Trimethyl orthoacetate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-07-29 - 2003-08-01 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC-Guideline C.7 as specified in Directive 92/69/EC (seventeenth adaption of Directive 67/548/EEC. Annex V)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, Landwirtschaft und Forsten, Mainzer Straße 80, D65189 Wiesbaden, Germany

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling method: The samples (filled in brown glass Vials) with a maximal test substance concentration of 0.01 mol/L were taken out of the water bath and cooled down rapidly to room temperature to stop the hydrolysis reaction. Then the pH was measured. One mililiter of this solution was pipetted into a 25 mL volumetric flask (dilution factor: 25). Then the flask was filled up to the mark with dimethyl sulfoxide (DMSO), thoroughly mixed and measured by the gas chromatograph immediatly.

Buffers:

- Standard-buffer-solution pH 4, Bernd Kraft GmbH, Art-No.: 03083.3000
- Standard-buffer-solution pH 7, Bernd Kraft GmbH, Art.-No.: 03086.3000
- Standard-buffer-solution pH 9, Riedel-de Haen, Art.-No.: 3354

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Volumetric flasks (100 mL)
Other Equipment:
Analytical balance, Mettler, AT 261 DeltaRange
Cryostat, Lauda, RMS 6
Titroprocessor with pH-Meter (indication 0.01 pH units), Metrohm, 716 DMS Titrino
Vacuum drying oven, Heraeus, VT 6060 M
Calibrated thermometer
- Sterilisation method:
All glassware and materials which were in contact with the measuring solutions were cleaned thoroughly in a laboratory cleaning machine at 80°C, washed with purified water, and dried in a vacuum drying oven at 80°C before they were used.

TEST MEDIUM
- Volume used/treatment: 100 mL
- Kind and purity of water: Reagent water generated by the Millipore system "Milli Q"
- Preparation of test medium: Amounts of the test substance were weighed exactly into volumetric flasks (100 ml). The test substance was dissolved and subsequently adjusted to the mark using the corresponding buffer solution for each test. A maximal test substance (TMOA) concentration of 0.01 mol/L was not exceeded.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

1 061.32 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1 072.64 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

1 059.93 mg/L

Number of replicates:

1 (preliminary test)

Positive controls:

no

Negative controls:

no

Preliminary study:

The measured values and calculated results of the preliminary test see "Any other information on results incl. tables".

Test performance:

Preliminary study: GC vials were filled with the test solutions at pH 4, pH 7 and pH 9. The brown glass vials were closed, packed into small plastic bags and incubated in a water bath at 50°C ± 0.5°C. Single vials at each pH-level were taken in order to estimate whether the half-life time (t/=) is below 2.4 hours or less than 10 % of hydrolysis is observed after five days. After each sampling, the samples were cooled down to room temperature, pH was measured and the sample was diluted according the analytical method (dilution factor = 25) and placed into the GC autosampler.
Main study: No main test for pH 9, 7 and 4 is necessary, because the half-life time ty2 in each of the preliminary tests at 50°C is below 2.4 hours

Transformation products:

yes

No.:

#1

No.:

#2

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

- Formation and decline of each transformation product during test: The mass balance of TMOA, methanol and methyl acetate after relatively short reaction times are in accordance with the following reaction step: TMOA + 1 H20 ->• Methyl acetate + 2 Methanol
The relative increase of methanol in comparison to the diminished amount of TMOA above the ratio of 2:1 at larger reaction times indicates the further hydrolysis of methyl acetate to acetic acid as final reaction product.
- Pathways for transformation: aqueous buffer pH 4, 7 and 9:

% Recovery:

> 100

pH:

9.01

Temp.:

50 °C

Duration:

0 h

Remarks on result:

other: The increased recovery value is a result of the test method variance, not a formation of the test substance.

% Recovery:

19.5

pH:

8.96

Temp.:

50 °C

Duration:

2.4 h

Remarks on result:

other: The hydrolysis of the test substance after 2.4 h is over 50%. Therefore no additional testing is necessary.

% Recovery:

7.1

pH:

8.92

Temp.:

50 °C

Duration:

4 h

% Recovery:

68.6

pH:

7.02

Temp.:

50 °C

Duration:

0 h

% Recovery:

0

pH:

7.02

Temp.:

50 °C

Duration:

1 h

Remarks on result:

other: The measured degradation of TMOA at pH 7 and 50°C corresponded to a half-life time below one day under normal outdoor conditions.

