Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 208-914-3 | CAS number: 546-89-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Based on ADI/NOAEL values of lithium (human data), a NOAEL for long-term oral toxicity of 11.41 mg lithium acetate/kg bw/day and 17.64 mg lithium acetate dihydrate bw/day was calculated. Performance of repeated dermal and inhalation toxicity studies were waived.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- Expert statement on chronic exposure
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1993, 2002, 2007, 2010, 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Expert statement
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Results based on Expert statement.
- GLP compliance:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 1.2 mg/kg bw/day (nominal)
- Based on:
- other: NOAEL Lithium
- Sex:
- male/female
- Basis for effect level:
- other: NOAEL refers to lithium in humans.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 11.41 mg/kg bw/day (nominal)
- Based on:
- other: NOAEL lithium acetate
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL value was based on the NOAEL value of lithium (human data, 1.2 mg/kg bw/day) and calculated for lithium acetate based on the moleculare weight.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 17.64 mg/kg bw/day (nominal)
- Based on:
- other: NOAEL lithium acetate dihydrate
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL value was based on the NOAEL value of lithium (human data, 1.2 mg/kg bw/day) and calculated for lithium acetate dihydrate based on the moleculare weight.
- Dose descriptor:
- NOAEL
- Effect level:
- >= 100 - <= 210 mg/kg bw/day (nominal)
- Based on:
- other: NOAEL/ADI of acetic acid
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL refers to acetic acid in humans.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 110 - <= 231 mg/kg bw/day (nominal)
- Based on:
- other: recalculated for lithium acetate anhydrous
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL value was based on the ADI value of acetic acid (human data, 100 - 210 mg/kg bw/day) and calculated for lithium acetate anhydrous based on the moleculare weight.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 170 - <= 357 mg/kg bw/day (nominal)
- Based on:
- other: recalculated for lithium acetate dihydrate
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL value was based on the ADI value of acetic acid (human data, 100 - 210 mg/kg bw/day) and calculated for lithium acetate dihydrate based on the moleculare weight.
- Key result
- Critical effects observed:
- no
- Conclusions:
- Based on human data obtained from routine long- term treatment of bipolar disorder with lithium (administered as lithium carbonate), a NOAEL for long-term oral toxicity of 1.2 mg lithium/kg bw/ day was calculated. Based on these data, NOAEL values of 11.41 and 17.64 mg/kg bw/day was calculated for lithium acetate and lithium acetate dihydrate, respectively.
- Executive summary:
No NOAEL/ DNEL/ ADI value was available for lithium acetate. Nevertheless, NOAEL/ DNEL/ ADI values form human data are available for lithium (see below). Thereof, NOAEL values based on human data could be derived and calculated for lithium acetate and lithium acetate dihydrate (see below).
Deduced NOAEL/ DNEL value for lithium
In humans, lithium has been used for decades in psychiatric therapy for the treatment of bipolar disorder. In case of long-term treatment, the recommended dose is 450 to 900 mg/day lithium carbonate, equivalent to 84 to 169 mg lithium / day, and corresponding to a desired sustained therapeutic serum concentration of 0.5 to 1.0 mmol lithium/L. Based on experience with long-term application e.g. lithium carbonate for therapy in humans, there is no evidence that lithium is of concern with respect to repeated oral toxicity at medical doses as the ones indicated above.
The effect level (NOAEL) determined for lithium for repeated dose toxicity by the oral route is based on human data and can be calculated in two ways that complete one another:
One option is based on the therapeutic serum concentrations of 0.5 to 1.0 mmol lithium/L and the extracellular fluid (ECF) volume. Lithium has a large volume of distribution of 0.6-0.9 L/kg (42 L – 63 L for a 70 kg adult). It is distributed throughout the body water both extra and intracellularly. Lithium shifts into the intracellular compartments of cells because of its large volume of distribution. Although in long-term use, the intracellular concentration increases, the intracellular concentration is not reflected by the plasma level which measures only the extracellular fluid concentration. Therefore, a desired concentration of 1 mmol/L of lithium is expected to be sustained and reflected in the extracellular fluid (ECF) only and not in the intracellular fluid. Thus, the volume considered is of the ECF only which comprises of plasma, interstitial fluid (spaces between cells) and transcellular fluid (lymph, cerebrospinal fluid, synovial fluid, serous fluid, gastrointestinal secretions) and is typically 15 L (reported in different references to be between 14 – 19 L (for 70 kg adult)). Based on this data the derived NOAEL (considering a lithium concentration of 1mmol/L and an ECF volume of 15 L) is 1.5 mg/kg bw/day. This NOAEL value can be considered as a conservative value as it is based on an bioavailable dose in humans after absorption and on a smaller volume than its actual distribution volume.
Another way to calculate NOAEL oral for lithium is based as well on data taken from the routine long-term treatment of bipolar disorder. Instead of calculating the NOAEL from the therapeutic serum concentration of lithium, the lithium NOAEL oral can be calculated from the administered oral dose for long-term treatment of bipolar disorder as detailed above: 84 to 169 mg lithium / day (corresponding to the desired sustained concentrations of 0.5 -1 mmol lithium/L in blood/serum). When dividing the oral doses (84 to 169 mg lithium / day) to 70 kg, the following values are obtained respectively: 1.2 to 2.4 mg/kg bw/day or when dividing to 60 kg the following values are obtained respectively: 1.4 to 2.8 mg/kg bw/day, representing the optional NOAEL values for lithium for the oral route.
In both ways of calculation, the values obtained are in same order of magnitude and similar to one another. As a worst–case value, a NOAEL repeated dose toxicity oral of 1.2 mg lithium/kg bw was chosen. Further, this value could be used as a starting value for route-to-route extrapolation in calculation of the repeated dose toxicity for the dermal and inhalation routes.
Deduced NOAEL/ DNEL value for acetic acid
According to the evaluation of SCOEL, 2012 (Recommendation from the Scientific Committee on Occupational Exposure Limits for acetic acid), an ADI value (comparable to DNEL) between 1 and 2.1 g acetic acid/day was determined for humans older than 2 years. Using the default body weight of a two year old child, the ADI value results to 100 to 210 mg/kg bw/d.
Derived NOAEL values for lithium acetate and the corresponding dihydrate
As detailed above, for calculation of the DNEL long-term oral of lithium acetate the following (human) data was available; the NOAEL/DNEL of lithium (1.2 mg lithium/kg bw/day) and the ADI value (comparable to DNEL) of acetic acid (100 – 210 mg/kg bw/day). Additionally, the molecular weights of lithium and acetic acid were considered.
The calculated NOAEL oral of lithium acetate and lithium acetate dihydrate (11.41 mg/kg bw/day and 17.64 mg/kg bw/day, respectively) based on the NOAEL of lithium are much smaller than the calculated NOAEL of lithium acetate and the corresponding dihydrate (110 - 231 mg/kg bw/day and 170 – 357 mg/kg bw/d, respectively) based on the ADI of acetic acid. Thus, the determined NOAEL oral of lithium acetate (dihydrate) is 11.41 mg/kg bw/day based on the ADI value of lithium being the toxicological limiting value for lithium acetate.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 11.41 mg/kg bw/day
- Study duration:
- chronic
- Species:
- other: Weight of evidence approach in which the NOAEL value is derived from reliable human data.
- Quality of whole database:
- Reliable human data was used.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated oral toxicity
No NOAEL/ DNEL/ ADI value is available for lithium acetate. Nevertheless, NOAEL/ DNEL/ ADI values from human data are available for lithium and for acetic acid (see below). Thereof, a NOAEL value based on human data could be derived and calculated for lithium acetate and lithium acetate dihydrate as detailed below.
Deduced NOAEL/ DNEL value for lithium
In humans, lithium has been used for decades in psychiatric therapy for the treatment of bipolar disorder. In case of long-term treatment, the recommended dose is 450 to 900 mg/day lithium carbonate, equivalent to 84 to 169 mg lithium / day, and corresponding to a desired sustained therapeutic serum concentration of 0.5 to 1.0 mmol lithium/L. Based on experience with long-term application e.g. lithium carbonate for therapy in humans, there is no evidence that lithium is of concern with respect to repeated oral toxicity at medical doses as the ones indicated above.
The effect level (NOAEL) determined for lithium for repeated dose toxicity by the oral route is based on human data and can be calculated in two ways that complete one another:
One option is based on the therapeutic serum concentrations of 0.5 to 1.0 mmol lithium/L and the extracellular fluid (ECF) volume. Lithium has a large volume of distribution of 0.6-0.9 L/kg (42 L – 63 L for a 70 kg adult). It is distributed throughout the body water both extra and intracellularly. Lithium shifts into the intracellular compartments of cells because of its large volume of distribution. Although in long-term use, the intracellular concentration increases, the intracellular concentration is not reflected by the plasma level which measures only the extracellular fluid concentration. Therefore, a desired concentration of 1 mmol/L of lithium is expected to be sustained and reflected in the extracellular fluid (ECF) only and not in the intracellular fluid. Thus, the volume considered is of the ECF only which comprises of plasma, interstitial fluid (spaces between cells) and transcellular fluid (lymph, cerebrospinal fluid, synovial fluid, serous fluid, gastrointestinal secretions) and is typically 15 L (reported in different references to be between 14 – 19 L (for 70 kg adult)). Based on this data the derived NOAEL (considering a lithium concentration of 1 mmol/L and an ECF volume of 15 L) is 1.5 mg/kg bw/day. This NOAEL value can be considered as a conservative value as it is based on a bioavailable dose in humans after absorption and on a smaller volume than its actual distribution volume.
Another way to calculate NOAEL oral for lithium is based as well on data taken from the routine long-term treatment of bipolar disorder. Instead of calculating the NOAEL from the therapeutic serum concentration of lithium, the lithium NOAEL oral can be calculated from the administered oral dose for long-term treatment of bipolar disorder as detailed above: 84 to 169 mg lithium / day (corresponding to the desired sustained concentrations of 0.5 -1 mmol lithium/L in blood/serum). When dividing the oral doses (84 to 169 mg lithium / day) to 70 kg, the following values are obtained respectively: 1.2 to 2.4 mg/kg bw/day or when dividing to 60 kg the following values are obtained respectively: 1.4 to 2.8 mg/kg bw/day, representing the optional NOAEL values for lithium for the oral route.
In both ways of calculation, the values obtained are in same order of magnitude and similar to one another. As a worst–case value, a NOAEL repeated dose toxicity oral of 1.2 mg lithium/kg bw was chosen. Further, this value could be used as a starting value for route-to-route extrapolation in calculation of the repeated dose toxicity for the dermal and inhalation routes. As no assessment factors are expected to be applied (no allometric, exposure duration, intra/interspecies, data quality factors are required), the NOAEL value of 1.2 mg/kg bw/day could be considered as the DNEL value.
Deduced NOAEL/ DNEL value for acetic acid
According to the evaluation of SCOEL, 2012 (Recommendation from the Scientific Committee on Occupational Exposure Limits for acetic acid), an ADI value (comparable to DNEL) between 1 and 2.1 g acetic acid/day was determined for humans older than 2 years. Using the default body weight of a two year old child, the ADI value results to 100 to 210 mg/kg bw/d.
Derived NOAEL values for lithium acetate and the corresponding dihydrate
As detailed above, for calculation of the DNEL long-term oral of lithium acetate the following (human) data was available; the NOAEL/DNEL of lithium (1.2 mg lithium/kg bw/day) and the ADI value (comparable to DNEL) of acetic acid (100 – 210 mg/kg bw/day). Additionally, the molecular weights of lithium and acetic acid were considered.
The calculated NOAEL oral of lithium acetate and lithium acetate dihydrate (11.41 mg/kg bw/day and 17.64 mg/kg bw/day, respectively) based on the NOAEL of lithium are much smaller than the calculated NOAEL of lithium acetate and the corresponding dihydrate (110 - 231 mg/kg bw/day and 170 – 357 mg/kg bw/d, respectively) based on the ADI of acetic acid. Thus, the determined NOAEL oral of lithium acetate (dihydrate) is 11.41 mg/kg bw/day based on the ADI value of lithium being the toxicological limiting value for lithium acetate.
Repeated dermal toxicity
Additional testing by dermal route is not applicable as data on repeated dose oral / systemic toxicity was provided. According to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.6.1, only one repeated dose toxicity study is required (with administration via the most appropriate route).
Repeated inhalation toxicity
Additional testing by inhalation route is not required as data on repeated oral / systemic toxicity is provided. According to Regulation (EC) No 1907/2006, Annex VIII, 8.6.1 only one repeated dose toxicity study with administration via the most appropriate route is required. Furthermore the vapour pressure of lithium acetate is negligible due to the high melting point of the substance (see IUCLID section 4.2).
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 does not need to be classified and labelled for repeated dose toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.