Esterification products of alkenylsuccinic anhydride and 2-dialkylaminoethanol

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 January 1994 to 19 September 1994

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:

- Sampling intervals for the parent/transformation products: 0, 1, 2, 3, 4, 24, 48/49, 72 and 96 hours (depending on pH and temperature)
- Sampling method: Aliquots (100 mL) of the test material in the buffer solutions were individually dispensed into septum-sealed vials.

Buffers:

1 litre stock buffer solutions were prepared
- pH: 4.0
- Composition of buffer: 12.396 g/L Citric acid, 12.058 g/L Tri-sodium citrate

- pH: 7.0
- Composition of buffer: 3.522 g/L potassium dihydrogen orthophosphate; 7.265 g/L disodium hydrogen orthophosphate.

- pH: 9.0
- Composition of buffer: 3.114 g/L boric acid; 3.714 g/L potassium chloride; 25.5 mM/L sodium hydroxide

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Septum sealed vials
- Measures taken to avoid photolytic effects: Incubated under light free conditions
- Measures to exclude oxygen: Septum sealed vials
- If no traps were used: Closed system used
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No
TEST MEDIUM
- Preparation of test medium: A solution of the test material in methanol was prepared at a nominal concentration of 22 mg/L. This solution was added at 0.5 % to water buffered at pH 4, 7 and 9, yielding solutions of approximately 110 µg/mL. Aliquots (100 mL) of the test solutions were added to septum-sealed vials.

The vials were incubated at the specified temperatures under light free conditions and analysed for the test material after specified intervals. Changes in concentration with respect to time were determined. The kinetics were examined to determine whether the reaction was pseudo-first order, and if so to determine the half life.

Positive controls:

no

Negative controls:

no

Statistical methods:

An Arrhenius plot for each temperature and pH was generated from the hydrolysis rate constants.
- First order reaction:
The following reaction:
RX + H2O = ROH + HX
Can be described by a pseudo first order rate constant since the water is present in great excess compared to the test substance.
The Arrhenius equation is described by:

kobs = Ae^(-E/RT)
Where Kobs = observed rate constant
E = Activation energy
R = Universal gas constant
T = Temperature (K)
If natural logarithms are take, the equation is:
logekobs = -E/RT + logeA
The linear form of the equation can be described by:
y = mx + c
The rate constants for each separate pH were plotted and the linear equation for each line derived. These 3equations are then used to calculate the rate constant and half lives.
The rate constant and half life of the hydrolysis reaction, assuming first order kinetics are given by:
Rate constant: (kobs) = - slope
Half life: (t1/2) = -(0.693/kobs)

Test performance:

At pH 4 the hydrolysis solutions were observed to be cloudy upon removal form the water bath. To check whether the cloudiness was caused by a reaction with the buffer system, the test material was also dissolved in hydrochloric acid at pH 4. These samples were also found to be cloud

Transformation products:

not measured

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.004 h-1

DT50:

184 h

Type:

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

Key result

pH:

4

Temp.:

50 °C

Remarks on result:

not determinable

Remarks:

No significant degradation

Key result

pH:

7

Temp.:

50 °C

Remarks on result:

not determinable

Remarks:

No significant degradation

Details on results:

TEST CONDITIONS
- Anomalies or problems encountered (if yes): The data for the rate constant at 50 °C were not used as these were inconsistent with the remaining data

Table 1: Results at pH 4 and 50 °C

Sample	Time (hours)	Concentration (mg/L)	pH
1	0	0.190	7.24
2	1	0.114	7.19
3	2	0.055	7.42
4	3	0.092	7.38
5	4	0.166	7.34
6	24	0.050	7.40
7	49	0.255	7.10
8	72	0.225	7.28
9	96	0.235	7.19
Rate constant (hours) -0.00964 R squared 0.3117 Half life (hours) -72 Half life (days) -3

 

Table 2: Results at pH 4 and 50 °C

Sample	Time (hours)	Concentration (mg/L)	pH
1	0	0.236	6.93
2	1	0.160	7.02
3	2	0.095	6.93
4	3	0.065	6.94
5	4	0.043	6.97
6	48	0.180	7.06
7	72	0.113	7.04
8	96	0.090	7.05
Rate constant (hours) -0.00052 R squared 0.0013 Half life (hours) -1337 Half life (days) -56

 

Table 3: Results at pH 9 and 50 °C

Sample	Time (hours)	Concentration (mg/L)	pH
1	0	0.101	9.15
2	1	0.078	8.99
3	2	0.048	8.92
4	3	0.038	8.93
5	4	0.051	8.85
6	24	0.040	9.00
7	48	0.034	8.97
8	72	0.024	8.97
9	96	0.002	9.00
Rate constant (hours) 0.02733 R squared 0.7481 Half life (hours) 25 Half life (days) 1

 

