N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 September 2017 to 07 December 2017

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)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Source and lot/batch No.of test material: Sponsor and AAN0680
- Expiration date of the lot/batch: 30 August 2018
- Purity test date: 09 September 2016

Radiolabelling:

no

Analytical monitoring:

no

Buffers:

Acetate buffer pH 4, 0.01 M Solution of 16.7% 0.01 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. Buffer contained 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.01 M Solution of 0.01 M potassium di-hydrogen-phosphate in water adjusted to pH 7 using 1N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.
Borate buffer pH 9, 0.01 M Solution of 0.01 M boric acid in water and 0.01 M potassium chloride in water adjusted to pH 9 using 1N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.

Details on test conditions:

pH code Temperature I Temperature II Temperature III
pH 7 19.7°C ± 0.1°C 40.1°C ± 0.1°C 49.5°C ± 0.1°C
pH 9 23.2°C ± 4.4°C 40.1°C ± 0.1°C 49.5°C ± 0.1°C

Preliminary study:

During method validation it was decided to prepare calibration curves in the buffers; however due to extreme hydrolysis it was not possible to create the calibration in buffers during the preliminary test. Therefore it was decided to proceed with the main study by preparation of the calibration solutions in water. Preliminary test is archived in raw data.

Test performance:

pH 4
Due to instantaneous hydrolysis it was technically not possible to perform the study at pH 4. Results are archived in raw data.

pH 7
The analytical results of the main study are given in Table 6 to Table 9 (see attached)
Small responses at the retention time of the test item were detected in the chromatograms in the blank buffer solutions. The concentrations were low and therefore considered not to have significant effect on the results of the hydrolysis.
The mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 70-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.
For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. At all temperatures linear relationships were obtained.
The rate constant (kobs) and half-life time of the test item at each temperature was obtained and the Arrhenius equation was used to determine the rate constant and half-life time at 25°C

pH 9
Small responses at the retention time of the test item were detected in the chromatograms in the blank buffer solutions. The concentrations were low and therefore considered not to have significant effect on the results of the hydrolysis.
(i.e. <70%). This had no impact on the hydrolysis parameters, since they are based on the difference in concentration. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.
For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time.
Nevertheless, when using those results hydrolysis appears to be faster at 40°C than at 50°C. This indicates that hydrolysis is not the only reaction that happens.

Transformation products:

not specified

pH:

7

Temp.:

20 °C

DT50:

1.5 h

pH:

7

Temp.:

25 °C

DT50:

1.2 h

pH:

7

Temp.:

40 °C

DT50:

0.61 h

pH:

7

Temp.:

50 °C

DT50:

0.36 h

pH:

9

Temp.:

20 °C

DT50:

91 h

pH:

9

Temp.:

25 °C

DT50:

9 h

pH:

9

Temp.:

40 °C

DT50:

0.007 h

pH:

9

Temp.:

50 °C

DT50:

4.2 h

Details on results:

The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride at pH values normally found in the environment (pH 7-9). Half life at pH7 at 25 °C was 1.2 hours and 9hrs for pH 9.

pH 7		pH 9
Temperature [°C]	t½	Temperature [°C]	t½
20	1.5 hours	20	91 hours
25	1.2 hours	25	9.0 hours
40	0.61 hours	40	0.0074 hours
50	0.36 hours	50	4.2 hours

Validity criteria fulfilled:

yes

Conclusions:

The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride at pH values normally found in the environment (pH 7-9).

Description of key information

The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride at pH values normally found in the environment (pH 7-9).

The half-life times of the test item were as follows:

pH 7		pH 9
Temperature [°C]	t½	Temperature [°C]	t½
20	1.5 hours	20	91 hours
25	1.2 hours	25	9.0 hours
40	0.61 hours	40	0.0074 hours
50	0.36 hours	50	4.2 hours

Key value for chemical safety assessment

Half-life for hydrolysis:

1.5 h

at the temperature of:

20 °C