Propyl propionate

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD TG 111 and in accordance with the Principles of Good Laboratory Practice (GLP).

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Remarks:

The only exception noted was that purity and characterization was done concurrent with the study

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Propyl propionate

EC Number:

203-389-7

EC Name:

Propyl propionate

Cas Number:

106-36-5

Molecular formula:

C6H12O2

IUPAC Name:

propyl propanoate

Details on test material:

- Name of test material (as cited in study report): Propyl propionate
- Physical state: clear liquid
- Analytical purity: 99.92% by gas chromatography
- Lot/batch No.: Lot Number QC1355V1C1

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
not applicable

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: A preliminary test (Tier 1) was conducted in buffered solutions (pH 4, 7, and 9) at 50°C for five days. A more extensive investigation of hydrolysis kinetics was conducted (Tier II) at pH values where the test compound was shown to be hydrolytically unstable in the preliminary test (extrapolated half- life at 25°C between 24 hours and one year). Experiments were run at 50, 60, and 70°C at pH 4, 7 and 9. These temperatures were within the range of 10 to 70°C recommended by the guidelines.
- Sampling intervals/times for pH measurements: TIER 1 - For each pH, duplicate test solutions were analyzed for propyl propionate at 0, 2.4, 4.3, 24.3, and 122 hours.
- Sampling intervals/times for sterility check: The Tier II experiments were terminated when 90 percent hydrolysis of the parent compound had occurred, or after 30 days. Selected test solutions were analyzed for microbial contamination at the conclusion of the Tier II experiments to confirm the sterility of the test solutions. Samples (1000 mL) from duplicate test solutions were transferred to BBL standard agar plates using sterile pipettes and spread with sterile glass rods. The plates were incubated in the dark at ambient temperature. Plates were visually inspected for microbial growth after five days.

Buffers:

- pH: 4, 7 and 9
- Type and final molarity of buffer: Buffered solutions (0.05M) were prepared with potassium biphthalate (pH 4), potassium phosphate (pH 7,) and sodium borate (pH 9). The pH was adjusted with 0.1N HCl or 0.1N NaOH to + 0.1 pH units as necessary. The prepared buffers were sterile filtered using 0.2 mm nylon sterile filter apparatus. The buffers were aggressively sparged with argon to minimize possible oxidation reactions. Sterility was verified by a total plate count analysis of representative reaction mixtures.

Estimation method (if used):

not applicable

Details on test conditions:

Due to the limited solubility of the test material, dose stock solutions of approximately 20,000 mg/l were prepared in acetonitrile. A 1.2 ml aliquot was of the stock was added to each respective 250 ml aliquot of sterile buffer solution. The nominal test concentrations of the test material were approximately 100 mg/l. Portions (10 ml) of the fortified test solutions were added to serum bottles and sealed with Teflon-coated rubber septa and aluminum crimp seals. Test solutions were incubated in a thermostatic water bath (temperature control + 0.5 °C).

The test solutions were incubated in the dark to minimize possible photochemical reactions. All solutions, glassware, and equipment were sterilized by filter sterilization or autoclaving as appropriate, to reduce the potential for biodegradation of the test compound. All buffer solutions were sterile filtered through a 0.2 m filter and aggressively sparged with argon to minimize possible oxidation reactions.

Tier I Hydrolysis
A preliminary test (Tier 1) was conducted in buffered solutions (pH 4, 7, and 9) at 50°C for five days. For each pH, duplicate test solutions were analyzed for propyl propionate at 0, 2.4, 4.3, 24.3, and 122 hours. Prior to GC analysis, test solutions were quenched with 55 L of 6N HCl. The quenched reaction was then combined 1:1 with acetonitrile in preparation for GC analysis. The pHs of selected test solutions were measured at the respective test temperatures prior to quenching. The extrapolated half- life for each pH @ 25°C was demonstrated be < 1 year and > 24 hours for each pH analyzed indicating the test material was hydrolytically unstable and further evaluation was required (Tier II).

Tier II Hydrolysis
A more extensive investigation of hydrolysis kinetics was conducted (Tier II) at pH values where the test compound was shown to be hydrolytically unstable in the preliminary test (extrapolated half- life at 25°C between 24 hours and one year). Experiments were run at 50, 60, and 70°C at pH 4, 7 and 9. These temperatures were within the range of 10 to 70°C recommended by the guidelines.

