The effect of occlusive and unocclusive exposure to xylene and benzene on skin irritation and molecular responses in hairless rats

Aromatic hydrocarbons readily penetrate the skin on dermal exposure, leading to irritation, inflammation and cytotoxicity. The effects of short-term occlusive and long-term unocclusive dermal exposure to benzene and xylene on the skin irritation response (transepidermal water loss (TEWL), skin moisture content and erythema) and cytokine/chemokine expression (interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1)) were investigated in hairless rats. Occlusive dermal exposure was carried out with 230 mu L of the chemicals for 1 h using Hill top chambers. In unocclusive dermal exposure, 15 mu L of the chemicals were applied to the skin every 2 h, for 8 h a day, for 4 days. The occlusive dermal exposure revealed a clear difference in the TEWL and erythema response of these chemicals (xylene > benzene) whereas unocclusive exposure revealed similar TEWL and erythema scores for both benzene and xylene. The expression of IL-1 alpha was elevated 2.5- and 3.8-fold in response to occlusive and unocclusive exposure, respectively, vs control (P < 0.01) for both the chemicals (benzene and xylene). Similarly, TNF-alpha levels were elevated about 2.4- and 6.0-fold as a result of occlusive and unocclusive exposure, respectively, vs control (P < 0.01). These results show that unocclusive exposure induced significantly higher TNF-alpha expression than occlusive exposure (P < 0.05). The MCP-1 expression in blood was slightly elevated compared with the control group, but this increase was not statistically significant (P > 0.05). Similarly, MCP levels in skin were increased approximately 1.7- and 1.8-fold by occlusive and unocclusive exposure, respectively, compared with the control group (P < 0.05). Our study demonstrates that the skin irritation profiles of benzene and xylene are similar and unocclusive long-term exposure to small amounts of these chemicals can induce more skin irritation and cytokine response than occlusive exposure.