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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Both constituents of Copper diethylenetriamine sulfate were evaluated for their mutagenic potential.

Diethylenetriamine (DETA) was predicted to be mutagenic based on the CAESAR QSAR for mutagenicity (Ames test). Similarly, a postive Ames test was found for the category member "reaction product of copper sulfate and tetraetylene pentamine". Further tests were required to decide on the mutagenicity of DETA and these were performed for the registration dossier of DETA. A large number of tests, both in-vitro and in-vivo were performed and the evidence if these in-vitro and three in-vivo shows that DETA is not mutagenic. DETA is therefore also not classified as a mutagenic.

CuSO4 has been extensively studied, both in vitro and in vivo. Although certain in vitro tests have shown signs of mutagenecity at very high copper sulfate concentrations, the weight of evidence of all available studies - with a large weight being given to in vivo tests where mutagenecity was not observed - leads to the conclusion that copper sulfate is not mutagenic.

Because both constituents of Copper diethylenetriamine sulfate were found to be non-mutagenic, the substance itself is also considered non-mutagenic.

Link to relevant study records

Referenceopen allclose all

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 (CAESAR) 2.1.13

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
NCCNCCN

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. As an experimental value is available for this substance in the QSAR dataset, the QSAR predictions are very reliable.
Guideline:
other: REACH Guidance on QSARs R.6
Specific details on test material used for the study:
SMILES: NCCNCCN
Remarks on result:
mutagenic potential (based on QSAR/QSPR prediction)
Conclusions:
Based on the CAESAR model for Mutagenicity (Ames test) v2.1.13, diethylenetriamine (DETA) is a mutagenic substance.
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 vivotests 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 isnorequirement for copper sulphate to be classified for mutagenicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification