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Diss Factsheets
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EC number: 218-451-9 | CAS number: 2155-60-4
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Type of information:
- experimental study planned
- Study period:
- Within two years after ECHA approval.
- Justification for type of information:
- TESTING PROPOSAL ON VERTEBRATE ANIMALS
NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Dibutyl itaconate
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: In an AMES test, performed according to OECD/EC guidelines and GLP principles, Dibutyl itaconate was found not to be mutagenic with or without metabolic activation. There are no other GLP studies available for genotoxicity.
- Available non-GLP studies: There are no non-GLP studies available for the endpoint genetic toxicity.
- Historical human data: There are no historical human data that can be considered for this endpoint.
- (Q)SAR: An OECD toolbox assessment resulted in alerts for genotoxic properties via DNA and protein binding (see attached supplementary information).
- In vitro methods: Itaconates have been shown to exhibit cytotoxicity (Cordes et al, THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 291, NO. 27; Lampropoulou et al, Cell Metab. 2016 July 12; 24(1)). The misleading effect of cytotoxicity on the outcome of an in vitro genotoxicity study with mammalian cells has been described by several authors (among which Armstrong et al, Mutation research 265 (1992), Kirkland et al, Mutation Research 628 (2007); Fowler et al., Mutation Research 742 (2012); Honda et al. Genes and Environment (2018)). It is therefore concluded that it is scientifically not justified to perform in vitro testing, as a positive outcome is expected related to cytotoxicity and not related to intrinsic genotoxic properties of the test item (“false positive” result).
- Weight of evidence: As no reliable outcome is expected from the required in vitro tests with mammalian cells due to cytotoxicity, it is proposed to address the potential genotoxic properties of DBI in an in vivo COMET assay. This is strengthened by the fact that structural analogues of DBI with shared chemical subgroups were found to give (false) positive results when tested in in vitro tests with mammalian cells. Performance of an in vivo study is considered to be the only strategy possible to address this endpoint.
- Grouping and read-across: Read across to structurally related itaconates (with shared sub-structures) has been considered. However based on the observed behaviour of the substance in aqueous solution, read-across was not considered scientifically justified.
- Substance-tailored exposure driven testing: Not applicable for genetic toxicity endpoint
- Approaches in addition to above: Not applicable
- Other reasons: Not applicable
CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
The specific rules for adaptation from column 1 as given in column 2 are not applicable for in vivo genotoxicity testing.
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design: As no reliable outcome is expected from the required in vitro tests with mammalian cells, it is proposed to address the potential genotoxic properties of DBI in an in vivo COMET assay. As this assay addresses all potential mode-of-actions (the COMET assay recognises primary DNA damage that would lead to gene mutations and/or chromosome aberrations, but will also detect DNA damage that may be effectively repaired or lead to cell death), performance of this in vivo study is considered to be sufficient to conclude on this endpoint. The oral route is considered to be the most appropriate route, as no sex-specific toxicity is expected, the test is performed in a single species. As no tissue-specific toxicity is expected, blood and liver samples will be tested.
Data source
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
- Version / remarks:
- most recent version
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian comet assay
Test material
- Reference substance name:
- Dibutyl itaconate
- EC Number:
- 218-451-9
- EC Name:
- Dibutyl itaconate
- Cas Number:
- 2155-60-4
- Molecular formula:
- C13H22O4
- IUPAC Name:
- 1,4-dibutyl 2-methylidenebutanedioate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
Results and discussion
Applicant's summary and conclusion
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.