Isotridecyl isononanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Acute Oral Toxicity of Isotridecyl isononanoate - TOPKAT
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
CAS 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 26 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 Acute oral toxicity
Dependent variable Oral rat LD50 -log10(mol/kg)
3.2 Algorithm (OECD Principle 2)
Model or submodel name BIOVIA (TOPKAT) toxicity prediction model – Rat Oral LD50
Model version 4.5
Reference to QMRF The corresponding QMRF with the identifier Q51-54-55-502 is available at http://qsardb.jrc.it/qmrf/index.jsp.
Predicted values (model result) Default model: LD50 = 16.838 g/kg bw
Extended model: LD50 = 21.136 g/kg bw
Predicted values (comments) The extended model contains a number of identified data points from published literature in addition to those already used by the software. In this instance, the nearest identified structures were the same for both models. While the extended model is considered reliable, was a worst case conservative estimate, the lowest of the two values is used for this assessment. The full printouts for both results and the model extension criteria are provided below.

Input for prediction Smiles
Descriptor values Descriptor Value
LogP 8.45
Molecular weight (g/mol) 340.584
Number of hydrogen bond donors 0
Number of hydrogen bond acceptors 2
Number of rotatable bonds in the molecule 18
The fraction of polar surface area over the total molecular surface area 0.06
ECFP_6: Unitless Extended-connectivity fingerprint with a maximum length of 6 bonds Not applicable
FCFP_6 Unitless Functional class fingerprint with a maximum length of 6 bonds Not applicable
MDL Public Keys Unitless Fingerprint based on the MDL public keys Not applicable

3.3 Applicability domain (OECD Principle 3)
Domains i. All properties and OPS components are within expected ranges.
ii. All fingerprint features of the query molecule are found in the training set
iii. Considerations on the mechanism domain are not applicable since statistical model
Structural analogues i Octadecanoic acid; butyl ester
ii Azelaic acid; dihexyl ester
iii. Oleic acid; 2;3-epoxypropyl ester
iv. 9;10 epoxystearic acid; allyl ester

Consideration on structural analogues With 56% the average similarity of the four most similar structures to the query structure is considered moderate. Predicted and experimental values of similar structures vary by a factor of up to 1.68 (2.24 extended) which is below a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*.Hence concordance between predicted and actual value is High.
3.4 The uncertainty of the prediction (OECD principle 4)
As there is only moderate similarity of structural analogues in the prediction, this may indicate some uncertainty in the prediction. However, accuracy and concordance of the measured and predicted results for the similar structures affords some confidence in the prediction.
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 Acute toxicity endpoint for REACh registration.

4.2 Approach for regulatory interpretation of the model result
Unit conversion not required for the non-extended results as these are reported as g/kg body weight.
For the extended results, the following calculation:
power (10, -TOPKAT_Rat_Oral_LD50)*molecular weight
(g/mol)

4.3 Outcome The predicted acute toxicity LD50 of 16.838 g/kg is greater than the thresholds for classification under CLP and GHS.

4.4 Conclusion There is some uncertainty in the prediction due to the moderate similarity of structural analogues. Confidence can be taken howver from the the identified accuracy and concordance of the measured and predicted results for the similar structures.
Therefore, the result is considered reliable, however, application of further QSAR models is recommended to create a weight of evidence.

*Stedeford, T.; Zhao, Q.J.; Dourson, M.L.; Banasik, M.; Hsu, C.H. The application of non-default uncertainty factors in the US EPA’s Integrated Risk Information System (IRIS). Part I: UFL, UFS, and “Other uncertainty factors”. J. Environ. Sci. Heal. C 2007, 25, 245–279.

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 - TOPKAT
- Short description of test conditions: n/a
- Parameters analysed / observed: 2 methods of LD50 prediciton

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

Effect levels

Effect levels 1

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

16 838 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Non extended model

Effect levels 2

Sex:

not specified

Dose descriptor:

LD50

Effect level:

21 136 mg/kg bw

Based on:

test mat.

