Registration Dossier

Environmental fate & pathways

Hydrolysis

Currently viewing:

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 January 2003 to 19 January 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products: 0, 2.4, 72 and 120 hours
- Sampling method: Two samples were removed from the bath and an aliquot (2.5 ml) of each was diluted to volume (5 ml) with methanol
- Sampling intervals/times for pH measurements: 0, 2.4, 72 and 120 hours
- Sample storage conditions before analysis: 50°C waterbath in the dark
Buffers:
Preparation of buffer solutions
Buffer solutions were prepared as follows:
pH 4: 0.2M aqueous potassium dihydrogen orthophosphate (550 ml) was mixed with 0.07M aqueous disodium hydrogen orthophosphate dodecahydrate (1250 ml) and purified water (3200 ml). The pH was adjusted to 4.0 ± 0.05 with orthophosphoric acid.

pH 7: 0.2M aqueous potassium dihydrogen orthophosphate (1250 ml) was mixed with 1M sodium hydroxide (150 ml) and purified water (3600 ml). The pH was adjusted to 7.0 ± 0.05 with 1M sodium hydroxide.

pH 9: 0.1M boric acid in 0.1M aqueous potassium chloride (2000 ml) was mixed with 1M sodium hydroxide (84 ml) and purified water (1920 ml). The pH was measured as 9.0 ± 0.05.

Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Aliquots (100 µl) of a stock solution of Rikabinol HB in methanol (9 g/l) were added to separate Wheaton vials containing buffer solution (10 ml).,
- Sterilisation method: Flasks had been purged with nitrogen and pre-equilibrated at test temperature (50 ± 0.5°C).
- Measures to exclude oxygen: Flasks had been purged with nitrogen and pre-equilibrated at test temperature (50 ± 0.5°C).

TEST MEDIUM
A stock calibration solution of approximate concentration 9 g/l was prepared by weighing test substance (approximately 225 mg) into a 25 ml volumetric flask and dissolving in and diluting to volume with methanol.
Calibration solutions in the range 9 to 90 mg/l were prepared by dilutions of the stock solution with methanol:water (1:1 v/v).


OTHER TEST CONDITIONS
- Adjustment of pH: buffer solutions
Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
ca. 9 mg/L
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
ca. 9 mg/L
Duration:
5 d
pH:
9
Temp.:
50 °C
Initial conc. measured:
ca. 9 mg/L
Number of replicates:
1
Positive controls:
no
Negative controls:
no
Preliminary study:
The preliminary study showed that at each of pH 4, 7 and 9 and 50 ± 0.5ºC, less than 10% hydrolysis had occurred after 120 hours (5 days), equivalent to a half-life of greater than 1 year under environmental conditions (25°C). No further testing was considered necessary.
Test performance:
Not required
Transformation products:
no
Details on hydrolysis and appearance of transformation product(s):
Rikabinol HB was determined to be hydrolytically stable under acidic, neutral and basic conditions.
Key result
pH:
4
Temp.:
50 °C
DT50:
> 1 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: regression coefficient of 0.9997
Key result
pH:
5
Temp.:
50 °C
DT50:
> 1 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: regression coefficient of 0.9997
Key result
pH:
9
Temp.:
50 °C
DT50:
> 1 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: regression coefficient of 0.9997
Details on results:
The preliminary study showed that at each of pH 4, 7 and 9 and 50 ± 0.5ºC, less than 10% hydrolysis had occurred after 120 hours (5 days), equivalent to a half-life of greater than 1 year under environmental conditions (25°C).

Preliminary test results for hydrolysis of Rikabinol HB

 

Ct (mg/l)

pH

t0h

t2.4h

t72h

t120h

 

Measured

Mean

Measured

Mean

Measured

Mean

Measured

Mean

 

 

 

 

 

 

 

 

 

4

90, 88

89

85, 87

86

86, 84

85

87, 91

89

 

 

 

 

 

 

 

 

 

7

88, 90

89

88, 85

87

87, 88

87

88, 86

87

 

 

 

 

 

 

 

 

 

9

86, 86

86

87, 86

86

86, 88

87

87, 84

86

 

 

 

 

 

 

 

 

 

where Ctis the concentration of Rikabinol HB in solution at time th(in hours)

Validity criteria fulfilled:
yes
Conclusions:
Rikabinol HB was determined to be hydrolytically stable under acidic, neutral and basic conditions. Equivalent to a half-life of greater than 1 year under environmental conditions (25°C).

Description of key information

HBPA was determined to be hydrolytically stable under acidic, neutral and basic conditions.

Key value for chemical safety assessment

Additional information

A study was performed (Huntingdon Life Sciences, 2013, Study MOG0020) to determine the rate of hydrolysis of HBPA as a function of pH. The procedure was designed to be compatible the EC Method C.7 and the OECD test guidelines 111, and was conducted in compliance with GLP.

 

The preliminary study showed that at each of pH 4, 7 and 9 and 50 ± 0.5ºC, less than 10% hydrolysis had occurred after 5 days, equivalent to a half-life of greater than

1 year under environmental conditions (25°C). No further testing was considered necessary.

 

HBPA was determined to be hydrolytically stable under acidic, neutral and basic conditions.