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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
At physiological pH, all category members dissociate and release boric acid and lithium ions as a result of relevant transformation pathways. It will the boric acid component of the substances which will drive the mammalian toxicity endpoints. In order to minimise animal testing, only one substance in the category was tested, dilithium tetraborate. For all other substances in the category, read-across is proposed.

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium tetrahydroxyborate
EC Number:
818-953-3
Cas Number:
12006-96-1
Molecular formula:
LiB(OH)4
IUPAC Name:
Lithium tetrahydroxyborate

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
The bacterial lawn was slightly reduced
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
The bacterial lawn was slightly reduced
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Note: The number of revertant colonies was within the historical control data for all concentrations

Applicant's summary and conclusion

Conclusions:
The test item induced dose related increases in tester strain TA100 in the absence and presence of S9-mix in two independent experiments (2.0 and 2.3-fold), respectively. The number of revertant colonies was within the historical control data range for all concentrations, with the exception of the highest concentration in the presence of S9-mix which was just above the historical control data range. The test result was equivocal in tester strain TA100 of the Salmonella typhimurium reverse mutation assay. However, the test item was not mutagenic in the other Salmonella typhimurium tester strains (TA1535, TA1537 or TA98) or the Escherichia coli reverse mutation assay using strain WP2uvrA.      

Read-across to these results are proposed for lithium tetrahydroxyborate since at physiological pH, both substances will dissociate and release boric acid and lithium ions as a result of relevant transformation pathways. The same mutagenic effects are therefore expected.
Executive summary:

An Ames test was conducted to determine the potential of dilithium tetraborate and/or its metabolites upto concentrations of 5000 µg/plate to induce reverse mutations at the histidine locus in several strains of Salmonella typhimurium (S. typhimurium; TA98, TA100, TA1535, and TA1537), and at the tryptophan locus of Escherichiacoli (E. coli) strain WP2uvrA in the presence or absence of an exogenous mammalian metabolic activation system (S9). The test result was equivocal in tester strain TA100 of the Salmonella typhimurium reverse mutation assay. However, the test item is not mutagenic in the other Salmonella typhimuriumtester strains (TA1535, TA1537 or TA98) or the Escherichia coli reverse mutation assay using strain WP2uvrA. Read-across to these results are proposed for lithium tetrahydroxyborate since at physiological pH, all category members dissociate and release boric acid and lithium ions as a result of relevant transformation pathways.  Variations in structure (trigonal vs tetrahedral) between the substances are not expected to lead to any changes to the results. As the results were equivocal, a testing proposal is submitted for dilithium tetraborate for further investogations of the mutagenic effect of these lithium borates.

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