monoesters of C16 and C18 (branched and linear) fatty acids with decan-1-ol

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

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

Remarks:

The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the overall internal quality check in VEGA v1.1.4 indicates that the prediction is reliable with a Klimisch score of 2.

Justification for type of information:

1. SOFTWARE
VEGA version 1.1.4

2. MODEL (incl. version number)
ALogP Model v. 1.0.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: VEGA v1.1.4
- Model(s) used: ALogP Model version 1.0.0
The model is based on the Ghose-Crippen-Viswanadhan LogP (ALogP) and consists of a regression equation based on the hydrophobicity contribution of 120 atom types as described in: A.K. Ghose and G.M. Crippen, J. Comput. Chem. 1986, 7, 565-577; V.N. Viswanadhan et al., J. Comput. Chem. 1993, 14, 1019-1026; A.K. Ghose, V.N. Viswanadhan, J.J. Wendoloski, J. Phys. Chem. A 1998, 102, 3762-3772. For the purpose of applicability domain assessment, the training set of the Meylan LogP model (9,961 compounds) has been considered, setting all molecules as belonging to the test set.
- Model description: see field 'Justification for type of information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'

GLP compliance:

no

Type of method:

other: QSAR

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

> 10

Remarks on result:

other: value predicted from QSAR

Decyl isostearate –LogP model (ALogP) 1.0.0 (VEGA)
1	Substance
	1.1	CAS number			84605-08-3
	1.2	EC number			306-448-6
	1.3	Chemical name
			IUPAC		Decyl 16-methylheptadecanoate
			Other (ISO)		Heptadecanoic acid, 16-methyl-, decyl ester
			Other		Decyl isostearate
	1.4	Structural formula
	1.5	Structure codes
			SMILES		See “Test material information”
			Other
			Stereochemical features		N/A
2	General Information
	2.1	Date of QPRF			06 March 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		Partition coefficient (Log KOW)
			Dependent variable		KOW                                  (unitless) Log KOW                      (unitless)
	3.2	Algorithm (OECD Principle 2)
			Model or submodel name		LogP model (ALogP) 1.0.0 within VEGA 1.1.4
			Model version		1.0.0
			Reference to QMRF		There is no QMRF available. Information to the VEGA models can be found at vega-qsar.eu
			Predicted values (model result)		11.39
			Predicted values (comments)		This is identical to the value predicted by the KOWWIN model
			Input for prediction		Smiles
			Calculated descriptor values		Not provided by the software
	3.3	Applicability domain (OECD Principle 3)
			Domains		i.	The predicted compound is outside the Applicability Domain of the model
					ii.	accuracy of prediction for similar molecules found in the training set is not optimal.
					iii.	similar molecules found in the training set have experimental values that disagree with the predicted value.
					iv	the maximum error in prediction of similar molecules found in the training set has a moderate value, considering the experimental variability.
			Structural analogues		i. 2-ethylhexyl laurate ii. Methyl docosanoate iii. Methyl icosanoate iv. Methyl stearate
			Consideration on structural analogues		With 91% the average similarity of the four most similar analogues in the training set to the query structure is considered high. Predicted and experimental values of similar structures vary by a factor of up to 7.2 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)
					The prediction is flawed by its failure to fulfil the domain criteria set out by the model, which brings the results into dispute. Also the model reports some variance in the measured results for the nearest structures. However the similarity for the dataset molecules to the target is high, and furthermore, there would appear to be concordance with the results vs. the predicted values as observed above. In short the results should not be considered reliable on their own, but some reassurance can be taken from the positive statistics reported above.
	3.5	The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
					LogP prediction based on Ghose-Crippen-Viswanadhan octanol-water partition coefficient (ALogP), calculated from the AlogP model consisting of a regression equation based on the hydrophobicity contribution of 115 atom types
4	Adequacy (Optional)
	4.1	Regulatory purpose			Partition coefficient endpoint for REACh registration.
	4.2	Approach for regulatory interpretation of the model result
					No unit conversion necessary (unitless).
	4.3	Outcome			Uncertainty is indicated by the substance falling outside of the applicability domain for the model as described above. The model identifies that similarity of nearest structures is high but that concordance of results with measured data for those structures is moderate. An assessment of these values shows some confidance can be taken from the consideration of structural analogues section in 3.3 above. As such the result here, while of poor reliability, should not be used alone but could contribute to a weight of evidence.
	4.4	Conclusion			The prediction is considered to be of poor reliability, but will be used as part of a weight of evidence,

