Boronic acid, (4-ethylphenyl)-

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-02-13 to 2007-06-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

The sample solutions were taken from the water bath at various times and the pH of each solution recorded before concentration was determined.

Buffers:

-pH 4: 21.01 g citric acid monohydrate were dissolved in 200 mL sodium hydroxide solution (conc. = 1 mol/L). This solution was filled up to a volume of 1000 mL with distilled water. 44 mL of hydrochloric acid (conc. = 1 mol/L) were added to 560 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 4 for each hydrolysis temperature.

-pH 7: 13.61 g potassium dihydrogen phosphate were dissolved in 1000 mL distilled water. 30 mL of sodium hydroxide solution (conc. = 1 mol/L) were added to 500 ml of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 7 for each hydrolysis temperature.

-pH 9: 7.46 g potassium chloride and 6.18 g boric acid were dissolved in 1000 mL distilled water. 21 mL of sodium hydroxide solution (conc. = 1 mol/L) were added to 500 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 9 for each hydrolysis temperature.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: General laboratory glassware
- Measures taken to avoid photolytic effects: The test solutions were shielded from light whilst maintaining the test temperature.
- Measures to exclude oxygen: The buffer solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.
- If no traps were used, is the test system closed/open: Closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus?: none was reported

PREPARATION OF THE TEST SAMPLES
For each test stock solutions of the test item, they were prepared by weighing about 11.1 mg to 13.0 mg of the test item and dissolving it in 50 mL distilled water using an ultrasonic bath for 1 h. 5 mL of these stock solutions were placed in 50 mL volumetric flasks diluted in the relevant buffers (filled up to the mark). This preparation was done in a glove box filled with nitrogen.

TEST MEDIUM
- Volume used/treatment: 50 mL
- Kind and purity of water: distilled water

OTHER TEST CONDITIONS
- Adjustment of pH: none

Duration:

5 d

pH:

4

Temp.:

70 °C

Initial conc. measured:

21.3 mg/L

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

24.9 mg/L

Duration:

5 d

pH:

4

Temp.:

40 °C

Initial conc. measured:

25.1 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

26.7 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

26.9 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

26.6 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

26.4 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Preliminary study:

The preliminary hydrolysis test was performed at 50 °C at pH values of 4, 7 and 9. The samples were incubated for five days and analyzed afterwards.
The decomposition at pH 4 is below 50 % after 2.4 hours at 50 °C and above 10 % after 5 days at 50 °C. The pretest at pH 4 indicates that an examination of the hydrolysis kinetics is essential.
The decomposition at pH 7 and pH 9 is below 50 % after 2.4 hours and below 10 % after 5 days at 50 °C. According to test guideline, no additional tests have to be performed for pH 7 and pH 9.

Transformation products:

no

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

1 176 h

Type:

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

pH:

4

Temp.:

40 °C

Hydrolysis rate constant:

>= 0.003 - <= 0.003 h-1

DT50:

>= 250.8 - <= 273.6 h

Type:

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

pH:

4

Temp.:

70 °C

Hydrolysis rate constant:

>= 0.035 - <= 0.036 h-1

DT50:

>= 19.4 - <= 19.5 h

Type:

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

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

>= 0.006 - <= 0.007 h-1

DT50:

>= 103.8 - <= 107.5 h

Type:

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

Individual Results

Pretests at 50 °C

Table 1: Results of the hydrolysis pre-tests (experiments 1 to 6)

 

Experiment	pH	Duration	C0 in mg/L^1	Ct in mg/L	Ct/C0	Decomposition in %
1	4	2.4 h	24.9	24.4	0.9774	2.26
		5 d		11.4	0.4581	54.2
2	4	2.4 h	27.3	26.6	0.9736	2.64
		5 d		12.2	0.4458	55.4
3	7	2.4 h	26.7	26.7	1.0022	-0.22
		5 d		26.3	0.9878	1.22
4	7	2.4 h	26.9	26.8	0.9931	0.69
		5 d		26.3	0.9774	2.26
5	9	2.4 h	26.6	26.5	0.9955	0.45
		5 d		26.0	0.9785	2.15
6	9	2.4 h	26.4	26.2	0.9938	0.62
		5 d		25.5	0.9661	3.39

The decomposition at pH 4 is below 50 % after 2.4 hours at 50 °C and above 10 % after 5 days at 50 °C. The pretest at pH 4 indicates that an examination of the hydrolysis kinetics is essential.

