1,4-Dihydroxy-2,2,6,6-tetramethylpiperidine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Preparation of samples:
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 1g/L in the three buffer solutions. 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 period of 120 hours.


Analysis of Sample Solutions:
Aliquots of the sample solutions were taken from the flasks at various times and the pH of each solution recorded.

The concentration of the sample solution was determined by GC

Samples:
pH 4 sample solutions were adjusted to approximately pH 7 then diluted by a factor of 1.25 using pH 7 buffer solution. pH 7 solutions were diluted by a factor of 1.25 using pH 7 buffer solution prior to further analysis.
An aliquot (5.0ml) of sample solution was passed through an isolute C18 (EC) cartridge which had been pre-conditioned with methanol (5ml) followed by appropriate buffer solution (5ml). The cartridge was dried under a stream of nitrogen and the test material eluted with methanol (5ml). The methanol was evaporated to dryness and the residue re- dissolved in pyridine (0.5ml), 0.2% 4-dimethylaminopyridine (DMAP) solution (0.85ml) and acetic anhydride (1.0ml). The solution was heated to approximately 60°C for approximately 1 hour, allowed to cool and isopropyl alcohol (0.85ml) added. The solution was quantitatively transferred to a volumetric flask and diluted to 20.0ml with methanol. This was performed in duplicate (A and B)

Standards:
A mass of test material was dissolved in pyridine (0.5ml), 0.2% 4-dimethylaminopyridine (DMAP) solution (0.85ml) and acetic anhydride (1.0ml). The solution was heated at approximately 60°C for approximately 1 hour, allowed to cool and isopropyl alcohol (0.85ml) added. The solution was quantitatively transferred to 100ml methanol to produce a nominal concentration of 250mg/l. This was peforme in duplicate (A and B)

Buffers:

Buffer solution
(pH) Components Concentration
(mol dm-3)
4 Citric acid 0.05
Sodium hydroxide 0.10
Hydrochloric acid 0.05
7 Disodium hydrogen orthophosphate 0.04
Potassium dihydrogen orthophosphate 0.03
9 Disodium tetraborate 0.05
Hydrochloric acid 0.02


The buffer solutions were passed through a 0.2μm membrane filter to ensure they were sterile before commencement of the test.These solutions were also subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen content.

Details on test conditions:

Duplicate

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

1.1 g/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.608 g/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.829 g/L

Number of replicates:

Duplicate

Positive controls:

no

Negative controls:

no

Preliminary study:

The man peak areas relating to the standard and sample solutions are shown in the attached background information

Transformation products:

not specified

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

Remarks on result:

other: The test material could not be prevented from oxidising at pH 9 and therefore a half life could not be estimated

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

pH 4 at 50 °C ± 0.5°C

Time (hours)	0	2.4	24	120
Concentration (g/l)	1.10	1.09	1.07	1.00
% of initial	100	99	97	91

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

pH 7 at 50 °C ± 0.5°C

Time (hours)	0	2.4	24	120
Concentration (g/l)	0.608	0.651	0.643	0.696
% of initial	100	107	106	114

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

pH 9 at 50°C ± 0.5°C

Time (hours)	0	2.4	24	120
Concentration (g/l)	0.829	0.783	0.668	0.399
% of initial	100	94	81	48

Result: test material oxidises over time; estimation of hydrolytic half life not possible

Validity criteria fulfilled:

yes

Conclusions:

The estimated half-life at 25 °C for the test item at pH 4 and 7 has been determined to be greater than a year. It was not possible to estimate a half-life at pH 9.

Executive summary:

Method

The determination was carried out using Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Directive 92/69/EEC.

The test system uses sterile buffer solutions at pH’s 4.0, 7.0 and 9.0.

Discussion

The test item was determined to be hydrolytically stable at pH 4 and 7. At pH 9 oxidation of the test material occurred despite efforts to exclude oxygen at all times from the test media and no estimate of half life could be made.

Conclusion

The estimated half-life at 25 °C for the test item at pH 4 and 7 has been determined to be greater than a year. It was not possible to estimate a half-life at pH 9.

Description of key information

The estimated half-life at 25 °C for the test item at pH 4 and 7 has been determined to be greater than a year. It was not possible to estimate a half-life at pH 9.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

The determination was carried out using Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Directive 92/69/EEC.

 

The test system uses sterile buffer solutions at pH’s 4.0, 7.0 and 9.0.

Results at pH 4 and pH 7 showed less than 10% hydroysis after 5 days at 50°C, equivalent to a half-life greater than 1 year. At pH 9 oxidation of the test material occurred despite efforts to exclude oxygen at all times from the test media and no estimate of half life could be made.