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Water solubility

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Reference
Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
key study
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™-Estimation Program Interface

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

3. SMILES
C=C(C)C(OCC1OCOC1)=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
This program (WSKOWWIN) estimates the water solubility (WSol) of an organic compound using the compounds log octanol-water partition coefficient (Kow).  WSKOWWIN requires only a chemical structure to estimate Wsol.  Structures are entered into WSKOWWIN through SMILES (Simplified Molecular Input Line Entry System) notations.  Users unfamiliar with SMILES notations can consult the document "A Brief Description of SMILES Notation".  Chemical Abstract Service (CAS) Registry numbers may be used to enter SMILES notations automatically through use of a supplemental database containing SMILES for 108,000+ compounds. 

The estimation methodology used by WSKOWWIN (Meylan and Howard, 1994a,b) is described in the following document prepared for the U.S. Environmental Protection Agency (OPPT): Upgrade of PCGEMS Water Solubility Estimation Method (May 1994).  A companion document (Validation of Water Solubility Estimation Methods Using Log Kow for Application in PCGEMS & EPI) also discusses the methodology.  WSKOWWIN uses equations 19 and 20 from these documents because they are the best available equations for estimating Wsol.

Equation 19 is:  log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Corrections
Equation 20 is:  log S (mol/L) = 0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + Corrections
(where MW is molecular weight, Tm is melting point (MP) in deg C [used only for solids]) ... Corrections are applied to 15 structure types (eg. alcohols, acids, selected phenols, nitros, amines, alkyl pyridines, amino acids, PAHS, multi-nitrogen types, etc); application and magnitude depends on available MP.  Equation 20 is used when a measured MP is available; otherwise, equation 19 is used. These equations were derived from a dataset consisting of 1450 compounds with measured log Kow, water sol, and MP. Eq 20 has the following statistical accuracy: correlation coefficient (r2) = 0.97, standard deviation = 0.409 log units, and absolute mean error = 0.313 log units.  Application to a validation dataset of 817 compounds gave the following statistical accuracy: correlation coefficient (r2) = 0.902, standard deviation = 0.615 log units, and absolute mean error = 0.480 log units.

A journal article that describes the methodology is also available (Meylan et al., 1996).  The EPA documents cited above (Meylan and Howard, 1994a,b) are available vis Internet download at:
http://esc.syrres.com/interkow/EpiSuiteData.htm

WSKOWWIN uses four data entry fields as follows:

SMILES: this is the structure of the compound as a SMILES notation (required)...a maximum of 360 characters is allowed in this field.
NAME: this is the name or ID of the compound; it is optional (not required for estimation).
Melting Pt: this is measured melting point of the compound in deg C; this field is optional (not required for estimation).  When left blank, WSKOWWIN uses an estimation equation that excludes melting point. In terms of method accuracy, this equation is not as good as the equation that uses a measured melting point... if a melting point is available, it should be entered here!
Log Kow: this is a known value for the log octanol-water partition coefficient; it is optional (not required for estimation). When a value is entered here, it is used to estimate WSol rather than the estimate Kow or a Kow retrieved from the experimental database.
 WSKOWWIN estimates a log Kow for every SMILES notation by using the estimation engine from the KOWWIN Program (SRC, 2000).  WSKOWWIN also automatically retrieves experimental log Kow values from a database containing more than 13200 organic compounds with reliably measured values.  When a SMILES structure matches a database structure (via an exact atom-to-atom connection match), the experimental log Kow value is retrieved and used to predict Wsol rather than the estimated value.

WSKOWWIN v1.4 includes an experimental water solubility database of 6230 compounds.  When experimental data are available for the SMILES being estimated, the data are retrieved and shown in the Results Window.

5. APPLICABILITY DOMAIN
- Descriptor domain:
The substance has a molecular weight of 172 g/mole and is therefore in the molecular weight range of the compounds in the training set (between 18 and 720)

- Structural and mechanistic domains:
The number of each fragment found in the substance does not exceed the maximum number of this fragment that occurs in any individual compound of the training set.


6. ADEQUACY OF THE RESULT
The substance fits in the applicability domain of the model. The prediction is valid and can be used for classification and risk assessment.
Principles of method if other than guideline:
- Justification of QSAR prediction: see field 'Justification for type of information'
GLP compliance:
no
Specific details on test material used for the study:
SMILES: C=C(C)C(OCC1OCOC1)=O
Key result
Water solubility:
20 250 mg/L
Temp.:
25 °C
pH:
ca. 7
Remarks on result:
other: QSAR

Description of key information

Water solubility calculated based on log Kow: 20250.0 mg/l

Key value for chemical safety assessment

Water solubility:
20 250 mg/L
at the temperature of:
28 °C

Additional information

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