sodium-dodecyl-sulfate and methyl-nicotinate

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.

Topics: Animals; Chemical Phenomena; Chemistry, Physical; Diffusion; Ethanol; In Vitro Techniques; Insecticides; Membranes; Nicotinic Acids; Pentachlorophenol; Permeability; Pharmaceutical Vehicles; Skin Absorption; Sodium Dodecyl Sulfate; Solvents; Viscosity

Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal risk assessment process, would be greatly improved by the elucidation and characterization of these interactions. Pentachlorophenol (PCP), a compound known to penetrate the skin readily, was used as a marker compound to examine mixture component effects using in vitro porcine skin models. PCP was administered in ethanol or in a 40% ethanol/60% water mixture or a 40% ethanol/60% water mixture containing either the rubefacient methyl nicotinate (MNA) or the surfactant sodium lauryl sulfate (SLS), or both MNA and SLS. Experiments were also conducted with 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB). Maximal PCP absorption was 14.12% of the applied dose from the mixture containing SLS, MNA, ethanol and water. However, when PCP was administered in ethanol only, absorption was only 1.12% of the applied dose. There were also qualitative differences among the absorption profiles for the different PCP mixtures. In contrast with the PCP results, absorption of TCB or PCB was negligible in perfused porcine skin, with only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being maximally absorbed. The low absorption levels for the PCB congeners precluded the identification of mixture component effects. These results suggest that dermal absorption estimates from a single chemical exposure may not reflect absorption seen after exposure as a chemical mixture and that absorption of both TCB and PCB are minimal in this model system.

Topics: Administration, Topical; Animals; Culture Techniques; Dermis; Dose-Response Relationship, Drug; Environmental Pollutants; Ethanol; Irritants; Nicotinic Acids; Pentachlorophenol; Perfusion; Polychlorinated Biphenyls; Risk Assessment; Skin Absorption; Sodium Dodecyl Sulfate; Surface-Active Agents; Swine

Topics: Alopecia; Animals; Body Water; Dermatitis, Irritant; Disease Models, Animal; Drug Evaluation, Preclinical; Erythema; Female; Histamine Release; Industrial Oils; Intradermal Tests; Irritants; Male; Nicotinic Acids; Ointments; Patch Tests; Permeability; Sodium Dodecyl Sulfate; Sodium Hydroxide; Swine; Swine, Miniature; Toluene

In order to investigate the influence of the application time of the day on skin reactions, test persons were treated with various substances inducing experimental inflammation in human skin. Additional tests provided us with data regarding the antiinflammatory activity of topical glucocorticoids on the experimental inflammation as well as the vasoconstrictive activity dependent on the application time of the day. Although all tests showed great individual scattering ranges, statistical evaluation did not reveal any clear evidence for the supposition that pharmacological responses of the skin may be influenced by the hour of the topical application. Thus, it seems not likely that the success of topical treatment of toxic dermatitis by means of glucocorticoids depends on the hour of application.

Topics: Adolescent; Adult; Betamethasone Valerate; Circadian Rhythm; Croton Oil; Dermatitis, Contact; Dose-Response Relationship, Drug; Female; Fluocinolone Acetonide; Humans; Male; Nicotinic Acids; Patch Tests; Pregnadienetriols; Sodium Dodecyl Sulfate; Vasoconstriction