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EC number: 610-288-5 | CAS number: 462-20-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
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- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
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- 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
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
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- Endpoint summary
- Stability
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- 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 the results of reliable studies on primary skin and eye irritation according to OECD 404 and 405
respectively Dihydrolipoic Acid to be moderately irritating to rabbit skin and highly irritating to rabbit eye.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 24.06.1999 - 20.07.1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12- 16 weeks
- Weight at study initiation: 2.55 - 282 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum; Stanrab SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: minimum five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 -70 %
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12 hours continous light and 12 hours darkness. - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,5 mL of the test substance - Duration of treatment / exposure:
- three time points: 3 minutes, 1 hour and 4 hours
- Observation period:
- 14 days
- Number of animals:
- three males
- Details on study design:
- TEST SITE
- Area of exposure: dorsal flank area
- Type of wrap if used: elasticated corset (TUBIGRIP)
REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4hours
SCORING SYSTEM:
Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.
Erythema and Eschar Formation:
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well-defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)
Oedema Formation:
0: No oedema
1: Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well-defined by definite raising)
3: Moderate oedema (raised approximately 1 millimeter)
4: Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24 h
- Score:
- 6
- Max. score:
- 6
- Reversibility:
- not specified
- Remarks on result:
- probability of moderate irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 48 h
- Score:
- >= 6
- Max. score:
- 6
- Reversibility:
- not specified
- Remarks on result:
- probability of moderate irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 72 h
- Score:
- >= 5
- Max. score:
- 5
- Reversibility:
- not specified
- Remarks on result:
- probability of moderate irritation
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- Dihydrolipoic Acid produced a primary irritation index of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.
- Executive summary:
A study (according to OECD 404 and 92/69/EEC B.4) was performed to assess the irritancy potential of Dihydrolipoic Acid to the skin of the New Zealand White rabbit.
A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined to moderate to severe erythema and moderate oedema. A thin margin of green-coloured dermal necrosis (approx. 2 mm wide) was noted adjacent to the lower edge of one treatment site with loss of skin elasticity and flexibility, crust formation, reduced regrowth of fur, an area of straw-coloured scabbing, glossy skin and oedema extending ventrally below the treatment site were also noted. Two treated skin sites appeared normal at the 14 -day observation. No evidence of full thickness tissue destruction was noted. 3 -minute and 1 -hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.
Dihydrolipoic Acid produced a primary irritation idex of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.
Reference
Interpretation of Results (Calculation of Primary Irritation Index and Grading of the Irritancy Potential Using Draize Scheme):
The score of the erythema and oedema at the 24 and 72 -hour readings (4 -hour exposure) were totalled for the three rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Daize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p. 47.
Primary Irritation Index: Classification of Irritancy:
0 Non-irritant
> 0 to 2 Mild irritant
> 2 to 5 Moderate irritant
> 5 to 8 Severe irritant
Results of 4 -hour exposure period:
Table 1: The individual scores for erythema/eschar and oedema of the 4 -hour exposure period.
Skin Reaction |
Observation Time |
Individual Scores - Rabbit Number, Sex and Bodyweight |
Total |
||
134 Male (2.82 kg) |
1 Male (2.55 kg) |
2 Male (2.64 kg) |
|||
Erythema/Eschar Formation |
1 hour |
2 (N) |
3 |
2 |
(7) |
24 hours |
2 (N) |
2 |
2 |
6 |
|
48 hours |
2 (N) |
2 |
2 |
(6) |
|
72 hours |
2 LeLf(N) |
2 Le |
1 Le |
5 |
|
7 days |
0 Cf(Sp) |
0 Cf |
0 D |
(0) |
|
14 days |
0 Fr(G) |
0 |
0 |
(0) |
|
Oedema Formation |
1 hour |
3 |
3 |
3 |
(9) |
24 hours |
3 Oe |
3 |
2 |
8 |
|
48 hours |
2 |
2 |
2 |
(6) |
|
72 hours |
2 |
2 |
1 |
5 |
|
7 days |
0 |
0 |
0 |
(0) |
|
14 days |
0 |
0 |
0 |
(0) |
|
Sum of 24 and 72-hour readings (S) |
24 |
||||
Primary Irritation Index (S/6) |
24/6 = 4.0 |
||||
Classification |
Moderate Irritant |
( ) = Total values not used for calculation of primary irritation index
Cf = Crust formation
D = slight desquamation
Fr = reduced regrowth of fur
(G) = glossy skin where necrosis and straw-coloured scabbing previously located
Le = loss of skin elasticity
Lf = loss of skin flexibility
(N) = narrow margin of green-coloured dermal necrosis (approx. 2 mm wide) running along bottom edge of treatment side. Grade 2 erythema present over treated area
Oe = oedema extending ventrally below treatment site
(Sp) = area of straw-coloured scabbing where necrosis previously located
Results of the 1 -hour exposure period:
Table 2: The individual scores for erythema/eschar and oedema of the 1 -hour exposure period.
