title: A critical evaluation of the creatinine correction approach: can it underestimate intakes of phthalates? A case study with di-2-ethylhexyl phthalate.
abstract: The creatinine correction approach has been used to estimate daily intake for contaminants whose primary route of elimination is through urine. This method is challenged using the phthalate di-2-ethylhexyl phthalate (DEHP) as an example. An alternate prediction approach based on human experimental metabolism and urinary excretion data on DEHP was developed. This alternate model was developed from urine measurements of four metabolites of DEHP from two individuals partaking in different experiments, for up to 44 h after known exposures. Particular attention was paid to the changing ratios of the metabolites over time: they took a certain form when exposure was in the "near" (the past few hours) versus the "distant" (24 h or more) past. The creatinine correction approach was applied to measurements of the same four metabolites from 18 individuals in the National Health And Nutrition Evaluation Survey (NHANES) 2003/2004. The alternate model was also applied to these individuals, and the results were compared. Predictions using the two methods were similar or the creatinine correction predicted higher concentrations when the ratio suggested that the DEHP exposure was "near" in time, but the alternate approach predicted intakes that were an order of magnitude higher when the ratios suggested that the intake was "distant". As much as 25% of all NHANES measurements contain metabolites whose key ratio suggest that exposure was "distant". Uncertainties notwithstanding, the analysis in this article suggests that the creatinine correction approach should be used cautiously for DEHP and possibly other contaminants with similar exposure characteristics: rapid metabolism with metabolite urine elimination half-lives on the order of hours, and exposure patterns that may not be continuous and ongoing.
authors.affiliation: Office of Research and Development, United States Environmental Protection Agency, Washington, District of Columbia 20460, USA. lorber.matthew@epa.gov
authors.forename: Matthew
authors.initials: M
authors.lastname: Lorber
authors.forename: Holger M
authors.initials: HM
authors.lastname: Koch
authors.forename: Jüergen
authors.initials: J
authors.lastname: Angerer
mesh_terms: D003404:Creatinine / Q000493:pharmacokinetics / Q000652:urine*; D004051:Diethylhexyl Phthalate / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D018570:Risk Assessment; D013997:Time Factors; D035501:Uncertainty
chemical_list: D004785:Environmental Pollutants; D003404:Creatinine; D004051:Diethylhexyl Phthalate