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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From January 21, 1999 to February 11, 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
RA study
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes
Analytical monitoring:
yes
Remarks:
HPLC and UV/Vis detector
Details on sampling:
Optimal concentration of the test substance: 98-176 mg/L
- Preparation of the samples:
5 to 9 mg test substance in a 50 mL volumetric flask with the relevant buffer (pH 4 or 7)
- Preparation of the standards:
3 to 8 mg standard test substance in a 50 mL volumetric flask with the relevant buffer (pH 4 or 7)
- Hydrolysis test procedure:
The flask containing the hydrolysis mixture was placed in a thermostatically controlled water bath at a selected temperature for a specified time. Thereafter it was cooled immediately. The pH was controlled. The HPLC analysis of the unhydrolysed test substance (main compound) was performed without any delay.
Buffers:
- pH 4:
21.008 g citric acid monohydrat are dissolved in 200 mL sodium hydroxyde solution (1 mole/L) and the solution is adjusted to a volume of 1000 mLwith distilled water. 44 mL of hydrochloric acid (1 mole/L) are then added to 560 mL of this solution and adjusted to a volume of 1000 mL with distilled water. The solution is finally adjusted to pH 4.0 with NaOH or HCl.
- pH 7:
13.61g potassium dihydrogen phosphate are dissolved in 1000 mL distilled water. 29.63 mL of sodium hydroxyde solution (1 mole/L) are then added to 500 mL of this solution and adjusted to a volume of 1000 mL with distilled water. The solution is finally adjusted to pH 7.0 with NaOH or HCl.
- pH 9:
7.46 g potassium chloride and 6.184g boric acid are dissolved in 1000 mL distilled water. 500 mL of this solution are added to 21.3 mL sodium hydroxyde (1 mole/L) and adjusted to a volume of 1000 mL with distilled water. The solution is finally adjusted to pH 9.0 with NaOH or HCl.
Estimation method (if used):
In order to estimate the half-life period of the test substance at room temperature for pH 4 and 7, an extrapolation according to the Arrhenius equation was performed for both pH-values.
Details on test conditions:
Pretest at 50°C and pH 4, 7 and 9 for 2.4 h or 5 d.
Test 1 at 50°C and pH 4 for 9 to 32 h.
Test 2 at 50°C and pH 7 for 2 to 5 h.
Test 3 at 55°C and pH4 for 0.5 to 24h.
Test 4 at 65°C and pH4 for 0.25 to 8h.
Test 5 at 35°C and pH7 for 1 to 24.25h.
Initial conc. measured:
>= 100 - <= 180 mg/L
Remarks:
duration, pH and temperature: cfr "Details on test conditions"
Preliminary study:
The decomposition at pH 9 was higher than 50% after 2.4 h at 50°C. The test substance was thus considered hydrolytically instable at pH 9. According to the guideline, a half-life period of less than 1 day under environmental conditions (25°C) may be estimated. The pretests at pH 4 and 7 indicated that an examination of the hydrolysis kinetics was essential.
Transformation products:
not specified
Key result
pH:
9
Temp.:
25 °C
DT50:
< 1 d
Remarks on result:
other: the test substance may be considered hydrotically instable at pH 9 (< 1 d at 25°C)
Key result
pH:
4
Temp.:
25 °C
DT50:
8.5 d
Key result
pH:
7
Temp.:
25 °C
DT50:
3 d

Table 1. Results at pH 4

 Temperature  t1/2 (by regression)  Experiment
 50°C  25.61h  1
 55°C  17.61h  3
 65°C  8.54h  4
 25°C  204.5h (=8.5d)  extrapolation

Table 2. Results at pH 7

 Temperature  t1/2 (by regression)  Experiment
 50°C  3.93h  2
 35°C  21.18h  5
 25°C  71.5h (=3.0d)  extrapolation
Validity criteria fulfilled:
yes
Conclusions:
Under the study conditions, the half-lives of the substance at 25°C and at pH 4 and 7 were determined to be 8.5 and 3.0 d, respectively and at pH 9 a half-life of less than 1 d was estimated.
Executive summary:

A study was conducted to determine the hydrolysis as a function of pH of the read-across substance according to EU Method C.7, in compliance with GLP. Five to nine mg of test substance were weighed in a 50 mL volumetric flask and the relevant buffer (pH 4, 7 or 9) was added. The flask containing the hydrolysis mixture was placed in a thermostatically controlled water bath at selected temperatures (35, 50, 55 or 65°C) for a specified time (0.5 to 32 h). Thereafter it was cooled immediately. The pH was controlled. The HPLC analysis of the unhydrolysed test substance (main compound) was performed without any delay. Values for 25°C were determined by extrapolating the results of the experiment at higher temperatures. Under the study conditions, the half-lives of the substance at 25°C and at pH 4 and 7 were determined to be 8.5 and 3.0 d, respectively and at pH 9 a half-life of less than 1 d was estimated (Mühlberger, 1999).

Description of key information

Key value for chemical safety assessment

Half-life for hydrolysis:
3 d
at the temperature of:
25 °C

Additional information

A study was conducted to determine the hydrolysis as a function of pH of the read-across substance according to EU Method C.7, in compliance with GLP. Five to nine mg of test substance were weighed in a 50 mL volumetric flask and the relevant buffer (pH 4, 7 or 9) was added. The flask containing the hydrolysis mixture was placed in a thermostatically controlled water bath at selected temperatures (35, 50, 55 or 65°C) for a specified time (0.5 to 32 h). Thereafter it was cooled immediately. The pH was controlled. The HPLC analysis of the unhydrolysed test substance (main compound) was performed without any delay. Values for 25°C were determined by extrapolating the results of the experiment at higher temperatures. Under the study conditions, the half-lives of the substance at 25°C and at pH 4 and 7 were determined to be 8.5 and 3.0 d, respectively and at pH 9 a half-life of less than 1 d was estimated (Mühlberger, 1999).