1,1,1,2,2,3,3-heptafluoro-3-[(trifluorovinyl)oxy]propane

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05-17-2017 to 07-25-2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

PPVE

IUPAC Name:

PPVE

Details on test material:

- Name of test material (as cited in study report): MTDID 16437, 1,1,1,2,2,3,3-heptafluoro-3-[(trifluoroethenyl)oxy]propane, PPVE
- Physical state: Clear colourless liquid
- Analytical purity: 98.5%
- Storage condition of test material: At room temperature in the dark under nitrogen

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 115B1065A
- Appearance: Colorless, clear liquid at room temperature
- Purity: 98.5%
- Purity test date:April 17, 2017
- Storage condition of test material:

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent compound: Nine discrete study samples were prepared in replicates for three pH level (pH, 4, 7, 9) at three temperature (10 °C, 20 °C, 50 °C ). For each pH and temperature combination, PPVE concentrations in aqueous buffer systems were measured at a minimum of eight discrete time points after initial dosing of the test system (Table 1).
- Sampling method: Test system vials were volatile organics analysis (VOA) vials. For each time point (TP), a pH monitor sample, a method blank (MB), a method blank spike, a lab matrix spike and three separate hydrolysis samples were prepared except for TP0 where five hydrolysis sample replicate vials were prepared. Using a microsryinge, 10 μL of the test system spiking solution was added to each non-method blank vial. After spiking, the test system vials were quickly vortex mixed and placed in an incubator/shaker set to the indicated temperature and shaking speed (100 rpm). Time point zero samples were aliquoted for analysis within 20-30 minutes after spiking. For each time point (TP), the elapsed time reported was the time spent in the incubator. Samples were aliquoted immediately upon removal from the incubator, generally within 10 minutes. Aliquots were prepared by inserting a disposable syringe/needle assembly through the vial’s septum and withdrawing the desired volume. The removed sample aliquot was then injected through the bonded septum-seal of a separate 40-mL VOA vial containing 10-mL of MilliQ reagent water. Given the volatile nature of the test substance, it is assumed that the test substance rapidly transfers into the available headspace of analysis vial and thus stops the aqueous hydrolysis. Therefore, the elapsed time remains the time the zero-headspace vials spent in the incubator and excludes the time the prepared analysis aliquots sit on the instrument autosampler awaiting analysis.
- Sampling methods for the volatile compounds, if any: Test system vials were filled to zero-headspace with the appropriate buffer and sealed with the bonded septum-seal caps.
- Sampling intervals/times for pH measurements: pH measurements were performed and recorded for the pH monitor samples, method blank samples and hydrolysis samples for each pH and temperature combination at each time point. Changes in pH of greater than 0.3 pH units were not observed over the course of the studies.
- Sampling intervals/times for sterility check: None
- Sample storage conditions before analysis: None
- Other observation, if any (e.g.: precipitation, color change etc.): None

Buffers:

- pH: 4, 7, 9
- Type of buffer:
pH 4: Potassium Biphthalate Buffer;
pH 7: Potassium Phosphate (Monobasic) Buffer;
pH 9: Boric Acid Buffer

- Composition of buffer:
pH 4 buffer: 500 mL of 0.1M Potassium Biphthalate + 4 mL of 0.1 N NaOH diluted to 1000 mL with MilliQ reagent water;
pH 7 buffer: 500 mL of 0.1M Potassium Phosphate (Monobasic) + 300 mL of 0.1N NaOH diluted to 1000 mL with MilliQ reagent water;
pH 9 buffer: 500 mL of 0.1M Boric Acid (H3BO3) + 210 mL of 0.1 N NaOH diluted to 1000 mL with MilliQ reagent water.

Prior to test system vial preparation, prepared buffers were sterilized via autoclave. Once cooled, the sterilized buffers were sufficiently purged with nitrogen to displace dissolved oxygen.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Test system vials were amber 20-mL VOA vials with 24-mm bonded septa caps. The average volume of the vials was experimentally determined to be 24.4 mL.
- Sterilisation method: prepared buffers were sterilized via autoclave.
- Lighting: None
- Measures taken to avoid photolytic effects: Test system vials were amber vials.
- Measures to exclude oxygen: purged with nitrogen.
- Details on test procedure for unstable compounds:
- Details of traps for volatile, if any: Test system vials were filled to zero-headspace with the appropriate buffer and sealed with the bonded septum-seal caps .
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

TEST MEDIUM
- Volume used/treatment Approximately 24 mL of each buffer solution
- Kind and purity of water: Milli-Q water
- Renewal of test solution: None
- Identity and concentration of co-solvent: No co-solvent

Duration of test

Duration of test 1

Duration:

48 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

>= 331 - <= 587 µg/L

Remarks:

Average concentration (n =5) = 440 ug/L, RSD% = 28%

Duration of test 2

Duration:

48 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

>= 264 - <= 637 µg/L

Remarks:

Average concentration (n =5) = 425 ug/L, RSD% = 40%

Duration of test 3

Duration:

