title: A real-time in-vivo method for studying the percutaneous absorption of volatile chemicals.
abstract: Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical to understanding human health risks. A method was developed to determine dermal uptake of solvents under non-steady-state conditions using real-time breath analysis in rats, monkeys, and humans. The exhaled breath was analyzed using an ion-trap mass spectrometer, which can quantitate chemicals in the exhaled breath stream in the 1-5 ppb range. The resulting data were evaluated using physiologically-based pharmacokinetic (PBPK) models to estimate dermal permeability constants (Kp) under various exposure conditions. The effects of exposure matrix (soil versus water), occlusion versus non-occlusion, and species differences on the absorption of methyl chloroform, trichloroethylene, and benzene were compared. Exposure concentrations were analyzed before and at 0.5-hour intervals throughout the exposures. The percentage of each chemical absorbed and the corresponding Kp were estimated by optimization of the PBPK model to the medium concentration and the exhaled-breath data. The method was found to be sufficiently sensitive for animal and human dermal studies at low exposure concentrations over small body surface areas, for short periods, using non-steady-state exposure conditions.
authors.affiliation: Molecular Biosciences Department, Pacific Northwest National Laboratory, P.O. Box 999, Mail Stop P7-59, Richland, WA 99352, USA. karla.thrall@pnl.gov
authors.forename: K D
authors.initials: KD
authors.lastname: Thrall
authors.forename: T S
authors.initials: TS
authors.lastname: Poet
authors.forename: R A
authors.initials: RA
authors.lastname: Corley
authors.forename: H
authors.initials: H
authors.lastname: Tanojo
authors.forename: J A
authors.initials: JA
authors.lastname: Edwards
authors.forename: K K
authors.initials: KK
authors.lastname: Weitz
authors.forename: X
authors.initials: X
authors.lastname: Hui
authors.forename: H I
authors.initials: HI
authors.lastname: Maibach
authors.forename: R C
authors.initials: RC
authors.lastname: Wester
mesh_terms: D000818:Animals; D001944:Breath Tests; D006801:Humans; D008253:Macaca mulatta; D008954:Models, Biological; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D009930:Organic Chemicals / Q000009:adverse effects / Q000378:metabolism*; D051381:Rats; D012869:Skin Absorption; D014835:Volatilization
chemical_list: D009930:Organic Chemicals