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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
Hydrolysis as a function of pH (2004)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Storage conditions: room temperature, dark, air-tight
Storage place: Desiccator
IR spectrum of the test substance was measured before the test and after. Spectrum were consistent indicating that the test substance was stable under the storage conditions
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
Samples taken at the start of the experiment (0 hours) and after 5 days
Buffers:
Prepared buffer solutions were put in an incubator and stood more than 24 hours. A pH of the buffer solutions was measured on the experimental starting day and adjusted by dropwise additional of HCl or NaOH aqueous solution as necessary. Then, the dissolved oxygen was excluded by bubbling nitrogen for approx. 5 minutes.

pH 4.0
Mixture of 4.0mL of 0.1N NaOH and 500mL of 0.1M potassium hydrogen phthalate was diluted to 100mL with ultra pure water

pH 7.0
Mixture of 296mL of 0.1N NaOH and 500mL of 0.1M KH2PO4 was diluted to 1000mL with ultra pure water

pH 9.0
Mixture of 213 mL of 0.1N NaOH and 500mL of 0.1M KCl / 0.1M H3BO3 was diluted to 1000mL with ultra pure water

Aq. solution of 0.1M potassium hydrogen phthalate:
20.42g of potassium hydrogen phthalate was diluted to 1000 mL with ultra pure water
Aq. solution of 0.1M KH2PO4:
13.61g of KH2PO4 was diluted to 1000mL with ultra pure water
Aq solution of 0.1M KCl/0.1M H3BO3
7.46g of KCl and 6.18g of H3BO3 were diluted to 1000mL with ultra pure water
Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Glass flask
- Apparatus: Thermostatic water bath: Water Bath Shaker MM-10 (No.1)
- Lighting: light shielded
- Glass flasks were capped with a lid during experiments

TEST MEDIUM
- Volume used: 300mL
- Kind and purity of water: Ultra pure water

PREPARATION OF TEST SOLUTION
Test substance (200mg) was weighed, then dissolved and filled up to 20mL with acetonitrile (HPLC grade) to prepared a 10000 mg/L stock solution. A 300 µL of the stock solution (10000 mg/L) was sampled by a micro syringe and added to 300 mL of buffer solution in a gas flask (Acetonitrile 0.1% v/v). Test solutions were shaken and left for more than 2 hours.

Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
10 mg/L
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
10 mg/L
Duration:
5 d
pH:
9
Temp.:
50 °C
Initial conc. measured:
10 mg/L
Number of replicates:
2 per pH
Positive controls:
no
Negative controls:
yes
Remarks:
Blank test
Statistical methods:
None required
Preliminary study:
Average rate of hydrolysis
pH 4 = 0% (5 days) at 50°C
pH 7 = 4% (5 days) at 50°C
pH 9 = 4% (5 days) at 50°C
Test performance:
Test was judged to be valid. All results satisfied the validity criteria.
Transformation products:
no
% Recovery:
> 93 - < 96
pH:
4
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
ca. 100
pH:
7
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
> 93 - < 100
pH:
9
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
pH:
4
Temp.:
25 °C
DT50:
> 1 yr
Remarks on result:
hydrolytically stable based on preliminary test
pH:
7
Temp.:
25 °C
DT50:
> 1 yr
Remarks on result:
hydrolytically stable based on preliminary test
pH:
9
Temp.:
25 °C
DT50:
> 1 yr
Remarks on result:
hydrolytically stable based on preliminary test
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

Results with reference substance:
Not applicable

Table 1 Rate of hydrolysis

 

A

B

C

D

E

Temperature

°C

Sample description

Date of measurement

(yyyy/m/d)

Correction day

Peak area of processed sample count

Peak area of standard solution count

Measured concentration of test substance

mg/L

Rate of residual

Rate of hydrolysis

50

Individual

%

Average

%

Individual

%

Average

%

pH 4 – 1

2019/6/13

0

3632.352

3893.565

9.3

-

100

-

0

2019/6/18

5

3734.925

3929.117

9.5

102

-2

pH 4 – 2

2019/6/13

0

3720.429

3893.565

9.6

-

-

2019/6/18

5

3701.957

3929.117

9.4

98

2

pH 7 – 1

2019/6/13

0

3880.287

3893.565

10.0

-

97

-

4

2019/6/18

5

3855.598

3929.117

9.8

98

2

pH 7 – 2

2019/6/13

0

3891.393

3893.565

10.0

-

-

2019/6/18

5

3743.789

3929.117

9.5

95

5

pH 9 – 1

2019/6/13

0

3619.607

3893.565

9.3

-

97

-

4

2019/6/18

5

3609.440

3929.117

9.2

99

1

pH 9 - 2

2019/6/13

0

3895.651

3893.565

10.0

-

-

2019/6/18

5

3699.402

3929.117

9.4

94

6

 

Concentration of standard solution: F = 10.0 mg/L

 

Equations:

C = A/B x F

D = C5day/C0 x 100

E = 100-D

Table 2: Recovery Test

 

A

B

C

D

Sample description

Date of measurement

(yyyy/md/)

Correction day

Peak area of processed sample count

Peak area of standard solution count

Measured concentration of test substance

mg/L

Recovery rate

Individual

%

Average

%

pH4 – 1

2019/6/13

0

3632.352

3893.565

9.3

93

95

pH4 – 2

3720.429

3893.565

9.6

96

pH7 – 1

2019/6/13

0

3880.287

3893.565

10.0

100

100

pH7 – 2

3891.393

3893.565

10.0

100

pH 9 – 1

2019/6/13

0

3619.607

3893.565

9.3

93

97

pH 9 - 2

3895.651

3893.565

10.0

100

Concentration of standard solution: E 10.0 mg/L

Equations

C=A/B x E

D=C/E x 100

Validity criteria fulfilled:
yes
Conclusions:
Hydrolysis test (Tier1) was performed at pH 4, 7 and 9. Since less than 10% of all rates of hydrolysis was observed after 5 days, the test substance was considered to be hydrolytically stable at pH 4, 7 and 9 (Half-life at 25°C > 1 year)

Description of key information

OECD guideline, GLP compliant study. Hydrolysis study was conducted at pH 4, 7 and 9 over 5 days at 50°C.

The test substance was considered hydrolytically stable during the test. The result was extrapolated to show that the half-life of the substance is expected to be >1 year at 25°C at environmentally relevant pH levels.

Key value for chemical safety assessment

Additional information