% Recovery:

0

pH:

7.02

Temp.:

50 °C

Duration:

2.4 h

Remarks on result:

other: There is no significant difference between the test samples after 1 h and 2.4 h heatstress at 50°C.

% Recovery:

0

pH:

4.02

Temp.:

50 °C

Duration:

0 h

Remarks on result:

other: At pH 4 the test substance hydrolysed immediately after adding the aqueous pH 4-buffer. Only methanol and methyl acetate could be determined in the test solutions.

% Recovery:

0

pH:

4.02

Temp.:

50 °C

Duration:

2.4 h

Remarks on result:

other: There's no significant difference between the solution at the start (t = 0 h and room temperature) and the sample after 2.4 h heat stress at 50°C.

Key result

pH:

7.02

Temp.:

50 °C

DT50:

<= 0 h

Type:

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

Remarks on result:

other: The measured degradation of TMOA at pH 7 and 50°C corresponded to a half-life time below one day under normal outdoor conditions.

pH:

4.02

Temp.:

50 °C

DT50:

<= 0 h

Type:

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

pH:

8.96

Temp.:

50 °C

DT50:

< 2.4 h

Type:

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

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

MAJOR TRANSFORMATION PRODUCTS
At pH5:
- Range of maximum concentrations in % of the applied amount and day(s) of incubation when observed:
- Range of maximum concentrations in % of the applied amount at end of study period:
on the - the and -th day of incubation, respectively. At the end of the study period, the corresponding concentrations were - and -- % of the applied amount, respectively.

At pH7:
- Range of maximum concentrations in % of the applied amount and day(s) of incubation when observed:
- Range of maximum concentrations in % of the applied amount at end of study period:
on the - the and -th day of incubation, respectively. At the end of the study period, the corresponding concentrations were - and -- % of the applied amount, respectively.

At pH9:
- Range of maximum concentrations in % of the applied amount and day(s) of incubation when observed:
- Range of maximum concentrations in % of the applied amount at end of study period:
on the - the and -th day of incubation, respectively. At the end of the study period, the corresponding concentrations were - and -- % of the applied amount, respectively.

MINOR TRANSFORMATION PRODUCTS
Maximum concentrations in % of the applied amount
- at pH5:
- at pH7:
- at pH9:

MINERALISATION (distinguish between dark and irradiated samples)
- % of applied radioactivity present as CO2 at end of study:

INDICATION OF UNSTABLE TRANSFORMATION PRODUCTS:

VOLATILIZATION (at end of study)
- Evolved CO2 in % of the applied: .. at pH 5, .. at pH 7, .. at pH 9
- Total volatile organics in % of the applied: .. at pH 5, .. at pH 7, .. at pH 9

UNIDENTIFIED RADIOACTIVITY (at end of study)
- at pH5:
- at pH7:
- at pH9:

PATHWAYS OF HYDROLYSIS
- Description of pathwayS:
- Figures of chemical structures attached: Yes/No

SUPPLEMENTARY EXPERIMENT (if any): RESULTS:

Validity criteria fulfilled:

not specified

Conclusions:

The study was conducted scientifically reasonable according to EC-Guideline C.7 under GLP and is sufficiently documented. Hence, it is sufficiently reliable to assess the hydrolysis behaviour of Trimethyl orthoacetate (TMOA) in unbuffered water. The hydrolytic degradation of Trimethyl orthoacetate can be described as a pseudo-first order kinetic and the half-life of Trimethyl orthoacetate was determined to be < 2.4 h at pH 4, 7 and 9 at 50°C. Under neutral (pH 7) and acidic (pH 4) conditions the half life was < 1 h. The measured degradation of TMOA at pH 7 and 50°C corresponded to a half-life time below one day under normal outdoor conditions. Methanol (CAS 67-56-1) and Methyl acetate (CAS 79-20-9) were identified as degradation products as expected. The mass balance of TMOA, methanol and methyl acetate after relatively short reaction times are in accordance with the following reaction step: TMOA + 1 H20 -> Methyl acetate + 2 Methanol. The relative increase of methanol in comparison to the diminished amount of TMOA above the ratio of 2:1 at larger reaction times indicates the further hydrolysis of methyl acetate to acetic acid as final reaction product.
It can be concluded that the substance hydrolyses very rapidly in water (100% hydrolysis after 1h at pH 7 at 50°C, and 34% hydrolysis at test initiation at pH 7 at 50°C already, corresponding to a half-life time well below one day under normal outdoor conditions). Accordingly, the half life is e.g. max. 1/2 of the test duration when put into aqueous test systems (e.g. daphnia (48 h test duration) or algae (72 h test duration) acute toxicity tests. Hence, the substance as such does not need to be tested in those systems, it is sufficient for hazard assesment to use data gained with the final reaction products Methanol (CAS 67-56-1) and Acetic acid (CAS 64-19-7).

