Methacrylic anhydride

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-01-17 - 2011-01-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD 111, GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

(2004) Council Regulation (EC) No. 440/2088, Method C.7

Deviations:

yes

Remarks:

Hydrolysis at pH 7 was tested in addition at 37 °C

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: Due to rapid transformation, replicates were sampled subsequently and automatically by employing an HPLC auto sampler system with temperature controlled sample compartment.

Buffers:

Buffer solution pH 4: 45 mL of 0.1 mol/L NaOH were mixed with 250 mL 0.1 mol/L KH2 Citrate and diluted to 500 ml with double distiiled water.

Buffer solution pH 7: 148.15 mL of 0.1 mol/L NaOH were mixed with 250 mL 0.1 mol/L KH2PO4 and diluted to 500 ml with double distiiled water.

Buffer solution pH 9: 106.5 mL of 0.1 mol/L NaOH were mixed with 250 mL 0.1 mol/L H3BO3 in 0.1 mol/L KCl and diluted to 500 ml with double distiiled water.

Buffers were freshly prepared from chemicals with analytical grade or better quantity. If necessary, volumes were adapted. Buffers were purged with nitrogen for 5 min. Then the pH of the test was checked to a precision of at least 0.1 at the required temperature and adjusted if necessary.

Details on test conditions:

Test item: Methacrylic anhydride
Test solution: Solutions of the test item with a concentration of 200 mg/l were prepared in buffer solution pH 4, 7 and 9
Co-Solvent: Acetonitrile, <= 1% (v/v)
Test item stock solution: Nominal 20000 mg/L in acetonitrile
Control: Buffer solutions (pH 4,7 and 9)
Test method:
One replicaate at each sampling interval
Test containers: Amber HPLC vials, volume: 2 mL
Test volume: 2 mL
Application: The stock solution was prepared at test start. Buffer solutions were spiked with the stock solution and filled into the test containers. After the vials were sealed they were transferred into the temperature controlled sample compartment of the HPLC autosampler. The time between test item application and transfer to the temperature controlled sample compartment of the HPLC autosampler did not exceed 10 min.
Incubation:
pH4; 25 °C
pH7: 25 °C and 37 °C
pH9: 25 °C
Temperature: 25 and 37 °C (only pH7) (+-0.5 °C)
Light: Photolytic effects were avoided by using amber glass vials.

Duration:

4.37 h

pH:

4

Temp.:

25 °C

Initial conc. measured:

193.63 mg/L

Duration:

2.13 h

pH:

7

Temp.:

25 °C

Initial conc. measured:

187.894 mg/L

Duration:

0.728 h

pH:

7

Temp.:

37 °C

Initial conc. measured:

178.431 mg/L

Duration:

0.136 h

pH:

9

Temp.:

25 °C

Initial conc. measured:

95.562 mg/L

Number of replicates:

One replicate at each observation time

Positive controls:

no

Negative controls:

no

Remarks:

Buffer solutions (pH 4, 7 and 9)

Transformation products:

yes

No.:

#1

No.:

#1

No.:

#2

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

Transformation products
With the used analytical method three transformation products were detected: Two major transformation products, methacrylic acid (GMAA) at relative retention time (RRT) 0.45 and one unidentified at RRT 0.27. A minor, although unidentified, transformation product was detected at RRT 0.93. The unidentified major transformation product at RRT 0.27 could only be detected in pH 7 samples. The unidentified transformation product 0.93 was detected at all pH conditions, but showed a relatively constant concentration over hydrolysis time, which might indicate that RRT 0.93 is an impurity of the test item.

For evaluation of the mass balance, the methacrylic acid (GMMA) was evaluated as the molar equivalent of methacrylic anhydride (MAAH), while unidentified transformation products were directly evaluated with the calibration data of methacrylic anhydride. All analytes have a comaprable but unspecific UV-spectrum, which did not allow coclusions on structural relations.