The decomposition at pH 7 and pH 9 is below 50 % after 2.4 hours and below 10 % after 5 days at 50 °C. According to test guideline no additional tests have to be performed for pH 7 and pH 9.

¹C₀ measured by HPLC

Table 2: Concentrations of Standards for recheck

 

Standard	Measured concentration (mg/L)	% Recovery (mean value)
Standard 3 (c = 27.4 mg/L)	27.4 / 27.3	99.6
	27.7 / 27.6	101
	27.7/27.7	101
	27.6 / 27.7	101
	27.8 / 27.8	101
Standard 4 (c = 25.6 mg/L)	25.4 / 25.3	99.0
	25.2 / 25.2	98.2
	25.5 / 25.4	99.3
	25.2 / 25.2	98.5
	25.3 / 25.4	98.9
	25.4 / 25.5	99.4
	25.5 / 25.5	100
Standard 10(c = 12.8 mg/L)	12.8 /12.8	99.7
	12.8 /12.8	99.9
Standard 11 (c = 2.56 mg/L)	2.63/2.61	102

Recoveries of the 'recheck samples' ranged from 98.2 % to 102 %, indicating a good accuracy of the analytical method.

 

Table 3: Results of test 1 at pH 4 and test temperature 50 °C (experiment 1)

 

Duration h	C0^1 mg/L	Ct mg/L	Ct/C0	log (Ct/C0)	Decomposition %
2.4	24.9	24.4	0.9774	-0.0099	2.26
120.0		11.4	0.4581	-0.3390	54.2
142.3		10.0	0.4008	-0.3971	59.9
165.9		8.37	0.3354	-0.4745	66.5
237.1		5.55	0.2223	-0.6530	77.8
261.0		4.65	0.1865	-0.7294	81.4
268.6		4.37	0.1752	-0.7564	82.5
286.7		3.98	0.1594	-0.7976	84.1

 

Regression:               -log (C_t/C₀) = t * k_obs / 2.303     with k_obs / 2.303 = b

b = 0.0028

coefficient of determination r²: 0.9996

Calculations based on the analysis lead to: k_obs = 0.0064 h^-1

t_1/2 = 107.5 h

 

Table 4: Results of test 1 at pH 4 and test temperature 50 °C (experiment 2)

 

Duration h	C0^1 mg/L	Ct mg/L	Ct/C0	log (Ct/C0)	Decomposition %
2.4	27.3	26.6	0.9736	-0.0116	2.64
120.0		12.2	0.4458	-0.3509	55.4
142.3		10.4	0.3813	-0.4187	61.9
165.9		8.73	0.3198	-0.4951	68.0
237.1		5.50	0.2013	-0.6961	79.9
261.0		4.73	0.1733	-0.7612	82.7
268.6		4.47	0.1641	-0.7848	83.6
286.7		3.95	0.1445	-0.8400	85.6

 

Regression:      -log (C_t/C₀) = t * k_obs / 2.303     with k_obs / 2.303 = b

b = 0.0029

coefficient of determination r²: 0.9998

Calculations based on the analysis lead to: k_obs = 0.0067 h^-1

t_1/2 = 103.8 h

Test 1 at pH 4 and 50 °C showed a linear relationship between -log (C_t/C₀) and t -> pseudo first order reaction

 

Table 5: Results of test 1 at pH 4 and test temperature 70 °C (experiment 9)

 

      

Duration h	C0^1 mg/L	Ct mg/L	Ct/C0	log (Ct/C0)	Decomposition %
3.87	21.3	18.5	0.8687	-0.0611	13.1
21.4		10.0	0.4672	-0.3305	53.3
23.3		9.21	0.4325	-0.3640	56.8
24.9		8.84	0.4150	-0.3820	58.5
26.9		8.03	0.3769	-0.4237	62.3
28.7		7.68	0.3607	-0.4429	63.9
47.1		4.04	0.1899	-0.7215	81.0

 

Regression:                     -log (C_t/C₀) = t * _kobs / 2.303     with k_obs / 2.303 = b

b = 0.0154

coefficient of determination r²: 0.9996

Calculations based on the analysis lead to: kobs = 0.0355 h^-1

t_1/2 = 19.5 h

Table 6: Results of test 1 at pH 4 and test temperature 70 °C (experiment 10)

