Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

no

Remarks:

The report represents data generated after the effective date of the GLP standards

Specific details on test material used for the study:

Pyridine label: Haloxyfop-R methyl ester, DE-535
Radiochemical purity: >99%
Specific activity: 28.1 mCi/mmol

Phenyl Label: Haloxyfop-R methyl ester, DE-535
Radiochemical purity: >97.9%
Specific activity: 18.3 mCi/mmol

Radiolabelling:

yes

Analytical monitoring:

yes

Details on sampling:

At each sampling point, duplicate samples were removed from the incubator. The time points for this study were 0, 1, 7, 14, 21 and 31 days. An additional set of pH 9 and natural water samples were dosed. The time points for the additional samples were 0, 2, 4, 12 and 24 hours. At each time point sterility and pH (no including the natural water) of each sample was measured and triplicate 100 µL aliquots were removed for LSC. A sub-sample was transferred to an amber vial and used for HPLC or normal phase TLC analysis.

Buffers:

- pH: 4, 7, and 9
- Final molarity of buffer: 0.05 M
- Composition of buffer: Buffer preparation for pH 4 used sodium acetate and was adjusted with glacial acetic acid, pH 7 was prepared with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) and adjusted with 1.0 N NaOH, and pH 9 was prepared with sodium borate and adjusted with concentrated HCl.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Sterile amber vials with Teflon lined septa caps
- Sterilisation method: 25°C for a minimum of 2 days
- Lighting: Samples were stored in a dark incubator
- Measures taken to avoid photolytic effects: Samples were stored in a dark incubator
- Is the test system closed/open: Closed

NATURAL WATER
Natural water was collected in Indianapolis, Indiana, USA. Collection location was the White River in Morgan County. After collection, a sub-sample was analyzed for pH, alkalinity, hardness, total suspended solids, conductivity, dissolved oxygen and microbial count. The natural water was stored in an incubator at a setting of 20°C prior to use.

Duration:

5 d

Temp.:

50 °C

Initial conc. measured:

0.5 other: mg/mL

Remarks:

Preliminary study (in natural water and pH 4, 7, and 9 sterile buffers)

Duration:

31 d

pH:

4

Temp.:

20 °C

Initial conc. measured:

0.5 other: mg/mL

Remarks:

Definitive study

Duration:

31 d

pH:

7

Temp.:

20 °C

Initial conc. measured:

0.5 other: mg/mL

Remarks:

Definitive study

Duration:

31 d

pH:

9

Temp.:

20 °C

Initial conc. measured:

0.5 other: mg/mL

Remarks:

Definitive study

Duration:

24 h

pH:

9

Temp.:

20 °C

Initial conc. measured:

0.5 other: mg/mL

Remarks:

Definitive study: Additional set of pH 9 and natural water

Duration:

31 d

Temp.:

20 °C

Initial conc. measured:

0.5 other: mg/mL

Remarks:

Definitive study (in natural water)

Number of replicates:

Duplicate samples

Statistical methods:

Statistical analyses included calculations of means, standard deviations, correlation coefficients, and t-tests for the interpretation and summarization of results. Regressions, means, standard deviations, tabular and calculated t-values, and correlation coefficients were calculated using Microsoft Excel. Radiochromatograms were reconstructed from liquid scintillation counts of the HPLC fractions using a macro in Excel.
Sample aliquot values were divided by the application rate and multiplied by 100 to obtain the percent applied radioactivity. Similarly, HPLC % of parent values were multiplied by percent of applied radioactivity and divided by 100 to obtain the percent of parent in the sample.

Preliminary study:

Material balance: The average material balance for the preliminary study was found to be 99.2% ± 4.78 (ranging from 91.4% to 109.9%) of applied during the study. Recovery of radiocarbon from HPLC analysis ranged from 96.0% to 108.1% of injected.

Test substance degradation: The preliminary test showed that the test substance was not stable to chemical hydrolysis in natural water and buffered water at pH 4, 7 and 9 during 5 days at 50°C.

Transformation products:

yes

Remarks:

The major degradation product was haloxyfop-R acid in natural water, pH 7 and pH 9

No.:

#1

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

In natural water, pH 7 and pH 9, the test substance hydrolyzed to haloxyfop-R acid, which was then observed to be stable. Two minor degradates were seen from both label forms, but did not exceed 3% of applied.

% Recovery:

99.4

St. dev.:

4

pH:

9

Temp.:

20 °C

Duration:

24 h

Remarks on result:

other: in natural water and pH 9

% Recovery:

97.6

St. dev.:

4.01

Temp.:

20 °C

Duration:

31 d

Remarks on result:

other: Average material balance in natural water and at pH 4, 7 and 9

Key result

pH:

7

Temp.:

20 °C

DT50:

43 d

Key result

pH:

9

Temp.:

20 °C

DT50:

0.63 d

Key result

Temp.:

20 °C

DT50:

3 d

Remarks on result:

other: In natural water

Key result

pH:

4

Temp.:

20 °C

Remarks on result:

other: No degradation was observed

Validity criteria fulfilled:

yes

Conclusions:

The observed half-lives for natural water, pH 7 and 9 buffers were 3 days, 43 days and 0.63 days, respectively. In natural water, pH 7 and 9 buffers, the test substance hydrolyzed to haloxyfop-R acid, which was then observed to be stable.

Executive summary:

A hydrolysis study was conducted with 14C-test substance to meet EEC Method C7 and OECD Method 111 guidelines. The preliminary test was conducted for five days in the dark at 50°C in natural water and pH 4, 7, and 9 sterile buffers. Natural river water was collected from the White River in Morgan County, Indiana, USA. Buffer solutions were prepared using 0.05 M acetate, HEPES and borate buffers for the nominal pH 4, 7 and 9 buffers, respectively. Natural water and buffers were dosed with a concentration of approximately 0.5 mg/mL 14C-test substance. Five time points (0, 2, 4, 24 and 120 hours) were taken during the preliminary test and analyzed by liquid scintillation counting (LSC) and high performance chromatography/thin layer chromatography (HPLC/TLC) analysis. The material balance averaged 99.2% ± 4.78% (ranging from 91.4% to 109.9%) of applied. The preliminary test indicated that degradation of the test substance occurred after 5 days at 50°C. A definitive test was therefore conducted at 20°C. Natural water and pH 9 samples were incubated for 24 hours and the material balance averaged 99.4% ± 3.98 (ranging from 93.4% to 108.7%) of applied. Additional samples were incubated for 31 days in natural water, and at pH 4, 7 and 9 buffers with an average material balance of 97.6% ± 4.01% (range 89.8% to 104.8%) of applied. No degradation was observed at pH 4 at 20°C. The observed half-lives for natural water, pH 7 and 9 buffers were 3 days, 43 days and 0.63 days, respectively. In natural water, pH 7 and 9 buffers, the test substance hydrolyzed to haloxyfop-R acid, which was then observed to be stable.

Description of key information

Study Type	Study Details	Value	Guideline	Reliability
Hydrolysis	Tested at pH 4, 7, and 9	DT50 values for natural water, pH 7 and 9 buffers were 3 days, 43 days and 0.63 days, respectively. In natural water, pH 7 and 9 buffers, the test substance hydrolyzed to haloxyfop-R acid, which was then observed to be stable.	OECD 111; EU Method C.7	1

Key value for chemical safety assessment

Half-life for hydrolysis:

43 d

at the temperature of:

20 °C