2-butoxyethyl benzoate

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014

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 og Good Laboratory Practices (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:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-butoxyethyl benzoate

EC Number:

226-685-8

EC Name:

2-butoxyethyl benzoate

Cas Number:

5451-76-3

Molecular formula:

C13H18O3

IUPAC Name:

2-butoxyethyl benzoate

Test material form:

other: clear liquid

Details on test material:

- Name of test material (as cited in study report): 2-butoxyethyl benzoate (Butyl Cellosolve™ Benzoate)
- Physical state: clear liquid
- Analytical purity: 99.2%
- Lot/batch No.: 20130443-19
- Expiration date of the lot/batch: 02 April 2016
- Storage condition of test material: Ambient

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:

Hydrolysis studies (1st tier) were conducted following the procedures established by the OECD Guideline 111 (OECD, 2004). Buffered solutions (0.05M) were prepared at pH 4 (phosphoric acid), pH 7 (monopotassium phosphate), and pH 9 (boric acid). Final pH adjustments (to within ± 0.2 pH units of target pH) were made using either 0.1N sodium hydroxide or 0.1N hydrochloric acid. To reduce the potential for biodegradation of the test material, the buffered solutions were passed through a 0.22-μm membrane filter sterilization units (Corning Incorporated, Corning, New York). An aliquot of the test material (2.0 mg for pH 4, 2.2 mg for pH 7, and 1.6 mg for pH 9) was directly weighed into a sterilized glass vessel, and 100 mL of the appropriate sterile buffer solution was added to prepare each test solution for each pH level. Aliquots of approximately 10 mL of the test solutions were transferred into sterile serum vials (identified by appropriate code), and sealed with sterile Teflon-coated rubber septa and aluminum crimp seals. To minimize possible oxidation reactions, test solutions were sparged with nitrogen. The pH 4, 7, and 9 test solutions were placed in a 50°C incubator (temperature control ±0.5°C). The test solutions were incubated in the dark to minimize possible photochemical reactions. Duplicate samples were collected after 0, 1, and 5 days of incubation at each pH. The pH of selected representative samples was measured during and at the end of the incubation period. Buffered solutions without test material (Blanks) were prepared and analyzed in the same fashion as the test solutions for each pH, to quantify any
background interferences.

Buffers:

Hydrolysis studies (1st tier) were conducted following the procedures established by the OECD Guideline 111 (OECD, 2004). Buffered solutions (0.05M) were prepared at pH 4 (phosphoric acid), pH 7 (monopotassium phosphate), and pH 9 (boric acid). Final pH adjustments (to within ± 0.2 pH units of target pH) were made using either 0.1N sodium hydroxide or 0.1N hydrochloric acid. To reduce the potential for biodegradation of the test material, the buffered solutions were passed through a 0.22-μm membrane filter sterilization units (Corning Incorporated, Corning, New York). An aliquot of the test material (2.0 mg for pH 4, 2.2 mg for pH 7, and 1.6 mg for pH 9) was directly weighed into a sterilized glass vessel, and 100 mL of the appropriate sterile buffer solution was added to prepare each test solution for each pH level. Aliquots of approximately 10 mL of the test solutions were transferred into sterile serum vials (identified by appropriate code), and sealed with sterile Teflon-coated rubber septa and aluminum crimp seals. To minimize possible oxidation reactions, test solutions were sparged with nitrogen. The pH 4, 7, and 9 test solutions were placed in a 50°C incubator (temperature control ±0.5°C). The test solutions were incubated in the dark to minimize possible photochemical reactions. Duplicate samples were collected after 0, 1, and 5 days of incubation at each pH. The pH of selected representative samples was measured during and at the end of the incubation period. Buffered solutions without test material (Blanks) were prepared and analyzed in the same fashion as the test solutions for each pH, to quantify any
background interferences.

