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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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
Fumaric acid is not considered a skin sensitiser.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The paper provides a comparison of GPMT and LLNA designs for assessment of sensitising potential rather than a method for assessing the sensitisation potential of fumaric acid. Fumaric acid is included as one of the range of test materials under consideration but the results are used to compare the relative merits of the two study designs. The results do supplement other studies that indicate fumaric acid is not a sensitiser.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS: SPF-Hsd Poc: DH guinea pigs
- Source:Harlan Winkelmann,Borchen Germany.
- Age at study initiation: not stated
- Weight at study initiation: 300-500g
- Housing:Group housed in Terlauronmakrolon type cages with saw fibre bedding
- Diet (e.g. ad libitum): Altromin 3122 maintenance diet or Ssniff Ms-H, 4mm V2233-000
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 55±10% RH
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: not stated To: not stated - Route:
- intradermal and epicutaneous
- Vehicle:
- cotton seed oil
- Concentration / amount:
- intradermal induction - 5%
topical induction - 25%
Challenge application - 10% - Route:
- epicutaneous, occlusive
- Vehicle:
- cotton seed oil
- Concentration / amount:
- intradermal induction - 5%
topical induction - 25%
Challenge application - 10% - No. of animals per dose:
- 10 test and 5 controls
- Details on study design:
- RANGE FINDING TESTS: various tests performed to determine suitable dose concentrations foreach phase of the main study
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 - intradermal and topical
- Exposure period:
- Test groups: 10 guinea pigs exposed to FCA and test material in vehicle on day 1, treated with SLS prior to topical application afte one week, topical induction applied over injection sites and occluded for 48 hours
- Control group: as test group but with test material. only 5 guinea pigs used
- Site:
- Frequency of applications: once on day 1 and 8
- Duration: intradermal injections unlimited, toppical induction exposure for 48 hours
- Concentrations: 5 and 25%
B. CHALLENGE EXPOSURE
- No. of exposures: two
- Day(s) of challenge: day 20 and 28
- Exposure period: 24 hours
- Test groups: ten animals
- Control group: five animals
- Site: dorsum
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 and 72 hours post patch removal - Positive control substance(s):
- not required
- Statistics:
- Not required.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- Fumaric acid was non-sensitising in the guinea pig maximisation test.
- Executive summary:
The skin sensitisation potential of one saturated and eight unsaturated lipid biochemicals was tested in a LLNA and guinea pig Maximisation test for comparative purposes to test the hypothesis that chemicals with unsaturated carbon-carbon double bonds may give a higher false positive rate in LLNA results than in the GPMT.
Fumaric acid was non-sensitising in the GPMT.
The relative merits of the two assays are further discussed in the paper but are not directly relevant to the assessment of fumaric acid sensitising potential.- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The paper provides a comparison of GPMT and LLNA designs for assessment of sensitising potential rather than a method for assessing the sensitisation potential of fumaric acid. Fumaric acid is included as one of the range of test materials under consideration but the results are used to compare the relative merits of the two study designs. The results do supplement other studies that indicate fumaric acid is not a sensitiser.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS: SPF-CBA/Ca01aHsd mice
- Source: Harlan Winkelmann,Borchen Germany.
- Age at study initiation: 6-12 weeks
- Weight at study initiation: not stated
- Housing: Group housed in makrolon type cages with saw fibre bedding
- Diet (e.g. ad libitum):Altromin 1324 maintenance diet
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 55±10% RH
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: not stated To: not stated - Vehicle:
- dimethyl sulphoxide
- Concentration:
- 5, 10 and 25%
- No. of animals per dose:
- five mice per group
- Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: three different concentrations tested to detct highest tolerable exosure concentration
- Irritation: local irritatiion measured by ear sweling
- Lymph node proliferation response: not determined in preliminary investigation
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: SI
TREATMENT PREPARATION AND ADMINISTRATION:
In the main test groups of 5 mice were treated by topical applications of 25 µl test or control solution, applied to the entire dorsal surface of the ear. Topical applications were performed once daily for 3 consecutive days. The negative control group was treated with vehicle alone. The positive control group was treated with 1% p-phenylenediamine. On day 6 all mice were injected with 20µCi tritiated methyl thymidine via the tail vein. Approximately 5 hours later the mice were sacrificed and the draining auricular lymph nodes were excised, weighed (right and left) and individually pooled per animal in PBS. The cell suspension was prepared according to standard methods. Tritated thymidine was measured using a scintillation counter and expressed as disintegrations per minute.
