title: In vitro human skin penetration model for organophosphorus compounds with different physicochemical properties.
abstract: A flow-through diffusion cell was validated for in vitro human epidermal penetration studies of organophosphorus compounds (OPCs) applied by infinite dosing. By testing OPCs with similar molecular weight but different physicochemical properties, it was shown that hydrophilic and lipophilic properties are major determinants for the penetration rate. Lipophilic OPCs displayed maximum cumulative penetration in the 20-75% agent concentration range whereas the hydrophilic OPCs displayed maximum cumulative penetration at 10 or 20% agent concentration. Low penetration was observed for all agents at 1% agent concentration or when applied as neat agents. The impact of the receptor solution composition was evaluated by comparing the penetration using receptor solutions of different ratios of ethanol and water. For diluted OPCs, a high concentration of ethanol in the receptor solution significantly increased the penetration compared to lower concentrations. When OPCs were applied as neat agents, the composition of the receptor solution only affected the penetration for one of four tested compounds. In conclusion, the flow-through diffusion cell was useful for examining the penetration of OPCs through the epidermal membrane. It was also demonstrated that the penetration rates of OPCs are strongly influenced by dilution in water and the receptor fluid composition.
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden. Electronic address: lina.thors@foi.se.
authors.forename: L
authors.initials: L
authors.lastname: Thors
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Koch
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Hägglund
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Bucht
mesh_terms: D004058:Diffusion; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption; D014867:Water / Q000378:metabolism
chemical_list: D009943:Organophosphorus Compounds; D014867:Water
keywords: Epidermal membrane; Human skin; In vitro skin penetration; Organophosphorus compounds