Registration Dossier

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Type of information:
(Q)SAR
Remarks:
CAESAR (VEGA)
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:
CAESAR (VEGA)
1 Substance
1.1 CAS number 2495-35-4
1.2 EC number 219-673-9
1.3 Chemical name
IUPAC 2-Propenoic acid, phenylmethyl ester
Other Benzyl acrylate
Other BZA
1.4 Structural formula

1.5 Structure codes
SMILES C=CC(=O)OCc1ccccc1
InChI 1S/C10H10O2/c1-2-10(11)12-8-9-6-4-3-5-7-9/h2-7H,1,8H2
Other
Stereochemical features Not applicable

2 General Information
2.1 Date of QPRF 26 March 2018
2.2 Author: Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland,


3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint Skin Sensitisation (None vs Sensitiser)
Dependent variable Classification as sensitiser or non-sensitiser
3.2 Algorithm (OECD Principle 2)
Model or submodel name Extension of the original CAESAR model for skin sensitisation (None vs Sensitiser) within VEGA 1.1.4
Model version 2.1.6
Reference to QMRF Not available
Predicted values (model result) Sensitiser
Predicted values (comments) According to VEGA's evaluation scheme the structure is a sensitizer, but the result shows some critical aspects, which require to be checked.
Input for prediction Smiles
Descriptor values Not provided
3.3 Applicability domain (OECD Principle 3)
Domains i. Predicted compound could be outside the applicability domain of the model.
ii. One infrequent fragments found.
iii. Considerations on the mechanism domain are not applicable since statistical model.
Structural analogues i. CAS: 17369-59-4
ii. CAS: 120-51-4
iii. CAS: 94-09-7
iv. CAS: 94-13-3

Consideration on structural analogues With 85.6%, the average similarity of the four most structurally similar analogues to the query structure is considered high. Two out of four structures are non-sensitisers thus indicating only moderate concordance with the query structure. Accuracy between predicted and actual result is moderate as only three out of were predicted correctly.
3.4 The uncertainty of the prediction (OECD principle 4)
Moderate concordance and accuracy indicate uncertainty.
3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
Not applicable since statistical model

4 Adequacy (Optional)
4.1 Regulatory purpose Skin sensitisation endpoint for assessing the skin sensitisation potential with in vitro and in silico methods according to ECHA Guidance, Chapter R.7a, 2016.

4.2 Approach for regulatory interpretation of the model result
Result is directly applicable since no conversion of the result is required.

4.3 Outcome There is evidence that the query structure is skin sensitising though the prediction is characterised by some uncertainties.

4.4 Conclusion The prediction is considered to be of moderate reliability and will be used together with predictions from other models in a weight of evidence conclusion.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test:
QSAR prediction of Skin sensitisation
- Parameters analysed / observed: Skin sensitisation

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vitro / in chemico

Results
Parameter:
other: Prediction result
Run / experiment:
QSAR prediction - CAESAR (VEGA)
Remarks on result:
other: sensitising

Any other information on results incl. tables

CAESAR (VEGA)

1

Substance

 

 

 

1.1

CAS number

 

2495-35-4

 

1.2

EC number

 

219-673-9

 

1.3

Chemical name

 

 

 

 

IUPAC

2-Propenoic acid, phenylmethyl ester

 

 

 

Other

Benzyl acrylate

 

 

 

Other

BZA

 

1.4

Structural formula

 

 

 

 

 

 

 

1.5

Structure codes

 

 

 

 

 

SMILES

C=CC(=O)OCc1ccccc1

 

 

 

InChI

1S/C10H10O2/c1-2-10(11)12-8-9-6-4-3-5-7-9/h2-7H,1,8H2

 

 

 

Other

 

 

 

 

Stereochemical features

Not applicable

 

2

General Information

 

 

 

2.1

Date of QPRF

 

26 March 2018

 

2.2

Author and contact details

Envigo CRS Switzerland Ltd.,
Rheinstrasse 74, 4414 Füllinsdorf, Switzerland,

 

3

Prediction

 

 

 

3.1

Endpoint (OECD Principle 1)

 

 

 

 

Endpoint

Skin Sensitisation (None vs Sensitiser)

 

 

 

Dependent variable

Classification as sensitiser or non-sensitiser

 

3.2

Algorithm (OECD Principle 2)

 

 

 

 

Model or submodel name

Extension of the original CAESAR model for skin sensitisation (None vs Sensitiser) within VEGA 1.1.4

 

 

 

Model version

2.1.6

 

 

 

Reference to QMRF

Not available

 

 

 

Predicted values (model result)

Sensitiser

 

 

 

Predicted values (comments)

According to VEGA's evaluation scheme the structure is a sensitizer, but the result shows some critical aspects, which require to be checked.

 

 

 

Input for prediction

Smiles

 

 

 

Descriptor values

Not provided

 

3.3

Applicability domain (OECD Principle 3)

 

 

 

Domains

i.

Predicted compound could be outside the applicability domain of the model.

ii.

One infrequent fragments found.

iii.

Considerations on the mechanism domain are not applicable since statistical model.

 

 

 

Structural analogues

i.

CAS: 17369-59-4

ii.

CAS: 120-51-4

iii.

CAS: 94-09-7

iv.

CAS: 94-13-3

 

 

 

Consideration on structural analogues

With 85.6%, the average similarity of the four most structurally similar analogues to the query structure is considered high. Two out of four structures are non-sensitisers thus indicating only moderate concordance with the query structure. Accuracy between predicted and actual result is moderate as only three out of were predicted correctly.

 

3.4

The uncertainty of the prediction (OECD principle 4)

 

 

 

 

Moderate concordance and accuracy indicate uncertainty.

 

3.5

The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

 

 

 

 

Not applicable since statistical model

 

4

Adequacy (Optional)

 

 

 

4.1

Regulatory purpose

Skin sensitisation endpoint for assessing the skin sensitisation potential with in vitro and in silico methods according to ECHA Guidance, Chapter R.7a, 2016.

 

 

 

 

 

4.2

Approach for regulatory interpretation of the model result

 

 

 

Result is directly applicable since no conversion of the result is required.

 

 

 

 

 

4.3

Outcome

There is evidence that the query structure is skin sensitising though the prediction is characterised by some uncertainties.

 

 

 

 

4.4

Conclusion

The prediction is considered to be of moderate reliability and will be used together with predictions from other models in a weight of evidence conclusion.

 

Applicant's summary and conclusion

Interpretation of results:
other: CAESAR (VEGA) prediction result: Sensitising
Conclusions:
There is evidence that the query structure is skin sensitising though the prediction is characterised by some uncertainties.
The prediction is considered to be of moderate reliability and will be used together with predictions from other models in a weight of evidence conclusion.