For each hydrolysis experiment, a sufficient number of replicate test solutions were prepared to meet the sampling requirements in the hydrolysis guidelines. A minimum of six data points between 10 and 90 percent hydrolysis were obtained to define the degradation kinetics for the parent compound. At regular time intervals duplicate samples were analyzed to determine the concentration propyl propionate in solution and the pH of selected, representative samples was determined. The Tier II experiments were terminated when 90 percent hydrolysis of the parent compound had occurred, or after 30 days. Selected test solutions were analyzed for microbial contamination at the conclusion of the Tier II experiments to confirm the sterility of the test solutions.

Samples (1000 L) from duplicate test solutions were transferred to BBL standard agar plates using sterile pipettes and spread with sterile glass rods. The plates were incubated in the dark at ambient temperature. Plates were visually inspected for microbial growth after five days.

Periodic measurements of the water bath temperature were made with an ASTM thermometer to confirm proper operation. The accuracy of the thermometer is checked annually with thermometers traceable to the National Institute of Standards and Technology.

The pH of test solutions was measured using an Orion 920A+ pH meter. Prior to pH measurements, the pH probe was calibrated with at least two standard buffer solutions (Fisher Scientific, Pittsburgh, Pennsylvania) at the appropriate test temperature. Sterility of the buffer solutions was confirmed using BBL Standard Methods agar plates and incubated at room temperature for 5 days.

Duration of test

Duration of test 1

Duration:

5 d

Temp.:

50 °C

Initial conc. measured:

>= 33 - <= 99.3 mg/L

Duration of test 2

Duration:

30 d

Initial conc. measured:

>= 21.7 - <= 93.6 mg/L

Number of replicates:

not applicable

Positive controls:

no

Negative controls:

no

Statistical methods:

Standard statistical methods were employed

Results and discussion

Preliminary study:

An initial probe experiment with propyl propionate (100 mg/L) was incubated in pH 4, 7, and 9 buffered solutions for five days at 50°C. Hydrolysis of propyl propionate reached 32.0%, 29.3%, and 34.1% after 2.3 hours and 12.2%, 25.9% and 49.1% after five days for pH 4, pH 7, and pH 9 respectively. Extrapolated half- lives for each respective pH was 29.2, 38.1, and 11.5 days.

Test performance:

Since greater than 10% hydrolysis was observed after five days and the half life is greater than 2.4 hours at 50°C, a more extensive evaluation of hydrolysis kinetics was required (Tier II testing).

Transformation products:

no

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

not applicable

Total recovery of test substance (in %)

Total recovery of test substance (in %) 1

% Recovery:

>= 18.3 - 57.9

pH:

4

Temp.:

50 °C

Duration:

>= 0 - <= 30 d

Total recovery of test substance (in %) 2

% Recovery:

>= 19.4 - <= 59.5

pH:

4

Temp.:

60 °C

Duration:

>= 0 - <= 30 d

Total recovery of test substance (in %) 3

% Recovery:

>= 2.9 - 77.5

pH:

4

Temp.:

70 °C

Duration:

>= 0 - <= 30 d

Total recovery of test substance (in %) 4

% Recovery:

>= 11.1 - <= 71.9

pH:

7

Temp.:

50 °C

Duration:

>= 0 - <= 30 d

Total recovery of test substance (in %) 5

% Recovery:

>= 19.4 - <= 100

pH:

7

Temp.:

60 °C

Duration:

>= 0 - <= 30 d

Total recovery of test substance (in %) 6

% Recovery:

>= 21.6 - <= 94.2

pH:

7

Temp.:

70 °C

Duration:

>= 1.9 - <= 16 d

Total recovery of test substance (in %) 7

% Recovery:

>= 13.1 - <= 100

pH:

9

Temp.:

50 °C

Duration:

>= 0 - <= 30 d

Total recovery of test substance (in %) 8

% Recovery:

>= 22.6 - <= 100

pH:

9

Temp.:

60 °C

Duration:

>= 0 - <= 1.7 d

Total recovery of test substance (in %) 9

% Recovery:

>= 27.3 - <= 100

pH:

9

Temp.:

70 °C

Duration:

>= 0 - <= 12 d

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

25 °C

DT50:

203 d

Type:

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

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

25 °C

DT50:

204 d

Type:

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

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

25 °C

DT50:

21.3 d

Type:

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

Other kinetic parameters:

None

Details on results:

