Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

IN VITRO DATA

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 reduction in the growth of the bacterial background lawn at any concentration. 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 chromosome aberration

The potential of the test material to induce structural chromosomal aberrations was determined in a study performed in accordance with the standardised guideline EU Method B.10. During the study primary lymphocyte cultures were exposed to test material, in distilled water, at concentrations of 45.6 - 7020 µg/mL or 87.0 - 2500 µg/mL with and without metabolic activation, respectively. The test material was tested up to precipitating concentrations.
Under the conditions of the study there was no evidence of chromosome aberration induced over background. Positive controls induced the appropriate response.

Therefore, the test material is considered to be non-clastogenic in this chromosome aberration test when tested up to precipitating concentrations.

In vitro gene mutation in mammalian cells

The potential of the test material to cause gene mutation or clastogenic effects in mammalian cells was determined in a GLP study which was conducted in accordance with the standardised guideline EU Method B.17. During the study Chinese hamster V79 cells were exposed to test material, in deionised water, at concentrations of 143.8 to 2300 µg/mL in the presence and absence of mammalian metabolic activation. The test material was tested up to precipitating concentrations. Under the conditions of the study there was no evidence of induced mutant colonies over background. The positive controls induced the appropriate response. Therefore, the test material is considered to be non-mutagenic in this HPRT assay.

The in vitro gene mutation assay in bacteria was conducted with the registration substance. It was a GLP study conducted to standardised guidelines. The study was therefore assigned a reliability score of 1 according to the criteria of Klimisch (1997).

The in vitro chromosome aberration assay and the mammalian cell gene mutation assay were conducted with the read across substance cerium carbonate. Since they were both conducted to GLP and in accordance with standardised guidelines, they were each assigned a reliability score of 2. The similar toxicological profiles of cerium carbonate and cerium oxalate, along with the structural similarity, mean that this is considered to be an acceptable read-across approach.


Justification for selection of genetic toxicity endpoint
Three studies have been selected as key in order to address the 3 different genetic toxicity endpoints under REACH. All three studies have been conducted in GLP certified laboratories, in line with recognised OECD guidelines and are considered sufficiently reliable in accordance with Klimisch (1997) to be key studies.

Short description of key information:
Reverse mutation in bacteria exposed to registration substance: Negative (S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and E. coli strain WP2uvrA with and without metabolic activation), OECD 471, EU Method B.13/14, Harlan 2012.

In vitro chromosome aberration exposed to read across substance (cerium carbonate): Negative (human lymphocytes with and without metabolic activation), EU Method B.10, RCC-CCR 2006.

In vitro gene mutation in mammalian cells exposed to read across substance (cerium carbonate): Negative (Chinese hamster V79 cells with and without metabolic activation), EU Method B.17, RCC-CCR 2006.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for genetic toxicity based on the overall negative response noted in the available genetic toxicity studies.