Urinary phthalate metabolites and their biotransformation products: predictors and temporal variability among men and women

Most epidemiology studies investigating the potential adverse health effects in relation to phthalates measure the urinary concentration of the free plus glucuronidated species of phthalate metabolites (i.e., total concentration) to estimate exposure. However, the free species may represent the biologically relevant dose. In this study, we collected 943 urine samples from 112 men and 157 women and assessed the between- and within-person variability and predictors of (1) the free and total urinary concentrations of phthalate metabolites, and (2) the percentage of free phthalate metabolites (a potential phenotypic indicator of individual susceptibility). We also explored the proportion of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites contributed to by the bioactive mono-2-ethylhexyl phthalate (MEHP), considered a possible indicator of susceptibility to phthalate exposure. The percentage of phthalate metabolites present in the free form was less stable over time than the total metabolite concentration, and, therefore, it is not likely a useful indicator of metabolic susceptibility. Thus, the added costs and effort involved in the measurement of free in addition to total metabolite concentrations in large-scale studies may not be justified. Conversely, the proportion of DEHP metabolites contributed to by MEHP was more stable within individuals over time and may be a promising indicator of susceptibility if time of day of sample collection is carefully considered.

[1]  J. Manson,et al.  Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year period. , 1995, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[2]  Frederica P. Perera,et al.  Characterization of Phthalate Exposure among Pregnant Women Assessed by Repeat Air and Urine Samples , 2008, Environmental health perspectives.

[3]  A. Calafat,et al.  Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers. , 2003, Environmental health perspectives.

[4]  J. Brock,et al.  Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. , 2000, Analytical chemistry.

[5]  J. Brock,et al.  Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[6]  A. Calafat,et al.  Analysis of human urine for fifteen phthalate metabolites using automated solid-phase extraction. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[7]  Holger M Koch,et al.  A critical evaluation of the creatinine correction approach: Can it underestimate intakes of phthalates? A case study with di-2-ethylhexyl phthalate , 2011, Journal of Exposure Science and Environmental Epidemiology.

[8]  A. Calafat,et al.  Determination of 16 phthalate metabolites in urine using automated sample preparation and on-line preconcentration/high-performance liquid chromatography/tandem mass spectrometry. , 2005, Analytical chemistry.

[9]  Holger M Koch,et al.  Human body burdens of chemicals used in plastic manufacture , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[10]  Antonia M. Calafat,et al.  Integrating Biomonitoring Exposure Data into the Risk Assessment Process: Phthalates [Diethyl Phthalate and Di(2-ethylhexyl) Phthalate] as a Case Study , 2006, Environmental health perspectives.

[11]  Antonia M. Calafat,et al.  Personal Care Product Use Predicts Urinary Concentrations of Some Phthalate Monoesters , 2005, Environmental health perspectives.

[12]  Erik Ropstad,et al.  Reproductive and Developmental Toxicity of Phthalates , 2009, Journal of toxicology and environmental health. Part B, Critical reviews.

[13]  A. Calafat,et al.  Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. , 2008, Environmental research.

[14]  Dana B Barr,et al.  Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. , 2003, Environmental health perspectives.

[15]  N. Skakkebaek,et al.  Metabolism of phthalates in humans. , 2007, Molecular nutrition & food research.

[16]  A. Calafat,et al.  Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. , 2009, Journal of andrology.

[17]  R. Hauser.  Urinary phthalate metabolites and semen quality: a review of a potential biomarker of susceptibility. , 2008, International journal of andrology.

[18]  D. Baird,et al.  Reproducibility of urinary phthalate metabolites in first morning urine samples. , 2002, Environmental health perspectives.

[19]  A. Calafat,et al.  Intra- and inter-individual variability of urinary phthalate metabolite concentrations in Hmong women of reproductive age , 2010, Journal of Exposure Science and Environmental Epidemiology.

[20]  Antonia M. Calafat,et al.  Di(2-ethylhexyl) Phthalate Metabolites May Alter Thyroid Hormone Levels in Men , 2007, Environmental health perspectives.

[21]  S. Swan,et al.  Phthalates and other additives in plastics: human exposure and associated health outcomes , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[22]  A. Calafat,et al.  Quantification of 22 phthalate metabolites in human urine. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[23]  Shanna H Swan,et al.  Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. , 2008, Environmental research.

[24]  K. Hungerbühler,et al.  What Are the Sources of Exposure to Eight Frequently Used Phthalic Acid Esters in Europeans? , 2006, Risk analysis : an official publication of the Society for Risk Analysis.

[25]  A. Just,et al.  Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York city , 2010, Journal of Exposure Science and Environmental Epidemiology.

[26]  A. Calafat,et al.  PHTHALATES AND HUMAN HEALTH , 2005, Occupational and Environmental Medicine.

[27]  J. Angerer,et al.  Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an update and latest results. , 2006, International journal of andrology.

[28]  C. C. Hodge,et al.  Glucuronidation patterns of common urinary and serum monoester phthalate metabolites , 2005, Archives of Toxicology.

[29]  Kelly K Ferguson,et al.  Urinary phthalate metabolites in relation to biomarkers of inflammation and oxidative stress: NHANES 1999-2006. , 2011, Environmental research.

[30]  Bernhard Liebl,et al.  Occurrence and daily variation of phthalate metabolites in the urine of an adult population. , 2007, International journal of hygiene and environmental health.

[31]  A. Calafat,et al.  DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. , 2007, Human reproduction.

[32]  Antonia M. Calafat,et al.  Temporal Variability of Urinary Phthalate Metabolite Levels in Men of Reproductive Age , 2004, Environmental health perspectives.

[33]  Antonia M. Calafat,et al.  Variability over 1 Week in the Urinary Concentrations of Metabolites of Diethyl Phthalate and Di(2-Ethylhexyl) Phthalate among Eight Adults: An Observational Study , 2010, Environmental health perspectives.