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Physical & Chemical properties

Water solubility

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Administrative data

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: WATERNT v1.01; integrated within the Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11; September 2010 (model development); November 2012 (model publication)

2. MODEL (incl. version number): WATERNT v1.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CAS RN

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL: There is no overt mechanistic basis for the model. The model correlates thermodynamic relationships of surrogates to chemical activity. The WATERNT run in standalone mode allows water solubility to be estimated based on measured values of analogues within the training set (if available). Then the model applies by adding/subtracting fragment constants and correction factors from the measured value. This therefore improves prediction since calculations are based on structural differences between target and analogue. The model domain ideally has at least one or more structurally similar substances to target substances on which to then apply ACF methodology.

Whilst there appears to be no direct analogues within the training set. The model has been has been validated externally (using > 4000) substances with a correlation coefficient (r2) = 0.815. The model is nonproprietary
and the training sets and validation sets can be downloaded from the internet. A summary of this information is presented by the applicant. Model predictivity could be improved by the assignment of additional substances into the training set. Inclusion of additional structural fragments and expansion of sub-structure correction factors and related rules. In addition, rules for stereochemical effects could feasibly improve modelling.

5. APPLICABILITY DOMAIN:
(i) All constituents fall within the Molecular Weight and Water Solubility (mol/L) training set domain
ranges.
(ii) No substances have functional groups or features not in the training set of the model and/or for which
no fragment constants and correction factors available. No constituents contain multiple fragment in
stances than the maximum of the training set.

6. ADEQUACY OF THE RESULT:
1) QSAR model is scientifically valid.
2) The substance falls within the applicability domain of the QSAR model.
3) The prediction is fit for regulatory purpose.

The prediction is adequate as supporting information for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3.

Data source

Reference
Reference Type:
other: QSAR predicted value
Title:
WATERNT v 1.01 (Epi Suite) - Water Solubility
Year:
2012
Bibliographic source:
Meylan, W.M. 1995. Preliminary Report: Water Solubility Estimation by Base Compound Modification. prepared for: Gary Thom & Robert S. Boethling, US EPA, OPPT, Washington, DC, USEPA Contract 68-D2-0141 (Task 3-14), Sep, 1995.

Materials and methods

Test guideline
Qualifier:
no guideline available
Version / remarks:
QSAR predicted value.
Principles of method if other than guideline:
WATERNT uses a "fragment constant" methodology to predict water solubility. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the solubility estimate. We call WATERNT’s methodology the Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups in WATERNT were derived by multiple regression of 1000 reliably measured water solubility values.
GLP compliance:
not specified
Type of method:
other: QSAR predicted value.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-pyridylmethanol
EC Number:
209-592-7
EC Name:
2-pyridylmethanol
Cas Number:
586-98-1
Molecular formula:
C6H7NO
IUPAC Name:
2-pyridylmethanol
Test material form:
liquid
Details on test material:
- State: Liquid
- Color: Clear light yellow to orange liquid.
- Moisture content (by KF method): 0.50% (max)

Results and discussion

Water solubility
Key result
Water solubility:
ca. 1 000 000 mg/L
Conc. based on:
not specified
Temp.:
25 °C
Remarks on result:
other: QSAR predicted value.

Applicant's summary and conclusion

Conclusions:
WATERNT v 1.01 (Epi Suite) predicted that 2-hydroxymethylpyridine has a water solubility of 1000000 mg/L at 25 °C.
Executive summary:

WATERNT v 1.01 (Epi Suite) predicted that 2-hydroxymethylpyridine has a water solubility of 1000000 mg/L at 25 °C. This is a valid model for this substance which falls into its applicability domain as explained in the attached reports.