THE EARLY CHANGES IN MOUSE SKIN FOLLOWING TOPICAL APPLICATION OF A RANGE OF MIDDLE DISTILLATE OIL PRODUCTS

A white spirit/naphtha, three kerosines, two gas oils and a catalytica lly cracked light cycle oil (LCO) were applied topically to mice, thre e times a week for up to 6 weeks, and skin changes were examined histo pathologically at intervals. The changes within 1 week of treatment ap peared to depend on the effect that the physicochemical properties of each type of product had on their penetration through the skin surface or via hair follicles. With white spirit the most prominent change wa s widespread epidermal necrosis occurring after the second treatment, implying that the lowest boiling point materials penetrate mainly thro ugh the surface epidermis. The earliest effects with kerosines were wi thin and around hair follicles with epidermal degeneration developing later, suggesting a predominance of follicular entry. Gas oils and LCO produced similar changes to kerosines within 1 week, gas oils produci ng a slower and less severe response and LCO a more severe response. I n skin examined after 1-6 weeks of treatment with all middle distillat es, repeated cycles of necrosis and healing responses were evident; th is implied that once the epidermal barrier layer had been damaged, fol licular entry became less important. The severity of the skin changes observed with these middle distillates was probably sufficient for ski n tumours to arise by a non-genotoxic mechanism if a similar treatment regime was used in a long-term skin painting study. A method of avoid ing excessive skin irritation is therefore essential in such a study i n order to obtain a reliable prediction of the human hazard of such ma terials.