Balmywood

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 6.35 (QSAR, EpiSuite)

Water solubility:

ca. 0.046 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.04558 mg/L at 25°C (log Kow: 6.35 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 0.04558  mg/L at 25°C (log Kow: 6.35 used as input, No MP used as input).

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 6.94 (QSAR, EpiSuite)

Water solubility:

ca. 0.014 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.01429 mg/L at 25°C (log Kow: 6.94 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 0.01429 mg/L at 25°C (log Kow: 6.94 used as input, No MP used as input).

Reference 3

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 4.84 (QSAR, EpiSuite)

Water solubility:

ca. 7.959 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No in Dataset
Alcohol, aliphatic	0.5100	18

which is applied to to compounds containing one  -OH  group attached  to an aliphatic carbon.Compounds with multiple  -OH  groups (e.g. ethylene glycol) are excluded.  Compounds containing acetamide, amino-azo-, or  -S(=O)  type functions (e.g. sulfonamides or sulfoxides) are also excluded.

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 7.959 mg/L at 25°C (log Kow: 4.84 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 7.959 mg/L at 25°C (log Kow: 4.84 used as input, No MP used as input).

Reference 4

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 6.12 (QSAR, EpiSuite)

Water solubility:

ca. 0.072 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.07164 mg/L at 25°C (log Kow: 6.12 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated (QSAR) water solubility of test item is estimated to be 0.07164 mg/L at 25°C (log Kow: 6.12 used as input, no MP used as input).

Reference 5

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 6.19 (QSAR, EpiSuite)

Water solubility:

ca. 0.22 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

No correction was appplicable.

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.2202 mg/L at 25°C (log Kow: 6.19 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 0.2202 mg/L at 25°C (log Kow: 6.19 used as input, No MP used as input).

Reference 6

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 4.33 (QSAR, EpiSuite)

Water solubility:

ca. 21.88 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No in Dataset
Alcohol, aliphatic	0.5100	18

which is applied to to compounds containing one  -OH  group attached  to an aliphatic carbon.Compounds with multiple  -OH  groups (e.g. ethylene glycol) are excluded.  Compounds containing acetamide, amino-azo-, or  -S(=O)  type functions (e.g. sulfonamides or sulfoxides) are also excluded.

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 21.88 mg/L at 25°C (log Kow: 4.33 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated (QSAR) water solubility of test item is estimated to be 21.88 mg/L at 25°C (log Kow: 4.33 used as input, no MP used as input).

Reference 7

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 5.74 (QSAR, EpiSuite)

Water solubility:

ca. 0.15 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.1504 mg/L at 25°C (log Kow: 5.74 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated (QSAR) water solubility of test item is estimated to be 0.1504 mg/L at 25°C (log Kow: 5.74 used as input, no MP used as input).

Reference 8

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 2.29 (QSAR, EpiSuite)

Water solubility:

ca. 2 083 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Acid, aliphatic	-0.395	70

which is applied to compounds with the aliphatic acid function.  Amino acids and compounds with the  C(=O)-N-C-COOH  structure are excluded.

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 2083 mg/L at 25°C (log Kow: 2.29 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 2083 mg/L at 25°C (log Kow: 2.29 used as input, No MP used as input).

Reference 9

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 5.82 (QSAR, EpiSuite)

Water solubility:

ca. 0.129 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.1292 mg/L at 25°C (log Kow: 5.82 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 0.1292 mg/L at 25°C (log Kow: 5.82 used as input, No MP used as input).

Reference 10

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 6.99 (QSAR, EpiSuite)

Water solubility:

ca. 0.013 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.01295 mg/L at 25°C (log Kow: 6.99 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 0.01295 mg/L at 25°C (log Kow: 6.99 used as input, No MP used as input).

Reference 11

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

March 2022

Reliability:

2 (reliable with restrictions)

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:

QSAR prediction:
The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. In addition, the substance investigated matches with the parameters of training set compounds and the result is considered fully reliable.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation

Specific details on test material used for the study:

Input: Log Kow: 6.26 (QSAR, EpiSuite)

Water solubility:

ca. 0.054 mg/L

Temp.:

25 °C

Remarks on result:

other: Conc. based, loading rate, incubation duration and pH not provided

Estimation Accuracy

Training

The regression equations used by the WSKOWWIN program were trained with a dataset of 1450 compounds.

