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EC number: 210-459-0 | CAS number: 616-02-4
- 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
WoE: No valid data available from animal studies for citraconic anhydride. K3: Limited publications, standard guideline not followed (different procedure for exposure and not enough animals used), not GLP. These studies show a positive result for skin sensitization. This is supported by predictions made by QSAR models for maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride. These structural analogs are Annex VI REACH registered skin and respiratory sensitizers. Therefore citraconic anhydride is classified as a skin and respiratory sensitizer.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Limited publication, standard guideline not followed (different procedure for induction and challenge), not GLP.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- See methods section below.
- GLP compliance:
- no
- Type of study:
- other: non standard guinea pig test
- Justification for non-LLNA method:
- conducted before LLNA method was adopted
- Species:
- guinea pig
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: olive oil and dioxane
- Concentration / amount:
- induction:
intradermal - 0.5% in olive oil
epicutaneous - 100%
challenge - 25% in dioxane - Route:
- other: epicutaneous intact and scratch-test
- Vehicle:
- other: olive oil and dioxane
- Concentration / amount:
- induction:
intradermal - 0.5% in olive oil
epicutaneous - 100%
challenge - 25% in dioxane - No. of animals per dose:
- 28
- Challenge controls:
- No controls included in the study
- Positive control substance(s):
- no
- Key result
- Reading:
- other:
- Hours after challenge:
- 0
- Group:
- test chemical
- Dose level:
- 25% in dioxane
- No. with + reactions:
- 9
- Total no. in group:
- 12
- Clinical observations:
- Not reported
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: expert judgment
- Conclusions:
- Based on the results of this experiment the substance can be considered a sensitizer.
- Executive summary:
Based on the results of this experiment the substance can be considered a sensitizer.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- no data
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Limited publication, standard guideline not followed (different procedure for exposure and not enough animals used), not GLP.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- See methods section below.
- GLP compliance:
- no
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- conducted before LLNA method was adopted
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- Most studies were conducted on randomly bred Hartley strain male guinea pigs weighing approximately 300g. The animals were maintained on Purina guinea pig chow supplemented with green vegetables and water ad libitum. All animals were maintained in rooms designed to control temperature, humidity and light cycle.
- Route:
- other: topical + injection of Freunds adjuvant
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.1 ml for induction for the challenge: no data.
- Route:
- other: topical
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.1 ml for induction for the challenge: no data.
- No. of animals per dose:
- 10
- Positive control substance(s):
- yes
- Remarks:
- diglycidyl ether of 2,2-di-(p,p'-hydroxyphenyl)propane (DER* 331 Epoxy Resin Dow Chemical U.S.A.)
- Reading:
- other: Not provided
- Hours after challenge:
- 24
- Group:
- other: Not provided
- Dose level:
- Not provided
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Clinical observations:
- Not provided
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- 3/10 guinea pigs showed a positive response.
- Executive summary:
3/10 guinea pigs showed a positive response.
Referenceopen allclose all
Examination of reactions obtained from citraconic anhydride sensitized guinea pigs have shown, as well as after a scratch-test as after
an epicutaneous test, immediate urticarial reactions, histologically characterized by the presence of eosinophilic leukocytes, intra- and perivascular. Afterwards erythematous reactions develop on the flank, which sometimes presents epidermal lesions and a leukocytic infiltrate extremely rich in eosinophilic leukocytes. On the nipple eczematous epidermal lesions and leukocytic infiltrate, rich in eosinophilic leukocytes were found regularly.
3/10 guinea pigs showed a positive response.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
Respiratory sensitisation
Link to relevant study records
- Endpoint:
- respiratory sensitisation, other
- Remarks:
- other: QSAR
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Justification for type of information:
- QSAR prediction
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Software used
OECD QSAR Toolbox v3
DEREK NEXUS 2.0.2 - Interpretation of results:
- sensitising
- Remarks:
- expert judgment
- Conclusions:
- The results of the QSAR analysis indicate that
1. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are potential skin and respiratory sensitizers and this agrees with experimental data.
2. Based on the similar profiles for these 4 substances, citraconic anhydride can be classified as skin Skin Sens. 1 H317) and respiratory (Resp. Sens. 1 H334) sensitizer. - Executive summary:
Software used
OECD QSAR Toolbox v3
DEREK NEXUS 2.0.2
Methods
Structures were drawn in Marvin Sketch software and used to generate the structure files (.mol) and SMILES codes, which were then checked for correctness and then used as input into the various software packages.
Results and discussion
A summary of the results of the analysis are shown in Table 1 on the next page. Table 2 shows a full human health profile of the four substances from the QSAR Toolbox. In Appendices 1 - 3 an explanation of the mechanisms of action identified in Table 1 is presented. Both QSAR Toolbox and DEREK NEXUS identify structural alerts for skin sensitization for all compounds. DEREK NEXUS identifies alerts for respiratory sensitization for all four compounds. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are REACH Tier I registered substances and are all classified as
Resp. Sens. 1 H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled.
Skin Sens. 1 H317: May cause an allergic skin reaction.
The predictions from the QSAR software agree with the measured data.
To determine whether the measured data from the three anhydrides can be read across to citraconic anhydride, parameters relevant to skin sensitization were compared for the 4 substances. Table 2 (highlighted in yellow) shows similar profiles for organic functional groups, groups of elements, chemical elements, protein binding, substance type and bioavailability (Lipinski). Additionally, Table 1 shows low values for log Kow and Log Kp (skin permeability coefficient). Based on these similar profiles, it can be concluded that experimental data (respiratory and skin sensitization) from these three anhydrides can be read across to citraconic anhydride.
For details see attached report.
Conclusions
The results of the QSAR analysis indicate that
1. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are potential skin and respiratory sensitizers and this agrees with experimental data.
2. Based on the similar profiles for these 4 substances, citraconic anhydride can be classified as skin Skin Sens. 1 H317) and respiratory (Resp. Sens. 1 H334) sensitizer.
References
United Nations Economic Commission for Europe (UNECE). (2004). Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Respiratory or Skin Sensitization, Chapter 3.4. pp. 151-158. Retrieved here Sept. 1, 2007.
Reference
The results of the QSAR analysis indicate that
1. Maleic anhydride, benzene-1,2,4-tricarboxylic acid 1,2-anhydride and phthalic anhydride are potential skin and respiratory sensitizers and this agrees with experimental data.
2. Based on the similar profiles for these 4 substances, citraconic anhydride can be classified as skin Skin Sens. 1 H317) and respiratory (Resp. Sens. 1 H334) sensitizer
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
Justification for classification or non-classification
Based on the available data the substance is classified cat.1 skin and respiratory sensitizer.
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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