1,3,4-thiadiazole-2,5-dithiol

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-10-05 - 2016-10-12 (experimental phase); 2016-08-18 - 2016-11-24 (study initiation - final report)

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 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, Germany

Specific details on test material used for the study:

The test item was tested as received. No further preliminary treatment such as drying or milling was performed.

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: only parent: upon preparation and day 5
- Sampling method: aliquots were taken
- Sampling intervals/times for pH measurements: upon preparation and day 5
- Other observation, if any (e.g.: precipitation, color change etc.): none stated

Buffers:

- pH: 4, 7, 9

pH 4:
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: 50 ml
- Sterilisation method: The used volumetric flasks are baked out at 110 °C and flooded with nitrogen. Solutions of the test item are prepared in the relevant buffers. The standards for calibration and recheck are freshly prepared.

TEST MEDIUM
- Volume used/treatment
- Kind and purity of water: demineralized water
- Preparation of test medium: The test item is added as an aqueous solution into the different buffer solutions (pH 4, 7 and 9). The concentration of the solution should not exceed 0.01 M or half of the saturation concentration of the test item. If it is necessary for adequate dissolution, the use of low amounts of water miscible solvents (such as acetonitrile, acetone, ethanol) is permitted as solubilizer for the test item but this should not normally exceed 1 % v/v.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

>= 488.5 - <= 586.5 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

>= 431.9 - <= 504.2 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

>= 484.1 - <= 599.2 mg/L

Number of replicates:

2 per pH

Positive controls:

no

Negative controls:

no

Preliminary study:

Table: Results of the preliminary test (experiments 1 to 6)
Experiment pH of buffer solution pH of test item solution Duration in d c0 / mg/l ct / mg/l ct / c0 Decomposition / %
1 4.0 4.0 5 488.5 472.9 0.968 3.2
2 4.0 4.0 5 586.5 495.6 0.848 15.5
3 7.0 7.0 5 504.2 520.6 1.033 -3.3
4 7.0 7.1 5 431.9 417.5 0.967 3.3
5 9.0 9.1 5 484.1 467.9 0.967 3.4
6 9.0 9.1 5 599.2 582.6 0.972 2.8
Experiment 2 showed an unusual deviation compared to the other five experiments. As there was no further indication (e.g. instable standard solutions) that the test item is not hydrolytic stable, this experiment was not taken into account for further evaluations. The deviation may be caused by a dilution error.
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

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

n/a

% Recovery:

96.8

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

100

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

96.9

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

3.2% decomposition

Key result

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

0.0% decomposition

Key result

pH:

9

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

3.1% decomposition

Details on results:

TEST CONDITIONS
- Anomalies or problems encountered (if yes): Experiment 2 showed an unusual deviation compared to the other five experiments. As there was no further indication (e.g. instable standard solutions) that the test item is not hydrolytic stable, this experiment was not taken into account for further evaluations. The deviation may be caused by a dilution error.

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 2,5-Dimercapto-1,3,4-thiadiazole at ca 431.9-599.2 mg/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, at pH 4, 7 and 9 less than 10 % of the test item hydrolysed within 5 days at 50°C (OECD 111, GLP)