Isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study in conformance with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar 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:

Isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol

EC Number:

246-771-9

EC Name:

Isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol

Cas Number:

25265-77-4

Molecular formula:

C12H24O3

IUPAC Name:

3-hydroxy-2,2,4-trimethylpentyl 2-methylpropanoate

Constituent 2

Reference substance name:

3-hydroxy-2,2,4-trimethylpentyl isobutyrate

EC Number:

201-049-2

EC Name:

3-hydroxy-2,2,4-trimethylpentyl isobutyrate

Cas Number:

77-68-9

Molecular formula:

C12H24O3

IUPAC Name:

3-hydoxy-2,2,4-trimethylpentyl isobutyrate

Details on test material:

CC(C)C(=O)OCC(C)(C)C(O)C(C)C
CC(C)C(=O)OC(C(C)(C))C(C)(C)CO

Study design

Analytical monitoring:

no

Buffers:

pH = 4; 0.01M Sodium Acetate; 0.82 grams NaOAc diluted to 1 liter with distilled water, pH adjusted to 4 with acetic acid.
pH = 7; 0.01M KH2PO4 / 0.01M K2PO4; 1.32 grams KH2PO4 and 1.74 grams K2PO4 diluted to 1 liter with distilled water, pH adjusted to 7 with acetic
acid.
pH = 9; 0.025M NaB4O7*10H20; 9.5 grams NaB407*10H20 diluted to 1 liter with distilled water.

Details on test conditions:

Test Solution Preparation and Test Conditions
The test chemical, Texanol, is only sparingly soluble in water. For such chemicals, the Guideline provides for use of a cosolvent to enhance the solubility of the test chemical. In this study methanol was used as a cosolvent. A stock solution was prepared by dissolving 0.3149 g of test chemical into 100 mL of methanol. The indiviudal aqueous test solutions were prepared by diluting 1 mL of this stock solution into 100 mL of the appropriate buffer, concentration of test solution = 31.49 mg-test chemical/L. These solutions were transferred to individual red, actinic Erlenmeyer flasks and placed into a controlled temperature water bath at 50.0 °C + or - 0.5 °C. An aliquot of each test solution was removed from each test vessel at 0, 20, 50, and 120 hours and directly analyzed for the isomers of the test chemical.

The preliminary test showed that hydrolysis occurred at pH 9 but not at pH 4 and pH 7. Therefore, the test Guideline requires that Test 1 be performed next at pH 9 and 50°C to determine if the hydrolysis follows first-order kinetics. A test solution was prepared by dissolving 0.3003 g of the test chemical into 100 mL of methanol, then diluting 1.0 mL of this solution to 100 mL with the pH 9 buffer solution. The aqueous test solution was transferred to a red, actinic Erlenmeyer flask and placed into a controlled temperature water bath at 50.0 °C ± 0.5 C. An aliquot of the test solution was removed from the test vessel at 0, 16, 25, 39, 48, 63 and 72 hours and directly analyzed for both isomers of the test chemical. Logarithm of concentration versus time values were plotted and the best fit line was obtained using linear regression. The log of concentration versus time data appeared to
be linear, indicating that the reaction was first order or pseudo-first order.

According to the Test Guideline, if the results of Test 1 show the reaction to be first order or pseudo-first order in nature, Test 2 is skipped and Test 3 is performed. In Test 3, the rate constant and half-life of hydrolysis is measured at temperatures other than 50°C. A stock solution containing 0.1257 grams of the test chemical in 25 mL of methanol was prepared. A second stock solution containing 0.0523 grams of p-dioxane (internal standard) in 25 mL of pH 9 buffer also was prepared. A 5.0 mL aliquot of the p-dioxane stock solution and a 1.0 mL aliquot of the test chemical stock solution were pipetted into a 100 mL volumetric flask and diluted to volume with the pH 9 buffer. The contents of the flask were then transferred into five scintillation vials and placed into separate controlled temperature water baths at 65.0 °C ± 0.5 °C, 55.0C ± 0.5°C, 45.0 °C ± 0.5 °C., 35.0 °C ± 0.5 °C. An aliquot of each test solution was removed from each test vessel at 0, 2, 4, 8, 20 and 46.5 hours and directly analyzed for both isomers of the test chemical.

