Contact sensitivity and bioavailability of chlorocresol

Chlorocresol sensitization from 5 topical preparations was determined in guinea pigs using the cumulative contact enhancement test. Chlorocresol 5% in olive oil/acetone (4/1), and 5% in aqueous suspension stabilized with carbomer 941 were more sensitizing (55% and 60% of the animals positive, respectively) than chlorocresol 5% in propylene glycol with or without carbomer 941 (20% positive). The sensitization from a saturated aqueous chlorocresol solution (about 0.38% w/v) was comparable to that of a 5% propylene glycol solution containing 13 times more chlorocresol. The fraction of the applied dose (from each preparation) that remained in the bandage material and the patch test skin site was determined by combined gas chromatography-mass spectrometry using an isotopic dilution technique. From 0.2% to 1.6% of the applied doses remained at the patch test skin sites as free chlorocresol. 75% of the chlorocresol in aqueous suspension permeated the skin in contrast to 34% and 35% of the chlorocresol in olive oil/acetone (4/1) and propylene glycol, respectively. In spite of the same amount of chlorocresol absorption from the 2 latter preparations, they showed a significant difference in sensitizing capacity. No simple relationship between the sensitization rates and the calculated bioavailability was observed with the preparations tested.