Isotridecyl isononanoate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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.

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

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

Sex:

not specified

Dose descriptor:

LD50

Effect level:

21 136 mg/kg bw

Based on:

test mat.

Remarks on result:

other: extened model

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.

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.

Reference 2

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:

1. SOFTWARE
QSAR Toolbox 4.2

2. MODEL (incl. version number)
QSAR Toolbox 4.2
Database version: 4.2
TPRF v4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)CCCCCCCCCCOC(=O)CCCCCC(C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
see attached justificaiton

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
see attached ustification

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
Prediction is considered to be of moderate reliability since the nearest neighbours are of only moderate (>60%) similarity to the target, and the mechanism is ill defined. However observation of the resulting category of substances from the subcategorization, concordance of results (all above 2000mg/kg bw) and fulfilment of the multiple categorisations offers some confidence in the prediction.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: QSAR -OECD QSAR Toolbox
- Short description of test conditions: n/a
- Parameters analysed / observed: LD50 prediciton

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

14 500 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

The toolbox prediction of 14,500 mg/kg bw shows some measure of poor similarity in the report, however a review of the category data shows that the average similarity to the target compound is 71% (see section 2.2 of the Category report below), implying that the similarity is not so poor as indicated in the report. The result is derived from the members of the category defined by the profilers identified in the software. All members of the category displayed toxicity ≥ 5,000 mg/kg bw, thus there is concordance between the dataset compounds further supporting the result.
Prediction to be used as part of a weight of evidence.

Reference 3

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 – T.E.S.T.
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 US EPA T.E.S.T Oral Rat LD50; Consensus method
Model version 4.2
Reference to QMRF Not available
Predicted values (model result) LD50 = 14583.87 mg/kg
Predicted values (comments) Unit conversion provided by the software. All single methods, hierarchical clustering, FDA, and nearest neighbour predicted values greater than the classification limit for CLP.
Input for prediction Smiles
Descriptor values Due to the large number of descriptors used all information are attached in the software printout section.
3.3 Applicability domain (OECD Principle 3)
Domains i. Query structure is within the domain of the model
ii. All descriptors of the query structure are within ranges
iii. Considerations on the mechanism domain are not applicable since statistical model
Structural analogues i Butyl stearate
ii Bis(2-ethylhexyl) azelaate
iii. Bis(2-ethylhexyl) dodecanedioate
iv. Dihexyl azelaate


Consideration on structural analogues With 94.5% the average similarity of the four most similar structures in the training set to the query structure is considered to be high. Predicted and experimental values of similar structures vary by a factor of up to 2.00 which is well 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)
The mean absolute error (MAE) for the prediction with the training set (0.17) is less than the MAE for the entire set (0.34) which provides confidence. The MAE for the prediction with external test set (0.35) is also less than the MAE of the entire set (0.43) supporting the conclusion from the training set. Additionally, high similarity of structural analogues, and high accuracy in the prediction of similar structures further supports 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
Result is directly applicable since no conversion of the result is required. Unit conversion is provided by the model.

4.3 Outcome Not classified : LD50 14583.87 mg/kg bw.

4.4 Conclusion The predicted LD50 of 14583.87 mg/kg is higher than the CLP classification threshold (2000 mg/kg bw). Furthermore, the results from the three individual models are each above the CLP classification value, further supporting this result.
The positive prediction statistics suggest reliability in the results.
*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.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: QSAR - US EPA TEST
- Short description of test conditions: n/a
- Parameters analysed / observed: 3 methods of LD50 prediciton, with a 4th consensus model.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

14 593 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Consensus Model

Sex:

not specified

Dose descriptor:

LD50

Effect level:

11 211 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Hierarchical clustering model

Sex:

not specified

Dose descriptor:

LD50

Effect level:

18 365 mg/kg bw

Based on:

test mat.

Remarks on result:

other: FDA model

Sex:

not specified

Dose descriptor:

LD50

Effect level:

15 066 mg/kg bw

Based on:

test mat.

Remarks on result:

