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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

There are no mutagenicity studies available for [citric acid, nickel salt]. However, extensive data exist on the read-across substance nickel chloride.


Parts of the data are taken from the EU-RAR for nickel chloride, dated 2008.

In vitro

Nickel chloride has been extensively studied in bacteria.

De Flora et al. (1984) performed a pre-incubation bacterial reverse mutation assay in S. typhimurium strains TA 98, TA 100, TA 97, TA 1535, TA 1537 and TA 1538. This study yielded a negative result like most of the studies performed. However, two studies which were both fluctuation tests reported positive results. One, in S. typhimurium, was reported only as an abstract (La Velle and Witmer 1981). In the other, in Corynebacterium, no positive controls were employed (Pikalet and Necasek 1983).


In mammalian cells, all in vitro mutation and chromosomal aberrations test gave positive results (For details refer to EU-RAR.).


In vivo

A high number of animal studies indicate that nickel chloride induces DNA damage and chromosome aberrations in somatic cells in vivo. Data from in vivo micronucleus studies are conflicting (see EU-RAR).

Dhir et al. (1991) studied the effects of nickel chloride on chromosome aberrations (CA) and micronuclei (MN) in Swiss albino mice after intraperitoneal administration of 10, 20 and 40 mg/kg bw. For the CA study, there were 3 exposure levels with a single dose and three bone marrow samples were taken 6, 12 and 24 h after a single dose. 50 metaphases/animal were scored. For the MN study, there were again three exposure levels with 2 doses separated by 24 h. Bone marrow samples were taken 24 and 48 h after the second dose and 500 cells/animal were counted. There was a significant and dose-related increase in the chromosomal aberration rate. In the MN study, there was also a significant and dose related increase in incidence of micronuclei. There are no major differences in the NCE/PCE ratio at the different dose levels.



La Velle JM, Witmer CM (1981). Mutagenicity of NiCl2 and the analysis of mutagenicity of metal ions in a bacterial fluctuation test. Environ Mutag 3: 320-321.

Pikalet P, Necasek J (1983): The mutagenic activity of nickel in Corynebacterium sp. Folia Microbiol 28: 17-21.

Short description of key information:
In vitro:
Negative Ames test with TA 97, TA 98, TA 100, TA 1535, TA 1537 and TA 1538.
Positive results in mutation tests and chromosomal aberration assays in mammalian cells
In vivo:
Positive chromosome aberration and micronucleus tests.

Endpoint Conclusion:

Justification for classification or non-classification

Based on the available information from the read-across substance nickel chloride [citric acid, nickel salt] needs to be classified:

EU: Muta Category 3, R68

CLP: Category 2 germ cell mutagenicity