N,N,4-trimethylpiperazine-1-ethylamine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 November 2017 to 20 March 2018

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)

Version / remarks:

13 April 2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Batch No.of test material: PFW160141
- Purity: 99.5%
- Expiration date of the lot/batch: 30 December 2018
- Stability under test conditions: Room temperature in the dark

Radiolabelling:

no

Buffers:

The test system consisted of buffer solutions at pH’s 4, 7 and 9.
Buffer Solution Specification:
Buffer solution (pH) Components Concentration (mmol dm-3)
4 Citric acid 6
Sodium chloride 4
Sodium hydroxide 7
7 Disodium hydrogen orthophosphate (anhydrous) 3
Potassium dihydrogen orthophosphate 2
Sodium chloride 2
9 Disodium tetraborate 1
Sodium chloride 2

The buffer solutions were passed through a 0.2 µm membrane filter to sterilize and subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen.

Details on test conditions:

Preparation of the Test Solutions
Stock solutions of test item were prepared at a nominal concentration of 1.0 g/L in the three buffer solutions. The stock solutions were adjusted to the nominal pH of the relevant buffer solution and then split into individual glass vessels, sealed with minimal headspace, for each data point. These sample 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 period of 120 hours.

Tier 2
Results from the Preliminary test/Tier 1 showed it was not necessary to undertake further testing at pH 4, 7 and 9.

Test performance:

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 2 to15 mg/L. The results were satisfactory with correlation coefficient (r) of ≥ 0.992 being obtained.

Transformation products:

no

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

No significant peaks were observed at the approximate retention time of the test item on analysis of any matrix blank solutions.

The mean peak areas relating to the standard and sample solutions are shown in Table 1

Table 1:

Solution	Mean Peak Area
Standard 10.0 mg/L, pH 4	1.397 x 10^7
Standard 10.1 mg/L, pH 4	1.457 x 10^7
Initial Sample A, pH 4	1.174 x 10^7
Initial Sample B, pH 4	1.044 x 10^7
24 Hour Sample A, pH 4	1.139 x 10^7
24 Hour Sample B, pH 4	1.080 x 10^7
Standard 10.0 mg/L, pH 7	1.370 x 10^7
Standard 10.1 mg/L, pH 7	1.371 x 10^7
Initial Sample A, pH 7	1.068 x 10^7
Initial Sample B, pH 7	1.042 x 10^7
24 Hour Sample A, pH 7	1.058 x 10^7
24 Hour Sample B, pH 7	1.036 x 10^7
Standard 10.0 mg/L, pH 9	1.366 x 10^7
Standard 10.1 mg/L, pH 9	1.374 x 10^7
Initial Sample A, pH 9	1.295 x 10^7
Initial Sample B, pH 9	1.276 x 10^7
24 Hour Sample A, pH 9	1.303 x 10^7
24 Hour Sample B, pH 9	1.276 x 10^7
Standard 10.0 mg/L, pH 4	1.397 x 10^7
Standard 10.1 mg/L, pH 4	1.400 x 10^7
120 Hour Sample A, pH 4	1.108 x 10^7
120 Hour Sample B, pH 4	1.116 x 10^7
Standard 10.0 mg/L, pH 7	1.389 x 10^7
Standard 10.1 mg/L, pH 7	1.402 x 10^7
120 Hour Sample A, pH 7	1.110 x 10^7
120 Hour Sample B, pH 7	1.080 x 10^7
Standard 10.0 mg/L, pH 9	1.377 x 10^7
Standard 10.1 mg/L, pH 9	1.404 x 10^7
120 Hour Sample A, pH 9	1.361 x 10^7
120 Hour Sample B, pH 9	1.335 x 10^7

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

Table 2          pH 4 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.826	0.734	-	-
24	0.801	0.760	103	97.4
120	0.796	0.802	102	103

pH 4 at 50 °C result:  Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

Table 3          pH 7 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.782	0.763	-	-
24	0.775	0.759	100	98.2
120	0.798	0.777	103	101

pH 7 at 50 °C result:  Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

Table 4          pH 9 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.950	0.935	-	-
24	0.956	0.935	101	99.3
120	0.983	0.964	104	102

pH 9 at 50 °C result:  Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

 Discussion

No significant peaks were observed at the approximate retention time of the test item on analysis of any matrix blank solutions.

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis as function of pH of JeffCat TAP has been determined according to OECD guideline 111 under GLP procedure. At pH 4, 7 and 9, a decrease in concentration < 10 % was observed after 5 days (half-life time > 1 year). Hence it was concluded that the test substancel is hydrolytically stable at pH 4, 7 and 9.

Description of key information

One study (Covance, 2019) was performed according to OECD guideline 111 and regarded as a key study (Klimisch score of 1). A half-life time of > 1 year at 25 °C was determined for the test substance.

Additional information

Hydrolysis was studied in a guideline study (OECD Guideline 111) during 5 days at pH 4, 7 and 9 and at 50°C. Less than 10% hydrolysis was observed at the end of testing at each pH level tested. Based on these results, no further testing was needed and it was concluded that the estimated half-life at 25°C is > 1 yr (substance hydrolytically stable). The results of the test can be considered reliable without restriction.