1,4-Diazabicyclo[2.2.2]octane-2-methanol

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP Compliance Monitoring Program, Health Care Inspectorate, Ministry of Health, Welfare and Sport, Den Haag, The Netherlands

Analytical monitoring:

yes

Details on sampling:

- Sampling method:
A preliminary test was performed with test substance solutions prepared in 0.01 M buffer solutions at pH 4, 7 and 9. Since the 0.01 M pH 4 and 7 buffers were not sufficient to maintain the pH at a range of ± 0.1 from the nominal pH, an additional preliminary test was performed using 0.1 M buffer solutions at pH 4 and 7.
All solutions were prepared at a concentration of 200 mg/L. Each solution was filter-sterilised through a 0.2 µmFP 30/0.2 CA-S filter (Whatman, Dassel, Germany) and transferred into a sterile vessel. To exclude oxygen, nitrogen gas was purged through the solution for 5 minutes. For each sampling time, duplicate sterile vessels under vacuum were filled with 6 mL test solution. The test solutions were stored in the dark at 49.9 ± 0.2 °C.

Buffers:

- Acetate buffer pH 4, 0.01 M: Solution of 16.7% 0.01 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. The buffer contains 0.0009% (w/v) sodium azide.
- Acetate buffer pH 4, 0.1 M: Solution of 16.7% 0.1 M sodium acetate in water and 83.3% 0.1 M acetic acid in water. The buffer contains 0.0009% (w/v) sodium azide.
- Phosphate buffer pH 7, 0.01 M: Solution of 0.01 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.
- Phosphate buffer pH 7, 0.1 M: Solution of 0.1 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.
- Borate buffer pH 9, 0.01 M: Solution of 0.01 M boric acid in water and 0.01 M potassium chloride in water adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Details on test conditions:

The concentration of the test substance in the test samples was determined immediately after preparation (t = 0) and after 5 days. The samples taken at t = 5 days were cooled to room temperature using running tap water. The samples were diluted with buffer solutions and analysed. Blank buffer solutions were treated similarly as the test samples and analysed at t = 0. The pH of each of the test solutions (except for the blank solutions) was determined at each sampling time.

Duration:

5 d

Initial conc. measured:

207 mg/L

Duration:

5 d

Initial conc. measured:

178 mg/L

Duration:

5 d

Initial conc. measured:

189 mg/L

Duration:

5 d

Initial conc. measured:

176 mg/L

Duration:

5 d

Initial conc. measured:

216 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Transformation products:

not measured

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

At each pH value a degree of hydrolysis of < 10 % was observed after 5 days. According to the guideline, performance of a tier 2 study is not required.

% Recovery:

100 - 108

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

95 - 108

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

95 - 98

pH:

9

Temp.:

50 °C

Duration:

5 d

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Details on results:

The determined average concentrations of 95 to 108% (at day 5) reveal that the test item is stable and not prone to hydrolysis over 5 days when employing pH values of 4, 7 and 9. According to the OECD procedure, no further testing is required.
A small peak was observed in the chromatograms of the blank buffer solutions. It was considered not to derive from the buffer solutions since a similar response was obtained in water. Since the rate of hydrolysis is determined as a relative value it does not affect the integrity of the study.

Description of key information

Hydrolysis is not relevant in regard to abiotic degradation in the environment (DT50 > 1 yr).

Additional information

One study investigating hydrolysis as a function of pH for the test substance is available. The study was performed according to OECD guideline 111.The potential of the substance to hydrolyse was tested over 5 days under conditions of a preliminary study at pH 4, 7and 9 at 50 °C. The determined average concentrations of 95 to 108% (w/w) after 5 days revealed that the test item is stable and not prone to hydrolysis over 5 days at pH values of 4, 7 and 9 (Tosoh Corporation, 2014). Thus, according to the OECD procedure, no further testing is required.