Babu R J, Chatterjee A, Ahaghotu E, Singh M
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA.
Toxicol Ind Health. 2004 Sep;20(6-10):109-18. doi: 10.1191/0748233704th197oa.
Even though the dermal toxicity of hydrocarbon fuels has been well established in the literature, there is little information available on the dermal penetration kinetics and irritation potential of the individual hydrocarbons. The penetration and skin retention of nonane, dodecane and tetradecane was assessed in vitro using hairless rats' skin. The effects of unocclusive dermal exposures of these chemicals (15 microL every 2 h for 8 h a day for four days) on the transepidermal water loss (TEWL) and erythema were measured in CD hairless rats. The expression of interleukin 1alpha (IL- 1alpha) and TNF-alpha in the skin and blood were measured at the end of dermal exposures. The flux of dodecane was 3- and 77-fold higher than nonane and tetradecane. The retention of chemicals in stratum corneum (SC) was in the order of tetradecane > dodecane > nonane, and directly correlated to the log Kp (r2 = 0.9900) and molecular weight of the chemicals (r2 = 0.8782). The TEWL and erythema data indicate that irritation was in the following order: tetradecane > dodecane > nonane. Likewise, the expression of IL-lalpha in the blood and TNF-alpha in the skin after dermal exposures was higher for tetradecane followed by dodecane and nonane compared to control. In conclusion, the aliphatic hydrocarbon chemicals of the present study induced cumulative irritation upon low-level repeat exposures for a four-day period. The affinity of the chemicals to SC and their gradual accumulation in the skin in the present study is the probable cause for the differences in the skin irritation profiles of different aliphatic chemicals. The findings of the present study will be helpful in understanding the skin irritation response of the chemicals in humans; indeed the reality check arises from dermal exposures in humans and human experience in occupational handling of these chemicals.
尽管碳氢化合物燃料的皮肤毒性在文献中已有充分记载，但关于单个碳氢化合物的皮肤渗透动力学和刺激潜力的信息却很少。使用无毛大鼠皮肤在体外评估壬烷、十二烷和十四烷的渗透和皮肤滞留情况。在CD无毛大鼠中测量了这些化学物质非封闭性皮肤暴露（每天8小时，每2小时15微升，持续4天）对经表皮水分流失（TEWL）和红斑的影响。在皮肤暴露结束时测量皮肤和血液中白细胞介素1α（IL - 1α）和肿瘤坏死因子α（TNF - α）的表达。十二烷的通量比壬烷和十四烷分别高3倍和77倍。化学物质在角质层（SC）中的滞留顺序为十四烷>十二烷>壬烷，并且与化学物质的log Kp（r2 = 0.9900）和分子量（r2 = 0.8782）直接相关。TEWL和红斑数据表明刺激程度顺序为：十四烷>十二烷>壬烷。同样，与对照组相比，皮肤暴露后血液中IL - 1α的表达和皮肤中TNF - α的表达在十四烷组最高，其次是十二烷组和壬烷组。总之，本研究中的脂肪族碳氢化合物化学物质在为期四天的低水平重复暴露后会引起累积性刺激。本研究中化学物质对角质层的亲和力及其在皮肤中的逐渐积累可能是不同脂肪族化学物质皮肤刺激特征存在差异的原因。本研究结果将有助于理解这些化学物质在人体中的皮肤刺激反应；实际上，实际情况源于人体的皮肤暴露以及人类在职业处理这些化学物质方面的经验。
