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      Age and Sex-Specific Relationships between Phthalate Exposures and Obesity in Chinese Children at Puberty

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          Abstract

          Objective

          To examine the age and sex-specific associations of urine levels of six mono-phthalates with body size and fat distribution in Chinese children at puberty.

          Materials and Methods

          Four hundred and ninety-three school-aged children (247 boys, 246 girls) were recruited. Obesity related anthropometric indices were measured and body fat proportion (BF%) was calculated. Spot urine samples were collected and phthalate monoesters were detected by an API 2000 electrospray triple quadrupole mass spectrometer (ESI-MS/MS). Associations between phthalate exposure and overweight/obesity measures and their trends were examined by multiple linear regression and Logistic regression analyses, respectively.

          Results

          Di-2-ethylhexyl phthalate (DEHP) metabolites and monobutyl phthalate (MBP) were found to be the most detectable chemicals. In 8–10 years (yrs) group, concentrations of MEHP and MBP were significantly higher in girls than those in boys. However, concentrations of all phthalate monoesters, except for MEP and MEHP, in 11–13 yrs boys were significantly higher than those in girls. After adjusting for confounders including puberty onset, urinary concentrations of MBP and sum of low molecular-weight phthalate metabolites (∑LMP) were positively associated with boys' obesity in a concentration-effect manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (∑MEHP) were negatively associated with girls' obesity. Associations between phthalate exposure levels and BMI z-score changes were age- and sex-specific in school-age children.

          Conclusion

          There are age and sex-specific concentration-effect associations between phthalate exposure and fat distribution in Chinese children. Urinary phthalate levels in 11–13 yrs boys were about 30 percent higher than those in girls, and ∑MEHP levels in younger boys (<10 yrs) were significantly higher than those in elder boys (>10 yrs). Associations were positive for MBP and ∑LMP with both BMI z-score and fat distribution in boys >10 years of age, and negative for ∑MEHP with fat distribution in girls <10 years of age.

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          Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males

          Richard Stahlhut, Edwin van Wijngaarden, Timothy Dye … (2007)
          Background Phthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes. Objectives Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance. Methods Subjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Results In model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values ≤ 0.013) and three with increased HOMA (MBP, MBzP, and MEP; p-values ≤ 0.011). When we also adjusted for renal and hepatic function, parameter estimates declined but all significant results remained so except HOMA-MBP. Conclusions In this national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abdominal obesity and insulin resistance. If confirmed by longitudinal studies, our findings would suggest that exposure to these phthalates may contribute to the population burden of obesity, insulin resistance, and related clinical disorders.
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            Overweight and obesity in China.

            Yangfeng Wu (2006)
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              Temporal Variability of Urinary Phthalate Metabolite Levels in Men of Reproductive Age

              Russ Hauser, John D. Meeker, Sohee Park … (2004)
              Phthalates are a family of multifunctional chemicals widely used in personal care and other consumer products. The ubiquitous use of phthalates results in human exposure through multiple sources and routes, including dietary ingestion, dermal absorption, inhalation, and parenteral exposure from medical devices containing phthalates. We explored the temporal variability over 3 months in urinary phthalate metabolite levels among 11 men who collected up to nine urine samples each during this time period. Eight phthalate metabolites were measured by solid-phase extraction–high-performance liquid chromatography–tandem mass spectrometry. Statistical analyses were performed to determine the between- and within-subject variance apportionment, and the sensitivity and specificity of a single urine sample to classify a subject’s 3-month average exposure. Five of the eight phthalates were frequently detected. Monoethyl phthalate (MEP) was detected in 100% of samples; monobutyl phthalate, monobenzyl phthalate, mono-2-ethylhexyl phthalate (MEHP), and monomethyl phthalate were detected in > 90% of samples. Although we found both substantial day-to-day and month-to-month variability in each individual’s urinary phthalate metabolite levels, a single urine sample was moderately predictive of each subject’s exposure over 3 months. The sensitivities ranged from 0.56 to 0.74. Both the degree of between- and within-subject variance and the predictive ability of a single urine sample differed among phthalate metabolites. In particular, a single urine sample was most predictive for MEP and least predictive for MEHP. These results suggest that the most efficient exposure assessment strategy for a particular study may depend on the phthalates of interest.
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                Author and article information

                Contributors
                Antonio Gonzalez-Bulnes: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2014
                Publication date (Electronic): 14 August 2014
                Volume: 9
                Issue: 8
                Electronic Location Identifier: e104852
                Affiliations
                [1 ]Department of Environment Health, School of Public Health/Key Laboratory of Public Health Safety of Chinese Ministry of Education, Fudan University, Shanghai, China
                [2 ]State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, China
                [3 ]Department of Maternal, Child and Adolescent Health, School of Public Health/Key Laboratory of Public Health Safety of Chinese Ministry of Education, Fudan University, Shanghai, China
                INIA, Spain
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HS. Performed the experiments: DL Y. Zhao LL. Analyzed the data: LC Y. Zhang. Contributed reagents/materials/analysis tools: XM LZ. Wrote the paper: Y. Zhang HS XM.

                Article
                Publisher ID: PONE-D-14-00549
                DOI: 10.1371/journal.pone.0104852
                PMC ID: 4133266
                PubMed ID: 25121758
                SO-VID: d31442d3-d2e7-4811-b8a0-ee69c86ec67e
                Copyright statement: Copyright @ 2014
                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 author and source are credited.

                History
                Date received : 10 January 2014
                Date accepted : 17 July 2014
                Page count
                Pages: 11
                Funding
                This research was supported by grants from the Natural Science Foundation of China (Grant 81072263, to Y. Z.; Grant 81172684, to H. S.), and by an award from the Shanghai Municipal Health Bureau (Grant 12GWZX0301, to X. Q.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Nutrition
                Subject: Physiology
                Subject: Physiological Parameters
                Subject: Body Weight
                Subject: Obesity
                Subject: Ecology and Environmental Sciences
                Subject: Environmental Chemistry
                Subject: Pollutants
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Pediatric Epidemiology
                Subject: Health Care
                Subject: Health Care Policy
                Subject: Child and Adolescent Health Policy
                Subject: Environmental Health
                Subject: Pediatrics
                Subject: Child Development
                Subject: Child Health
                Subject: Public and Occupational Health
                Subject: Preventive Medicine
                Subject: Urology

                ScienceOpen disciplines: Uncategorized
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