2,2,3,3,4,4,5,5-octafluoropentyl methacrylate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

non-GLP

GLP compliance:

no

Remarks:

The non-GLP data is considered to be acceptable as the results are adequate for the purpose of risk assessment; there was adequate and reliable coverage of key parameters; and there was adequate and reliable documentation of the study.

Specific details on test material used for the study:

Purity: 99.8%

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Tier 1: Monitoring
- Sampling intervals for the parent/transformation products: two time points (initial and 5 days)
- Sampling method: 25 mL aliquot of the buffered solution was extracted with 5 mL of chloroform. The extraction procedure was repeated 5 times. One mL of chloroform extract was placed in a 2 mL vial and evaporated to dryness with compressed air. The extract was reconstituted in 1 mL of 45% acetonitrile/water and 0.1% trifluoroacetic acid.
- Sampling intervals/times for pH measurements: two time points (initial and 5 days)

Tier 2: Monitoring
- Sampling intervals for the parent/transformation products:
pH 4, 3.5°C: Day 0, 1, 2, 3, 6, 8, 13, 15, and 30
pH 4, 36°C: Day 0, 1, 2, 3, 5, and 6
pH 4, 50°C: Day 0, 1, 2, 3, 4, and 5
pH 7, 3.5°C: Day 0, 1, 2, 7, 8, 16, 21, and 30
pH 7, 36°C: Day 0, 1, 2, 3, 4, and 7
pH 7, 50°C: Day 0, 1, 2, 3, 4, and 7
pH 9, 3.5°C: Day 0, 1, 2, 3, 7, 11, and 14
pH 9, 36°C: Day 0, 1, and 2
pH 9, 50°C: Day 0, 1, and 2
- Sampling method: 25 mL aliquots of the buffered solution were extracted with 5 mL of chloroform each. The chloroform layer was dried over sodium sulfate for approximately 20 minutes. The solution was filtered through a 0.45 µm PTFE syringe filter into another vial.
- Sampling intervals/times for pH measurements:
pH 4, 3.5°C: Day 0, 1, 2, 3, 6, 8, 13, 15, and 30
pH 4, 36°C: Day 0, 1, 2, 3, 5, and 6
pH 4, 50°C: Day 0, 1, 2, 3, 4, and 5
pH 7, 3.5°C: Day 0, 1, 2, 7, 8, 16, 21, and 30
pH 7, 36°C: Day 0, 1, 2, 3, 4, and 7
pH 7, 50°C: Day 0, 1, 2, 3, 4, and 7
pH 9, 3.5°C: Day 0, 1, 2, 3, 7, 11, and 14
pH 9, 36°C: Day 0, and 1
pH 9, 50°C: Day 0, and 1

Buffers:

Tier 1, pH 4: 500 mL of a 0.1 M monopotassium citrate solution was added to a glass bottle and heated to 50 °C. 130 mL of 0.1 N sodium hydroxide was added to the solution and stirred. The buffer was brought to pH 4.00 with additional 0.1 N sodium hydroxide. Once cooled to room temperature, the solution was brought to volume with deionized water to total 1 L.

Tier 1, pH 7: 500 mL of a 0.1 M monopotassium phosphate solution was added to a glass bottle and heated to 50 °C. 320 mL of 0.1 N sodium hydroxide was added to the solution and stirred. The buffer was brought to pH 7.00 with additional 0.1 N sodium hydroxide. Once cooled to room temperature, the solution was brought to volume with deionized water to total 1 L.

Tier 1, pH 9: 500 mL of a 0.1 M boric acid solution in 0.1 M potassium chloride was added to a glass bottle and heated to 50 °C. 270 mL of 0.1 N sodium hydroxide was added to the solution and stirred. The buffer was brought to pH 9.00 with additional 0.1 N sodium hydroxide. Once cooled to room temperature, the solution was brought to volume with deionized water to total 1 L.

Tier 2, pH 4: 1000 mL of a 0.1 M monopotassium citrate solution was added to a glass bottle and heated to 50 °C. The buffer was brought to pH 4.00 with 0.1 N sodium hydroxide. Once cooled to room temperature, the solution was brought to volume with deionized water to total 2 L. This buffer preparation was repeated to total 4 L for the entire study.

Tier 2, pH 7: 1000 mL of a 0.1 M monopotassium phosphate solution was added to a glass bottle and heated to 50 °C. The buffer was brought to pH 7.00 with 0.1 N sodium hydroxide. Once cooled to room temperature, the solution was brought to volume with deionized water to total 2 L. This buffer preparation was repeated to total 4 L for the entire study.

