The present study investigated the epirubicin (EPI) permeability of various commercially available glove types, as well as toxicity mechanisms and effects on human keratinocyte cell line (HaCaT). Permeability experiments were carried out on various commercially available gloves, differing as regards material and thickness. Permeability was evaluated after different "contact times" and the influence of EPI solution's pH (acid and neutral) on permeability was also examined. Toxicity of EPI toward skin was tested by evaluating the effects of the drug on cell growth and apoptosis, by using an in vitro model based on cultured immortalized human keratinocytes. No permeation was detected in the case of EPI neutral solutions; in contrast, acid solutions were found to penetrate low thickness nitrile gloves. Obtained results also showed the induction of apoptosis in epithelial cells through the activation of intrinsic pathway p53-independent occurring even when cells are exposed at low drug concentration. EPI solution's pH influences the glove's permeability; once penetrated, EPI at concentrations lower than those able to penetrate the nitrile glove during the 8-h work-shift can cause apoptosis in epithelial cells. The findings reported here highly support the choice of either natural rubbers gloves or high thickness nitrile ones for preventing the occupational exposure to EPI.