1-(2,4-dimethylcyclohex-3-en-1-yl)propan-1-ol

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 September 2016 to 4 October 2016

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:

(version 2004)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(version 2008)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

not required

Remarks:

Tier 1 showed no degradation of >10% at any of the tested pHs.

Details on sampling:

Complete vessels were used for analysis at the beginning and after 5 days.

Buffers:

- pH4: 80 mL 2M CH3COOH + 40 mL 1M CH3COONa filled up to 1000 mL with demineralised water. pH adjusted to 4.00 with NaOH.
- pH7: 8.7086 g KH2PO4 in 250 mL demineralised water + 14.9 mL 2M NaOH filled up to 1000 mL with demineralised water. pH adjused to 7.00 with NaOH.
- pH9: 3.0932 g K3BO3 + 3.7292 g KCl in 500 mL demineralised water + 10.75 mL NaOH filled up to 1000 mL with demineralised water. pH adjused to 9.00 with NaOH.

Details on test conditions:

TEST SYSTEM
- Glass Material: All glassware was sterilized before use. Amber glass 2 mL HPLC Vials with Teflon septa were used. A large head space above the liquid was avoided.
- Incubation Chamber: Memmert ICP 600 set to 50 °C

PERFORMANCE OF THE STUDY
- Preparation of test solutions: A test item solution with a concentration of 200 mg/L was prepared. 20.4 mg test item were weighed into a 100 mL flask and water was added. The mixture was sonicated, but as after 1 h sonication non-dissolved particles were still visible, 2 mL acetonitrile were added to facilitate complete dissolution. As the solution was clear after addition of acetonitrile, the flask was filled to the mark and 2 mL water were added to reach the final concentration 200 mg/L. 10 mL test item solution were mixed with 10 mL of each hydrolysis buffer solution, resulting in 100 mg/L test item in hydrolysis buffer. These mixtures were drawn into syringes, and sterile filtrated into sterile HPLC vessels (filled nearly to the top). The pH values after mixing with the test item were 4.05, 7.12 and 9.04, respectively.
- Incubation: The solutions were purged with sterilised argon to remove oxygen, closed tightly and incubated for 120 h at 50 ± 0.5 °C in an incubation chamber.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

100 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

100 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

100 mg/L

Number of replicates:

Four vials were prepared for each pH, one for analysis at t = 0 h and three for t = 120 h.

Positive controls:

no

Negative controls:

yes

Remarks:

Blanks (demineralised water mixed with hydrolysis buffer solutions) were prepared and incubated identically.

Preliminary study:

No significant signs of hydrolysis were observed at all three pH values in the preliminary test.

Transformation products:

no

pH:

4

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

- No significant signs of hydrolysis were observed at all three pH values. The test item can be considered as hydrolytically stable at pH values 4.05, 7.12 and 9.04.

Table: test substance measured concentrations and recovery at t = 0 h and t = 120 h

	pH 4	pH 7	pH 9
Test item concentration at t = 0 h (mg/L)	93.1	95.0	95.5
Test item concentration at t = 120 h (mg/L)	88.9	95.6	96.7
Recovery after 120 h (%)	95.5	100.7	101.3
Change over 120 h (%)	-4.5	+1.7	+1.3

Notes:

- The slight increase of test item concentration in hydrolysis buffers pH 7 and 9 was not caused by sample preparation errors, the most likely cause is evaporation of water during the purging step with argon.

- The slight decrease of test item concentration in hydrolysis buffer pH 4 is uncritical

Validity criteria fulfilled:

not applicable

Conclusions:

FRET 11-0571 is hydrolytically stable.

Executive summary:

The hydrolytic stability of FRET 11 -0571 was investigated in a study according to OECD 111 and in compliance with GLP criteria (LAUS, 2016). In this study, the substance at a nominal concentration of 100 mg/L was incubated at pH4, 7 and 9 at 50 °C for 5 days. After 5 days no significant signs of hydrolysis were observed at all three pH values. The test item can be considered as hydrolytically stable at pH values 4.05, 7.12 and 9.04.

Description of key information

The substance is hydrolytically stable in an OECD TG 111 test. For chemical safety assessment the half-life for hydrolysis is determined at 1 year

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C