Conclusions:

The octanol/water partition coefficient of Decyl Isostearate was estimated to be log Kow > 10 (QSAR prediction, VEGA v1.1.4/ALogP v1.0.0)

Executive summary:

The predicted value of log Kow = 11.39 is considered to be of moderate reliability. Uncertainty is indicated by the substance not fully complying with the applicability domain of the model. The predicted value is therefore used to conclude that the log Kow of the substance is > 10. Results obtained from other QSAR models support this conclusions and are therefore used in a weight of evidence approach.

Reference 2

Endpoint:

partition coefficient

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

Remarks:

The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the overall internal quality check in VEGA v1.1.4 indicates that the prediction is reliable with a Klimisch score of 2.

Justification for type of information:

1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

2. MODEL (incl. version number)
KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Overall remarks, attachments" section.

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: KOWWIN v1.68
The octanol-water partition coefficient of organic compounds is estimated starting from the chemical structure, which is divided into fragments (atom or larger functional groups). Coefficient values of each fragment or group are summed together to yield the log P estimate. For the complete method's description see field 'Any other information on materials and methods incl. tables'.
The datasets used for the model development (2447 molecules) and for the external validation (10946 molecules) are described in the field 'Any other information on materials and methods incl. tables'.
- Model description: see field 'Justification for type of information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and 'overall remarks'

GLP compliance:

no

Type of method:

other: QSAR

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

> 10

Remarks on result:

other: value predicted from QSAR

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 3 | -CH3   [aliphatic carbon]               | 0.5473 | 1.6419

 Frag | 23 | -CH2-  [aliphatic carbon]               | 0.4911 | 11.2953

 Frag | 1 | -CH    [aliphatic carbon]               | 0.3614 | 0.3614

 Frag | 1 | -C(=O)O [ester, aliphatic attach]       |-0.9505 | -0.9505

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  = 12.5771

 

The number of -CH2- identified in the structure of the evaluated molecule (23) exceeds the maximum number identified in the molecules of the dataset (18).

Conclusions:

The octanol/water partition coefficient of decyl isostearate was estimated to be log Kow > 10 (QSAR prediction, EPI Suite v4.11/Kowwin v1.68)

Executive summary:

The predicted value of log Kow = 12.5771 is considered to be of moderate reliability, to be used as a weight of evidence.

Uncertainty is indicated by the substance not fully complying with the applicability domain of the model. The predicted value is therefore used to conclude that the log Kow of the substance is > 10. Results obtained from other QSAR models support this conclusions and are therefore used in a weight of evidence approach.

Reference 3

Endpoint:

partition coefficient

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

Remarks:

The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the overall internal quality check in VEGA v1.1.4 indicates that the prediction is reliable with a Klimisch score of 2.

Justification for type of information:

1. SOFTWARE
VEGA version 1.1.4

2. MODEL (incl. version number)
Meylan/Kowwin v. 1.1.4

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: VEGA v1.1.4
- Model(s) used: Meylan/Kowwin LogP Model version 1.1.4
The model is based on the Atom/Fragment Contribution (AFC) method from the work of Meylan and Howard (W.M. Meylan and P.H. Howard, Atom/fragment contribution method for estimating octanol-water partition coefficients, 1995, J. Pharm. Sci. 84: 83-92.), as implemented in the EPI Suite KOWWIN module (http://www.epa.gov/oppt/exposure/pubs/episuite.htm). The calculated model has a lower bound of -5.0 log units (all predictions lower than this value are set to -5.0). A dataset of compounds with experimental logP values has been built starting from the original dataset provided in EPI suite. The set has been processed and cleared from compounds that were replicated or that had problems with the provided molecule structure. The final dataset has 9,961 compounds.
- Model description: see field 'Justification for type of information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'

GLP compliance:

no

Type of method:

other: QSAR

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

> 10

Remarks on result:

other: value predicted from QSAR

Decyl isostearate – LogP model (Meylan/Kowwin) 1.1.4(VEGA)
1	Substance
	1.1	CAS number			84605-08-3
	1.2	EC number			306-448-6
	1.3	Chemical name
			IUPAC		Decyl 16-methylheptadecanoate
			Other (ISO)		Heptadecanoic acid, 16-methyl-, decyl ester
			Other		Decyl isostearate
	1.4	Structural formula
	1.5	Structure codes
			SMILES		See “Test material information”
			Other
			Stereochemical features		N/A
2	General Information
	2.1	Date of QPRF			06 March 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		Partition coefficient (Log KOW)
			Dependent variable		KOW                                  (unitless) Log KOW                      (unitless)
	3.2	Algorithm (OECD Principle 2)
			Model or submodel name		LogP model (Meylan/Kowwin) 1.1.4within VEGA 1.2.4
			Model version		1.1.4
			Reference to QMRF		There is no QMRF available. Information to the VEGA models can be found at vega-qsar.eu
			Predicted values (model result)		12.58
			Predicted values (comments)		This is identical to the value predicted by the KOWWIN model
			Input for prediction		Smiles
			Calculated descriptor values		Not provided by the software
	3.3	Applicability domain (OECD Principle 3)
			Domains		i.	The predicted compound is outside the Applicability Domain of the model
					ii.	Similar molecules found in the training set have experimental values that disagree with the predicted value.
					iii.	the maximum error in prediction of similar molecules found in the training set has a moderate value, considering the experimental variability.
			Structural analogues		i. 2-ethylhexyl laurate ii. Methyl docosanoate iii. Methyl icosanoate iv. Methyl stearate
			Consideration on structural analogues		With 91% the average similarity of the four most similar analogues in the training set to the query structure is considered high. Predicted and experimental values of similar structures vary by a factor of up to 4.1 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 prediction is flawed by its failure to fulfil the domain criteria set out by the model, which brings the results into dispute. Nevertheless, the similarity for the dataset molecules to the target are high, and furthermore, there would appear to be concordance with the results vs. the predicted values for the dataset as reported by the model (despite its claim that there are values that disagree with the conclusion). In short the results should not be considered reliable on their own, but some reassurance can be taken from the positive statistics reported above.
	3.5	The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
					LogP prediction based on Meylan work (W.M. Meylan, P.H. Howard, "Atom/fragment contribution method for estimating octanol-water partition coefficients", 1995, J. Pharm. Sci. 84:83-92) and implemented in EPI Suite software as KowWin. Model developed inside the VEGA platform.
4	Adequacy (Optional)
	4.1	Regulatory purpose			Partition coefficient endpoint for REACh registration.
	4.2	Approach for regulatory interpretation of the model result
					No unit conversion necessary (unitless).
	4.3	Outcome			Uncertainty is indicated by the substance falling outside of the applicability domain for the model as described above. The model identifies that similarity fo nearest structures and concordance of results with those structures is high, this was also confirmed in the assessment made in the consideration of structural analogues section in 3.3 above. It is also recognised that this result is identical to the KOWWIN value which has been deemed to be within the domain of that model. As such the result here, while of poor reliability, should not be used alone but could contribute to a weight of evidence.
	4.4	Conclusion			The prediction is considered to be of poor reliability, but will be used as part of a weight of evidence.

Conclusions:

The octanol/water partition coefficient of decyl isostearate was estimated to be log Kow > 10 (QSAR prediction, VEGA v1.1.4/Meylan-Kowwin v1.1.4)

Executive summary:

The predicted value of log Kow = 12.58 is considered to be of moderate reliability. Uncertainty is indicated by the substance not fully complying with the applicability domain of the model. The predicted value is therefore used to conclude that the log Kow of the substance is > 10. Results obtained from other QSAR models support this conclusions and are therefore used in a weight of evidence approach.

Description of key information

Log Pow > 10 (QSAR: Vega version 1.1.4 - two models: Meylan/Kowwin version 1.1.4, ALogP version 1.0.0; EPI Suite version 4.11 - Kowwin version 1.68)

Additional information

The following Log Pow values were obtained by means of three QSAR models:

12.58 (EPI Suite Kowwin)

12.58 (VEGA Meylan/Kowwin)

11.39 (VEGA ALogP)

In all cases, the molecule does not fully comply with the applicability domains of the models. A log Pow > 10 is taken as a conservative key value for the chemical safety assessment for this substance.