2-(3,3-dimethylcyclohex-1-enyl)-2,5,5-trimethyl-1,3-dioxane

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

October 16th, 2019 to October 18th, 2019

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(C)C=C(C2(OCC(C)(C)CO2)C)CCC1
experimental log Kow (4.37) used as input value for the QSAR model

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

Reason / purpose for cross-reference:

reference to other study

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.
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" (OECD, 1995). 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

Type of method:

other: QSAR model

Specific details on test material used for the study:

log Kow (experimental) = 4.37

Key result

Water solubility:

15.4 mg/L

Temp.:

25 °C

Remarks on result:

other: pH not relevant by QSAR calculation

Details on results:

Applicability Domain:

Descriptor domain:
The log Kow used as the descriptor for this prediction falls within the descriptor domain of the model between a log Kow of 0.03 to 5.52. The test item falls within the response domain of the training set between a log water solubility (in log (mol.L-1)) of -5.38 to 0.88.

Structural fragment domain:
All chemical groups within the molecular structure are represented within the datasets used by the model.

Mechanistic 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. iSafeRat® Holistic HA-QSAR includes the following submodels:
· Water Solubility submodel for NonPolar Organic compounds:
for compounds which are neither donor, nor acceptor for hydrogen bonds (e.g. alkanes, halides, alkenes, thiols… etc.)
· Water Solubility submodel for Oxygenated, NonHydroxylated compounds (classical):
for hydrogen bond acceptor compounds which are not donors (e.g. ethers, mono-esters, ketones, aldehydes, epoxides, lactones, carbonates, (meth)acrylates)
· Water Solubility submodel for Oxygenated, NonHydroxylated compounds (diesters):
specific submodel for diester compounds.
· Water Solubility submodel for Oxygenated, Hydroxylated compounds:
for hydrogen bond acceptor and donor compounds (i.e. alcohols, ethoxylated alcohols, lactates and carboxylic acids).
· Water Solubility model for Alkyl/Alkoxyphenols:
for hydrogen bond acceptor and donor compounds which can participate to strong hydrogen bonds.
· Water Solubility model for Amino compounds:
for hydrogen bond acceptor and donor compounds which can be ionised (i.e. primary, secondary and tertiary amines).
Given the molecular structure of the substance (ether), the submodel used to predict its water solubility is the one dedicated to Oxygenated, Non-Hydroxylated compounds (classical), which are hydrogen bond acceptors but not donors.

95% confidence interval (α = 0.05): 12.8 – 18.6 mg/L.

QSAR statistical parameters are given in the QMRF and the QPRF

Executive summary:

A validated Quantitative Structure-Property Relationship (QSPR) model was used to calculate the water solubility of the test item.

The determination was performed using a regression method in which validated log Kow values are plotted against the log of subcooled liquid water solubility from studies of high quality.

The experimentally determined log Kow was used as input.

The test item 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.

The water solubility at 25°C of the test item was determined as 15.4 mg/L.

95% confidence interval (α = 0.05): 12.8 – 18.6 mg/L.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

Test dates: July 24 to August 6, 2015

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

The determination was conducted with the column elution method, which is not suitable for a liquid test substance.

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

GLP compliance:

yes (incl. QA statement)

Remarks:

issued 05 March 2015

Type of method:

column elution method

Specific details on test material used for the study:

- Physical state: Colourless translucent liquid
- Storage condition: Room temperature protected from direct sun light.

Water solubility:

7.1 mg/L

Temp.:

20 °C

pH:

ca. 7.1 - ca. 7.6

Executive summary:

The water solubility of the test substance was determined according to EU A.6 guideline, column elution method.

As this method is considered not suitable for liquid test items, the solubility result was not retained.

But the information on the pH of the solution is considered of scientific interest : ca 7.1 -7.6 at 7.1 mg/L.

Description of key information

Calculated water solubility = 15.4 mg/L at 25°C.

pH ca 7.1-7.6 for a 7.1 mg/L solution.

Key value for chemical safety assessment

Water solubility:

15.4 mg/L

at the temperature of:

25 °C

Additional information

An experimental study was available, but the result was disregarded, as the elution method, not suitable for liquids, was used. However the pH of the resulting solution was included as supporting scientific information of interest.

Therefore, the water solubility was reliably estimated by a validated QSAR, using the fully valid experimental logKow as input.