Butyl 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 test material characterization of identity and purity was performed by a laboratory that did not operate under GLP guidelines

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Butyl propionate

EC Number:

209-669-5

EC Name:

Butyl propionate

Cas Number:

590-01-2

Molecular formula:

C7H14O2

IUPAC Name:

butyl propanoate

Details on test material:

- Name of test material (as cited in study report): UCAR n-butyl propionate
- Physical state: clear liquid
- Analytical purity: 99.92%
- Lot/batch No.: 0000369856

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 as 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 n-butyl propionate at 0, 2.3, 5.3, 24, and 120 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 µL) 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:

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 filter sterilized using 0.2 mm nylon sterile filter apparatus. The buffers were sparged with argon to remove dissolved oxygen and thereby minimize possible oxidation reactions. Sterility was verified by a total plate count bacterial assay 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 solution was added to the respective 250 mL of sterile buffer solution. The nominal test concentration of the test material was approximately 100 mg/L. This concentration was below 0.01M and less than one- half the water solubility, as specified in the test guideline. The 0.5% solvent concentration was below the < 1% maximum solvent concentration specified in the test guideline.

Portions (10 mL) of the fortified test solutions were added to serum bottles and sealed with Teflon-coated rubber septa and aluminum crimp seals (E.I. du Pont de Nemours and Company or its affiliates, Wilmington, Delaware). 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.

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 n-butyl propionate at approximately 0, 2.3, 5.3, 24, and 120 hours. Prior to gas chromatographic analysis (GC), test solutions were quenched with 55 µL of 6N HCl to reduce the pH of the reaction mixtures in order to minimize further hydrolysis. The quenched reaction was then combined 1:1 with acetonitrile in preparation for GC analysis. The pH of selected test solutions were measured at the respective test temperatures prior to quenching.

A more extensive investigation of hydrolysis kinetics was conducted (Tier II) at pH values since 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 outlined in the OECD 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 n-butyl 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.

Hydrolysis of n-butyl propionate was expected to involve cleavage of the ester functionality to form 1-butanol and butanoic acid. Standard solutions containing 1-butanol were routinely analyzed to confirm the presence of 1-butanol in test mixtures based on a match of retention times. Butanoic acid was not resolved under the defined analytical conditions.

Periodic measurements of the water bath temperature were made with an ASTM thermometer to confirm proper operation. The accuracy of the thermometer was 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:

>= 98.5 - <= 102 mg/L

Duration of test 2

Duration:

30 d

Initial conc. measured:

>= 83 - <= 108 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 n-butyl propionate (104 mg/L) was incubated in pH 4, 7, and 9 buffered solutions for five days at 50°C. Hydrolysis of n-butyl propionate reached 20.7%, 18.6%, and 32.4% after 2.3 hours and 26.6%, 27.6% and 100% after five days for pH 4, pH 7, and pH 9 respectfully. Extrapolated half- lives for each respective pH was 24.9, 21.7, and 0.8 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).

Transformation products:

yes

Identity of transformation products

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

butan-1-ol

Inventory number:

InventoryMultipleMappingImpl [inventoryEntryValue=EC 200-751-6]

CAS number:

71-36-3

Identity:

1-Butanol

Identity:

1-Butyl alcohol

Identity:

Butanol

Identity:

Butyl alcohol

Identity:

Propylcarbinol

Identity:

n-Butanol

Identity:

n-Butyl alcohol

Molecular formula:

C4H10O

Molecular weight:

74.122

SMILES notation:

CCCCO

InChl:

InChI=1/C4H10O/c1-2-3-4-5/h5H,2-4H2,1H3

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

The hydrolysis product 1-butanol was routinely observed in test solutions after 20 to 30% hydrolysis of the parent compound occurred. Following >90 % hydrolysis of the test material, 1-butanol concentrations exceeded 50 mg/L or 83 + 9 % of the mole fraction of the parent material.

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

25 °C

DT50:

174 d

Type:

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

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

25 °C

DT50:

131 d

Type:

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

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

25 °C

DT50:

13.2 d

Type:

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

Other kinetic parameters:

None

Details on results:

Test mixtures were dosed at approximately 100 mg/L at each pH and temperature. Hydrolysis rates for n-butyl propionate in pH 4 buffer increased with temperature following pseudo- first of order kinetics. Hydrolysis half- lives for n-butyl propionate at pH 4 was determined to be 35.2, 19.2, and 11.6 days, at 50, 60 and 70 °C respectively. Similarly, hydrolysis rates in pH 7 buffer also increased with temperature and followed pseudo- first order kinetics. The hydrolytic half- lives were determined to be 20.1, 12.5, and 5.7 days at each respective temperature. Finally, hydrolysis rates in pH 9 buffer also increased as the temperature increased, following pseudo-first order kinetics. Hydrolysis half- lives for n-butyl propionate was determined to be 0.92, 0.27 and 0.14 days at the respective temperatures.

Using the Arrhenius relationship (logarithm of pseudo-first order rate vs. reciprocal of temperature in °K), the predicted hydrolysis half- lives of n-butyl propionate at 25 °C in pH 4, 7, and 9 buffered solutions are 174, 131, and 13.2 days respectively.

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

None

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of the study, the predicted hydrolysis half- lives of n-butyl propionate at 25 °C in pH 4, 7, and 9 buffered solutions are 174, 131, and 13.2 days, respectively

Executive summary:

The hydrolysis kinetics of n-butyl 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 104 mg/L of the test material. After 5 days, 76.4 mg/L (pH 4), 75.3 mg/L (pH 7), and 0 mg/L (pH 9) of the test material remained, translating into half- lives of 24.9, 21.7, and 0.8 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 n-butyl propionate increased with temperature and followed pseudo- first order kinetics. Buffered solutions were dosed with approximately 100 mg/L of the test material. Half- lives at 50, 60, and 70°C were determined to be 35.2, 19.2, and 11.6 days at pH 4; 20.1, 12.5, and 5.6 days at pH 7 and 0.9, 0.3, and 0.1 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 n-butyl propionate in pH 4, 7, and 9 buffered solutions are 174, 131, and 13.2 days, respectively.