Lithium benzoate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity, carcinogenicity and teratogenicity of lithium compounds

Author:

A Leonard, et al

Year:

1994

Bibliographic source:

Mutation Research 339 (1995) 131-137

Materials and methods

Test guideline

Test guideline 1

Qualifier:

no guideline followed

Version / remarks:

In-vivo human chromosome aberration

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)

Version / remarks:

Rat, 12 months exposure in drinking water

Principles of method if other than guideline:

Chromosome effects in 19 manic-depressive patients receiving lithium treatment were compared to 23 controls
Other human evaluations made on specific patients
Rat study looked at unscheduled DNA synthesis after 3, 6 or 12 months

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lithium carbonate

EC Number:

209-062-5

EC Name:

Lithium carbonate

Cas Number:

554-13-2

Molecular formula:

CH2O3.2Li

IUPAC Name:

dilithium carbonate

Test animals

Sex:

not specified

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

Rat study was using oral administration in drinking water

Details on exposure:

Rat study was using oral administration in drinking water

Duration of treatment / exposure:

For rat study, up to 12 months
Length of human treatment not specified, but some patients had been receiving treatment for up to 2 years

Applicant's summary and conclusion

Conclusions:

No adverse treatment related effects were observed in humans or rats in these studies

Executive summary:

The review document cites many in-vitro and in-vivo (including human) researcvh projects and primary reference sources are provided. However, many of these research projects were conducted before fomalisation of test methods. The authors if this review conclude that in balance Lithium is not considered to be mutagenic, although there is limited evidence of some effects on mutagenic activity under certain conditions.

The only positive resposne was noted when 3 mg/ml lithium carbonate slightly inhibited DNA synthesis in V79 Chinese hamster cells and human fibroblasts. This effect was reduced in the presence of S9 fraction. More single-strand breaks in DNA and a small increase in gene mutations (HGPRT) in V79 Chinese hamster ceils without S9 was also noted. No other studies reported indications of positive effects.

To quote the counclusion in the report:

It is concluded that lithium compounds have no significant clastogenic and, based on studies on microorganisms, only a doubtful mutagenic activity.