Research Commentary Assessing Human Exposure to Phthalates Using Monoesters and Their Oxidized Metabolites as Biomarkers

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Author	Malek, Nicole A. Reidy, John A. Silva, Manori J. Needham, Larry L. Kato, Kayoko Barr, Dana B. Sadowski, Melissa Calafat, Antonia M. Hurtz, Donald
Abstract	Phthalates are a group of industrial chemicals with many commercial uses, such as solvents, additives, and plasticizers. For example, di-(2-ethylhexyl) phthalate (DEHP) is added in varying amounts to certain plastics, such as polyvinyl chloride, to increase their flexibility. In humans, phthalates are metabolized to their respective monoesters, conjugated, and eliminated. However, despite the high production and use of DEHP, we have recently found that the urinary levels of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in 2,541 persons in the United States were lower than we anticipated, especially when compared with urinary metabolite levels of other commonly used phthalates. This finding raised questions about the sensitivity of this biomarker for assessing DEHP exposure. We explored the utility of two other DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), as additional DEHP biomarkers. These metabolites are formed by oxidative metabolism of MEHP. In urine from 62 people, both the range and the mean urinary levels of MEOHP and MEHHP were on average 4-fold higher than those of MEHP; the mean of the individual ratios of MEHHP/MEOHP, MEHHP/MEHP, and MEOHP/MEHP were 1.4, 8.2, and 5.9, respectively. These data suggest that MEOHP and MEHHP are more sensitive biomarkers of exposure to DEHP than is MEHP. These findings also suggest a predominant human metabolic route for DEHP hydrolysis to MEHP followed by oxidation of MEHP; they also imply that a similar mechanism may be relevant for other high-molecular–weight phthalates, such as di-n-octyl, di-isononyl, and di-isodecyl phthalates. Key words: DEHP, exposure, human, phthalate, urine. Environ Health
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Subject Keyword	Dehp Metabolite High Production Respective Monoesters Meohp Mehp Certain Plastic Many Commercial Us Urinary Metabolite Level Additional Dehp Biomarkers Oxidized Metabolite Dehp Hydrolysis Phthalates Using Monoesters Sensitive Biomarkers High-molecular Weight Phthalates Mehhp Meohp Industrial Chemical Predominant Human Metabolic Route Polyvinyl Chloride Research Commentary Assessing Human Exposure Environ Health Individual Ratio Di-isodecyl Phthalates Mean Urinary Level Urinary Level Mehhp Mehp Oxidative Metabolism Dehp Exposure Similar Mechanism
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