N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide]

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 20, 2017 - February 27, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature.

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: sampling at day 0 and 5.

Buffers:

- pH: 4, 7 and 9
- Type and final molarity of buffer: Buffer solution from Avantor Performance Materials Poland S.A. (formerly POCh S.A) for calibration of pH electrode and for determination of the hydrolysis rate constants.
0,8032 g of V-BA was weighed and dissolved in 10 mL of acetone (about 73.02 g/L). The portions of 0.5 mL of this obtained stock V-BA solution was added to each of 49.5 mL of the three buffer solutions (pH values: 4.0; 7.0 and 9.0). The obtained initial test item concentration, in the buffer solutions, should have achieved about 0.73 g/L of test item or 0.63 g/l of N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide], which is 0.002 M (less than 0.01 M).

Estimation method (if used):

The rate constant can be calculated using the Arrhenius equation, which gives the temperature dependence of the rate constant. From the linear plot of the logarithm of the rate constant, as determined at appropriate temperature, as a function of the reciprocal of the absolute temperature [K], it is possible to extrapolate the rate constant value which was not directly obtainable.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: glass flasks fitted with glass stoppers; analytical balance WAS 220/C/2, accuracy of readings ± 0.1 mg; incubator; laboratory centrifuge MPW-350 RH; laboratory multifunctional device CX-505, accuracy of readings ± 0.01 pH; magnetic stirrer.

TEST MEDIUM
- Volume used/treatment: 25 mL
- Preparation of test medium: 0.50 ml of tested samples, withdrawn from the buffer solutions, were added to 25.0 ml of acetonitrile, and were directly injected into the HPLC column.0,8032 g of V-BA was weighed and dissolved in 10 mL of acetone (about 73.02 g/L). The portions of 0.5 mL of this obtained stock V-BA solution was added to each of 49.5 mL of the three buffer solutions (pH values: 4.0; 7.0 and 9.0). The obtained initial test item concentration, in the buffer solutions, should have achieved about 0.73 g/L of test item or 0.63 g/l of N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide], which is 0.002 M.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

ca. 0.583 g/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

ca. 0.587 g/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

ca. 0.609 g/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Preliminary study:

The preliminary test indicates that less than 10% of the test substance has been hydrolyzed after five days at pH 4, 7 and 9 and no additional testing is required.

Transformation products:

no

% Recovery:

100

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

100

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

99.01

pH:

9

Temp.:

50 °C

Duration:

5 d

Key result

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

Determination ofV-BA contentin buffer solutions of pH 4, pH 7 and pH 9.

 

Table 1: Calibration solution

Weight [mg]	Dilution [mL]	Cw [mg/mL]	Peak area		Average peak area Aw	f×10^3	Average  f × 10^3
35.25	25-0.8-25-2.5-5	0.01918	674477	656831	665654.0	0.000029	0.000027
42.65	25-0.6-25-2.5-5	0.01740	704530	708223	706376.5	0.000025

 

Table 2. Study solution

Sample day/ flask		Peak area		Average peak area Ap	X [g/kg]
0	pH4-1	429479	439905	434692	0.5808
	pH4-2	435635	439054	437344.5	0.5843
	pH7-1	437353	463677	450515	0.6019
	pH7-2	423294	431463	427378.5	0.5710
	pH9-1	459756	459891	459823.5	0.6143
	pH9-2	455873	447313	451593	0.6034
	VERNETZER/AC^*	1208548	1202731	1205639.5	63.11
5	pH4-3	432763	444997	438880	0.5864
	pH4-4	452024	450440	451232	0.6029
	pH7-3	462883	468207	465545	0.6220
	pH7-4	469782	474093	471937.5	0.6305
	pH9-3	469715	468459	469087	0.6267
	pH9-4	440436	427442	433939	0.5798

*VERNETZER/AC: weighed amount of N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide in acetone stock solution.

Table 3.Measurements in buffer solution at pH 4.0

Time, days		0	5
concentration, [g/L]	1 flask	0.5808	0.5864
	2 flask	0.5843	0.6029
average concentration, [g/L]		0.583 ± 0.003	0.595 ± 0.012
concentration loss,  [%]		-2.06

 

Table 4.Measurements in buffer solution at pH 7.0

Time, days		0	5
concentration, [g/L]	1 flask	0.6019	0.6220
	2 flask	0.5710	0.6305
average concentration,  [g/L]		0.587 ± 0.022	0.626 ± 0.006
concentration loss,  [%]		-6.64

 

The increase in N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide] concentration – negative value of concentration loss - after 5 days results from the used analytical method properties: possible solvent vaporization, non ideal volumes withdrawals etc.

The obtained negative concentration loss should be assumed to be close to 0.0%.

 

Table 5.Measurements in buffer solution at pH 9.0

Time, days		0	5
concentration, [g/L]	1 flask	0.6143	0.6267
	2 flask	0.6034	0.5798
average concentration, [g/L]		0.609 ± 0.008	0.603 ± 0.033
concentration loss,  [%]		0.99%

Validity criteria fulfilled:

yes

Remarks:

Selectivity: equivalent; Linearity R2= 0.9971 (R2≥0.99); Precision 0.0106 mg/mL, RSD= 1.13% (RSDr ≤ 7.58%); Precision of the repeatibility RSD= 1.12% (RSDr ≤ 1.37%)

Conclusions:

The test item hydrolysed less than 10% after 5 days at pH of 4, 7 and 9. Then, the test item is considered hydrolytically stable.

Executive summary:

A hydrolysis study of the test item as a function of pH was performed according to OECD 111, following GLP. A preliminary test (Tier 1) was conducted at pH 4.0, 7.0 and 9.0 at 50ºC in the darkness. A validated HPLC method was used to determine the amount of test item in the samples. All the validity criteria were met. In the preliminary test, less than 10% of the test item has been hydrolyzed after five days. Therefore, according to the OECD guidelines, this substance is considered hydrolytically stable and no additional testing is required.

Description of key information

Key study: OECD 111. GLP study. The test item hydrolysed less than 10% after 5 days at pH of 4, 7 and 9. Then, the test item is considered hydrolytically stable.  

Additional information

Key study: A hydrolysis study of the test item as a function of pH was performed according to OECD 111, following GLP. A preliminary test (Tier 1) was conducted at pH 4.0, 7.0 and 9.0 at 50ºC in the darkness. A validated HPLC method was used to determine the amount of test item in the samples. All the validity criteria were met. In the preliminary test, less than 10% of the test item has been hydrolyzed after five days. Therefore, according to the OECD guidelines, this substance is considered hydrolytically stable and no additional testing is required.