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□ To assess how the permeability of phenol is altered by thermal injury, it was first necessary to have baselines of comparison on normal skin. Using in vitrodiffusion cells and the skin of the hairless mouse, [14C]phenol was applied to skin in an aqueous medium with a reference copermeating species, [3H]methanol, and 37° permeability coefficients of the pair were evaluated as functions of animal age, skin hydration, stripping of the skin, dermis isolation, and phenol concentration. Age proved to be of little consequence to permeability over a wide age range. Prolonged aqueous soaking of the skins was also without much effect. Stripping of the skin and isolating the dermis by soaking techniques allowed assessment of individual skin strata diffusional resistances. When applied to skin in trace radiochemical concentrations, phenol behaved diffusionally as an alkanol with a chain length of six. But at concentrations >2% w/v, phenol facilitated the permeation rates of itself and methanol; the effect was markedly concentration sensitive and only fractionally reversible. Concentration studies using silicone rubber membranes proved that the effects on the skin were the results of destroyed barrier integrity. At 6% phenol concentration there was an essentially instantaneous, 10-fold increase in the phenol permeability coefficient, raising it to two-thirds that observed with fully stripped skin. Overall, the data suggest that the stratum comeum is proportionally impaired as the phenol concentration is increased.

□ The safe antiseptic use of phenol over the burn-traumatized surface depends on knowledge of how the systemic accumulation of phenol is affected by burn processes. To gain insight into the underlying permeation phenomenon, the diffusion of phenol and a reference cosolute, methanol, through both scalded and branded dorsal skin sections of the hairless mouse was studied as a function of burn temperature using in vitro diffusion cells. Temperatures up to 100 and 150° were used for scalding and branding, respectively, using a 60-sec exposure time. Permeability coefficients of the traumatized skins were assessed at 37° and compared with control values. Coefficients of both permeating species were not increased significantly by burn temperatures up to 70° applied either by scalding or branding, however, at higher temperatures exaggerated increases in permeation rates were noted. A limiting increase of ~7 times the control value was noted for phenol irrespective of the burn method. Permeability of methanol was altered even more dramatically and at 100° by scalding and 150° by branding was over 50 times the control rate. At 80 and 100° for methanol and at 80° for phenol, scalding produced larger increases in the permeability coefficients than branding. Since contact for 1min at 60° is capable of producing a full-thickness burn injury, it is clear that eschar permeability to phenol immediately postburn is not related to the clinical degree of burning, but is a function of the thermal intensity (hotness) of the burn stimulus. Full-thickness wounds can be expected to have highly variable rates of systemic absorption as a direct consequence of the wide-ranging permeability possible for such burns, with the risks of topical application varying accordingly.