title: Estimating uptake of phthalate ester metabolites into the human nail plate using pharmacokinetic modelling.
abstract: There is a lack of knowledge regarding uptake of phthalate esters (PEs) and other chemicals into the human nail plate and thus, clarity concerning the suitability of human nails as a valid alternative matrix for monitoring long-term exposure. In particular, the relative importance of internal uptake of phthalate metabolites (from e.g. blood) compared to external uptake pathways is unknown. This study provides first insights into the partitioning of phthalate-metabolites between blood and nail using pharmacokinetic (PK) modelling and biomonitoring data from a Norwegian cohort. A previously published PK model (Lorber PK model) was used in combination with measured urine data to predict serum concentrations of DEHP and DnBP/DiBP metabolites at steady state. Then, partitioning between blood and nail was assessed assuming equilibrium conditions and treating the nail plate as a tissue, assuming a fixed lipid and water content. Although calculated as a worst-case scenario at equilibrium, the predicted nail concentrations of metabolites were lower than the biomonitoring data by factors of 44 to 1300 depending on the metabolite. It is therefore concluded that internal uptake of phthalate metabolites from blood into nail is a negligible pathway and does not explain the observed nail concentrations. Instead, external uptake pathways are more likely to dominate, possibly through deposition of phthalates onto the skin/nail and subsequent metabolism. Modelling gaseous diffusive uptake of PEs from air to nail revealed that this pathway is unlikely to be important. Experimental quantification of internal and external uptake pathways of phthalates and their metabolites into the human nail plate is needed to verify these modelling results. However, based on this model, human nails are not a good indicator of internal human exposure for the phthalate esters studied.
authors.affiliation: IVL Swedish Environmental Research Institute, SE-100 31 Stockholm, Sweden; Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University, SE-106 91 Stockholm, Sweden. Electronic address: thuy.bui@ivl.se.
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Bui
authors.affiliation: VITO NV Flemish Institute for Technological Research, Boeretang 200, 2400 Mol, Belgium; Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitplein 1, B-2610 Wilrijk, Belgium.
authors.forename: Andreia
authors.initials: A
authors.lastname: Alves
authors.affiliation: IVL Swedish Environmental Research Institute, SE-100 31 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Palm-Cousins
authors.affiliation: VITO NV Flemish Institute for Technological Research, Boeretang 200, 2400 Mol, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Voorspoels
authors.affiliation: Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitplein 1, B-2610 Wilrijk, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
authors.affiliation: Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Cousins
mesh_terms: D015331:Cohort Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D004952:Esters / Q000493:pharmacokinetics*; D006801:Humans; D008956:Models, Chemical; D009262:Nails / Q000737:chemistry*; D009664:Norway; D010795:Phthalic Acids / Q000493:pharmacokinetics*
chemical_list: D004785:Environmental Pollutants; D004952:Esters; D010795:Phthalic Acids
keywords: Human nail; Partitioning; Pharmacokinetic modelling; Phthalates