Diethyl bis(2-hydroxyethyl)aminomethylphosphonate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

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)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Intervals were selected to obtain a minimum of six samplings showing between 20 and 70% hydrolysis

Buffers:

Sterile buffer solutions at pH 4, 7 and 9:
- Acetate buffer (pH 4)
- Phosphate buffer (pH 7)
- Borate buffer (pH 9)

Estimation method (if used):

The rate of hydrolysis was determined for samples prepared in buffers maintained at 15°C and 25°C by measuring the decrease in concentration versus time. The hydrolysis rate constant was calculated assuming pseudo first order kinetics. Linear regression analysis was performed.

Details on test conditions:

1. TEST SYSTEM:
The study was conducted using sterile solutions buffered at pH 4, 7 and 9. Acetate (pH 4), phosphate (pH 7) and borate (pH 9) buffers were used. Aqueous buffer solutions (4 liters each) were prepared using HPLC grade water and aqueous solutions of salts, acids and bases as follows:
- pH4 buffer: 16.691 grams of acetic acid and 4.102 grams of sodium acetate were added to 1.0 L volumetric flask containing some HPLC-grade water and shaken to dissolve. The flask was brought to volume with water
- pH 7 buffer: 6.805 grams of monopotassium phosphate and 1.185 grams of sodium hydroxide were added to 1.0 L volumetric flask containing some HPLC-grade water and shaken to dissolve. The flask was brought to volume with water
- pH 9: 0.852 grams of sodium hydroxide, 3.092 grams of boric acid and 3.728 grams of potassium chloride were added to 1.0 L volumetric flask containing some HPLC-grade water and shaken to dissolve. The flask was brought to volume with water
- pH 9: (definitive) 0.426 grams of sodium hydroxide, 1.546 grams of boric acid and 1.864 grams of potassium chloride were added to 500 mL volumetric flask containing some HPLC-grade water and shaken to dissolve. The flask was brought to volume with water.

The pH of each buffer solution was measured using a pH meter with an accuracy of 0.01 pH unit. Prior to use, buffers were sterilised by filtering through 0.2-µm filters.

2. DEFINITIVE TEST:
- Definitive test samples in pH 4, 7 and 9 buffer solution were prepared in a similar manner as the preliminary test
- Samples were decanted into 10 separate scintillation vials for storage at 15°C; 20 samples were prepared and stored at 25°C

Duration:

30 d

pH:

4

Temp.:

15 °C

Initial conc. measured:

15 mg/L

Remarks:

Nominal concentration

Duration:

30 d

pH:

4

Temp.:

25 °C

Initial conc. measured:

15 mg/L

Remarks:

Nominal concentration

Duration:

30 d

pH:

7

Temp.:

15 °C

Initial conc. measured:

15 mg/L

Remarks:

Nominal concentration

Duration:

30 d

pH:

7

Temp.:

25 °C

Initial conc. measured:

15 mg/L

Remarks:

Nominal concentration

Duration:

51 h

pH:

9

Temp.:

15 °C

Initial conc. measured:

15 mg/L

Remarks:

Nominal concentration

Duration:

51 h

pH:

9

Temp.:

25 °C

Initial conc. measured:

15 mg/L

Remarks:

Nominal concentration

Number of replicates:

Triplicate samples of each solution were taken for immediate analysis.

Preliminary study:

Results from the analyses of the preliminary study demonstrated that the test substance resulted in degradation at pH 4 (37.2% change), pH 7 (57.6% change) and pH 9 (greater than 85.4% change).

Test performance:

PRELIMINARY TEST/TEST DESIGN:
- The hydrolytic stability for the preliminary study was evaluated at pH 4 (acetate buffer), pH 7 (phosphate buffer) and pH 9 (borate buffer) at 50°C over a five day period (Day 0 and Day 5).
- Samples were prepared at a nominal concentration of 15.0 mg a.i./L, collected and analyzed on Days 0 and 5.

Transformation products:

not specified

% Recovery:

101

pH:

4

Temp.:

15 °C

Duration:

30 d

% Recovery:

87.8

pH:

4

Temp.:

25 °C

Duration:

30 d

% Recovery:

77.7

pH:

7

Temp.:

15 °C

Duration:

30 d

% Recovery:

42.6

pH:

7

Temp.:

25 °C

Duration:

30 d

% Recovery:

40.7

pH:

9

Temp.:

15 °C

Duration:

51 h

% Recovery:

7.83

pH:

9

Temp.:

25 °C

Duration:

51 h

pH:

4

Temp.:

15 °C

Hydrolysis rate constant:

0 h-1

DT50:

5 159 d

Type:

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

Remarks on result:

other: stable

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

-0.004 h-1

DT50:

179 d

Type:

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

Remarks on result:

other: stable

Key result

pH:

7

Temp.:

15 °C

Hydrolysis rate constant:

