Isopropyl trifluoroacetate

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 25 November 2016 to 12 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

see below "Principles of method"

Principles of method if other than guideline:

Deviation from OECD 111 method:
- Due to the high hydrolysis rate, the OECD 111 method is adapted to determine the degradation of Isopropyl Trifluoroacetate into Trifluoroacetic acid.
The determination is perfomed only in water at 25°C and 50°C as the hydrolysis is extremely rapid (see Solubility in water report No. R B6195).
- Complementary hydrolysis results (50°C) for confirmation of high hydrolysis and of interaction of buffer signals during analysis were performed until 25/12/2016, after expiration date 11/12/2016.
There is no impact on the conclusion of the study as the experimental part at 25°C was performed until 03/12/2016 (before the expiry date defined by the sponsor).

GLP compliance:

yes (incl. QA statement)

Remarks:

January 14th, 2016

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl trifluoroacetate

EC Number:

206-922-1

EC Name:

Isopropyl trifluoroacetate

Cas Number:

400-38-4

Molecular formula:

C5H7F3O2

IUPAC Name:

propan-2-yl 2,2,2-trifluoroacetate

Test material form:

liquid

Details on test material:

Name: Isopropyl trifluoroacetate

Study design

Analytical monitoring:

yes

Details on sampling:

PREAPARATION OF TEST SOLUTIONS FOR ANALYSIS (preliminary test)
Test solutions were prepared by dissolving an aliquot (approximately 20 mg) of the test item into the required buffer solution (50 mL) to obtain a concentration of approximately 400 µg/mL expressed as Isopropyl trifluoroacetate (TFAiP) content.
Test solutions (in water or in buffer solutions) were transferred into several Teflon test tubes which were incubated at the test temperatures (25°C and 50°C). The incubation of the test tubes was performed in a water bath (Lauda model E100 / Ecoline 025) equilibrated at the test temperature and covered with an opaque lid to avoid incidence of direct light.
Test tubes were removed from the water bath at different time intervals after the beginning of the test.
1 mL of each tube was taken and 1 mL of methanol was added to immediately stop hydrolysis in water.
Dilute 0.2 mL of each solution to 10 mL in water before analysis.
These extracts were then analysed to determine the Trifluoroacetic acid (TFA) content.

SAMPLING INTERVALS
- At 25°C: 0, 25, 97, 121, 172 and 196 hours after preparation of test solutions
- At 50°C: 0, 5.2, 22, 29, 53, 71, 77, 93 and 98 hours after preparation of test solutions

Buffers:

- Buffer solution pH 4 (without phosphate):
• 0.2M acetic acid solution:
Transfer approximately 900 mL of water to a 1 L volumetric flask. Add 11.5 mL of acetic acid, then complete to volume with water.
• 0.2M sodium acetate solution:
Transfer 4.14 g of sodium acetate and approximately 200 mL of water to a 250 mL volumetric flask. Mix well then complete to volume with water.

Mix 820 mL of 0.2M acetic acid solution and 180 mL of 0.2M sodium acetate solution in a 2 L volumetric flask; mix well and complete to the mark with water. Measure and control the pH.

- Buffer solution pH 7 (without phosphate):
• 0.2M hydrochloric acid solution:
Transfer approximately 450 mL of water to a 500 mL volumetric flask. Add 8.3 mL of hydrochloric acid 37%, then complete to volume with water.
• 0.2M tris(hydroxymethyl)aminomethane solution:
Transfer 12.1 g of tris(hydroxymethyl)aminomethane and approximately 450 mL of water to a 500 mL volumetric flask. Mix well then complete to volume with water.

Mix 221 mL of 0.2M hydrochloric acid solution and 250 mL of 0.2M tris(hydroxymethyl)aminomethane solution in a 1 L volumetric flask; mix well and complete to the mark with water. Measure and control the pH.

- Buffer solution pH 9 (without phosphate):
• 0.2M hydrochloric acid solution:
Transfer approximately 450 mL of water to a 500 mL volumetric flask. Add 8.3 mL of hydrochloric acid 37%, then complete to volume with water.
• 0.2M tris(hydroxymethyl)aminomethane solution:
Transfer 12.1 g of tris(hydroxymethyl)aminomethane and approximately 450 mL of water to a 500 mL volumetric flask. Mix well then complete to volume with water.

