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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-07-27 to
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
adopted 13 April 2004
Deviations:
no
Principles of method if other than guideline:
Study was performed to determine the stability of the test substance in different aqueous media to clarify the feasibility and design of experimental studies regarding physico-chemical, environmental fate and ecotoxicological properties.
GLP compliance:
no
Analytical monitoring:
yes
Remarks:
Liquid chromatography and mass spectrometry
Details on sampling:
- Sample storage conditions before analysis: 100 mg/L test item was dissolved in buffer solution pH 4, 7 and 9, respectively and analysed directly.
Buffers:
- pH: 4, 7 and 9
- Type and final molarity of buffer: n/a
- Composition of buffer: n/a
Number of replicates:
2
Positive controls:
no
Negative controls:
no
Transformation products:
yes
No.:
#1
No.:
#2
Remarks on result:
not measured/tested
Key result
pH:
4
DT50:
0.059 h
Type:
not specified
Remarks on result:
other: Temperature and Hydrolysis rate constant not reported
Key result
pH:
7
DT50:
0.257 h
Type:
not specified
Remarks on result:
other: Temperature and Hydrolysis rate constant not reported
Key result
pH:
9
DT50:
0.712 h
Type:
not specified
Remarks on result:
other: Temperature and Hydrolysis rate constant not reported

Determination of Hydrolysis in Aqueous Phase – pH 4

Nominal concentration, test item: 100 mg/L

pH 4

Time [h]

Peak Area

ln Peak Area

%

0.000

33509948

17.3

-

0.183

675904

13.4

2

0.364

179466

12.1

0.5

0.547

43528

10.7

0.1

%          = percent of initial concentration, t0set to 100%

Hydrolysis in Aqueous Phase – pH 4

pH 4

Slope of regression graph

-0.117

Correlation factor [r2]

0.923

Reaction rate constantk[1/s]

3.24 ∙ 10-3

Half-life[h]

0.0594

Half-life[min]

3.56

 

 Determination of Hydrolysis in Aqueous Phase – pH 7

Nominal concentration, test item: 100 mg/L

pH 7

Time [h]

Peak Area

ln Peak Area

%

0.000

56905440

17.9

-

0.183

29781291

17.2

52

0.3651)

52813611)

15.51)

91)

0.736

7279096

15.8

13

0.919

4985612

15.4

9

1.10

3174099

15.0

6

1.28

1808882

14.4

3

1.47

1143522

14.0

2

1.65

600828

13.3

1

1.83

357862

12.8

1

% = percent of initial concentration, t0set to 100%

1)= outlier, not taken into account

Hydrolysis in Aqueous Phase – pH 7

pH 7

Slope of regression graph

-2.70

Correlation factor [r2]

0.997

Reaction rate constantk[1/s]

7.49 ∙ 10-4

Half-life[h]

0.257

Half-life[min]

15.4

Determination of Hydrolysis in Aqueous Phase – pH 9

Nominal concentration, test item: 100 mg/L

pH 9

Time [h]

Peak Area

ln Peak Area

%

0.000

128982791

18.7

-

0.183

86149063

18.3

67

0.365

64018083

18.0

50

0.547

50905504

17.8

39

0.730

43442552

17.6

34

0.913

35485067

17.4

28

1.10

30533632

17.2

24

1.28

26036767

17.1

20

1.46

22208419

16.9

17

1.64

19819906

16.8

15

2.01

15356634

16.6

12

2.19

12085931

16.3

9

2.38

10140678

16.1

8

% = percent of initial concentration, t0set to 100%

Hydrolysis in Aqueous Phase – pH 9

pH 9

Slope of regression graph

-0.974

Correlation factor [r2]

0.977

Reaction rate constantk[1/s]

2.70 ∙ 10-4

Half-life[h]

0.712

Half-life[min]

42.7

Validity criteria fulfilled:
not applicable
Conclusions:
The present study was conducted in order to provide information about the stability of Tetrahydrofolic acid in aqueous solutions. The water solubility could not be determined due to fast hydrolysis of the substance.The half-lifes were determined in 0.01 M CaCl2 solution, in buffer solutions at pH 4, 7 and 9 and in Algae Dilution Medium. T1/2 was 0.4 h in 0.01M CaCl2, and 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9 with LC-MS. Plots of the stability of Tetrahydrofolic acid in Algae Dilution Medium showed a decline of the parent substances and an increase of two hydrolysis products 2-amino-6-methylpteridin-4(1H)-one and (2S)-2-(4-aminobenzamido)pentanedioic acid.

Description of key information

- study on hydrolysis performed similar to OECD guideline 111, non-GLP test, half-lifes T1/2 was 0.4 h in 0.01M CaCl2, and 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9 with LC-MS, determination of two hydrolysis products 2-amino-6-methylpteridin-4(1H)-one and (2S)-2-(4-aminobenzamido)pentanedioic acid.

Key value for chemical safety assessment

Additional information

The present study was conducted in order to provide information about the stability of Tetrahydrofolic acid in aqueous solutions. The water solubility could not be determined due to fast hydrolysis of the substance.The half-lifes were determined in 0.01 M CaCl2 solution, in buffer solutions at pH 4, 7 and 9 and in Algae Dilution Medium. T1/2 was 0.4 h in 0.01M CaCl2, and 0.0594 h for pH 4, 0.257 h for pH 7 and 0.712 h for pH 9 with LC-MS. Plots of the stability of Tetrahydrofolic acid in Algae Dilution Medium showed a decline of the parent substances and an increase of two hydrolysis products 2-amino-6-methylpteridin-4(1H)-one and (2S)-2-(4-aminobenzamido)pentanedioic acid.