Non-GLP NMR-analysis, provided by the sponsor (sponsor test ID: PLOS 011180898448), strongly indicated that the transformation product is an intermediary methacrylic acid phosphoric acid anhydride (CAS-RN: 1052286-52-8) which was formed in the phosphoric buffer at pH 7.

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.737 h-1

DT50:

56.4 min

St. dev.:

24.9

Type:

not specified

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

1.63 h-1

DT50:

25.5 min

Type:

not specified

pH:

7

Temp.:

37 °C

Hydrolysis rate constant:

4.05 h-1

DT50:

10.3 min

Type:

not specified

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

1.82 h-1

DT50:

2.29 min

Type:

not specified

Hydrolysis Results forMethacrylic anhydride

 

Hydrolysis Results forMethacrylic anhydride at pH 4 and 25 °C

 

Hydrolysis Time   [h]	Concentration   [mg/L]	ln Concentration
0.00	193.630	5.27
0.146	175.046	5.17
0.292	158.466	5.07
0.519	133.984	4.90
0.832	106.909	4.67
1.23	79.947	4.38
1.71	56.358	4.03
2.10	42.456	3.75
2.58	30.049	3.40
3.23	17.923	2.89
4.37	7.787	2.05
6.02	(3.100)	(1.13)

 

Hydrolysis Results for Methacrylic anhydride at pH 7 and 25 °C

                  

Hydrolysis Time   [h]	Concentration   [mg/L]	ln Concentration
0.00	187.894	5.24
0.146	148.687	5.00
0.291	116.241	4.76
0.437	90.692	4.51
0.601	68.641	4.23
0.764	52.441	3.96
0.944	38.854	3.66
1.14	28.358	3.34
1.37	19.217	2.96
1.68	11.914	2.48
2.13	6.034	1.80
2.78	(1.805)	(0.591)

             ( )    =     < LOQ, not taken into account for kinetic calculations

 

Hydrolysis Results for Methacrylic anhydride at pH 7 and 37 °C

 

Hydrolysis Time   [h]	Concentration   [mg/L]	ln Concentration
0.00	178.431	5.18
0.145	105.195	4.66
0.291	57.324	4.05
0.437	31.110	3.44
0.583	17.018	2.83
0.728	9.690	2.27
0.874	(5.342)	(1.68)
1.02	(3.126)	(1.14)
1.17	(1.575)	(0.454)
1.31	(0.568)	(-0.566)

             ( )    =     < LOQ, not taken into account for kinetic calculations

 

Hydrolysis Results for Methacrylic anhydride at pH 9 and 25 °C

 

Hydrolysis Time   [h]	Concentration   [mg/L]	Log Concentration
0.00	95.562	4.56
0.136	8.113	2.09

 

Reaction Rate Constants and Half Lives of Methacrylic anhydride

 

	pH 4	pH 7		pH 9^1)
	25 °C	25 °C	37 °C	25 °C
Reaction rate constantkobs [1/h]	7.37 x 10^-1	1.63 x 10^0	4.05 x 10^0	1.82 x 10^1
Half lifeT½[h]	0.94	0.425	0.171	0.0381
Half lifeT½[min]	56.4	25.5	10.3	2.29

                  1)  Due to rapid transformation the kinetic data was calculated on basis of only two data points and should be treated carefully and with respect to the weak data basis.   

 Transformation products

With the used analytical method three transformation products were detected: Two major transformation products,Methacrylic acid (GMAA) at relative retention time (RRT) 0.45 and one unidentified at RRT 0.27. A minor, although unidentified, transformation product was detected at RRT 0.93.The unidentified major transformation product at RRT 0.27 could only be detected in pH 7 samples. The unidentified transformation product at RRT 0.93 was detected at all pH conditions, but showed a relatively constant concentration over hydrolysis time, which might indicate that RRT 0.93 is an impurity of the test item.  

 

For evaluation of the mass balance, theMethacrylic acid (GMAA) was evaluated as the molar equivalent ofMethacrylicanhydride(MAAH), while the unidentified transformation products were directly evaluated with the calibration data ofMethacrylicanhydride. All analytes have a comparable but unspecific UV- spectrum, which did not allow conclusions on structural relations.