Tier 2, pH 9: 1000 mL of a 0.1 M boric acid solution in 0.1 M potassium chloride was added to a glass bottle and heated to 50 °C. The buffer was brought to pH 9.00 with 0.1 N sodium hydroxide. Once cooled to room temperature, the solution was brought to volume with deionized water to total 2 L. This buffer preparation was repeated to total 4 L for the entire study.

Details on test conditions:

Tier 1: Test Conditions
Test Substance Addition: A stock solution of OFPMA in acetonitrile was made at a concentration of 80 ppm. For each buffer prepared, 100 mL of the stock solution was added to a 1 L volumetric flask. The solution was brought to volume with the appropriate buffer to create an 8 ppm solution of the test substrate in the buffer. One control solution was made using deionized water in place of the buffer.

One liter of each buffer and control was transferred to a low actinic bottle and placed in a 50 °C ± 0.5 °C oven.

Tier 2: Test Conditions
Test Substance Addition: A stock solution of OFPMA in acetonitrile was made at a concentration of 80 ppm. For each buffer prepared, 200 mL of the stock solution was added to a 2 L volumetric flask. The solution was brought to volume with the appropriate buffer to create an 8 ppm solution of the test substrate in the buffer. One control solution was made using acetonitrile in place of the buffer to evaluate the effect of the solvent on hydrolysis.

Each buffer and control was transferred to 70 x 50 mL polypropylene conical tubes. Each tube represents two extractions per time point. The tubes were split into three groups and placed in a 3.5 °C ± 0.5 °C refrigerator, 36 °C ± 0.5 °C oven, and 50 °C ± 0.5 °C oven. Ten tubes of each buffered solution were placed at 50 °C, and 30 tubes of each buffered solution were placed at 3.5°C and 36 °C. Five tubes of the acetonitrile control were placed at 3.5°C. Samples were extracted as needed to capture at least 6 points over the degradation profile up to 90% degraded, or over 30 days.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 1

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 1

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 1

Duration:

30 d

pH:

4

Temp.:

3.5 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

6 d

pH:

4

Temp.:

36 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

30 d

pH:

7

Temp.:

3.5 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

7 d

pH:

7

Temp.:

36 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

7 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

14 d

pH:

9

Temp.:

3.5 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

2 d

pH:

9

Temp.:

36 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Duration:

2 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

8 mg/L

Remarks:

Tier 2

Number of replicates:

Tier 1: 1 buffered solution per pH, 5 replicate extractions
Tier 2:
10 tubes of each buffered solution at 50°C
30 tubes of each buffered soltuion at 36°C
30 tubes of each buffered soltuion at 3.5°C
5 tubes of the acetonitrile control at 3.5°C

Positive controls:

no

Negative controls:

no

Statistical methods:

Tier 1: Statistics
While the variation in the Tier 1 method is not acceptable, these results provide qualitative information in the relative amounts of OFPMA left after 5 days. A Student’s T-Test was performed comparing the initial data sets to the data after 5 days. For buffers at pH 7 and 9.

Tier 2: Statistics
Regression analysis for Arrhenius Plot

Preliminary study:

The extraction method used proved to be too variable to provide reliable data needed to satisfy the Tier 1 test requirements. However, the qualitative interpretation of the data shows hydrolysis has occurred at pH 7 and pH 9 and a Tier 2, 30 day study should be performed.

Test performance:

Tier 1: HPLC method proved to be too variable to provide reliable data.

Tier 2: GC/MS method provided reiiable data. The concentration of OFPMA in the acetonitrile control did not go below 10% over the 30-day study duration. The control did show some degradation, but not to the extent of the other solutions at 3.5°C, indicating the acetonitrile contributed very little to the hydrolysis of OFPMA.

Transformation products:

yes

No.:

#1

No.:

#2

% Recovery:

100

St. dev.:

0.011

pH:

4

Temp.:

3.5 °C

Duration:

0 d

% Recovery:

47.19

St. dev.:

0.003

pH:

4

Temp.:

3.5 °C

Duration:

6 d

% Recovery:

27.4

St. dev.:

0.002

pH:

4

Temp.:

3.5 °C

Duration:

30 d

% Recovery:

100

St. dev.:

0.011

pH:

4

Temp.:

36 °C

Duration:

0 d

% Recovery:

15.01

St. dev.:

0.001

pH:

4

Temp.:

36 °C

Duration:

3 d

% Recovery:

9.07

St. dev.:

0.003

pH:

4

Temp.:

36 °C

Duration:

6 d

% Recovery:

100

St. dev.:

0.011

pH:

4

Temp.:

50 °C

Duration:

0 d

% Recovery:

8.14

St. dev.:

0.002

pH:

4

Temp.:

50 °C

Duration:

3 d

% Recovery:

4.48

St. dev.:

0

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

100

St. dev.:

0.01

pH:

7

Temp.:

3.5 °C

Duration:

0 d

% Recovery:

