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Physical & Chemical properties

Water solubility

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Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2018-04-13
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
CCCCCC1CC=CC(=O)O1

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:
OECD Guideline 105 (Water Solubility)
Deviations:
not applicable
Remarks:
QSAR model
Principles of method if other than guideline:
The water solubility of the test item was determined using an algorithm based on Quantitative Structure-Property Relationship (QSPR) models which have been validated as QSAR models to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). The determination was performed using regression method in which validated log KOW values are plotted against the log of subcooled 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
Type of method:
other: QSAR model
Specific details on test material used for the study:
not applicable
Key result
Water solubility:
1.64 g/L
Conc. based on:
test mat.
Temp.:
25 °C
Remarks on result:
other: applicable for the non-ionised form
Details on results:
- 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 0.03 to 5.52. The test item falls within the response domain of the training set between a log water solubility (in log (mol/L)) of -5.38 to 0.88.

- 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. iSafeRat® Holistic HA-QSAR includes the following submodels:
· Water Solubility submodel for Non-Polar Organic compounds: for compounds which are neither donors, nor acceptors for hydrogen bonds (e.g. alkanes, halides, alkenes, thiols…etc.)
· Water Solubility submodel for Oxygenated, Non-Hydroxylated 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, Non-Hydroxylated 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-/Alkoxy-phenols: for hydrogen bond acceptor and donor compounds which can participate in 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, 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.

- Metabolic domain, if relevant: Not relevant.

- 95% confidence interval (α = 0.05): 1.39 – 1.94 g/L

no data

Conclusions:
The water solubility of the test item was predicted as 1.64 g/L at 25°C and pH 7.
The uncertainty of the prediction is given with the 95% confidence interval (α = 0.05) as 1.39 – 1.94 g/L.
Test item falls within the applicability domain of the model and was therefore reliably predicted for this endpoint.
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, converted to g/L.

The water solubility of the test item was determined using an algorithm based on Quantitative Structure-Property Relationship (QSPR) models which have been validated as QSAR models to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). The determination was performed using regression method in which validated log KOW values are plotted against the log of subcooled 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.

Based on the log KOW value, the water solubility of the test item was predicted as 1.64 g/L at 25°C and pH 7.

The uncertainty of the prediction is given with the 95% confidence interval (α = 0.05) as 1.39 – 1.94 g/L.

Test item falls within the applicability domain of the model and was therefore reliably predicted for this endpoint.

Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2018-04-13
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
CCCCCCCC1CC=CC(=O)O1

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:
OECD Guideline 105 (Water Solubility)
Deviations:
not applicable
Remarks:
QSAR model
Principles of method if other than guideline:
The water solubility of the test item was determined using an algorithm based on Quantitative Structure-Property Relationship (QSPR) models which have been validated as QSAR models to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). The determination was performed using regression method in which validated log KOW values are plotted against the log of subcooled 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
Type of method:
other: QSAR model
Specific details on test material used for the study:
Not applicable
Key result
Water solubility:
102 mg/L
Conc. based on:
test mat.
Temp.:
25 °C
Remarks on result:
other: applicable for the non-ionised form
Details on results:
Applicability Domain:

Domains:

i. 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 0.03 to 5.52. Test item falls within the response domain of the training set between a log water solubility (in log (mol/L)) of -5.38 to 0.88.

ii. Structural fragment domain
All chemical groups within the molecular structure are represented within the datasets of the model.

iii. 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. iSafeRat® Holistic HA-QSAR includes the following submodels:

• Water Solubility submodel for Non-Polar Organic compounds: for compounds which are neither donors, nor acceptors for hydrogen bonds (e.g. alkanes, halides, alkenes, thiols… etc.)
• Water Solubility submodel for Oxygenated, Non-Hydroxylated 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, Non-Hydroxylated 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-/Alkoxy-phenols: for hydrogen bond acceptor and donor compounds which can participate in 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, 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.

iv. Metabolic domain, if relevant
Not relevant.

The uncertainty of the prediction (OECD principle 4)
95% confidence interval (α = 0.05): 86.4 – 120 mg/L



No data

Conclusions:
The water solubility of the test item was predicted as 102 mg/L at 25°C and pH 7.
The uncertainty of the prediction is given with the 95% confidence interval (α = 0.05) as 86.4 – 120 mg/L.
Test item falls within the applicability domain of the model and was therefore reliably predicted for this endpoint.
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, converted to mg/L.

The water solubility of the test item was determined using an algorithm based on Quantitative Structure-Property Relationship (QSPR) models which have been validated as QSAR models to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). The determination was performed using regression method in which validated log KOW values are plotted against the log of subcooled 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.

The water solubility of the test item was predicted as 102 mg/L at 25°C and pH 7.

The uncertainty of the prediction is given with the 95% confidence interval (α = 0.05) as 86.4 – 120 mg/L.

Test item falls within the applicability domain of the model and was therefore reliably predicted for this endpoint.

Description of key information

Solubility of each constituent ranging between 0.028 and 1.19 g/L (calculated values for parent reaction mass) at 25°C.

Key value for chemical safety assessment

Additional information

No experimental study was available on the substance.

Calculated values from a validated QSAR are proposed for the two constituents. Individual solubilities of the pure consituents were calculated first, then converted, using thermodynamic rules, to apparent solubilities when present together from the multi-constituent substance. The result is expressed as a range, no key value was determined.