Mix 25 mL of 0.2M hydrochloric acid solution and 250 mL of 0.2M tris(hydroxymethyl)aminomethane solution in a 1 L volumetric flask; mix well and complete to the mark with water. Measure and control the pH.

Details on test conditions:

PRINCIPLE OF THE METHOD
Preliminary test
The test substance is known to be unstable.
In this study TFA content is used to determine hydrolysis rate.

The first preliminary test was run at 25°C with the test item at a nominal concentration of approximately 400 µg/mL. Concentrations of test item were determined after a 8 days period of incubation at the test temperature.

The second preliminary test was run at 50°C in water with the test item at a nominal concentration of approximately 400 µg/mL. Concentrations of test item were determined after a 4 days period of incubation at the test temperature.

Results and discussion

Preliminary study:

The results obtained are summarised in Table 1, see "Any other information on results incl. tables".

According to the results of these preliminary tests:
• the determination of Trifluoroacetic acid in buffer solutions is not possible due to the background noise coming from the components of these buffer solutions.
• additional tests are not required for all pH.

Confirmation tests were not required as the hydrolysis rate is extremely rapid (see also Solubility in water report No. R B6195).
The Trifluoroacetic acid content is quantified in water immediately after dilution of the test item and the concentration in water is stable after 25 hours.

Transformation products:

yes

Remarks:

Trifluoroacetic acid

Identity of transformation products

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

trifluoroacetic acid

Inventory number:

InventoryMultipleMappingImpl [inventoryEntryValue=EC 200-929-3]

CAS number:

76-05-1

Identity:

Acetic acid, trifluoro-

Molecular formula:

C2HF3O2

Molecular weight:

114.023

SMILES notation:

OC(=O)C(F)(F)F

InChl:

InChI=1/C2HF3O2/c3-2(4,5)1(6)7/h(H,6,7)

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

Key result

Temp.:

25 °C

DT50:

< 25 h

Dissipation DT50 of parent compound 2

Key result

Temp.:

50 °C

DT50:

< 5 h

Details on results:

The hydrolysis half-life times of Isopropyl Trifluoroacetate (TFAiP) referenced as batch No. BWF151211 was performed through the detection of the degradation product defined as Trifluoroacetic acid (TFA). The hydrolysis rate is extremely rapid since TFA is already quantified in water immediately after preparation of the test solutions. The concentration of TFA is determined as constant 5 hours after dilution in water at 50°C and 25 hours after dilution in water at 25°C.

Any other information on results incl. tables

Table 1: Results of the preliminary test

		TFAiP concentration (µg/mL)	TFA concentration (µg/mL) (after 4 days )	TFA concentration (µg/mL) (after 8 days )
Water (25°C)		408.0	-	72.67
Water (50°C)		349.0	69.73	-
pH 4 (50°C)		391.4	ND	-
pH 7 (50°C)		317.2	ND	-
pH 9 (50°C)		361.8	ND	-

Applicant's summary and conclusion

Conclusions:

The hydrolysis rate of isopropyl trifluoroacetate is extremely rapid since the degradation product trifluoroacetic acid is already quantified in water immediately after preparation of the test solutions. The concentration of TFA is determined as constant 5 hours after dilution in water at 50°C and 25 hours after dilution in water at 25°C.

Executive summary:

The determination of the hydrolysis of isopropyl trifluoroacetate (TFAiP) was performed according to OECD Test Guideline 111 and GLP.

Since TFAiP is known to be hydrolytically unstable, the half-life times were determined through the detection of the degradation product trifluoroacetic acid (TFA). TFA was quantified by Ion chromatography coupled to a conductimetry detector following external standardisation.

The results of the preliminary tests show that the determination of TFA in buffer solutions (pH 4, 7 and 9) is not possible due to the background noise coming from the components of these buffer solutions. Therefore no additional tests were performed in buffer solutions.

In water TFA is already quantified in water immediately after preparation of the test solutions. The concentration of TFA is determined as constant 5 hours after dilution in water at 50°C and 25 hours after dilution in water at 25°C. Confirmation tests were not required as the hydrolysis rate is extremely rapid (see also Solubility in water report No. R B6195).