Executive summary:

The purpose of this study was to determine the function of hydrolysis in dependance of the pH of aqueous solutions of Trimethyl orthoacetate (TMOA) in accordance with EC-Guideline C.7 as specified in Directive 92/69/EC (seventeenth adaptation of Directive 67/548/EEC. Annex V) to meet regulatory requirements. The study was conducted under GLP.

The rate of degradation was estimated in preliminary tests at three different pH-values (4, 7, and 9) and a temperature of 50°C.

It could be stated that the hydrolysis of the test substance grew faster, the lower the pH of the aqueous medium was. At pH 4 the hydrolysis was already accomplished completely in the short mixing time of the substance with the buffer solution before the first analysis could be carried out.

The relevant results of the preliminary test with TMOA are summarized in the following table:

Test	Temperature [°C]	pH 9		pH 7		pH 4
preliminary test	50	Time (h)	Hydrolysis (%)	Time (h)	Hydrolysis (%)	Time (h)	Hydrolysis (%)
		0	< 1	0	31.4	0	100
		1	-	1	100	1	-
		2.4	80.5	2.4	100	2.4	100
		4	92.9	4	-	4	-
further necessary	testing (yes/no)	no		no		no

  In addition to the determination of the test substance it was possible to examine reaction products (methanol and methyl acetate) of the hydrolysis.

Description of key information

- Trimethyl orthoacetate hydrolyses very rapidly in water at pH 4, 7 and 9 with a half-life < 2.4 h at 50 °C.

- Hydrolysis products: Methanol and methyl acetate, while methyl acetate further hydrolyses to acetic acid as final reaction product.

Key value for chemical safety assessment

Half-life for hydrolysis:

2.4 h

at the temperature of:

50 °C

Additional information

The study was conducted scientifically reasonable according to EC-Guideline C.7 under GLP and is sufficiently documented. Hence, it is sufficiently reliable to assess the hydrolysis behaviour of Trimethyl orthoacetate (TMOA) in unbuffered water.

The hydrolytic degradation of Trimethyl orthoacetate can be described as a pseudo-first order kinetic and the half-life of Trimethyl orthoacetate was determined to be < 2.4 h at pH 4, 7 and 9 at 50°C. Under neutral (pH 7) and acidic (pH 4) conditions the half life was < 1 h. The measured degradation of TMOA at pH 7 and 50°C corresponded to a half-life time below one day under normal outdoor conditions. Methanol (CAS 67-56-1) and methyl acetate (CAS 79-20-9) were identified as degradation products as expected. The mass balance of TMOA, methanol and methyl acetate after relatively short reaction times are in accordance with the following reaction step: TMOA + 1 H20 -> Methyl acetate + 2 Methanol. The relative increase of methanol in comparison to the diminished amount of TMOA above the ratio of 2:1 at larger reaction times indicates the further hydrolysis of methyl acetate to acetic acid as final reaction product.

It can be concluded that the substance hydrolyses very rapidly in water (100% hydrolysis after 1h at pH 7 at 50°C, and 34% hydrolysis at test initiation at pH 7 at 50°C already, corresponding to a half-life time well below one day under normal outdoor conditions). Accordingly, the half life is e.g. max. 1/2 of the test duration when put into aqueous test systems (e.g. daphnia (48 h test duration) or algae (72 h test duration) acute toxicity tests. Hence, the substance as such does not need to be tested in those systems, it is sufficient for hazard assesment to use data gained with the final reaction products Methanol (CAS 67-56-1) and Acetic acid (CAS 64-19-7).