Derivation of Biomonitoring Equivalents for di(2-ethylhexyl)phthalate (CAS No. 117-81-7).

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of an environmental chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for di(2-ethylhexyl)phthalate (DEHP) from Health Canada, the United States Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), the European Chemicals Bureau (ECB), and the European Food Safety Authority (EFSA). BE values corresponding to the oral reference dose (RfD), minimal risk level (MRL) or tolerable daily intake (TDI) estimates from these agencies were derived based on data on excretion fractions of key urinary metabolites. BE values based on the sum of three, four, and five of the most predominant and commonly-measured metabolites of DEHP are presented. These values may be used as screening tools for evaluation of biomonitoring data for DEHP metabolites in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for DEHP relative to other chemicals.

[1]  Bernhard Liebl,et al.  Intake of phthalates and di(2-ethylhexyl)adipate: results of the Integrated Exposure Assessment Survey based on duplicate diet samples and biomonitoring data. , 2007, Environment international.

[2]  Dana B Barr,et al.  Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-III) , 2004, Journal of Exposure Analysis and Environmental Epidemiology.

[3]  Samuel P. Caudill,et al.  Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements , 2004, Environmental health perspectives.

[4]  R Tardif,et al.  A PBPK modeling-based approach to account for interactions in the health risk assessment of chemical mixtures. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[5]  Richard A Fenske,et al.  Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State , 2005, Journal of Exposure Analysis and Environmental Epidemiology.

[6]  U. Magnusson,et al.  Kinetics of orally administered di(2-ethylhexyl) phthalate and its metabolite, mono(2-ethylhexyl) phthalate, in male pigs , 2004, Archives of Toxicology.

[7]  L L Needham,et al.  Human exposure estimates for phthalates. , 2000, Environmental health perspectives.

[8]  Jesper Kristiansen,et al.  Comparison of uncertainties related to standardization of urine samples with volume and creatinine concentration. , 2004, The Annals of occupational hygiene.

[9]  T. Remer,et al.  Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. , 2002, The American journal of clinical nutrition.

[10]  Ibrahim Chahoud,et al.  Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets. , 2004, Toxicology and applied pharmacology.

[11]  Holger M. Koch,et al.  Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP , 2004, Archives of Toxicology.

[12]  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.

[13]  Sean M Hays,et al.  Biomonitoring Equivalents (BE) dossier for 2,4-dichlorophenoxyacetic acid (2,4-D) (CAS No. 94-75-7). , 2008, Regulatory toxicology and pharmacology : RTP.

[14]  D. Shen,et al.  Effects of route of administration and repetitive dosing on the disposition kinetics of di(2-ethylhexyl) phthalate and its mono-de-esterified metabolite in rats. , 1985, Toxicology and applied pharmacology.

[15]  Pakalin Sazan,et al.  European Union Risk Assessment Report - bis (2-ethylhexyl) phthalate (DEHP) , 2008 .

[16]  Sean M Hays,et al.  Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context , 2009, Journal of applied toxicology : JAT.

[17]  L. Bankir,et al.  Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[18]  K Krishnan,et al.  Physiologically based modeling of the maximal effect of metabolic interactions on the kinetics of components of complex chemical mixtures. , 2000, Journal of toxicology and environmental health. Part A.

[19]  J. Furr,et al.  A mixture of five phthalate esters inhibits fetal testicular testosterone production in the sprague-dawley rat in a cumulative, dose-additive manner. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  Bruce H Alexander,et al.  Agreement of pesticide biomarkers between morning void and 24-h urine samples from farmers and their children , 2007, Journal of Exposure Science and Environmental Epidemiology.

[21]  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.

[22]  A. Calafat,et al.  Measurement of eight urinary metabolites of di(2-ethylhexyl) phthalate as biomarkers for human exposure assessment , 2006, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[23]  Michigan.,et al.  Toxicological profile for dichloropropenes , 2008 .

[24]  Shoma Berkemeyer,et al.  Longitudinal examination of 24-h urinary iodine excretion in schoolchildren as a sensitive, hydration status-independent research tool for studying iodine status. , 2006, The American journal of clinical nutrition.

[25]  A. Appendices,et al.  European Union Risk Assessment Report , 2008 .

[26]  P. Albro,et al.  Metabolism of di(2-ethylhexyl)phthalate. , 1989, Drug metabolism reviews.

[27]  R A Becker,et al.  Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective. , 2007, Regulatory toxicology and pharmacology : RTP.

[28]  P. Albro,et al.  Toxic potential of the plasticizer Di(2-ethylhexyl) phthalate in the context of its disposition and metabolism in primates and man. , 1982, Environmental health perspectives.

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

[30]  Conrad Brunk,et al.  Guidelines for the derivation of Biomonitoring Equivalents: report from the Biomonitoring Equivalents Expert Workshop. , 2008, Regulatory toxicology and pharmacology : RTP.

[31]  Holger M Koch,et al.  A simple pharmacokinetic model to characterize exposure of Americans to Di-2-ethylhexyl phthalate , 2010, Journal of Exposure Science and Environmental Epidemiology.

[32]  Holger M. Koch,et al.  New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP , 2005, Archives of Toxicology.

[33]  C Springall,et al.  A biomarker approach to measuring human dietary exposure to certain phthalate diesters , 2001, Food additives and contaminants.

[34]  M. O'Rourke,et al.  Pesticide exposure and creatinine variation among young children , 2000, Journal of Exposure Analysis and Environmental Epidemiology.

[35]  Conrad Brunk,et al.  Guidelines for the communication of Biomonitoring Equivalents: report from the Biomonitoring Equivalents Expert Workshop. , 2008, Regulatory toxicology and pharmacology : RTP.

[36]  H. Koo,et al.  Toxicokinetic Relationship Between Di(2-ethylhexyl) Phthalate (DEHP) and Mono(2-ethylhexyl) Phthalate in Rats , 2007, Journal of toxicology and environmental health. Part A.