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EC number: 204-612-0 | CAS number: 123-25-1
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Negative
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- April - May 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: EPFS 201
- Expiration date of the lot/batch: 2005-06-30
- Species / strain / cell type:
- S. typhimurium, other: 97a
- Species / strain / cell type:
- S. typhimurium TA 98
- Species / strain / cell type:
- S. typhimurium TA 100
- Species / strain / cell type:
- S. typhimurium TA 102
- Species / strain / cell type:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- A maximum dose-level of 5000 ug/plate and four lower concentrations of 1667, 556, 185 and 62 ug/plate
- Vehicle / solvent:
- Solvent used: water
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- Strains TA 100 and TA 1535; -S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylenediamine
- Remarks:
- Strain TA 97a; -S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Strain TA98; -S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- Strains TA 98, TA 100 and TA 1535; +S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Remarks:
- Strain TA 97a; +S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 1,8-dihydroxyanthraquinone
- Remarks:
- Strain TA 102; +S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; in agar (plate incorporation)
DURATION
- Exposure duration: 2 days
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: Reduced number of spontaneous revertants, microcolony formation, thinning of background lawn - Evaluation criteria:
- For the test item to be considered mutagenic, 1.7-fold (for strains TA 97a, TA 100 and TA 102)) or 2.5 fold (for strains TA 98 and TA 1535) increases in mean revertant numbers
- Species / strain:
- S. typhimurium, other: TA 97a
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- In the initial toxicity test no toxicity was observed.
No precipitation was observed. - Conclusions:
- It is concluded that the substance does not induce reverse mutation in Salmonella typhimurium or Escherichia coli under the reported experimental conditions.
- Executive summary:
A bacterial reverse mutation assay (Ames test) has been undertaken following OECD/EU test methods. The substance does not induce reverse mutation in the strains of examined.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- 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:
- guideline study with acceptable restrictions
- Justification for type of information:
- HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are substances are structurally similar and belong to the structural class of aliphatic diesters. Both substances share a carboxylic diester group, the only difference being that one is a methyl ester of succinic acid while the other is an ethyl ester of succinic acid. Both are expected to be metabolised in a similar manner. The common structure does not include any functional group of concern with regard to genotoxic activity and, as a result, they are regarded as sharing a common mechanism of (lack of) action.
ANALOGUE APPROACH JUSTIFICATION
QSAR tools allow an examination of the structure of both the source substance, dimethyl succinate, and the target substance, diethyl succinate. These tools examine structural alerts for potential activity with regard to genotoxic activity and do not flag alerts for either substance. Given the commonality of structure between the source and target substances and the lack of structural alerts within the two, it is reasonable that the experimental data available on the source substance, dimethyl succinate is indicative of the genotoxic properties of diethyl succinate. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- 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:
- guideline study with acceptable restrictions
- Justification for type of information:
- HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances are substances are structurally similar and belong to the structural class of aliphatic diesters. Both substances share a carboxylic diester group, the only difference being that one is a methyl ester of succinic acid while the other is an ethyl ester of succinic acid. Both are expected to be metabolised in a similar manner. The common structure does not include any functional group of concern with regard to genotoxic activity and, as a result, they are regarded as sharing a common mechanism of (lack of) action.
ANALOGUE APPROACH JUSTIFICATION
QSAR tools allow an examination of the structure of both the source substance, dimethyl succinate, and the target substance, diethyl succinate. These tools examine structural alerts for potential activity with regard to genotoxic activity and do not flag alerts for either substance. Given the commonality of structure between the source and target substances and the lack of structural alerts within the two, it is reasonable that the experimental data available on the source substance, dimethyl succinate is indicative of the genotoxic properties of diethyl succinate. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Referenceopen allclose all
The substance was tested at the maximum concentration of 5000 μg/plate and at four lower concentrations. No relevant toxicity was observed with any tester strain at any dose-level. No relevant increase in revertant numbers was observed at any concentration tested.
No precipitation of the tested substance was observed at the end of the incubation period at any concentration.
The substance did not induce increases in the number of revertant colonies in the plate incorporation or pre-incubation assay, at any dose-level, in any tester strain, in the absence or presence of S9 metabolism.
Marked increases in revertant numbers were obtained in these tests following treatment with the positive control items, indicating that the assay system was functioning correctly.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
Non-classification is justified on the basis of negative findings / predictions in 3 separate in-vitro tests for gene mutation / mutagenicity.
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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