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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 214-071-2 | CAS number: 1077-28-7
- 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
Genetic toxicity in vitro
Description of key information
No genotoxicity and mutagenicity of alpha-lipoic acid was observed in bacteria (AMES-test) V79 Chinese Hamster Fibroblasts (HPRT-test, chromosomal aberration study).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1996-04-22 - 1996-07-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1983-05-26
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Species / strain / cell type:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-Mix
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Remarks:
- Solvent treated (DMSO)
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- other: 2-Aminoanthracene
- Positive controls:
- yes
- Positive control substance:
- cumene hydroperoxide
- other: Benzo(a)pyren-4,5-oxide; TA1535; TA1537, TA100, TA97; TA98; w/o metabolic activation
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with
- Genotoxicity:
- other: extremely weak
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Alpha-Lipoic acid is not mutagenic in the Salmonella typhimurium standard strains TA 100, TA98, TA1535, TA1537 and TA 102 with and w/o S-9 mix.
The observed extremely weak effect of alpha-Lipoic acid only with metabolic actication is lower than it is with physiological endigenous compounds like L-systeine and glutathione.
Alpha-Lipoic acid is considered negative in the Salmonella Typhimurium Reverse Mutation Assay - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1996-07-08 - 1996-10-31
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- May 1995
- GLP compliance:
- yes
- Type of assay:
- other: chormosomal aberrations
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Remarks:
- A2
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-Mix (Aroclor 1254-induced Wistar rats)
- Test concentrations with justification for top dose:
- 5000 µg/mL, according to relevant international test guidelines.
Aim: approx. 50 % reduction of mitotic index coompared do negative controls - Vehicle / solvent:
- Dimethyl sulphoxide (DMSO), 1 %
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- - two independant experiments
- 18 h and 28 h treatment - Statistics:
- Chi-spuare test
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduced cell number and mitotic index at higher concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Conclusions:
- Under the conditions described solutions from Thioctic Acid, Racemate w/o as well as with a metabolic activation system are considered not to induce structural and numerical chromosomal aberrations in V79 Chinese hamster fibroblasts in vitro.
- Executive summary:
Chromosomal aberrations:
No statistically significant, biological relevant and reproducible increase in the incidence of cells with structural chromosomal aberrations was present for any experimental group treated with solutions of Thioctic acid compared to negative control groups during both experiments. This was true for treatment w/o exogenous metabolic activation and with exogenous metabolic activation, as well as for both teh 18 h sampling time and the 28 h sampling time.
In the positive control groups treated with ethyl methane sulphonate or cyclophosphamide, predominantly distinct and statistically significant increases in the number of metaphases with structural cromosomal aberations occured.
No increase in polyploidy considered to be related to the treatment with solutions from Thioctic Acid, Racemate, or with the positive control substances, ethyl methyl sulphonate or cyclophosphamide, discernible.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1998-02-18 - 1998-04-02
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- other: in vitro gene mutation study in mamalian cells
- Target gene:
- hypoxantine-guanine phosphoribosyl transferase (hprt)
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-Mix from liver of Aroclor 1254-induced Sprague Dawley rats
- Test concentrations with justification for top dose:
- alpha-Lipoic acid: 156 - 5000 µg/mL -> 5000 µg/mL is maximum concentration according to current guidelines, precipitaion was observed in this solutions.
- Vehicle / solvent:
- dimethylsulfoxide (DMSO)
- Untreated negative controls:
- yes
- Remarks:
- with and w/o metabolic activation
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO, 1 %; with and w/o metabolic activation
- Positive controls:
- yes
- Positive control substance:
- 9,10-dimethylbenzanthracene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- Two independent experiments.
treatment: 4 h (with and w/o metabolic activation) => according to guideline incubation time of 3 - 6 h is effecticve to induce mutation at the HPRT-gene
Two parallel cultures in each experimental group.
