Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

other information

Study period:

2001-12-28 to 2002-02-02

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 1992

Deviations:

yes

Remarks:

preliminary test was performed at pH 4 and 9. No analytical dose verfication performed.

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: pH 4: 0, 2.4 and 120 hours after test initiation, pH 9: 0, 2.4 and 120 hours after test initiation (2 replicates per sampling point)

Buffers:

- pH Composition of buffer: pH 4: citric acid - sodium hydroxide - hydrochloric acid, pH 7: potassium dihydrogen phosphate - sodium hydroxide, pH 9: boric acid - potassium chloride - sodium hydroxide

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: not reported

TEST MEDIUM
- Volume used/treatment: 50 mL 450 ml of the test item in pH4 buffer solution diluted 1 : 2 (v : v) with water, pH 9: 50 mL/450 ml of the test item in buffer solution, pH 7: 50 ml of the test item were tried to dissolve in 450 mL standard buffer pH 7
- Kind and purity of water: not reported

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.87 other: Area determined by HPLC and divided by the area of the standard solution

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

0.5 other: Area determined by HPLC and divided by the area of the standard solution

Positive controls:

no

Negative controls:

no

Transformation products:

not measured

% Recovery:

99

pH:

9

Temp.:

50 °C

Duration:

120 h

% Recovery:

85

pH:

9

Temp.:

50 °C

Duration:

2.4 h

% Recovery:

130

pH:

4

Temp.:

50 °C

Duration:

120 h

% Recovery:

78.5

pH:

4

Temp.:

50 °C

Duration:

2.4 h

Details on results:

- A complete dissolution of the test item could not be achieved at pH 7; a milky white precipitate was found on the bottom of the reaction flask. Because of the low sensitivity of the analytical method for the test item in buffer solutions a lower concentrated test mixture was not applicable.

Validity criteria fulfilled:

not specified

Conclusions:

Hydrolysis of the test item can not be found at pH 9. The probability of hydrolysis is not very high at pH 4. A complete dissolution could not be achieved at pH 7. Finally the degrees of hydrolysis can not be stated.

Executive summary:

The hydrolysis as a function of pH of the test item was determined according EEC-Directive 92/69 EEC, Part C. As a result of pretesting at pH 7 no sufficient solubility of the test item in the aqueous buffer solution was found and no further tests were carried out at this pH. As a result from the preliminary tests additional testing at pH 9 was not required because the degree of hydrolysis was lower than 10% within 5 days.
The shape of the compared chromatograms of the test item at pH 4 at 0 h reaction time and after 5 days do not show big differences so the probability of hydrolysis (generating degradation products and new peaks in the chromatogram) is not very high. In addition the solubility of the test item in the buffer solution is not optimal: a milky white haze could be seen after dissolution of the test item and throughout the HPLC-analysis. Finally the degrees of hydrolysis can not be stated.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-12-2612 to 2008-02-08

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:

2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

yes

Analytical monitoring:

yes

Details on sampling:

Day 0, 1, 3 and 5

Buffers:

see Section "Any other information on materials and methods", Table A7.1.1.1.1- 4

Details on test conditions:

Please refer to Table A7.1.1.1.1- 6.
The tubes were incubated for 5 days in darkness in a thermostatically controlled bath.

Duration:

5 d

Initial conc. measured:

>= 26.45 - <= 27.18 mg/L

Number of replicates:

The samples were analysed at day 0 (one sample), 1 (in duplicate), 3 (in duplicate), and 5 (in duplicate) as described in OECD guideline 111.

Preliminary study:

Recoveries of 14C from the test solutions decreased to 59.3 % (for pH 7) and 58.6 % (for pH 9) at day 5 of the experiment respectively, whereas at pH 4, 105.6 % could be recovered. Low recoveries at pH 7 and 9 were explained by adsorption of the test substance onto the walls of the glass vials. Rinsing of the vial walls with 1 ml acetonitrile/water (3:7, v/v) and sonification resulted in improved recoveries of close to 100 % (see Table A7.1.1.1.1- 7).
Significant chromatographic peaks other than those attributable to the lead components of the test item were not detected: Any other signals accounted for less than 2.5 % ITR at any sampling time.

Since less than 10 % of the test item hydrolysed at 50 °C at pH 4, 7, and 9 within 5 days, corresponding to a DT50 (25°C) > 1 year (tier 1), no further hydrolysis testing was considered to be necessary (see below).

Transformation products:

not measured

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

Not applicable because the preliminary test results indicate that the substance is hydrolytically stable.

% Recovery:

>= 97.1 - <= 97.8

pH:

7

Temp.:

50 °C

Duration:

120 h

% Recovery:

>= 103.91 - <= 107.2

pH:

4

Temp.:

50 °C

Duration:

120 h

% Recovery:

> 92.9 - <= 93.3

pH:

9

Temp.:

50 °C

Duration:

120 h

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

From day 1 to day 5 of the experiment, recoveries of ¹⁴C in the test solution decreased from approx. 100 % to 59.3 % (at pH 7) and 58.6 % (at pH 9), respectively, whereas at pH 4 105.6 % of the radioactivity were recovered on day 5. It was clearly demonstrated that the test material had adsorbed onto the walls of the glass vials at pH 7 and 9, but was removable by rinsing the vial walls with acetonitrile/water, leading to total recovery rates of 92.9 and 102% as the sum of the test item solutions and the rinsing solutions. Less than 10 % of the test item hydrolysed in the preliminary test during five days at 50 ± 5 °C. Hence, k_H and DT₅₀ or DT₉₀ values could not be established. In conclusion, the test substance is considered to be hydrolytically stable. The half-life periods at pH 4, 7 and 9 can be expected to exceed one year at 25 °C.

