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Key value for chemical safety assessment

Additional information

There is little data on the in vitro genotoxicity of nickel nitrate. The two studies of gene mutation in S. typhimurium show the same negative effects normally seen for other nickel compounds. The two other tests provide little evidence on the in vitro genotoxicity of nickel nitrate in mammalian cells.

Thein vivogenotoxicity of both nickel chloride and nickel sulphate has been studied more extensively than nickel nitrate. The evidence from the different studies has been discussed in the risk assessment reports for nickel chloride and nickel sulphate.

There is little evidence concerning hereditable effects on germ cells. Whilst there is evidence that nickel ions reach the testes, the effects seen in the Deknudt & Léonard (1982) dominant lethal study may reflect toxic effects on germ cells rather than chromosomal damage.

There are two studies on micronucleus induction in peripheral lymphocytes of mice after oral exposure to nickel nitrate. Oller and Erexson (2007) examined the protocols used in these studies compared to current accepted guidelines for this kind ofin vivostudies. According to Oller and Erexson (2007), the studies by Sharma et al (1987) and Sobti and Gill (1989) had design issues that made the results equivocal, even if they were considered to be positive by their authors. A guidance-compliant oral study of micronucleus in bone marrow of rats repeatedly exposed to nickel sulphate hexaydrate yielded negative results even though elevated Ni levels were measured in blood and bone marrow of exposed animals and even though absorbed doses were calculated to be higher than in the previously conducted studies in mice (Oller and Erexson, 2007). This guideline compliant study can be read across to nickel nitrate and adds to the weight of evidence forin vivomutagenicity. Similarly a repeated dose inhalation study with nickel sulphate hexahydrate in rats can be read across to nickel dinitrate (Benson et al., 2002). This study found that inhalation exposures to soluble nickel at toxic levels can cause genotoxicity in the respiratory tractin vivo.

The opinion of the EU Specialised Experts was sought in 2004 with regard to the classification of nickel nitrate for mutagenicity. The Specialised Experts concluded that nickel sulphate, nickel chloride and nickel nitrate should be classified as Muta. Cat. 3; R68 (European Commission, 2004). This conclusion was based on evidence ofin vivogenotoxicity in somatic cells, after systemic exposure. Hence the possibility that the germ cells are affected cannot be excluded. The Specialised Experts did not consider that further testing of effects on germ cells was practicable (European Commission, 2004).

 

The following information is taken into account for any hazard / risk assessment:

 

The Specialised Experts concluded that nickel sulphate, nickel chloride and nickel nitrate should be classified as Muta. Cat. 3; R68 (European Commission, 2004). This conclusion is based on evidence ofin vivogenotoxicity in somatic cells, after systemic exposure. Hence the possibility that the germ cells are affected cannot be excluded. The Specialised Experts did not consider that further testing of effects on germ cells was practicable (European Commission, 2004).

Value used for CSA:Genetic toxicity: positive

Justification for classification or non-classification

Ni nitrate is classified as Muta. 2; H341 according to the 1st ATP to the CLP Regulation. Background information can be found in the discussion section. Recently, nickel compounds have been recognized as genotoxic carcinogens with threshold mode of action by ECHA RAC opinion on nickel and nickel compounds OELs (see ECHA 2018 report discussion inAppendix C2).