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 impor tant to identify those chemicals that possess significant ability to c ause skin irritation. This process must then be followed by risk asses sment and risk management. Historically, animal tests have played a ma jor role in this process, but human volunteer studies are of increasin g importance in this field. Where the appropriate safety and ethical c ontrols are in place, human testing can give data that identifies skin irritation hazard. To be of widest value, these human studies must no t be flawed due to inter-individual, inter-ethnic or seasonal variatio n. 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 approxim ately 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 s cored at 24, 48 and/or 72 h after patch application. The German and Ch inese studies were completed in a few weeks under similar winter condi tions, whereas the UK work was spread fairly evenly over about a 15-mo nth period. Some relatively minor differences were observed in the dos e-response curves obtained, probably due to weather conditions. The ef fect of the weather on the intensity, but not the pattern, of irritant reactivity was also evident in the smaller specific study that assess ed 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 b oth studies, substantial inter-individual variations in response to SD S dominated the pattern of response. When designing a human patch test to discriminate skin irritant substances from those that are of minim al effect, it is this inter-individual variability, rather than any sm all inter-ethnic or seasonal variation, which must be taken into accou nt. This can be achieved by the routine inclusion of a suitable positi ve irritant control, which then calibrates each human volunteer panel.