2,3-dihydroxypropyl methacrylate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental starting date: 03 August 2017. Experimental completion date: 18 October 2017.

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)

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

Remarks:

HPLC

Details on sampling:

Samples
For duplicate aliquots of the stock solution for the initial time point and duplicate incubated vessels (samples A and B) removed at each time point, 5 mL aliquots of each sample solution were mixed with 10 mL of purified water*, before diluting to a total volume of 20 mL using acetonitrile (dilution factor of 4).

Standards
Duplicate standard solutions at a nominal concentration of 250 mg/L of test item were prepared in 25:25:50% v/v relevant buffer solution:acetonitrile:purified water*.

Matrix blanks
25:25:50% v/v relevant buffer solution:acetonitrile:purified water*.

* For pH 9 matrix, the purified water contained 1% v/v phosphoric acid.

Buffers:

The test system used sterile buffer solutions at pH’s 4, 7 and 9.
The buffer solutions were subjected to filtration through 0.2 µm filters, ultrasonication and degassing with nitrogen to minimize dissolved oxygen content.

Details on test conditions:

Preparation of the Test Solutions
Stock solutions of test item were prepared at a nominal concentration of 1.0 g/L in the three buffer solutions. The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility. The stock solutions were split into individual glass vessels, sealed with minimal headspace, for each data point. These sample solutions were shielded from light whilst maintained at the test temperature.

Preliminary Test (Tier 1)
Sample solutions at pH 4, pH 7 and pH 9 were maintained at 50.0 ± 0.5 °C for the following periods of time: up to 120 h for the pH 4 samples, 720 h for the pH 7 samples and 29 h for the pH 9 samples.

Tier 2
Results from the Preliminary Test/Tier 1 showed it was necessary to undertake further testing at pH 7 and pH 9. pH 7 sample solutions were maintained up to 452 h at 60.0 ± 0.5 °C and 120 h at 70.0 ± 0.5 °C. pH 9 sample solutions were maintained up to 216 h at 30.0 ± 0.5 °C and 55 h at 40.0 ± 0.5 °C.

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

1 g/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.995 g/L

Duration:

452 h

pH:

7

Temp.:

60 °C

Initial conc. measured:

1 g/L

Duration:

120 h

pH:

7

Temp.:

70 °C

Initial conc. measured:

1.01 g/L

Duration:

29 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.985 g/L

Duration:

55 h

pH:

9

Temp.:

40 °C

Initial conc. measured:

0.993 mg/L

Duration:

216 h

pH:

9

Temp.:

30 °C

Initial conc. measured:

0.972 mg/L

Number of replicates:

2

Preliminary study:

pH 4 at 50 ºC
Less than 10% hydrolysis after 120 hours (5 days) at 50 °C, which is equivalent to a half-life greater than 1 year at 25 °C. Therefore, no further testing was required as the test item was confirmed to be hydrolytically stable at pH 4.

pH 7 at 50 ºC
The extent of hydrolysis after 120 hours indicated that further testing (Tier 2) was required to estimate the rate constant and half-life at 25 °C.

pH 9 at 50 ºC
The extent of hydrolysis after 2 hours indicated that further testing (Tier 2) was required to estimate the rate constant and half-life at 25 °C.

Transformation products:

yes

No.:

#1

No.:

#2

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

Based on the chemical structure of the test item, the hydrolysis products were considered to be methacrylic acid (CAS 79-41-4) and glycerol (CAS 56-81-5). The reaction is hydrolysis of an ester into a carboxylic acid and an alcohol.

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

514 h

Type:

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

pH:

7

Temp.:

60 °C

Hydrolysis rate constant:

0.004 h-1

DT50:

164 h

Type:

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

pH:

7

Temp.:

70 °C

Hydrolysis rate constant:

0.012 h-1

DT50:

57.7 h

Type:

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

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.069 h-1

DT50:

10 h

Type:

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

pH:

9

Temp.:

40 °C

Hydrolysis rate constant:

0.024 h-1

DT50:

29.6 h

Type:

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

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

0.008 h-1

DT50:

91.5 h

Type:

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

Details on results:

Validation
The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 10 to 350 mg/L in 25:25:50% v/v relevant buffer solution:acetonitrile:purified water.. These were satisfactory with a goodness of fit coefficient (r2) of 1.000 being obtained for all three matrices.