 

      

Duration h	C0^1 mg/L	Ct mg/L	Ct/C0	log (Ct/C0)	Decomposition %
3.87	21.1	18.7	0.8823	-0.0544	11.8
21.4		9.81	0.4618	-0.3355	53.8
23.3		9.15	0.4329	-0.3636	56.7
24.9		8.67	0.4101	-0.3872	59.0
26.9		8.07	0.3819	-0.4180	61.8
28.7		7.54	0.3565	-0.4479	64.4
47.1		3.97	0.1878	-0.7264	81.2

Regression:                     -log (C_t/C₀) = t * k_obs / 2.303     with k_obs / 2.303 = b

b = 0.0155

coefficient of determination r²: 0.9998

Calculations based on the analysis lead to: kobs = 0.0357 h^-1

t_1/2 = 19.4 h

 

Test 1 at pH 4 and 70 °C showed a linear relationship between -log (C_t/C_o) and t -> pseudo first order reaction.

 

Table 7: Results of test 1 at pH 4 and test temperature 40 °C (experiment 7)

 

Duration h	C0^1 mg/L	Ct mg/L	Ct/C0	log (Ct/C0)	Decomposition %
118.3	25.1	18.3	0.7312	-0.1360	26.9
144.3		17.1	0.6824	-0.1659	31.8
166.5		16.2	0.6440	-0.1911	35.6
191.3		15.0	0.5994	-0.2223	40.1
214.4		14.1	0.5625	-0.2499	43.8
306.7		11.1	0.4422	-0.3544	55.8
381.1		9.14	0.3644	-0.4385	63.6
450.7		7.68	0.3060	-0.5142	69.4

 

Regression:                     -log (C_t/C₀) = t * k_obs / 2.303     with k_obs / 2.303 = b

b = 0.0011

coefficient of determination r²: 0.9998

Calculations based on the analysis lead to: k_obs = 0.0025 h^-1

t_1/2 = 273.6 h

 

Table 8: Results of test 1 at pH 4 and test temperature 40 °C (experiment 8)

 

Duration h	C0^1 mg/L	Ct mg/L	Ct/C0	log (Ct/C0)	Decomposition %
118.3	25.0	18.3	0.7299	-0.1368	27.0
144.3		17.0	0.6784	-0.1685	32.2
166.5		15.9	0.6368	-0.1960	36.3
191.3		15.0	0.5987	-0.2228	40.1
214.4		14.1	0.5617	-0.2505	43.8
306.7		11.0	0.4399	-0.3567	56.0
381.1		9.04	0.3608	-0.4427	63.9
450.7		7.59	0.3030	-0.5185	69.7

 

Regression:                     -log (C_t/C₀) = t * k_obs / 2.303     with k_obs / 2.303 = b

b = 0.0012

coefficient of determination r²: 0.9998

Calculations based on the analysis lead to: k_obs = 0.0028 h^-1

t_1/2 = 250.8 h

 

Test 1 at pH 4 and 40 °C showed a linear relationship between -log (C_t/C₀) and t -> pseudo first order reaction.

 

Table 9: Concentrations of Standards for recheck

 

Standard	Measured concentration (mg/L)	% Recovery (mean value)
Standard 4 (c = 25.6 mg/L)	25.6 / 25.5	99.7
	25.5 / 25.5	99.6
	27.8 / 27.8	101
	27.8 / 27.7	101
Standard 12 (c = 27.4 mg/L)	27.7 / 27.7	101
	27.8 / 27.8	101
	27.8 / 27.8	101
	27.8 / 27.8	101
Standard 13 (c = 13.7 mg/L)	13.9 / 13.9	101
Standard 14 (c = 13.7 mg/L)	14.0 /14.0	102
	14.0 /14.0	102
	5.46 / 5.47	99.5
	5.54 /5.52	101
	5.53 / 5.54	101
Standard 15 (c = 5.49 mg/L)	5.52 / 5.54	101
	5.52 / 5.51	101
	5.51 / 5.52	101
	5.50 / 5.50	100
	5.49 / 5.50	100

Recoveries of the 'recheck samples' ranged from 99.5 % to 102 %, indicating a good accuracy of the analytical method.

