Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

Abstract

Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 pg Ni/ml for particulate nickel compounds and 45 to 60 pg Ni/ml for water-soluble salts (NiCI2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 pg Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 pg Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of -1:1.5 to 1:5 (except -1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 1 0-fold range in cytoplasmic and nuclear nickel concentrations, [Nil. 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 [Nil; high cytosolic [Nil), and slightly soluble compounds (relatively high cytosolic and nuclear [Nil). 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. -Environ Health Perspect 1 02(Suppl 3): 69-79 (1994).

Respiratory carcinogenicity assessment of soluble nickel compounds.

“…The higher concentrations required to see these effects with soluble nickel compounds are attributed to the less efficient cellular uptake of Ni 2+ ion from soluble than from insoluble nickel compounds. For example, the percentages of nickel in the nucleus of Chinese hamster ovary cells exposed to nickel sulfide/ subsulfide are up to 300-to 500-fold higher than the percentage levels of Ni 2+ in the nucleus of cells exposed to equivalent levels of nickel chloride (32,33).…”

Bioavailability of Nickel in Single‐Wall Carbon Nanotubes

“…The "nickel-ion hypothesis" states that the nickel toxicity, mutagenesis and carcinogenesis mainly depend on the intracellular nickel(II) ion concentration, independent of the original nickel compounds to which an organism is exposed. [25,26] Overall, the existing literature is sufficient to raise the issue of nickel effects in the biological response to CNTs, but there is major uncertainty due to the lack of information about the bioavailability of CNT-associated nickel. The known molecular mechanisms of nickel toxicity all involve soluble species which must be created by dissolution or "mobilization" from the condensed phase, [13,22] and this requires that the metalcontaining particles be accessible to the surrounding physiological fluid.…”

Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cells

“…Both insoluble and soluble nickel compounds can cause chromosome aberrations [e.g., Sen et al, 1987;Deng et al, 1988;Conway and Costa, 1989], oxidative DNA base damage, and DNA-protein cross-links [Patierno et al, 1985;Kasprzak, 1991]. Exposure to both insoluble and soluble nickel compounds is associated with increased mutations [Higinbotham et al, 1992;Kargacin et al, 1993;Rosetto et al, 1994;Harty et al, 1996;Zienolddiny et al, 2000] and malignant transformation [Costa et al, 1979;DiPaolo and Casto, 1979;Hansen and Stern, 1983;Patierno et al, 1993;Costa, 1996;Kerckaert et al, 1996], although in vivo, insoluble nickel generally demonstrates greater carcinogenicity, presumably because of the long-term production of Ni 2þ . Nickel has broad epigenetic effects on cultured cells.…”