Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 June 2017 to 04 September 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Study design

Analytical monitoring:
yes
Details on sampling:
Samples were taken at t=0 hours, 24 hours and at 5 days (at pH 4 only). Blank buffer solutions containing a similar content of blank spiking solution were treated similarly as the test samples and analysed at t=0 hours.
Buffers:
Acetate buffer pH 4, 0.01 M:
solution of 16.7% 0.01 M sodium acetate and 83.3% 0.01 M acetic acid. The buffer contains 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.01 M:
solution of 0.01 M potassium di-hydrogenphosphate 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 and 0.01 M potassium chloride adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.
Duration of testopen allclose all
Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
14.2 mg/L
Duration:
24 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
14.5 mg/L
Duration:
24 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
14.2 mg/L
Number of replicates:
2/sampling time

Results and discussion

Preliminary study:
At pH 4, a degree of hydrolysis of ≥ 10% was observed after 5 days.
At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was already observed after 24 hours.
No test item was detected in the blank buffer solutions.

The mean recoveries of the test item containing buffer solutions at t=0 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.
Transformation products:
not measured
Dissipation half-life of parent compoundopen allclose all
Key result
pH:
4
Temp.:
20 °C
Half-life:
>= 41 - <= 138 d
Type:
not specified
Remarks on result:
other: based on extrapolation of the results at 50 °C
Key result
pH:
7
Temp.:
20 °C
Half-life:
>= 1 - <= 5 d
Type:
not specified
Remarks on result:
other: based on extrapolation of the results at 50 °C
Key result
pH:
9
Temp.:
20 °C
Half-life:
>= 0.2 - <= 0.7 d
Type:
not specified
Remarks on result:
other: based on extrapolation of the results at 50 °C

Any other information on results incl. tables

Preliminary Test: Hydrolysis of the Test Item at pH 4, pH 7 and pH 9

pH code

Sampling time

Analyzed concentration
[mg/L]

Degree of hydrolysis
[%]

pH

Individual

Mean

pH 4

0 hours

14.2

 

 

4.0

 

 

14.1

 

 

4.0

 

24 hours

11.1

22

21

4.0

 

 

11.4

20

 

4.0

 

5 days

1.79

87

87

4.0

 

 

1.97

86

 

4.0

pH 7

0 hours

14.4

 

 

7.1

 

 

14.5

 

 

7.1

 

24 hours

n.d.

100

100

7.1

 

 

n.d.

100

 

7.1

 

5 days

n.a.

n.a.

n.a.

n.a.1

 

 

n.a.

n.a.

 

n.a.1

pH 9

0 hours

14.3

 

 

9.0

 

 

14.1

 

 

9.0

 

24 hours

n.d.

100

100

9.1

 

 

n.d.

100

 

9.1

 

5 days

n.a.

n.a.

n.a.

n.a.1

 

 

n.a.

n.a.

 

n.a.1

n.a.                                 Not applicable. n.d.                                Not detected.              1 Determination over 5 days was not performed since the test item was 100% hydrolyzed after 24 hours.                   

 

Applicant's summary and conclusion

Conclusions:
At pH 4, a degree of hydrolysis of ≥ 10% was observed after 5 days.
At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was already observed after 24 hours.
The half-life time of the substance at 20°C was:
t½ pH 4: > 41 d
pH 7 1-5 d
pH 9 0.2-0.7 d
Executive summary:

The rate of hydrolysis of the substance as a function of pH was determined at pH values normally found in the environment (pH 4-9).

The buffer solutions were filter-sterilised through a 0.2 μm FP 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. The test substance was spiked to the solutions at a target concentration of 15 mg/L using a spiking solution in acetonitrile.  For each sampling time, duplicate sterile vessels under vacuum were filled with 6 mL test solution and placed in the dark in a temperature controlled environment at 50.1°C ± 0.1°C. Since at pH 7 and pH 9 the test item was completely hydrolysed after 24 hours, only pH 4 was sampled after 5 days.  The samples taken at t=24 hours and t=5 days were cooled to room temperature using running tap water.  

Blank buffer solutions containing a similar content of blank spiking solution were treated similarly as the test samples and analysed at t=0.

The pH of each of the test solutions (except for the blanks) was determined at each sampling time.

At pH 4, a degree of hydrolysis of ≥ 10% was observed after 5 days. At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was already observed after 24 hours.  No test item was detected in the blank buffer solutions.

Predicted t1/2and 90% hydrolysis based on pre-test results

pH

Estimated t1/2
[days]

Estimated 90% hydrolysis
[days]

Minimum

Maximum

Minimum

Maximum

 

 

 

 

 

pH 4

41

138

135

458

 

 

 

 

 

 

 

 

 

 

pH 7

1

5

4

14

 

 

 

 

 

 

 

 

 

 

pH 9

0.2

0.7

0.7

2