Registration Dossier

Administrative data

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 June 2017 to April 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
Version / remarks:
27 July 1995
Deviations:
no
Qualifier:
no guideline available
Principles of method if other than guideline:
Calculation of Partition Coefficient and Water Solubility
Due to the characteristics of the test substance, it was not possible to determine experimental values for the partition coefficient (log Pow); in addition the water solubility was below the limit of quantification of the analytical method. It was decided that estimated values would be calculated for the partition coefficient using appropriate software and as part of this procedure also produced estimated values for water solubility these have also been reported.

Summary
The octanol-water partition coefficient (as log Kow) and water solubility are predicted using the Estimation Program Interface (EPI ver. 4.1) developed by the United States Environmental Protection Agency (US EPA) (US EPA 2012). EPI Suite is used in the US EPA Pollution Prevention framework for the review of pre-manufacturing notice chemicals under the Toxic Substance Control Act (TSCA) and for the evaluation of the potential for chemicals to have persistent, bioaccumulative and toxic properties.
The programs within EPI Suite are able to predict physical chemical properties from chemical structure (in SMILES notation), chemical name or CAS number entries. The three models within the suite, used to estimate the required properties are:

• KOWWIN: Estimates the log octanol-water partition coefficient (log Kow) of chemicals.
• WSKOW and WATERNT: Estimate water solubility.

Water Solubility

Water Solubility (WSol) provides information on the degree to which a chemical will dissolve in 1L of water. EPI Suite™ uses two QSAR models to estimate water solubility: WSKOW and WATERNT. WSKOW accepts experimental octanol-water partition coefficient (log KOW) and melting (MP) values, and its accuracy greatly improved if an experimental MP is entered. WATERNT is a fragment-based method and like all fragment-based method the accuracy of its estimates is influenced by the relative number of fragments covered by the model – generally the more fragments included in the model domain, the more accurate the estimate will be.
The predicted water solubility values are interpreted as follows:
For WSol (mg/L) > 10,000 – the substance is classified as highly soluble in water
For WSol (mg/L) > 1,000 – 10,000 – the substance is classified as soluble in water
For WSol (mg/L) > 100 – 1,000 – the substance is classified as moderate solubility
For WSol (mg/L) > 0.1 - 100 – the substance is classified as slightly soluble in water
For WSol (mg/L) < 0.1 – indicates a substance of negligible solubility

The EPI suite has no statistical test that can be used to judge the reliability of the predicted values. Since for WATERNT this is a fragment method a surrogate method to judge the reliability of the predictions is to check that all the substructures are in the compound of interest. If all the substructures are in the model domain and are accounted for, then this increases the confidence in the predictions and the respective model result may be assumed to provide relevant information.
GLP compliance:
yes (incl. certificate)
Other quality assurance:
ISO/IEC 17025 (General requirements for the competence of testing and calibration laboratories)
Type of method:
other: Calculation

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
The test substance, was allocated the code ESTS 185/17 for reference throughout the study.
Physical state: Clear liquid
Arrival date: 12 June 2017
Re-test date: 23 January 2019
Storage conditions: Room temperature (15 to 30°C)

Results and discussion

Water solubilityopen allclose all
Key result
Water solubility:
< 0.1 µg/L
Conc. based on:
test mat.
Incubation duration:
ca. 9 d
Temp.:
19.9 °C
pH:
> 4.43 - < 5.48
Key result
Water solubility:
ca. 0 mg/L
Conc. based on:
other: Calculation
Remarks:
WSKOW model
Temp.:
25 °C
Remarks on result:
not measured/tested
Key result
Water solubility:
ca. 0 mg/L
Conc. based on:
other: Calculation
Remarks:
WATERNT model
Temp.:
25 °C
Remarks on result:
not measured/tested
Details on results:
In all water solubility samples there was no chromatographic response for the test substance. The mean test temperature was 19.9°C (min 19.8°C, max 19.9°C).

The full results are shown in Table 6 (attached).

For the analysis 10 mL of water was taken from the vessels and extracted with hexane (2 x 2.5 mL). The hexane extract was then blown down to less than 1 ml and then made up to a final volume of 1 mL in hexane. This was a concentration factor of 10.

The lowest calibration standard was 1 µg/mL and with a concentration factor of 10 this is equivalent to a concentration of 0.1 µg/mL. This demonstrates the water solubility is lower than 0.1µg/mL.

Example chromatograms are shown in Figure 24 to Figure 36 (attached).

Calculated Values
Calculated values for the water were determined using the WSKOW and WATERNT models in the EPI ver. 4.1 software.
The calculated, estimated water solubility values were:
0.00003418 mg/L at 25°C using the WSKOW model.
0.00012053 mg/L at 25°C using the WATERNT model.
The full EPI Ver. 4.1 data are shown in Appendix 3 (attached).

Applicant's summary and conclusion

Conclusions:
The water solubility of the test substance was found to be <0.1 µg/l at 19.9 °C, under the conditions of the test.
The calculated, estimated water solubility values were:
0.00003418 mg/L at 25°C using the WSKOW model.
0.00012053 mg/L at 25°C using the WATERNT model.
Executive summary:

In this guideline (OECD 105) study, [conducted with GLP certification], the water solubility of the test substance was found to be <0.1 µg/l at 19.9 °C.

The calculated, estimated water solubility values were:

0.00003418 mg/L at 25°C using the WSKOW model.

0.00012053 mg/L at 25°C using the WATERNT model.