title: Percutaneous absorption and distribution of organophosphates (chlorpyrifos and dichlorvos) following dermal exposure and decontamination scenarios using in vitro human skin model.
abstract: To date, there has been little research investigating low-level human exposure to chemicals, and so the aim of this study was to examine the percutaneous penetration of organophosphates (dichlorvos and chlorpyrifos) using low-level exposure scenarios in vitro. Dermal absorption of chlorpyrifos applied in different vehicles was measured at 0, 4, 8 and 24 h, after dose application for 4 and 24 h exposure (finite dose, 500 ng/cm(2)) in isopropanol (IPA), isopropyl myristate (IPM) and propylene glycol (PG). Dichlorvos was applied to the skin for 24 h (infinite dose, 1 mg/cm(2) and 10 mg/cm(2); finite dose, 5 μg/cm(2)) using the same vehicles. Human skin was mounted in flow through diffusion cells with minimum essential medium eagle pH 7.4 (supplemented with 2% BSA) as receptor fluid. Following exposure, the skin surface dose was removed by tissue swabbing, the stratum corneum removed by sequential tape stripping, and the skin digested prior to scintillation counting (chlorpyrifos), or GC/MS analysis (dichlorvos). The dermal absorption of chlorpyrifos was the greatest following application in PG (19.5% of dose), when compared with absorption from the IPA and IPM vehicles (10.3% and 1.9% absorbed respectively). However, dichlorvos showed greater dermal absorption than chlorpyrifos from all vehicles used, with greatest absorption from the IPA vehicle (38.6% absorbed). Although dichlorvos exhibited a short lag time (0.6 h from IPA and IP vehicles, and 0.4 h from PG), chlorpyrifos displayed greater propensity to accumulate in the stratum corneum and epidermis/dermis. These results demonstrate that prompt skin surface decontamination would be required for both dichlorvos and chlorpyrifos (and chemicals with similar properties) in the event of skin contact. The magnitude of the skin reservoir formed with chlorpyrifos was time dependent, therefore, prompt decontamination of this and similar chemicals would be required to reduce delayed systemic absorption.
authors.affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Newcastle upon Tyne, NE2 4AA, UK. Electronic address: craig.moore@unilever.com.
authors.forename: C A
authors.initials: CA
authors.lastname: Moore
authors.affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Newcastle upon Tyne, NE2 4AA, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Wilkinson
authors.affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Newcastle upon Tyne, NE2 4AA, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Blain
authors.affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Newcastle upon Tyne, NE2 4AA, UK.
authors.forename: M
authors.initials: M
authors.lastname: Dunn
authors.affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Newcastle upon Tyne, NE2 4AA, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Aust
authors.affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Newcastle upon Tyne, NE2 4AA, UK.
authors.forename: F M
authors.initials: FM
authors.lastname: Williams
mesh_terms: D019840:2-Propanol / Q000737:chemistry; D004390:Chlorpyrifos / Q000493:pharmacokinetics*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D003666:Decontamination; D004006:Dichlorvos / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D009226:Myristates; D014677:Pharmaceutical Vehicles; D019946:Propylene Glycol; D012869:Skin Absorption / Q000502:physiology*; D012997:Solvents; D014018:Tissue Distribution
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009226:Myristates; D014677:Pharmaceutical Vehicles; D012997:Solvents; C008205:isopropyl myristate; D019946:Propylene Glycol; D004006:Dichlorvos; D004390:Chlorpyrifos; D019840:2-Propanol
keywords: Dermal absorption; Exposure; Organophosphates