2,4-dimethyl-4-phenyltetrahydrofuran

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 28, 2020 to November 16, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2110 (Hydrolysis as a Function of pH)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes (incl. QA statement)

Remarks:

Statement of GLP compliance signed on September 18, 2019

Radiolabelling:

no

Buffers:

pH 4: Ready-made concentrate (Titrisol®, MERCK, Darmstadt, Germany, art. No. 9884,
citrate/ hydrochloric acid buffer) pH 4.00 ± 0.02 at 20°c,
pH 7: Ready-made concentrate (Titrisol®, MERCK, Darmstadt, Germany, art. No. 9887,
phosphate buffer) pH 7.00 ± 0.02 at 20°c,
pH 9: Ready-made concentrate (Titrisol®, MERCK, Darmstadt, Germany, art. No. 9889,
boric acid / potassium chloride / sodium hydroxide buffer) pH 9.00 ± 0.02 at 20°C,
In order to avoid any unnecessary excess of inorganic salts that could reduce the
solubility of the test substance, these buffer solutions were diluted to 10% with ultrapure water before being used as test media.

Details on test conditions:

TEST SYSTEM:
Hydrolysis reactions are performed in amber glass bottles (repeated sampling from recipient) or 20 ml amber-glass vials (crimp caps with Teflon coated rubber septa; a minimum of two vials is sacrificed for each sampling point).
A constant temperature water bath (JULABO MP, JULABO Labortechnik GmbH,
Seelbach, Germany) is used to maintain to ±0.1 °C the test vessel temperature.
Analytical equipment capable of detecting a 10 % depletion of the concentration of aqueous solutions is used (HPLC or GC).

TEST CONDITIONS:
- test substance solution: The water solubility of Rhubafuran at 20°C is 650 mg/I (13-E156). According to the guidelines, the initial concentration to be used for the hydrolysis reaction should not exceed the half of the saturation concentration, or a concentration of 0.01 mol/1. A nominal concentration of 325 mg/I was used in the preliminary test. Therefore, 325 mg of test substance were added in a 1000 ml volumetric flask and completed with buffer solution. The HPLC method is capable of quantifying concentrations of this magnitude.

- Preliminary test at 50°C (Tier 1)
Solutions of Rhubafuran in the different buffer solutions were prepared as described below.
For each pH, a minimum of 24 amber glass crimp cap vials (20 ml) were filled
with 20 ml of the respective solution, sealed with Teflon coated rubber septa crimp cap, and placed in the water bath at 50°C. After temperature equilibration, a first pair of vials was extracted for each pH as described in Appendix 1. This is time zero of the experiment.
At given times, namely after 6 h, 120 h and 126 h, other two vials per buffer solution were sacrificed for analysis.

Duration:

0 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

0 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

0 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

126 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

6 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

126 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

6 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

126 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Duration:

6 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

325 mg/L

Number of replicates:

2 replicates per condition

Positive controls:

no

Negative controls:

no

Preliminary study:

The criterion given in the guidelines for the preliminary test is: If less than 10%
degradation after 120 h (equivalent to a half-life time higher than 1 year at 25°C) is observed, no further testing is necessary.
This criterion is fulfilled for pH 4, pH 7 and pH 9. For all three pH <10% degradation was observed at 50°C over a 120 h period (0 h to 120 h).

Transformation products:

no

Key result

pH:

9

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Samples	Measured pH	Calculated concentration [mg/l) of Rhubafuran	Dilution fd 5	Average Concentration[mg/l] of Rhubafuran
pH4a at 0h	4.19	67.05	335.24	334.85
pH4b at 0h	4.19	66.89	334.45
pH7a at 0h	7.18	67.08	335.40	335.19
pH7b at 0h	7.19	66.99	334.97
pH9a at 0h	8.97	63.53	317.63	324.30
pH9b at 0h	8.99	66.19	330.97
pH4a at 6h	4.20	64.83	324.13	328.66
pH4b at 6h	4.19	66.64	333.19
pH7a at 6h	7.16	66.08	330.39	331.09
pH7b at 6h	7.18	66.36	331.79
pH9a at 6h	8.96	63.63	318.16	321.80
pH9b at 6h	8.98	65.09	325.43
pH4a at 120h	4.18	62.66	313.28	318.10
pH4b at 120h	4.18	64.58	322.91
pH7a at 120h	7.18	67.89	339.45	330.27
pH7b at 120h	7.19	64.22	321.09
pH9a at 120h	8.96	65.89	329.47	328.42
pH9b at 120h	8.94	65.47	327.37
pH4a at 126h	4.17	61.79	308.95	299.37
pH4b at 126h	4.17	57.96	289.79
pH7a at 126h	7.16	61.08	305.41	314.58
pH7b at 126h	7.15	64.75	323.76
pH9a at 126h	8.89	64.07	320.33	318.05
pH9b at 126h	8.92	63.16	315.78

Validity criteria fulfilled:

yes

Conclusions:

Only the preliminary test needed to be performed at pH 4, pH 7 and pH 9 since, at
50°C, less than 10% hydrolysis occurred after 120 h. A hydrolysis of less than 10% after
120 h, or more, at 50°C corresponds to a half-life time of more than one year at 25°C.
Therefore:
The half-life time of Rhubafuran at 25°C is higher than one year at pH 4, pH 7 and pH 9.

Executive summary:

An abiotic degradation study (hydrolysis as a function of pH) was carried out with Rhubafuran according to OECD guideline n° 111.
Only the preliminary test needed to be performed at pH 4, pH 7 and pH 9 since, at
50°C, less than 10% hydrolysis occurred after 120 h. A hydrolysis of less than 10% after 120 h, or more, at 50°C corresponds to a half-life time of more than one year at 25°C.
Therefore:
The half-life time of Rhubafuran at 25°C is higher than one year at pH 4, pH 7 and pH 9.

Description of key information

OECD Guideline 111, EU Method C.7, GLP, key study, validity 2:

The half-life time of Rhubafuran at 25°C is higher than one year at pH 4, pH 7 and pH 9

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

One key study (OECD 111) is available to assess the abiotic degradation of the tested substance:

Only the preliminary test needed to be performed at pH 4, pH 7 and pH 9 since, at
50°C, less than 10% hydrolysis occurred after 120 h. A hydrolysis of less than 10% after 120 h, or more, at 50°C corresponds to a half-life time of more than one year at 25°C. Therefore, the half-life time of Rhubafuran at 25°C is higher than one year at pH 4, pH 7 and pH 9.