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Genetic toxicity in vitro:

Bacterial reverse mutation assay:

Thompson (2013) performed an Ames (preliminary toxicity test, plate incorporation assay and preincubation method) test with S. typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrA in the presence and absence metabolic activation (10% S9 -mix). The study was performed according to OECD 471 and in accordance with GLP, and thus was scored as K1 according to Klimisch criteria.

 

Cells were exposed in triplicate in both experiments to the test substance from 5 to 5000 µg/plate (cerium trichloride as active ingredient).

 

The test item caused a visible reduction in the growth of the bacterial background lawns in all tester strains (except TA98 dosed in the presence of S9-mix in Experiment 2) in both the presence and absence of S9-mix at 5000 µg/plate in both experiments. A slight reduction in TA98 revertant colony frequency was noted at 5000 µg/plate in Experiment 2 (presence of S9-mix) without a weakening of the bacterial background lawns. These results were not indicative of toxicity sufficiently severe enough to prevent the test item being tested up to the maximum recommended dose level of 5000 µg/plate. A test item precipitate (particulate in appearance) was noted at 5000 µg/plate in both the presence and absence of S9-mix in Experiments 1 and 2, this observation did not prevent the scoring of revertant colonies.

 

No significant increases in the frequency of revertant colonies were recorded for any of the strains of bacteria, at any dose level either with or without metabolic activation or exposure method.

 

All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies thus confirming the activity of the S9-mix and the sensitivity of the bacterial strains.

 

Solvent, negative and positive controls were valid. The test item, cerium trichloride, was considered to be non-mutagenic under the conditions of this test.

 

Chromosome Abberation:

Read across to cerium trinitrate is suggested for this endpoint. We refer to the read across justification added in section 13 to the IUCLID file for extrapolation to cerium trichloride. Bowles (2013) performed an in vitro Chromosome Aberration test in human lymphocytes (OECD Guideline 473 and EU Method B10). Two experiments were performed using different test concentrations with and without S9 activation (4h or 24h exposure; 20h expression period). In both experiments cerium trinitrate exhibited a modest dose-related inhibition of mitotic index in the dose levels tested. However, the substance did not induce any statistically significant increases in the frequency of cells with aberrations in either exposure group, which included a dose level that was generally within the optimal 50% mitotic inhibition. The test item did not induce a statistically significant increase in the numbers of polyploid cells at any dose level in any of the exposure groups. Cerium trinitrate was considered to be non-clastogenic both in the presence and absence of metabolic activation.

 

In vitro mammalian cell gene mutation:

Morris (2013) performed a CHO hprt forward mutation assay with the read-across substance cerium trinitrate, targeting the HPRT locus of Chinese hamster ovary (CHO) cells, according to OECD Guideline 476 and EU Method B.17. The technique used is a plate assay using tissue culture flasks and 6-thioguanine (6-TG) as the selective agent. The vehicle and positive control were considered to be valid and the test item did not demonstrate dose related increases in mutant frequency either with or without metabolic activation, either in the first or the second experiment. Therefore, the test item was considered to be non-mutagenic to CHO cells at the HPRT locus under the conditions of this test.

Genetic toxicity in vivo:

According to REACH Annex IX section 8.4, column 2, no further in vivo testing is required as no positive results were obtained in any of the three in vitro studies performed according to REACH Annexes VII and VIII section 8.4.

 


Justification for selection of genetic toxicity endpoint
No study is selected as three key studies are used to cover this endpoint.

Short description of key information:
Genetic toxicity in vitro:
In an Ames test according to OECD Guideline 471, EU Method B.13/14 and EPA OPPTS 870.5100 (Thompson, 2013), cerium trichloride proved to be negative for mutagenicity with and without metabolic activation.

Chromosome aberration: performed with the read-across substance cerium trinitrate according to OECD 473 in human lymphocytes (Bowles, 2013). According to the test results of the study, cerium trinitrate is considered to be non-clastogenic in either the presence and the absence of metabolic activation. We refer to the read across justification added in section 13 to the IUCLID file for extrapolation to cerium trichloride.

In vitro mammalian cell gene mutation: performed with the read-across substance cerium trinitrate according to OECD 476 in Chinese hamster Ovary (CHO) cells (Morris, 2013). According to the test results of the study, cerium trinitrate is considered to be non-mutagenic with and without metabolic activation. We refer to the read-across justification added in section 13 to the IUCLID file for extrapolation to cerium trichloride.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

On the basis of the available information and according to the criteria of the DSD and CLP Regulation, cerium trichloride should not be classified as mutagenic.

 

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