-0.008 h-1

DT50:

86.9 d

Type:

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

Remarks on result:

other: moderate stability

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

-0.026 h-1

DT50:

26.4 d

Type:

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

Remarks on result:

other: moderate stability

pH:

9

Temp.:

15 °C

Hydrolysis rate constant:

-0.018 h-1

DT50:

38.3 h

Type:

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

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

-0.051 h-1

DT50:

13.6 h

Type:

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

Details on results:

The results suggest that the hydrolysis potential of diethyl bis(2-ydroxyethyl)aminomethylphosphonate is both pH and temperature dependent. Under acidic conditions (pH 4) the substance is quite stable, showing a half-life of over 100 days. At neutral pH, the half- life was determined to be less than 100 days. Diethyl bis(2-hydroxyethyl)aminomethylphosphonate as shown to be unstable under alkaline (pH 9) conditions.

Validity criteria fulfilled:

yes

Conclusions:

The hydrolytic stability of diethyl bis(2-hydroxyethyl)aminomethylphosphonate was evaluated at pH 4, 7 and 9 at 15°C and 25°C. Half-lives of 5159 and 179 days at 15°C and 25°C, respectively, were determined at pH 4. At pH 7 yielded half-lives of 87 and 26 days at 15°C and 25°C, respectively. At pH 9 yielded half-lives of 38 and 14 hours at 15°C and 25°C, respectively.

Executive summary:

The objective of this study was to determine the rate of hydrolysis of diethyl bis(2-hydroxyethyl)aminomethylphosphonate in aqueous media in the environmentally relevant pH range of 4 to 9 at approximately l5°C and 25°C. The procedures used in the study were based on those found in the U.S. EPA Product Properties Test Guideline 835.2110 and OECD Guideline for Testing of Chemicals, 111. Hydrolysis in aqueous buffered media (pH 4, 7 and 9) was investigated at a concentration of approximately 15.0 mg a.i./L. The preliminary test was conducted with fortified samples in pH 4, 7 and 9 buffer solutions over a five day period at 50 ± 1 °C. The definitive test was conducted with fortified samples in pH 4, 7 and 9 buffer solutions maintained at 15°C and 25°C. Calibration curves were prepared from external standards of the test substance at each interval to determine the test substance concentrations in the samples. Minimal degradation of the test item was observed in samples prepared in pH 4 and 7 buffered solution maintained at l5°C and 25°C. Rapid degradation was however observed in pH 9 buffered solution at both l5°C and 25°C. Regression analysis was performed on all sets of data and hydrolysis rate constants and half-lives were calculated. The hydrolytic half-life at pH 4, at 15°C and 25°C was estimated to be 5159 and 179 days, respectively. The hydrolytic half-life at pH 7, at 15°C and 25°C was estimated to be 87 and 26 days, respectively. The hydrolytic half-life at pH 9, at 15°C and 25°C was estimated to be 38 and 14 hours, respectively. The hydrolytic stability of the test substance was evaluated at pH 4 and 7, at 15°C and 25°C, over a 30-day period. Evaluation of the stability at pH 9, at l5°C and 25°C, required frequent sampling over a three day period. The stability of the test substance in buffered solutions showed a clear dependence on both pH and temperature. Under acidic conditions, the test substance was clearly stable, irrespective of temperature (half-lives greater than 100 days at both 15°C and 25°C). At neutral pH, displays moderate stability with half-lives less than 100 days at both 15°C and 25°C. Under alkaline conditions, diethyl bis(2-hydroxyethyl)aminomethylphosphonate was clearly unstable with degradation increasing with increasing temperature.

Description of key information

The hydrolytic stability of diethyl bis(2-hydroxyethyl)aminomethylphosphonate was evaluated at pH 4, 7 and 9 at 15°C and 25°C (OECD TG 111; Kendall, 2005). Half-lives of 5, 159 and 179 days at 15°C and 25°C, were determined at pH 4, respectively. At pH 7 yielded half-lives were 87 and 26 days at 15°C and 25°C, respectively. At pH 9 yielded half-lives were 38 and 14 hours at 15°C and 25°C, respectively. 

Key value for chemical safety assessment

Half-life for hydrolysis:

26 d

at the temperature of:

25 °C

Additional information

A fully reliable, guideline, GLP study is available, and therefore considered as key.  The results suggest that the hydrolysis potential of diethyl bis(2-ydroxyethyl)aminomethylphosphonate is both pH and temperature dependent. Under acidic conditions, the test substance was clearly stable, irrespective of temperature (half-lives greater than 100 days at both 15°C and 25°C). At neutral pH, displays moderate stability with half-lives less than 100 days at both 15°C and 25°C. Under alkaline conditions, diethyl bis(2-hydroxyethyl)aminomethylphosphonate was clearly unstable with degradation increasing with increasing temperature.