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Diss Factsheets
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EC number: 807-715-4 | CAS number: 1354569-12-2
- 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
Repeated dose toxicity: other routes
Administrative data
- Endpoint:
- repeated dose toxicity: other route
- Remarks:
- other: DEREK Nexus 3.0.1
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Study period:
- 2013
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: DEREK QSAR Modelling
- Justification for type of information:
- QSAR prediction: migrated from IUCLID 5.6
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: ECHA Guidance R.6 on QSARs and grouping of substances, May 2008
- Principles of method if other than guideline:
- Derek Nexus v. 3.0.1, knowledge base Derek KB 2012 v. 1.0, last modified 29. November 2012.
Please see the description of the DEREK model in section 13, Attachment 5.
The test was conduted in accordance with the instructions from LHASA UK, the software supplier by a trained and experienced user.
The Derek method is in the ECHA Guidance R.6 Guidance on QSARs and grouping of substances, R.6.1.8.5. - GLP compliance:
- no
Test material
- Reference substance name:
- 1,4-bis(2-ethylhexyl) (2Z)-2-methylbut-2-enedioate
- EC Number:
- 807-715-4
- Cas Number:
- 1354569-12-2
- Molecular formula:
- C21 H38 O4
- IUPAC Name:
- 1,4-bis(2-ethylhexyl) (2Z)-2-methylbut-2-enedioate
- Reference substance name:
- CC(C(=O)(OCC(CC)CCCC))=CC(=O)(OCC(CC)CCCC)
- IUPAC Name:
- CC(C(=O)(OCC(CC)CCCC))=CC(=O)(OCC(CC)CCCC)
- Test material form:
- other: in silico
- Details on test material:
- Input data used: molecular structure of the parent compound, MW 354.52, log Kp 0.97 (Potts & Guy), log P 8.24 (BioByte Corp., version 4.0)
Constituent 1
Constituent 2
Test animals
- Species:
- other: none
- Strain:
- other: none
- Details on test animals or test system and environmental conditions:
- Species in the knowledge base: bacterium Escherichia coli, Salmonella typhimurium, all mammalian species
Hydrogen options: perceive implicit and explicit hydrogens.
Settings: evaluations were made on all DEREK endpoints including in vitro non-mammalian and mammalian cell systems. (A list of the endpoints is attached in section 13 as attachment 5.)
Results and discussion
Effect levels
- Dose descriptor:
- other: peroxisome proliferation in mammal
- Effect level:
- other: Alert 258 DOUBTED
- Based on:
- other: Alkylalkane carboxylic acid or precursor
- Sex:
- male/female
- Basis for effect level:
- other: Alert 258 - 2-Alkylalkane carboxylic acid or precursor. Peroxisome proliferation in mammal: DOUBTED.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Comments (please see details in attachment 2):
Peroxisome proliferation induced by these compounds is likely to be weak.
Examples of active compounds which fire the alert:
2-Ethylhexanoic acid
Di-(2-ethylhexyl)sebacate
2-Propylhexanoic acid
Mono-(2-ethylhexyl)phthalate
2-Ethylhexanol
Di-(2-ethylhexyl)phosphate
Di-(2-ethylhexyl)adipate
The alert also covers ester, amide, aldehyde and alcohol precursors of the acid, and carbon and phosphorus ester derivatives of alcohol precursors.
Repeated oral dosing or feeding of mice or rats with peroxisome proliferators produces liver hyperplasia and hypertrophy. Histology shows the hypertrophy to be characterised by proliferation of the peroxisomes and the smooth endoplasmic reticulum. Such effects are not seen in higher mammals, including man.
The peroxisome proliferation is accompanied by selective increases in the specific activities of certain peroxisomal enzymes, particularly those involved in the beta-oxidation of fatty acids (e.g. acyl CoA oxidase). The proliferation of the endoplasmic reticulum is accompanied by specific induction of cytochrome P450 4A which exhibits high specificity for the omega-oxidation of fatty acids (e.g. lauric acid hydroxylation).
Chronic oral administration of many peroxisome proliferators, including clofibrate and ciprofibrate, has produced liver carcinomas considered to be directly related to peroxisome proliferation in mice and rats, but not in man.
Peroxisome proliferation appears to be related to resistance to beta-oxidation by liver peroxisomes, and requires a long alkyl chain, e.g. as in tetradecylthioacetic acid, or an aryl or heteroaryl group, e.g. as in Wy-14643. Peroxisome proliferators have been shown to activate one or more nuclear steroid hormone-like receptors (PPARs) which induce increases in the oxidative enzyme activity associated with peroxisome proliferators.
The strength of the binding with the PPAR sites is expected to be a factor in determining the potency of peroxisome proliferators. Both hydrophilic groups (e.g. carboxylic acid or carboxylate groups) and lipophilic groups (e.g. long chain alkyl groups) are required. The high potency of Wy-14643, for example, may be related to the presence of two aromatic rings in the substituent on the acid-linked group, giving strong receptor binding. The structural similarity to thyroxine, which interacts with a steroid-type receptor, is notable, and may reflect a similar structural requirement.
The type and the level of expression of PPARs strongly influence differences in species responses
Applicant's summary and conclusion
- Conclusions:
- The peroxisome proliferator alert refers to a hepatic effect only seen in rats, so it has no human health consequences. Chemicals that cause this effect it rats are seen to cause liver enlargement, with characteristic changes at the cellular level.
- Executive summary:
Bis-(2-ethylhexyl)-citraconate had DEREK alert for Peroxisome proliferation (Alkylalkane carboxylic acid or precursor) as doubted. The expert assessment concludes that the peroxisome proliferator alert refers to a hepatic effect only seen in rats, so it has no human health consequences. Chemicals that cause this effect it rats are seen to cause liver enlargement, with characteristic changes at the cellular level. The reliablility of the modelling result is not assignable (Klimisch 4).
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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