O-(ethoxycarbonyl)-N-(1-methyl-2-oxo-2-phenylethylidene)hydroxylamine

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 July 2017 to 05 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

0.128 g/L

Conc. based on:

test mat.

Incubation duration:

24 h

Temp.:

20 °C

pH:

3.4

Details on results:

PRELIMINARY TEST
- The preliminary estimate of water solubility was 0.137 g/L at 20 °C.

MAIN TEST
- The mean areas relating to the main test material peak of the standard, sample and blank solutions are shown in Tables 1 and 2.
- The concentration (g/L) of test material in the sample solutions is shown in Tables 3 and 4.
- Overall result samples 1 to 3: The concentration of test material decreased when increasing the shaking period, possibly due to test material degradation.
- Overall result samples 4 to 7: Samples appeared to have reached saturation after 3 hours of shaking.

VALIDATION
- The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 1.00 to 100 mg/L in 75:25 v/v acetonitrile:water. The results were satisfactory with a goodness of fit coefficient (r^2) of 1.000 being obtained.

DISCUSSION
- On removal of the samples from the static 20 °C water bath, all seven sample solutions were observed to be clear and colourless with excess, undissolved test material present. Aliquots of the solutions were centrifuged and then sampled using a syringe and needle. Each supernatant was then observed to be clear, colourless and free from undissolved test material.
- The chromatography obtained for the first three samples (1 to 3), suggested hydrolysis of the test material. The main test material peak at approximately 3.3 min decreased with shaking time, while the peaks at approximately 1.5 and 1.9 min increased. Therefore, the first two peaks in the chromatography were attributed to degradation products. The area of the peak at approximately 5.0 min did not change significantly and was attributed to an impurity.
- Four extra samples (4 to 7) were prepared using reduced shaking and equilibration times, in an attempt to minimise test material hydrolysis. The sample and standard analysis matrices were also acidified to this effect (peak at approximately 1.3 min in the chromatography corresponds to phosphoric acid). The results indicate that the sample solutions reached saturation after 3 hours of shaking; hence, the concentrations determined for samples 6 and 7 have been used to generate the final water solubility result.

Table 1: The mean areas relating to the main test material peak of the standard, sample and blank solutions in samples 1 to 3

Solution	Mean PeakArea
Matrix Blank	None detected
Standard Solution 37.7 mg/L	1.3591 x 10^7
Standard Solution 37.7 mg/L	1.3469 x 10^7
Sample 1, Replicate Dilution A	8.6634 x 10^6
Sample 1, Replicate Dilution B	8.7186 x 10^6
Sample 2, Replicate Dilution A	7.3517 x 10^6
Sample 2, Replicate Dilution B	7.4554 x 10^6
Sample 3, Replicate Dilution A	2.7741 x 10^6
Sample 3, Replicate Dilution B	2.7271 x 10^6

Table 2: The mean areas relating to the main test material peak of the standard, sample and blank solutions in samples 4 to 7

Solution	Mean Peak Area
Standard Matrix Blank	None detected
Standard Solution 37.7 mg/L	1.4356 x 10^7
Standard Solution 37.7 mg/L	1.4351 x 10^7
Sample 4, Replicate Dilution A	1.1329 x 10^7
Sample 4, Replicate Dilution B	1.1239 x 10^7
Sample 5, Replicate Dilution A	1.1741 x 10^7
Sample 5, Replicate Dilution B	1.1749 x 10^7
Sample 6, Replicate Dilution A	1.2142 x 10^7
Sample 6, Replicate Dilution B	1.2235 x 10^7
Sample 7, Replicate Dilution A	1.2173 x 10^7
Sample 7, Replicate Dilution B	1.2234 x 10^7
Sample Matrix Blank	None detected

