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      Transdermal Uptake of Diethyl Phthalate and Di( n-butyl) Phthalate Directly from Air: Experimental Verification

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          Abstract

          Background

          Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been experimentally evaluated and has been largely overlooked when assessing uptake of phthalate esters.

          Objectives

          This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di( n-butyl) phthalate (DnBP) in humans.

          Methods

          In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air concentrations of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concentrations substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 hr later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, corrected for background and hood air exposures.

          Results

          For DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m 3 in air) compared with an inhalation intake of 3.8 μg/(μg/m 3 in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m 3 in air) compared with an inhalation intake of 3.9 μg/(μg/m 3 in air).

          Conclusions

          This study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile organic compounds (SVOCs) whose molecular weight and lipid/air partition coefficient are in the appropriate range, direct absorption from air is also anticipated to be significant.

          Citation

          Weschler CJ, Bekö G, Koch HM, Salthammer T, Schripp T, Toftum J, Clausen G. 2015. Transdermal uptake of diethyl phthalate and di( n-butyl) phthalate directly from air: experimental verification. Environ Health Perspect 123:928–934;  http://dx.doi.org/10.1289/ehp.1409151

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          Most cited references50

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          Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust.

          Chemicals identified as endocrine-disrupting compounds (EDCs) have widespread consumer uses, yet little is known about indoor exposure. We sampled indoor air and dust in 120 homes, analyzing for 89 organic chemicals identified as EDCs. Fifty-two compounds were detected in air and 66 were detected in dust. These are the first reported measures in residential environments for over 30 of the compounds, including several detected at the highest concentrations. The number of compounds detected per home ranged from 13 to 28 in air and from 6 to 42 in dust. The most abundant compounds in air included phthalates (plasticizers, emulsifiers), o-phenylphenol (disinfectant), 4-nonylphenol (detergent metabolite), and 4-tert-butylphenol (adhesive) with typical concentrations in the range of 50-1500 ng/m3. The penta- and tetrabrominated diphenyl ethers (flame retardants) were frequently detected in dust, and 2,3-dibromo-1-propanol, the carcinogenic intermediate of a flame retardant banned in 1977, was detected in air and dust. Twenty-three pesticides were detected in air and 27 were detected in dust, the most abundant being permethrins and the synergist piperonyl butoxide. The banned pesticides heptachlor, chlordane, methoxychlor, and DDT were also frequently detected, suggesting limited indoor degradation. Detected concentrations exceeded government health-based guidelines for 15 compounds, but no guidelines are available for 28 compounds, and existing guidelines do not consider endocrine effects. This study provides a basis for prioritizing toxicology and exposure research for individual EDCs and mixtures and provides new tools for exposure assessment in health studies.
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            What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?

            Phthalic acid esters (phthalates) are used as plasticizers in numerous consumer products, commodities, and building materials. Consequently, phthalates are found in human residential and occupational environments in high concentrations, both in air and in dust. Phthalates are also ubiquitous food and environmental contaminants. An increasing number of studies sampling human urine reveal the ubiquitous phthalate exposure of consumers in industrialized countries. At the same time, recent toxicological studies have demonstrated the potential of the most important phthalates to disturb the human hormonal system and human sexual development and reproduction. Additionally, phthalates are suspected to trigger asthma and dermal diseases in children. To find the important sources of phthalates in Europeans, a scenario-based approach is applied here. Scenarios representing realistic exposure situations are generated to calculate the age-specific range in daily consumer exposure to eight phthalates. The scenarios demonstrate that exposure of infant and adult consumers is caused by different sources in many cases. Infant consumers experience significantly higher daily exposure to phthalates in relation to their body weight than older consumers. The use of consumer products and different indoor sources dominate the exposure to dimethyl, diethyl, benzylbutyl, diisononyl, and diisodecyl phthalates, whereas food has a major influence on the exposure to diisobutyl, dibutyl, and di-2-ethylhexyl phthalates. The scenario-based approach chosen in the present study provides a link between the knowledge on emission sources of phthalates and the concentrations of phthalate metabolites found in human urine.
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              Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010

              Background: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures. Objective: We examined temporal trends in urinary concentrations of phthalate metabolites in the general U.S. population and whether trends vary by sociodemographic characteristics. Methods: We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001–2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models. Results: LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and ΣDEHP metabolites decreased between 2001–2002 and 2009–2010 [percent change (95% CI): –42% (–49, –34); –17% (–23, –9); –32% (–39, –23) and –37% (–46, –26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of ΣDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (p interaction < 0.01). Conclusions: Exposure of the U.S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends. Citation: Zota AZ, Calafat AM, Woodruff TJ. 2014. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001–2010. Environ Health Perspect 122:235–241; http://dx.doi.org/10.1289/ehp.1306681
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                NLM-Export
                0091-6765
                1552-9924
                07 April 2015
                October 2015
                : 123
                : 10
                : 928-934
                Affiliations
                [1 ]Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA
                [2 ]International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby, Denmark
                [3 ]Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany
                [4 ]Department of Material Analysis and Indoor Chemistry, Fraunhofer WKI, Braunschweig, Germany
                Author notes
                Address correspondence to C.J. Weschler, Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Rd., Piscataway, NJ 08854 USA. Telephone: (848) 445-2073. E-mail: weschlch@ 123456rwjms.rutgers.edu
                Article
                ehp.1409151
                10.1289/ehp.1409151
                4590762
                25850107
                12e19769-c0da-4f09-a0c8-e559ff60e0b9

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                : 30 August 2014
                : 03 April 2015
                : 07 April 2015
                : 01 October 2015
                Categories
                Research

                Public health
                Public health

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