Over the years a number of methods have been developed to assess the potential contact irritancy of cosmetic-related surfactants. These methods include in vitro exposure using skin equivalent cultures, proteins, enzymes, etc. These methods are exaggerated in so far as the time of exposure, concentration of material tested, and/or material composition do not represent typical use. Moreover, these in vitro data generally do not show a relationship with in vivo outcome. We present a method that utilizes an in vitro skin equivalent model and limited product exposure that more closely simulates typical product use. Under these exposure conditions there is robust excretion of the irritant-associated cytokine, interleukin-1alpha, but minimal effect on skin culture viability. We show a consistent relationship between in vivo irritant contact dermatitis as evaluated using a mildly exaggerated exposure protocol and in vitro interleukin-1alpha excretion. Using this modified in vitro methodology and related methods, our data suggest that the irritant potential of Na-soap is largely related to the bio-availability of its Na-laurate content and interaction with the skin surface.