Experimental studies of sensitization to beryllium, zirconium, and aluminum compounds in the rabbit

In a study designed to assess the potential sensitizing and granulomagenic capacities of selected metallic salts, rabbits were inoculated intradermally with zirconium aluminum glycinate (ZAG), sodium zirconium lactate (NZL), aluminum chlorhydrate (ACH), BeSO₄, and ovalbumin (OVA) by single and multiple injections. Animals immunized with BeSO₄ and with OVA developed delayed skin reactivity as well as antigen-specific alveolar macrophage migration inhibition. Neither single nor multiple injections of ZAG or ACH resulted in clear-cut positive skin reactivity, macrophage migration inhibitory factor (MIF) production, or lymphocyte stimulation. Rabbits inoculated with multiple injections of NZL (500 μg) showed some marginally positive macrophage migration inhibition and skin reactivity. Histologically, ZAG and ACH were found to induce well-organized foreign-body granulomas after intradermal injection in both normal and inoculated rabbits. NZL and BeSO₄ also induced skin granulomas, but these were less organized and distinct. Cell viability and ultrastructural studies indicated that BeSO₄ was highly toxic for isolated alveolar macrophages in vitro at concentrations above 10 μg/ml, but NZL and ZAG did not exert such an effect at these dose levels. BeSO₄ also depressed lymphocyte stimulation in sensitized animals which demonstrated delayed skin reactivity and macrophage migration inhibition.