Determination of skin:air partition coefficients for volatile chemicals: experimental method and applications.
The partition coefficient (PC) of a chemical in skin is an indicator of the capacity for a chemical in the skin and may reflect the rate at which a chemical penetrates the skin and enters into systemic circulation. In this study we present a simple method to measure the skin:air PC for volatile organic chemicals. Important considerations in the development of this method for a skin:air PC were the effect of size and shape of the skin sample, initial chemical concentration, and time to equilibrium in the skin. Clipped, whole-thickness skin was obtained from the dorsal surface of 8- to 16-week-old male F-344 rats. After removal of the hypodermis, skin was cut into strips and placed on the side of a glass vial. An organic chemical vapor was introduced into a sealed sample vial (initial concentration before equilibration was 203 ppm) and a corresponding reference vial, which were equilibrated at 32 degrees C. Headspace concentrations at equilibrium were used to determine a skin:air PC value. After developing the technique using dibromomethane, a skin:air PC value was determined for perchloroethylene, trichloroethylene, benzene, hexane, toluene, m-xylene, styrene, methyl chloroform, methylene chloride, carbon tetrachloride, halothane, and isoflurane. The skin:air PC values correlated with previously determined vapor permeability constants but correlated poorly with octanol/water PC values. This method provides a screening technique for predicting skin penetration of volatile chemicals.
Mattie
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DR
Armstrong Laboratory, Occupational and Environmental Health Directorate, Toxicology Division, Wright-Patterson AFB, Ohio 45433-7400.
Bates
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Jepson
G W
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Fisher
J W
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McDougal
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D000388:Air / Q000032:analysis*; D000818:Animals; D002625:Chemistry, Organic / Q000379:methods*; D008297:Male; D000442:Octanols; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D014835:Volatilization
D000442:Octanols