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Diss Factsheets
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EC number: 287-673-6 | CAS number: 85566-63-8
- 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
A read-across and weight of evidence approach has been taken to fulfill the acute toxicity endpoints. Data was not available on the registered substance, and testing cannot be conducted as the substance is solely used as a cosmetic ingredient. Existing data on similar substances has been used to fulfill the endpoint requirements.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Full read-across information is appended.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are composed of two esters and two branched alkoxy component of the diesters. The source substance and target substances have similar molecular weight ranges, low water solubility, high partition coefficient, and are in the physical form of a liquid. The source substance meets Lipinski’s rule of five, indicating that the substance is orally active. The target substance also meets Lipinski’s rule of five, indicating that the substance is likely to be similarly orally active. The potential for acute oral toxicity is therefore the same in both substances.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both substances are diesters, with the ester groups separated by two carbons in the centre. The only difference in the central section is that the source substance, bis(2-ethylhexyl) malate, has saturated carbons and a hydroxy group, whereas the target substance bis(1-methylheptyl) maleate has unsaturated carbons (i.e. they share a double bond).
In both substances there are two branched chains on the alcohol part of the ester, and in both cases, this is made of eight carbons, however the difference is that in the source substance the branching occurs two carbons away from the O, whereas in the target substance the branching occurs on the first carbon after the O. In addition, the branching in the source substance is made up of an ethyl and a butyl chain (both even branching), whereas in the target substance the branching is a methyl group (odd branching) and a hexyl group (even branching).
The source and target substances contain low levels of structurally similar impurities to the source and target substances themselves. These impurities are considered to be substantially similar to the source and target substances, and are likely to possess substantially similar properties.
The impact of “impurities” is therefore considered not to affect the reliability of the read-across prediction.
3. ANALOGUE APPROACH JUSTIFICATION
Due to the similarities of the source and target substance with regards to chemical structure, physico-chemical properties, and Lipinski’s rule of 5, the target substance is expected to behave in a substantially similar manner in vivo.
The target substance is therefore predicted to fail to induce acute oral toxicity in the CFR 16: 1500.3 study when conducted in the rat. By extension, the target substance is considered not to fulfil the criteria for acute oral toxicity under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).
4. DATA MATRIX
See appended pdf document. - Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- GHS criteria not met
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Justification for type of information:
- Study conducted outside the EU over 10 years before the EU cosmetic testing ban came into effect.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- other: Code of Federal Regulations 16, Part 1500.3 (USA)
- GLP compliance:
- no
- Test type:
- fixed dose procedure
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not detailed
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- Animals were observed for pharmacologic activity and drug toxicity 1,3,6 and 24 hours after treatment, and daily thereafter for a total of 14 days.
- Doses:
- 5 grams per kg
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 other: g/kg
- Mortality:
- two animals died during the study
- Clinical signs:
- other: not reported
- Gross pathology:
- Not reported
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- 20% of the animals used at the dose level of 5g/kg died. LD50 is greater than 5ml/kg
- Executive summary:
In this guideline (CFR 1500.3) study the LD50 of the test material was determined to be 5g/kg bw. 5 male and 5 female rats were dosed orally by gavage at 5g/kg and observed for 2 weeks post-dose. 2 deaths were observed.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 000 mg/kg bw
- Quality of whole database:
- 2
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Study conducted outside the EU over 10 years before the EU cosmetic testing ban came into effect.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No information on the methodology is reported by the chemical review.
- GLP compliance:
- not specified
- Remarks:
- Study performed prior to GLP adoption
- Test type:
- other: Not reported by the chemical review
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- not specified
- Type of coverage:
- not specified
- Vehicle:
- not specified
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 2 620 mg/kg bw
- Based on:
- not specified
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The acute dermal LD50 of the registered substance to rabbits was reported to be 2620 mg/kg bw in the chemical review.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Study conducted outside the EU over 10 years before the EU cosmetic testing ban came into effect.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The testing guideline and methodology is not reported by the handbook.
- GLP compliance:
- not specified
- Remarks:
- The GLP status of the result is not reported by the handbook.
- Test type:
- other: The test type is not reported by the handbook.
- Specific details on test material used for the study:
- No details on the test material are reported by the handbook.
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- not specified
- Type of coverage:
- not specified
- Vehicle:
- not specified
- Control animals:
- not specified
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 1 560 mg/kg bw
- Based on:
- not specified
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The acute dermal LD50 of maleic anhydride to rabbits was reported as 1650 mg/kg bw in the handbook.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Study conducted outside the EU over 10 years before the EU cosmetic testing ban came into effect.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- Test conducted prior to adoption of guideline.
- Deviations:
- not specified
- Principles of method if other than guideline:
- The review article does not include full test methodology for this entry.
- GLP compliance:
- not specified
- Remarks:
- The review article was published prior to GLP adoption.
- Test type:
- other: The review article does not include test methodology for this entry.
- Specific details on test material used for the study:
- The review article does not provide information on the test material.
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- female
- Type of coverage:
- occlusive
- Vehicle:
- not specified
- No. of animals per sex per dose:
- 3 female
- Control animals:
- not specified
- Details on study design:
- The method used for skin absorption toxicity was essentially that of Smyth et al (1962), except that three female albino New Zealand rabbits were used per dose and the doses were kept in place by 8-ply gauze patches under a latex rubber film.
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 2 620 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1 930 - <= 3 550
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The acute dermal LD50 of the registered substance to rabbits was reported to be 2620 (2620 - 3550) mg/kg bw.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 620 mg/kg bw
- Quality of whole database:
- 2
Additional information
A weight of evidence approach and read-across to a metabolically similar substance was taken to fulfil the dermal route endpoint. The available data provide acute dermal LD50 values of between 1650 -2620 mg/kg bw. The registered substance is much larger in size than the read-across substance and has a lower dermal absorption coefficient. A higher acute toxicity value for the dermal route is therefore expected. To allow the greatest margin of safety possible the LD50 of the registered substance by the dermal route is expected to be ca. 2620 mg/kg bw.
Justification for classification or non-classification
Based upon the information presented in the weight of evidence approach on similar substances, the registered substance does not fulfill the criteria for classification as acutely toxic of the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).
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.