Individual, ethnic and seasonal variability in irritant susceptibility of skin: The implications for a predictive human patch test

Since irritants are the major cause of contact dermatitis, it is important to identify those chemicals that possess significant ability to cause skin irritation. This process must then be followed by risk assessment and risk management. Historically, animal tests have played a major role in this process, but human volunteer studies are of increasing importance in this field. Where the appropriate safety and ethical controls are in place, human testing can give data that identifies skin irritation hazard. To be of widest value, these human studies must not be flawed due to inter-individual, inter-ethnic or seasonal variation. We conducted a large dose-response study and studied the impact of summer and winter weather on a predictive human assay. Sodium dodecyl sulphate (SDS) was tested at 0.1%-20% in 3 national groups Of approximately 100 volunteers, using 25 mm Hill Top chambers loaded with 0.2 ml solution and applied to the upper outer arm for 4 h. Reactions were scored at 24, 48 and/or 72 h after patch application. The German and Chinese studies were completed in a few weeks under similar winter conditions, whereas the UK work was spread fairly evenly over about a 15-month period. Some relatively minor differences were observed in the dose-response curves obtained, probably due to weather conditions. The effect of the weather on the intensity, but not the pattern, of irritant reactivity was also evident in the smaller specific study that assessed reactions to SDS in summer and in winter. Whereas 45% of the panel reacted to 20% SDS in summer, 91% reacted in the winter. However, in both studies, substantial inter-individual variations in response to SDS dominated the pattern of response. When designing a human patch test to discriminate skin irritant substances from those that are of minimal effect, it is this inter-individual variability, rather than any small inter-ethnic or seasonal variation, which must be taken into account. This can be achieved by the routine inclusion of a suitable positive irritant control, which then calibrates each human volunteer panel.