Dilanthanum tricarbonate

Endpoint summary

Additional information

Damment et al. (2005) evaluated Lanthanum carbonate for potential genotoxicity using a range of in vitro and in vivo assays. Furthermore, a reverse mutation test in bacterial cells was available as study report (Sokolowsky and Wollny, 2006).

 

In vitro

Mutagenicity in bacteria

Lanthanum carbonate (containing water) was tested in a reverse mutation test according to OECD 471 using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (Sokolowsky and Wollny, 2006). In the absence of any cytotoxicity , no increase in revertant numbers was observed up to and including the highest test concentration of 5000 µg/plate with and without metabolic activation.

In a further reverse gene mutation assay, Salmonella strains TA 98, TA 100, TA 102, TA 1535 , TA 1537 and TA 1538 as well as E. coli WP2 uvr A and E. coli WP2 uvr A (pkm101) were exposed to Lanthanum carbonate at concentrations of 3 to 5000 µg/plate in the presence and absence of a mammalian metabolic activation system (Damment et al., 2005). In this assay Lanthanum carbonate was tested up to precipitating concentrations. Again, there was no evidence of induced revertant colonies over background in all strains tested with and without metabolic activation.

 

Mutagenicity in mammalian cells

A gene mutation assay (HPRT) in Chinese hamster ovary cells was performed according to OECD 476 in two independet experiments (Damment et al., 2005). There were no significant effects on mutation frequency in the presence of S9 mix. In the absence of S9 mix, increases in mutation frequency were obtained at isolated concentrations in the first experiment. However, there was no obvious dose-response relationship and the effects were not reproducible in a second experiment, indicating that they had arisen by chance and do not indicate a mutagenic effect by Lanthanum carbonate. Thus, under the conditions of the test, Lanthanum carbonate does not induce mutations in mammalian cells.

 

Cytogenicity

Furthermore, the potential of Lanthanum carbonate to induce chromosomal aberrations in mammalian cells in vitro was investigated according to OECD 473 (Damment et al., 2005). Three independent experiments were performed showing statistically significant increases in the number of aberrant cells at several concentrations in the absence and presence of S9 -mix. These effects, although small and not dose-related, were shown to be reproducible. However, the majority of these increases fell within the historical control range for this cell line (0-6%) and were only apparent at test concentrations where cytotoxicity was on the borderline of the acceptable range for this experimental design (i.e. < 50% reduction in mitotic index relative to concurrent vehicle controls). There was also considerable precipitation of the test material at these concentrations. Consequently, the results from this assay were judged to be equivocal and probably caused by cell toxicity or by the confounding effects of precipitation.

 

In vivo

An in vivo micronucleus test according to OECD 474 was performed in CD-1 mice after single gavage administration of Lanthanum carbonate at concentrations of 800, 1250 and 2000 mg/kg bw (Damment et al., 2005). Samples of the bone marrow were taken 24, 48 and 72 h after administration. The incidence of micronuclei was scored in polychromatic erythrocytes (2000/mouse) and the ratio of polychromatic to normochromatic cells was also determined from a sample of 1000 total cells. All treatment and vehicle control groups exhibited normal frequencies of micronucleated polychromatic erythrocytes (MNPCE), with the exception of the vehicle control group (male mice) sampled at 48 h. Since this result was not considered to be biologically relevant, Lanthanum carbonate is considered not to induce micronuclei of doses up to the maximum practicable oral dose of 2000 mg/kg bw.

 

Short description of key information:
In vitro:
Negative Ames test with S. typhimurium TA 1535, TA 1537, TA1538, TA 98, TA 100 and TA 102, E. coli WP2 uvr A and E. coli WP2 uvr A (pkm101)
Negative in vitro Mammalian Cell Gene Mutation Assay
Ambiguos in vitro Mammalian Chromosome Aberration Test

In vivo:
Negative Mammalian Erythrocyte Micronucleus Test

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The data on genetic toxicity is conclusive but not sufficient for classification according to the criteria of Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).