6-(2,4,4-trimethylcyclopentylidene)hexanal

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

Test dates: Apr.19 to Jul.5, 2013

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)

Deviations:

yes

Remarks:

Coloum eluition method not suitable for liquids.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

GIPC; effective Jun.14, 2012, signed on Jan.10, 2013

Type of method:

column elution method

Specific details on test material used for the study:

Storage conditions of test material: At room temperature protected from direct sunlight.

Water solubility:

3.3 mg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

>= 6.8 - <= 7.5

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 6.8 - 7.5 at ca 3.3 mg/L.

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

08 November to 22 November 2021

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® – in Silico Algorithms For Environmental Risk And Toxicity

2. MODEL (incl. version number)
iSafeRat® WatSol v1.9

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC1CC(C)(C)C/C1=C\CCCCC=O

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

5. APPLICABILITY DOMAIN
See attached Study Report with QPRF in Annex

6. ADEQUACY OF THE RESULT
See attached Study Report with QPRF in Annex

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.
The determination is performed using a regression method in which log Kow values are plotted against the log of Subcooled Liquid Water Solubility (SLWS) following the methodology outlined in Ran et al. (2001) using a General Solubility Equation. However, the methodology has been improved by grouping substances into specific categories according to the capability of the substance to participate in hydrogen bonding with water and octanol (depending on their structure). Therefore, several local models with their respective algorithms have been developed and validated.

GLP compliance:

no

Type of method:

other: QSAR model

Remarks:

The data used for water solubility values come from studies which have been carried out using the method recommended in the OECD guideline 105, i.e. shake-flask or an adaptation (slow-stir method) for liquids with an expected solubility below 10 mg/L.

Key result

Water solubility:

2.73 mg/L

Temp.:

25 °C

Remarks on result:

other: pH not relevant by QSAR calculation

Details on results:

95% confidence interval (α = 0.05): 2.18 – 3.42 mg/L

Applicability Domain

 

Descriptor domain
The log Kow (4.98) given as the input to the iSafeRat® WatSol model falls within the descriptor domain of the model between a log Kow of 0.03 to 5.52.

 

Response domain
The predicted log SLWS (-4.883) falls within the response domain of the model between a log SLWS of -5.38 and 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 HAQSAR 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.

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 can was therefore reliably predicted for its WATER SOLUBILITY. Therefore, this endpoint value can be considered valid and fit for purpose.

 

The WATER SOLUBILITY of the test item was predicted as 2.73 mg/L at 25°C.

95% confidence interval (α = 0.05): 2.18 – 3.42 mg/L.

Description of key information

Calculated water solubility = 2.73 mg/L at 25°C (calculated).

pH: 6.8-7.5 for a 3.3 mg/L solution at 20°C (exp).

Key value for chemical safety assessment

Water solubility:

2.73 mg/L

at the temperature of:

25 °C

Additional information

The water solubility was reliably estimated by QSAR, using the experimental logKow as input.

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.