Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro gene mutation in bacteria

The potential of the test material to cause mutagenic effects in bacteria was assessed in accordance with the standardised guidelines OECD 471 and EU Method B.13/14. Furthermore, the test method was designed to be compatible with the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including METI, MHLW and MAFF and the USA, EPA (TSCA) OPPTS harmonised guidelines.

Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA were treated with the test material, using the plate incorporation and pre-incubation methods, at five dose levels, both with and without metabolic activation. The dose levels assessed were 50, 150, 500, 1500 and 5000 µg/plate.

The test material caused no visible reduction in the growth of the bacterial background lawn at any dose level. The test material was, therefore, tested up to the maximum recommended dose level of 5000 μg/plate.

No toxicologically significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains. 

The vehicle controls gave revertant colony counts within the normal range. The positive controls gave the expected increases in revertants, validating the sensitivity of the assay and the efficacy of the S9-mix.

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

 

In vitro gene mutation in mammalian cells

In a mammalian cell gene mutation assay (HPRT locus) (Wollny, 2006), Chinese hamster V79 cells cultured in vitro were exposed to Cerium carbonate, in deionised water, at concentrations of 143.8 to 2300 µg/mL in the presence and absence of mammalian metabolic activation. Cerium carbonate was tested up to precipitating concentrations.

The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background.

Therefore, Cerium carbonate is considered to be non-mutagenic in this HPRT assay.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline EU Method B.17.

 

In vitro cytogenicity in mammalian cells

In a mammalian cell cytogenetics assay (chromosome aberration assay) (Schulz, 2006), primary lymphocyte cultures were exposed to Cerium carbonate (65.62 % of purity), in distilled water, at concentrations of 45.6 - 7020 µg/mL or  87.0 - 2500 µg/mL with and without metabolic activation. Cerium carbonate was tested up to precipitating concentrations.
Positive controls induced the appropriate response.
There was no evidence of chromosome aberration induced over background.

Therefore, Cerium carbonate is considered to be non-clastogenic in this chromosome aberration test when tested up to precipitating concentrations.
This study is classified as acceptable. This study satisfies the requirement for Test Guideline EU Method B.10 for in vitro cytogenetic mutagenicity data.


Justification for selection of genetic toxicity endpoint
Three studies have been selected as key to address the genetic toxicity endpoint. All are well reported studies conducted in accordance with standardised testing guidelines and performed under GLP conditions. The study (in vitro gene mutation in bacteria) performed on the registered substance were assigned reliability score of 1 accordance with Klimisch (1997). All other studies were performed on a suitable analogue, therefore, both studies were assigned a reliability score of 2.

Short description of key information:
In vitro gene mutation in bacteria (Ames): Harlan (2013): Negative with and without metabolic activation.
In vitro gene mutation in mammalian cells (V79): Wollny HE (2006): Negative with and without metabolic activation.
In vitro cytogenicity in mammalian cells (Chrom Ab): Schulz M and Kunz S (2006): Negative with and without metabolic activation.

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 (EC) No. 1272/2008, the test material does not require classification for genetic toxicity.