Sodium 4-(2-hydroxyethyl)piperazin-1-ylethanesulphonate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2012-11-09 to 2013-12-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: day 0 and day 5
- Sampling intervals/times for pH measurements: day 0 and day 5

Buffers:

- pH: 4, 7, 9
- Type and final molarity of buffer: Composition was taken from the annex of the OECD method (buffer solutions 7 and 9) resp. Küster et al. (buffer solution 4). All chemicals used were of analytical grade. The pH was measured with a pH-meter with an uncertainty of 0.01 units and pH was adjusted to the nominal pH value ± 0.02 units.
The buffer solutions were filtrated (0.45 µm) after preparation, resulting in sterile solutions.
- Composition of buffer:
Buffer-Solution, pH 4
CH3COOH, 2-m: 160 mL
CH3COONa, 1-m: 80 mL
Water: ad 2000 mL

Buffer-Solution, pH 7
KH2PO4: 17.4171 g
Water: 500 mL
NaOH, 2-m: 29.8 mL
Water: ad 2000 mL

Buffer-Solution, pH 9
H3BO3: 6.1863 g
KCl: 7.4579 g
Water: 1000 mL
NaOH, 2-m: 21.5 mL
Water: ad 2000 mL

Details on test conditions:

TEST SYSTEM
- Test flaks: Test tubes
- Sterilisation method: filters
- Measures taken to avoid photolytic effects: incubation chamber
- Measures to exclude oxygen: teflon seals
- If no traps were used, is the test system closed: yes
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

TEST MEDIUM
- Volume used/treatment: 1.5 mL
- Kind and purity of water: Deionised water from an ion exchanger with TOC < 1 ppm and conductivity below 0.1 µS/cm
- Preparation of test medium: A solution of the test item was prepared by dissolving 200 mg with 50 mL of water by means of an ultrasonic bath (resulting concentration 4000 mg/L). This solution was mixed 1:1 with the appropriate buffer solution, giving a nominal concentration of 2000 mg/L and filtrated using sterilised 0.2 µm filters.

Duration:

5 d

Temp.:

50 °C

Initial conc. measured:

> 1 707 - < 1 815 mg/L

Number of replicates:

3

Positive controls:

no

Negative controls:

no

Statistical methods:

none

Preliminary study:

The preliminary study indicates that the substance is hydrolytically stable and no further studies need to be conducted.

Test performance:

The validity criteria were met.

Transformation products:

no

Details on hydrolysis and appearance of transformation product(s):

At pHs 4, 7 and 9, no signs of hydrolysis were observed in the preliminary study (tier 1). Therefore, the test item can be considered as hydrolytically stable at these pH values.

% Recovery:

> 100

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

> 100

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

> 100

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Temp.:

50 °C

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

Measured Values

	pH 4.0	pH 7.0	pH 9.0
Concentration mg/L d = 0 Replicate 1	1797.66	1777.21*	1722.36
Concentration mg/L d = 0 Replicate 2	1781.90	1814.82*	1742.25
Concentration mg/L d = 0 Replicate 3	1792.32	1707.72*	1712.84
Concentration mg/L d = 5 Replicate 1	2032.37	1885.36**	1929.37
Concentration mg/L d = 5 Replicate 2	1946.19	1857.97**	1877.85
Concentration mg/L d = 5 Replicate 3	2002.28	1829.14**	1882.00
Concentration blank mg/L d = 5	< 200	< 200	< 200

* Concentrations in the test item solutions pH 7 were calculated after baseline subtraction of the blank pH 7 (automatically performed by evaluation software Chromeleon), measured on day 0, because the blank at pH 7 gave a disturbing signal on day 0. This may have been caused by change in column properties, compared with the column properties during validation.

** Because the recovery of the QC-samples was 104.9 % (mean), the measured concentrations were divided through 1.049.

 

Mean Concentrations and recoveries

	pH 4.0	pH 7.0	pH 9.0
Mean Concentration mg/L d = 0	1790.63	1766.58	1725.82
Mean Concentration mg/L d = 5	1993.61	1857.49	1896.41
Recovery after 5 days	111.3 %	105.1 %	109.9 %

 

Validity criteria fulfilled:

yes

Conclusions:

The assessment of hydrolytic stability of the test substance was carried out according to OECD 111 (2004). The test item was determined to be hydrolytically stable (t1/2 > 1 year at 25 °C) at pH 4, 7 and 9.

Executive summary:

The assessment of hydrolytic stability of the test substance was carried out according to OECD 111 (2004) under GLP conditions. A solution of the test substance in demineralized water was mixed with buffer solutions (pH values: 4, 7 and 9). The resulting solutions were sterilized by filtration using sterile 0.2 µm filters and stored at 50 °C for a period of five days. Samples were taken at the beginning and after five days. The analysis of the samples (performed with HPLC/UVD) showed no decrease of the concentration of the test item within five days. At pHs 4, 7 and 9, no signs of hydrolysis were observed in the preliminary study. Therefore the test item was determined to be hydrolytically stable (t1/2 > 1 year at 25 °C) at pH 4, 7 and 9.

Reference 2

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to the attached read-across justification in section 13.

Reason / purpose for cross-reference:

read-across source

Transformation products:

not measured

Key result

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Description of key information

The assessment of hydrolytic stability of the read-across source substance was carried out according to OECD 111 (2004), (reference 5.1.2-1). The source substance was determined to be hydrolytically stable (t1/2 > 1 year at 25 °C) at pH 4, 7 and 9.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

No experimental data on the hydrolysis of the registration substance is available, but information of a GLP-compliant guideline study with the read-across source substance HEPES (CAS no. 7365-45-9).

 

The assessment of hydrolytic stability of the read-across source substance was carried out according to OECD 111 (2004) under GLP conditions. A solution of the test substance in demineralized water was mixed with buffer solutions (pH values: 4, 7, and 9). The resulting solutions were sterilized by filtration using sterile 0.2 µm filters and stored at 50 °C for a period of five days. Samples were taken at the beginning and after five days. The analysis of the samples (performed with HPLC/UVD) showed no decrease of the concentration of the test item within five days. At pHs 4, 7 and 9, no signs of hydrolysis were observed in the preliminary study. Therefore the read across source substance was determined to be hydrolytically stable (t1/2 > 1 year at 25 °C) at pH 4, 7 and 9.

 

Conclusion

Based on reliable data for the read-across source substance the target substance is considered to be hydrolytically stable (t1/2 > 1 year at 25 °C) at pH 4, 7 and 9.