2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

other: QSAR, read-across

Type of information:

(Q)SAR

Adequacy of study:

key study

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:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Principles of method if other than guideline:

• TIMES modeling approach (Skin sensitization model);
• Available experimental data;
• Toolbox 3.3 read-across analysis.

Type of study:

other: QSAR, read-across

Test material

Test material information

Constituent 1

Reference substance name:

2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

EC Number:

292-054-9

EC Name:

2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

Cas Number:

90530-16-8

IUPAC Name:

2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

Results and discussion

In vitro / in chemico

Results

Value:

1

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

The assessment of2-Propenenitrile, reaction products with 1,3-benzenedimethanamineis separated in two parts:

·        Analysis of the individual constituents: Based on the TIMES Skin sensitization model and TB read-across analysis performed the constituents of analyzed UVCB 2-Propenenitrile, reaction products with 1,3-benzenedimethanamine (CAS 90530-16-8) are predicted as follows:

 

-         ConstituentsMXDA, C and E are not expected to be skin-sensitizers;

-         ConstituentsA, B and D are expected to cause Skin sensitization effect.

 

The predictions provided by TIMES SS model and Toolbox are consistent and supported by the experimental skin sensitization data of structural analogues. The only inconsistency is for MXDA: documented positive skin sensitizer but negative predictions by TIMES SS and Toolbox read-across. The analysis also showed that the structural analogues of the simulated skin metabolites of MXDA do not cause skin sensitization effect. Our assumption is that the corrosivity of MXDA may affect the outcome from skin sensitization tests and give false positive results [3].

 

·        Analysis of the whole substance based on the predictions for the constituents and the concentration information provided by the client:

According to the classification criteria for mixtures discussed inCLP Annex I, 3.4.3.3.1. [30, 31]2-Propenenitrile, reaction products with 1,3-benzenedimethanamine(CAS 90530-16-8) is assessed as a skin sensitizer because three of its constituents (A,B and D) are predicted as Strong skin sensitizers by TIMES SS model and their concentrations in the analyzed UVCB are greater than the specified threshold of 1.0%.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Skin sensitiser category 1 H317

Executive summary:

The assessment of 2-Propenenitrile, reaction products with 1,3-benzenedimethanamineis separated in two parts:

·        Analysis of the individual constituents:Based on the TIMES Skin sensitization model and TB read-across analysis performed the constituents of analyzed UVCB 2-Propenenitrile, reaction products with 1,3-benzenedimethanamine(CAS 90530-16-8) are predicted as follows:

 

-         ConstituentsMXDA, CandEare not expected to be skin-sensitizers;

-         ConstituentsA, BandDare expected to cause Skin sensitization effect.

 

The predictions provided by TIMES SS model and Toolbox are consistent and supported by the experimental skin sensitization data of structural analogues. The only inconsistency is for MXDA: documented positive skin sensitizer but negative predictions by TIMES SS and Toolbox read-across. The analysis also showed that the structural analogues of the simulated skin metabolites of MXDA do not cause skin sensitization effect. Our assumption is that the corrosivity of MXDA may affect the outcome from skin sensitization tests and give false positive results [3].

 

·        Analysis of the whole substance based on the predictions for the constituents and the concentration information provided by the client:

According to the classification criteria for mixtures discussed inCLP Annex I, 3.4.3.3.1. [30, 31]2-Propenenitrile, reaction products with 1,3-benzenedimethanamine(CAS 90530-16-8) is assessed as a skin sensitizer because three of its constituents (A,B and D) are predicted as Strong skin sensitizers by TIMES SS model and their concentrations in the analyzed UVCB are greater than the specified threshold of 1.0%.