Guidelines for Metals and Metalloids in Ambient ... - ARCHIVE: Defra

Expert Panel on Air Quality Standards
piercing and handling of coins and other nickel-containing products.
Rare cases of asthmatic lung disease have been reported after
occupational exposure to inorganic nickel compounds (WHO, 1991)
but there is no evidence that airborne nickel causes allergic reactions in
the general population.
3.3.1.2 Mechanism(s) of acute toxicity
135. Although nickel compounds cause the oxidation of lipids (Stinson
et al., 1992; Athar et al., 1987), proteins (Zhuang et al., 1994) and
nucleic acids (Stinson et al., 1992, Lynn et al., 1997), intracellular
radical production (Huang et al., 1994a,b), and glutathione depletion
(Rodriguez et al., 1991; Herrero et al., 1993; Li et al., 1993) there is
little evidence that free nickel undergoes redox cycling reactions, in
contrast to metals such as iron, copper, chromium, vanadium and
cobalt. Hydrated Ni 2+ ions react slowly with hydrogen peroxide to form
hydroxyl radicals and are not efficient catalysts of peroxide
decomposition. Their activity in models where lipid, protein and DNA
oxidation have been observed reflects the binding of nickel to
biological ligands such as the imidazole nitrogen of histidine that
reduces its oxidation potential allowing it to be oxidised to Ni 3+ by
strong oxidants, such as hydrogen peroxide and organic
hydroperoxides (Datta et al., 1992). This ligand-dependent Ni 2+ /Ni 3+
redox cycling of nickel results in the formation of oxygen radicals via
Fenton-type reactions (Klein et al., 1991; Lin et al., 1992). Consistent
with this view, studies have shown that the formation of alkyl, alkoxyl
and peroxyl radicals by nickel and cumene hydroperoxide occurs only
in the presence of glutathione, carnosine, homocarnosine or anserine
(Shi et al., 1992). This ligand-dependent reaction may also occur with
histones: these nuclear protein-Ni 2+ complexes permit hydroxyl radical
generation in the presence of hydrogen peroxide resulting in extensive
DNA base modification (Nackerdien et al., 1991). The above reactions,
which are summarised schematically in Figure 3.2, are associated with
soluble nickel salts and may be important in the induction of an
inflammatory response. Further evidence suggests that insoluble nickel
particulate compounds, including the sulphide and subsulphide, can
also induce the release of reactive oxygen species from phagocytic cells
(Costa and Mollenhauer, 1980). These insoluble forms of nickel have
been shown to be more carcinogenic than soluble nickel and in vitro
studies have demonstrated that they induce greater intracellular free
radical production than soluble nickel salts (Huang et al., 1994a,b).
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