Lanthanum trinitrate

Endpoint summary

Additional information

Genetic toxicity in vitro:

Bacterial reverse mutation assay:

Zeiger (1992) performed an Ames test (pre-incubation test) with S. typhimurium strains TA 1535, TA 98, TA 100 and TA 97 with and without metabolic activation.

Following test concentrations were applied in triplicate:

0, 3.3, 10, 33, 100, 333, 1000, 3333 µg/plate for strains TA100 and TA1535

0, 33, 100, 333, 1000, 3333, 10000 µg/plate for strain TA97 and TA98

Solvent and positive controls were run in triplicate and were considered to be valid. According to the results of the study, the test substance is not mutagenic in the Ames with and without metabolic activation. This study is scored Klimisch 2 because of the deficiencies observed.

In the abovementioned study no strain having an AT base pair at the primary reversion site was tested. Therefore read-across to an Ames test with the read-across substance lanthanum acetate (another 'water soluble' lanthanum salt) is used in a 'weight-of-evidence' approach.Thompson (2013) performed an Ames test (OECD 471; EU B.13/14 and EPA OPPTS 870.5100) withS. typhimuriumstrains TA 1535, TA 1537, TA 98, TA 100 andE. colistrain WP2 uvrA with and without metabolic activation.

Following test concentrations were applied in triplicate: 50, 150, 500, 1500, 5000 µg/plate for experiment 1 and 5, 15, 50, 150, 500, 1500, 5000 µg/plate for experiment 2. Negative controls and positive controls were run in triplicate and were considered to be valid. According to the results of the study, the test substance is not mutagenic in the Ames with and without metabolic activation. This study is scored Klimisch K2 because the study has been used for read-across purposes in this dossier.

Chromosome Aberrations:

For Chromosome aberration, read across was performed to lanthanum acetate. Bowles A (2013) performed an in vitro Chromosome Aberration test in human lymphocytes (OECD 473). Two experiments were performed using different test concentrations with and without S9 activation (4h or 24h exposure; 20h expression period):

Experiment 1

4-hour exposure without S9 followed by 20-hour culture in treatment-free media: 25, 50, 100, 200, 400 and 800 μg/mL.

4 -hour exposure with S9 followed by 20-hour culture in treatment-free media: 25,50, 100, 200, 400 and 800 μg/mL.

Experiment 2

24-hour without S9:25, 50, 100, 200, 400 and 800 μg/mL.

4-hour with S9 and followed by 20-hour culture in treatment-free media: 25, 50, 100, 200, 400 and 800 μg/mL.

Both negative and positive controls were considered to be valid. In both experiments lanthanum acetate considered not to induce any significant increases in the frequency of cells with aberrations, which included at least one precipitating dose level, either in the absence or presence of metabolic activation. Therefore, lanthanum acetate and lanthanum trinitrate were considered to be non-clastogenic.

CHO hprt test:

For gene mutation, read across was performed to lanthanum acetate. Morris A (2013) performed a CHO hprt forward mutation assay, targeting the HPRT locus of Chinese hamster ovary (CHO) cells, according to OECD 476. The technique used is a plate assay using tissue culture flasks and 6-thioguanine (6-TG) as the selective agent. CHO cells were treated with the test item at up to 8 dose levels, together with solvent (dimethyl sulphoxide) and positive controls (ethyl methane sulphonate). Four treatment conditions (4h or 24h exposure, with or without metabolizing system, 1% or 2% final concentration) were used in 2 experiments.

Experiment 1:

4h without S9: 98.75; 197.5; 395; 790; 1185; 1580; 3160 µg/ml

4h with S9 (2%): 98.75; 197.5; 395; 790; 1580; 3160 µg/ml

Experiment 2:

4h without S9: 98.75; 197.5; 395; 592.5; 790; 1185; 1580; 3160 µg/ml

4h with S9 (2%): 197.5, 395; 790; 1185; 2370; 3160 µg/ml

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. 

Based on all the available information on lanthanum trinitrate and on the read-across substance lanthanum acetate (another 'water-soluble' substance), it can be concluded that lanthanum trinitrate is not mutagenic in vitro with and without metabolic activation.

Genetic toxicity in vivo:

According to REACH Annex VIII section 8.4.3, column 2, no further in vivo testing is required as no positive result is observed in any of the genotoxicity studies performed.

Justification for selection of genetic toxicity endpoint

No endpoint is selected as multiple studies are considered to be key studies. In addition, a 'weight-of-evidence' approach is used to evaluate the potential genotoxicity to bacteria. The read-across justification is included in the Section 13.

Short description of key information:

Genetic toxicity in vitro:

Bacterial reverse mutation assay: performed according to a method equivalent to OECD Guideline 471 in S. typhimurium TA 1535, TA 98 ,TA 100 and TA 97 (Zeiger et al., 1992). According to the results of the study, lanthanum trinitrate is not mutagenic in the Ames test with and without metabolic activation. However, only four strains were tested. Therefore, read-across to the Ames test with lanthanum acetate (Thompson 2013) is proposed to substantiate this endpoint. In this study it is concluded that lanthanum acetate is not mutagenic with and without metabolic activation.

In vitro mammalian chromosome aberration test: performed according to OECD Guideline 473 and EU Method B.10 in human lymphocytes (Bowles 2013). The read-across substance lanthanum acetate was not clastogenic in the absence and presence of metabolic activation.

In vitro mammalian cell gene mutation test:  CHO hprt forward mutation assay performed according to OECD Guideline 476 and targeting the HPRT locus of Chinese hamster ovary (CHO) cells (Morris 2013). The read-across substance lanthanum acetate was not mutagenic under the experimental conditions in the absence and presence of metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data on lanthanum trinitrate and lanthanum acetate used as read-across substance and according to the criteria of the CLP Regulation (EC) 1272/2008, lanthanum trinitrate should not be classified for mutagenicity.