Registration Dossier

Administrative data

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

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
May 31, 2008
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
April 13, 2004
Qualifier:
according to
Guideline:
EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)
Version / remarks:
October 2008
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
white to brownish
Details on test material:
Batch 151222
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products: The concentrations of the test item were determined immediately after preparation (t=0) and at several sampling points after t=0.
- Sampling method: 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.
- Sampling intervals/times for pH measurements: The pH of each of the test solutions (except for the blanks) was determined at each sampling time.
- Sample storage conditions before analysis: The samples not analyzed on the sampling day were stored in the freezer. Storage stability under these conditions was determined by the analysis of additional quality control (QC) samples prepared at half the nominal concentration of the test samples.
Buffers:
Acetate buffer pH 4, 0.1 M
A solution of 16.7% 0.1 M sodium acetate in water and 83.3% 0.1 M acetic acid in water. Buffer contained 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.1 M
A solution of 0.1 M potassium di-hydrogen-phosphate in water adjusted to pH 7 using 10N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.
Borate buffer pH 9, 0.1 M
A solution of 0.1 M boric acid in water and 0.1 M potassium chloride in water adjusted to pH 9 using 10N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.
Details on test conditions:
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 item was spiked to the solutions at a target concentration of 2 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.
The spiking volume was < 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.

Duration of testopen allclose all
Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
1.96 mg/L
Remarks:
Tier I
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
2.04 mg/L
Remarks:
Tier I
Duration:
5 d
pH:
9
Temp.:
20 °C
Initial conc. measured:
>= 1.98 - <= 1.99 mg/L
Remarks:
Tier I
Duration:
790 h
pH:
7
Temp.:
20 °C
Initial conc. measured:
2.13 mg/L
Remarks:
Tier II
Duration:
455 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
2.12 mg/L
Remarks:
Tier II
Duration:
120 h
pH:
7
Temp.:
60 °C
Initial conc. measured:
2.12 mg/L
Remarks:
Tier II
Duration:
766 h
pH:
9
Temp.:
20 °C
Initial conc. measured:
2.18 mg/L
Remarks:
Tier II
Duration:
770 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
2.18 mg/L
Remarks:
Tier II
Duration:
145 h
pH:
9
Temp.:
60 °C
Initial conc. measured:
>= 2.18 - <= 2.19 mg/L
Remarks:
Tier II
Number of replicates:
duplicate test samples
Positive controls:
no
Negative controls:
yes
Remarks:
blank buffer solutions

Results and discussion

Preliminary study:
At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was observed after 5 days. According to the guideline, the higher Tier test was required to determine the half-life time of the test item.
A degree of hydrolysis of < 10% was observed at pH 4 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.
No test item was detected in the blank buffer solutions.
The mean recoveries of the 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.
Test performance:
The mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 90-110% for both pH 7 and 9. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.
The pH was in the range 7.0 – 7.1 and 9.0-9.1.
No test item was detected in the blank buffer solutions.
Transformation products:
not measured
Total recovery of test substance (in %)open allclose all
% Recovery:
>= 95 - <= 100
pH:
7
Temp.:
20 °C
Duration:
>= 0 - <= 790 h
% Recovery:
>= 2.4 - <= 100
pH:
7
Temp.:
50 °C
Duration:
>= 0 - <= 455 h
% Recovery:
>= 3.2 - <= 100
pH:
7
Temp.:
60 °C
Duration:
>= 0 - <= 120 h
% Recovery:
>= 95 - <= 100
pH:
9
Temp.:
20 °C
Duration:
>= 0 - <= 766 h
% Recovery:
>= 3.9 - <= 100
pH:
9
Temp.:
50 °C
Duration:
>= 0 - <= 770 h
% Recovery:
>= 7.8 - <= 100
pH:
9
Temp.:
60 °C
Duration:
>= 0 - <= 145 h
Dissipation DT50 of parent compoundopen allclose all
pH:
7
Temp.:
20 °C
Hydrolysis rate constant:
0 h-1
DT50:
283 d
Type:
(pseudo-)first order (= half-life)
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0 h-1
DT50:
128 d
Type:
(pseudo-)first order (= half-life)
pH:
7
Temp.:
50 °C
Hydrolysis rate constant:
0.008 h-1
DT50:
3.5 d
Type:
(pseudo-)first order (= half-life)
pH:
7
Temp.:
60 °C
Hydrolysis rate constant:
0.029 h-1
DT50:
1 d
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
20 °C
Hydrolysis rate constant:
0 h-1
DT50:
269 d
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
0 h-1
DT50:
139 d
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
50 °C
Hydrolysis rate constant:
0.004 h-1
DT50:
6.8 d
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
60 °C
Hydrolysis rate constant:
0.017 h-1
DT50:
1.7 d
Type:
(pseudo-)first order (= half-life)
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered (if yes): /

Any other information on results incl. tables

pH 7:

Table 16        
Main Test pH 7: Statistical Parameters Regression Curves

Temperature
(°C)

Slope
[hours-1]

Intercept

Coefficient of correlation

20

-4.42´10-5

1.99

0.574

50

-3.62´10-3

2.08

0.997

60

-1.24´10-2

2.11

0.98

pH 9:

Table 21        
Main Test pH 9: Recoveries

Temperature

(°C)

Nominal concentration
[mg/L]

Analyzed concentration
[mg/L]

Recovery
[%]

Individual

Mean

20

2.00

2.18

109

109

 

2.00

2.18

109

 

50

2.00

2.18

109

109

 

2.00

2.18

109

 

60

2.00

2.19

109

109

 

2.00

2.18

109

 

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Executive summary:

The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of CH02906 at pH values normally found in the environment (pH 4-9).

Hydrolysis of the test item followed first-order reaction rates and the associated half-life times were as follows:

pH 4

pH 7

pH 9

Temperature
[°C]

t½

Temperature
[°C]

t½

Temperature
[°C]

t½

 

 

20

283 days

20

 269 days

25

> 1 year

25

128 days

25

139 days

 

 

50

3.5 days

50

6.9 days

 

 

60

1.0 days

60

1.7 days