Reaction mass of cerium dioxide and lanthanum oxide and lanthanum fluoride

Endpoint summary

Additional information

One key in vitro study (Ames test) is available on the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride (Klimisch 1). Other studies (Ames test - OECD 471, gene mutation assay in mammalian cells - OECD 476 and in vivo mouse bone marrow micronucleus assay - OECD 474) are available on cerium dioxide, the majority constituent of the reaction mass. In addition, one reliable in vitro study is available on the other constituent lanthanum oxide (Ames test - OECD 471). No reliable in vivo data were available on lanthanum oxide or lanthanum fluoride. However, lanthanum oxide tested negative in an in vitro study and therefore no in vivo mutagenicity tests should be performed with this substance.

As these constituents showed similar physicochemical, toxicological, ecotoxicological and environmental properties, results of studies performed on cerium dioxide and lanthanum oxide are used as supportive evidence for the full assessment of the genetic toxicity potential of the reaction mass.

Further genetic toxicity studies on the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride are therefore not regarderd as scientifically necessary according to section 1 of Reach Annex XI and are not recommended under animal protection considerations.

 

Study on the reaction mass:

The potential of the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride to induce reverse gene mutations in Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 was evaluated in a study performed according to OECD Guideline n° 471and in compliance with GLP. This study (Klimisch 1) was used as key study. The reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride was tested in 2 independent experiments performed according to direct plate incorporation method except for the second test with S9 mix which was performed according to the pre-incubation method, at concentration levels ranging between 156.3 and 2500 µg/plate. No noteworthy increase in the number of revertants was observed following treatment with the test substance, either with or without metabolic activation, in any of the five tester strains. An important precipitate was observed when scoring the revertants at dose-levels >= 625 µg/plate. The number of revertants for the vehicle and positive controls was as specified in the acceptance criteria. The study was therefore considered valid.

Under these experimental conditions, the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium.

 

Studies on the constituents:

The ability of cerium dioxide to induce genetic damage was assessed both in vitro and in vivo.

In vitro, two bacterial reverse mutation assays (Amestests; both quoted as Klimisch 2) are available and were used as supporting studies. Both Ames tests gave negative results up to the limit concentration of 5000 µg/plate of cerium dioxide with or without exogenous metabolic activation. In a gene mutation assay at the HPRT locus of V79 cells (RCC-CCR, 2006; Klimisch 2), cerium dioxide also induced no mutations up to 1800µg/mL with or without metabolic activation.

In vivo, cerium dioxide was tested in a mouse bone marrow micronucleus assay (CIT, 1993; Klimisch 2). There was no indication of clastogenic effects at 24 h or 48 h following a single oral administration of a limit dose level of 2000 mg/kg bw.

Therefore, cerium dioxide is considered to be devoid of genetic toxicity.

The ability of lanthanum oxide to induce genetic damage was assessed in vitro.

One reliable Ames test (Klimisch 2) was performed according to EU method B13/14 (RCC-CCR, 2006). ThisAmestests gave negative results up to the limit concentration of 5000 µg/plate of lanthanum oxide with or without exogenous metabolic activation.

No reliable data were available on the in vivo genetic toxicity of lanthanum oxide or lanthanum fluoride. However lanthanum oxide tested negative in an in vitro test and therefore no in vivo mutagenicity tests should be performed with this substance.

 

Genetic Toxicity	Reaction mass	Cerium dioxide	Lanthanum oxide	Lanthanum fluoride
In vitro Ames test	Negative +/- metabolic activation	Negative +/- metabolic activation	Negative +/- metabolic activation	-
In vitro gene mutation assay in mammalian cells	-	Negative +/- metabolic activation	-	-
In vivo mouse bone marrow micronucleus assay	-	Negative at 2000 mg/kg bw (oral route)	-	-

 

Short description of key information:
No indication of mutagenicity was observed in an Ames test performed with the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride. Furthermore, no indication of genetic toxicity of cerium dioxide, the majority constituent of the reaction mass, was observed in in vitro (Ames test and gene mutation assay in mammalian cells) and in vivo (mouse bone marrow micronucleus assay) studies. In addition, no indication of genetic toxicity of lanthanum oxide, another constituent of the reaction mass, was observed in an in vitro study (Ames test). No in vivo data were available on lanthanum oxide or lanthanum fluoride. However, lanthanum oxide tested negative in in vitro studies and therefore no in vivo mutagenicity tests should be performed with this substance.
As these constituents showed similar physicochemical, toxicological, ecotoxicological and environmental properties, results of studies performed on cerium dioxide and lanthanum oxide are used as supporting evidence for the full assessment of the genetic toxicity potential of the reaction mass.
Further genetic toxicity studies on the reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride are therefore not regarded as scientifically necessary according to section 1 of Reach Annex XI and are not recommended under animal protection considerations.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the classification criteria of Annex VI Directive 67/548/CEE or UN GHS/EU CLP, and considering the negative results in all in vitro and in vivo genetic toxicity tests using either the reaction mass of cerium dioxide and lanthanum oxide and lanthanum fluoride or its constituents, no classification for mutagenicity is required for the reaction mass of cerium dioxide and lanthanum oxide and lanthanum fluoride.