other: nearest neighbour model

Acute Oral Toxicity of Isotridecyl isononanoate – T.E.S.T.
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		US EPA T.E.S.T Oral Rat LD50; Consensus method
			Model version		4.2
			Reference to QMRF		Not available
			Predicted values (model result)		LD50= 14583.87 mg/kg
			Predicted values (comments)		Unit conversion provided by the software. All single methods, hierarchical clustering, FDA, and nearest neighbour predicted values greater than the classification limit for CLP.
			Input for prediction		Smiles
			Descriptor values		Due to the large number of descriptors used all information are attached in the software printout section.
	3.3	Applicability domain (OECD Principle 3)
			Domains		i.	Query structure is within the domain of the model
					ii.	All descriptors of the query structure are within ranges
					iii.	Considerations on the mechanism domain are not applicable since statistical model
			Structural analogues		i Butyl stearate ii Bis(2-ethylhexyl) azelaate iii. Bis(2-ethylhexyl) dodecanedioate iv. Dihexyl azelaate
			Consideration on structural analogues		With 94.5% the average similarity of the four most similar structures in the training set to the query structure is considered to be high. Predicted and experimental values of similar structures vary by a factor of up to 2.00 which is well 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)
					The mean absolute error (MAE) for the prediction with the training set (0.17) is less than the MAE for the entire set (0.34) which provides confidence. The MAE for the prediction with external test set (0.35) is also less than the MAE of the entire set (0.43) supporting the conclusion from the training set. Additionally, high similarity of structural analogues, and high accuracy in the prediction of similar structures further supports 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
					Result is directly applicable since no conversion of the result is required. Unit conversion is provided by the model.
	4.3	Outcome			Not classified : LD5014583.87 mg/kg bw.
	4.4	Conclusion			The predicted LD50of 14583.87 mg/kg is higher than the CLP classification threshold (2000 mg/kg bw). Furthermore, the results from the three individual models are each above the CLP classification value, further supporting this result. The positive prediction statistics suggest reliability in the results.
*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.

Interpretation of results:

GHS criteria not met

Conclusions:

The TEST predictions all show high similarity and good prediction statistics, both for concordance and error, suggesting confidence can be placed in these predictions. The individual methods, hierarchical clustering, FDA, and nearest neighbour, were used to produce the consensus model which is reviewed below, the individual models are also reported in the software printout section. The consensus model, taking into account the other models, predicts a value of 14,593 mg/kg bw.

Reference 4

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 – DEREK
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 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 Oral toxicity
Dependent variable Not applicable
3.2 Algorithm (OECD Principle 2)
Model or submodel name Adrenal gland toxicity, High acute toxicity, alpha-2-mu-Globulin nephropathy, Kidney disorders, Bladder disorders, Kidney function-related toxicity, Bladder urothelial hyperplasia, Nephrotoxicity, Bone marrow toxicity, Ocular toxicity, Bradycardia, Pulmonary toxicity, Cardiotoxicity, Splenotoxicity, Cumulative effect on white cell count and immunology, Thyroid toxicity, Hepatotoxicity, Urolithiasis, HERG channel inhibition in vitro
Model version Knowledge Base: Derek KB 2018 1.1, Version 1.1 from 23/11/2017
Reference to QMRF There is no QMRF available. Further information can be obtained from Lhasa Ltd.
Predicted values (model result) No alerts matched
Predicted values (comments) No alerts fired for the listed targeted endpoints:
Adrenal gland toxicity, High acute toxicity, alpha-2-mu-Globulin nephropathy, Kidney disorders, Bladder disorders, Kidney function-related toxicity, Bladder urothelial hyperplasia, Nephrotoxicity, Bone marrow toxicity, Ocular toxicity, Bradycardia, Pulmonary toxicity, Cardiotoxicity, Splenotoxicity, Cumulative effect on white cell count and immunology, Thyroid toxicity, Hepatotoxicity, Urolithiasis, HERG channel inhibition in vitro
Input for prediction Smiles
Descriptor values Not applicable
3.3 Applicability domain (OECD Principle 3)
Domains Alert description image:
as no alerts were fired, there are no identified structural alerts to provide a domain.


Structural analogues as no alerts were fired, there are no structural analogues to report
Consideration on structural analogues n/a.
3.4 The uncertainty of the prediction (OECD principle 4)
As no alerts were fired no conclusion is made on the toxicity of the compound.
3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
No mechanism to report as no alerts were identified.

4 Adequacy (Optional)
4.1 Regulatory purpose Oral toxicity endpoint for REACh registration.

4.2 Approach for regulatory interpretation of the model result
Result may support prediction of toxicity/non-toxicity.

4.3 Outcome The report indicates that no alerts were identified for the target substance from the list of endpoints assessed.


4.4 Conclusion The reliability of the prediction is not possible to assess since no alerts were identified and thus no criteria are available to assess. The lack of identified alerts does not equate to an identified lack of toxicity, thus the report cannot be considered to conclude anything in isolation. However, it could provide supporting information in a weight of evidence.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: QSAR
- Short description of test conditions: n/a
- Parameters analysed / observed: Adrenal gland toxicity, High acute toxicity, alpha-2-mu-Globulin nephropathy, Kidney disorders, Bladder disorders, Kidney function-related toxicity, Bladder urothelial hyperplasia, Nephrotoxicity, Bone marrow toxicity, Ocular toxicity, Bradycardia, Pulmonary toxicity, Cardiotoxicity, Splenotoxicity, Cumulative effect on white cell count and immunology, Thyroid toxicity, Hepatotoxicity, Urolithiasis, HERG channel inhibition in vitro

Remarks on result:

other: The listed series of profilers which are related to oral toxicity were assessed. In each case no alerts were highlighted, supporting the predictions made by the other software.