48 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

>= 388 - <= 500 µg/L

Remarks:

Average concentration (n =5) = 456 ug/L, RSD% = 10%

Duration of test 4

Duration:

76 h

pH:

4

Temp.:

20 °C

Initial conc. measured:

>= 402 - <= 1 140 µg/L

Remarks:

Average concentration (n =5) = 723 ug/L, RSD% = 43%

Duration of test 5

Duration:

77 h

pH:

7

Temp.:

20 °C

Initial conc. measured:

>= 297 - <= 644 µg/L

Remarks:

Average concentration (n =5) = 420 ug/L, RSD% = 33%

Duration of test 6

Duration:

168 h

pH:

9

Temp.:

20 °C

Initial conc. measured:

>= 476 - <= 650 µg/L

Remarks:

Average concentration (n =5) = 604 ug/L, RSD% = 12%

Duration of test 7

Duration:

79 h

pH:

4

Temp.:

10 °C

Initial conc. measured:

>= 476 - <= 646 µg/L

Remarks:

Average concentration (n =3) = 567 ug/L, RSD% = 15%. Results bracketed by a non-compliant low-level CCV recovery=229%.

Duration of test 8

Duration:

79 h

pH:

7

Temp.:

10 °C

Initial conc. measured:

>= 486 - <= 722 µg/L

Remarks:

Average concentration (n =5) = 634 ug/L, RSD% = 15%. Results bracketed by a non-compliant low-level CCV recovery=229%.

Duration of test 9

Duration:

168 h

pH:

9

Temp.:

10 °C

Initial conc. measured:

>= 393 - <= 937 µg/L

Remarks:

Average concentration (n =5) = 590 ug/L, RSD% =39%

Number of replicates:

For each time point (TP), three separate hydrolysis samples were prepared except for TP0 where five hydrolysis sample replicate vials were prepared

Positive controls:

no

Negative controls:

no

Results and discussion

Transformation products:

yes

Identity of transformation products

Identity of transformation products 1

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

fluoride

Inventory number:

InventoryMultipleMappingImpl [inventoryEntryValue=EC 231-634-8]

CAS number:

7664-39-3

Identity of transformation products 2

No.:

#2

Reference

Reference substance name:

Unnamed

IUPAC name:

Perfluoropropionic acid

Identifier:

common name

Identity:

Perfluoropropionic acid

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

- Formation and decline of each transformation product during test: The primary hydrolysis products of PPVE at pH 7 were the deprotonated form of perfluoropropionic acid (CF3CF2-CO2-) and fluoride ion (F-).
- Pathways for transformation: See Fig 1

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

0.061 h-1

DT50:

11.4 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 10.1 - 13.1

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.061 h-1

DT50:

11.3 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 9.58-13.8

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.062 h-1

DT50:

11.2 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 9.71 - 13.1

Dissipation DT50 of parent compound 4

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0.032 h-1

DT50:

21.6 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 18.5 -26.1

Dissipation DT50 of parent compound 5

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.022 h-1

DT50:

33.3 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 27.3 -42.5

Dissipation DT50 of parent compound 6

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.021 h-1

DT50:

33.5 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 31.2 - 36.2

Dissipation DT50 of parent compound 7

pH:

4

Temp.:

10 °C

Hydrolysis rate constant:

0.016 h-1

DT50:

43.4 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 37.9 - 50.9

Dissipation DT50 of parent compound 8

Key result

pH:

7

Temp.:

10 °C

Hydrolysis rate constant:

0.024 h-1

DT50:

29.2 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 26.6 - 32.2

Dissipation DT50 of parent compound 9

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

0.021 h-1

DT50:

32.6 h

Type:

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

Remarks on result:

other: 95% Confidence Limits Half-Life (hours): 30.1 - 35.4

Other kinetic parameters:

The hydrolytic rate constant k, and hydrolytic half-life t1/2, were determined by plotting the natural logarithmic transform of the measured PPVE concentration as a function of elapsed time and performing linear regression, assuming that the hydrolysis followed pseudo first-order reaction kinetics. The slope of the resulting linear regression provided the rate constant k in units of hours-1. The resulting half-life was calculated using the following equation.
t1/2 = ln(2)/ k

Rate constants at other temperatures not explicitly measured can be calculated using the Arrhenius equation:
k=Ae^-(Ea/RT)
where: k=rate constant (hours-1);
A=pre-exponential factor;
Ea=Activation Energy (J*mol-1);
R=ideal gas constant=8.314 J*mol/K;

The pre-exponential factor and activation energy at a given pH can be determined by using the graphical form of the Arrhenius equation ln(K) = -Ea/RT + ln A and plotting ln(k) versus (1/T) where the resulting slope will give –Ea/R and y-intercept will be lnA (Fig 2).

Details on results:

The hydrolytic rate constants for PPVE ranged from 0.0606 -0.0621 hours^ -1 at 50°C, 0.0207 -0.0321 hours^ -1 at 20°C, and 0.0160 -0.0238 hours^ -1 at 10°C. The Coefficient of Determination for the 1st Order Kinetics Linear Regression Equation ranged from 0.830 to 0.957. Calculated half-lives ranged from 11.2-11.4 hours (50°C), 21.6-33.5 hours (20°C), and 29.2-43.4 hours (10°C).

