Registration Dossier
Registration Dossier
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EC number: 287-673-6 | CAS number: 85566-63-8
Toxicological information
Acute Toxicity: dermal
Currently viewing:
Administrative data
- Endpoint:
- acute toxicity: dermal
- 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 substance and target substances behave in substantially similar ways in water, and are considered to be functionally similar when inside the body. The target substance has a higher molecular weight and lower dermal absorption coefficient, and is therefore considered to be less likely to enter the body through the skin or via oral absorption. The potential for acute dermal toxicity, repeated dose toxicity and toxicity to reproduction is therefore lower in the target substance than the source substance.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both substances are esters, with the carbonyl (C=O) part of each ester separated by 2 carbons. In addition, the two carbons are unsaturated as they share a double bond. In both cases this double bond is present in the cis geometry. The principle difference between the two substances is that the maleic anhydride is a ring structure, with the esters sharing the hydroxy group between them; whereas in the target substance there are two distinct ester components with branching chains (a methyl (odd) and a hexyl (even)).
Both substances can undergo hydrolysis to produce the same carboxylic acid as shown in the appended .pdf (Table 4). However, Maleic anhydride undergoes this process more readily as it is hygroscopic. The carboxylic acid formed is maleic acid, which can undergo hydration upon further reaction with water to produce malic acid.
The principle difference between how the source and target substances undergo hydrolysis is that one mole of maleic anhydride only produces one mole of maleic acid and no other organic species, whereas one mole of the target substance bis(1-methylheptyl) maleate produces one mole of maleic acid and two moles of 2-octanol. The 2-octanol is a branched alcohol, with an odd numbered branch (due to the methyl chain) and an even numbered branch (due to the hexyl chain).
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 dermal toxicity in the LD50 studies when conducted in the rabbit. By extension, the target substance is considered not to fulfil the criteria for acute dermal toxicity under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).
4. DATA MATRIX
See appended read-across justification.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across source
Reference
- 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.
- Reason / purpose for cross-reference:
- read-across source
Reference
- 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.
- Reason / purpose for cross-reference:
- read-across source
Reference
- 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.
Data source
Materials and methods
Test material
- Reference substance name:
- Dioctyl maleate, branched
- EC Number:
- 287-673-6
- EC Name:
- Dioctyl maleate, branched
- Cas Number:
- 85566-63-8
- Molecular formula:
- C20H36O4
- IUPAC Name:
- 1,4-bis(octan-2-yl) (2Z)-but-2-enedioate
Constituent 1
Results and discussion
Effect levels
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 620 mg/kg bw
- Based on:
- test mat.
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.