Selection of mutatants: Preparation of 6 petri dishes from each culture. - Evaluation criteria:
- If a test substance produced neither a biologically relevant and reproducible positive response at any test point nor a concentration related and biologically relevant increase in teh mutant frequency compared to the respective negative control group, it is considered as non-mutagenic in this system.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Under the conditions described, solutions from Thioctic Acid up to concentration of 5000 µg/mL w/o as well as with a metabolic activation system are considered to induce no gene mutations at the HPRT gene in V79 Chinese hamster fibroblasts in vitro.
- Executive summary:
General:
Two independent experiments were carried out. The treatment interval was 4 h in test parts with and w/o metabolic activation. After the treatment the cells were allowed for expression of a possible treatment induced mutant phenotype for 7 d. Then cells were seeded for selection of mutants in a 6-tihioguanine containing mediumg and incubated for further 7 days. in each experimental group two parallel cultures were used. for selection of mutants form each cell culture 6 petri dishes were prepared.
Results:
The pH- and osmolality values determined for concentrations of 5000 µg/mL Tioctic Acid with and w/o metabolic activation were considered acceptable for in vitro tests using cultivated mammalian cells w/o going the risk to induces artificial findings.
During both experiments the mutant frequency was not influenced by treatment with the test subatance with or w/o metabolic activation up to a maximum concentration of 5000 µg/mL.
The positive control groups, treated with ethyl methane sulphonate (EMS) or 9,10-dimethyl-1,2 -benzanthracene (DMBA), predominantly predominantly distinct increases in the mutant frequency occured.
Cytotoxicity:
During the main trials only in the 2nd experiment a moderate cytotoxic effect was noted with a decrease of the cell number at the end of the treatment period as compared to concurrent negative controls. This only was present at the highest concentration of the test substance of 5000 µg/mL, but observed in both parts (with and w/o metabolic activation).
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
No genotoxicity of alpha-lipoic acid was observed in mice (in vivo micronucleus test).
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1995-09-19 - 1995-09-21
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Study owner prepared study while seeking authorisation of the substance as active incredient for medical treatment.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- other: in vivo micronucleus test
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Caging: Macrolon cages, type II
Animals per cage: 1
Bedding: Animal bedding softwood garnulation HW 300/500W
Diet: Standard diet ad libitum
Water: ad libitum
Room temperature: 21.0 - 22.0 °C
Relative humidity: 48 - 52 %
Room lighting: 6:00 - 18:00 (cet) artificial lighting
18:00 - 6:00 (cet) darknes - Route of administration:
- oral: gavage
- Vehicle:
- propylene glycol
- Frequency of treatment:
- single administration
- Post exposure period:
- 24 h and 48 h
- Dose / conc.:
- 825 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Negative control: 12 m + 12 f
Positive control: 6 m + 6 f
Test material group: 19 m + 17 f - Control animals:
- yes
- Positive control(s):
- Cyclophosphamid
- Tissues and cell types examined:
- Bone marrow cells from both femurs.
Polychromatic erythrocytes - Details of tissue and slide preparation:
- Bone marrow was suspended in approx. 1.5 ml FCS and centrifuged at 180 g for 5 min.
Supernatand was discarded and cells were suspended in FCS.
Small drop of this suspension was smeared on a slide and dried overnight. - Statistics:
- POISSON test
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- ten test material group animals died
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- Thioctic acid, racemate, at 825 mg/kg body weight (males and females, single oral administration) is non-genotoxic in the mouse micronucleus test under the described conditions.
- Executive summary:
Ten (10) test mateial group animals died.
After a singele oral admission of the test material à 825 mg/kg b. w. no statistically significant test material-related increase im micronucleated PCEs was observed in both, male and female animals, respectively males and females combined, when compared with corresponding negative control group animals at 24 h or 48 h after administration. No reduction in PCE/NCE ratio was present in test material group animals, when compared to the corresponding control group animals.
The positive control group animals, wich recieved cyclophosphamide, exhibited a significant increase in the number of micronucleated polychromatic erythrocytes and thus validated the test system.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
According to the GHS regulation alpha-Lipoic acid is not classified as genotoxic or mutagenic.
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.