Registration Dossier

Administrative data

Endpoint:
partition coefficient
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:
accepted calculation method

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Calculation of Partition Coefficientand 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.
Partition Coefficient (log Kow)

The KOWWIN model uses a "fragment constant" method to predict the partition coefficient (Kowusually reported as the logarithm log Kow). In the "fragment constant" method, a molecule is divided into fragments (atoms or larger functional groups) and the assigned coefficient values for each fragment are added to give the Kowestimate, which is reported as log Kow.
Interpreting Results:
The predicted partition coefficients are interpreted as follows:
For log Kow< 1 – the substance is classified as highly soluble in water (hydrophilic)
For log Kow> 4 – the substance is classified as not very soluble in water (hydrophobic)
For log Kow> 8 – the substance is classified as not readily bioavailable
For log Kow> 10 – the substance is classified as not bioavailable – partitioning properties are difficult to measure experimentally
The EPI suite has no statistical test that can be used to judge the reliability of the predicted values. For KOWWIN that is a fragment approach, a surrogate method to judge the reliability of the predictions is to check that all the substructures in the compound of interest are represented in the calculations. If all the substructures are in the model domain and are accounted for, then this increases the confidence in the predictions and the model result may be assumed to provide relevant information.
GLP compliance:
yes (incl. certificate)
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water

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)

Study design

Analytical method:
other: Calculation

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
ca. 8.953
Temp.:
20 °C
Remarks on result:
other: Calculated
Details on results:
Due to the low water solubility, which was below the limit of quantification of the analytical method, the partition coefficient could not be determined experimentally using the shake flask or slow stir methods.

The OECD 117 HPLC method was investigated but no quantifiable peaks were found in any of the test substance solutions. Example chromatograms are shown in Figure 37 to Figure 42 (attached).

Based on this it was decided that partition coefficient would be calculated using the Estimation Program Interface EPI ver. 4.1.

Calculated Values
The calculated value for log Pow was 8.9532. The full EPI Ver. 4.1 data are shown in Appendix 3 (attached).

Applicant's summary and conclusion

Conclusions:
Due to the low water solubility, which was below the limit of quantification of the analytical method, the partition coefficient could not be determined experimentally using the shake flask or slow stir methods.

The OECD 117 HPLC method was investigated but no quantifiable peaks were found in any of the test substance solutions.

Based on this it was decided that partition coefficient would be calculated using the Estimation Program Interface EPI ver. 4.1.

The calculated value for log Pow was 8.9532.
Executive summary:

Due to the low water solubility, which was below the limit of quantification of the analytical method, the partition coefficient could not be determined experimentally using the shake flask or slow stir methods.

The OECD 117 HPLC method was investigated but no quantifiable peaks were found in any of the test substance solutions. Example chromatograms are shown in Figure 37 to Figure 42 (attached).

Based on this it was decided that partition coefficient would be calculated using the Estimation Program Interface EPI ver. 4.1.

Calculated Values

The calculated value for log Pow was 8.9532.