Statistical methods:

Logarithm of the peak area ratio (e.g., test chemical: internal standard) versus time were plotted and the best fit line was obtained for each isomer assuming first order kinetics and using linear regression. The linear regression analysis gave good linear correlation coefficients for most of the log peak ratio versus time plots. The Arrhenius relationship, e.g., In(k) is proportional to (1/Temp), and linear regression analysis were used to calculate the hydrolysis rate constant and half-life for each isomer at 25°C. For Isomer 1, the rate constant and half-life were calculated twice. In the first calculation all of the data from 25°C to 65 °c were used. In the second calculation, only the data from 45°C to 65 °C were used. The experimental values at 25°C and 35 °C were not used because of their relatively poor correlation coefficients.

Results and discussion

Transformation products:

no

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

9

Temp.:

25 °C

DT50:

396 h

Type:

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

Remarks on result:

other: Isomer 1

Dissipation DT50 of parent compound 2

pH:

9

Temp.:

25 °C

DT50:

103 h

Type:

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

Remarks on result:

other: Isomer 2

Details on results:

Values at 25°C Estimated from Arrenhius Plots
k half life (hours)
Isomer 1 0.00345 201 (using all data)
0.00175 396 (excluding 25°C and 35 °C)
Isomer 2 0.00674 103

Any other information on results incl. tables

Isomer 1

Temp (C)	1/Temp (K)	k	ln k	r
65	0.00296	0.0366	-3.31	-0.9862
55	0.00305	0.0184	-4.00	-0.9937
50	0.00309	0.0136	-4.30	-0.8949
45	0.00314	0.0089	-4.72	-0.9408
35	0.00325	0.0038	-5.57	-0.7071
25	0.00335	0.0053	-5.24	-0.6623

Isomer 2

Temp (C)	1/Temp (K)	k	ln k	r
65	0.00296	0.0500	-3.00	-0.9547
55	0.00305	0.0357	-3.33	-0.9782
50	0.00309	0.0221	-3.81	-0.9822
45	0.00314	0.0250	-3.69	-0.9858
35	0.00325	0.0111	-4.50	-0.9921
25	0.00335	0.0065	-5.04	-0.9537

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Executive summary:

The hydrolysis of the test chemical was studied in GLP conformance with Annex 2 of the OECD Guidelines for Testing Of Chemicals (C(81)30(final)), as required by Council Directive 87/18/EC of December 18, 1986 and according to EEC Test Guideline, Annex V, C.10 and OECD Guideline 111. The test chemical consists of two isomers which were separated analytically using gas chromatography. Due to the limited water solubility of the test chemical, methanol was used as a cosolvent to prepare solutions of the test chemical in aqueous buffers at pH 4, 7 and 9. The final concentration of methanol in the aqueous solutions was 1%. The results of the first phase of testing (preliminary test) showed evidence of greater than 10% hydrolysis within five days for both isomers at pH 9 at 50.0 °C. There was no evidence of hydrolysis for either isomer within five days at pH 4 and 7 at 50 °C. Based on the results of the preliminary test and the provisions of the test guideline, further studies were carried out only at pH 9. The second phase of testing (Test 1) was performed to determine if the hydrolysis is first-order. Test 1, performed at 50 °C, showed that both isomers of the test chemical hydrolysed with log(concentration)-time profiles that closley resembled first-order kinetics. Based on the results of Test 1, the third phase of testing (Test 3 in the Guideline) consisted of determining hydrolysis rate constants and half-lives of both isomers at several temperatures. The data from Test 1 and Test 3 were analyzed using the Arrhenius relationship to calculate rate constants and half-lives for hydrolysis at 25°C and pH 9. The half life of Isomer 1 was determined to be 396 hours at 25C, and the half life of Isomer 2 was determeined to be 103 hours at 25C.