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Additional information

A single study was identified characterizing the genotoxicity of nickel sulphamate (tetrahydrate); however, because the primary reference (JETOC 1996) was not able to be obtained, information was based on summary findings presented in the Chemical Carcinogenesis Research Information System (CCRIS 2003) and data provided via personal communication (Okubo T, 2009). Collectively, these secondary sources reported the findings of mutagenicity testing in the Ames Salmonella Typhimurium assay. Results were negative in all six strains tested both in the presence and absence of metabolic activation, with the exception of the metabolically activated E. coli. However, because the documentation was insufficient, these data were not sufficient to characterize the genetic toxicity of nickel sulphamate.

Data regarding genotoxicity of nickel sulphamate are read-across from Ni sulphate. From the data reviewed above there is clear evidence indicating that nickel sulphate is genotoxic in vitro, and in particular, is clastogenic. There are a number of in vivo studies in both animals and man. The study by Benson et al. (2002) is the most comprehensive part of the database onin vivogenotoxicity of Ni compounds and shows that nickel sulphate given by inhalation seems to induce inflammation and genotoxicity in lung cells at approximately the same concentrations. Results of a recent micronucleus study, after oral administration is negative (Oller and Erexson, 2007). Evidence from human studies is limited.

The opinion of the Specialised Experts has been sought with regard to the classification of nickel sulphate as Muta. Cat. 3; R68 at their meeting in April 2004. The Specialised Experts concluded that nickel sulphate, nickel chloride and nickel nitrate should be classified as Muta. Cat. 3; R68. This conclusion is based on evidence of in vivo genotoxicity 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).

Further testing in an in vivo comet assay in lung cells after inhalational exposure is also considered to be unnecessary for the purposes of risk characterisation. A positive result would not alter the conclusions for the classification as a mutagen, and a negative result would not be regarded as sufficient evidence to justify the use of a threshold approach in the carcinogenicity risk characterisation. Hence, further testing for this effect would not produce additional information that would significantly change the outcome of this risk assessment.

In addition, bacterial mutagenicity tests have been shown to have little utility for the testing of metals, thus further limiting the usefulness of the available data. Since nickel sulphamate is read across from Ni sulphate it carries a classification as Muta. 2;H341.

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

Data regarding genotoxicity are read-across from Ni sulphate. There is clear evidence indicating that nickel sulphate is genotoxic in vitro, and in particular, is clastogenic. There are a number of in vivo studies in animals. The study by Benson (2002) shows that nickel sulphate given by inhalation seems to induce inflammation and genotoxicity in lung cells at approximately the same concentrations. Some in vivo studies were positive while a recent repeated dose oral micronucleus study (Oller and Erexson, 2007) was negative. Evidence from human studies is limited. There are no definitive studies on germ cells, and little evidence concerning hereditable effects. Recently, nickel compounds have been recognized as genotoxic carcinogens with threshold mode of action in ECHA RAC opinion on nickel and nickel compounds OELs (see ECHA 2018 report discussion inAppendix C2).

Justification for classification or non-classification

Nickel sulphamate is classified as Muta. 2: H341 in the 1st ATP to the CLP Regulation. Background information regarding this classification is provided in the discussion section above.