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Toxicological information

Skin sensitisation

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Administrative data

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, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
CAESAR (VEGA)
1 Substance
1.1 CAS number 534-15-6
1.2 EC number 208-589-8
1.3 Chemical name
IUPAC 1,1-dimethoxyethane
Other Dimethyl acetal
Other
1.4 Structural formula

1.5 Structure codes
SMILES COC(C)OC
InChI 1S/C4H10O2/c1-4(5-2)6-3/h4H,1-3H3
Other
Stereochemical features Not applicable

2 General Information
2.1 Date of QPRF 29 May 2018
2.2 Author and contact details Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd.,
Rheinstrasse 74, 4414 Füllinsdorf, Switzerland,
Email: stefan.pudenz@envigo.com

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) Non-Sensitiser
Predicted values (comments) According to VEGA's evaluation scheme the structure is a sensitizer but the result may be not reliable.
Input for prediction Smiles
Descriptor values Not provided
3.3 Applicability domain (OECD Principle 3)
Domains i. According to CAESARs evaluation scheme the predicted compound could be outside the applicability domain of the model.
ii. One fragment of the query structure only infrequently found in the compounds of the training set.
iii. Considerations on the mechanism domain are not applicable since statistical model.
Structural analogues i. CAS: 57-55-6
ii. CAS: 140-88-5
iii. CAS: 2426-08-6
iv. CAS: 67-63-0

Consideration on structural analogues With 75% the average similarity of the four most structurally similar analogues to the query structure may be considered high. Two out of four structures are sensitiser, thus indicating only moderate concordance with the query structure. The two sensitising structures (epoxide and ester) do trigger a protein binding alert for skin sensitisation (OASIS profiler in Toolbox), while the query does not trigger an alert. This may suggest a different mode of action of the two structures. In addition, not any of the similar structures is an acetal. Similarity is therefore considered low. Accuracy is high as all four structure were predicted correctly.
3.4 The uncertainty of the prediction (OECD principle 4)
Uncertainty is indicated by moderate concordance and low similarity. The query structure is out of the model’s applicability domain.
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 The query structure is out of the applicability domain of the model and there is only low confidence in the prediction.

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

Data source

Reference
Reference Type:
other: QPRF and Expert statement
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 prediciton of Skin senistisation
- Short description of test conditions: n/a
- Parameters analysed / observed: Skin senistisation

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vitro / in chemico

Results
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

1

Substance

 

 

 

1.1

CAS number

 

534-15-6

 

1.2

EC number

 

208-589-8

 

1.3

Chemical name

 

 

 

 

IUPAC

1,1-dimethoxyethane

 

 

 

Other

Dimethyl acetal

 

 

 

Other

 

 

1.4

Structural formula

 

 

 

 

 

 

1.5

Structure codes

 

 

 

 

 

SMILES

COC(C)OC

 

 

 

InChI

1S/C4H10O2/c1-4(5-2)6-3/h4H,1-3H3

 

 

 

Other

 

 

 

 

Stereochemical features

Not applicable

 

2

General Information

 

 

 

2.1

Date of QPRF

 

29 May 2018

 

2.2

Author and contact details

Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd.,
Rheinstrasse 74, 4414 Füllinsdorf, Switzerland,
Email: stefan.pudenz@envigo.com

 

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)

Non-Sensitiser

 

 

 

Predicted values (comments)

According to VEGA's evaluation scheme the structure is a sensitizer but the result may be not reliable.

 

 

 

Input for prediction

Smiles

 

 

 

Descriptor values

Not provided

 

3.3

Applicability domain (OECD Principle 3)

 

 

 

Domains

i.

According to CAESARs evaluation scheme the predicted compound could be outside the applicability domain of the model.

ii.

One fragment of the query structure only infrequently found in the compounds of the training set.

iii.

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

 

 

 

Structural analogues

i.

CAS: 57-55-6

ii.

CAS: 140-88-5

iii.

CAS: 2426-08-6

iv.

CAS: 67-63-0

 

 

 

Consideration on structural analogues

With 75% the average similarity of the four most structurally similar analogues to the query structure may be considered high. Two out of four structures are sensitiser, thus indicating only moderate concordance with the query structure. The two sensitising structures (epoxide and ester) do trigger a protein binding alert for skin sensitisation (OASIS profiler in Toolbox), while the query does not trigger an alert. This may suggest a different mode of action of the two structures. In addition, not any of the similar structures is an acetal. Similarity is therefore considered low. Accuracy is high as all four structure were predicted correctly.

 

3.4

The uncertainty of the prediction (OECD principle 4)

 

 

 

 

Uncertainty is indicated by moderate concordance and low similarity. The query structure is out of the model’s applicability domain.

 

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

The query structure is out of the applicability domain of the model and there is only low confidence in the prediction.

 

 

 

 

4.4

Conclusion

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

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The query structure is out of the applicability domain of the model and there is only low confidence in the prediction.
The prediction is considered to be of low reliability and may be used together with predictions from other models in a weight of evidence conclusion.