The proliferative response of the lymph node cells was expressed as number of disintegrations per node (DPM/node) adjusted for background values. The Stimulation Index was calculated as the ratio of the arithmetic mean of DPM/node values forthe test and control groups - Positive control substance(s):
- other: 1% p-phenylenediamine
- Statistics:
- DPM/node and SI calculated as per standard methods
- Parameter:
- SI
- Remarks on result:
- other: SI = 1.3 at 5%; 2.3 at 10% and 1.4 at 25% LNWI - 1.3 at 55; 1.5 at 10% and 1.3 at 25% SI = stimulation index - no linear dose response and no value exceeding 3.0 LNWI = lymph node weight index
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Individual values not presented in publication
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- Fumaric acid gave a clearly negative response in the murine LLNA, which supported the conclusion that the GPMT also indicated so sensitising potential for this material and reinforced the conclusion drawn from the key study presented in this data point that no classification is necessary in respect of sensitisation for fumaric acid.
- Executive summary:
The skin sensitisation potential of one saturated and eight unsaturated lipid biochemicals was tested in a LLNA and guinea pig Maximisation test for comparative purposes to test the hypothesis that chemicals with unsaturated carbon-carbon double bonds may give a higher false positive rate in LLNA results than in the GPMT.
The results of the LLNA test for fumaric acid, as part of the test series, are presented in this summary. It was concluded that fumaric and succinic acids gave clearly negative LLNA results and that neither material would be classified for hypersensitivity potential based on the results of the GPMT . The relative merits of the two assaysare further discussed in the paper but are not directly relevant to the assessment of fumaric acid sensitising potential.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- GLP compliance:
- no
- Remarks:
- GLP was not yet legally implemented when the study was conducted.
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Study report from 1989 available.
- Species:
- guinea pig
- Strain:
- other: Bor: DHPW
- Sex:
- female
- Details on test animals and environmental conditions:
- One to five animals were kept in type IV Makrolon cages for an acclimation period of 5-8 days. Average weight of animals was 400 g. G4 general diet for guinea pigs and water were provided ad libitum. Room temperature was 20 °C with 60 % relative humidity. There were 15 air exchanges per hour with a 12 hr light-dark rhythm.
- Route:
- intradermal and epicutaneous
- Vehicle:
- corn oil
- Concentration / amount:
- Induction, intradermal: 0.5%
Induction, epicutaneous: 25% test material - Day(s)/duration:
- 7
- Adequacy of induction:
- non-irritant substance, but skin pre-treated with 10% SDS
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- corn oil
- Concentration / amount:
- Challenge: 25 %
- Day(s)/duration:
- 2
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- 19 animals per dose
- Details on study design:
- A total of six intracutaneous injections were made in the right and left shoulder area of animals: a mixture of Freunds Complete Adjuvant and water, 0.5 % test material in corn oil, and 0.5 % test material in a mixture of FCA and corn oil. A patch test was carried out a week later. Twenty-four hours prior to the patch test, the shoulder region was shaved and 10 % SDS prepared in vaseline was massaged into the skin to provoke a mild skin irritation. Filter paper was coated with 25 % test material in corn oil, applied to the injection region and covered with an adhesive bandage. The patch was secured for 48 hrs with an elastic bandage.
