Mixture component effects on the in vitro dermal absorption of pentachlorophenol.
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.
Riviere
J E
JE
Center for Cutaneous Toxicology and Residue Pharmacology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA. Jim_Riviere@NCSU.EDU
Qiao
G
G
Baynes
R E
RE
Brooks
J D
JD
Mumtaz
M
M
D000287:Administration, Topical; D000818:Animals; D046508:Culture Techniques; D020405:Dermis / Q000098:blood supply / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000431:Ethanol / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology; D009539:Nicotinic Acids / Q000494:pharmacology; D010416:Pentachlorophenol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010477:Perfusion; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000493:pharmacokinetics; D018570:Risk Assessment; D012869:Skin Absorption; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D013552:Swine
D004785:Environmental Pollutants; D007509:Irritants; D009539:Nicotinic Acids; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D000431:Ethanol; C008473:methyl nicotinate; D010416:Pentachlorophenol; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl; C028451:3,4,3',4'-tetrachlorobiphenyl