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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
Description of key information
Four studies were performed to determine the acute oral toxicity of alpha-Lipoic acid.
The studies from the year 1974, using mice and rats as test animals, show silmilarities to the OECD-guideline 401 adopted later in 1987.
Because of more than 3 dosing levels and a greater number of animals, these studies give a more precise result.
In rats the LD50 is 1200 mg/kg BW (m + f).
In mice the LD50 is 502 mg/kg BW (m) and 460 mg/kg BW (f).
The studies from the year 2013 follow an other guiudeline (OECD 423) and are not compareble to the older studies.
The
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11/1973 - 12/1973
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- OECD 401: at least 5 rodents of each sex in each group; at least three dose levels; limit test at least 2000 mg/kg b.w. This Study: 10 rats of each sex in each group; 6 dose levels, spaced with factor 1.26
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Surviving animals were held in macrolon cages (B II) at 24.0 +/- 0.5 °c and 60 +/- 3 % relative humidity.
During 4 weeks after treatment behaviour, feed and water intake and body weigth were observed.
After 4 weeks animals were dissectet and examinded macroscopic. - Route of administration:
- oral: gavage
- Vehicle:
- other: 1 % aequous methyl-hydroxyethylcellulose gel MH300
- Doses:
- Lowest dose: 504 mg/kg b.w.
Step per dose: factor 1.26
Highest dose: 1590 mg/kg b.w. - No. of animals per sex per dose:
- 10
- Control animals:
- no
- Statistics:
- Litchfield and Wilcoxon
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 1 190 mg/kg bw
- Based on:
- test mat.
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 1 210 mg/kg bw
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Median lethal dose (LD50)
- Male rats: 1190 (1090 - 1300) mg/kg b.w.
- Female rats: 1210 (1110 - 1320) mg/kg b.w. - Executive summary:
Symptoms of intoxication showed:
- Sedation
- ataxis (635 mg/kg b.w.)
- reduced feed intake (1000 mg/kg b.w.)
- abdominal position
- slow and breathing
- tonic-clonic spasms (1260 mg/kg b.w.)
Death occured within 2 and 24 h after after treatment after tonic-clonic spasms.
Lowest lethal dose: 1000 mg/kg b.w.
Surviving animals recovered within 2 d.
Necopsy showed pale and parencymatic organs in animals that died after treatment. Other animals showed no pahological findings.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 10/1973 - 12/1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- OECD 401: at least 5 rodents of each sex in each group; at least three dose levels; limit test at least 2000 mg/kg b.w. This Study: 10 mice of each sex in each group; 9 dose levels, spaced with factor 1.26
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Surviving animals were held in macrolon cages (B II) at 24.0 +/- 0.5 °c and 60 +/- 3 % relative humidity.
During 4 weeks after treatment behaviour, feed and water intake and body weigth were observed.
After 4 weeks animals were dissectet and examinded macroscopic. - Route of administration:
- oral: gavage
- Vehicle:
- other: 1 % aequous methyl-hydroxyethylcellulose gel MH300
- Doses:
- Lowest dose: 129 mg/kg b.w.
Step per group: factor 1.26
Highest dose: 790 mg/kg b.w. - No. of animals per sex per dose:
- 10
- Control animals:
- no
- Statistics:
- Litchfield u Wilcoxon
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 502 mg/kg bw
- Based on:
- test mat.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- ca. 460 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Median lethal dose (LD50)
- Male mice: 502 (452 - 556) mg/kg b.w.
- Female mice: 460 (418 - 506) mg/kg b.w. - Executive summary:
Symptoms of intoxication showed:
- Sedation (159 mg/kg b.w.)
- ataxis
- abdominal position
- reduced feed intake (200 mg/kg b.w.)
- slow and deep breathing (318 mg/kg b.w.)
- nervousness and tremor
- tonic-clonic spasms (400 mg/kg b.w.)
Death occured within 0.5 and 3 h after treatment after tonic-clonic spasms.
Lowest lethal dose: 400 mg/kg b.w.
Surviving animals recovered within 3 d.
Necopsy showed no pahological findings.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2013-05-07 - 2013-06-19
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Justification for type of information:
- The test with concentrated impurities is not comparable with the older tests in which the acute oral toxicity of alpha-Lipoic acid was determined by an other method.