As noted in the methodology section, WSKOWWIN estimates water solubility with one of two possible equations.  When an experimental melting point is available, WSKOWWIN applies the equation containing both a melting point and the molecular weight (MW) parameters.  In the absence of a melting point, the equation containing just the molecular weight is used to make the estimate.  All compounds in the 1450 compound training set have known melting points or are known to be liquids at 25°C.  In this particular case, where the melting point of the test item has not been used as input the accurancy statistic is as follows:

r2: 0.934

std deviation: 0.585

avg deviation: 0.442

Validation

The WSKOWWIN estimation equations were initially validated on two datasets of compounds that were not included in the model training.  A relatively small dataset was tested that consisted of 85 compounds having experimental log Kow values, but no available melting points.  Many compounds in the 85 compound test set decompose before melting and would theoretically have very high melting points (e.g. amino acids and compounds having multiple nitrogens).  The accuracy statistics for the equation used by WSKOWWIN are:

number: 85

r2: 0.865

std deviation: 0.961

avg deviation: 0.714

A much larger dataset of 817 compounds was also tested.  All 817 compounds had experimental melting points, but none of the 817 compounds had a reliable experimental log Kow.  The log Kow values used for the validation-testing were estimated (primarily using the KOWWIN program available at that time); therefore, the water solubility estimates are based on estimates for log Kow.  Typically, estimates based on estimates reduce estimation accuracy, but this type of validation can provide insight into the ability of the method.  The accuracy statistics for this dataset are:

number: 817

r2: 0.902

std deviation: 0.615

avg deviation: 0.480

Estimation Domain

Appendix E of the Help section in EpiSuite gives the number compounds in the 1450 compound training set containing each of the correction factors.  The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure.  The minimum number of instances is zero and the maximum is one.

In this particular case:

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

and the following correction has been applied:

Correction Factor shown in Wskowwin Program	Without MP Coef	No. In   Dataset
Hydrocarbon	-0.5370	33

which is applied to any aliphatic hydrocarbon that contains just carbons and hydrogens. 

 

Range of water solubilities in the Training set:

Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)

Maximum =  completely soluble (various)

 

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)

Maximum =  627.62 (hexabromobiphenyl)

 

Range of Log Kow values in the Training set:

Minimum  =  -3.89 (aspartic acid)

Maximum =  8.27 (decachlorobiphenyl)

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no correction factor was developed.  These points should be taken into consideration when interpreting model results.

Conclusions:

The calculated (QSAR) water solubility of test item is estimated to be 0.0544 mg/L at 25°C (log Kow: 6.26 used as input, no MP used as input).

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKOWwin v1.42. Even if the result shall be considered with restrictions considering the type of information (QSAR), the test item properties are within the application of domain of the model, so validation apply with acceptable restrictions.

The calculated water solubility is 0.0544 mg/L at 25°C (log Kow: 6.26 used as input, No MP used as input).

Description of key information

The Water Solubility of the test item based on water solubility of known constituents is estimated to be in the range between 0.01295 and 2083 mg/L at 25°C.

Additional information

No study was conducted on the test chemical iself, as not relevant for an UVCB.

The water solubility, WS, of the test item was estimated from data on its known constituents (covering almost the 64% of the composition). Data on the known constituents were reliably calculated using the recommended QSAR(EpiSuite). All the constituents fall inside the Applicability domain of the model.

The results are listed below:

Constituent	Wate Solubility (mg/L) at 25°C
Thujopsene	0.07164
Cedrol	21.88
Cedrene alpha	0.1504
Cedrene beta	0.1292
Cuparene	0.2202
Widdrol	7.959
alpha Chamigrene	0.01429
β-himachalene	0.04558
Alpha-Pseudowiddrene	0.0544
Beta-Acoradiene	0.01295
3-phenylpropionic acid	2083

As the substance is an UVCB the water solubility of the test item will be determined using the lowest and the highest water solubility values of known constituents.