Use of the local lymph node assay for the estimation of relative contact allergenic potency

The effective toxicological evaluation of skin sensitization demands that p otential contact allergens are identified and that the likely risks of sens itization among exposed populations assessed. By definition, chemicals whic h possess the toxicological property of skin sensitization potentially are capable of causing allergic contact dermatitis (ACD) in humans. However, th is hazard is not an all-or-none phenomenon; clear dose-response relationshi ps can be discerned and thresholds identified for both the induction of sen sitization and the elicitation of contact dermatitis. Commonly, these param eters are grouped under the heading of potency, determination of which is v ital for risk assessment. In the present investigation, the local lymph nod e assay (LLNA) has been employed to determine the relative potency of a ran ge of 20 chemicals. The parameter used is the estimated concentration requi red to produce a 3-fold increase in draining lymph-node cell proliferative activity, the EC3 value. These measurements have been compared with an asse ssment of the human sensitizing potency of the 20 selected chemicals, each being assigned to 1 of 5 classes based on their human sensitizing potency. The EC3 value, derived from LLNA work carried out in acetone/olive oil vehi cle, correlated well with the human classification, with the strongest sens itizers having low EC3 values (<0.1%), weaker sensitizers having EC3 values generally in the 1-10% range, and non-sensitizing chemicals having EC3 val ues in excess of 100%. In conclusion, the derivation of the EC3 for a chemi cal provides an objective and quantitative estimate of potency that is of c onsiderable utility for skin sensitization risk assessment.