Skin Reaction |
Observation Time |
Individual Scores - Rabbit Number, Sex and Bodyweight |
|
134 Male (2.82 kg) |
|||
3-minute exposure |
1-hour exposure |
||
Erythema/Eschar Formation |
1 hour |
0 |
0 |
|
24 hours |
0 |
2 |
|
48 hours |
0 |
2 |
|
72 hours |
0 |
2 Le |
|
7 days |
0 |
0 Cf |
|
14 days |
0 |
0 |
Oedema Formation |
1 hour |
0 |
0 |
|
24 hours |
0 |
2 |
|
48 hours |
0 |
1 |
|
72 hours |
0 |
1 |
|
7 days |
0 |
0 |
|
14 days |
0 |
0 |
Cf = crust formation
Le = loss of skin elasticity
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 21.07.1999 - 25.07.1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.78 kg
- Housing: housed in a suspended metal cage
- Diet: ad libitum, Stanrab SQC Rabbit Diet, Special Diets Services, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 -70 %
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): twelve hours light and twelve hours darkness - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,1 mL of the test substance - Duration of treatment / exposure:
- no data
- Observation period (in vivo):
- The animal was killed for humane reasons four days after treatment. An additional observation was performed immediately prior to termination.
- Number of animals or in vitro replicates:
- one male
- Details on study design:
- SCORING SYSTEM: Draize Scale for Scoring Ocular Irrritation
1. CONJUNCTIVAE
a) Redness (refers to palpebral and bulbar conjunctivae exluding cornea and iris)
0: Vessels normal
1: Vessels definitely injected above normal
2: More diffuse, deeper crimson red, individual vessels not easily discernible
3: Diffuse beefy red
b) Chemosis
0: No swelling
1: Any Swelling above normal (includes nictitating membrane)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids half closed to completely closed
c) Discharge
0: No discharge
1: Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs a considerable area around the eye
THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20
2. IRIS
d) Values
0: Normal
1: Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive
2: No reaction to light, haemorrhage, gross destruction (any or all of these)
THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10
3. CORNEA
e) Degree of Opacity (most dense area used)
0: No opacity
1: Scattered or diffuse areas, details of iris clearly visible
2: Easily discernible translucent areas, details of iris slightly obscured
3: Opalescent areas, no details of iris visible, size of pupil barely discernible
4: Opaque, iris not discernible through the opacity
f) Area of Cornea Involved
1: One quarter (or less) but not zero
2: Greater than one quarter but less than half
3: Greater than half but less than three quarters
4: Greater than three quarters, up to whole area
THE TOTAL SCORE = (E x F) x5 MAXIMUM TOTAL = 80
MAXIMUM TOTAL SCORE POSSIBLE = 100 - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- >= 30 - <= 40
- Max. score:
- 40
- Reversibility:
- not specified
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- >= 5
- Max. score:
- 5
- Reversibility:
- not specified
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- >= 14 - <= 16
- Max. score:
- 16
- Reversibility:
- not specified
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- Dihydrolipoic Acid produced a maximum total score of 81.0 and was considered to be at least a very severe irritant (Class 7 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit only).
- Executive summary:
In order to assess the irritancy potential of Dihydrolipoic Acid to the eye of the New Zealand White rabbit a study according to OECD 405 ("Acute Eye Irritation/Corrosion") and 92/69EEC B.5 was performed.
A single instillation of the test material to the non-irrigated eye of one rabbit produced opalescent corneal opacity, iridial inflammation and severe conjunctival irritation. Sloughing of the cornea and alopecia were also noted. The animal was killed for humane reasons four days after treatment. In the test Dihydrolipoic Acid produced a maximum total score of 81.0 and was considered to be at least a very severe irritant (Class 7 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit only).
