2-[(2-[2-(dimethylamino)ethoxy]ethyl)methylamino]ethanol

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-09-20 to 1990-12-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: EEC Directive 67/548, Annex V, C10 as published in EC Directive 84/449.

Deviations:

yes

Remarks:

Buffer solutions with a higher buffering capacity were used (nominal strength 0.5 M).

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): Texacat ZF-10, 2-[[2-[2-(dimethylamino)ethoxy]ethyl]methylamino]ethanol
- Physical state: Clear colorless liquid
- Analytical purity: 97%
- Lot/batch No.: 90/329
- Expiration date of the lot/batch: approximately two years from receipt (received on 30 March 1990)
- Storage condition of test material: dark at room temperature

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0 hours, 2.4 hours, and 5 days
- Sampling method: An aliquot of the cooled test solution (10.0 ml) was pipetted into a 20 ml volumetric flask and made to volume with 0.1M sodium
hydroxide. Into a flask containing chloroform (10.0 ml) was added 2.0 ml of the diluted test solution. The chloroform was then dried by adding anhydrous sodium sulphate

Buffers:

- pH: The test was initially carried out at pH 4, 7 and 9 using about 0.1 M buffer solution. A repeat test was then conducted at pH 4 and 9 using 0.5 M buffer solutions.

pH 4.00 buffer (0.1 M)
Potassium hydrogen phthalate (20.42 g) was dissolved in one liter of distilled water. A 500 ml aliquot of the solution was stirred and heated to 50 degrees C, by means of a magnetic stirrer/hotplate, and adjusted to pH 4.00 with 0.1 M sodium hydroxide (ca. 10 ml).

pH 7.00 buffer (0.1 M)
Potassium dihydrogen orthophosphate (13.62 g) was dissolved in one liter of distilled water. A 500 ml aliquot of the solution was stirred and heated to 50 degrees C by means of a magnetic stirrer/hotplate. The solution was adjusted to pH 7.00 with 0.1 M sodium hydroxide (ca. 330 ml).

pH 9.00 buffer (0.1 M)
Potassium chloride (7.46 g) and boric acid (6.18 g) were dissolved in one liter of distilled water. A 500 ml aliquot of the solution was stirred and heated to 50 degreesC by means of a magnetic stirrer/hotplate. The solution was adjusted to pH 9.00 with 0.1 M sodium hydroxide solution (ca. 270 ml).

pH 4.00 buffer (0.5 M)
Potassium hydrogen phthalate (102.00 g) was dissolved in one liter of distilled water. The solution was stirred and heated to 50 degrees C and adjusted to pH 4.00 with phosphoric acid.

pH 9.00 buffer (0.5 M)
Potassium chloride (37.42 g) and boric acid (30.92 g) were dissolved in one liter of distilled water. An aliquot (200 ml) was stirred and heated to 50 degrees C. The solution was adjusted to pH 9.00 with 0.5 M sodium hydroxide.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 100 ml Volumetric flasks

- Sterilisation method: The buffer solutions were sterilized in an autoclave at 120 degrees C and 120 psi for 15 minutes. Volumetric flasks (100 ml) which had been pre-calibrated to 100 ml at 50°C were sterilized by rinsing with ethanol. Prior to the test the buffers were purged with nitrogen for 10 minutes and equilibrated at 50 degrees C.

TEST MEDIUM
- Volume used/treatment: 100ml (Buffer and test substance)

Duration:

5 d

pH:

9

Initial conc. measured:

ca. 1 900 other: micrograms/ml

Duration:

5 d

pH:

7

Initial conc. measured:

ca. 1 900 other: micrograms/ml

Duration:

5 d

pH:

4

Initial conc. measured:

ca. 1 900 other: micrograms/ml

Positive controls:

no

Negative controls:

no

Preliminary study:

No measurable hydrolysis over 5 days at 50 °C at pH 4 and 7. Greater than 10% hydrolysis was observed over 5 days at 50 °C and pH of 9.

