2-Propenoic acid, 2-methyl-, tris(1-methylethyl)silyl ester

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 June to 10 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recent study conducted by a GLP certified laboratory in accordance with a suitable study guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Version / remarks:

and OECD Guideline No. 111, ”Hydrolysis as a Function of pH”

Deviations:

yes

Remarks:

The reaction solutions were not thermostated, because rapid degradation of TIS-M did not permit incubation of the test solutions. The test was carried out at room temperature. Sterility confirmation test was disregarded because of rapid hydrolysis.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

EC Number:

700-182-8

Cas Number:

134652-60-1

Molecular formula:

C13 H26 O2 Si

IUPAC Name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

Details on test material:

- Name of test material (as cited in study report): TIS-M
- Lot/batch No.: 9925
- Expiration date of the lot/batch: 2 December 2010
- Storage condition of test material: Under nitrogen at room temperature, continuously protected form all light.

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
None

Radiolabelling:

not specified

Study design

Analytical monitoring:

yes

Details on sampling:

Sampling:
Samples stored in the autosampler were injected consecutively every 9 minutes.

Analysis of the samples: Samples were analysed with the above presented HPLC method below

Sterility confirmation
Sterility confirmation test was disregarded because of the fast reaction.

Buffers:

pH 4.0: 0.2 ml 0.2 M Sodium hydroxide and 25 ml 0.2 M Potassium hydrogen phthalate will be diluted to 100 ml with ultra-pure water.
pH 7.0: 14.8 ml 0.2M Sodium hydroxide and 25 ml 0.2 M Potassium dihydrogen phosphate will be diluted to 100 ml with ultra-pure water.
pH 9.0: 10.7 ml 0.2 M Sodium hydroxide and 25 ml 0.2 M Boric acid and Potassium chloride will be diluted to 100 ml with ultra-pure water.

Estimation method (if used):

Not applicable.

Details on test conditions:

TEST CONDITIONS

Test temperature: room temperature
As the reaction is very fast, it is impossible to regulate the test temperature

pH: 4.0, 7.0, 9.0

Buffer solutions:
pH 4.0: 0.2 ml 0.2 M Sodium hydroxide and 25 ml 0.2 M Potassium hydrogen phthalate will be diluted to 100 ml with ultra-pure water

pH 7.0: 14.8 ml 0.2M Sodium hydroxide and 25 ml 0.2 M Potassium dihydrogen phosphate will be diluted to 100 ml with ultra-pure water

pH 9.0: 10.7 ml 0.2 M Sodium hydroxide and 25 ml 0.2 M Boric acid and Potassium chloride will be diluted to 100 ml with ultra-pure water

Light: The hydrolysis reaction was carried out using dark HPLC vials to avoid photolytic effects.

Oxygen: Nitrogen was bubbled into the water before the preparation of the solution in order to exclude oxygen.

PERFORMANCE OF THE TEST

Test solution:

25 ml sterile solutions were prepared. The nominal test item concentration in the buffer solution was 5 μg/ml. The pH of the solution was checked with a calibrated pH meter.

Storage of the solutions:
Test solution was transferred into 1.5 ml HPLC vials. The vials were entirely filled with the solution.
7 vials of test solution and 1vial of control buffer were placed in the autosampler of the HPLC, in the dark.

Sampling:
Samples stored in the autosampler were injected consecutively every 9 minutes.

Analysis of the samples: Samples were analysed with the above presented HPLC method.

Sterility confirmation
Sterility confirmation test was disregarded because of the fast reaction.

- Measures taken to avoid photolytic effects: The hydrolysis reaction was carried out using dark HPLC vials to avoid photolytic effects.
- Measures to exclude oxygen: Nitrogen was bubbled into the water before the preparation of the solution in order to exclude oxygen.
-Temperature: Room temperature. As the reaction is very fast, it is impossible to regulate the test temperature

Duration of test

Duration of test 1

Duration:

54 min

pH:

4

Temp.:

25 °C

Initial conc. measured:

5 other: μg/ml

Duration of test 2

Duration:

54 min

pH:

7

Temp.:

25 °C

Initial conc. measured:

5 other: μg/ml

Duration of test 3

Duration:

54 min

pH:

9

Temp.:

25 °C

Initial conc. measured:

5 other: μg/ml

Number of replicates:

2

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

Evaluation:
The chromatograms were evaluated with the help of “LaChrom Chromatogram Processor".
Calculations were carried out using “EXCEL for Windows". The calibration curves were constructed with “STATISTICA for Windows" using weighted linear regression. The factor was 1/concentration.

