Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27/11/2017 to 08/12/2017

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester

EC Number:

609-496-9

Cas Number:

379685-94-6

Molecular formula:

C18H23F3N2O4

IUPAC Name:

Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester

Test material form:

solid: particulate/powder

Remarks:

Off white to beige powder with agglomerates

Specific details on test material used for the study:

- Analytical purity: 98.5% (HPLC) - Lot/batch No.: 0161045 - Expiration date of the lot/batch: 2018/06/16

Results and discussion

Water solubility

Key result

Water solubility:

ca. 259.56 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

1.5 g/L

Incubation duration:

> 0 - <= 72 h

Temp.:

20 °C

pH:

>= 4.53 - <= 4.86

Any other information on results incl. tables

All measurements of the main test were included in the calculation of the mean.

Table8.3‑a     Measurements used for Calculation of Solubility

Day	Flask	Concentration [mg/L]	Total Mean [mg/L]	Total Standard Deviation [mg/L] (RSD* [%])
3	1A	262.14	259.56	15.58 (6.0)
3	1B	237.08
3	1C	232.54
3	2	268.41
3	3	272.13
3	4	267.21
3	5	269.62
3	6	267.40

*RSD = relative standard deviation

Mean at the plateau is 259.56 ± 15.58 mg/L.

The solubility of the test itemin water was determined from the measured concentrations of test item in the filtrated test solutions.

Equilibration time can be considered as approximately 1 day, as the values which were measured were within ± 15 % of the measurements on previous days and no rising tendency was observed.

The concentration was measured in the flasks 2 – 6 after 3 days of shaking. The solubility of the test itemin water at 20 ± 0.4 °C was 259.56 mg/L (mean from two measurements in eight individual flasks). All replicates showed good correspondence. The standard deviation of the samples which were used for the calculation of water solubility at the plateau was 15.58 mg/L, corresponding to a relative standard deviation of 6.0 %.

No observations arousing doubts concerning the accuracy of the results and the validity of the study were made.

 

 

 

Applicant's summary and conclusion

Conclusions:

At the plateau, the concentration of the test item in water had reached 259.56 ± 15.58 mg/L at 20.0 ± 0.4 °C (mean value ± standard deviation of eight individual vessels).

Executive summary:

The solubility of the test item in water was determined in GLP compliance according to the OECD TG 105 with the shake flask method, and measured in the filtrated test solutions using HPLC.

In the pre-test, flasks with nominal concentrations of 200 mg/L, 1000 mg/L and
10000 mg/L, no concentration dependency was observed. According to the guideline, the flask method was used for the determination of the solubility of the test item in water.

In the main test,six identical loading rates of the test item were chosen: 1.5 g/L (nominal). Three flasks 1A - C with the same loading rate (1.5 g/L) were used during equilibration. Seven vessels (flasks blank, 1C (for the sampling point 72 h) and 2 – 6) were set onto the shaking apparatus immediately. After 24 ± 2 hours, flask 1B (for the sampling point 48 h) and after 48 ± 2 hours, flask 1A (for the sampling point 24 h) were set on the shaker and all flasks were shaken for further 24 ± 2 hours at room temperature (20.0 ± 0.5 °C). Then, flasks 1A - 1C were taken from the shaker, samples were taken, membrane filtered and analysed. No differences above 15 % and no rising tendency in the test item concentration of the solutions were observed on day 3. Equilibrium was considered as reached 1 d after test start.

No Tyndall effect (i.e. a laser beam was not scattered when transmitted through the liquid) could be observed indicating that no colloidal dispersed particles are present.

At the plateau, the concentration of the test item in water had reached

259.56 ± 15.58 mg/L at 20.0 ± 0.4 °C

= 2.5956 ± 0.1558 * 10^-4kg/m³(SI units)

(mean value ± standard deviation of eight individual vessels).