Concentrations of Transformation Products and Mass Balance at Test Condition
                                            pH 4 and 25 °C

 

Hydrolysis Time   [h]	Conc. GMAA   [mg/L]	Eq. Conc. MAAH    [mg/L]	Conc. RRT 0.93   [mg/L]	Conc. MAAH   [mg/L]	Sum     [mg/L]	Mass balance [%]
0.000	12.798	11.5	1.718	193.630	206.8	-
0.146	34.816	31.2	3.333	175.046	209.6	101.3
0.292	53.004	47.5	3.910	158.466	209.8	101.5
0.519	77.045	69.0	3.982	133.984	207.0	100.1
0.832	103.258	92.5	4.066	106.909	203.4	98.4
1.23	128.594	115	4.151	79.947	199.2	96.3
1.71	150.561	135	3.882	56.358	195.1	94.3
2.10	163.876	147	4.168	42.456	193.4	93.5
2.58	174.837	157	3.774	30.049	190.4	92.1
3.23	184.502	165	3.531	17.923	186.7	90.3
4.37	194.180	174	4.012	7.787	185.7	89.8
6.02	199.048	178	2.673	(3.100)	184.0	(89.0)

 

-   =      not applicable

Conc.  = Concentration

Eq. Conc. =   molar equivalent concentration

( )  =  < LOQ, not taken into account for kinetic calculations

 

Concentrations of Transformation Products and Mass Balance at Test Condition
                                                             pH 7 and 25 °C

                  

Hydrolysis Time   [h]	Conc. GMAA   [mg/L]	Eq. Conc. MAAH    [mg/L]	Conc. RRT 0.27   [mg/L]	Conc. RRT 0.92   [mg/L]	Conc. MAAH   [mg/L]	Sum     [mg/L]	Mass balance   [%]
0.000	17.310	15.5	2.493	1.654	187.894	207.5	-
0.146	52.639	47.1	10.330	3.756	148.687	209.9	101.1
0.291	78.710	70.5	17.338	4.068	116.241	208.1	100.3
0.437	98.756	88.4	22.557	4.315	90.692	206.0	99.3
0.601	116.036	104	26.637	4.311	68.641	203.5	98.0
0.764	128.959	115	30.197	3.708	52.441	201.8	97.2
0.944	139.296	125	32.602	4.054	38.854	200.2	96.5
1.14	147.666	132	34.830	4.073	28.358	199.5	96.1
1.37	154.741	139	35.926	3.866	19.217	197.6	95.2
1.68	160.568	144	38.080	4.415	11.914	198.2	95.5
2.13	165.375	148	39.295	4.443	6.034	197.8	95.3
2.78	168.522	151	40.363	4.263	(1.805)	197.3	(95.1)

-   =   not applicable

Conc. = Concentration

Eq. Conc. =  molar equivalent concentration

( )  =  < LOQ, not taken into account for kinetic calculations

Concentrations of Transformation Products and Mass Balance at Test Condition
                                                             pH 7 and 37 °C

 

Hydrolysis Time   [h]	Conc. GMAA   [mg/L]	Eq. Conc. MAAH    [mg/L]	Conc. RRT 0.27   [mg/L]	Conc. RRT 0.92   [mg/L]	Conc. MAAH   [mg/L]	Sum     [mg/L]	Mass balance   [%]
0.000	24.169	21.6	4.218	2.067	178.431	206.4
0.145	85.447	76.5	20.121	4.179	105.195	206.0	99.8
0.291	122.262	109	29.987	3.963	57.324	200.7	97.3
0.437	142.354	127	35.107	4.213	31.11	197.9	95.9
0.583	153.664	138	37.530	3.990	17.018	196.1	95.0
0.728	159.641	143	39.211	3.952	9.690	195.8	94.9
0.874	163.190	146	39.5580	3.9730	5.342	195.0	94.5
1.02	165.314	148	39.1280	4.1830	3.126	194.5	94.2
1.17	166.438	149	40.4260	4.0640	1.575	195.1	94.5
1.31	167.223	150	39.6850	3.9360	0.568	193.9	94.0

 

-   =   not applicable

Conc. = Concentration

Eq. Conc. =  molar equivalent concentration

( )  =   < LOQ, not taken into account for kinetic calculations

 

                           Mass Balance at pH 9 and 25 °C

 

Hydrolysis Time   [h]	Conc. GMAA   [mg/L]	Eq. Conc. MAAH    [mg/L]	Conc. RRT 0.92   [mg/L]	Conc. MAAH   [mg/L]	Sum     [mg/L]	Mass balance   [%]
0.000	112.505	101	3.294	95.562	199.6	-
0.136	192.866	173	4.462	8.113	185.3	92.8
0.273	199.532	179	4.505	n.d.	183.2	91.8

-  =    not applicable

Conc.  =  Concentration

Eq. Conc. =  molar equivalent concentration

n.d. =  not detectable

 

 

Validity criteria fulfilled:

yes

Remarks:

The regression graphs, for graphs with slopes significantly non zero, have a correlation factor of >= 0.9. Test temperature ± 0.5 °C. pH values of ± 0.1 pH at test temperature. Analyytical sensitivity at least down to 10 % of the applied substance.

Conclusions:

The test item Methacrylic anhydride is seen to be hydrolytically instable at all tested conditions, with increasing instability to higher pH and higher temperature.
Methacrylic acid was identified as the dominating transformation product. At the pH 7 test conditions an additional, unidentified major transformation product was observed at relative retention time 0.27 and concentrations, evaluated with the calibration data of Methacrylic anhydride, of up to 39 mg/L (approx. 20 %, calculated to a nominal application concentration of 200 mg/L of the test item) were determined. Mass balance evaluation indicate overall mass balance of > 90 % at test end, therefore no further major transformation products were expected.

The existence of the transformation product RRT 0.27 is, as the reactions and reaction mechanisms of the anhydride hydrolysis is well known, uncommon. On the basis of the available scientific information no side reaction during the hydrolysis of Methacrylic anhydride should occur. Nevertheless, a clear defined and not chromatographically induced signal was observed and the experiment was repeated with comparable results.

Non-GLP NMR-analysis, provided by the sponsor (sponsor test ID: PLOS 011180898448), strongly indicated that the transformation product is an intermediary methacrylic acid phosphoric acid anhydride (CAS-RN: 1052286-52-8).

Executive summary:

The hydrolysis of methacrylic anhydride was tested OECD 111. Methacrylic anhydride is seen to be hydrolytically instable at all tested conditions, with increasing instability to higher pH and higher temperature. Half-lives at 25 °C were determined with 56.4 min at pH 4, 25.5 min at pH 7 and 2.29 min at pH 9. Half-life at 37 °C and pH 7 was 2.29 minutes. An unexpected transformation product was identified as an intermediary methacrylic acid phosphoric acid anhydride (CAS-RN: 1052286-52-8) which was formed in the phosphoric buffer at pH 7.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Description of key information

Hydrolyses fast in water at pH 4, 7 and 9

Key value for chemical safety assessment

Half-life for hydrolysis:

25.5 min

at the temperature of:

25 °C

Additional information

Like other acid anhydrides, methacrylic anhydride was found to be hydrolytically unstable in water at pH 4, 7 and 9. The half lives (DT50) were found to be 56.4 min at pH 4 (25 °C), 25.5 min at pH 7 (25 °C) respectively 10.3 min at 37 °C and 2.29 min at pH 9. The initial hydrolysis product is methacrylic acid (Noack 2012).

This is supported by a second study, which found 92,5 % hydrolysis after 24 h at pH 1.2 and complete hydrolysis at all other pH values (pH 4, 7 and 9; Defitraces 2007).