Ranking in Skin Permeability

Investigations on the usefulness, and predictability of animal models have been of two types: (a) those in which percutaneous absorption of one or more permeants is measured in several species; and (b) those in which absorption of one or more chemicals is compared between the experimental animal and human. If the data from animal models are to be used for extrapolation to human, it is important that the investigators appreciate the differences in the behavior of the animal model and human tissue. The skin permeability of the animal tissue model must be the same as that of the human, or easily related to it by a constant ratio (4). Furthermore, any response to permeation modulators (physical or chemical), formulation excipients, and occlusion must mimic the response in humans (235,236).

Norgaard (237) reported that the species ranking of skin permeability rates for cobalt ions was rabbit > guinea pig > human. Tregear (238) ranked the species permeabilities for metal ions as rabbit > rat > guinea pig > human, whereas that given by McCreesh (239) (for two ill-defined organophosphorus solutes) was rabbit, rat > guinea pig > cat, goat, monkey > dog > pig. Scott et al. (240) reported the permeability coefficients of the dicationic herbicide paraquat in a range of species. The observed permeabilities for paraquat relative to water are shown in Table 7. Two features of paraquat permeability are readily apparent: (a) human skin is much

Table 7 The Observed Permeabilities for Paraquat and Water Through the Skin of Various Species as Measured Using In Vitro Techniques

Permeability coefficient (cm2/h X 10~5)

Animal/human ratio for

Table 7 The Observed Permeabilities for Paraquat and Water Through the Skin of Various Species as Measured Using In Vitro Techniques

Permeability coefficient (cm2/h X 10~5)

Animal/human ratio for

Species

Type

Water

Paraquat

paraquat

Man

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