Test mixtures were dosed at approximately 96.4 mg/L at each pH and temperature. Hydrolysis rates for propyl propionate in pH 4 buffer increased with temperature following pseudo- first of order kinetics. Half- lives at pH 4 were determined to be 39.4, 30.5, and 13.4 days, at the respective temperatures. Similarly, hydrolysis rates in pH 7 buffer also increase with temperature and followed pseudo-first order kinetics. The hydrolytic half life was determined to be 21.6, 5.2, and 4.0 days at each respective temperature Finally, hydrolysis rates in pH 9 buffer increased in the same manner as pH 4 and 7 buffers at elevated temperatures. Hydrolysis rates were determined to be 0.78, 0.29, and 0.08 days at the respective temperatures.

Using the Arrhenius relationship (logarithm of psuedo-first order rate vs. reciprocal of temperature in °K), the predicted hydrolysis half- lives of propyl propionate at 25 °C in pH 4, 7, and 9 buffered solutions were determined to be 203, 204, and 21.3 days respectively. The hydrolysis product 1-propanol was routinely observed in test solutions after approximately 40% hydrolysis of the parent compound occurred. Following >90 % hydrolysis of the test material, 1-propanol concentrations exceeded 30 mg/L or 77 + 8 % of the mole fraction of the parent material.

Selected test solutions from the Tier II experiments were assayed for microbial contamination at the conclusion of the studies. No microbial growth was observed on agar plates inoculated with the test solutions after five days of incubation. These results indicate that sterility was maintained in the test solutions over the course of the study.

Any other information on results incl. tables

Propyl propionate hydrolysis summary and extrapolated half-life at 25 °C

pH	Test temperature (° C)	Rate constant (days-1)	Natrural log of the rate constant	Half life (days)	r2	Extrapolated half life @ 25  ° C (days)
4	25					203
4	50	-0.0176	5.17	39.4	0.8832
4	60	-0.0227	5.42	30.5	0.8785
4	70	-0.0518	6.25	13.4	0.9855
7	25					204
7	50	-0.0321	5.77	21.6	0.9093
7	60	-0.1344	7.20	5.2	0.8587
7	70	-0.1715	7.45	7.45	0.9834
9	25					21.3
9	50	-08937	9.10	0.78	0.9823
9	60	-2.406	10.1	0.29	0.9820
9	70	-8.1624	11.4	0.08	0.9862

 

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of the study, the predicted hydrolysis half- life at 25 °C for propyl propionate in pH 4, 7, and 9 buffered solutions are 203, 204,
and 21.3 days, respectively.

Executive summary:

The hydrolysis kinetics of propyl propionate was evaluated according to the OECD Guideline 111: Hydrolysis as a Function of pH. Hydrolysis rates were determined at 50, 60, and 70 °C in 0.05M buffered solutions at pH 4, 7, and 9. The buffered solutions were prepared with potassium biphthalate, potassium phosphate, and sodium borate, respectfully. Precautions were taken to minimize biodegradation, oxidation, and photodegradation reactions.

A Tier I probe was conducted at 50 °C at pH 4, 7, and 9. Each buffered solution was dosed with 100 mg/l of the test material. After 5 days, 88.2 mg/l (pH 4), 74.4 mg/l (pH 7), and 51.2 mg/l (pH 9) of the test material remained, translating into half- lives of 29.2, 38.1, and 11.5 days, respectively. These measured half- lives at 50 °C can be extrapolated to half- lives between 24 hours and 1 year at 25 °C. Thus, more extensive kinetic evaluations were necessary to comply with the test guidelines.

Tier II evaluations were conducted in pH 4, 7, and 9 buffers at 50, 60, and 70 °C. Hydrolysis rates for propyl propionate increased with temperature and followed pseudo- first order kinetics. Buffered solutions were dosed at approximately 100 mg/l of the test material. Half- lives at 50, 60, and 70 °C were determined to be 39.4, 30.5, and 13.4 days at pH 4; 21.6, 5.2, and 4.0 days at pH 7; and 0.78, 0.29, and 0.08 days at pH 9, for each respective temperature. Using the Arrhenius relationship (logarithm of pseudo- first order rate constant vs. reciprocal of temperature in °K) the predicted hydrolysis half- life at 25 °C for propyl propionate in pH 4, 7, and 9 buffered solutions are 203, 204, and 21.3 days, respectively.