Surfactant effects on skin absorption of model organic chemicals: implications for dermal risk assessment studies.
Occupational and environmental exposures to chemicals are major potential routes of exposure for direct skin toxicity and for systemic absorption. The majority of these exposures are to complex mixtures, yet most experimental studies to assess topical chemical absorption are conducted neat or in simple aqueous vehicles. A component of many industrial mixtures is surfactants that solubilize ingredients and stabilize mixtures of oily components when present in aqueous vehicles. The purpose of this series of experiments was to use two well-developed experimental techniques to assess how solution interactions present in a pure nonbiological in vitro system (membrane coated fibers, MCF) compare to those seen in a viable ex vivo biological preparation (isolated perfused porcine skin flap, IPPSF). Two widely encountered anionic surfactants, sodium lauryl sulfate (SLS) and linear alkylbenzene sulfonate (LAS), were studied in 10% solutions. The rank orders of absorption were: water: pentachlorophenol (PCP) > 4-nitrophenol (PNP) > parathion > fenthion > simazine > propazine; SLS: PNP > PCP > parathion > simazine > fenthion > propazine; and LAS: PNP > PCP > simazine > parathion > fenthion > propazine. For all penetrants, absorption was greater in SLS compared to LAS mixtures, a finding consistent with smaller micelle sizes seen with SLS. For these low-water-solubility compounds, absorption was greater from aqueous solutions in nearly every case. The inert three-fiber MCF array predicted absorptive fluxes seen in the ex vivo IPPSF, suggesting lack of any biological effects of the surfactants on skin.
Riviere
Jim E
JE
Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina 27606, USA. Jim_Riviere@ncsu.edu
Brooks
James D
JD
Yeatts
James L
JL
Koivisto
Elisha L
EL
D000279:Administration, Cutaneous; D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D000818:Animals; D045424:Complex Mixtures / Q000737:chemistry / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D008567:Membranes, Artificial; D009930:Organic Chemicals / Q000493:pharmacokinetics*; D018570:Risk Assessment; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*; D012995:Solubility; D013501:Surface-Active Agents / Q000494:pharmacology*; D013524:Surgical Flaps; D013552:Swine; D014867:Water / Q000737:chemistry
D017738:Alkanesulfonic Acids; D045424:Complex Mixtures; D008567:Membranes, Artificial; D009930:Organic Chemicals; D013501:Surface-Active Agents; C030641:alkylbenzyl sulfonic acid; D014867:Water; D012967:Sodium Dodecyl Sulfate