1-acetyl-4-(3-dodecyl-2,5-dioxo-1-pyrrolidinyl)-2,2,6,6-tetramethylpiperidine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-04-08 to 1991-07-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study performed according to relevant guideline and compliant with GLP; however, the test followed the EU method C.10 adopted 1984, which did not require testing at a minimum of three temperatures at all relevant pH values compared to newer guidelines (e.g. OECD 111 (2004)). Nonetheless, the main results of the study are reliable.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1984: 84/449/EEC, C.10 (Abiotic degradation: hydrolysis as a function of pH)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Preliminary test:
Sampling occurred in duplicates for each pH value (4, 7, 9) after 0, 2.4 and 120 hours (50°C).

Test1:
Sampling occurred in duplicates for
- pH 4 after 0, 2, 7, 24, 31, and 48 hours (50°C);
- pH 7 after 0, 2.4, 24, 96, and 168 hours (50°C);
- pH 9 after 0, 2, 7, 24, 31, and 48 hours (50°C).

Test 2:
Sampling occurred in duplicates for pH 7 after
(1) 0, 39, 46, 63, 70, 88, and 94 hours (60°C);
(2) 0, 23, 26, 30, 47, 49, 51 and 54 hours (70°C).

The test performed at 70°C was conducted two times in parallel. The sampling time points were identical. Sampling after 49, 51 and 54 hours occurred in single measurements because of limited test solution (2 liters).

Test 3:
Sampling occurred in duplicates for
- pH 4 after 0, 18, 20.5 and 44 hours (40°C)
- pH 9 after 0, 18 and 20.5 hours (40°C).

- Sampling intervals/times for pH measurements: repeated measurements at the beginning of the tests.
- Sampling intervals/times for sterility check: not performed

Buffers:

Preparation of buffer solution:
- pH 4: 2 g of sodium acetate were dissolved in 2000 mL distilled water. The pH was adjusted with acidic acid.
- pH 7: 2 g of sodium acetate were dissolved in 2000 mL distilled water. The pH was adjusted with acidic acid or 0.01 N NaOH.
- pH 9: according to Sörensen (see guideline)

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: glassware, 2.5 L
- Sterilisation method: no
- Measures to exclude oxygen:
Buffer solutions were sparged with nitrogen before the addition of test substance.

- Temperature monitoring:
The temperature of each test vessel was constantly measured.

Duration:

20.5 h

pH:

4

Temp.:

40 °C

Initial conc. measured:

ca. 0.541 mg/L

Duration:

94 h

pH:

7

Temp.:

60 °C

Initial conc. measured:

0.409 mg/L

Duration:

54 h

pH:

7

Temp.:

70 °C

Initial conc. measured:

>= 0.364 - <= 0.366 mg/L

Duration:

44 h

pH:

9

Temp.:

40 °C

Initial conc. measured:

ca. 0.626 mg/L

Number of replicates:

For each measurement two samples were taken from different vessels. Only for the two test run in parallel and performed at pH 7 at 70 °C, the last three samples (out of eight) consisted of a single replicate, each, because of limited amount of test solution.

Positive controls:

no

Negative controls:

no

Statistical methods:

Regression analysis or manual determination of half-lives from graphic illustrations.

Preliminary study:

Results of the preliminary study showed that the test substance was hydrolytically unstable. In a test performed at 50 °C for the duration of 5 days, the percentage hydrolysis for the different pH values were as follows:
- pH 4: 90%
- pH 7: 52%
- pH 9: >10%

Thus, for all pH values higher tier test had to be performed.

Test performance:

The test substance significantly decreased at pH values of 4, 7 and 9 at 50 °C during a testing period of 5 days. Thus, higher tier testing was necessary. In the follow-up tests, hydrolysis of the test substance at pH 4 and 9, 50 °C followed a first order rate constant (guideline Test 1). Thus, further testing was performed for pH 4 and 9 at 40 °C until a minimum of ca. 70% hydrolysis of the test substance was reached (guideline Test 3). As the oder of the rate constant for the test substance at pH 7, 50 °C was equivocal (guideline Test 1), further testing at 60 and 70 °C was necessary (guideline Test 2). In these tests, it could be confirmed that hydrolysis followed a first-order rate constant.

