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EC number: 210-514-9 | CAS number: 617-48-1
- 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
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Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 25 April 1984 to 16 May 1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline-compliant, proprietary study. Read across to fumaric acid.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 984
- Report date:
- 1984
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Fumaric acid/ Fumaril
- IUPAC Name:
- Fumaric acid/ Fumaril
- Details on test material:
- - Physical state: Solid
- Analytical purity: 99.5%
- odour: odourless
- Name of test material (as cited in study report): fumaric acid
- Impurities (identity and concentrations): benzoic, maleic and phthalic acid <0.05%
- Composition of test material, percentage of components:
- Stability under test conditions:
- Storage condition of test material:
- Other: pH 2.1 at 4.9 g/L density 1.63 g/cm3
Constituent 1
Test animals / tissue source
- 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.
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: left eyelid of each animal
- 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
Results and discussion
In vivo
Results
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 72 hrs
- Score:
- 42.8
- Reversibility:
- not fully reversible within: 21 days
- Irritant / corrosive response data:
- The mean values over the 24, 48 and 72 hour post-instillation observations were:
corneal opacity = 2.0
Iris = 0.28
Conjunctival redness = 2.83
conjunctival chemosis = 1.72
Any other information on results incl. tables
Table 1. Cornea Evaluation: Degree of Opacity (A) x Extent of Opacity (B) x 5
Animal number | 1 hr | 24 hr | 48 hr | 72 hr | ||||||||||||
A | B | AxBx5 | A | B | AxBx5 | A | B | AxBx5 | A | B | AxBx5 | |||||
1 | 1 | 4* | 20 | 1 | 4 | 20 | 1 | 4 | 20 | 1 | 4 | 20 | ||||
2 | 1 | 4 | 20 | 1 | 4 | 20 | 1 | 4 | 20 | 2 | 4 | 40 | ||||
3 | 2 | 4 | 20 | 2 | 4+ | 40 | 2 | 4+ | 40 | 3 | 2- | 30 | ||||
4 | 2 | 4 | 20 | 3 | 2 | 30 | 4 | 2- | 40 | 4 | 2- | 40 | ||||
5 | 2 | 4 | 20 | 1 | 4+ | 20 | 4 | 2- | 40 | 3 | 2- | 30 | ||||
6 | 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
Animal number | 1 hr | 24 hrs | 48 + 72 hrs | |||
A | A x 5 | A | A x 5 | A | A x 5 | |
1 | 0 | 0 | 0 | 0 | 0 | 0 |
2 | 0 | 0 | 0 | 0 | 0 | 0 |
3 | 0 | 0 | 0 | 0 | 1* | 5 |
4 | 0 | 0 | 0 | 0 | 0 | 0 |
5 | 0 | 0 | 1* | 5 | 1* | 5 |
6 | 0 | 0 | 0 | 0 | 0 | 0 |
Mean | 0 | 0.83 | 1.67 | |||
*Circumcorneal injection |
Table 3. Conjunctive Evaluation: Redness (A) + Swelling (B) + Exudation (C)
Animal number | 1 hr | 24 hrs | 48 hrs | 72 hrs | ||||||||||||
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 | 2 | 2 | 2 | 12 | 3 | 2 | 2 | 14 | 3 | 1 | 2 | 12 | 3 | 1 | 1 | 10 |
2 | 2 | 3 | 2 | 14 | 3 | 2 | 2 | 14 | 2 | 2 | 2 | 12 | 3- | 2 | 1 | 12 |
3 | 2* | 3 | 2 | 14 | 2 | 2 | 2 | 12 | 3- | 2 | 2 | 14 | 3- | 2 | 1 | 12 |
4 | 2 | 3 | 2 | 14 | 3+ | 2 | 3 | 16 | 3 | 2 | 3 | 16 | 3- | 2 | 2 | 14 |
5 | 2* | 2 | 2 | 12 | 2 | 2 | 2 | 12 | 3 | 1 | 2 | 12 | 3- | 1 | 2 | 12 |
6 | 2 | 2 | 2 | 12 | 3 | 2 | 2 | 14 | 3 | 2 | 2 | 14 | 3 | 1 | 2 | 12 |
Mean | 13 | 13.67 | 13.33 | 12.0 | ||||||||||||
*Necrotic spots on mucous membrane; +Skin-like mucous on the cornea; -White layer is exuded from the mucous membrane |
Applicant's summary and conclusion
- Interpretation of results:
- moderately irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: OECD GHS
- Conclusions:
- This study supports the conclusion that fumaric acid and malic are moderate eye irritants requiring classification.
- Executive summary:
Read across to fumaric acid is considered valid and malic acid is concluded to be irritating to eyes and classification is required
It is not considered valid to perform further animal tests on malic acid.
Application of 0.1 g fumaric acid to the eyes of male and female rabbits was considered moderately 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".
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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