Table A7.1.1.1.1-7:Hydrolysis of test compound, transformation products and reference substance, expressed as percentage of initial concentrations, at pH 4, pH 7 and pH 9. n.d. = not determined.

Buffer	Sampling time [h]	Replicate	Concentration of^14C-test item [µg/mL]	Recovery of applied radioactivity [%]	Recovery of applied radioactivity [%] in washing solution	^14C-test item concentration in washing solution [µg/mL]	Sum: µg^14C-test item/mL	Sum: recovery of applied radioactivity [%]
pH 4
	0	0d	27.18	100.00
	24	1d/1	27.65	101.75
		1d/2	27.98	102.94
	72	3d/1	27.63	101.68
		3d/2	28.31	104.16
	120	5d/1	28.24	103.91
		5d/2	29.14	107.20
pH 7
	0h	0d	26.45	100.00
	24h	1d/1	18.80	71.06	29.51	7.81	26.6	100.6
		1d/2	19.16	72.44	29.53	7.81	27.0	102.0
	72h	3d/1	16.20	61.23	34.14	9.03	25.2	95.4
		3d/2	17.39	65.74	34.43	9.11	26.5	100.2
	120h	5d/1	15.61	59.01	38.09	10.07	25.7	97.1
		5d/2	15.77	59.62	38.19	10.10	25.9	97.8
pH 9
	0h	0d	26.60	100.00
	24h	1d/1	20.37	76.58	20.70	5.51	25.9	97.3
		1d/2	18.30	68.79	28.36	7.54	25.8	97.1
	72h	3d/1	18.25	68.60	26.56	7.06	25.3	95.2
		3d/2	16.22	60.97	34.32	9.13	25.3	95.3
	120h	5d/1	16.34	61.42	31.89	8.48	24.8	93.3
		5d/2	14.84	55.79	37.12	9.87	24.7	92.9
Applied radioactivity: pH = 4: 38.68 KBq/mL, equivalent to 27.18 µg test item/mL pH = 7: 37.64 KBq/mL, equivalent to 26.45 µg test item/mL pH = 9: 37.85 KBq/mL, equivalent to 26.60 µg test item/mL.

 

Validity criteria fulfilled:

yes

Conclusions:

The test substance can be characterised as being hydrolytically stable (half-life periods at pH 4, 7 and 9 can be expected to exceed one year at 25°C.

Executive summary:

The registration substance was tested for hydrolysis according to OECD guideline 111 (2002). The test item was dissolved in buffered aqueous media of defined pH-values (pH 4, 7, or 9) and maintained at constant temperature (50 °C) in the darkness. The concentrations of the lead compounds of the test item were measured as a function of time. At 0, 1, 3 and 5 days radioactivity as well as the identity of the components of the test item and potential hydrolysis products were verified by HPLC-MS/MS.

The results of the preliminary test indicated no need for further testing. Deviations from the guidelines were not reported.

From day 1 to day 5 of the experiment, recoveries of ¹⁴C in the test solution decreased from approx. 100 % to 59.3 % (at pH 7) and 58.6 % (at pH 9), respectively, whereas at pH 4 105.6 % of the radioactivity were recovered on day 5. It was clearly demonstrated that the test material had adsorbed onto the walls of the glass vials at pH 7 and 9, but was removable by rinsing the vial walls with acetonitrile/water, leading to total recovery rates in the range of 92.9 and 102% as the sum of the test item solutions and the rinsing solutions. Less than 10 % of the test item hydrolysed in the preliminary test during five days at 50 ± 5 °C. Hence, k_H and DT₅₀ or DT₉₀ values could not be established. In conclusion, the test substance is considered to be hydrolytically stable. The half-life periods at pH 4, 7 and 9 can be expected to exceed one year at 25 °C.

Description of key information

Amines, N-C10-C16-alkyltrimethylenedi-, reaction products with chloroacetic acid is considered to be hydrolytically stable, half-life periods at pH 4, 7 and 9 can be expected to exceed one year at 25°C (OECD guideline 111, GLP). 

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

Hydrolysis of C14-labelled test substance was tested for hydrolysis according to OECD guideline 111 (2002). The test item was dissolved in buffered aqueous media of defined pH-values (pH 4, 7, or 9) and maintained at constant temperature (50 °C) in the darkness. The concentrations of the lead compounds of the test item were measured as a function of time. At 0, 1, 3 and 5 days, radioactivity as well as the identity of the components of the test item and potential hydrolysis products were verified by HPLC-MS/MS.

The results of the preliminary test indicated no need for further testing. From day 1 to day 5 of the experiment, recoveries of¹⁴C-labelled test substance in the test solution decreased from approx. 100 % to 59.3 % (at pH 7) and 58.6 % (at pH 9), respectively, whereas at pH 4 105.6 % of the radioactivity were recovered on day 5. It was clearly demonstrated that the test material had adsorbed onto the walls of the glass vials at pH 7 and 9, but was removable by rinsing the vial walls with acetonitrile/water, leading to total recovery rates in the range of 92.9 and 102% as the sum of the test item solutions and the rinsing solutions. Less than 10 % of the test item hydrolysed in the preliminary test during five days at 50 ± 5 °C. Hence, k_H and DT₅₀ or DT₉₀ values could not be established.

In conclusion, Amines, N-C10-C16-alkyltrimethylenedi-, reaction products with chloroacetic acid is considered to be hydrolytically stable. The half-life periods at pH 4, 7 and 9 can be expected to exceed one year at 25 °C.