Acute Oral Toxicity of Isotridecyl isononanoate – DEREK
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			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		Oral toxicity
			Dependent variable		Not applicable
	3.2	Algorithm (OECD Principle 2)
			Model or submodel name		Adrenal gland toxicity, High acute toxicity, alpha-2-mu-Globulin nephropathy, Kidney disorders, Bladder disorders, Kidney function-related toxicity, Bladder urothelial hyperplasia, Nephrotoxicity, Bone marrow toxicity, Ocular toxicity, Bradycardia, Pulmonary toxicity, Cardiotoxicity, Splenotoxicity, Cumulative effect on white cell count and immunology, Thyroid toxicity, Hepatotoxicity, Urolithiasis, HERG channel inhibition in vitro
			Model version		Knowledge Base: Derek KB 2018 1.1, Version 1.1 from 23/11/2017
			Reference to QMRF		There is no QMRF available. Further information can be obtained from Lhasa Ltd.
			Predicted values (model result)		No alerts matched
			Predicted values (comments)		No alerts fired for the listed targeted endpoints: Adrenal gland toxicity, High acute toxicity, alpha-2-mu-Globulin nephropathy, Kidney disorders, Bladder disorders, Kidney function-related toxicity, Bladder urothelial hyperplasia, Nephrotoxicity, Bone marrow toxicity, Ocular toxicity, Bradycardia, Pulmonary toxicity, Cardiotoxicity, Splenotoxicity, Cumulative effect on white cell count and immunology, Thyroid toxicity, Hepatotoxicity, Urolithiasis, HERG channel inhibition in vitro
			Input for prediction		Smiles
			Descriptor values		Not applicable
	3.3	Applicability domain (OECD Principle 3)
			Domains		Alert description image: as no alerts were fired, there are no identified structural alerts to provide a domain.
			Structural analogues		as no alerts were fired, there are no structural analogues to report
			Consideration on structural analogues		n/a.
	3.4	The uncertainty of the prediction (OECD principle 4)
					As no alerts were fired no conclusion is made on the toxicity of the compound.
	3.5	The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
					No mechanism to report as no alerts were identified.
4	Adequacy (Optional)
	4.1	Regulatory purpose			Oral toxicity endpoint for REACh registration.
	4.2	Approach for regulatory interpretation of the model result
					Result may support prediction of toxicity/non-toxicity.
	4.3	Outcome			The report indicates that no alerts were identified for the target substance from the list of endpoints assessed.
	4.4	Conclusion			The reliability of the prediction is not possible to assess since no alerts were identified and thus no criteria are available to assess. The lack of identified alerts does not equate to an identified lack of toxicity, thus the report cannot be considered to conclude anything in isolation. However, it could provide supporting information in a weight of evidence.

Interpretation of results:

GHS criteria not met

Conclusions:

With the DEREK model, the following series of profilers were assessed which are related to oral toxicity:
Adrenal gland toxicity, High acute toxicity, alpha-2-mu-Globulin nephropathy, Kidney disorders, Bladder disorders, Kidney function-related toxicity, Bladder urothelial hyperplasia, Nephrotoxicity, Bone marrow toxicity, Ocular toxicity, Bradycardia, Pulmonary toxicity, Cardiotoxicity, Splenotoxicity, Cumulative effect on white cell count and immunology, Thyroid toxicity, Hepatotoxicity, Urolithiasis, HERG channel inhibition in vitro.
In each case no alerts were highlighted, supporting the predictions made by the other software.
Prediction to be used as part of a weight of evidence.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

The toxicological properties of 11-Methyldodecyl 7-methyloctanoate (CAS: 42131-27-1, EC: 255-673-5) have been evaluated by quantitative structure activity relationship (QSAR) modelling performed by Biovia Discovery Studio (TOPKAT) 4.5 (extensible), US EPA TEST 4.2, DEREK NEXUS and OECD QSAR Toolbox 4.2.

There is confidence in the prediction of acute toxicity for Isotridecyl isononanoate and together with expert reasoning the results are regarded as conclusive. The summarized results of the predictions are presented in the table below.

 

Model	Acute Oral Toxicity (LD50, mg/kg bw)
Biovia Discovery Studio (TOPKAT) 4.5 (extensible)	16,838 (non-extended) 21,136 (extended)
US EPA TEST 4.2	14,593 (Consensus) 11,211 (Hierarchical clustering) 18,365 (FDA) 15,066 (Nearest neighbour)
OECD QSAR Toolbox 4.2.	14,500
DEREK	No alerts identified

 

The reliability of these predictions has also been assessed below, there are deficiencies in some of the predictions, mainly due to similarity of the dataset to the target molecule, but these are elaborated upon and discussed further below. Overall it was determined that all the results were useable as part of an overall the weight of evidence.

All models predicted the LD50 to be well above the 2000 mg/kg bw value for acute toxicity category 4 according to CLP, and above the GHS category 5 criteria of 5000 mg/kg bw. The DEREK assessment highlighted no alerts for the molecule further supporting the predictions.

In conclusion, from the models used it has been assessed that it is unlikely that the substance should be classified for acute oral toxicity and its toxicity can be assumed to be >5000 mg/kg