Two weeks later, a filter paper patch coated with 25% test substance in corn oil was applied to the left flank of animals and covered with an adhesive bandage. An elastic bandage was used to secure the patch for 24 hours. A patch containing only corn oil was applied to the right flank of animals. - Challenge controls:
- A total of six intracutaneous injections were made in the right and left shoulder area of animals: A mixture of Freunds Complete Adjuvant and water, corn oil, and a mixture of FCA and corn oil. A patch test was carried out a week later. Filter paper was coated with corn oil, applied to the injection region and covered with an adhesive bandage. The patch was secured for 48 h with an elastic bandage. Two weeks later, a filter paper patch coated with 25 % test substance in corn oil was applied to the left flank of animals and covered with an adhesive bandage. An elastic bandage was used to secure the patch for 24 hours. A patch containing only corn oil was applied to the right flank of animals.
- Positive control substance(s):
- not required
- Positive control results:
- None - not necessary according to guideline.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25 %
- No. with + reactions:
- 0
- Total no. in group:
- 19
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 25 %
- No. with + reactions:
- 0
- Total no. in group:
- 19
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 45
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Interpretation of results:
- not sensitising
- Conclusions:
- This study supports the conclusion that fumaric acid is not a skin sensitiser.
- Executive summary:
Fumaric acid shows no sensitisation effect on the skin of female guinea pigs according to the Magnusson-Kligman maximization test.
Referenceopen allclose all
No signs of systemic toxicity were observed. Fumaric acid caused a grade 1 skin reaction in one animal at 24 and 48 h after patch removal. This animal did not show a reaction when re-challenged.
No signs of systemic toxicity were observed. No clinical signs of local irritation were observed by visual inspection of the ears. Fumaric acid gave clear negative results, with SI values below 3. A weak but statistically significant LNWI increase was observed at 10% but not 5% or 25%. As the lymph node weight reaction was weak and lacked a dose-response relationship, the SI result was given precendence and it was concluded that fumaric acid was not sensitising in the LLNA.
Local reactions during experiment
After intracutaneous injection: All injection sites treated with FCA showed intense redness and swelling, as well as necrosis, in both control and treated animals. Mild redness and swelling was also seen in control animals treated with corn oil. Twenty-four hours after patch removal, all injection sites treated with FCA were crusted and scabby.
After patch test of 48 h duration: Intense inflammation, at times bloody, was seen in control and test animals treated with FCA and demineralised water. 24 hours after patch removal: all injections sites treated with FCA were crusted and scabby.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
A total of six intracutaneous injections were made in the right and left shoulder area of female guinea pigs: a mixture of Freunds Complete Adjuvant and water, 0.5 % fumaric acid in corn oil, and 0.5 % fumaric acid in a mixture of FCA and corn oil. A patch test was carried out a week later with 25 % fumaric acid in corn oil, applied to the injection region and covered with an adhesive bandage. The patch was secured for 48 h with an elastic bandage. Two weeks later, a filter paper patch coated with 25 % fumaric acid in corn oil was applied to the left flank of animals and covered with an adhesive bandage for 24 hours. At 48 h post challenge, none of the animals showed any positive skin reactions. Fumaric acid at a concentration of 25 % showed no sensitization effect on the skin of female guinea pigs according to the Magnusson-Kligman maximization test.
In the LLNA, groups of 5 mice were treated by topical applications of 25 µl test or control solution, applied to the entire dorsal surface of the ear. Topical applications were performed once daily for 3 consecutive days. The negative control group was treated with vehicle alone. The positive control group was treated with 1% p-phenylenediamine. On day 6 all mice were injected with 20µCi tritiated methyl thymidine via the tail vein. Approximately 5 hours later the mice were sacrificed and the draining auricular lymph nodes were excised, weighed (right and left) and individually pooled per animal in PBS. The cell suspension was prepared according to standard methods. Tritiated thymidine was measured using a scintillation counter and expressed as disintegrations per minute.
The proliferative response of the lymph node cells was expressed as number of disintegrations per node (DPM/node) adjusted for background values. The Stimulation Index was calculated as the ratio of the arithmetic mean of DPM/node values for the test and control groups.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Fumaric acid is not classified as a skin sensitiser based on results of a guideline-comparable Magnusson-Kligman maximization study which showed no evidence of skin sensitisation.
No evidence of skin sensitisation was seen in a guideline-compliant Local Lymph Node Assay with fumaric acid.
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.