4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2017-12-15

Reliability:

1 (reliable without restriction)

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
iSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.4

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.8

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC1(O)CC(OCC1)C(CC)CC

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
See attached QPRF.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

not applicable

Remarks:

QSAR model

Principles of method if other than guideline:

The purpose of the in silico study was to determine the water solubility of test item in pure water at 25°C. The determination was performed using a regression method in which validated log Kow values are plotted against the log of sub-cooled liquid water solubility from studies of high quality. These have been carried out using one of the methods recommended in the OECD guideline 105 or an adaptation of these.

GLP compliance:

no

Remarks:

QSAR model

Type of method:

other: QSAR model

Key result

Water solubility:

6 886 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

pH:

ca. 7

Remarks on result:

other: 95% confidence interval (α = 0.05): 5629 – 8424 mg/L

Applicability domains of the model have been verified.

• Descriptor domain: The log Kow used as the descriptor for this prediction was reliably predicted using the iSafeRat® log Kow module and it falls within the descriptor domain of the model between a log Kow of 0.79 to 6.03. 2-(1-ethylpropyl)-4-methyl-tetrahydro-pyran-4-ol falls within the response domain of the training set between a log water solubility (in log (mol/L)) of -5.92 to 0.01.
• Structural fragment domain: All chemical groups within the molecular structure are represented within the datasets of the model.
• Mechanism domain: Water solubility of the substance is determined using log Kow as the descriptor. The submodel used is dependent on the capability of the substance to participate in hydrogen bonding with water and octanol. Given the molecular structure of the substance, the submodel used to predict its water solubility is the one dedicated to Oxygenated, Hydroxylated compounds (which are both bond acceptor and donor compounds).

Conclusions:

Soluble in water.

Executive summary:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the water solubility of the test item. This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 105, "Water Solubility". The criterion predicted was the solubility in water in mol.L^-1, converted to mg.L^-1.

The determination was performed using a regression method in which validated log Kow values are plotted against the log of sub-cooled liquid water solubility.

The substance falls within the applicability domain of the model and was therefore reliably predicted for its water solubility.

Therefore, this endpoint value can be considered valid and fit for purpose.

Using the exerimental log Kow value of 2.20, the water solubility was predicted as 6886 mg/L at 25°C.

Description of key information

Soluble in water (calculated value).

Key value for chemical safety assessment

Water solubility:

6.89 g/L

at the temperature of:

25 °C

Additional information

An experimental study, conducted according similarly to EC guideline and under GLP, is available, but the media used (buffers) was not suitable. Moreover, results show pH-dependency, with significantly lower (ca 3x less) solubility in basic medium, despite the structural formula shows no ionisable feature. The test fulfilled the validity criteria, but results are not suitable for purpose.

Therefore, a calculation from a fully valid QSAR was additionally performed.

It is interesting to notice that the prediction is consistent with experimental results at pH 5 and 7. However, due to experimental deviations, the calculated value was prefered, and retained as key data.