Vulvar tissue is more permeable than exposed skin due to differences in structure, occlusion, hydration and susceptibility to friction. The safety assessment of products that contact the vulva should account for this potentially heightened permeability. Standard clinical patch tests may not sufficiently mimic vulvar exposures. Because testing on the vulva is not routinely feasible, we are investigating new and modified cutaneous test methods to increase the degree of conservatism of the safety assessment. To this end, we have 1) developed a method to assess chemical and frictional effects by means of repeated application to the popliteal fossa (the behind-the-knee test); 2) modified the quantitative risk assessment for the induction of allergic contact dermatitis; and 3) proposed a modified human repeat insult patch test for assessing materials intended for vulvar contact. Modification of the traditional 4-day, irritation patch test by using wet samples or compromized skin sites failed to enhance test sensitivity. Future studies will evaluate testing in subjects with heightened susceptibility to chemical and sensory irritation, in order to increase test sensitivity to chemical irritants. These approaches can be employed to augment the margin of safety when cutaneous test methods are applied to agents that contact the vulva.