Reference
Interpretation of Results (Classification According to a Modified Version of the Kay and Calandra System):
The numerical values corresponding to the tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letter A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the iris designated by the letter E (degree of opacity) and F (area of opacity). For each tissue the score was calculated as follows:
Score for conjunctivae = (A+B+C) x 2
Score for iris = Dx5
Score for cornea = (ExF) x 5
Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C, J. Soc. Cosmet. Chem., 1962 13 281- 289 was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point. The total score enabled assessment of the eye irritancy potential of the test material.
If the rabbit shows irriversible ocular damage the test material will be classified as corrosiv to the eye.
Results:
Individual and total scores for ocular irritation are give in Table 1.
Table 1: Indivídual and total scores for ocular irritation.
Rabbit Number and Sex (Bodyweight kg) |
IPR = 0 + |
||||
192 Male (2.78) |
|||||
Time after Treatment |
1 hour |
24 hours |
48 hours |
72 hours |
4 days K |
CORNEA E = Degree of Opacity F = Area of Opacity |
2 3 |
2SI 4 |
3SI* 4 |
3SI* 4 |
3SI* 4 |
Score (E x F) x 5 |
30 |
40 |
40 |
40 |
40 |
IRIS D |
1 |
1 |
1 |
1 |
1 |
Score (D x 5) |
5 |
5 |
5 |
5 |
5 |
CONJUNCTIVAE A = Redness B = Chemosis C = Discharge |
2 2 3 |
2AI 3 3 |
3AI 2 3 |
3AI 2 3 |
3AI 2 3 |
Score (A + B + C) x 2 |
14 |
16 |
16 |
16 |
16 |
Total Score |
49 |
61 |
81 |
81 |
81 |
IPR = initial pain reaction; AI = alopecia; SI = sloughing of the cornea; K = animal killed for humane reasons;
* = grade 3 opacity around lower outer edge of cornea with grade 1opacity over rest of cornea; + = one drop of Ophthaine instilled into both eyes 1 to 2 minutes before dosing
Translucent corneal opacity was noted in the treated eye one hour after treatment and at the 24 -hour observation with opalescent corneal opacity at the 48, 72- hour and 4 -day observations.
Iridial inflammation was noted in the treated eye one hour after treatment and at subsequent 24, 48, 72 -hour and 4 -day observations.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment with severe conjunctival irritation at subsequent 24, 48, 72 and 4 -day observations.
Sloughing of the cornea was noted in the treated eye with alopecia around the treated eye at 24, 48, 72 -hour and 4 -day observations.
The animal was killed, for humane reasons four days after treatment.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
A dermal irritation study with Dihydrolipoic Acid in the rabbit (4 -hours exposure, semiocclusive) was conducted based on the OECD guideline No. 404, "Acute Dermal Irritation/Corrosion". The application produced well-defined to moderate to severe erythema and moderate oedema. A thin margin of green-coloured dermal necrosis (approx. 2 mm wide) was noted adjacent to the lower edge of one treatment site with loss of skin elasticity and flexibility, crust formation, reduced regrowth of fur, an area of straw-coloured scabbing, glossy skin and oedema extending ventrally below the treatment site were also noted. Two skin sites appeared normal at the 14 -day observation. No evidence of full thickness tissue destruction was noted. 3 -minute and 1 -hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects. The test material produced a primary irritation index of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.
An eye irritation study according to the OECD guideline 405 "Acute Eye Irrritation/Corrosion" was conducted. A single installation of the test material to the non-irrigated eye of one rabbit produced opalescent corneal opacity, iridial inflammation and severe conjunctival irritation. Sloughing of the cornea and alopecia were also noted. The animal was killed, for humane reasons four days after treatment.
The test material produced a maximum total score of 81.0 and was considered to be at least a very severe irritant (Class 7 on a 1 to 8 scale) to the rabbit eye according a modified Kay and Calandra classification system (based on one rabbit only).
Effects on skin irritation/corrosion: moderately irritating
Effects on eye irritation: highly irritating
Justification for classification or non-classification
Based on the available data Dihydrolipoic Acid is considered to be moderately irritating to rabbit skin and highly irritating to rabbit eye. Therefore the substance was classified with H315 (Skin Irritation, Cat. 2) and H318 (Serious Eye Damage, Cat. 1).
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