For that reason two tests under the same conditions were performed:
- alpha-Lipoic acid as described in the composition (1.2) this study
- alpha-Lipoic acid with concentrated impurities (50.1 % impurities) Study titled "disregarded" - Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Test animals: healthy feamale, non-pregnant, nulliparous rats
Temperature: 22 +/- 3 °C
Relative humidity: 55 +/- 10 %
Arificial light: 12 h light, 12 h dark
Diet: free access
Water: free access
Cages: IVC III H
Acclimatization : at least 5 days under laboratory conditions - Route of administration:
- oral: gavage
- Vehicle:
- cotton seed oil
- Doses:
- 2000 mg/kg b.w.
300 mg/kg b.w. - No. of animals per sex per dose:
- 2000 mg/kg b.w.: 3 female rats
300 mg/kg b.w.: 6 female rats (2 groups à 3 animals) - Control animals:
- no
- Key result
- Sex:
- female
- Dose descriptor:
- LD50 cut-off
- Effect level:
- ca. 500 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The median lethal dose of alpha-Lipoic acid after single oral administration to female rats, observed over a period of 14 d is:
LD50 cut-off(rat): 500 mg/kg b.w. - Executive summary:
2000 mg/kg b.w., step 1: 2 animals died on day of treatment
1 animals was found dead on day after administration
300 mg/kg b.w., step 2: all animals survived
300 mg/kg b.w., step 3: all animals survived
Surviving animals showed symptoms of toxicity, but symptoms recovered after 3 days post dose.
Necropsy:
Step 1 (2000 mg/kg b.w.)
3 animals showed yellowish residues of the test item in the stomach
Step 2 (300 mg/kg b.w.)
3 animals showed no specific findings
Step 3 (300 mg/kg b.w.)
3 animals showed no specific findings
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 20113-05-15 - 2015-06-26
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- unsuitable test system
- Justification for type of information:
- This Study was performed to show the toxicity of the impurities in alpha-Lipoic acid.
For that reason the impurities were concentrated up to 50.1 %. - Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- 2001-12-17
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Version / remarks:
- 2002-12
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Test animals: healthy feamale, non-pregnant, nulliparous rats
Temperature: 22 +/- 3 °C
Relative humidity: 55 +/- 10 %
Arificial light: 12 h light, 12 h dark
Diet: free access
Water: free access
Cages: IVC III H
Acclimatization : at least 5 days under laboratory conditions - Route of administration:
- oral: gavage
- Vehicle:
- cotton seed oil
- Doses:
- 2000 mg/kg b.w.
300 mg/kg b.w. - No. of animals per sex per dose:
- 2000 mg/kg b.w.: 3 female rats
300 mg/kg b.w.: 6 female rats (2 groups à 3 animals) - Control animals:
- no
- Key result
- Sex:
- female
- Dose descriptor:
- LD50 cut-off
- Effect level:
- ca. 500 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The median lethal dose of alpha-Lipoic acid with concentrated impurities after single oral administration to female rats, observed over a period of 14 d is:
LD50 cut-off(rat): 500 mg/kg b.w. - Executive summary:
This Study was performed to show the toxicity of the impurities in alpha-Lipoic acid.
2000 mg/kg b.w., step 1: 1 animal died spontaneously on day of treatment
2 animals were found dead on study day 2
300 mg/kg b.w., step 2: 1 animal was found dead on study day 2
300 mg/kg b.w., step 3: 1 animal was sacrificed for ethical reasons on day of treatment
All remaining animals survived until the end of the study.
Necropsy:
Step 1 (2000 mg/kg b.w.)
2 animals showed a bloated stomach with residues of the test item
1 animal showed yellowish residues of the test item in the stomach
Step 2 (300 mg/kg b.w.)
1 animal showed residues of the test item in the stomach
1 animal showed a bloated colon
1 animal showed no specific findings
Step 3 (300 mg/kg b.w.)
2 animals showed no specific findings
1 animal showed a bloated stomach
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 200 mg/kg bw
- Quality of whole database:
- Result is based on a OECD study rated Klimisch 1. Therefore the quality is considered good.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
According to the CLP regulation test substances with an LD50 between 300 and 2000 mg/kg b.w. are classified as hamful (category 4).
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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