title: Urinary DEHP metabolites and fasting time in NHANES.
abstract: Exposure assessment analyses conducted in Europe have concluded that the primary pathway of exposure to di(2-ethylhexyl) phthalate (DEHP) is through the diet. The purpose of this study is to evaluate whether urinary DEHP metabolite data from the 2007-2008 National Health and Nutritional Examination Survey (NHANES) demonstrate relationships with reported food-fasting time consistent with diet as the predominant exposure pathway. Previous controlled-dosing data demonstrate that DEHP metabolite concentrations in urine first rise and then decline over time, with first-order elimination becoming evident at about 6 h post exposure. Regression of the concentrations of four key DEHP metabolites vs reported fasting times between 6 and 18 h in adults resulted in apparent population-based urinary elimination half-lives, consistent with those previously determined in a controlled-dosing experiment, supporting the importance of the dietary pathway for DEHP. For fasting times less than about 6 h, sampling session (morning, afternoon, or evening) affected the measured metabolite concentrations. Evening samples showed the highest metabolite concentrations, supporting a hypothesis of recent daily dietary exposures from multiple meals, whereas morning and afternoon samples for fasting times less than 6 h were similar and somewhat lower than evening samples, consistent with less-substantial early day dietary exposure. Variations in children's bodyweight-normalized creatinine excretion and food intake rates contribute to a strong inverse relationship between urinary DEHP metabolite concentrations and age under age 18. Finally, a previously published pharmacokinetic model for DEHP demonstrates that time since previous urinary void, a parameter not measured in NHANES, is predicted to result in non-random effects on measured urinary concentrations.
authors.affiliation: Summit Toxicology, LLP, Falls Church, Virginia 22044, USA. laylward@summittoxicology.com
authors.forename: Lesa L
authors.initials: LL
authors.lastname: Aylward
authors.forename: Matthew
authors.initials: M
authors.lastname: Lorber
authors.forename: Sean M
authors.initials: SM
authors.lastname: Hays
mesh_terms: D000328:Adult; D004051:Diethylhexyl Phthalate / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D004781:Environmental Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D009749:Nutrition Surveys; D010968:Plasticizers / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D010968:Plasticizers; D004051:Diethylhexyl Phthalate