 

Summary of the hydrolysis results and extrapolation

Table 10: Summary and extrapolation of the results at pH 4

 

Temperature in °C	t1/2 in h	k in h^-1	Experiment
50	107.5	0.0064	experiment 1
50	103.8	0.0067	experiment 2
70	19.5	0.0355	experiment 9
70	19.4	0.0357	experiment 10
40	273.6	0.0025	experiment 7
40	250.8	0.0028	experiment 8
25°C	1176	0.00059	extrapolation

 

In k_obs = - E/R * 1/T + const   with - E/R = b and T in K

b = -9316.5

const = 23.8

coefficient of determination r² = 0.9993

 

t_1/2 at 25 °C = 1176 hours = 49 days

 

Validity criteria fulfilled:

yes

Conclusions:

At pH 4 the half-life period was determined by the extrapolation of the results of the experiments at temperatures 40 °C, 50 °C and 70 °C to a temperature of 25 °C and it was found to be 49.0 days (1176 h). At pH 9 and pH 7 less than 10 % of the reaction was observed after 5 days at 50 °C (t1/2 at 25 °C > 1 year). Thus, the test item may be considered hydrolytically stable and with reference to OECD TG 111, no additional testing is required.

Executive summary:

The abiotic degradation of the test item was determined by hydrolysis rate as a function of the pH-value according to OECD TG 111 and EU method C.7. initially, a pretest test (Tier 1) was done at 20 °C with buffers at pH 4, 7 and 9. The decomposition at pH 4 was found to be below 50 % after 2.4 hours at 50 °C and above 10 % after 5 days at 50 °C. The decomposition at pH 7 and pH 9 were below 50 % after 2.4 hours and below 10 % after 5 days at 50 °C. The pretest at pH 4 indicated that the examination of the hydrolysis kinetics was essential. According to OECD TG 111, no additional tests were performed for pH 7 and pH 9. Thus, a Tier 2 hydrolysis test was conducted for pH 4 at 40, 50 and 70 °C. At pH 4 the half-life period was determined by the extrapolation of the results of the experiments at temperatures 40 °C, 50 °C and 70 °C to a temperature of 25 °C and it was found to be 49.0 days (1176 h). At pH 9 and pH 7 less than 10 % of the reaction was observed after 5 days at 50 °C (t_1/2 at 25 °C > 1 year). Thus, the test item may be considered hydrolytically stable and with reference to OECD TG 111 no additional testing is required.

Description of key information

At pH 4 the half-life period was determined by the extrapolation of the results of the experiments at temperatures 40 °C, 50 °C and 70 °C to a temperature of 25 °C and it was found to be 49.0 days (1176 h). At pH 9 and pH 7 less than 10 % of the reaction was observed after 5 days at 50 °C (t_1/2 at 25 °C > 1 year). Thus, the test item may be considered hydrolytically stable and with reference to OECD TG 111, no additional testing is required (reference 5.1.2-1).

Key value for chemical safety assessment

Half-life for hydrolysis:

1 176 h

at the temperature of:

25 °C

Additional information

The abiotic degradation of the test item was determined by hydrolysis rate as a function of the pH-value according to OECD TG 111 and EU method C.7. Initially, a pretest test (Tier 1) was done at 20°C with buffers at pH 4, 7 and 9. The decomposition at pH 4 was found to be below 50 % after 2.4 hours at 50 °C and above 10 % after 5 days at 50 °C. The decomposition at pH 7 and pH 9 were below 50 % after 2.4 hours and below 10 % after 5 days at 50 °C. The pretest at pH 4 indicated that the examination of the hydrolysis kinetics was essential. According to OECD TG 111, no additional tests were performed for pH 7 and pH 9. Thus, a Tier 2 hydrolysis test was conducted for pH 4 at 40, 50 and 70 °C. At pH 4 the half-life period was determined by the extrapolation of the results of the experiments at temperatures 40 °C, 50 °C and 70 °C to a temperature of 25 °C and it was found to be 49.0 days (1176 h). At pH 9 and pH 7 less than 10 % of the reaction was observed after 5 days at 50 °C (t_1/2 at 25 °C > 1 year). Thus, the test item may be considered hydrolytically stable and with reference to OECD TG 111 no additional testing is required.