TOXICITY, UPTAKE, AND MUTAGENICITY OF PARTICULATE AND SOLUBLE NICKEL COMPOUNDS

Toxicin testing in AS52 cells (24-hr exposures) gave LC(50) values of 2 to 130 mu g Ni/ml for particulate nickel compounds and 45 to 60 mu g Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)(2)). The Ni(OH)(2), NiCO3, and sulfides (Ni3S2, Ni7S6, ''amorphous NiS'') exhibited similar toxicities (LC(50)'s of 2 to 8 mu g Ni/ml), while three nickel oxides were more variable and less toxic (LC(50)'s of 18 to 130 mu g Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of approximate to 1:1.5 to 7:5 (except approximate to 1:20 for nickel salts). At the LC(50)'s, a 75-fold range in exposure levels occurred corn pared to a 10-fold range in cytoplasmic and nuclear nickel concentrations, [Ni]. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Nil); water-soluble salts (very low nuclear [Ni]; high cytosolic [Ni]), and slightly soluble compounds (relatively high cytosolic and nuclear [Ni]). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing ''weak'' mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds.