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Diss Factsheets
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EC number: 701-291-3 | CAS number: -
- 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
Key value for chemical safety assessment
Effects on fertility
Description of key information
A dermal reprotoxicity screening study in rats conducted according to OECD 422 in which no adverse effect was seen in any of the reproductive parameters examined at any dose.
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 089.75 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- GLP study conducted according to standard guideline
Additional information
The substances in the category are considered to be similar on the basis that they have common structures of a lithium ion varying only by the length of the fatty acid chain and the presence of unsaturated and/or hydroxyl functional groups. As a result, it is expected that the substances will have similar, predictable properties. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Provided that they are obtained from natural sources and are not chemically modified, the substances included in REACH Annex V, Entry 9 are exempt from registration, unless they are classified as dangerous (except for flammability, skin irritation or eye irritation) or they meet the criteria for PBT/vPvB substances. The fatty acid components of the category members are therefore not expected to be hazardous. As all category members are lithium salts, any toxicity is expected to be driven by the lithium ion. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the reproductive toxicity is expected to be similar across the category.
Although fatty acids C18 (unsaturated) lithium salts is not in the list of substances being registered, this substance falls within the definition of the lithium salts of fatty acids C14-C22 category (see Appendix 1 – Category Justification Document) by virtue of its chemical structure and therefore read across from data on fatty acids C18 (unsaturated) lithium salts to other members of the category is considered to be justified (see below).
A key toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on fatty acids C18 (unsaturated) lithium salts via dermal administration. The test material was administered at dose levels of 0, 100, 300 and 1000 mg/kg/day nominal, equating to 111.25, 345 and 1089.75 mg/kg/day by analysis, and were based on local dermal effects from a dose range finding study. There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study, or in any of the developmental parameters evaluated. Based on these data, the NOAEL for reproductive and developmental toxicity was 1089.75 mg/kg/day.
Overall, on the basis of the category justification for the C14 to C22 fatty acid lithium salts, and supporting evidence, the lack of reproductive and developmental toxicity when C18 (unsaturated) lithium salts was administered to rats can be read across to other members of the category, and no classification for this endpoint is required.
The consideration concerning the margin of safety between the human therapeutic dose and the NOAELs found in the relevant studies is presented in the Repeated Dose Toxicity section above. The same proposals regarding the use of the human data for DNEL derivation are applicable for the developmental toxicity endpoint.
Effects on developmental toxicity
Description of key information
A dermal reprotoxicity screening study in rats conducted according to OECD 422 in which no adverse effect was seen in any of the reproductive/developmental parameters examined at any dose.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 089.75 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- GLP study conducted according to standard guideline
Additional information
The substances in the category are considered to be similar on the basis that they have common structures of a lithium ion varying only by the length of the fatty acid chain and the presence of unsaturated and/or hydroxyl functional groups. As a result, it is expected that the substances will have similar, predictable properties. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Provided that they are obtained from natural sources and are not chemically modified, the substances included in REACH Annex V, Entry 9 are exempt from registration, unless they are classified as dangerous (except for flammability, skin irritation or eye irritation) or they meet the criteria for PBT/vPvB substances. The fatty acid components of the category members are therefore not expected to be hazardous. As all category members are lithium salts, any toxicity is expected to be driven by the lithium ion. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the developmental toxicity is expected to be similar across the category.
Although fatty acids C18 (unsaturated) lithium salts is not in the list of substances being registered, this substance falls within the definition of the lithium salts of fatty acids C14-C22 category (see Appendix 1 – Category Justification Document) by virtue of its chemical structure and therefore read across from data on fatty acids C18 (unsaturated) lithium salts to other members of the category is considered to be justified (see below).
A key toxicity and reproductive toxicity screen, using the OECD 422 study design, was conducted in rats on fatty acids C18 (unsaturated) lithium salts via dermal administration. The test material was administered at dose levels of 0, 100, 300 and 1000 mg/kg/day nominal, equating to 111.25, 345 and 1089.75 mg/kg/day by analysis, and were based on local dermal effects from a dose range finding study. There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study, or in any of the developmental parameters evaluated. Based on these data, the NOAEL for reproductive and developmental toxicity was 1089.75 mg/kg/day.
A supporting dermal developmental toxicity study in rats using a grease containing ca 8% lithium 12-hydroxystearate in base oil, together with additives, is reported. This showed no adverse reproductive or developmental effects. The NOAEL (developmental) was 2000 mg/kg bw/day, and the NOAEL (maternal) was 500 mg/kg bw/day of the grease (160 and 40 mg/kg bw/day of lithium 12-hydroxystearate respectively).
Overall, on the basis of the category justification for the C14 to C22 fatty acid lithium salts, the lack of developmental toxicity when C18 (unsaturated) lithium salts and grease containing lithium 12-hydroxystearate were administered to rats can be read across to other members of the category, and no classification for this endpoint is required.
The consideration concerning the margin of safety between the human therapeutic dose and the NOAELs found in the relevant studies is presented in the Repeated Dose Toxicity section above. The same proposals regarding the use of the human data for DNEL derivation are applicable for the developmental toxicity endpoint.
The use of lithium in bipolar disorder has been reviewed by Horton et al (2012). This disease is more prevalent in women and is often concurrent with peak reproductive age. This review considers a therapeutic regimen based on PBPK modelling, simulating the concentration of lithium in the organs and tissues of a pregnant woman and her foetus. In the USA, lithium has been classified as a Class D drug (legal to use during pregnancy, but may cause birth defects). The maximum dosage regimen suggested by the modelling based on avoidance of any adverse developmental sequelae was 400 mg lithium carbonate, three times per day (1200 mg/day). This is slightly higher than the lithium carbonate treatment levels of 450 – 900 mg/day referred to in the Repeated dose toxicity discussion, section 5.6.3. Therefore, this paper presents further evidence, based on PBPK modelling, that the use of human therapeutic data is a valid approach for consideration of a human NOAEL and DNEL based on serum concentrations during long-term therapy.
As indicated in the first paragraph of this section and in the Category Justification Document, the fatty acid anions are not considered to be hazardous under anticipated exposure conditions, and under certain conditions would be exempt from registration. Any hazard would be expected to be driven by the lithium cation. On this basis, prenatal developmental toxicity data generated on a soluble inorganic lithium salt would be appropriate to read across to the lithium fatty acid salts in the C14-C22 category.
Justification for classification or non-classification
Not classified. No adverse reproductive or developmental toxicity effects observed.
Additional information
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.
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