Estimation method (if used):

not applicable

Details on test conditions:

Hydrolysis studies (1st tier) were conducted following the procedures established by the OECD Guideline 111 (OECD, 2004). Buffered solutions (0.05M) were prepared at pH 4 (phosphoric acid), pH 7 (monopotassium phosphate), and pH 9 (boric acid). Final pH adjustments (to within ± 0.2 pH units of target pH) were made using either 0.1N sodium hydroxide or 0.1N hydrochloric acid. To reduce the potential for biodegradation of the test material, the buffered solutions were passed through a 0.22-μm membrane filter sterilization units (Corning Incorporated, Corning, New York). An aliquot of the test material (2.0 mg for pH 4, 2.2 mg for pH 7, and 1.6 mg for pH 9) was directly weighed into a sterilized glass vessel, and 100 mL of the appropriate sterile buffer solution was added to prepare each test solution for each pH level. Aliquots of approximately 10 mL of the test solutions were transferred into sterile serum vials (identified by appropriate code), and sealed with sterile Teflon-coated rubber septa and aluminum crimp seals. To minimize possible oxidation reactions, test solutions were sparged with nitrogen. The pH 4, 7, and 9 test solutions were placed in a 50°C incubator (temperature control ±0.5°C). The test solutions were incubated in the dark to minimize possible photochemical reactions. Duplicate samples were collected after 0, 1, and 5 days of incubation at each pH. The pH of selected representative samples was measured during and at the end of the incubation period. Buffered solutions without test material (Blanks) were prepared and analyzed in the same fashion as the test solutions for each pH, to quantify any
background interferences.

Number of replicates:

two

Positive controls:

no

Negative controls:

yes

Statistical methods:

Standard statistical methods were employed

Results and discussion

Preliminary study:

not applicable

Test performance:

The chromatographic peak for the test material was well-separated from the HPLC solvent front, and resolved from any detected peaks in the blank samples. The lowest level quantified (LLQ) for the analyses was 0.25 mg/L, which is < 1.5% of the initial concentrations in the hydrolysis test solutions.
The concentrations of the test material in the test solutions were measured at day 0, 1, and 5. The calculated half-lives for the test material in the pH 4, pH 7, and pH 9 buffered test solutions at 50ºC were approximately 26, 17, and 0.8 days, respectively. By the end of the incubation period, day 5, the concentrations of the test material were below the lowest level quantified (LLQ = 0.25 mg/L) in test solutions at pH 9. As a result, the half life of the test material at pH 9 was calculated using the pseudo-first order rate constant assuming the concentration of the test material was 0.25 mg/L at day 5.
The incubator was maintained at 50ºC ± 0.5 ºC, averaging 50.1 ºC during the study based on measurements at the time of sampling: 50.4 ºC (at day 0), 50.2 ºC (at day 1) and 49.7 ºC at (day 5).
There was a minimal pH shift noted in the test solutions and blanks throughout the course of the study. The final pH of the test solutions and blanks on day 5 differed by ≤ 0.06 units from the initial pH values (day 0).

Transformation products:

not specified

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

A 1st tier hydrolysis study was conducted for 2-Butoxyethyl Benzoate with the test procedure described in the OECD “Hydrolysis as a Function of pH” guideline (method 111). The test material exhibited increasing hydrolysis rates (i.e., shorter half-lives) with increasing pH. The half-lives for the test material at 50 ºC were 26 days, 17 days, and 0.8 days, at pH 4, pH 7, and pH 9, respectively. Assuming a 25 °C change in temperature causes a 10-fold change in rate constants (Lyman et al., 1990), the half-lives for the test material at 25 °C are expected to be approximately 9 months, 6 months, and 0.3 months at pH 4, pH 7, and pH 9, respectively.

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

50 °C

DT50:

26 d

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

50 °C

DT50:

17 d

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

50 °C

DT50:

0.8 d

Dissipation DT50 of parent compound 4

pH:

4

Temp.:

25 °C

DT50:

9 mo

Type:

not specified

Dissipation DT50 of parent compound 5

pH:

7

Temp.:

25 °C

DT50:

6 mo

Type:

not specified

Dissipation DT50 of parent compound 6

pH:

9

Temp.:

25 °C

DT50:

0.3 mo

Type:

not specified

Other kinetic parameters:

none

Details on results:

A 1st tier hydrolysis study was conducted for 2-Butoxyethyl Benzoate with the test procedure described in the OECD “Hydrolysis as a Function of pH” guideline (method 111). The test material exhibited increasing hydrolysis rates (i.e., shorter half-lives) with increasing pH. The half-lives for the test material at 50 ºC were 26 days, 17 days, and 0.8 days, at pH 4, pH 7, and pH 9, respectively. Assuming a 25 °C change in temperature causes a 10-fold change in rate constants (Lyman et al., 1990), the half-lives for the test material at 25 °C are expected to be approximately 9 months, 6 months, and 0.3 months at pH 4, pH 7, and pH 9, respectively.

