3-methylthiazolidine-2-thione

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-06-14 - 2016-06-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

European Commission Regulation (EC) No. 440/2008, C.7. abiotic degradation: hydrolysis as a function of pH

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

OECD test guideline OECD 111 Hydrolysis as a function of pH

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, Energie, Landwirtschaft und Verbraucherschutz, Mainzer Straße 80, D65189 Wiesbaden

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: after 5 days

Buffers:

Preparation of buffer solutions
pH4:
21.01 g citric acid monohydrate was dissolved in 200 ml sodium hydroxide solution (c = 1 mol/l). This solution was filled up to a volume of 1000 ml with demineralized water. 44 ml of hydrochloric acid (c = 1 mol/l) was added to 560 ml of this solution and filled up to a volume of 1000 ml with demineralized water. The pH value of the buffer solution was adjusted to pH 4 with hydrochloric acid or sodium hydroxide solution for each hydrolysis temperature.
pH 7:
13.61 g potassium dihydrogen phosphate was dissolved in 1000 ml demineralized water. 30 ml of sodium hydroxide solution (c = 1 mol/l) was added to 500 ml of this solution and filled up to a volume of 1000 ml with demineralized water. The pH of the buffer solution value was adjusted to pH 7 with hydrochloric acid or sodium hydroxide solution for each hydrolysis temperature.
pH 9:
7.46 g potassium chloride and 6.18 g boric acid were dissolved in 1000 ml demineralized water. 21 ml of sodium hydroxide solution (c = 1 mol/l) was added to 500 ml of this solution and filled up to a volume of 1000 ml with demineralized water. The pH value of the buffer solution was adjusted to pH 9 with hydrochloric acid or sodium hydroxide solution for each hydrolysis temperature.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used / Sterilisation method: The used volumetric flasks are baked out at 110 °C and flooded with nitrogen.

TEST MEDIUM
- Volume used/treatment 50 ml
- Kind and purity of water: Demineralized water (pH 5 - 7), Roth
- Preparation of test medium: According to information by the sponsor the water solubility of the test item is 3.65 g/l. As the test item concentration should not exceed 0.01 mol/l solutions of the test item were prepared by dissolving approx. 100 - 130 mg of the test item in 50 ml of the relevant buffers (filled up to the mark).

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

111.1 mg/L

Remarks:

Experiment 1

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

120 mg/L

Remarks:

Experiment 2

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

134.7 mg/L

Remarks:

Experiment 3

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

111.4 mg/L

Remarks:

Experiment 4

Duration:

5 d

pH:

9.2

Temp.:

50 °C

Initial conc. measured:

102.4 mg/L

Remarks:

Experiment 5

Duration:

5 d

pH:

9.2

Temp.:

50 °C

Initial conc. measured:

98.9 mg/L

Remarks:

Experiment 6

Number of replicates:

2 per pH

Positive controls:

no

Negative controls:

no

Preliminary study:

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days, therefore the test item was hydrolytically stable. No additional testing (Tier 2 and 3) was required.

Transformation products:

no

% Recovery:

99.9

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

Experiment 1

% Recovery:

101.6

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

Experiment 2

% Recovery:

106

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

Experiment 3

% Recovery:

100.1

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

Experiment 4

% Recovery:

101

pH:

9.2

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

Experiment 5

% Recovery:

99.8

pH:

9.2

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

Experiment 6

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days.

Key result

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days.

pH:

9.2

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days.

Individual results

 

Table Results of the preliminary test (experiments 1 to 6)

Experiment	pH of buffer solution	pHof test item solution^3	Duration in d	c0/ mg/l	ct/mg/l	ct/c0	Decomposition/ %
1	4.0	4.0	5	111.1	111.0	0.999	0.1
2	4.0	4.0	5	120.0	121.9	1.016	-1.6
3	7.0	7.0	5	134.7	142.8	1.060	-6.0
4	7.0	7.0	5	111.4	111.4	1.001	-0.1
5	9.0	9.2	5	102.4	103.4	1.010	-1.0
6	9.0	9.2	5	98.9	98.7	0.998	0.2

 

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days, therefore the test item was hydrolytically stable. No additional testing (Tier 2 and 3) was required.

 

 

Final results

 

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days. The results for these determinations are summarized below:

 

Table Summarized results of the preliminary test (tier 1)

Experiment	pHof buffer solution	Decomposition/ %	Decomposition I (mean value)/ %
1	4.0	0.1	-0.7
2	4.0	-1.6
3	7.0	-6.0	-3.0
4	7.0	-0.1
5	9.0	-1.0	-0.4
6	9.0	0.2

 

The test item was hydrolytically stable. No additional testing (tier 2 and 3) was required.

Validity criteria fulfilled:

not specified

Conclusions:

The study was performed according to OECD TG 111 with no deviations, the results were so obtained via a scientifically reasonable method. Hence, there is no doubt that the obtained results are not reliable: At pH 4, 7 and 9 and at 50±0.5°C less than 10 % of the test item hydrolysed within 5 days, therefore the test item was hydrolytically stable. No additional testing (Tier 2 and 3) was required. This conclusion is in congruence with the stipulations set out in OECD TG 111, no further testing, i.e. determination of the hydrolysis rate and products is required, as the substance is stable.

Executive summary:

Hydrolysis of 3-Methyl-thiazolidin-thion-2 at ca 99 - 135mg/L was studied at 50ºC in sterile aqueous buffered solutions at pH 4, pH 7 and pH 9 for 5 days.  The experiment was conducted in accordance with EU method C.7 and OECD TG 111, and in compliance with GLP.  Samples were analysed at 0 and 5 days, and the test material was analysed by HPLC/UV-Vis.

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days, therefore the test item was hydrolytically stable. No additional testing (Tier 2 and 3) was required. This study is classified acceptable and satisfies the guideline requirement for hydrolysis study.

Description of key information

Hydrolysis: Hydrolytically stable based on tier 1 results at pH 4, 7, 9 (OECD 111, GLP)

Additional information

At pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days, therefore the test item was hydrolytically stable. No additional testing (Tier 2 and 3) was required.