Table 3: The concentration (g/L) of test material in the sample solutions 1 to 3

Sample Number	Time Shaken at 30 ºC (h)	Time Equilibrated at 20 ºC (h)	Concentration (g/L)	Solution pH
1	24	24	9.68 x 10^-2	3.37
2	48	24	8.25 x 10^-2	3.28
3	72	24	3.07 x 10^-2	3.27

Table 4: The concentration (g/L) of test material in the sample solutions 4 to 7

Sample Number	Time Shaken at 30 ºC (h)	Time Equilibrated at 20 ºC (h)	Concentration (g/L)	Solution pH
4	1	1	0.119	4.11
5	2	1	0.123	3.78
6	3	1	0.128	3.73
7	24	1	0.128	3.40

Conclusions:

Under the conditions of this study, the water solubility of the test material has been determined to be 0.128 g/L of solution at 20.0 ± 0.5 °C.

Executive summary:

The water solubility of the test material was determined in accordance with the standardised guidelines OECD 105 and EU Method A.6, under GLP conditions.

The test was performed using the flask method and samples were analysed using HPLC. The preliminary estimate of water solubility was 0.137 g/L at 20 °C.

On removal of the samples from the static 20 °C water bath, all seven sample solutions were observed to be clear and colourless with excess, undissolved test material present. Aliquots of the solutions were centrifuged and then sampled using a syringe and needle. Each supernatant was then observed to be clear, colourless and free from undissolved test material.

The chromatography obtained for the first three samples (1 to 3), suggested hydrolysis of the test material. The main test material peak at approximately 3.3 min decreased with shaking time, while the peaks at approximately 1.5 and 1.9 min increased. Therefore, the first two peaks in the chromatography were attributed to degradation products. The area of the peak at approximately 5.0 min did not change significantly and was attributed to an impurity. Four extra samples (4 to 7) were prepared using reduced shaking and equilibration times, in an attempt to minimise test material hydrolysis. The sample and standard analysis matrices were also acidified to this effect (peak at approximately 1.3 min in the chromatography corresponds to phosphoric acid). The results indicate that the sample solutions reached saturation after 3 hours of shaking; hence, the concentrations determined for samples 6 and 7 have been used to generate the final water solubility result.

Under the conditions of this study, the water solubility of the test material has been determined to be 0.128 g/L of solution at 20.0 ± 0.5 °C.

Description of key information

Under the conditions of this study, the water solubility of the test material has been determined to be 0.128 g/L of solution at 20.0 ± 0.5 °C.

Key value for chemical safety assessment

Water solubility:

0.128 g/L

at the temperature of:

20 °C

Additional information

The water solubility of the test material was determined in accordance with the standardised guidelines OECD 105 and EU Method A.6, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The test was performed using the flask method and samples were analysed using HPLC. The preliminary estimate of water solubility was 0.137 g/L at 20 °C.

On removal of the samples from the static 20 °C water bath, all seven sample solutions were observed to be clear and colorless with excess, undissolved test material present. Aliquots of the solutions were centrifuged and then sampled using a syringe and needle. Each supernatant was then observed to be clear, colourless and free from undissolved test material.

The chromatography obtained for the first three samples (1 to 3), suggested hydrolysis of the test material. The main test material peak at approximately 3.3 min decreased with shaking time, while the peaks at approximately 1.5 and 1.9 min increased. Therefore, the first two peaks in the chromatography were attributed to degradation products. The area of the peak at approximately 5.0 min did not change significantly and was attributed to an impurity.Four extra samples (4 to 7) were prepared using reduced shaking and equilibration times, in an attempt to minimise test material hydrolysis. The sample and standard analysis matrices were also acidified to this effect (peak at approximately 1.3 min in the chromatography corresponds to phosphoric acid). The results indicate that the sample solutions reached saturation after 3 hours of shaking; hence, the concentrations determined for samples 6 and 7 have been used to generate the final water solubility result.

Under the conditions of this study, the water solubility of the test material has been determined to be 0.128 g/L of solution at 20.0 ± 0.5 °C.