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Water solubility

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Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 Jan 2010 to 25 Feb 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Water solubility was covered in the Bioaccumulation: aquatic / sediment endpoint (IUCLID 5.3.1). The study information was extracted from the bioaccumulation test report (A090324).
Qualifier:
according to guideline
Guideline:
other: OECD 305 (Bioaccumulation in Fish: Aqueous and Dietary Exposure) -I: Aqueous Exposure Bioconcentration Fish Test
Version / remarks:
Reliable experimental study following Standards for test facilities to conduct tests on new chemic
al substances” (Pharmaceutical and Food Safety Bureau Notice No. 1121003 dated November 21
, 2003, Manufacturing Industries Bureau Notice No. 3 dated November 17, 2003; Environmental
Health Policy Planning Division Notice No. 031121004, Final Amendment: July 4, 2008 and OECD and GLP standards.
GLP compliance:
yes
Type of method:
other: no data
Key result
Water solubility:
0.027 mg/L
Conc. based on:
test mat.
Temp.:
20 °C
pH:
7
Details on results:
Water solubility is reported as 0.027 mg/L.
Conclusions:
The water solubility of the test substance in the preliminary examination of bioaccumulation study is reported to be 0.027 mg/L.
Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
supporting study
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 as supporting information, 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 prediction is evaluated on the basis of the model performance on similar substances. For more details see section `overall remarks, attachments´.
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 v1.02

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:
0.093 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

10

-CH3   [aliphatic carbon]

-0.3213

-3.2127

Frag

2

-CH2-  [aliphatic carbon]

-0.5370

-1.0740

Frag

2

Aromatic Carbon (C-H type)

-0.3359

-0.6717

Frag

4

Aromatic Carbon (C-substituent type)

-0.5400

-2.1598

Frag

1

-OH [combined multiple aromatic attach]

2.6237

2.6237

Frag

4

-tert Carbon [3 or more carbon attach]

-0.5774

-2.3094

Const

Equation Constant

0.2492

 

Log Water Sol (mol/L) at 25 °C = -6.5548

Water Solubility (mg/L) at 25 °C = 0.093258

Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
supporting study
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 as supporting information, 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 prediction is evaluated on the basis of the model performance on similar substances. For more details see section `overall remarks, attachments´.
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:
0.365 mg/L
Temp.:
25 °C
Remarks on result:
other: QSAR result, no information on pH available.

Log Kow used by Water solubility estimates: 5.81 (experimental)

Melting point: 132 °C. The appropriate equation was used:

Log S (mol/L) = 0.693-0.96 log Kow-0.0092(Tm-25)-0.00314 MW + Correction

Correction(s): Value

Phenol: 0.961

Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
supporting study
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 as supporting information, 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 prediction is evaluated on the basis of the model performance on similar substances. For more details see section `overall remarks, attachments´.
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:
0.84 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 (-Log10(mol/L))

6.46

Group contribution (-Log10(mol/L))

5.35

FDA (-Log10(mol/L))

5.37

Nearest neighbor (-Log10(mol/L))

5.23

Consensus model (-Log10(mol/L))

5.60

Consensus model (mg/L)

0.84

 

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).

 

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

732-26-3

TR

0.90

3.88

5.07

Poor

119-47-1

TR

0.88

7.23

5.83

Poor

1918-11-2

TR

0.86

4.60

4.24

Good

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

0.027 mg/L at 20 °C, pH 7

Key value for chemical safety assessment

Water solubility:
0.027 mg/L
at the temperature of:
20 °C

Additional information

Water solubility was covered in the Bioaccumulation: aquatic / sediment endpoint (IUCLID 5.3.1). The study information was extracted from the bioaccumulation test report (A090324, OECD TG 305).

Three estimated values were also obtained by means of three (Q)SAR models: 0.36 mg/L at 25 °C (EPI Suite WSKOWWIN), 0.09 mg/L at 25 °C (EPI Suite WATERNT) and 0.84 mg/L at 25 °C (US EPA T.E.S.T.). The obtained results were evaluated to be of insufficient reliability on their own; altogether, they support a low water solubility of the target substance, hence supporting the available experimental value.