Remarks on result:

other: extened model

Any other information on results incl. tables

Acute Oral Toxicity of Isotridecyl isononanoate - TOPKAT
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
			CAS		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			26 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		Acute oral toxicity
			Dependent variable		Oral rat LD50 -log10(mol/kg)
	3.2	Algorithm (OECD Principle 2)
			Model or submodel name		BIOVIA (TOPKAT) toxicity prediction model – Rat Oral LD50
			Model version		4.5
			Reference to QMRF		The corresponding QMRF with the identifier Q51-54-55-502 is available at http://qsardb.jrc.it/qmrf/index.jsp.
			Predicted values (model result)		Default model:      LD50= 16.838 g/kg bw Extended model:   LD50= 21.136 g/kg bw
			Predicted values (comments)		The extended model contains a number of identified data points from published literature in addition to those already used by the software. In this instance, the nearest identified structures were the same for both models. While the extended model is considered reliable, was a worst case conservative estimate, the lowest of the two values is used for this assessment. The full printouts for both results and the model extension criteria are provided below.
			Input for prediction		Smiles
			Descriptor values		Descriptor Value LogP 8.45 Molecular weight (g/mol) 340.584 Number of hydrogen bond donors 0 Number of hydrogen bond acceptors 2 Number of rotatable bonds in the molecule 18 The fraction of polar surface area over the total molecular surface area 0.06 ECFP_6: Unitless Extended-connectivity fingerprint with a maximum length of 6 bonds Not applicable FCFP_6 Unitless Functional class fingerprint with a maximum length of 6 bonds Not applicable MDL Public Keys Unitless Fingerprint based on the MDL public keys Not applicable
	3.3	Applicability domain (OECD Principle 3)
			Domains		i.	All properties and OPS components are within expected ranges.
					ii.	All fingerprint features of the query molecule are found in the training set
					iii.	Considerations on the mechanism domain are not applicable since statistical model
			Structural analogues		i Octadecanoic acid; butyl ester ii Azelaic acid; dihexyl ester iii. Oleic acid; 2;3-epoxypropyl ester iv. 9;10 epoxystearic acid; allyl ester
			Consideration on structural analogues		With 56% the average similarity of the four most similar structures to the query structure is considered moderate. Predicted and experimental values of similar structures vary by a factor of up to 1.68 (2.24 extended) which is below a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*.Hence concordance between predicted and actual value is High.
	3.4	The uncertainty of the prediction (OECD principle 4)
					As there is only moderate similarity of structural analogues in the prediction, this may indicate some uncertainty in the prediction. However, accuracy and concordance of the measured and predicted results for the similar structures affords some confidence in the prediction.
	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			Acute toxicity endpoint for REACh registration.
	4.2	Approach for regulatory interpretation of the model result
					Unit conversion not required for the non-extended results as these are reported as g/kg body weight. For the extended results, the following calculation: power (10, -TOPKAT_Rat_Oral_LD50)*molecular weight (g/mol)
	4.3	Outcome			The predicted acute toxicity LD50of 16.838 g/kg is greater than the thresholds for classification under CLP and GHS.
	4.4	Conclusion			There is some uncertainty in the prediction due to the moderate similarity of structural analogues. Confidence can be taken howver from the the identified accuracy and concordance of the measured and predicted results for the similar structures. Therefore, the result is considered reliable, however, application of further QSAR models is recommended to create a weight of evidence.
*Stedeford, T.; Zhao, Q.J.; Dourson, M.L.; Banasik, M.; Hsu, C.H. The application of non-default uncertainty factors in the US EPA’s Integrated Risk Information System (IRIS). Part I: UFL, UFS, and “Other uncertainty factors”. J. Environ. Sci. Heal. C 2007, 25, 245–279.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The two predictions for the extended (21,136 mg/kg bw) and non-extended model (16,838 mg/kg bw) from the TOPKAT software both show moderate similarity between the closest structures to the target compound and the target compound itself. The default prediction shows a lower value than the extended model. The extension is built upon published data which has been included into the model. An assessment for the predicted and measured values for the nearest structures in the dataset showed that the concordance between these values was high. However, while the prediction statistics suggest the model is reliable, there is some concern regarding the similarity of the closest structures.