reaction mass of 1-[2-(2-aminobutoxy)ethoxy]but-2-ylamine and 1-({[2-(2-aminobutoxy)ethoxy]methyl}propoxy)but-2-ylamine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 October 2003 - 17 October 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Validation details for the analytical method applied were not reported.

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

GLP compliance:

yes

Specific details on test material used for the study:

- Batch: 8191-34
- Purity: 97.8% (expressed as primary amine, % of total)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: at t = 0h, 2.4h and 5 days
- Sampling method: not indicated
- Sampling methods for the volatile compounds, if any: not applicable
- Sampling intervals/times for pH measurements: 0h, 2.4h and 5 days
- Sampling intervals/times for sterility check: no sterility check
- Sample storage conditions before analysis: not indicated
- Other observation, if any (e.g.: precipitation, color change etc.): none indicated

Buffers:

- pH: 4, 7 and 9
- Type and final molarity of buffer: 0.05 M acetate / 0.05 M phosphate / 0.05 M borate
- Composition of buffer: sodium acetate / acetic acid (pH 4); potassium dihydrogen phosphate / sodium hydroxide (pH 7); boric acid / potassium chloride / sodium hydroxide (pH 9)

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 50 mL volumetric flasks
- Sterilisation method: filter sterilized over 0.2 microm membrane filter
- Lighting: light was excluded
- Measures taken to avoid photolytic effects: study was performed in the dark (not further specified)
- Measures to exclude oxygen: nitrogen gas was bubbled through the test solutions (for 5 min)
- Details on test procedure for unstable compounds: not applicable
- Details of traps for volatile, if any: no traps for volatiles included in the test design
- If no traps were used, is the test system closed/open: closed (vessels were tightly sealed with a septum-crimpcap)
- Is there any indication of the test material adsorbing to the walls of the test apparatus? Not reported
TEST MEDIUM
- Volume used/treatment: 50 mL
- Kind and purity of water: tap water purified by reversed osmosis and subsequently passed over activated carbon and ion-exchange cartridges
- Preparation of test medium: filter sterilized over 0.2 microm membrane filter; 9.20 - 10.4 mg substance per 50 mL medium
- Renewal of test solution: no renewal of test solutions
- Identity and concentration of co-solvent: no co-solvent applied
OTHER TEST CONDITIONS
- Adjustment of pH: pH not adjusted
- Dissolved oxygen: not measured

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

161 mg/L

Duration:

5 d

pH:

7.2

Temp.:

50 °C

Initial conc. measured:

200 mg/L

Duration:

5 d

pH:

9.1

Temp.:

50 °C

Initial conc. measured:

173 mg/L

Number of replicates:

Each pH was tested in a single experiment

Positive controls:

no

Negative controls:

no

Statistical methods:

No statistical methods used

Preliminary study:

The pH was measured to be 4.0 /4.0 / 4.2, 7.2/7.2/7.2 and 9.1/9.0/9.1 after 0h, 2.4h and 5 days. The submission substance appeared to be stable under the test conditions. A main study was thus concluded not to be required.

Test performance:

No validation results and example HPLC chromatograms were provided. The results of the sample measurements indicate a significant spread in the analytical results; for instance at pH 9 the 0h, 2.4h and 5 days results were 173 mg/L, 147 mg/L and 207 mg/L, respectively. Results should thus be treated with care.

Transformation products:

no

Key result

pH:

4

Temp.:

50 °C

DT50:

> 8 760 h

Remarks on result:

other: Temp.: CA 50 °C

Key result

pH:

7

Temp.:

50 °C

DT50:

> 8 760 h

Remarks on result:

other: Temp.: CA 50 °C

Key result

pH:

9

Temp.:

50 °C

DT50:

> 8 760 h

Remarks on result:

other: Temp.: CA 50 °C

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes (sterility not checked)
- Anomalies or problems encountered (if yes): significant spread in analytical results, see "Results and discussion".

MAJOR TRANSFORMATION PRODUCTS: no transformation products

Validity criteria fulfilled:

not specified

Conclusions:

The substance is concluded to be hydrolytically stable at pH 4, 7 and 9 (half-life time at 25 °C > 1 year).

Description of key information

The substance was determined to be hydrolytically stable at pH 4, 7 and 9 (extrapolated half-life time at 25 °C > 1 year) in a GLP study according to test method EC C.7 (Baltussen, 2004). This Klimisch 2 study is considered as the key study.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

A single study is available on hydrolysis (Baltussen, 2004). As the substance appeared to be hydrolytically stable in the preliminary test, the extrapolated half-life time at 25 °C is concluded to be > 1 year. This study is a well performed GLP study in accordance with accepted test guidelines. Validation details for the analytical method applied were not reported and therefore the study was assigned a Klimisch 2 score.