Registration Dossier
Registration Dossier
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EC number: 915-008-8 | CAS number: -
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The substance is a mixture of copper (Cu), DTPA and HEEDTA. None of these substances have known mutagenic properties, based on literature, QSAR predictions and classification of individual components:
Cu: Copper and copper compounds such as CuSO4 are not considered as mutagenics. The case of CuSO4 is provided here because in vitro tests on free copper ions are lacking. Based on a weight of evidence approach from a large number of available studies (both bacterial assays as in vitro tests with mammalian cells), copper sulphate was assessed to be not mutagenic.
DTPA and HEEDTA are classified as non-mutagenic on the ECHA dissemination website. To support this claim, QSAR results for DTPA and HEEDTA are provided.
Because of the lack of mutagenic potential in CuSO4, DTPA and HEEDTA, it is concluded that the reaction mixture of CuDTPA and CuHEEDTA also should not be classified for genetic toxicity.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
VEGA v1.4.4
2. MODEL (incl. version number)
Mutagenicity (Ames test) model (CONSENSUS) 1.0.2.
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
DTPA = C(CN(CC(=O)O)CC(=O)O)N(CCN(CC(=O)O)CC(=O)O)CC(=O)OC(CN(CC(=O)O)CC(=O)O)N(CCN(CC(=O)O)CC(=O)O)CC(=O)O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
See attached QMRF
5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
See attached QMRF
6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
An in-vitro gene mutation study in bacteria is required for REACH dossiers in the 1-10 tonnage band. This QSAR provides a prediciton for this endpoint. - Guideline:
- other: REACH Guidance on QSARs R.6
- Specific details on test material used for the study:
- SMILES: C(CN(CC(=O)O)CC(=O)O)N(CCN(CC(=O)O)CC(=O)O)CC(=O)O
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- Based on the CAESAR model for Mutagenicity (Ames test) v2.1.13, DTPA is non-mutagenic.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
VEGA v1.4.4
2. MODEL (incl. version number)
Mutagenicity (Ames test) model (CONSENSUS) 1.0.2.
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
HEEDTA = C(CN(CC(=O)O)CC(=O)O)N(CCO)CC(=O)O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
See attached QMRF
5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
See attached QMRF
6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
An in-vitro gene mutation study in bacteria is required for REACH dossiers in the 1-10 tonnage band. This QSAR provides a prediciton for this endpoint. - Guideline:
- other: REACH Guidance on QSARs R.6
- Specific details on test material used for the study:
- SMILES: C(CN(CC(=O)O)CC(=O)O)N(CCO)CC(=O)O
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- Based on the CAESAR model for Mutagenicity (Ames test) v2.1.13, HEEDTA is non-mutagenic.
- Endpoint:
- genetic toxicity in vitro, other
- Remarks:
- review of all available mutagenecity studies
- Type of information:
- other: Voluntary risk assessment of all available studies
- 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:
- This voluntary risk assessment report of copper and copper compounds has been submitted to the European Chemicals Agency by the European Copper Institute. This report is based on the industry initiative to perform a voluntary risk assessment on a substance according to the mechanisms of the implementation of the Existing Substance Regulation (EEC) No 793/93 (ESR). The procedure was agreed by the 11 Joint Meeting of the Competent Authorities for the Implementation of Directive 67/548/EEC and ESR Regulation.
Italy has been acting as a reviewing Member State for the substance and the risk assessment report has been reviewed by the Technical Committee on New and Existing Substances (TC NES) according to standard operational procedures of the Committee. - Qualifier:
- no guideline available
- Principles of method if other than guideline:
- This voluntary risk assessment report of copper and copper compounds gives an overview of all available test results for copper (compounds) relevant for the mutagenecity endpoint.
- Type of assay:
- other: review
- Remarks on result:
- other: Not mutagenic based on all available information
- Conclusions:
- Consideration of the available in vitro and in vivo mutagenicity data for copper sulphate against EU classification criteria as contained in Annex VI of Directive 67/548/EEC results in the conclusion that there is no requirement for copper sulphate to be classified for mutagenicity.
- Executive summary:
Copper sulphate
Current classification for mutagenicity: none
The potential mutagenicity of copper sulphate has been investigated in a number of in vitro assays in bacterial and mammalian cells, and in several in vivo assays.
The overwhelming weight of evidence indicates that copper sulphate is negative in vitro in bacterial cell reverse mutation assays, andin several other bacterial cell assays up to and including cytotoxic doses (1000-~3000 μg/plate). Similar negative findings have also been reported for copper chloride.
Results from in vitro mammalian cell tests show that copper sulphate is genotoxic only at high, cytotoxic concentrations (up to 250 mg/l). This effect may be a result of copper-mediated generation of reactive oxygen species and/or inhibition of DNA-repair enzymes. Such concentrations of copper are irrelevant under normal conditions in vivo, where copper is generally bound to amino acid or protein ligands.
The most reliable in vivo data for copper sulphate come from two well-conducted, oral-dosing studies which were conducted according to Annex V guidelines and assigned the highest quality rating. In both of these studies, a micronucleus assay and a UDS test, copper sulphate was clearly negative. Results of these two studies provide no evidence that copper sulphate is mutagenic in vivo. Two other in vivo studies, both with a lower quality rating generated conflicting results, the basis of which remains uncertain, although strain variation has been suggested. Otherin vivostudies deviated from Annex V methodology in such a way as to make the results unreliable.
Consideration of the weight of evidence from in vitro and in vivo tests, with greatest emphasis being placed on thosein vivo tests which had the highest study rating, leads to the conclusion that copper sulphate is not mutagenic.
Consideration of the available in vitro and in vivo mutagenicity data for copper sulphate against EU classification criteria as contained in Annex VI of Directive 67/548/EEC results in the conclusion that there is no requirement for copper sulphate to be classified for mutagenicity.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
Because none of the constituent are considered mutagenic, the reaction mixture of CuDTPA and CuHEEDTA was assessed to be not mutagenic.
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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