Table 4: Results at pH 9 and 60 °C

Sample	Time (hours)	Concentration (mg/L)	pH
1	0	0.241	8.94
2	1	.0115	9.07
3	2	0.056	9.08
4	3	0.199	9.06
5	4	0.231	9.08
6	24	0.110	9.00
7	48	0.095	8.98
8	72	0.116	9.04
9	96	0.000	9.01
Rate constant (hours) 0.00524 R squared 0.0801 Half life (hours) 132 Half life (days) 6

 

Table 5: Results at pH 9 and 70 °C

Sample	Time (hours)	Concentration (mg/L)	pH
1	0	0.301	9.02
2	1	0.611	9.06
3	2	0.749	90.8
4	3	0.353	9.04
5	4	0.066	9.08
6	24	0.061	9.11
7	48	0.023	8.95
8	72	0.022	9.05
Rate constant (hours) 0.0418 R squared 0.7035 Half life (hours) 16 Half life (days) 1

 

Table 6: Results at pH 9 and 80 °C

Sample	Time (hours)	Concentration (mg/L)	pH
1	0	0.214	9.16
2	1	0.093	9.18
3	2	0.100	9.09
4	3	0.043	9.04
5	4	0.074	9.13
6	24	0.039	9.14
Rate constant (hours) 0.04494 R squared 0.4241 Half life (hours) 15 Half life (days) 1

Validity criteria fulfilled:

not specified

Conclusions:

The preliminary hydrolysis of the test material at pH 4 and 7 at 50 °C showed no significant degradation. At pH 9, the preliminary data at 50 °C indicated a reaction which was further investigated at 60, 70 and 80 °C. The half life and rate constanct at 20 °C were calculated to be:
Rate constant (Kobs) = 3.8E-03 h-1
Half life (t1/2) = 184 h

Executive summary:

The abiotic degradation of the test material was determined a study performed in accordance with OECD 111. Septum sealed vials of the test material in buffer solutions at pH 4, 7 and 9 were sampled over a 96 hour period at 50 °C under light free conditions. Further investigations were performed at pH 9 at 60, 70 and 80 °C. The samples were removed at each time period, derivatised, then analysed via HPLC (UV).

The preliminary hydrolysis of the test material at pH 4 and 7 at 50 °C showed no significant degradation. At pH 9, the preliminary data at 50 °C indicated a reaction which was further investigated at 60, 70 and 80°C. The half life and rate constanct at 20 °C were calculated to be:

Rate constant (Kobs) = 3.8E-03 h-1

Half life (t1/2) = 184 h

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12th October 1998 and 1 December 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products:
Aliquots were taken from pH 4 solutions at 0, 2.4, 24 and 120 hours
Aliquots were taken from pH 7 solutions at 0, 2.4, 25, 120 and 219 hours
Aliquots were taken from pH 9 solutions at 0, 2.4, 25 and 120 hours

The pH of the samples were measured

Buffers:

- pH: 4
- Composition of buffer: citric acid mol/dm³, sodium hydroxide 0.1 mol/dm³, hydrochloric acid 0.05 mol/dm³
- pH: 7
- Composition of buffer: disodium hydrogen orthophosphate 0.04 mol/dm³, potassium dihydrogen orthophosphate 0.03 mol/dm³
- pH: 9
- Composition of buffer: disodium tetraborate 0.05 mol/dm³, 0.02 mol/dm³

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Stoppered glass flasks
- Sterilisation method: The buffer solutions were filtered through a 0.2 µm membrane filter to ensure they were sterile before commencement of the test.
- Lighting: Shielded from light
- Measures to exclude oxygen: The solutions were also subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.
TEST MEDIUM
- Preparation of test medium: Sample solutions were prepared at nominal concentrations of 0.01 g/L at pH 4 and 0.1 g/L at pH 7 and 9, respectively.
- Identity and concentration of co-solvent: 1 % v/v Tetrahydrofuran

Duration:

219 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.087 g/L

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

0.008 g/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.081 g/L

Number of replicates:

Performed in duplicate

Positive controls:

no

Negative controls:

no

Statistical methods:

The mean total peak area of each standard was corrected to a nominal concentration and the mean value taken.
The concentration of the samples solutions (g/L) was calculated using the following:

Cspl = (Pspl/Pstd)*Cstd*D*(1/1000)

Where :

Csple = Concentration of sample solution (g/L)
Cstd = Nominal standard concentration (mg/L)
Pspl = Mean total peak are of sample solution
Pstd = Mean total peak are of standard solution, corrected to nominal standard concentration
D = Sample dilution factor (0.05 or 0.2)

Test performance:

At pH 7, the concentration after 120 hours was 84 % of the initial concentration. The preliminary test at pH 7 was therefore continued at 50 °C to investigate for pseudo-first order hydrolysis. After 219 hours, the measured concentration was 101 % of the initial concentration, which was consistent with the results observed at pH 4 and pH 9. It was considered that the test material is hydrolytically stable at pH 7 at temperature at 50 °C. The low measured concentration after 120 hours was anticipated to be due to an analytical error.

