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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Review of human data
Type of information:
other: Literature review
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Lithium and benzoate salts are used extensively in drug and food applications and there has been a lot of research into human toxicity.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
no guideline followed
Version / remarks:
Literature review
Principles of method if other than guideline:
A review of literature from a number of national and international reviews relating to use of lithium and benzoates salts in food and pharmaceuticals has been made to assess potential toxicity of lithium benzoate. In view of the wealth of data on these ions, and in view of the necessity to avoid new animal testing, it is considered justified to perform this review

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium benzoate
EC Number:
209-042-6
EC Name:
Lithium benzoate
Cas Number:
553-54-8
Molecular formula:
C7H6O2.Li
IUPAC Name:
lithium benzoate
Specific details on test material used for the study:
Literature review includes examination of food additive sodium benzoate and the drugs lithium carbonate and lithium citrate.

Test animals

Species:
other: Human

Administration / exposure

Route of administration:
oral: unspecified
Duration and frequency of treatment / exposure:
Chronic / Long-term
Doses / concentrations
Dose / conc.:
40 mg/kg bw/day (nominal)
Remarks:
Examination of human exposure to theraputic dose levels of lithium

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Rapid oral absorption
Type:
distribution
Results:
Readily distributed as dissociated ions
Type:
metabolism
Results:
Lithium not metabolised. Benzoate rapidly metabolised
Type:
excretion
Results:
Lithium rapidly excreted as inorganic salt. Benzoate is metabolised and not excreted.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
For water soluble forms of lithium, absorption is complete within 6 hours of oral administration from conventional tablets and capsules. To maintain blood Li levels, repeated administration is needed with recommendations for dosage 3 times a day.

Benzoate ions rapidly absorb orally.

Dermal penetration of lithium salts and benzoates has not been well evaluated, but in view of the relatively low molecular weight and solubility in water, it is likely that there is some dermal penetration.

Lithium undergoes ion exchange with sodium and potassium and for this reason is thought to adsorb into the skin and not necessarily penetrate. This ion-exchange is two-way and loss through sweat from skin could reverse and local absorption. This has not been well researched, although one human study suggests low absorption into blood from repeated dermal exposure
Details on distribution in tissues:
Lithium and benzoate are distributed widely throughout the body. In the case of lithium, this has been found to include breast milk, thyroid gland, bone, and brain tissue. In some cases, concentrations exceed serum levels suggesting some accumulation into these areas.

Research has shown steady state serum level of lithium is achieved in 12 hours and therapeutic effect begins in 5 to 10 days and is maximal within 3 weeks. Therapeutic and toxic serum levels and therapeutic effects show good correlation. Therapeutic range is 0.6 to 1.2 mEq/l in blood serum
Transfer into organs
Key result
Test no.:
#1
Transfer type:
blood/brain barrier
Remarks:
Lithium
Observation:
distinct transfer
Details on excretion:
Benzoates are not excreted, but are instead metabolised and metabolites will ultimately include carbon dioxide and water. There is evidence of carbon from benzoates being found in other organic substances formed by the body.

Inorganic lithium salts are typically excreted 95% unchanged in urine with about 50% to 80% of a given dose is excreted within 24 hours. The kidney has been found to accumulate lithium during periods of treatment.

Lithium from organic sources, such as benzoate salts, is also considered to be extruded at a similar rate, but in the form of inorganic salts such as chlorides. Lithium citrate is used for therapeutic applications with similar dosing recommendations to the more common carbonate forms.

Metabolite characterisation studies

Details on metabolites:
Benzoate ions are readily metabolised and metabolic pathways have been described in public literature

Lithium is not metabolised and is not considered to be an essential element in mammals

Applicant's summary and conclusion

Conclusions:
Benzoate ions are readily metabolised and metabolic pathways have been described in public literature

Lithium is not metabolised and is not considered to be an essential element in mammals