Reaction mass of aluminium fluoride and chromium trifluoride and nickel difluoride

Endpoint summary

Additional information

Nickel compounds have been extensively assessed for genotoxic effects in vitro or in vivo. Four in vitro studies and 3 in vivo studies have been selected for the purpose of the PBN1 mixture genotoxicity assessment. These studies were qualified as key or supportive studies, based on their respective reliability and the different endpoints covered.

The available weight of evidence suggests that nickel does not alter the frequency of gene mutations in non-mammalian

organisms (De Flora, 1984; Arlauskas, 1985). Increases in the frequency of gene mutations have been found in mouse lymphoma cells (Amacher, 1980). Overall evidence indicate that nickel compounds do not induce point mutations in bacteria but may exert mutagenic activity in mammalian cells in vitro.

There is also some evidence to suggest that nickel is clastogenic and able to damage DNA. Chromosome gaps or chromosome aberrations have been observed in mouse bone marrow cells following intraperitoneal injection (Dhir, 1991; Mohanty, 1987), and in in vitro assays using hamster cells (Sen, 1987). Micronucleus formation was increased in mouse bone marrow cells following intraperitoneal exposure (Dhir, 1991). DNA single strand breaks and damage, as assessed using comet analysis, were observed in leukocytes from mice exposed orally (Danadevi, 2004).

There are no definitive tests of nickel compounds on the germ cells and evidence for a possible effect is limited. However there is evidence that the nickel ion reaches the testis, so a possible effect cannot be excluded.

In conclusion, the classification of nickel chloride and nickel fluoride as Mutagenic Cat. 3; R68 was based on evidence of in vivo genotoxicity in somatic cells, after systemic exposure. The possibility that the germ cells are affected cannot be excluded.

Short description of key information:
Overall evidence indicate that nickel compounds do not induce point mutations in bacteria but may exert mutagenic activity in mammalian cells in vitro. There is also some evidence that nickel is clastogenic and able to damage DNA both in vitro and in vivo. A possible effect on germ cells cannot be excluded.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

According to the Annex I of Directive 67/548/EEC, nickel fluoride (CAS No.: 10028 -18 -9) and nickel chloride (CAS No.: 7718 -54 -9) are classified Mutagenic Category 3; R68 (irreversible effects).As they are both present at 9.5 and 4.5%, respectively in the mixture, PBN1 mixture should be classified as Mutagenic Category 3; R68 taking into account the classification criteria of Directive 1999/45/EC or Mutagenic cat. 2 (H341) taking into account the classification criteria of Directive1272/2008/EC (CLP).