Isotridecyl isononanoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, and documentation / justification is limited

Justification for type of information:

CAESAR (VEGA)
1 Substance
1.1 CAS number 42131-27-1
1.2 EC number 255-673-5
1.3 Chemical name
IUPAC 11-Methyldodecyl 7-methyloctanoate
Other Octanoic acid, 7-methyl-, 11-methyldodecyl ester
Other Isotridecyl isononanoate
1.4 Structural formula

1.5 Structure codes
SMILES O=C(OCCCCCCCCCCC(C)C)CCCCCC(C)C
InChI InChI=1S/C22H44O2/c1-20(2)16-12-9-7-5-6-8-10-15-19-24-22(23)18-14-11-13-17-21(3)4/h20-21H,5-19H2,1-4H3
Other
Stereochemical features N/A

2 General Information
2.1 Date of QPRF 20 April 2018
2.2 Author and contact details Envigo, Shardlow Business Park London Road, Shardlow, Derbyshire, DE72 2GD

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 may be not reliable.
Input for prediction Smiles
Descriptor values Not provided
3.3 Applicability domain (OECD Principle 3)
Domains i. The predicted compound is into the Applicability Domain of the model.
ii. Strongly similar compounds with known experimental value in the training set have been found.
iii. Accuracy of prediction for similar molecules found in the training set is good.
iv. Similar molecules found in the training set have experimental values that agree with the predicted
value.
v. Descriptors for this compound have values inside the descriptor range of the compounds of the
training set.
vi. All atom centered fragment of the compound have been found in the compounds of the training
set.
Structural analogues i. Isopropyl myristate
ii. 4,4-Dimethyl-2-pentadecyl-1,3-oxazol-5(4H)-one
iii. 2-heptadecyl-4,4-dimethyl-4,5-dihydro-1,3-oxazol-5-one
iv. 4,4-dimethyl-2-nonadecyl-4,5-dihydro-1,3-oxazol-5-one

Consideration on structural analogues With 89.6% the average similarity of the four most structurally similar analogues to the query structure is considered high. All four of the structures are sensitizers, thus indicating high concordance with the query structure. Three of the four structures trigger an alert from the OASIS protein binding profiler for skin sensitisation in OECD Toolbox, whereas the target molecule does not show any alerts in the profiling. Furthermore, the metabolism predictions for these molecules show different pathways and again no alerts for the query structure. It is therefore assumed to be likely that mode of action followed by the three oxazolone structures is not relatable to the target compound.

3.4 The uncertainty of the prediction (OECD principle 4)
The models own statistics indicate high reliability in the prediction, with high similarity, recognition of all compound fragments in the training set, good concordance of results with measured data etc. However it is clear to the assessor that the nearest molecules in the dataset used for the prediction have considerably different properties and functional groups to the target compound.
An assessment of these differences using the profilers in the OECD QSAR Toolbox identifies alerts for the oxazolone containing structures compared with the target structure. Furthermore assessment of the predicted metabolism of these compounds has shown different routes to breakdown products again which the target molecule does not display any alerts for.
This indicates uncertainty in the results from the model.
The Isopropyl myristate is also predicted to be sensitising.
The Data matrix with this information in has been included in the printouts section below for reference.

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 within the applicability domain of the model, and the prediction is made with good statistics, however due to concerns regarding the mode of action displayed by the similar structures in the training set, there is some uncertainty in the result.

4.4 Conclusion The prediction is not considered reliable and will not be considered with predictions from other models in a weight of evidence conclusion.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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

Test material information

Constituent 1

Reference substance name:

Isotridecyl isononanoate

EC Number:

255-673-5

EC Name:

Isotridecyl isononanoate

Cas Number:

42131-27-1

Molecular formula:

C22H44O2

IUPAC Name:

Isotridecyl isononanoate

Results and discussion

In vitro / in chemico

Results

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

CAESAR (VEGA)
1	Substance
	1.1	CAS number			42131-27-1
	1.2	EC number			255-673-5
	1.3	Chemical name
			IUPAC		11-Methyldodecyl 7-methyloctanoate
			Other		Octanoic acid, 7-methyl-, 11-methyldodecyl ester
			Other		Isotridecyl isononanoate
	1.4	Structural formula
	1.5	Structure codes
			SMILES		O=C(OCCCCCCCCCCC(C)C)CCCCCC(C)C
			InChI		InChI=1S/C22H44O2/c1-20(2)16-12-9-7-5-6-8-10-15-19-24-22(23)18-14-11-13-17-21(3)4/h20-21H,5-19H2,1-4H3
			Other
			Stereochemical features		N/A
2	General Information
	2.1	Date of QPRF			20 April 2018
	2.2	Author and contact details			Envigo, Shardlow Business Park London Road, Shardlow, Derbyshire, DE72 2GD
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 may be not reliable.
			Input for prediction		Smiles
			Descriptor values		Not provided
	3.3	Applicability domain (OECD Principle 3)
			Domains		i.	The predicted compound is into the Applicability Domain of the model.
					ii.	Strongly similar compounds with known experimental value in the training set have been found.
					iii.	Accuracy of prediction for similar molecules found in the training set is good.
					iv.	Similar molecules found in the training set have experimental values that agree with the predicted value.
					v.	Descriptors for this compound have values inside the descriptor range of the compounds of the training set.
					vi.	All atom centered fragment of the compound have been found in the compounds of the training set.
			Structural analogues		i. Isopropyl myristate ii. 4,4-Dimethyl-2-pentadecyl-1,3-oxazol-5(4H)-one iii. 2-heptadecyl-4,4-dimethyl-4,5-dihydro-1,3-oxazol-5-one iv. 4,4-dimethyl-2-nonadecyl-4,5-dihydro-1,3-oxazol-5-one
			Consideration on structural analogues		With 89.6% the average similarity of the four most structurally similar analogues to the query structure is considered high. All four of the structures are sensitizers, thus indicating high concordance with the query structure. Three of the four structures trigger an alert from the OASIS protein binding profiler for skin sensitisation in OECD Toolbox, whereas the target molecule does not show any alerts in the profiling. Furthermore, the metabolism predictions for these molecules show different pathways and again no alerts for the query structure. It is therefore assumed to be likely that mode of action followed by the three oxazolone structures is not relatable to the target compound.
	3.4	The uncertainty of the prediction (OECD principle 4)
					The models own statistics indicate high reliability in the prediction, with high similarity, recognition of all compound fragments in the training set, good concordance of results with measured data etc. However it is clear to the assessor that the nearest molecules in the dataset used for the prediction have considerably different properties and functional groups to the target compound. An assessment of these differences using the profilers in the OECD QSAR Toolbox identifies alerts for the oxazolone containing structures compared with the target structure. Furthermore assessment of the predicted metabolism of these compounds has shown different routes to breakdown products again which the target molecule does not display any alerts for. This indicates uncertainty in the results from the model. The Isopropyl myristate is also predicted to be sensitising. The Data matrix with this information in has been included in the printouts section below for reference.
	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 within the applicability domain of the model, and the prediction is made with good statistics, however due to concerns regarding the mode of action displayed by the similar structures in the training set, there is some uncertainty in the result.
	4.4	Conclusion			The prediction is not considered reliable and will not be considered 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 within the applicability domain of the model, and the prediction is made with good statistics, however due to concerns regarding the mode of action displayed by the similar structures in the training set, there is some uncertainty in the result.

The prediction is not considered reliable and will not be considered with predictions from other models in a weight of evidence conclusion.