Juniper, Juniperus mexicana, ext., isomerized, acetylated

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2015

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:

1. SOFTWARE
Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11
Contact EPISuite:
U.S. Environmental Protection Agency
1200 Pennsylvania Ave.
N.W. (Mail Code 7406M)
Washington, DC 20460
2. MODEL (incl. version number)
WSKOWWIN v1.42
September 2010 (model development); November 2012 (model publication)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See QPRF attached: ‘QPRF Title: Substance: Juniper, Juniperus mexicana, ext., isomerized, acetylated using the model WATERNT v1.01 for the endpoint: Water Solubility)’ version 1.0; 15 June 2015.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named ‘QMRF Title: WATERNT v1.01 : Water Solubility’ version 1.0; 10 June 2015

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See attached QPRF attached: ‘QPRF Title: Substance: Juniper, Juniperus mexicana, ext., isomerized, acetylated using the model WATERNT v1.01 for the endpoint: Water Solubility)’ version 1.0; 15 June 2015.

6. ADEQUACY OF THE RESULT
1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose. The prediction is adequate as supporting information for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3.

Guideline:

other: REACH Guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

Full details of the method are provided in the attached QMRF named ‘QMRF Title: WATERNT v1.01 : Water Solubility’ version 1.0; 10 June 2015 which has been newly compiled.
- The model applies the following methodology to generate predictions:
Fragment based (group contribution) QSAR; based on multivariate linear-regression modelling
- The model and the training and validation sets are published by US Environmental Protection Agency (USA).
The experimental water solubility values in the training set and validation set were measured using one or more methods equivalent or similar to the following guidelines:
- Flask or column elution methods (OECD TG 105)
- Slow Stirring methods (modified OECD TG 105) according to methods similar to those described by Letinksi and coworkers: Slow-stir water solubility measurements of selected alcohols and diesters”, Chemosphere, 48, 257 – 265 (2000).
Plus relevant EU and US EPA OPPTS methods may be also used where appropriate.
A full list of experimental water solubility reference citations is provided in the WATERNT help menu with additional reference citations.
- Justification of QSAR prediction: The result should be considered in relation to corresponding information presented and in accordance with the tonnage driven information requirements of REACH Regulation (EC) 1907/2006 in a weight of evidence.
Specifically the substance is presented to assess the solubility of known constituents of the multi-constituent substance that yields results by expert judgement that are consistent with the weight of evidence. Substance consists of constituents within two bands of solubility: >= 0.01 mg/L (insoluble) to <= 2.80 mg/L (slightly soluble) range.

Specific details on test material used for the study:

Detailed information on the 'test material identity' is provided in the attached QSAR Prediction Reporting Format (QPRF) document including information on individual constituents.

Water solubility:

>= 0.01 - <= 2.8 mg/L

Temp.:

25 °C

pH:

ca. 7

Remarks on result:

other: Value represents the range of predicted water solubility for all constituents

Water solubility:

>= -6.681 - <= -4.944 other: moles/L

Temp.:

25 °C

pH:

ca. 7

Remarks on result:

other: Value represents the range of predicted water solubility for all constituents

1. Defined Endpoint:

QMRF 1. Physical Chemical Properties

QMRF 1.3. Water Solubility

Reference to type of model used and description of results:

WATERNT v1.01; integrated within the Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11; September 2010 (model development); November 2012 (model publication)

 

2. Description of results and assessment of reliability of the prediction:

The predicted values are provided within the QPRF attached: ‘QPRF Title: Substance: Juniper, Juniperus mexicana, ext., isomerized, acetylated using the model WATERNT v1.01 for the endpoint: Water Solubility)’ version 1.0; 15 June 2015 which has been newly compiled.

The range of constituents water solubility was: 0.01 – 2.80 mg/L

Several or more constituents had water solubility < 0.1 mg/L ('insoluble' band)

The majority of constituents had water solubility < 1 mg/L ('slightly soluble' band)

Several or more constituents had solubility > 1 mg/L

It is noted by the applicant there is no universally acknowledged applicability domain for the model. However, assessment of the substance within the applicability domains recommended by the developers is documented within the corresponding QMRF named ‘QMRF Title: WATERNT v1.01 : Water Solubility’ version 1.0; 10 June 2015 – section 5; indicates the substance (constituents):

(i) All constituents fall within the Molecular Weight and Water Solubility (mol/L) training set domain ranges.

(ii) No substances have functional groups or features not in the training set of the model and/or for which no fragment constants and correction factors available. No constituents contain multiple fragment instances than the maximum of the training set (see QMRF title section 9.3 for more information).

 

3. Uncertainty of the prediction and mechanistic domain:

The training set of the model has the following statistics and coefficients of determination:

Total Training Set Statistics: number in dataset = 1128 ; correlation coef (r2) = 0.940 ; standard deviation = 0.537 ; avg Molecular Weight = 187.74

The model has been externally validated on a set of 4636 substances and the following statistics and coefficients of determination are presented:

Total Validation Set Statistics: number in dataset = 4636 ; correlation coef (r2) = 0.815 ; standard deviation = 1.045 ; avg Molecular Weight = 227.52

Data for the training set are available via external validation (see attached QMRF prepared by the applicant for full citations).

There is no overt mechanistic basis for the model. The model correlates thermodynamic relationships of surrogates to chemical activity. The WATERNT run in standalone mode allows water solubility to be estimated based on measured values of analogues within the training set (if available). Then the model applies by adding/subtracting fragment constants and correction factors from the measured value. This therefore improves prediction since calculations are based on structural differences between target and analogue. The model domain ideally has at least one or more structurally similar substances to target substances on which to then apply ACF methodology. Whilst there appears to be no direct analogues within the training set. The model has been has been validated externally (using > 4000) substances with a correlation coefficient (r2) = 0.815. The model is non-proprietary and the training sets and validation sets can be downloaded from the internet. A summary of this information is presented by the applicant. Model predictivity could be improved by the assignment of additional substances into the training set. Inclusion of additional structural fragments and expansion of sub-structure correction factors and related rules. In addition, rules for stereochemical effects could feasibly improve modelling.

Conclusions:

The results are adequate for the for the regulatory purpose.
Interpretation of results : Substance consists of constituents within two bands of solubility: i. insoluble and ii.slightly soluble
Water Solubility range (all known constituents): >= 0.01 mg/L (insoluble) to <= 2.80 mg/L (slightly soluble).

Executive summary:

WATERNT (model publication: November 2012)

Water Solubility range (all known constituents): >= 0.01 mg/L (insoluble) to <= 2.80 mg/L (slightly soluble).

Adequacy of the QSAR:

1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose.

The prediction is adequate as supporting information for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3.

Description of key information

Water Solubility range (all main constituents): >= 0.01 mg/L (insoluble) to <= 2.80 mg/L (slightly soluble) at 25 °C and ca. pH 7, QSAR Prediction – WATERNT v1.01, EpiSuite 4.11 - US EPA, 2015

Substance consists of constituents within two bands of solubility: >= 0.01 mg/L (insoluble) to <= 2.80 mg/L (slightly soluble) range.

Additional information

QSAR Predictions WATERNT v1.01 model, 2015 – water solubility range (all known constituents): >= 0.01 to <= 2.80 mg/L at 25 °C; ca. pH 7

 

References for further information:

1. QMRF Title: WATERNT v1.01 : Water Solubility, version 1.0; dated: 10-06-2015

2. QPRF Title: Substance: Juniper, Juniperus mexicana, ext., isomerized, acetylated using the model WATERNT v1.01 for the endpoint: Water Solubility, version 1.0; dated: 15-06-2015