61.98

St. dev.:

0.001

pH:

7

Temp.:

3.5 °C

Duration:

8 d

% Recovery:

31.01

St. dev.:

0.005

pH:

7

Temp.:

3.5 °C

Duration:

30 d

% Recovery:

100

St. dev.:

0.01

pH:

7

Temp.:

36 °C

Duration:

0 d

% Recovery:

15.93

St. dev.:

0

pH:

7

Temp.:

36 °C

Duration:

3 d

% Recovery:

8.63

St. dev.:

0.001

pH:

7

Temp.:

36 °C

Duration:

7 d

% Recovery:

100

St. dev.:

0.01

pH:

7

Temp.:

50 °C

Duration:

0 d

% Recovery:

8.79

St. dev.:

0.001

pH:

7

Temp.:

50 °C

Duration:

3 d

% Recovery:

3.93

St. dev.:

0

pH:

7

Temp.:

50 °C

Duration:

7 d

% Recovery:

100

St. dev.:

0.003

pH:

9

Temp.:

3.5 °C

Duration:

0 d

% Recovery:

33.57

St. dev.:

0.002

pH:

9

Temp.:

3.5 °C

Duration:

3 d

% Recovery:

8.43

St. dev.:

0.001

pH:

9

Temp.:

3.5 °C

Duration:

14 d

% Recovery:

100

St. dev.:

0.003

pH:

9

Temp.:

36 °C

Duration:

0 d

% Recovery:

2.08

St. dev.:

0.002

pH:

9

Temp.:

36 °C

Duration:

1 d

% Recovery:

0

St. dev.:

0

pH:

9

Temp.:

36 °C

Duration:

2 d

% Recovery:

100

St. dev.:

0.003

pH:

9

Temp.:

50 °C

Duration:

0 d

% Recovery:

0.87

St. dev.:

0.001

pH:

9

Temp.:

50 °C

Duration:

1 d

% Recovery:

0

St. dev.:

0

pH:

9

Temp.:

50 °C

Duration:

2 d

Key result

pH:

4

Temp.:

20 °C

DT50:

65.1 h

Type:

second order

Remarks on result:

other: rate constant k (per hour per molar concentration) 577.10

Remarks:

Fit of this data was more linear, regression data is also more significant.

Key result

pH:

7

Temp.:

20 °C

DT50:

98 h

Type:

second order

Remarks on result:

other: rate constant k (per hour per molar concentration) 383.46

Remarks:

Fit of this data was more linear, regression data is also more significant.

Key result

pH:

9

Temp.:

20 °C

DT50:

3.9 h

Type:

second order

Remarks on result:

other: rate constant k (per hour per molar concentration) 9595.08

Remarks:

Fit of this data was more linear, regression data is also more significant.

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

4.7 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: rate constant for pseudo first-order was only modestly linear

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.005 h-1

DT50:

5.5 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: rate constant for pseudo first-order was only modestly linear

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.057 h-1

DT50:

0.5 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: rate constant for pseudo first-order was only modestly linear

Validity criteria fulfilled:

yes

Conclusions:

The rate of hydrolysis of OFPMA was found to be fast, with half lives of 2.7 days for pH 4, 4.1 days for pH 7, and 3.9 hours for pH 9 at 20°C, using second order kinetics.

Executive summary:

The rate of hydrolysis of OFPMA as a function of pH was determined according to a non-GLP OECD Guideline 111 study. While the extraction method of the Tier 1 assessment was not reliable, the data did indicate hydrolysis did occur within 5 days at 50°C and Tier 2 analysis was required.

 

The Tier 2 analysis employed a different analytical sample preparation and analytical assessment method than Tier 1. The rate of hydrolysis of OFPMA was found to be fast, with half lives of 2.7 days for pH 4, 4.1 days for pH 7, and 3.9 hours for pH 9 at 20°C, using second order kinetics.

 

The products of the hydrolysis were confirmed with NMR analysis to be octafluoropentanol and methacrylic acid.

Description of key information

The rate of hydrolysis of OFPMA as a function of pH was determined according to a non-GLP OECD Guideline 111 study. While the extraction method of the Tier 1 assessment was not reliable, the data did indicate hydrolysis did occur within 5 days at 50°C and Tier 2 analysis was required.

 

The Tier 2 analysis employed a different analytical sample preparation and analytical assessment method than Tier 1. The rate of hydrolysis of OFPMA was found to be fast, with half lives of 2.7 days for pH 4, 4.1 days for pH 7, and 3.9 hours for pH 9 at 20°C, using second order kinetics.

 

The products of the hydrolysis were confirmed with NMR analysis to be octafluoropentanol and methacrylic acid.

Key value for chemical safety assessment

Half-life for hydrolysis:

4.1 d

at the temperature of:

20 °C