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EC number: 203-743-0 | CAS number: 110-17-8
- 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
When tested in guideline-compliant studies for skin irritation and eye irritation, fumaric acid was a slight or mild skin irritant not requiring classification, and a moderate eye irritant.
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:
- key study
- Study period:
- 25 April to 9 May 1984
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- 12 May 1981
- GLP compliance:
- no
- Remarks:
- GLP was not yet legally implemented when the study was conducted.
- Species:
- rabbit
- Strain:
- other: small white Russian
- Details on test animals or test system and environmental conditions:
- Male and female rabbits between 1.9 and 2.8 kg were housed in individual stainless steel cages and acclimated for 14 days. Rabbits received K4 single diet for rabbits (Ssniff Special Feed GmbH) and water ad libitum. Room temperature was 20 °C with 60 % relative humidity. Air was exchanged 15 times per hour and a 12 hr light-dark cycle was employed.
- Type of coverage:
- occlusive
- Preparation of test site:
- shaved
- Vehicle:
- other: paraffin oil
- Controls:
- not required
- Amount / concentration applied:
- 0.5 g test material wetted with paraffin oil
- Duration of treatment / exposure:
- 4 hrs
- Observation period:
- 1, 24, 48 and 72 hours as well as 5, 7, 8, 12 and 14 days
- Number of animals:
- 3 males and 3 females
- Details on study design:
- TEST SITE
- Area of exposure: 6 cm² patch of skin
- Type of wrap if used: Linen cloth (2.5 × 2.5 cm) covered with a polyethylene foil (6 × 6 cm). The application site was secured with an elastic band.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water
SCORING SYSTEM:
Erythema and eschar formation:
No erythema...0
Very slight erythema (barely perceptible)...1
Well-defined erythema...2
Moderate to severe erythema...3
Severe erythema to slight eschar formation...4
Oedema formation:
No oedema...0
Very slight oedema...1
Slight oedema...2
Moderate oedema...3
Severe oedema...4
Reaction values for redness and swelling were calculated for 1, 24, 48 and 72 hours after patch removal. These absolute values were added together and divided by the number of assessment times (4) to determine the irritation index:
0–0.5 Not irritating
0.6–3.0 Mildly irritating
3.1–5.0 Moderately irritating
5.0–8.0 Highly irritating - Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 72 hrs
- Score:
- 0.63
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- ca. 1
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- ca. 1.67
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- ca. 0.67
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- ca. 1
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- ca. 1
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- ca. 0.33
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- ca. 0.33
- Max. score:
- 4
- Irritant / corrosive response data:
- The mean score over 24-72 hours for redness was calculated to be 0.72.
The mean score over 24-72 hours for swelling was calculated to be 0.11.
Neither score warrants classification for skin irritation. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- This study supports the conclusion that fumaric acid is a mild skin irritant that does not require classification for dermal irritation according to EU and GHS systems.
- Executive summary:
Dermal application of 0.5 g fumaric acid was mildly irritating to the skin of male and female rabbits. Fumaric acid did not elicit dermal reactions that would exceed the threshold for classification in accordance with EU criteria.
Reference
Individual and average redness (R) and swelling (S) values
Animal number | 1 hr | 24 hr | 48 hr | 72 hr | ||||
R | S | R | S | R | S | R | S | |
1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
3 | 0 | 0 | *2 | 0 | *1 | 1 | *2 | 0 |
4 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
6 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 |
Total | 0 | 0.5 | 0.83 | 1.17 | ||||
Average | 2.50/4 = 0.63 | |||||||
*Redness directly on the application surface |
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:
- key study
- Study period:
- 25 April 1984 to 16 May 1984
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- GLP compliance:
- no
- Remarks:
- GLP was not yet legally implemented when the study was conducted.
- Species:
- rabbit
- Strain:
- other: small white Russian
- Details on test animals or tissues and environmental conditions:
- Male and female rabbits between 1.9 and 2.1 kg were housed in individual stainless steel cages and acclimated for 14 days. Rabbits received K4 single diet for rabbits (Ssniff Special Feed GmbH) and water ad libitum. Room temperature was 20C with 60% relative humidity. Air was exchanged 15 times per hour and a 12 hr light-dark cycle was employed.
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- 0.1 g fumaric acid
- Duration of treatment / exposure:
- The test material was not washed out.
- Observation period (in vivo):
- 1, 24, 48 and 72 hours and 5, 7, 9, 12, 15, 19 and 21 days.
- Number of animals or in vitro replicates:
- 3 males and 3 females
- Details on study design:
- Test material was applied to the lower conjunctival sac of the right eye by pulling away the lower eyelid. The left eye was treated in one animal.
The contralateral eye served as a concurrent, inherent control. - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0.28
- Max. score:
- 2
- Reversibility:
- not reversible
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 2.83
- Max. score:
- 3
- Reversibility:
- fully reversible within: 19d
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 1.72
- Max. score:
- 4
- Reversibility:
- fully reversible within: 19 d
- Remarks on result:
- positive indication of irritation
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- This study supports the conclusion that fumaric acid is an eye irritant.