Any other information on results incl. tables

2 -butoxyethyl benzoate hydrolysis results at 50 °C

	pH 4 (mg/l)	% of initial conc.	in conc. (**)	pH 7 (mg/l)	% of initial conc.	in conc. (**)	pH 9	% of initial conc.	in conc. (**)
Blank - day 0	< LLQ*		N/A	< LLQ*		N/A	< LLQ*		N/A
Blank - day 1	< LLQ*		N/A	< LLQ*		N/A	< LLQ*		N/A
Blank - day 5	< LLQ*		N/A	< LLQ*		N/A	< LLQ*		N/A
Sample - day 0 -1	18.7		2.93	23.2		3.14	18.4		2.91
Sample - day 0 -2	19.0		2.94	23.0		3.13	18.5		2.92
Average	18.8			23.1			18.4
std. dev.	0.2			0.1			0.1
Sample - day 1 -1	18.1	96	2.89	21.9	95	3.08	6.44	35	1.86
Sample - day 1 -2	18.1	96	2.89	21.9	95	3.09	6.51	35	1.87
Average	18.1	96		21.9	95		6.5	35
std. dev.	0.0	0.1		0.1	0.3		0.0	0.3
Sample - day 5 -1	16.5	87	2.80	18.6	80	2.92	< LLQ*	< 1.4***	- 1.39***
Sample - day 5 -2	16.3	87	2.79	18.8	82	2.94	< LLQ*	< 1.4***	- 1.39***
Average	16.4	87		18.7	81		N/A	N/A
std.dev.	0.1	0.6		0.2	0.8		N/A	N/A
Half life (days)	26			17			0.8***

* < lowest level quantified (0.25 mg/l)

** natural logarithm of the concentration

*** assuming day 5 concentration is the lowest level quantified (0.25 mg/l)

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

A 1st tier hydrolysis study was conducted for 2-Butoxyethyl Benzoate with the test procedure described in the OECD “Hydrolysis as a Function of pH” guideline (method 111). The test material exhibited increasing hydrolysis rates (i.e., shorter half-lives) with increasing pH. The half-lives for the test material at 50 ºC were 26 days, 17 days, and 0.8 days, at pH 4, pH 7, and pH 9, respectively. Assuming a 25 °C change in temperature causes a 10-fold change in rate constants (Lyman et al., 1990), the half-lives for the test material at 25 °C are expected to be approximately 9 months, 6 months, and 0.3 months at pH 4, pH 7, and pH 9, respectively.

Executive summary:

A 1st tier assessment of hydrolytic degradation of 2-butoxyethyl benzoate was determined in accordance with the test procedure described in the OECD Guideline No. 111: “Hydrolysis as a Function of pH.” Buffered solutions were prepared at pH 4, 7, and 9 and were each dosed with approximately 15 mg/L of the test material. Test solutions were incubated at 50 °C for five days in the dark. At selected time intervals (0, 1, and 5 days) the concentrations of the test material remaining in the test solutions were determined by high performance liquid chromatography (HPCL) with Diode Array Detector (DAD).

The test material exhibited increasing hydrolysis rates (i.e., shorter half-lives) with increasing pH. After 5 days, 87% and 81% of the test material remained in pH 4 and pH 7 solutions, respectively, while the test material was not detected (lowest level quantified was 0.25 mg/L) in pH 9 solutions. The half-lives for the test material at 50 °C were approximately 26 days, 17 days and 0.8 days, at pH 4, pH 7, and pH 9, respectively. Assuming a 25 °C change in temperature causes a 10-fold change in rate constants, the half-lives for the test material at 25 °C are expected to be approximately 9 months, 6 months and 0.3 months at pH 4, pH 7, and pH 9, respectively.