title: Linking a dermal permeation and an inhalation model to a simple pharmacokinetic model to study airborne exposure to di(n-butyl) phthalate.
abstract: Six males clad only in shorts were exposed to high levels of airborne di(n-butyl) phthalate (DnBP) and diethyl phthalate (DEP) in chamber experiments conducted in 2014. In two 6 h sessions, the subjects were exposed only dermally while breathing clean air from a hood, and both dermally and via inhalation when exposed without a hood. Full urine samples were taken before, during, and for 48 h after leaving the chamber and measured for key DnBP and DEP metabolites. The data clearly demonstrated high levels of DnBP and DEP metabolite excretions while in the chamber and during the first 24 h once leaving the chamber under both conditions. The data for DnBP were used in a modeling exercise linking dose models for inhalation and transdermal permeation with a simple pharmacokinetic model that predicted timing and mass of metabolite excretions. These models were developed and calibrated independent of these experiments. Tests included modeling of the "hood-on" (transdermal penetration only), "hood-off" (both inhalation and transdermal) scenarios, and a derived "inhalation-only" scenario. Results showed that the linked model tended to duplicate the pattern of excretion with regard to timing of peaks, decline of concentrations over time, and the ratio of DnBP metabolites. However, the transdermal model tended to overpredict penetration of DnBP such that predictions of metabolite excretions were between 1.1 and 4.5 times higher than the cumulative excretion of DnBP metabolites over the 54 h of the simulation. A similar overprediction was not seen for the "inhalation-only" simulations. Possible explanations and model refinements for these overpredictions are discussed. In a demonstration of the linked model designed to characterize general population exposures to typical airborne indoor concentrations of DnBP in the United States, it was estimated that up to one-quarter of total exposures could be due to inhalation and dermal uptake.
authors.affiliation: Office of Research and Development, US EPA, Washington, District of Columbia, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lorber
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA.|International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Weschler
authors.affiliation: Civil, Architectural and Environmental Engineering, Missouri University of Science and Technology, Rolla, Missouri, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Morrison
authors.affiliation: International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bekö
authors.affiliation: National Institute of Standards and Technology, Gaithersburg, Maryland, USA.
authors.forename: Mengyan
authors.initials: M
authors.lastname: Gong
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Koch
authors.affiliation: Department of Material Analysis and Indoor Chemistry, Fraunhofer WKI, Braunschweig, Germany.
authors.forename: Tunga
authors.initials: T
authors.lastname: Salthammer
authors.affiliation: Department of Material Analysis and Indoor Chemistry, Fraunhofer WKI, Braunschweig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schripp
authors.affiliation: International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Toftum
authors.affiliation: International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Geo
authors.initials: G
authors.lastname: Clausen
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000652:urine*; D003718:Denmark; D003993:Dibutyl Phthalate / Q000652:urine*; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000652:urine*; D006801:Humans; D001239:Inhalation; D008297:Male; D008875:Middle Aged; D012869:Skin Absorption; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D004785:Environmental Pollutants; D003993:Dibutyl Phthalate