Predictive testing for contact allergy : comparison of some guinea pig and mouse protocols including dose-response designs

Contact allergy (delayed hypersensitivity) may develop as a result of skin exposure to contact allergens (haptens) and can lead to allergic contact dermatitis. The purpose of this study was to evaluate some predictive animal test methods for contact allergens. It was done with the aim that the test methods giving the clinically most relevant results should be used in risk assessment of chemicals and in research. A slightly modified multi-dose-response induction protocol was evaluated with two model contact allergens when applied to three guinea pig predictive test methods. The protocol was easily applied to the cumulative contact enhancement test (CCET) and the Freund's complete adjuvant test (FCAT), which have only one induction route. However, for the guinea pig maximization test (GPMT) with two induction routes, the topical doses at induction interacted with the logistic model. The protocol would benefit from further development and some modifications are suggested. Calculations of the estimated concentration sensitizing 50 % of the animals (EC 50 ) improves the possibility for proper ranking of contact allergens and augments the information used in risk assessment. The calculated EC 50 -values for the model allergens were: 0.00045 % in the FCAT, 0.0025 % in the GPMT and 0.0042 % in the CCET for potassium dichromate (K 2 Cr 2 O 7 ), and 0.068 % in the GPMT, 0.89 % in the FCAT and 1.8 % in the CCET for hydroxycitronellal (HC). A multi-dose-response induction protocol was applied on a modified mouse ear swelling test (MEST) and evaluated with four contact allergens and one irritant. This protocol could detect the moderate to strong contact allergens as sensitizers, but not one (HC) of the two weak contact allergens. The irritant (negative control) gave a Ônegative' response. The EC 50 -values calculated for the three detected allergens were 0.002 % for oxazolone, 0.03 % for K 2 Cr 2 O 7 and 0.7 % for methyldibromo glutaronitrile (MDBGN). The murine local lymph node assay (LLNA) is a predictive test method, but its ability to discriminate between allergens and irritants has been questioned. Eight contact allergens and six irritants were investigated in the evaluation of the LLNA. The moderate to strong allergens gave clearly Ôpositive' results (stimulation index (SI) = 12.8 - 39.9), but one weak allergen (benzocaine) was not classified as a sensitizer (SI