Transformation products:

not measured

% Recovery:

97.3

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

> 100

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

73.3

pH:

9

Temp.:

50 °C

Duration:

5 d

pH:

9

Temp.:

25 °C

DT50:

>= 1 - <= 365 d

Type:

(pseudo-)first order (= half-life)

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Type:

(pseudo-)first order (= half-life)

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Type:

(pseudo-)first order (= half-life)

Details on results:

The results show that no measurable hydrolysis occurs at pH 4 or 7. Interpretation of pH 9 test results is more difficult since a greater than normal variation was obtained. However, the mean values of percent test substance remaining after 5 days for original and repeat tests were in close agreement (77.8% and 73.3% respectively) and it can be concluded with reasonable certainty that greater than 10% hydrolysis occurred over 5 days at 50°C at pH 9.

Validity criteria fulfilled:

yes

Conclusions:

The test substance was found to undergo no measurable hydrolysis over 5 days at 50 °C at pH 4 and 7.
At pH 9, the indications were that slight hydrolysis had occurred. Although quantitation was difficult, the extent of hydrolysis is likely to be greater than 10%. A further investigation was needed for hydrolysis at this pH (see supportive study), which showed no hydrolysis (see supporting study).

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1992-03-02 to 1992-03-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: Extended tests described in EEC Directive 67/548, Annex V, Part C test C10 as published in 84/449/EEC

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): Texacat ZF-10, 2-[{2-[2-(dimethylamino)ethoxy]ethyl}methylamino]ethanol
- Physical state: clear liquid
- Analytical purity: 98.3%
- Lot/batch No.: U186-1-0791

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0, 96, and 264 hours

Buffers:

- pH: 9
- Type and final molarity of buffer: 0.5M pH 9.0 buffer solution
- Composition of buffer: Potassium chloride (112.26 g) and boric acid (92.76 g) were dissolved in distilled water (3 litres). The solution was stirred and heated to 50 °C on a magnetic stirrer/hotplate. The solution was adjusted to pH 9.0 at 50 °C using 0.5 M sodium hydroxide solution.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Test substance (ca. 0.38 g) was added to each of two, 200 ml volumetric flasks (alibrated at 50 °C). The test substance was dissolved in, and diluted to volume with pH 9 buffer at 50 °C. The solutions were mixed and stored at 50 °C in 15 ml trident vials. The vials were completely filled to minimise any loss of test substance due to evaporation.
- Sterilisation method: The buffer solutions were autoclaved at 121 °C for 15 minutes then purged with nitrogen for 10 minutes prior to use.

Duration:

11 d

pH:

9

Initial conc. measured:

> 50.92 - <= 254.6 other: µg/ml

Number of replicates:

2

Positive controls:

no

Negative controls:

yes

Remarks:

A blank was run concurrently with the test solutions and prepared as for the test solutions, except omitting the test substance.

Statistical methods:

The peak response of Texacat ZF-10 in each calibration standard was measured and a calibration curve constructed by linear regression of standard response versus standard concentration. The response of the peak observed at the characteristic retention time of Texacat- ZF-10 in sample chromatograms was measured and then test solution concentration (micrograms/ml) calculated. Due to slightly low but consistent recovery values the analysed concentration of the test solutions was corrected for mean recovery.

Preliminary study:

No noticeable hydrolysis occurred at pH 9 over 11 days at 50 degrees C.

Test performance:

The overall mean recovery for the quality control solutions in both the test and the validation has been determined as 96.9%. Therefore the analysed concentrations of the test solutions have been corrected for recovery. No peak was obtained at the retention time of Texacat ZF-10 in any of the blanks indicating that the analytical procedure is free from interference.

Transformation products:

not measured

% Recovery:

96.9

pH:

9

Temp.:

50 °C

Duration:

11 d

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Type:

(pseudo-)first order (= half-life)

Validity criteria fulfilled:

yes

Conclusions:

No noticeable hydrolysis occurred at pH 9 over 11 days at 50 °C.

Description of key information

The Determination of Hydrolysis of the test substance as a function of pH is conducted using a non-OECD guidance and according to GLP. The test substance has been found to undergo no measurable hydrolysis over 5 days at 50°C at pH 4 and 7 (Macdonald et al, 1991). At pH 9, the indications were that slight hydrolysis had occurred. Although quantitation was difficult, the extent of hydrolysis is likely to be greater than 10%. A further investigation was needed for hydrolysis at this pH, which showed no hydrolysis in an extended hydrolysis study (Macdonald, 1992).

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C