copper sulfate;N'-[2-[2-(2-aminoethylamino)ethylamino]ethyl]ethane-1,2-diamine

Endpoint summary

Description of key information

The reaction product of copper sulfate and tetraethylenepentamine is formed by mixing tetraethylenepentamine

(TEPA) and copper sulfate (CuSO4).

TEPA is known as a skin sensitiser (ECHA dissemination database), which was confirmed by QSAR predictions (TOXTREE).

CuSO4 is not known as a skin sensitiser, as indicated by an extensive review in the context of the voluntary risk assessment of copper.

As a worst-case approach, the reaction product of copper sulfate and tetraethylenepentamine is regarded as a skin sensitiser based on the known skin sensitisation properties of TEPA.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

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 limited documentation / justification

Justification for type of information:

1. SOFTWARE
ToxTree 2.6.13

2. MODEL (incl. version number)
Skin sensitisation reactivity domain (Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
N(CCNCCNCCN)CCN

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]
A QMRF is not available for this substance, but see Enoch et al. 2008 for more information on used algorithm, training dataset and applicability domain.

5. APPLICABILITY DOMAIN
See attached report of the QSAR predictions.

6. ADEQUACY OF THE RESULT
The QSAR predicts a high class (III) skin sensitisation based on the Cramer rules for TEPA.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

http://toxtree.sourceforge.net

Specific details on test material used for the study:

SMILES: N(CCNCCNCCN)CCN

Parameter:

other: QSAR Prediction

Remarks on result:

other: Alert for Schiff base formation identified.

 QSNAR.SNAr-Nucleophilic Aromatic Substitution No   NCCNCCN
 QSB.Schiff Base Formation Yes Class Alert for Schiff base formation identified.NCCNCCN
 QMA.Michael Acceptor No   NCCNCCN
 Qacyl.Acyl Transfer Agents No   NCCNCCN
 QSN2.SN2-Nucleophilic Aliphatic Substitution No   NCCNCCN
 Q6.At least one alert for skin sensitisation? Yes   NCCNCCN

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on the predictions of the ToxTree Skin Sensitisation QSAR (SMARTS pattern based approach), TEPA was identified as a potential skin sensitiser: alert for Schiff base formation.

Reference 2

Endpoint:

skin sensitisation, other

Remarks:

review of all available skin sensitisation 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.

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 skins sensitisation endpoint.

Type of study:

other: review of available skin sensitisation studies of copper sulfate and other copper compounds

Remarks on result:

no indication of skin sensitisation

Copper sulphate pentahydrate failed to induce skin sensitisation in a GPMT (Mercier 1994 a– unpublished). Concentrations of test substance selected for induction and challenge were based on results of a sighting study. Induction involved intradermal injection of test substance (0.1% in water) on day 0, a concentration which produced weak to moderate irritation in the sighting study. This was followed by topical application of test substance (10% in water) on day 7 for 48 hours. Sodium lauryl sulphate (10%) was also applied at topical induction, prior to the test substance, as the test substance alone at a concentration of 10% failed to provoke signs of irritation in the sighting study. The skin response at topical induction in the main study was not reported. After an 11-day treatment-free period, animals were challenged by topical application of the test substance (10% in water) under an occlusive dressing for 24 hours. Skin response was assessed in animals (20 treated and 9 controls) at 24 and 48 hours after challenge. Slight erythema was observed in one treated animals at 24 hours, but not at 48 hours. No skin reactions occurred other treated animals or in controls at either time-point. In conclusion, copper sulphate pentahydrate produced a 0% sensitisation rate under the conditions of this test and is therefore considered to have no skin sensitising potential in guinea pigs. 

Interpretation of results:

GHS criteria not met

Conclusions:

No published studies are available which report on the potential of copper or its compounds to cause skin sensitisation in animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)