Discussion
In most sequences, the analysis of the matrix blank solutions showed a small peak at the approximate retention time of the test item. The peak decreased significantly or even disappeared in the second injection of the blank solution, suggesting that it was caused by carryover. It has to be noted that this carryover did not exceed 10% of the sample response and affected both standard and sample solutions. It has therefore been considered that its overall effect on the results was not significant.
The 216 hours data points for pH 9 at 30 °C were not used in calculating the half-life as they were significantly inconsistent with the other data points. The reason for this was not known.
The kinetics of the study have been determined to be consistent with that of a pseudo-first order reaction, as the graphs of log10 concentration versus time are straight lines.

pH 4 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	1.00	1.00	-	-
24	0.997	0.994	99.5	99.1
120	1.02	1.04	102	104

pH 7 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.995	0.994	-	-
24	0.957	0.960	96.2	96.5
120	0.844	0.833	84.8	83.8
240	0.710	0.710	71.4	71.4
362½	0.604	0.601	60.8	60.4
480	0.499	0.504	50.1	50.7
600¼	0.441	0.433	44.3	43.5
720	0.387	0.378	38.9	38.0

pH 7 at 60 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	1.00	0.995	-	-
48	0.783	0.793	78.4	79.5
96	0.630	0.618	63.1	62.0
144	0.516	0.505	51.7	50.6
192	0.408	0.409	40.9	41.0
264	0.300	0.303	30.1	30.3
360	0.206	0.208	20.6	20.8
452	0.146	0.146	14.7	14.7

pH 7 at 70 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	1.01	1.00	-	-
7	0.902	0.897	89.9	89.3
24	0.734	0.725	73.2	72.2
31	0.637	0.667	63.4	66.4
48	0.532	0.527	53.0	52.5
72	0.402	0.392	40.0	39.1
96	0.308	0.311	30.7	31.0
120	0.234	0.236	23.3	23.5

pH 9 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.985	0.984	-	-
2	0.829	0.824	84.2	83.7
4	0.697	0.699	70.8	71.0
6	0.593	0.594	60.2	60.3
8	0.514	0.513	52.2	52.1
23	0.186	0.186	18.8	18.9
26	0.152	0.156	15.5	15.9
29	0.130	0.129	13.2	13.1

pH 9 at 40 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.993	0.994	-	-
2½	0.899	0.917	90.5	92.3
5	0.854	0.855	85.9	86.1
7½	0.793	0.789	79.9	79.4
24	0.522	0.523	52.6	52.6
31	0.445	0.443	44.7	44.6
48	0.316	0.310	31.8	31.2
55	0.271	0.273	27.2	27.5

pH 9 at 30 ºC

Time (Hours)	Concentration (g/L)		% of Mean Initial Concentration
	A	B	A	B
0	0.972	0.969	-	-
24	0.802	0.790	82.6	81.4
48	0.645	0.645	66.5	66.4
72	0.532	0.531	54.8	54.7
96	0.445	0.440	45.9	45.4
120	0.372	0.367	38.3	37.8
168	0.276	0.277	28.4	28.5
216*	0.038	0.041	3.96	4.23

*Not used – See Discussion.

The Arrhenius plots for pH 7 and pH 9 were constructed using the data shown in the following tables:

pH 7 Arrhenius Data

T (ºC)	T (K)	1/T (K^-1)	kobs(h^-1)	ln kobs
50	323	3.10 x 10^-3	1.35 x 10^-3	-6.61
60	333	3.00 x 10^-3	4.24 x 10^-3	-5.46
70	343	2.91 x 10^-3	1.20 x 10^-2	-4.42

pH 9 Arrhenius Data

T (ºC)	T (K)	1/T (K^-1)	kobs(h^-1)	ln kobs
30	303	3.30 x 10^-3	7.58	-4.88
40	313	3.19 x 10^-3	2.35	-3.75
50	323	3.10 x 10^-3	6.92	-2.67

Validity criteria fulfilled:

yes

Conclusions:

The estimated rate constants and half-lives at 25 °C of the test item are shown below:
Ph 4
Estimated rate constant at 25 °C: not applicable.
Estimated half-life at 25 °C: > 1 year
Ph 7
Estimated rate constant at 25 °C: 5.83 x 10^-5 h-1
Estimated half-life at 25 °C: > 1 year (496 days)
Ph 9
Estimated rate constant at 25 °C: 4.15 x 10^-5 h-1
Estimated half-life at 25 °C: 6.97 days

Executive summary:

The hydrolytic stability of 2,3-dihydroxypropyl methacrylate as a function of pH was determine dusing a procedure designed to be compatible with Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. The results are as follows:

pH	Estimated rate constant at 25 °C	Estimated half-life at 25 °C
4	Not applicable	>1 year
7	5.83 x10^-5h^-1	>1 year (496 days)
9	4.15 x 10^-3h^-1	6.97 days

Description of key information

The estimated rate constants and half-lives at 25 °C of the test item are shown below:

pH 4

Estimated rate constant at 25 °C: not applicable.

Estimated half-life at 25 °C: > 1 year

pH 7

Estimated rate constant at 25 °C: 5.83 x 10^-5 h-1

Estimated half-life at 25 °C: > 1 year (496 days)

pH 9

Estimated rate constant at 25 °C: 4.15 x 10^-5 h-1

Estimated half-life at 25 °C: 6.97 days