ASSESSMENT OF THE SENSITIZATION POTENTIAL OF 5 METAL-SALTS IN THE MURINE LOCAL LYMPH-NODE ASSAY

The murine local lymph node assay (LLNA) has been proposed as a predic tive test for the identification of sensitizing agents. We used this t est to compare the sensitization potential of NiSO4, K2Cr2O7, CoCl2, N a2PtCl6 and BeSO4, salts of metals which have all been associated with allergic contact dermatitis and either bronchial asthma or interstiti al lung disease, by either humoral or cell-mediated allergic mechanism s. BALB/c mice (n = 3 per concentration studied, three concentrations studied per metal) received three daily applications of the metal salt (in DMSO) on the dorsum of both ears. On the fourth day the draining auricular lymph nodes were removed and the incorporation of [H-3]-thym idine in the lymphocytes in culture was compared to that of concurrent vehicle-treated control mice, thus enabling to derive a stimulation i ndex (SI), indicative of immunological sensitization potential. Each e xperiment was performed three times. Oxazolone and toluene diisocyanat e, chosen as positive controls, yielded strongly positive SI values (> 20 and 30 respectively). Na2PtCl6 (SI 2.6 +/- 1.0 at 2.5%), CoCl2 (SI 2.8 +/- 0.5 at 5%) and possibly also K2Cr2O7 (SI 2.1 +/- 1.2 at 0.5%) were positive in the LLNA, whereas NiSO4 (SI 0.9 +/- 0.2 at 5%) and B eSO4 (SI 1.3 +/- 0.6 at 4%) were negative. Although our results are st ill limited by the fact that only one mice strain was tested, they ind icate that there is no strict relationship between the sensitization p otential of metal salts, as evaluated in the murine LLNA, and their po tential to cause either respiratory or dermal allergic disease. Conseq uently, caution should be exercised before proposing the murine LLNA a s a valid test to predict the sensitization potential of low molecular weight chemicals. (C) 1997 Elsevier Science Ireland Ltd.