Results and discussion

Preliminary study:

No data.

Test performance:

Based on the measured concentrations (see Table 3 below) decomposition of TIS-M proved to be very fast. Compared to the start concentration 10 % or less was measured in the vials after nine minutes.
Half lives of the reactions can not be calculated, it is estimated to be less than 9 minutes.

Transformation products:

not specified

Details on hydrolysis and appearance of transformation product(s):

Not measured

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

25 °C

DT50:

< 9 min

Type:

other: estimate

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

25 °C

DT50:

< 9 min

Type:

other: estimate

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

25 °C

DT50:

< 9 min

Type:

other: estimate

Details on results:

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

Based on the measured concentrations decomposition of TIS-M proved to be very fast. Compared to the start concentration 10 % or less was measured in the vials after nine minutes. Half lives of the reactions can not be calculated, it is estimated to be less than 9 minutes.

Any other information on results incl. tables

Table 1.: Results of the Method Validation (Study Code: 09/285-316AN)

Selectivity	No interfering component was observed
Reinjection repeatability (7 injections)	Coefficient of Variation < 1.5 %
Linear range	0.2-10ug/ml
Limit of Detection	0.1 ug/ml
Limit of Quantification	0.2 ug/ml
Recovery from sunflower oil	81 % (1 mg/ml) 108 % (20 mg/ml) 110 % (600 mg/ml)
Recovery from aqueous test media	51-62% (1 ug/ml)
Stability of the samples	At least 21 hours in the autosampler
Stock solution stability	At least seven days at 5 ± 3 °C
Stability of the test item in dried sunflower oil	At least 24 hours at room temperature At least 120 hours at 5 ± 3 °C days
Stability of the test item in Water	Less than 30 minutes

Table 2.: Regression data from calibration series.

Analytical occasion	Intercept	Slope	Correlation Coefficient.
07 June 2010	-4832	34674	0.999
10 June 2010	-1277	35946	0.998

Table 3.: Measured pH values

Nominal pH	Control	Replicate 1	Replicate 2
4	4.02	4.27	4.25
7	7.00	7.25	7.25
9	9.00	9.33	9.31

Table 4.: Measured data

	Time	TIS-M concentration
pH	minutes	replicate 1	replicate 2
		[j,g/ml	[j,g/ml
	Start	2.6	2.0
	9	0.26	n.d.
	18	< 0.2	n.d.
4	27	n.d.	n.d.
	36	n.d.	n.d.
	45	n.d.	n.d.
	54	n.d.	n.d.
	Start	2.1	1.8
	9	n.d.	n.d.
	18	n.d.	n.d.
7	27	n.d.	n.d.
	36	n.d.	n.d.
	45	n.d.	n.d.
	54	n.d.	n.d.
	Start	0.5	2.6
	9	n.d.	< 0.2
	18	n.d.	n.d.
9	27	n.d.	n.d.
	36	n.d.	n.d.
	45	n.d.	n.d.
	54	n.d.	n.d.

n.d. stands for "not detected"

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

The study deviated from the Guidelines in that the reaction solutions were not thermostated, because rapid degradation of TIS-M did not permit incubation of the test solutions. The test was carried out at room temperature. Sterility confirmation test was

Conclusions:

Decomposition of the substance proved to be very fast, so the half lives of the reactions could not be calculated. The half life is estimated to be less than 9 minutes.

Executive summary:

The hydrolysis of the registered substance was assessed according to EC C.7 using a HPLC method. It was calibrated using the following concentrations of calibration samples: 0.2, 0.5, 1, 2, 5 and 10 μg/ml. The half life of the registered substance was estimated to be less than 9 minutes.