Ahaghotu E, Babu R J, Chatterjee A, Singh M
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Toxicol Lett. 2005 Dec 15;159(3):261-71. doi: 10.1016/j.toxlet.2005.05.020. Epub 2005 Aug 8.
The permeation rate and skin retention of benzene and methylbenzenes were assessed in vitro using hairless rat skin. The effects of unocclusive dermal exposures of these chemicals (15 microl every 2h for 8h a day for 4 days) on the transepidermal water loss (TEWL), erythema and skin histopathology were measured in CD hairless rats. The expression of IL-1 alpha and TNF-alpha in the skin and blood were measured at the end of dermal exposures. The flux of benzene was about 1.5-, 2.5- and 80-fold higher than toluene, xylene and tetramethyl benzene isomers (TMB), respectively, and the values were inversely correlated with molecular weight (r(2)=0.7455) and logoctanol-water partition coefficient (r(2)=0.7831). The retention of chemicals in stratum corneum (SC) was in the order of TMB>xylene>toluene approximately benzene. The TEWL and erythema data demonstrated that the irritation was in the following order: TMB>xylene>benzene. The histo-pathological examination showed that xylene and TMB induced granulocyte infiltration, swelling of the epidermis, and extensive disruption and damage of stratum corneum. Likewise, the expression of IL-1 alpha in the blood and TNF-alpha in the skin after dermal exposures was higher for TMB followed by xylene and benzene compared to control. In conclusion, the aromatic hydrocarbon chemicals induced cumulative irritation upon low-level repeat exposures for a 4-day period and the irritation increased with the number of methyl groups of benzene. The affinity of the chemical to SC and their gradual accumulation in the skin in the present study is the reason for the differences in the skin irritation profiles of different aromatic chemicals. Our ultimate goal is to develop a biologically based model that connects skin retention of chemical to the skin irritation response. The findings of the present study will be helpful in understanding the role of these chemicals in the jet fuel and various petroleum based fuels in inducing skin irritation response.
使用无毛大鼠皮肤在体外评估了苯和甲基苯的渗透速率及皮肤滞留情况。在CD无毛大鼠中测量了这些化学物质（每天8小时，每2小时15微升，持续4天）非封闭性皮肤暴露对经表皮水分流失（TEWL）、红斑和皮肤组织病理学的影响。在皮肤暴露结束时测量皮肤和血液中IL-1α和TNF-α的表达。苯的通量分别比甲苯、二甲苯和四甲基苯异构体（TMB）高约1.5倍、2.5倍和80倍，这些值与分子量（r² = 0.7455）和正辛醇 - 水分配系数（r² = 0.7831）呈负相关。化学物质在角质层（SC）中的滞留顺序为TMB>二甲苯>甲苯>苯。TEWL和红斑数据表明刺激性顺序为：TMB>二甲苯>苯。组织病理学检查显示，二甲苯和TMB诱导粒细胞浸润、表皮肿胀以及角质层广泛破坏和损伤。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TMB组中更高，其次是二甲苯和苯。总之，芳香烃化学物质在4天的低水平重复暴露后会引起累积性刺激，且刺激性随着苯甲基数量的增加而增强。在本研究中，化学物质对角质层的亲和力及其在皮肤中的逐渐积累是不同芳香族化学物质皮肤刺激特征存在差异的原因。我们的最终目标是建立一个基于生物学的模型，将化学物质的皮肤滞留与皮肤刺激反应联系起来。本研究结果将有助于理解这些化学物质在喷气燃料和各种石油基燃料中诱导皮肤刺激反应的作用。
