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Water solubility

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Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2017-02-20
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. SOFTWAREiSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.22. MODEL (incl. version number)iSafeRat® holistic HA-QSAR v1.73. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODELC1C(CCC)COC(=O)C14. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL See attached QMRF5. APPLICABILITY DOMAINSee attached QPRF:6. ADEQUACY OF THE RESULT See attached QPRF
Qualifier:
equivalent or similar to
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 Quantitative Structure-Property Relationship (QSPR) model which have been validated as QSAR models to be compliant with the OECD (2004) recommendations for QSAR modeling (refer to the QMRF with JRC QMRF identifier: Q19-46-51-448 for further details). This model is applicable for the substances generally classified as MOA 1 substances (non-polar narcotics) and ethers, esters, ketones, aldehydes, alcohols, acids and phenols. The algorithm is based on 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 105 guideline or an adaptation of these.
GLP compliance:
no
Specific details on test material used for the study:
not applicable
Key result
Water solubility:
26 128 mg/L
Temp.:
25 °C
Remarks on result:
other: pH not determinable by QSAR calculation
Details on results:
- Descriptor domain: The log KOW used as descriptor for this prediction was calculated and it falls within the descriptor domain of the model between log KOW of 0.03 to 5.52. The test substance falls within the response domain of the training set between log water solubility (in log (mol/l)) of 0.88 to -5.38.- Structural fragment domain: Currently, the water solubility module of the iSafeRat® Holistic HA-QSAR can reliably predict the water solubility for chemicals generally classified as MOA 1 substances (non-polar narcotics) and ethers, esters, ketones, aldehydes, alcohols and acids. 5-propyl-tetrahydropyran-2-one as an ester can be taken into account for water solubility prediction. All chemical groups within the molecular structure are taken into account by the model.- Mechanism domain: Water solubility of the substance is determined using log KOW as descriptor. The submodel used is depending of 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 sub-model for diesters compounds.- Water Solubility submodel for Oxygenated, Hydroxylated compounds: for hydrogen bond acceptor and donor compounds (i.e. alcohols, ethoxylated alcohols, lactates and carboxylic acids).CONCLUSION: 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 95% confidence interval (α = 0.05) for the result is 22148 – 30824 mg/L.

Conclusions:
Very soluble in water.
Executive summary:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the water solubility of the test item. This calculation method predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following Guideline for Testing of Chemicals No. 105, "Water Solubility". The criterion predicted was the solubility in pure water in mg.L-1 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 105 guideline or an adaptation of these.

Using the calculated log Kow value of 1.3, the water solubility is predicted as follows: 26128 mg/L at 25°C (95% CL 22148 - 30824 mg/L).

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
other information
Study period:
03-25 April 2006
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Remarks:
The study was conducted according to an internationally recognised guideline, and under GLP. However, the method used is not suitable, and surface-active behaviour is suspected. Therefore validation cannot be granted.
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
GLP compliance:
yes (incl. certificate)
Remarks:
signed 24 February 2006
Type of method:
column elution method
Water solubility:
19 mg/L
Incubation duration:
>= 16 - <= 19 h
Temp.:
20 °C
pH:
6.6

Preliminary assessments were aimed at the estimation of the hydrosolubility with no success: it was this suspected that the test item was able to form micro-drops of oily matter in suspension in water, and analysis of the hydrosolubility was not feasible. The micro-elution method was thus justified, even though final hydrosolubility was higher than 10 mg/L recommended for this testing method as a maximum.

Experiment n°1 - 25 mL/h flow rate

A 4.0103g sand portion was coated with 256.9 mg of test item. A sample of 1.0219g was introduced in the micro-column thus corresponding to 65 mg of test item.

About 31 mg of the test item were controlled to be voided in the rinsed volume (15 mL).

A total of five successive samples were submitted to the analysis which corresponded to the elution throughout a 16-h period.

Mean concentration in water = 17.9 (+/- 1.7) mg/L.

pH of the resulting solution = 6.62

Experiment n°2 - 13 mL/h flow rate

The micro-column was charged with a new 1 g sample of coated sand. About 30 mg test item were controlled to be voided in the rinsed volume (15 mL).

A total of five successive samples were submitted to the analysis which corresponded to the elution throughout a 19-h period.

Mean concentration in water = 20.8 (+/- 1.9) mg/L.

pH of the resulting solution = 6.59

Executive summary:

The water solubility of the test substance was determined under GLP according to EU A.6 guideline, elution method. In the preliminary testing, no saturation concentration could be determined, suggesting surface-active potential. The main test fulfilled the validity criteria, and the average value was retained. However, reliability is highly questionable.

The solubility has been determined to be 19 mg/L at 20°C.

Description of key information

Considered as very soluble in water.

Key value for chemical safety assessment

Water solubility:
26.1 g/L
at the temperature of:
25 °C

Additional information

An experimental study, conducted according to EC guideline and under GLP, is available, but the method used (elution) was not suitable. Moreover, preliminary testing and inconsistency with experimental partition coefficient suggest that the substance may exhibit surface-activity, despite the structural formula shows no alert. The final test fulfilled the validity criteria, but reliability cannot be granted.

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

Due to experimental issues and inconsistencies, the calculated value was prefered, and retained as key data.