4,4',4''-(ethan-1,1,1-triyl)triphenol

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

Qualifier:

according to guideline

Guideline:

other: EEC Directive 67/548, Annex V, Part C, Test C10-Preliminary Test

Deviations:

no

Remarks:

The study was conducted according to the test guidelines in effect at the time of study conduct.

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0, 2.4 hours, and 5 days
- Sampling method: a 3 mL aliquot of the cooled test solution was measured by bulb pipette into a 25 mL volumetric flask
- Sampling intervals/times for pH measurements: pH 4, 7, and 9 buffers were prepared and adjusted with 0.1 M hydrochloric acid or sodium hydroxide. No further pH measurements were reported.
- Sample storage conditions before analysis: not reported

Buffers:

- pH: 4
- Composition of buffer: potassium hydrogen phthalate (20.7 g) was dissolved in 1 litre of distilled water. The pH was adjusted to 4.00 with 0.1 M hydrochloric acid.

-pH: 7
-Composition of buffer: potassium dihydrogen orthophosphate (13.61 g) was dissolved in 1 litre of distilled water. The solution was adjusted to pH 7.00 with 0.1M sodium hydroxide solution.

-pH: 9
-Composition of buffer: potassium chloride (7.46 g) and boric acid (6.18 g) were dissolved in 1 litre of distilled water. The solution was adjusted to pH 9.00 with 0.1M sodium hydroxide.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 100 mL volumetric flasks
- Sterilisation method: buffer solutions and all glassware were sterilised in an autoclave at 121ºC for 15 minutes
- Measures taken to avoid photolytic effects: flasks were covered with aluminum foil during the test
- Measures to exclude oxygen: nitrogen was bubbled through each buffer for 10 minutes before use
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no
TEST MEDIUM
- Volume used/treatment: after 210 µL of the test substance solution was added, the 100 mL volumetric flasks were made to volume with the appropriate buffer solution and equilibrated at 50 ± 0.5ºC, two flasks at each pH.
- Kind and purity of water: glass distilled water prepared at HRC
- Preparation of test medium: Test medium was prepared as described above. The test substance (0.25438 g) was dissolved in and made to volume with acetone in a 50 mL volumetric flask. The resulting solution had a concentration of 5087.6 µg/mL. Calibration solutions of test substance were also prepared in methanol in the range of about 0.5-1.6 µg/mL by dilution of a stock solution with methanol and water to produce final solutions in methanol/water, 50:50 v/v.
- Renewal of test solution: not done

Duration:

5 d

Initial conc. measured:

10.159 - 10.356 mg/L

Number of replicates:

two

Positive controls:

no

Negative controls:

no

Statistical methods:

The peak response of the test substance in each calibration standard was measured and a calibration curve constructed by linear regression of standard response versus standard concentration. The response of the peak observed at the characteristic retention volume of the test substance in sample chromagrams was measured and then test solution concentration (µg/mL) calculated using the equation below:
Test phase concentration ((µg/mL) =( Y - I/S) x F
where Y = peak response in sample chromatogram
I = intercept derived from linear regression of calibration data
S = slope derived from linear regression of calibration data
F = dilution factor (25/3)
Note: concentrations of test substance found at t = 2.4 hours and 5 days were expressed as a percentage of the t = 0 hours analysed concentrations

Preliminary study:

No preliminary study was performed.

Transformation products:

not measured

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

other: Slope and intercept derived from linear regression of calibration data

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

other: Slope and intercept derived from linear regression of calibration data

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

other: Slope and intercept derived from linear regression of calibration data

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: temperature was maintained

Table 1: Analytical data: Hydrolysis test

 

Time	pH	DUPLICATE	Integrated peak area	Concentrations found in buffer solution (μg/ml)	Expressed as a percentage of t = 0 hours analysed concentration	Mean result at each pH (%)
0	4	A	112577	10.356	-	-
0	4	B	111880	10.291
0	7	A	110449	10.159	-	-
0	7	B	112018	10.304
0	9	A	111047	10.214	-	-
0	9	B	112186	10.320
2.4 hours	4	A	112048	10.307	99.5	99.6
2.4 hours	4	B	111579	10.263	99.7
2.4 hours	7	A	110610	10.174	100.1	100.3
2.4 hours	7	B	112457	10.345	100.4
2.4 hours	9	A	111201	10.228	100.1	99.8
2.4 hours	9	B	111588	10.264	99.5
5 days	4	A	112566	10.644	102.8	102.8
5 days	4	B	111825	10.574	102.7
5 days	7	A	108295	10.241	100.8	101.9
5 days	7	B	112166	10.606	102.9
5 days	9	A	106975	10.117	99.1	98.0
5 days	9	B	105653	9.9919	96.8

 

Validity criteria fulfilled:

yes

Conclusions:

The test substance was found to undergo less than 10% hydrolysis over 5 days at 50ºC at pH 4, 7, and 9. Such stability indicates that the test substance possesses a half-life of greater than one year at 25ºC at all three pH's.

Executive summary:

The purpose of the study was to assess the hydrolytic behaviour of the test substance as a function of pH. The work was carried out in accordance with EEC Directive 67/548, Annex V, Part C, test C10 as published in EEC Directive 84/449. Hydrolysis was evaluated over five days at 50ºC at pH 4, 7, and 9. The starting concentration was 10.684 µg/mL. At each time point (0 hour, 2.4 hours and 5 days) an aliquot (3 mL) of the test solution was diluted with methanol and the test substance quantitatively determined by high performance liquid chromatography using an ultra-violet detector. The test substance was found to undergo less than 10% hydrolysis over 5 days at 50 ºC at pH 4, 7, and 9. According to the test method this indicates a half-life of greater than 1 year at 25ºC at all three pH's.

Description of key information

DT50 >1 year at 25°C and pH 4, 7, and 9 (less than 10% degradation at 50°C)

Additional information

No significant hydrolysis will occur under environmental conditions.