Partitioning of chemicals into human stratum corneum: implications for risk assessment following dermal exposure.
Assessment of the health hazard associated with chemical contamination of the skin is a complex problem of occupational and environmental relevance. A particularly important question is to what extent can the skin permeability of a given compound be predicted from simple experiments. The literature on percutaneous absorption identifies two key observations: (i) the stratum corneum (SC), the skin's outermost layer, is the major barrier to chemical transport, and (ii) there are qualitative correlations between penetrant permeability and various oil/water partition coefficients (PCs). To obtain more quantitative predictions of permeation, we have evaluated SC/water and SC/isopropyl myristate (IPM, a model lipophilic vehicle) PCs of (a) para-substituted phenols of diverse physicochemical properties (4-acetamido-, 4-cyano-, 4-iodo-, and 4-pentyloxyphenol), (b) polychlorinated biphenyls (54%), and (c) 1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane. Partition coefficients were determined as a function of the following variables: length of equilibration, initial drug concentration in the vehicle, SC delipidization, and SC source and preparation technique. The data demonstrate that reproducible partitioning can be obtained using the biological tissue of greatest relevance, and that the pattern of behavior observed, for the two different vehicles studied, is compatible with physicochemical expectations. We suggest that the PC values measured may be useful predictors of in vitro and in vivo skin transport and valuable assets, therefore, in the evaluation of risk following dermal exposure.
Surber
C
C
Department of Dermatology, School of Medicine, University of California, San Francisco 94143.
Wilhelm
K P
KP
Maibach
H I
HI
Hall
L L
LL
Guy
R H
RH
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012867:Skin / Q000166:cytology / Q000648:ultrastructure*; D012869:Skin Absorption; D013045:Species Specificity; D015262:Xenobiotics / Q000493:pharmacokinetics*
D015262:Xenobiotics