Cumulative effect of subthreshold concentrations of irritants in humans

Background: The effect of subthreshold concentrations of irritants on the skin and the interactions between such substances are not fully understood. Objective: The objective of this study was to test the hypothesis that there is a cumulative effect of subthreshold concentrations of irritants using bioengineering methods for the detection of invisible cutaneous changes. Methods: Ten subjects were patch tested for 24 hours with half of the minimal irritant dose (MID) to aqueous sodium lauryl sulfate and lactic acid (10 patches of each). At 25 hours, additional patches were applied to the same sites containing five successive twofold dilutions of each irritant, starting with half of the MID. Each chemical was thus applied onto itself and onto the other chemical as well. In addition, mixtures of half of the MID of each substance and twofold dilutions of the other were also applied for two consecutive periods of 24 hours. At 25 and 49 hours, the cutaneous changes were monitored using the noninvasive methods of laser Doppler flowmetry, reflectance spectrophotometry, and electrical capacitance in addition to visual scoring. Results: Only faint visual changes were detected, whereas significant differences between the various patch testing combinations were instrumentally detected. Cutaneous blood flow at sites treated with half of the MID of one substance increased on an additional 24-hour period of occlusion with half of the MID of the other substance (P < .05) and, on several occasions, even with a quarter of the MID. Application of certain mixtures of the substances resulted in an elevated blood flow as well. Reflectance spectrophotometric measurements gave similar results with the additional finding of an elevation on reapplication of the same substance (P < .05). On the other hand, electrical capacitance was the same over all of the sites at all time points. Conclusion: The results indicate that subthreshold concentrations of irritants alter the skin, making it susceptible to a further insult with even lower concentrations. An augmentation of the response is suggested.