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      Prenatal Phthalate Exposure Is Associated with Childhood Behavior and Executive Functioning

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          Abstract

          Background

          Experimental and observational studies have reported biological consequences of phthalate exposure relevant to neurodevelopment.

          Objective

          Our goal was to examine the association of prenatal phthalate exposure with behavior and executive functioning at 4–9 years of age.

          Methods

          The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 ( n = 404). Third-trimester maternal urines were collected and analyzed for phthalate metabolites. Children ( n = 188, n = 365 visits) were assessed for cognitive and behavioral development between the ages of 4 and 9 years.

          Results

          In multivariate adjusted models, increased log e concentrations of low molecular weight (LMW) phthalate metabolites were associated with poorer scores on the aggression [β = 1.24; 95% confidence interval (CI), 0.15– 2.34], conduct problems (β = 2.40; 95% CI, 1.34–3.46), attention problems (β = 1.29; 95% CI, 0.16– 2.41), and depression (β = 1.18; 95% CI, 0.11–2.24) clinical scales; and externalizing problems (β = 1.75; 95% CI, 0.61–2.88) and behavioral symptom index (β = 1.55; 95% CI, 0.39–2.71) composite scales. Increased log e concentrations of LMW phthalates were also associated with poorer scores on the global executive composite index (β = 1.23; 95% CI, 0.09–2.36) and the emotional control scale (β = 1.33; 95% CI, 0.18– 2.49).

          Conclusion

          Behavioral domains adversely associated with prenatal exposure to LMW phthalates in our study are commonly found to be affected in children clinically diagnosed with conduct or attention deficit hyperactivity disorders.

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          Most cited references25

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          Prenatal Phenol and Phthalate Exposures and Birth Outcomes

          Background Many phthalates and phenols are hormonally active and are suspected to alter the course of development. Objective We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth. Methods We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. Results Median urinary concentrations were > 10 μg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07–1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (−210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71–348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. Conclusions We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.
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            Temporal Variability of Urinary Phthalate Metabolite Levels in Men of Reproductive Age

            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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              Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta).

              To determine the physiological roles of peroxisome proliferator-activated receptor beta (PPARbeta), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPARbeta gene. Homozygous PPARbeta-null term fetuses were smaller than controls, and this phenotype persisted postnatally. Gonadal adipose stores were smaller, and constitutive mRNA levels of CD36 were higher, in PPARbeta-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPARbeta-null mice. PPARbeta was not required for induction of mRNAs involved in epidermal differentiation induced by O-tetradecanoylphorbol-13-acetate (TPA). The hyperplastic response observed in the epidermis after TPA application was significantly greater in the PPARbeta-null mice than in controls. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than in similarly treated PPARbeta-null mice. These results are the first to provide in vivo evidence of significant roles for PPARbeta in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                April 2010
                28 January 2010
                : 118
                : 4
                : 565-571
                Affiliations
                [1 ] Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA
                [2 ] Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, New York, USA
                [3 ] National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
                Author notes
                Address correspondence to S. Engel, Department of Preventive Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1057, New York, NY 10029 USA. Telephone: (212) 824-7030. Fax: (212) 966-0407. E-mail: stephanie.engel@ 123456mssm.edu

                The authors declare they have no competing financial interests.

                Article
                ehp-118-565
                10.1289/ehp.0901470
                2854736
                20106747
                bdb0026a-9ad8-4f1c-bb11-338e9d0599fe
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 16 September 2009
                : 8 January 2010
                Categories
                Research
                Children's Health

                Public health
                basc,environmental exposure,phthalate,brief,attention deficit hyperactivity disorder
                Public health
                basc, environmental exposure, phthalate, brief, attention deficit hyperactivity disorder

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