Transformation products:

not measured

% Recovery:

74.3

St. dev.:

6.5

pH:

4

% Recovery:

82.2

St. dev.:

9.9

pH:

7

% Recovery:

68.2

St. dev.:

10

pH:

9

pH:

4

Temp.:

40 °C

Hydrolysis rate constant:

0.04 h-1

DT50:

17 h

Type:

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

Remarks on result:

other: regression analysis, pseudo-first order rate constant

pH:

7

Temp.:

60 °C

Hydrolysis rate constant:

0.005 h-1

DT50:

135 h

Type:

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

Remarks on result:

other: graphical determination of half-life, pseudo-first order rate constant

pH:

7

Temp.:

70 °C

Hydrolysis rate constant:

0.02 h-1

DT50:

35 h

Type:

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

Remarks on result:

other: graphical determination of half-life, pseudo-first order rate constant

pH:

9

Temp.:

40 °C

Hydrolysis rate constant:

0.015 h-1

DT50:

44.9 h

Type:

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

Remarks on result:

other: regression analysis, pseudo- first order rate constant

Details on results:

The determined hydrolysis rate constant and half-life for pH 4 and pH 9, 40 °C were 0.04 1/h and 17 hours, and 0.015 1/h and 45 hours, respectively. The determined hydrolysis rate constant and half-life for pH 7, 60 °C were 0.005 1/h and 135 hours, respectively; and at 70 °C 0.02 1/h and 35 hours, respectively. The given range of determined half-life for pH 7, 70 °C was due to parallel testing as required by the guideline.

TEST CONDITIONS
- temperature maintained throughout the study:

During the lower tier test (guideline Test 1) at pH 7, 50 ° C the temperature increased at the end of the test. The temperature was corrected successfully. During all higher tier tests (guideline Test 2 and 3) temperatures were maintained constantly.

Validity criteria fulfilled:

not applicable

Conclusions:

The substance is weakly hydrolytically unstable.

Executive summary:

The test was performed to investigate the abiotic degradation of the test substance. The test followed the EU method 84/449/EEC adopted 1984 and was in compliance with GLP.

The test substance significantly decreased at pH values of 4, 7 and 9 at 50 °C during a testing period of 5 days. Thus, higher tier testing was necessary. In the follow-up tests, hydrolysis of the test substance at pH 4 and 9, 50 °C followed a first order rate constant (guideline Test 1). Thus, further testing was performed for pH 4 and 9 at 40 °C until a minimum of ca. 70% hydrolysis of the test substance was reached (guideline Test 3). As the order of the rate constant for the test substance at pH 7, 50 °C was equivocal (guideline Test 1), further testing at 60 and 70 °C was necessary (guideline Test 2). In these tests, it could be confirmed that hydrolysis followed a first-order rate constant.

The determined hydrolysis rate constant and half-life for pH 4 and pH 9, 40 °C were 0.04 1/h and 17 hours, and 0.015 1/h and 45 hours, respectively. The determined hydrolysis rate constant and half-life for pH 7, 60 °C were 0.005 1/h and 135 hours, respectively; and at 70 °C 0.02 1/h and 35 hours, respectively.

In conclusion, the test substance was hydrolytically instable under the test conditions, and abiotic degradation may occur at pH values relevant for the environment.

Furthermore, requirements of the followed guideline were fulfilled. However, the test followed the EU method C.10 adopted 1984, which in contrast to the OECD guideline 111 (2004) did not require testing at a minimum of three temperatures at pH values where hydrolysis was observed. Nonetheless, the results of the study were considered reliable.  

Description of key information

The substance is weakly hydrolytically unstable at pH 7: determined hydrolysis rate constants and half-lives for pH 7, 60 °C were 0.005 1/h and 135 hours, respectively, and at 70 °C 0.02 1/h and 35 hours, respectively.

Relevant hydrolysis was determined at pH 4 (at 40 °C: k= 0.04 1/h; half-life 17 h; extrapolate to 20 °C: k= 0.20/d; half-life: 3.5 d) and at pH 9 (at 40 °C: k= 0.015 1/h; half-life 45 hours; extrapolated to 20°C: k= 0.075/d; half-life: 9.3 d).

Key value for chemical safety assessment

Half-life for hydrolysis:

35 h

at the temperature of:

70 °C

Additional information

The test was performed to investigate the abiotic degradation of the test substance. The test followed the EU method 84/449/EEC adopted 1984 and was in compliance with GLP.

The determined hydrolysis rate constant and half-life for pH 4 and pH 9, 40 °C were 0.04 1/h and 17 hours, and 0.015 1/h and 45 hours, respectively. Extrapolated to 20°C according to equation R.16 -9 (ECHA guidance document R.16) this leads to k= 0.20/d; half-life: 3.5 d at pH 4 and k= 0.075/d; half-life: 9.3 d at pH 9.

The determined hydrolysis rate constant and half-life for pH 7, 60 °C were 0.005 1/h and 135 hours, respectively; and at 70 °C 0.02 1/h and 35 hours, respectively.

In conclusion, the test substance was hydrolytically instable under the test conditions, and abiotic degradation will occur at pH values relevant for the environment especially in the more acidic and alkaline pH range.

The requirements of the followed guideline were fulfilled; however, the test followed the EU method C.10 adopted 1984, which in contrast to the OECD guideline 111 (2004) did not require testing at a minimum of three temperatures at pH values where hydrolysis was observed. Nonetheless, the results of the study were considered reliable (RL2).