(1R)-1-[(4R,4aR,8aS)-2,6-bis(3,4-dimethylphenyl)tetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5th March 1993 to 1st October 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

The study report states that the test was performed in accordance with EEC 84/449 Method C10. However, this test method does not refer to a hydrolysis study and hence is considered to be a typographical error in the report.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

Purity: 97.3% (considered as 100%)
Batch number: 9236-23

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

Samples were taken at different time intervals (0, 17, 21, 27, 41, 65, 89, 113 and 120 h) and stored at 4°C until assay by high performance liquid chromatography (HPLC).
At pH 4 degradation was observed to occur before time point 17 hours; therefore, a second test was performed with two additional time points 2.4 and 3.5 hours.

Buffers:

- pH: pH 4, 7 and 9 buffers were used
- Type and final molarity of buffer: Not specified
- Composition of buffer: Not specified

Estimation method (if used):

N/A

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: The test was performed in 25 mL volumetric flasks.
- Sterilisation method: Not specified
- Lighting: The samples were placed in the dark at 50 °C.
- Measures taken to avoid photolytic effects: The samples were placed in the dark.
- Measures to exclude oxygen: Not specified
- Details on test procedure for unstable compounds: N/A
- Details of traps for volatile: N/A
- If no traps were used, is the test system closed/open: Not specified
- Is there any indication of the test material adsorbing to the walls of the test apparatus?: Not specified

TEST MEDIUM
- Volume used/treatment: Not specified
- Kind and purity of water: Not specified
- Preparation of test medium: Not specified
- Renewal of test solution: Not specified
- Identity and concentration of co-solvent: The stock solution of the test article was prepared in acetonitrile.

OTHER TEST CONDITIONS
- Adjustment of pH: Not specified
- Dissolved oxygen: Not specified

Duration of test

Duration:

120 d

Temp.:

50 °C

Initial conc. measured:

50 other: mg/L in acetonitrile (concentration of stock solution)

Number of replicates:

For each pH, two samples of 12.5 µL each were prepared in a volumetric flask and the volume made up with the appropriate buffer.

Positive controls:

no

Negative controls:

no

Statistical methods:

Not specified

Results and discussion

Preliminary study:

A preliminary study was performed but the results are not specified.

Test performance:

None specified

Transformation products:

not measured

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

Not specified

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

50 °C

DT50:

1.78 h

Remarks on result:

other: Hydrolysis rate constant is essentially zero. r2 = 0.786

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

50 °C

DT50:

> 120 h

Remarks on result:

other: Hydrolysis rate constant is essentially zero. r2 = 0.292

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

50 °C

DT50:

> 120 h

Remarks on result:

other: Hydrolysis rate constant is essentially zero. r2 = 0.180

Other kinetic parameters:

Not specified

Details on results:

Under the experimental conditions described, the half-time (T1/2) of the test article was :
- pH 4: T1/2 = 1.78 hours
- pH 7: T1/2 > 5 days
- pH 9: T1/2 > 5 days

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

At each pH 4, the half life was equal to 1.78 hours.
At pH 7 and 9, less than 10% hydrolysis is observed after 5 days.

Executive summary:

The hydrolysis study was performed in accordance with OECD Guideline 111 and EEC Directive 84/449 Method C.7.

At each pH 4, the half life was equal to 1.78 hours. At pH 7 and 9, less than 10% hydrolysis is observed after 5 days.