N,N-bis(2-hydroxypropyl)benzamide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 13th to Aufust 2nd, 2001

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

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:

During the preliminary test at 50 °C, aliquots of each test solution were analysed at the beginning and after 2.4 and 120 hours.
Further sampling were performed at 65 and 75 °C for the buffered test solutions at pH 7 and 9.

Buffers:

Buffer pH4, Biphtalate
Buffer pH7, Phosphate
Buffer pH9, Borate/Potassium chloride/NaOH

Estimation method (if used):

The reaction rate constant k was calculated for pH 7 and 9 by regression analysis using Arrhenius equation.

Details on test conditions:

EQUIPMENT
The buffer solutions were sterilized for 25 minutes in an autoclave prior to first use. Nitrogen was passed through the buffer solutions for 5 minutes except when freshly sterilized.
All glassware, which must be inert at pH range applied, were rinsed with sterile buffer. The hydrolysis was carried out in flasks which were stoppered or sealed with an inert material (e.g. PTFE).
The water bath used was the thermostatically controlled GFL 1086.

PERFORMANCE OF THE TEST
The test item was dissolved in the buffer solutions and incubated at specific temperatures with the water bath kept constant at ± 0.1 °C, usually.
The concentration of test item was determined as a function of time at each pH.
The preliminary hydrolysis tests were performed at 50 °C ± 0.1 °C at pH 4, 7 and 9.
Further hydrolysis tests were performed at 65 °C and 75 °C in the buffered test solution at pH 7 and 9, due to instability of test item found in preliminary tests.
At pH 4 test item was stable at 50 °C, therefore no further testing was perfomed.

Test solutions were prepared by dissolving 11 ± 0.5 mg of test item in 100 mL buffer solution, different for each pH. The solutions were treated in an ultrasonic bath for 3 minutes and then filtrated (0.45 μm). Two aliquots of test solutions of approximately 50 mL each were transferred into 50 mL Erlenmeyer flasks in order to perform a duplicate test.

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

>= 99 - <= 100 mg/L

Remarks:

Preliminary study

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

>= 107 - <= 108 mg/L

Remarks:

Preliminary study

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

ca. 106 mg/L

Remarks:

Preliminary study

Duration:

1 037 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

>= 107 - <= 108 mg/L

Remarks:

Main study

Duration:

628 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

106 mg/L

Remarks:

Main study

Duration:

260.8 h

pH:

7

Temp.:

65 °C

Initial conc. measured:

>= 105.5 - <= 106.3 mg/L

Duration:

106.5 h

pH:

7

Temp.:

75 °C

Initial conc. measured:

>= 99.5 - <= 100.5 mg/L

Duration:

209.7 h

pH:

9

Temp.:

65 °C

Initial conc. measured:

>= 109.7 - <= 110 mg/L

Duration:

67.5 h

pH:

9

Temp.:

75 °C

Initial conc. measured:

>= 110.5 - <= 111.1 mg/L

Number of replicates:

2 for each pH and temperature

Positive controls:

no

Negative controls:

no

Preliminary study:

At pH 4, substance was completely stable after 120 hours (2% degradation) at 50 °C. No further testing was performed at pH 4.
At pH 7 and 9 substance was unstable after 120 hours (degradation 12-16%) at 50 °C. Testing was prolonged to calculate half-life time at 50 °C.

Test performance:

At pH 7 and 9 further studies were performed at 65 °C and 75 °C in order to calculate rate constants and half-life time at those temperatures and then to determine parameters at 25 °C.

Transformation products:

not measured

Details on hydrolysis and appearance of transformation product(s):

Not applicable

% Recovery:

98

pH:

4

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

>= 86 - <= 88

pH:

7

Temp.:

50 °C

Duration:

120 h

Remarks on result:

other: Unstable after preliminary study

% Recovery:

>= 84 - <= 85

pH:

9

Temp.:

50 °C

Duration:

120 h

Remarks on result:

other: Unstable after preliminary study

% Recovery:

>= 36 - <= 39

pH:

7

Temp.:

50 °C

Duration:

1 037 h

Remarks on result:

other: Main study result

% Recovery:

>= 36 - <= 37

pH:

7

Temp.:

65 °C

Duration:

260.8 h

% Recovery:

>= 32 - <= 33

pH:

7

Temp.:

75 °C

Duration:

106.5 h

% Recovery:

>= 38 - <= 39

pH:

9

Temp.:

50 °C

Duration:

628 h

Remarks on result:

other: main study result

% Recovery:

30

pH:

9

Temp.:

65 °C

Duration:

209.7 h

% Recovery:

38

pH:

9

Temp.:

75 °C

Duration:

67.5 h

Key result

pH:

4

Temp.:

25 °C

DT50:

> 365 d

Type:

other: estimated from preliminary study results

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

>= 0.001 - <= 0.001 h-1

DT50:

31 d

Type:

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

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

>= 0.002 - <= 0.002 h-1

DT50:

37 d

Type:

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

pH:

7

Temp.:

65 °C

Hydrolysis rate constant:

>= 0.004 - <= 0.004 h-1

DT50:

7.5 d

Type:

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

pH:

7

Temp.:

75 °C

Hydrolysis rate constant:

>= 0.01 - <= 0.01 h-1

DT50:

2.8 d

Type:

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

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0 h-1

DT50:

514 d

Type:

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

pH:

9

Temp.:

65 °C

Hydrolysis rate constant:

>= 0.006 - <= 0.006 h-1

DT50:

4.9 d

Type:

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

pH:

9

Temp.:

75 °C

Hydrolysis rate constant:

>= 0.014 - <= 0.015 h-1

DT50:

2 d

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0 h-1

DT50:

253 d

Type:

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

Results with reference substance:

Not applicable

Validity criteria fulfilled:

yes

Conclusions:

The substance does not rapidly hydrolyse at 25 °C at all pH values evaluated (4,7 and 9).
The substance was stable at pH 4. Its half-life time at 25 °C is longer than one year.
Half-life time of the substance at pH 7 (25 °C) was found to be 514 days (12336 hours).
Half-life time of the substance at pH 9 (25 °C) was found to be 253 days (6072 hours).

Executive summary:

The hydrolysis of the substance was tested in a study according to OECD TG 111.

The preliminary experiment was performed at 50 °C and pH 4.0, 7.0 and 9.0. Test item was found to be stable at pH 4.0, therefore no further testing was performed at this pH value.

Substance was not stable at pH 7 and 9, thus further testing was perfomed at 65 and 75 °C in order to calculate the rate constant (k₂₅) and the half-life time of hydrolysis at 25 °C (using Arrhenius equation).

The substance was stable at pH 4. Its half-life time at 25 °C is longer than one year.

Half-life time of the substance at pH 7 (25 °C) was found to be 514 days (12336 hours).

Half-life time of the substance at pH 9 (25 °C) was found to be 253 days (6072 hours).

Description of key information

In a study according to OECD TG 111, half-life time of the substance was evaluated at different pHs:

The substance was stable at pH 4. Its half-life time at 25 °C is longer than one year.

Half-life time of the substance at pH 7 (25 °C) was found to be 514 days (12336 hours).

Half-life time of the substance at pH 9 (25 °C) was found to be 253 days (6072 hours)

Key value for chemical safety assessment

Half-life for hydrolysis:

513 d

at the temperature of:

25 °C