For each of the temperatures studied, the hydrolytic rate constant and resultant half-life showed no significant dependence on pH. Arrhenius plots as a function of pH (ln k vs 1/T) also produced similar slopes suggesting that the activation energy for the reaction does not appreciably depend on the pH (Fig 2).

The hydrolysis products, perfluoropropionic acid, was detected at an average concentration of 0.00127±0.00001 wt% and 0.00138 ± 0.00002 wt % (weight percent), equivalent to 12.7 and 13.8 PPM (part per million) for the duplicate samples. The fluoride ion was detected at an average concentration of 0.00021 wt %, equivalent to 2.1 PPM.

Any other information on results incl. tables

Table 2. Summary of Hydrolytic Rate Constants and Calculated Half-Lives of PPVE

Study Condition	Elapsed Time  (hours)	Avg. conc. at  TP0 (ng/mL)	Avg. conc. at end time point  (ng/mL)	% Hydrolyzed at  end time point	Rate constant k (hours-1)	R^2*	Calculated Half-Life (hours)**
pH 4, 50°C	0-48	440	20.3	95.4%	0.0606	0.9035	11.4 (10.1 -13.1)
pH 7, 50°C	0-48	425	26.2	93.8%	0.0614	0.8298	11.3 (9.58-13.8)
pH 9, 50°C	0-48	456	22.9	95.0%	0.0621	0.8758	11.2 (9.71-13.1)
pH 4, 20°C	0-76	723	43.4	94.0%	0.0321	0.8422	21.6 (18.5-26.1)
pH 7, 20°C	0-77	420	69.6	83.4%	0.0224	0.8544	33.3 (27.3-42.5)
pH 9, 20°C	0-168	604	18.0	95.5%	0.0207	0.9572	33.5 (31.2-36.2)
pH 4, 10°C	0-79	567	159	72.0%	0.0160	0.8873	43.4 (37.9-50.9)
pH 7, 10°C	0-79	634	92.0	85.6%	0.0238	0.9452	29.2 (26.6-32.2)
pH 9, 10°C	0-168	590	13.8	96.1%	0.0213	0.9518	32.6 (30.1-35.4)

 

*Coefficient of Determination for the 1st Order Kinetics Linear Regression Equation

**Numbers in parentheses are 95% Confidence Limits Half-Life (hours).

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

PPVE is hydrolytically unstable with hydrolysis half-lives ranged from 11.2-11.4 hours (50°C), 21.6-33.5 hours (20°C), and 29.2-43.4 hours (10°C).
The hydrolytic rate constant and resultant half-life showed no significant dependence on pH.

Executive summary:

Hydrolysis of PPVE was investigated at three pHs (4, 7, and 9) and at three different temperatures (10°C, 20°C, and 50°C) according to OECD 111 guideline “Hydrolysis as a Function of pH”. Nine discrete hydrolysis study samples were prepared in replicates for three pH level (pH, 4, 7, 9) at three temperature (10 °C, 20 °C, 50 °C ). For each pH and temperature combination, PPVE concentrations in aqueous buffer systems were measured at a minimum of eight discrete time points after initial dosing of the test system using purge and trap gas chromatography/mass spectrometry (PT-GC/MS). The hydrolytic rate constant,k, and hydrolytic half-life, t1/2, were determined by plotting the natural logarithmic transform of the measured PPVE concentration as a function of elapsed time and performing linear regression, assuming that the hydrolysis followed pseudo first-order reaction kinetics.

The hydrolytic rate constants ranged from 0.0606 - 0.0621 hours-1 at 50°C, 0.0207 -0.0321 hours-1 at 20°C, and 0.0160 -0.0238 hours-1 at 10°C. The Coefficient of Determination for the 1st order kinetics linear regression equation ranged from 0.830 to 0.957. Calculated half-lives ranged from 11.2-11.4 hours (50°C), 21.6-33.5 hours (20°C), and 29.2-43.4 hours (10°C). For each of the temperatures studied, the hydrolytic rate constant and resultant half-life showed no significant dependence on pH. Arrhenius plots as a function of pH (ln k vs 1/T) also produced similar slopes suggesting that the activation energy for the reaction does not appreciably depend on the pH.

Duplicated samples of saturated PPVE in pH 7 buffer were also analyzed for the hydrolysis product using 19F NMR. The primary hydrolysis products of PPVE at pH 7 were the deprotonated form of perfluoropropionic acid (CF3CF2-CO2-) and fluoride ion (F-). This experiment was not conducted under GLP compliance.

The hydrolysis study is conducted according to OECD guideline and in compliance with GLP. Although high variations were observed in some of the measured concentrations, in addition to poor recoveries in the quality control samples, they are not likely to affect the PPVE hydrolysis rate constants and hydrolysis half-life. This study is considered reliable with restriction and a key study.