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Hydrolysis

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Description of key information

Substance is not hydrolytically stable

Key value for chemical safety assessment

Half-life for hydrolysis:
8 d
at the temperature of:
25 °C

Additional information

The objective of this study was the determination of the abiotic degradation of the test substance SA01 under hydrolysis conditions according to guideline 84/449/EWG, appendix V, C. 10.;hydrolysis rate as a function of the pH-value. Study conducted in compliance with GLP.

From the result of the pretest at pH 4 a half-life period at 25°C of ≥1 year can be estimated. From the result of the pretest at pH 9 and pH 11 a half-life period at 25°C < 1 d can be estimated.

For pH 7 the rate coefficient and the half-life period at 25°C were obtained from the results of tests 1 and 3 by extrapolation according to the Arrhenius equation. The half-life period was determined to be 6.0 days at pH7, 25°C.

A study was performed to determine the abiotic degradation of the test substance SA03, i.e. the determination of the hydrolysis rate as a function of the pH-value according to EU Method C.7. in compliance with GLP.

Solutions of the test substance were prepared by weighing between 10 and 15 mg of the test substance in a 50 mL volumetric flask and dissolving in the relevant buffer. The resulting solution was subjected immediately to the hydrolysis procedure.

The flask containing the hydrolysis mixture was placed in a thermostatically controlled water bath at the selected temperature for the specified time. Thereafter it was cooled immediately. The pH was controlled. The HPLC analysis of the unhydrolysed test substance (main compound) was performed without any delay

At pH 4 the half-life period was determined by extrapolating the results of the experiments at 50, 60 and 70 °C to a temperature of 25 °C. It was found to be 7.95 d.

At pH 7 the half-life period was determined by extrapolating the results of the experiments at 50, 60 and 70 °C to a temperature of 25 °C. It was found to be 12.6 d.

At pH 9 the decomposition is higher than 50 % after 2.4 h at 50 °C. Thus the test substance may be considered hydrolytically instable at pH 9.

Under the test conditions, the extrapolated half life values of the test substance SA03 at pH 4 and 7 were found to be 7.95 and 12.6 d respectively at 25 °C.

In the course of the hydrolysis preliminary test performed at 50°C, significant decomposition was observed at pH 4, 7 and 9. Therefore the purpose of this study was to perform the hydrolysis main test and evaluate the abiotic degradation of SA04 at pH 4, 7 and 9 at different temperatures.

Rate constants and half-lives based on the measured data

pH

Temperature

Slope

kobs

t1/2

regression coefficient

4

25°C

-0.0038

0.0088

79 h

0.995

37°C

-0.0135

0.0311

22 h

0.995

50°C

-0.0277

0.0637

11 h

0.988

7

25°C

-0.0017

0.0039

176 h

0.989

37°C

-0.0120

0.0276

25 h

0.994

50°C

-0.0384

0.0885

8 h

0.975

9

25°C

-0.1122

0.2585

2.7 h

0.999

37°C

-0.4239

0.9764

0.7 h

0.963

50°C

-0.5268

1.2133

0.6 h

0.930

 

At the end of the study, solutions of the most likely degradation products, DYDJ 5305, DYDJ 5310, DYDJ 5312 and DYDJ 5313 (provided by the Sponsor) were also injected in the series of the test samples in order to confirm the identity of the degradation products.

At pH 7 and pH 9 retention time of the main hydrolysis product (11.0 min) significantly deviates from the retention time of the above standards. Its amount corresponds to approximately 50-77% of the main hydrolysis product. Main component of the provided standards elutes at different retention times: DYDJ 5313 (7.4 min), DYDJ 5310 (8.6 min), DYDJ 5305 (8.9 min) DYDJ 5312 (12.1 min). Therefore, identity of the main hydrolysis product was not supported by this experiment. However, the retention time of a main hydrolysis product at pH 4 confirms to the retention time of DYDJ 5310. Its amount corresponds to approximately 65-74% of the main hydrolysis product.