Andersen K E, Carlsen L, Egsgaard H, Larsen E
Contact Dermatitis. 1985 Oct;13(4):246-51. doi: 10.1111/j.1600-0536.1985.tb02558.x.
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.
采用累积接触增强试验在豚鼠中测定了5种局部用制剂的氯甲酚致敏性。橄榄油/丙酮(4/1)中5%的氯甲酚以及用卡波姆941稳定的水悬浮液中5%的氯甲酚比含或不含卡波姆941的丙二醇中5%的氯甲酚致敏性更强(分别有55%和60%的动物呈阳性)。饱和氯甲酚水溶液(约0.38% w/v)的致敏性与氯甲酚含量高13倍的5%丙二醇溶液相当。使用同位素稀释技术通过气相色谱 - 质谱联用测定了留在绷带材料和斑贴试验皮肤部位的(每种制剂)给药剂量的比例。0.2%至1.6%的给药剂量以游离氯甲酚的形式留在斑贴试验皮肤部位。水悬浮液中75%的氯甲酚渗透过皮肤,相比之下,橄榄油/丙酮(4/1)和丙二醇中氯甲酚的渗透率分别为34%和35%。尽管后两种制剂吸收的氯甲酚量相同,但它们的致敏能力存在显著差异。在所测试的制剂中,未观察到致敏率与计算出的生物利用度之间存在简单关系。