2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-10-26 to 2017-10-31

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:

April 13, 2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Official Journal of the European Union L 142; May 31, 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0 and 120 h
- Sampling method: -
- Sampling intervals/times for pH measurements: 0 and 120 h
- Other observation: none

Buffers:

Buffer solutions at pH 4.0, 7.0 and 9.0 were prepared.
pH 4.0: 76.5 mL 0.1 M Sodium acetate and 423.5 mL 0.1 M Acetic acid were mixed
pH 7.0: 250 mL 0.1 M TRIS buffer and 233 mL 0.1 M Hydrochloric acid were diluted to 500 mL with ultra-pure water
pH 9.0: 53.5 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Boric acid and Potassium chloride were diluted to 500 mL with ultra-pure water

Details on test conditions:

TEST SYSTEM
- Material: glass
- Type, volume of headspace: 20 mL headspace vials
- Is there any indication of the test material adsorbing to the walls of the test apparatus? none
TEST MEDIUM
- Volume used/treatment: 20 mL
- Kind and purity of water: ultra-pure sterile water
- Preparation of test medium: 250 mg dissolved in each buffer solution to a total volume of 250 mL

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

0.99 µg/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.99 µg/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.95 µg/L

Number of replicates:

5 per pH

Positive controls:

no

Negative controls:

yes

Preliminary study:

Recovery after 120 h at 50 °C:
- pH 4: 105%
- pH 7: 95%
- pH 9: 96%
Therefore, it was concluded that the substance is hydrolytically stable and no further experiments were conducted.

Transformation products:

not measured

% Recovery:

105

pH:

4

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

95

pH:

7

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

96

pH:

9

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

Key result

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

The hydrolysis test was performed at 50 ± 0.5 °C, at pH 4, 7 and 9. Measured concentrations and pH values are summarised in the table in the section “Any other information on results incl. table”

Table 5: Measured data

pH	Sampling time, hour	Concentration of BIS-TRIS				Measured pH
		Results of the replicates in m/mL	Mean, mg/mL	Measured Nominal. %	End/Start
4	0 (Start)	Control buffers		-	-	3.96
		0.99	0.99	99	-	4.21
		0.99
		0.97
		0.99
		1.00
	120	Control buffers		-	-	4.11
		1.36*	1.03	103	105	4.21
		1.02
		1.04
		1.04
		1.04
7	0 (Start)	Control buffers		-	-	7.00
		0.99	0.99	98	-	7.47
		0.96
		0.99|
		1.00
		1.00
	120	Control buffers		-	-	7.02
		0.97	0.93	93	95	7.52
		0.90
		0.94
		0.92
		0.94
9	0 (Start)	Control buffers		-	-	S.9S
		0.95	0.95	94	-	9.00
		0.93
		0.95
		0.96
		0.95
	120	Control buffers		-	-	9.08
		0.92	0.91	90	96	9.01
		0.91
		0.91
		0.91
		0 9C

*Wrong dilution; this value was not taken into consideration for further calculations.

Validity criteria fulfilled:

yes

Conclusions:

The hydrolysis of the substance as a function of pH was determined in a preliminary test according to OECD Test Guideline 111 under GLP conditions.
As no hydrolysis was observed at pH 4, 7 and 9 at 50 °C for 120 h, it was concluded that the substance is hydrolytically stable and the hydrolysis was not investigated further.

Executive summary:

The hydrolysis of the test item in solutions of three different pH values at 50 ± 0.5 °C was evaluated according to OECD Guideline No. 111, ”Hydrolysis as a Function of pH” and Council Regulation (EC) No. 440/2008, Part C, C.7, "Degradation - Abiotic Degradation: Hydrolysis as a Function of pH”. During the course of this study, a preliminary test was carried out. There was a slight increase in the pH value at the start of the experiment at pH 4 (actual value: pH 4.21) and pH 7 (actual value: 7.47). From the start onwards the pH was stable and the variation was not more than 0.1 pH units until the end of the measurement as it was noted for the other measurement at pH 9. These small differences were considered to have no effect on the outcome of the study in the absence of any indication for degradation at the actual values. It is considered that the test item would have been stable also at pH values of 4.0 and 7.0. Therefore, this study is considered valid and no repetition of the experiment was necessary. No hydrolysis was observed at pH 4, pH 7 and pH 9 at temperature 50 °C after 120-hours, thus, it was concluded that the substance is hydrolytically stable and the hydrolysis was not investigated further.

Description of key information

The hydrolysis of the substance as a function of pH was determined in a preliminary test according to OECD Test Guideline 111 under GLP conditions.

As no hydrolysis was observed at pH 4, 7 and 9 at 50 °C for 120 h, it was concluded that the substance is hydrolytically stable and the hydrolysis was not investigated further (reference 5.1.2-1).

Additional information

The hydrolysis of the test item in solutions of three different pH values at 50 ± 0.5 °C was evaluated according to OECD Guideline No. 111, ”Hydrolysis as a Function of pH” and Council Regulation (EC) No. 440/2008, Part C, C.7, "Degradation - Abiotic Degradation: Hydrolysis as a Function of pH”. During the course of this study, a preliminary test was carried out. There was a slight increase in the pH value at the start of the experiment at pH 4 (actual value: pH 4.21) and pH 7 (actual value: 7.47). From the start onwards the pH was stable and the variation was not more than 0.1 pH units until the end of the measurement as it was noted for the other measurement at pH 9. These small differences were considered to have no effect on the outcome of the study in the absence of any indication for degradation at the actual values. It is considered that the test item would have been stable also at pH values of 4.0 and 7.0. Therefore, this study is considered valid and no repetition of the experiment was necessary. No hydrolysis was observed at pH 4, pH 7 and pH 9 at temperature 50 °C after 120-hours, thus, it was concluded that the substance is hydrolytically stable and the hydrolysis was not investigated further.