Lithium Nickel Cobalt Aluminium Oxide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Ames Test

The potential of the test material to cause genetic toxicity was investigated in a bacterial reverse mutation assay.

The method conforms to the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including METI, MHLW and MAFF. It also meets the requirements of the OECD Guidelines for Testing of Chemicals No. 471 "Bacterial Reverse Mutation Test", Method B13/14 of Commission Directive 2000/32/EC and the, EPA (TSCA) OPPTS harmonised guidelines.

Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA^-were treated with suspensions of the test material using the Ames plate incorporation method at five dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolising system.

The test material caused no visible reduction in the growth of the bacterial background lawn at any dose level and was, therefore, tested up to the maximum recommended dose level of 5000 µg/plate. A dark, particulate precipitate was observed under an inverted microscope at 5000 µg/plate, this did not prevent the scoring of revertant colonies.

No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation.

The test material was considered to be non-mutagenic under the conditions of this test.

 

In Vitro Chromosome Aberration Test

The potential of the test material to cause structural chromosomal aberrations in cultured mammalian cells was investigated. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1997) No. 473 "Genetic Toxicology: Chromosome Aberration Test" and Method B10 of Commission Directive 2000/32/EC. The study design also meets the requirements of the UK Department of Health Guidelines for Testing of Chemicals for Mutagenicity.

Duplicate cultures of human lymphocytes, treated with the test material, were evaluated for chromosome aberrations at three dose levels and for different exposure durations.

The test material appeared to be non toxic at the maximum recommended dose level in the 4(20)‑hour exposure groups but induced approximately 50% mitotic inhibition in the 24-hour continuous exposure group. The test material did not induce any statistically significant increases in the frequency of cells with aberrations, in either of two separate experiments.

The test material was considered to be non-clastogenic to human lymphocytes in vitro.

 

In vitro Mammalian Gene Mutation Test

The study was conducted to assess the potential mutagenicity of the test material on the thymidine kinase, TK +/-, locus of the L5178Y mouse lymphoma cell line in accordance with the standardised guidelines OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test) and EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test).

L5178Y TK +/- 3.7.2c mouse lymphoma cells (heterozygous at the thymidine kinase locus) were treated with the test material at six dose levels, both in the absence and presence of metabolic activation. 

The maximum dose level used was the maximum recommended dose level (5000 µg/mL). A precipitate of test material was observed at and above 312.5 µg/mL. The test material did not induce any toxicologically significant increases in the mutant frequency at any dose level, either with or without metabolic activation. 

The test material was considered to be non-mutagenic to L5178Y cells under the conditions of the test.

Justification for selection of genetic toxicity endpoint
No single endpoint was selected as the three studies are not comparable. All are key and investigate different aspects of genetic toxicity.

The key bacterial study was conducted in accordance with the standardised guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including METI, MHLW and MAFF. It also meets the requirements of the OECD Guidelines for Testing of Chemicals No. 471 "Bacterial Reverse Mutation Test", Method B13/14 of Commission Directive 2000/32/EC and the, EPA (TSCA) OPPTS harmonised guidelines.
It complies with GLP and was awarded a reliability score of 1 in accordance with the principles laid out by Klimisch (1997).

The key in vitro chromosome aberration study was conducted in accordance with the standardised guidelines OECD Guidelines for Testing of Chemicals (1997) No. 473 "Genetic Toxicology: Chromosome Aberration Test" and Method B10 of Commission Directive 2000/32/EC. The study design also meets the requirements of the UK Department of Health Guidelines for Testing of Chemicals for Mutagenicity.
It complies with GLP and was awarded a reliability score of 1 in accordance with the principles laid out by Klimisch (1997).

The key in vitro mammalian gene mutation study was conducted in accordance with the standardised guidelines OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test) and EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test).
It complies with GLP and was awarded a reliability score of 1 in accordance with the principles laid out by Klimisch (1997).

Short description of key information:
The bacterial reverse mutation assay result was negative.
The in vitro mammalian chromosome aberration test was negative.
The mammalian gene mutation assay result was negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for genetic toxicity as all the in vitro routes of exposure failed to induce any toxic effects.

This conclusion is supported by the assessment of the genetic toxicity properties of NCA which was based on the genetic toxicity properties of its constituents (oxide forms of Al, Co, Li, Ni) (Assessment Entity Approach). This assessment, based on the CLP mixture rules and using the MeClas Classification Tool, was conducted on a generic NCA sample (composition based on worst-case concentrations for each constituent, as defined in IUCLID section 1.2). According to MeClas, the assessed generic NCA composition is not classified for genetic toxicity.