3-[[3-(dimethylamino)propyl]amino]propiononitrile

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

This study was conducted between 09 April 2016 and 16 December 2016

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)

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

13 April 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

The sample solutions were taken from the waterbath at various times and the pH of each solution recorded.
The concentration of the sample solution was determined by high performance liquid chromatography (HPLC).

Buffers:

Specification of Buffer Solutions

Buffer solution
(pH) Components Concentration (mol dm-3)
4 Potassium hydrogen phthalate 0.05
7 Disodium hydrogen orthophosphate (anhydrous) 0.03
Potassium dihydrogen orthophosphate 0.02
Sodium chloride 0.02
9 Disodium tetraborate 0.01
Sodium chloride 0.02
These solutions were subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen content.

Details on test conditions:

Performance of the Test

Preparation of the Test Solutions
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 500 mg/L in the three buffer solutions.
The test solutions were split into individual vessels for each data point.
The solutions were shielded from light whilst maintained at the test temperature.

Preliminary Test/Tier 1
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5 °C for a minimum period of 120 hours.

Tier 2
Results from the Preliminary test/Tier 1 showed it was necessary to undertake further testing at pH 7 and pH 9, with solutions being maintained at 50.0 ± 0.5 °C for a period of 144 hours.

Testing at pH 7 and 9 maintained at 50.0 ± 0.5 °C showed half-life in excess of 300 hours, therefore further testing at pH 7 and pH 9, with solutions being maintained at 25.0 ± 0.5 °C for a period of approximately 30 days.

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Preliminary study:

Preliminary Test/Tier 1
The test item concentrations at the given time points are shown in the following tables:
Table 1 pH 4 at 50.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration
A B A B
0 0.621 0.634 - -
24 0.650 0.640 104 102
120 0.594 0.579 94.6 92.2
144 0.582 0.576 92.7 91.8

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

Table 2 pH 7 at 50.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration
A B A B
0 0.508 0.491 - -
24 0.488 0.479 97.6 95.9
120 0.402 0.417 80.5 83.5
144 0.409 0.404 81.9 80.9

Result: The extent of hydrolysis after 144 hours indicated that a further test (Tier 2) was required to estimate the rate constant and half-life at 25 °C.

Table 3 pH 9 at 50.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration
A B A B
0 0.506 0.490 - -
24 0.459 0.472 92.1 94.7
120 0.396 0.404 79.5 81.0
144 0.415 0.419 83.2 84.1

Result: The extent of hydrolysis after 144 hours indicated that a further test (Tier 2) was required to estimate the rate constant and half-life at 25 °C

Test performance:

Validation
The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 2 to 10 mg/L, due to the instrumentation a linear or quadratic fit was necessary and therefore a linearity was run with all samples.

Transformation products:

no

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

Identification of Hydrolysis Products – Tier 3
Usually, hydrolysis products should be identified using LC-MS or GC-MS. However, this procedure implies sufficient separation of the individual components that are present in the incubated test item solution (i.e. parent compound and hydrolysis products). Hydrolysis of the test item showed no product peaks when monitored by HPLC mass spectrometry. Therefore as detection of the products was not possible the identification of the hydrolysis products was technically not feasible. The chemical structure of the hydrolysis product(s) is most probably quite similar to the one of the parent compound.

% Recovery:

> 14.1 - < 17.4

pH:

7

Temp.:

50 °C

Duration:

ca. 672 h

% Recovery:

> 93.5 - < 94.9

pH:

7

Temp.:

25 °C

Duration:

ca. 672 h

% Recovery:

> 59.3 - < 67.4

pH:

9

Temp.:

50 °C

Duration:

ca. 768.4 h

% Recovery:

> 93.9 - < 98.5

pH:

9

Temp.:

25 °C

Duration:

ca. 672 h

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

ca. 1 yr

Key result

pH:

9

Temp.:

25 °C

DT50:

ca. 1 yr

Details on results:

Tier 2:
The test item concentrations at the given time points are shown in the following tables:

Table 4 pH 7 at 50.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration Log Concentration
A B A B A B
0 0.678 0.711 - - -0.168 -0.148
120 0.452 0.441 65.0 63.4 -0.345 -0.356
219 0.374 0.369 53.9 53.1 -0.427 -0.433
360 0.319 0.313 45.9 45.0 -0.497 -0.505
480 0.338 0.342 48.6 49.2 -0.471 -0.466
672 0.121 9.77 x 10-2 17.4 14.1 -0.918 -1.01
Result: Slope = -1.00 x 10-3
kobs = 2.30 x 10-3 hour-1
t½ = 301 hours
= 13 days

Table 2 pH 7 at 25.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration Log Concentration
A B A B A B
0 0.575 0.554 - - -0.240 -0.257
168 0.489 0.471 86.6 83.4 -0.311 -0.327
336 0.550 0.546 97.5 96.7 -0.259 -0.263
480 0.488 0.456 86.4 80.8 -0.312 -0.341
672 0.536 0.528 94.9 93.5 -0.271 -0.277
Result: Slope = -3.24 x 10-5
kobs = 7.47 x 10-5 hour-1
t½ = 9.28 x 103 hours
= 387 days
Table 3 pH 9 at 50.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration Log Concentration
A B A B A B
0 0.589 0.593 - - -0.230 -0.227
120 0.454 0.455 76.8 77.1 -0.343 -0.342
219 0.405 0.400 68.5 67.6 -0.393 -0.398
360 0.372 0.373 62.9 63.1 -0.430 -0.428
480 0.510 0.504 86.4 85.3 -0.292 -0.297
672 0.368 0.314 62.3 53.1 -0.434 -0.503
768.4 0.350 0.398 59.3 67.4 -0.456 -0.400
Result: Slope = -2.05 x 10-4
kobs = 4.73 x 10-4 hour-1
t½ = 1.47 x 103 hours
= 61 days

Table 4 pH 9 at 25.0 ± 0.5 ºC
Time (Hours) Concentration (g/L) % of mean initial concentration Log Concentration
A B A B A B
0 0.479 0.475 - - -0.319 -0.323
168 0.466 0.473 97.7 99.2 -0.331 -0.325
336 0.482 0.481 101 101 -0.317 -0.318
480 0.435 0.436 91.2 91.3 -0.361 -0.361
672 0.448 0.470 93.9 98.5 -0.348 -0.328
Result: Slope = -3.83 x 10-5
kobs = 8.81 x 10-5 hour-1
t½ = 7.87 x 103 hours
= 328 days

Validity criteria fulfilled:

yes

Conclusions:

The estimated rate constant and half-life at 25 °C of the test item are shown in the following table:

pH Estimated half-life at 25 °C
4 > 1 year
7 Approximately 1 year
9 Approximately 1 year

Executive summary:

The general physico-chemical properties of 3-[[3-(Dimethylamino)propyl]amino]propanenitrile (TK2710) have been determined.  

Hydrolysis as a Function of pH.

Assessment of hydrolytic stability was carried out using a procedure designed to be compatible with Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. The results are as follows:

pH       Estimated half-life at 25 °C

4       > 1 year

7       Approximately 1 year

9       Approximately 1 year

Description of key information

Hydrolysis as a function of pH for Aradur 1019 was determined according to OECD test guideline 111

pH	Estimated half-life at 25 °C
4	> 1 year
7	Approximately 1 year
9	Approximately 1 year

Result:       The extent of hydrolysis after 144 hours indicated that a further test (Tier 2) was required to estimate the rate constant and half-life at 25 °C