5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-11-11 to 2015-11-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

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:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: A15CB1464
- Expiration date of the lot/batch: 2016-02-29 (retest date)
- Purity test date: 2015-06-01 (certificate of analysis release date)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: no data

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products:
* Tier 1: at the beginning and after 5 days.

- Sampling method:
* Tier 1: Concentration of the test item in the test sample was determined immediately after preparation. The samples taken at t=5 days were cooled to room temperature using running tap water. The samples were diluted in a 8.5:1.5 (v:v) ratio with acetonitrile and analysed.

Buffers:

- pH:
* Tier 1: 4.0, 7.0, and 9.0

- Type, final molarity and composition of buffer:
* buffer pH 4: 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.
* buffer pH 7: solution of 0.1 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 10 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.
* buffer pH 9: solution of 0.1 M boric acid in water and 0.1 M potassium chloride in water adjusted to pH 9 using 10 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: sterile vessel
- Sterilisation method: buffer solutions were filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Wathman, Dassel, Germany) and transferred into a sterile vessel.
- Lighting: in the dark
- Measures taken to avoid photolytic effects: vessels placed in the dark
- Measures to exclude oxygen: nitrogen gas was purged through the solution for 5 minutes
- Details on test procedure for unstable compounds: no data
- Details of traps for volatile, if any: not applicable
- If no traps were used, is the test system closed/open: under vacuum
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no

TEST MEDIUM
- Volume used/treatment: 6 mL
- Kind and purity of water: Milli-Q
- Preparation of test medium: The test item was spiked to the solutions at a target concentration of 8 mg/L using a spiking solution in methanol.
- Renewal of test solution: not applicable
- Identity and concentration of co-solvent: not applicable

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Dissolved oxygen: no data

Duration:

5 d

pH:

4

Temp.:

50.2 °C

Initial conc. measured:

8.47 - 8.48 mg/L

Duration:

5 d

pH:

7

Temp.:

50.2 °C

Initial conc. measured:

8.08 - 8.1 mg/L

Duration:

5 d

pH:

9

Temp.:

50.2 °C

Initial conc. measured:

8.31 - 8.34 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Statistical methods:

no data

Preliminary study:

The preliminary hydrolysis tests were performed at 50.2°C +/- 0.1°C. At pH 4, pH 7 and pH 9 a degree of hydrolysis of < 10% was observed after 5 days. It demonstrated that the half-life time of the test item at 25°C is > 1 year. According to the guideline, no further tests were required.

Transformation products:

no

% Recovery:

106

pH:

4

Temp.:

50.2 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

106% for both replicates

% Recovery:

101

pH:

7

Temp.:

50.2 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

101% for both replicates

% Recovery:

104

pH:

9

Temp.:

50.2 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

104% for both replicates

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Validity criteria fulfilled:

yes

Remarks:

No test item was detected in the blank buffer solutions. The mean recoveries of the buffer solutions fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.

Conclusions:

T000990 was found to be hydrolytically stable at pH 4.0, pH 7.0 and pH 9.0 with an estimated half-life time higher than 1 year at 25°C. Therefore, no further testing was performed.

Description of key information

One study (Brekelmans, 2016) was performed according to OECD guideline 111 and regarded

as a key study (Klimisch score of 1). A half-life time of > 1 year at 25 °C and pH 7 was determined for T000990.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

The determination of the hydrolysis as a function of pH of T000990 was performed according to OECD guideline 111 (Brekelmans, 2016). A preliminary test was performed at 50°C at pH 4.0, 7.0 and 9.0. As the test item was found to be stable according to the criteria given in the guideline, no main test was performed. A half-life time of > 1 year at 25 °C and pH 7 was determined for T000990.