title: Effect of chemical interactions in pentachlorophenol mixtures on skin and membrane transport.
abstract: Pentachlorophenol (PCP) has been widely used as a pesticide, and topical exposure to a chemical mixture can alter its dermal absorption. The purpose of this study was to evaluate the influence of single and binary solvent systems (ethanol, EtOH, and water), a surfactant (6% sodium lauryl sulfate, SLS), and a rubifacient/vasodilator (1.28% methyl nicotinate, MNA) on PCP membrane transport, and to correlate these effects with physiochemical characteristics of the PCP mixtures. Partitioning, diffusion, and absorption parameters of (14)C-PCP at low (4 microg/cm(2)) and high (40 microg/cm(2)) doses were assessed in porcine skin and silastic membranes in vitro. In these 8-h, flow-through diffusion studies, PCP was dosed with the following vehicles: 100% EtOH, 100% water, 40% EtOH + 60% water, 40% EtOH + 60% water + SLS, 40% EtOH + 60% water + MNA, and 40% EtOH + 60% water + SLS + MNA. PCP absorption ranged from 1.55-15.62% for the high dose and 0.43-7.20% for the low dose. PCP absorption, flux, and apparent permeability were influenced by PCP solubility, and PCP apparent permeability was correlated with log PC (r2 = 0.66). Although PCP was very soluble in pure ethanol (100%), this vehicle evaporated very rapidly, and PCP absorption in ethanol was the lowest with this vehicle when compared to pure water (100%) or aqueous ethanol mixtures in general. MNA had no significant effect on membrane absorption or relative permeability R(P) in aqueous ethanol solutions, but the presence of the surfactant, SLS, significantly reduced PCP absorption and R(P) in both membrane systems. In conclusion, these studies demonstrated that modification in mixture composition with either a solvent and/or a surfactant can influence PCP diffusion in skin. Physicochemical interactions between these mixture components on the skin surface and stratum corneum contributed significantly to PCP transport, and these interactions were identified by simultaneously assessing chemical diffusion in biological and inert membrane systems.
authors.affiliation: Center for Chemical Toxicology Research and Pharmacokinetics, Department of Food Animal Health and Resource Management, College Of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. ronald_baynes@ncsu.edu
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Baynes
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
authors.forename: Moiz
authors.initials: M
authors.lastname: Mumtaz
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D007306:Insecticides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity*; D008566:Membranes / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology; D010416:Pentachlorophenol / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology; D014783:Viscosity
chemical_list: D007306:Insecticides; D009539:Nicotinic Acids; D014677:Pharmaceutical Vehicles; D012997:Solvents; D012967:Sodium Dodecyl Sulfate; D000431:Ethanol; C008473:methyl nicotinate; D010416:Pentachlorophenol