Edema-inducing effects of solvents following topical administration

It was demonstrated in a previous study that skin irritancy reactions could be accurately assessed by skin-fold measurements using a caliper. Eight solvents (trichloroethylene, toluene,1,1,2- trichloroethane, carbon tetrachloride, 1,1,1-trichloroethane,n-hexane, methyl ethyl ketone, ethanol--all neat) were applied once daily for at least 10 days to rabbit, guinea pig and human (volar forearm) skin and the sites were left open. All solvents caused various degrees of fluid accumulation, and trichloroethylene, toluene and 1,1,2-trichloroethane were found to be most potent in inducing edema in both animal species. The effect of ethanol was marginal compared to the untreated control sites. In rabbits a peak value was observed at the 24 h reading, then a minimum at 72 h, and from the 96 h reading a gradual increase. No real difference was observed in the interspecies comparison (rabbit vs guinea pig). On the other hand no increase in skin-fold thickness nor any persistent erythema was observed in man. By using guinea pigs with initial weights above 600 g the previously observed disadvantage of this animal species could be eliminated. It is claimed that skin-fold measurements could be used as a complement for the assessment and discernment of the irritant effects of solvents.