- Executive summary:
Application of 0.1 g fumaric acid to the eyes of male and female rabbits was considered irritating to the eye and ocular mucous membrane. Fumaric acid is classified as an eye irritant. It is assigned the symbol Xi and the risk-phrase R36 - irritating to the eyes according to Directive 67/548/EEC. It is assigned the pictogram GHS07 with the signal word warning and the hazard statement H319 "causes serious eye irritation".
Reference
Table 1:Cornea evaluation: Degree of opacity (A) × extent of opacity (B) × 5
|
|
1 h |
24 h |
48 h |
72 h |
||||||||
Animal # |
Sex |
A |
B |
A × B × 5 |
A |
B |
A × B × 5 |
A |
B |
A × B × 5 |
A |
B |
A × B × 5 |
1 |
M |
1 |
4 |
20 |
1 |
4 |
20 |
1 |
4 |
20 |
1 |
4 |
20 |
2 |
M |
1 |
4 |
20 |
1 |
4 |
20 |
1 |
4 |
20 |
2 |
4 |
40 |
3 |
M |
2 |
4 |
40 |
2 |
4+ |
40 |
2 |
4+ |
40 |
3 |
2– |
30 |
4 |
F |
2 |
4 |
40 |
3 |
2 |
30 |
4 |
2– |
40 |
4 |
2– |
40 |
5 |
F |
2 |
4 |
40 |
1 |
4+ |
20 |
4 |
2- |
40 |
3 |
2– |
30 |
6 |
F |
1 |
4 |
20 |
1 |
4 |
20 |
1 |
4 |
20 |
1 |
4 |
20 |
Mean |
|
|
|
30 |
|
|
25 |
|
|
30 |
|
|
30 |
*) Circular streak (0–4 mm) on the pupil; + Spot on the cornea with opacity up to white coloration; – Remaining surface: reduction in normal clarity |
Table 2:Iris evaluation: A = Change
|
|
1 h |
24 h |
48 + 72 h |
|||
Animal # |
Sex |
A |
A × 5 |
A |
A × 5 |
A |
A × 5 |
1 |
M |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
M |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
M |
0 |
0 |
0 |
0 |
1* |
5 |
4 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
5 |
F |
0 |
0 |
1* |
5 |
1* |
5 |
6 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
Mean |
|
|
0 |
|
0.83 |
|
1.67 |
*) Circumcorneal injection |
Table 3:Conjunctive evaluation: Redness (A) + swelling (B) + exudation (C)
|
|
1 h |
24 h |
48 h |
72 h |
||||||||||||
Animal # |
Sex |
A |
B |
C |
(A + B + C) × 2 |
A |
B |
C |
(A + B + C) × 2 |
A |
B |
C |
(A + B + C) × 2 |
A |
B |
C |
(A + B + C) × 2 |
1 |
M |
2 |
2 |
2 |
12 |
3 |
2 |
2 |
14 |
3 |
1 |
2 |
12 |
3 |
1 |
1 |
10 |
2 |
M |
2 |
3 |
2 |
14 |
3 |
2 |
2 |
14 |
2 |
2 |
2 |
12 |
3– |
2 |
1 |
12 |
3 |
M |
2* |
3 |
2 |
14 |
2 |
2 |
2 |
12 |
3– |
2 |
2 |
14 |
3– |
2 |
1 |
12 |
4 |
F |
2 |
3 |
2 |
14 |
3+ |
2 |
3 |
16 |
3 |
2 |
3 |
16 |
3– |
2 |
2 |
14 |
5 |
F |
2* |
2 |
2 |
12 |
2 |
2 |
2 |
12 |
3 |
1 |
2 |
12 |
3– |
1 |
2 |
12 |
6 |
F |
2 |
2 |
2 |
12 |
3 |
2 |
2 |
14 |
3 |
2 |
2 |
14 |
3 |
1 |
2 |
12 |
Mean |
|
|
|
|
13 |
|
|
|
13.37 |
|
|
|
13.33 |
|
|
|
12 |
*) Necrotic spots on mucous membrane; + Skin-like mucous on the cornea; – White layer is exuded from the mucous membrane |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Male and female small white Russian rabbits were exposed to 0.5 g fumaric acid wetted with paraffin oil under an occlusive patch for 4 hours. Dermal application of fumaric acid was mildly irritating to the skin of male and female rabbits with an irritation index of 0.63.
Male and female small white Russian rabbits administered 0.1 g fumaric acid by application to the eyelid pocket showed an irritation index of 42.8 after 72 hours. Fumaric acid was considered moderately irritating to the eye and ocular mucous membrane.
Effects on skin irritation/corrosion: slightly irritating
Effects on eye irritation: moderately irritating
Justification for classification or non-classification
Fumaric acid is listed on Annex I of Directive 67/548/EEC as an irritant to eyes (Xi; R36).
The mild skin irritation observed was insufficient to justify classification. Moderate, reversible eye irritation seen in the study discussed above shows that fumaric acid should remain classified for ocular irritation according to current EU criteria.
Fumaric acid is classified as an eye irritant. It is assigned the symbol Xi and the risk-phrase R36 - irritating to the eyes according to Directive 67/548/EEC. It is assigned the pictogram GHS07 with the signal word warning and the hazard statement H319 "causes serious eye irritation".
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