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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Lithium hydroxide and lithium hydroxide monohydrate was found to be non-mutagenic in three in vitro tests (AMES tests, Chromosome aberration test, In vitro Mammalian Cell Gene Mutation Test).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

In vitro assay with bacteria

Lithium Hydroxide was tested in the Salmonella typhimurium reverse mutation assay according to OECD Guideline 471. The test was performed with four histidine-requiring strains of Salmonella typhimurium (TA 1535, TA 1537, TA 100 and TA 98) and in the Escherichia coli reverse mutation assay with a tryptophan-requiring strain of Escherichia coli WP2uvrA in two independent experiments. Lithium Hydroxide was tested up to concentrations of 5000 µg/plate in the absence and presence of S9 -mix. Lithium Hydroxide did not precipitate on the plates at this dose level. The bacterial background lawn was not reduced at all concentrations tested. Reduction in the number of revertants was observed in the tester strain TA 1535, TA 98, TA 100 and WP2uvrA at the limit concentration of 5000 ug/plate, indicating some bacterial toxicity. Lithium Hydroxide did not induce a dose-related, two-fold, increase in the number of revertant (His+) colonies in each of the four tester strains (TA 1535, TA 1537, TA 98 and TA 100) and in the number of revertant (Trp+) colonies in the tester strain WP2uvrA both in the absence and presence of S9 -metabolic activation. These results were confirmed in an independently repeated experiment. Based on the results of this study it is concluded that lithium hydroxide is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

In vitro assay with cultured Peripheral Human Lymphocytes

The effect of lithium hydroxide on the induction of chromosome aberrations in culture peripheral human lymphocytes in the presence and absence of a metabolic activation system (Aroclor-1254 induced rat liver S9-mix) was investigated according to OECD Guideline 473 and EU method B.10.

In the absence of S9-mix lithium hydroxide was tested up to 560 µg/mL for a 3 h treatment time with a 24 h fixation time in experiment 1A and up to 375 µg/mL in experiment 1C. In the presence of 1.8 % (v/v) S9-fraction lithium hydroxide was tested up to 560 ug/mL for a 3 h treatment time with a 24 h fixation time in experiment 1A and up to 400 µg/mL in experiment 1C. In both experiments 1A and 1C, lithium hydroxide did not induce a statistically or biologically significant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix.

In the second experiment Lithium Hydroxide was tested up to 350 µg/mL for a 24 hours continuous treatment time and up to 400 µg/mL for a 48 hours continuous treatment time (both without S9-mix). In the second experiment lithium hydroxide was tested up to 450 ug/mL for a 3 h treatment time with a 48 h fixation time with S9-mix. In the absence of S9-mix, at the 24 hours continuous treatment time, lithium hydroxide induced statistically significant increases in the number of cells with chromosome aberrations at the lowest tested concentration of 275 ug/mL (only when gaps were included) and at the highest cytotoxic concentration of 350 µg/mL both when gaps were included and excluded. At the intermediate concentration of 300 ug/mL lithium hydroxide did not induce a statistically significant increase in the number of cells with chromosome aberrations. Since the increase of chromosome aberrations at 275 ug/mL was observed only when gaps were included and furthermore the increase was within the historical control data range and revealed no dose-response-relationship, the increase was not considered biologically relevant. At the continuous treatment time of 48 hours exposure of cells to 350, 375 or 400 ug/mL lithium hydroxide did not induce a significant increase in the number of cells with chromosome aberrations. In the presence of S9-mix, lithium hydroxide did not induce a statistically or biologically significant increase in the number of cells with chromosome aberrations.

Finally, it is concluded that this test is considered valid and that lithium hydroxide is not clastogenic under the experimental conditions of this test. Positive control chemicals mitomycin C and cyclophosphamide indicated that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.

In vitro assay with mammalian cells

An in vitro mammalian cell assay was performed in mouse lymphoma L5178Y TK +/- cells to test the potential of lithium hydroxide to cause gene mutation and/or chromosome damage according to OECD Guideline 476 and the EU method B.17. Lithium hydroxide monohydrate was assayed in a gene mutation assay in cultured mammalian cells (L5178Y TK +/-) both in the presence and absence of metabolic activation by a liver post-mitochondrial fraction (S9 mix) from Aroclor 1254-induced rats. The test was carried out employing 2 exposure times without S9 mix: 3 and 24 hours, and one exposure time with S9 mix: 3 hours; this experiment with S9 mix was carried out twice. In the preliminary experiment without and with metabolic activation, concentrations tested were 0.25, 1, 2.5, 10, 25, 100 and 200 ug/mL. Cytotoxicity (decreased survival) was noted at the top concentration of 200 μg/mL. Hence, in the experiments without or with metabolic activation the concentrations of 12.5, 25, 50 100 and 200 ug/mL were used. In the main study, cytotoxicity (decreased survival) was noted immediately after treatment (plating efficiency step 1) and in the following plating for 5-trifluoro-thymidine (TFT) resistance (plating efficiency step 2) in the presence and absence of metabolic activation at the top concentration of 200 μg/mL. The mean values of mutation frequencies of the negative controls ranged from 61.61 to 98.34 per 106 clonable cells in the experiments without metabolic activation, and from 68.23 to 82.61 per 106 clonable cells in the experiments with metabolic activation and, hence, were well within the historical data-range. The mutation frequencies of the cultures treated with Lithium hydroxide monohydrate ranged from 64.74 to 92.63 per 106 clonable cells (3 hours exposure) and 50.42 to 92.34 per 106 clonable cells (24 hours exposure) in the experiments without metabolic activation and 75.88 to 105.59 per 106 clonable cells (3 hours exposure, first assay) and 45.04 to 99.10 per 106 clonable cells (3 hours exposure, second assay) in the experiments with metabolic activation. These results were within the range of the negative control values and, hence, no mutagenicity was observed according to the criteria for assay evaluation.

Methylmethanesulfonate was employed as positive control in the absence of exogenous metabolic activation and 3-Methylcholanthrene in the presence of exogenous metabolic activation and indicated that the test conditions were adequate and that the metabolic activation system functioned properly.

Lithium hydroxide monohydrate, tested up to a pronounced cytotoxic concentration in the absence and presence of metabolic activation in two independent experiments, was negative with respect to the mutant frequency in the L5178Y TK +/- mammalian cell mutagenicity test. Therefore, lithium hydroxide monohydrate also did not exhibit clastogenic potential at the concentration-range investigated. According to the evaluation criteria for this assay, these findings indicate that lithium hydroxide monohydrate, tested up to a cytotoxic concentration in the absence and presence of metabolic activation did neither induce mutations nor had any chromosomal aberration potential.

These negative findings for lithium hydroxide are supported by experience with long-term administration of e.g. lithium carbonate in humans for therapy of bipolar disorder.


Short description of key information:
Lithium hydroxide and lithium hydroxide monohydrate was found to be non-mutagenic in three in vitro tests (AMES tests, Chromosome aberration test, In vitro Mammalian Cell Gene Mutation Test).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified and labelled as mutagenic under Regulation (EC) No 1272/2008.