Transformation products:

not measured

% Recovery:

94

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

101

pH:

7

Temp.:

50 °C

Duration:

9 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

94

pH:

9

Temp.:

50 °C

Duration:

9 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Type:

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

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Type:

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

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Type:

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

Remarks on result:

hydrolytically stable based on preliminary test

Table 1: Mean Total Peak Areas

Solution	Mean Total Peak Area
Standard 225 mg/L	1.358E+05
Standard 225 mg/L	1.257E+05
pH 4 Initial Sample A	9.023E+04
pH 4 Initial Sample B	9.549E+04
pH 4 2.4 Hour Sample A	9.031E+04
pH 4 2.4 Hour Sample B	9.366E+04
Standard 197 mg/L	1.096E+05
Standard 216 mg/L	1.242E+05
pH 4 24 Hour Sample A	7.901E+04
pH 4 24 Hour Sample B	8.033E+04
Standard 240 mg/L	1.262E+05
Standard 203 mg/L	1.127E+05
pH 4 120 Hour Sample A	7.711E+04
pH 4 120 Hour Sample B	8.481E+04
Standard 534 mg/L	2.443E+05
Standard 579 mg/L	2.668E+05
pH 7 Initial Sample A	1.996E+05
pH 7 Initial Sample B	2.016E+05
pH 7 2.4 Hour Sample A	2.063E+05
pH 7 2.4 Hour Sample B	2.118E+05
Standard 582 mg/L	2.257E+05
Standard 523 mg/L	2.239E+05
pH 7 25 Hour Sample A	1.791E+05
pH 7 25 Hour Sample B	1.805E+05
Standard 537 mg/L	2.256E+05
Standard 541 mg/L	2.288E+05
pH 7 120 Hour Sample A	1.485E+05
pH 7 120 Hour Sample B	1.613E+08
Standard 492 mg/L	3.003E+05
Standard 540 mg/L	3.527E+055
pH 7 219 Hour Sample A	2.769E+05
pH 7 219 Hour Sample B	2.810E+05
Standard 534 mg/L	2.160E+05
Standard 579 mg/L	2.377E+05
pH 9 Initial Sample A	1.636E+05
pH 9 Initial Sample B	1.671E+05
pH 9 2.4 Hour Sample A	1.768E+05
pH 9 2.4 Hour Sample B	1.774E+05
Standard 582 mg/L	2.257E+05
Standard 523 mg/L	2.239E+05
pH 9 25 Hour Sample A	1.705E+05
pH 9 25 Hour Sample B	1.700E+05
Standard 537 mg/L	2.256E+05
Standard 541 mg/L	2.288E+05
pH 9 120 Hour Sample A	1.584E+05
pH 9 120 Hour Sample B	1.618E+05

 

Table 2: Results with pH 4 at 50.0 ± 0.5 °C

Time (hours)	0	2.4	24	120
Concentration (g/L)	7.99E-03	7.92E-03	7.03E-03	7.48E-03
% of initial	100	99	88	94

Less than 10 % hydrolysis after 5 days at 50 °C equivalent to a half life of greater than 1 year at 25 °C.

 

Table 3: Results with pH 7 at 50.0 ± 0.5 °C

Time (hours)	0	2.4	25	120	219
Concentration (g/L)	8.73E-02	9.10E-02	8.82E-02	7.53E-02	8.83E-02
% of initial	100	104	101	84	101

Less than 10 % hydrolysis after 9 days at 50 °C equivalent to a half life of greater than 1 year at 25 °C.

 

 

Table 4: Results with pH 9 at 50.0 ± 0.5 °C

Time (hours)	0	2.4	25	120
Concentration (g/L)	8.11E-02	8.68E-02	8.35E-02	7.60E-02
% of initial	100	107	103	104

Less than 10 % hydrolysis after 5 days at 50 °C equivalent to a half life of greater than 1 year at 25 °C.

Validity criteria fulfilled:

yes

Conclusions:

The estimated half life of the test material at 25 °C at pH 4, 7 and 9 was determined to be greater than 1 year.

Executive summary:

The abiotic degradation of the test material was examined in a test performed in accordance with EU Method C.7. Under the conditions of the test, the test material was found to be hydrolytically stable. The estimated half life of the test material at 25 °C at pH 4, 7 and 9 was determined to be greater than 1 year.

Description of key information

In the key study, the abiotic degradation of the test material was determined a study performed in accordance with OECD 111. Septum sealed vials of the test material in buffer solutions at pH 4, 7 and 9 were sampled over a 96 hour period at 50 °C under light free conditions. Further investigations were performed at pH 9 at 60, 70 and 80 °C. The samples were removed at each time period, derivatised, then analysed via HPLC (UV).

The preliminary hydrolysis of the test material at pH 4 and 7 at 50 °C showed no significant degradation. At pH 9, the preliminary data at 50 °C indicated a reaction which was further investigated at 60, 70 and 80°C. The half life and rate constanct at 20 °C were calculated to be:

Rate constant (Kobs) = 3.8E-03 h-1

Half life (t1/2) = 184 h

Key value for chemical safety assessment

Half-life for hydrolysis:

184 h

at the temperature of:

20 °C