Eucalyptus radiata australiana, ext.

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:

October 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: 4.57 (peer reviewed).

Water solubility:

ca. 3.153 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 3.153 mg/L at 25°C (log Kow: 4.57 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 v1.43.

The test item properties are within the application of domain of the model. Considering the type of information (QSAR), validation apply with acceptable restrictions. 

The calculated water solubility is 3.153  mg/L at 25°C (log Kow: 4.57 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:

October 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: 2.98 (peer- reviewed)

Water solubility:

ca. 670.4 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  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 670.4 mg/L at 25°C (log Kow: 2.98 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 v1.43. The test item properties are within the application of domain of the model. Considering the type of information (QSAR), validation apply with acceptable restrictions.

The calculated water solubility is 670.4 mg/L at 25°C (Log Kow: 2.98 used as input, No MP used as input).

Reference 3

Endpoint:

water solubility

Type of information:

not specified

Adequacy of study:

weight of evidence

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data on water solubility comes from an online compilation using secondary data sources. Even if the details on method are missing and the substance is not deeply identified, the reference cited is peer-reviewed, and therefore considered to be reliable with acceptable restriction according to REACH TGD.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Data on Water Solubility come from a secondary source (HSDB). No information on TEST GUIDELINE available

Principles of method if other than guideline:

No data

GLP compliance:

not specified

Type of method:

other: Data on Water Solubility comes from a secondary source. No information on type of method available.

Water solubility:

3 500 mg/L

Temp.:

21 °C

Remarks on result:

other: pH is not specified

Details on results:

No further details.

No further details.

Conclusions:

The water solubility of test item is stated to be 3500 mg/L at 21°C.

Executive summary:

The HSDB database provides, as secondary source, some physico-chemical properties.

A water solubility value of 3500 mg/L at 21°C is cited for 1,8-cineol (pH not reported).

Description of key information

The Water Solubility of the test item, based on the three known majour constituents, is estimated to be in the range 3.153 - 3500 mg/L at 25°C and 21°C respectively.

Key value for chemical safety assessment

Water solubility:

3.153 mg/L

at the temperature of:

25 °C

Additional information

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

The water solubility of the test item was reliably estimated from data on its three major constituents (covering more than 83% of the composition).

The water solubility of one of the three major consituents, 1,8-cineol, comes from literature (peer-reviewed). The water solubility of the the others two major constituents (d,l-limonene and alpha-terpineol) was determined by a validated QSAR model using the log Kow as input. No melting point was used. These two components fall inside the Applicability domain of the model.

The results are listed below:

- 1,8 -cineol, water solubility = 3500 mg/L at 21°C

- d,l-limonene, water solubility = 3.153 mg/L at 25°C

- alpha-tepineol, water solubility = 670.4 mg/L at 25°C 

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 the three major constituents.