triiodothyronine (T3). After categorizing each exposure into three groups, urinary DEHP metabolites were positively associated with free T3 levels in boys. Our results suggested that DEHP is associated with free T4 in girls and that DBP is associated with free T3 in boys. Higher DEHP metabolite concentrations exerted larger effects on free T3 in boys. These results reveal the gender-specific relationships between phthalate metabolites and thyroid hormones.

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A critical analysis of the biological impacts of plasticizers on wildlife.

Werner Kloas, Jörg Oehlmann, Oana Jagnytsch … (2009)

This review provides a critical analysis of the biological effects of the most widely used plasticizers, including dibutyl phthalate, diethylhexyl phthalate, dimethyl phthalate, butyl benzyl phthalate and bisphenol A (BPA), on wildlife, with a focus on annelids (both aquatic and terrestrial), molluscs, crustaceans, insects, fish and amphibians. Moreover, the paper provides novel data on the biological effects of some of these plasticizers in invertebrates, fish and amphibians. Phthalates and BPA have been shown to affect reproduction in all studied animal groups, to impair development in crustaceans and amphibians and to induce genetic aberrations. Molluscs, crustaceans and amphibians appear to be especially sensitive to these compounds, and biological effects are observed at environmentally relevant exposures in the low ng l(-1) to microg l(-1) range. In contrast, most effects in fish (except for disturbance in spermatogenesis) occur at higher concentrations. Most plasticizers appear to act by interfering with the functioning of various hormone systems, but some phthalates have wider pathways of disruption. Effect concentrations of plasticizers in laboratory experiments coincide with measured environmental concentrations, and thus there is a very real potential for effects of these chemicals on some wildlife populations. The most striking gaps in our current knowledge on the impacts of plasticizers on wildlife are the lack of data for long-term exposures to environmentally relevant concentrations and their ecotoxicity when part of complex mixtures. Furthermore, the hazard of plasticizers has been investigated in annelids, molluscs and arthropods only, and given the sensitivity of some invertebrates, effects assessments are warranted in other invertebrate phyla.

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Reproductive and developmental toxicity of phthalates.

Erik Ropstad, Jan Lyche, Arno C. Gutleb … (2009)

The purposes of this review are to (1) evaluate human and experimental evidence for adverse effects on reproduction and development in humans, produced by exposure to phthalates, and (2) identify knowledge gaps as for future studies. The widespread use of phthalates in consumer products leads to ubiquitous and constant exposure of humans to these chemicals. Phthalates were postulated to produce endocrine-disrupting effects in rodents, where fetal exposure to these compounds was found to induce developmental and reproductive toxicity. The adverse effects observed in rodent models raised concerns as to whether exposure to phthalates represents a potential health risk to humans. At present, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) have been demonstrated to produce reproductive and developmental toxicity; thus, this review focuses on these chemicals. For the general population, DEHP exposure is predominantly via food. The average concentrations of phthalates are highest in children and decrease with age. At present, DEHP exposures in the general population appear to be close to the tolerable daily intake (TDI), suggesting that at least some individuals exceed the TDI. In addition, specific high-risk groups exist with internal levels that are several orders of magnitude above average. Urinary metabolites used as biomarkers for the internal levels provide additional means to determine more specifically phthalate exposure levels in both general and high-risk populations. However, exposure data are not consistent and there are indications that secondary metabolites may be more accurate indicators of the internal exposure compared to primary metabolites. The present human toxicity data are not sufficient for evaluating the occurrence of reproductive effects following phthalate exposure in humans, based on existing relevant animal data. This is especially the case for data on female reproductive toxicity, which are scarce. Therefore, future research needs to focus on developmental and reproductive endpoints in humans. It should be noted that phthalates occur in mixtures but most toxicological information is based on single compounds. Thus, it is concluded that it is important to improve the knowledge of toxic interactions among the different chemicals and to develop measures for combined exposure to various groups of phthalates.

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Childhood Exposure to Phthalates: Associations with Thyroid Function, Insulin-like Growth Factor I, and Growth

Malene Boas, Hanne Frederiksen, Ulla Feldt-Rasmussen … (2010)

Background Phthalates are widely used chemicals, and human exposure is extensive. Recent studies have indicated that phthalates may have thyroid-disrupting properties. Objective We aimed to assess concentrations of phthalate metabolites in urine samples from Danish children and to investigate the associations with thyroid function, insulin-like growth factor I (IGF-I), and growth. Methods In 845 children 4–9 years of age, we determined urinary concentrations of 12 phthalate metabolites and serum levels of thyroid-stimulating hormone, thyroid hormones, and IGF-I. Results Phthalate metabolites were detected in all urine samples, of which monobutyl phthalate was present in highest concentration. Phthalate metabolites were negatively associated with serum levels of free and total triiodothyronine, although statistically significant primarily in girls. Metabolites of di(2-ethylhexyl) phthalate and diisononyl phthalate were negatively associated with IGF-I in boys. Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes. Conclusions Our study showed negative associations between urinary phthalate concentrations and thyroid hormones, IGF-I, and growth in children. Although our study was not designed to reveal the mechanism of action, the overall coherent negative associations between urine phthalate and thyroid and growth parameters may suggest causative negative roles of phthalate exposures for child health.

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Author and article information

Contributors

Huixiao Hong: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Environ Res Public Health

Journal ID (iso-abbrev): Int J Environ Res Public Health

Journal ID (publisher-id): ijerph

Title: International Journal of Environmental Research and Public Health

Publisher: MDPI

ISSN (Print): 1661-7827

ISSN (Electronic): 1660-4601

Publication date (Electronic): 29 January 2017

Publication date (Print): February 2017

Volume: 14

Issue: 2

Electronic Location Identifier: 123

Affiliations

[1 ]Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan; wengtei2@ 123456ntu.edu.tw (T.-I.W.); paishanchen@ 123456ntu.edu.tw (P.-S.C.)

[2 ]Forensic and Clinical Toxicology Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10051, Taiwan; conrad@ 123456ntu.edu.tw

[3 ]Department of Emergency Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; lovingbest@ 123456yahoo.com.tw

[4 ]Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 10055, Taiwan; miffych@ 123456gmail.com (M.-H.C.); f92844007@ 123456gmail.com (G.-W.L.)

[5 ]Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10051, Taiwan

[6 ]Department of Public Health, National Taiwan University College of Public Health, Taipei 10055, Taiwan

Author notes

[* ]Correspondence: pchen@ 123456ntu.edu.tw ; Tel.: +886-2-2358-2402

Article

Publisher ID: ijerph-14-00123

DOI: 10.3390/ijerph14020123

PMC ID: 5334677

PubMed ID: 28146055

SO-VID: 24ecbc25-edcd-4e85-9444-664977502e3d

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

History

Date received : 06 November 2016

Date accepted : 20 January 2017

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Effects of Gender on the Association of Urinary Phthalate Metabolites with Thyroid Hormones in Children: A Prospective Cohort Study in Taiwan

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Chinese Journal of School Health

Most cited references 28

A critical analysis of the biological impacts of plasticizers on wildlife.

Reproductive and developmental toxicity of phthalates.

Childhood Exposure to Phthalates: Associations with Thyroid Function, Insulin-like Growth Factor I, and Growth

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Cited by 11

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