Alkane-induced edema formation and cutaneous barrier dysfunction

Certain mineral oils and hydrocarbons require repeated topical application to cause irritation. A structure activity relationship of pure n-alkanes was undertaken in a mouse ear edema model to investigate the mechanism of cumulative irritancy. Alkanes were applied twice daily over a 4-day period. Dodecane was found to be non-irritating, while tridecane elicited a response only at 96 h. Tetradecane was the strongest irritant with significant increases (p less than 0.05) in ear thickness observed at 48 h. Hexadecane, octadecane, and eicosane exhibited progressively decreasing activity. Permeability of the ears to hydrocortisone was monitored in vitro during tridecane- and tetradecane-induced irritation. Significant increases in permeability were observed 24 h before edema formation. A positive correlation was found between the extent of edema formation and enhancement of permeability. Loss of barrier function would result in increased cutaneous availability of the alkanes. Increased permeability prior to edema formation indicates that induction of barrier dysfunction may be a factor in the mechanism of alkane-induced irritation.