4,4'-methylenebis(2,6-xylidine)

Endpoint summary

Description of key information

A consensus of the predictions from all the three below-mentioned QSAR models and structural alert systems was used as the key result:

a) Nexus DEREK v6.0.1

b) VEGA v1.1.4

c) Danish QSAR Database

Consensus result: Combining the all the results, the query substance was classified as Skin Sensitiser (Category 1B).

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:

supporting study

Study period:

17/04/2018

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

Remarks:

The substance falls within the applicability domain of LeadScope model integrated into Danish QSAR Database. Relevant QMRF was also provided. Prediction report generated as model output was also included.

Justification for type of information:

1. SOFTWARE
Danish QSAR Database

2. MODEL (incl. version number)
Leadscope model incorporated into Danish QSAR Database was used:


3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Nc1c(C)cc(Cc2cc(C)c(N)c(C)c2)cc1C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to the attached QMRF for the Leadscope model.

5. APPLICABILITY DOMAIN
The substance falls within the applicability domain of the applied model. Please refer to the attached QMRF.

6. ADEQUACY OF THE RESULT
As the substance falls within the applicability domain of the applied model, the final prediction was considered as reliable.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Leadscope model integrated into the Danish QSAR Database was applied. Please refer to the attached QMRF for further details on the model methodology and validation.

GLP compliance:

no

Other effects / acceptance of results:

The substance falls within the applicability domain of the Leadscope model integrated into the Danish QSAR Database.

Parameter:

other: Skin Sensitiser

Remarks on result:

other: QSAR result

Interpretation of results:

other: QSAR result

Conclusions:

The query substance was predicted as skin sensitiser based on the results derived from Leadscope model integrated into the Danish QSAR Database.

Executive summary:

The query substance falls with the applicability domain of the Leadscope model integrated into the Danish QSAR Database. It was predicted as a skin sensitiser. Prediction was considered as reliable based on the applicability domain status. The two other models (SciQSAR and Case Ultra) which are also integrated into the Danish QSAR Database were not considered based the substance falls outside their applicability domain.

Reference 2

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Remarks:

Nexus DEREK v6.0.1 provides structural alerts for skin sensitisation

Adequacy of study:

key study

Study period:

17/04/2018

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

Remarks:

QMRF is available. No QPRF was provided as model output

Justification for type of information:

1. SOFTWARE
Nexus DEREK

2. MODEL (incl. version number)
Nexus DEREK v6.0.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Nc1c(C)cc(Cc2cc(C)c(N)c(C)c2)cc1C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to the attached QMRF for Nexus DEREK

5. APPLICABILITY DOMAIN
No alerts or issues related to applicability domain were triggered for the query substance. As skin sensitisation related structural alerts were triggered, the substance can be considered within the applicability domain of the model.

6. ADEQUACY OF THE RESULT
As the substance can be considered to fall within the applicability domain of the model, the final result and EC3 value provided by tool can be considered as reliable.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The query substance was provided as input to the Nexus DEREK v6.0.1 to see if any structural alerts for skin sensitisation were triggered by the system. Please refer to the attached QMRF and the prediction report generated using this tool for further information about the methodology.

GLP compliance:

no

Key result

Parameter:

EC3

Value:

9.3

Remarks on result:

positive indication of skin sensitisation based on QSAR/QSPR prediction

Remarks:

moderate skin sensitiser

The query substance was predicted as skin sensitiser with Nexus DEREK v6.0.1 based on the following structural alert:

427 Aromatic primary or secondary amine

LLNA EC3 value was predicted using the Derek EC3 Model - 1.2.0.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Remarks:

QSAR result predicted using Nexus DEREK

Conclusions:

The query substance was predicted as moderate skin sensitiser with an predicted LLNA EC3 of 9.3%

Executive summary:

The query substance was predicted as moderate skin sensitiser with an predicted LLNA EC3 of 9.3% using the Nexus DEREK v6.0.1. This result was based on the following structural alert triggered for this substance:427 Aromatic primary or secondary amine. The predicted LLNA EC3% suggests that the substance is a moderate skin sensitiser.

Reference 3

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

17/04/2018

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
VEGA v1.1.4

2. MODEL (incl. version number)
Skin Sensitisation model incorporated into VEGA v.1.1.4

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Nc1c(C)cc(Cc2cc(C)c(N)c(C)c2)cc1C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to the user guide of VEGA to retrieve inforamtion regarding the model development and validation approach.

5. APPLICABILITY DOMAIN
The substance falls outside the applicability domain.

6. ADEQUACY OF THE RESULT
As the substance falls outside the applicability domain, the results cannot be used on their own. The results needs to be supported by results from other tools.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Please refer to the VEGA user guide for further information about the model methodology and validation

GLP compliance:

no

Parameter:

other: Skin Sensitiser

Remarks on result:

other: QSAR result

The query substance was predicted as skin sensitiser but the substance falls outside the applicability domain of the model.

Interpretation of results:

other: QSAR result

Conclusions:

The query substance was predicted as skin sensitiser with VEGA.

Executive summary:

The query substance was predicted for its skin sensitisation potential using VEGA. It was predicted as skin sensitiser however the substance falls outside the applicability domain of the model. This result cannot be used on its own and for this substnace it was used only as a supporting study to derive a consensus result along with the results from other models.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Consensus result for the query substance: Based on the results derived from multiple QSAR models/structural alert systems, the query substance was classified as a Skin Sensitiser (Category 1B).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Consensus result for the query substance: Based on the results derived from multiple QSAR models/structural alert systems, the query substance was classified as a Skin Sensitiser (Category 1B), especially according to the prediction using the Nexus DEREK v6.0.1: the query substance was predicted as moderate skin sensitiser with an predicted LLNA EC3 of 9.3%. This result was based on the following structural alert triggered for this substance: 427 Aromatic primary or secondary amine. The predicted LLNA EC3% suggests that the substance is a moderate skin sensitiser.