2,6-diisopropylnaphthalene

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

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
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)
WATERNT v1.01

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: WATERNT v1.01
The water solubility of organic compounds is estimated using a "fragment constant" methodology. The structure is divided into fragments and coefficient values of each fragment or group are summed together to yield the solubility estimate. For more information see ‘attached justification’ and/or 'Any other information on materials and methods incl. tables'.
The datasets used for the model development (1128 molecules) and for the external validation (4636 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 materials and methods incl. tables'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and 'overall remarks'

GLP compliance:

no

Type of method:

other: QSAR

Water solubility:

0.115 mg/L

Temp.:

25 °C

Remarks on result:

other: QSAR result, no information on pH available.

TYPE	NUM	WATER SOLUBILITY FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	4	-CH3   [aliphatic carbon]	-0.3213	-1.2851
Frag	2	-CH    [aliphatic carbon]	-0.5285	-1.057
Frag	6	Aromatic Carbon (C-H type)	-0.3359	-2.0152
Frag	4	Aromatic Carbon (C-substituent type)	-0.54	-2.1598
Const		Equation Constant		0.2492

Reference 2

Endpoint:

water solubility

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
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)
WSKOWWIN v1.42

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: WSKOWWIN v1.42
The water solubility of organic compounds is estimated starting from the log octanol-water partition coefficient (log Kow). 12 compound classes are identified, associated to correction factors, and used in a multi-linear regression including log Kow and melting point and/or molecular weight. The water solubility is then estimated with one of two possible equations. For more information see ‘attached justification’ and/or 'Any other information on materials and methods incl. tables'.
The datasets used for the model development (1450 molecules) and for the external validation (85 and 817 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 materials and methods incl. tables'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and 'overall remarks'

GLP compliance:

no

Type of method:

other: QSAR

Water solubility:

0.242 mg/L

Temp.:

25 °C

Remarks on result:

other: QSAR result, no information on pH available.

Log Kow used by Water solubility estimates: 6.08 (calculated)

 

Melting point was not used as descriptor. The appropriate equation was used.

Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

 

Correction(s):   Value

No Applicable Correction Factors

Reference 3

Endpoint:

water solubility

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
US EPA T.E.S.T. version 4.2

2. MODEL
Water solubility at 25 °C

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, extracted from the official documentation 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:

Calculation based on T.E.S.T. version v4.2, consensus method

- Software tool(s) used including version: T.E.S.T. v4.2
- Model(s) used: Water solubility at 25 °C
The model is a consensus result of four independent models built using different approaches: Hierarchical Clustering, FDA Method, Group contribution method, and Nearest neighbor method. For the complete methods' descriptions see field 'Justification for type of information / Attached justification'.
The dataset used for the model development and for the external validation is derived from US EPA EPI Suite and includes 5020 chemicals with experimentally determined water solubility in a temperature range 10 - 25 °C.
- 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

Water solubility:

0.22 mg/L

Temp.:

25 °C

Remarks on result:

other: QSAR result, no information available on pH

The results of the individual models and the consensus are reported in the table below.

Method	Predicted value
Hierarchical clustering	6.66
Group contribution	4.76
FDA	6.04
Nearest neighbor	6.45
Consensus model (-Log10(mol/L))	5.98
Consensus model (mg/L)	0.22

 

The target molecule is evaluated as compliant with the applicability domain of the models (the prediction is not provided if a molecule fails the applicability domain assessment).

 

 

Evaluation of the Mean Absolute Error (MAE)

The MAE of the predictions obtained for the most similar molecules to the query molecule (similarity coefficient ≥ 0.5) from the external test set of the model is calculated and compared to the MAE obtained for the whole test set. Results are reported in the table below.

Chemicals	MAE*
Entire set	0.58
Similarity coefficient ≥ 0.5	0.48

*Mean absolute error in -Log10(mol/L)

 

The MAE calculated for the subset of similar substances is lower than the one calculated for the whole test set. This increases the confidence in the value predicted for the query compound.

Similarly, the MAE calculated for the subset of similar substances from the training set (0.46) is lower than the one calculated for the whole training set (0.50).

 

 

Performance on similar molecules

The model performance (predicted vs experimental water solubility values) on the three most similar molecules present in the model’s training set or in the model test set is presented in the table below.

CAS	From dataset	Similarity Coefficient	Experimental value (-Log10(mol/L))	Predicted value (-Log10(mol/L))	Performance
25640-78-2	TR	0.9	5.51	4.93	Moderate
52251-71-5	TR	0.84	6.89	6.17	Moderate
781-43-1	TE	0.83	6.57	6.07	Moderate

TR = training set; TE = test set

 

The performances of the model on the similar molecules are evaluated on the basis of the absolute differences between experimental and predicted values:

-Good if difference ≤ 0.5

-Moderate if difference ≤ 1.0

-Poor if difference > 1.0

Description of key information

The water solubility of 2,6-diisopropylnaphthalene is estimated to be < 1 mg/L at 25 °C (QSAR models: EPI Suite / WSKOWWIN version 1.42, EPI Suite / WATERNT version 1.01 and US EPA T.E.S.T. / water solubility consensus method)

Key value for chemical safety assessment

Water solubility:

1 mg/L

at the temperature of:

25 °C

Additional information

The water solubility of the target substance has been evaluated using three scientifically valid QSAR models: EPI Suite / WSKOWWIN, EPI Suite / WATERNT and US EPA T.E.S.T. / water solubility consensus method; The generated results were 0.24 mg/L, 0.11 mg/L and 0.22 mg/L, respectively. It is concluded that the water solubility of 2,6-diisopropylnaphthalene can be reliably estimated to be < 1 mg/L.