4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Phototransformation in water

Link to relevant study record(s)

Reference

Endpoint:

phototransformation in water

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Study type:

direct photolysis

Qualifier:

according to guideline

Guideline:

OECD Guideline 316 (Phototransformation of Chemicals in Water - Direct Photolysis)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

yes

Analytical method:

liquid chromatography

high-performance liquid chromatography

mass spectrometry

other: Liquid Scintillation

Details on sampling:

Duplicate samples: 0, 1, 4, 7, 10, 15 and 20 days after treatment

Buffers:

The direct photolytic behavior of the test item was investigated in sterile buffer solution at pH 4. A buffer solution of pH 4 was chosen to minimise hydrolytic degradation.
The solution was prepared by adjusting 0.1 M sodium acetate solution (1000 mL) with acetic acid to pH 4. Ultrapure water was then added to achieve a final volume of 2 L and a final concentration of 0.05 M. The buffer solution was sterilized prior to use via autoclave (121 °C for 15 minutes). The pH of the sterilized solution was checked using a calibrated pH meter (± 0.01 pH units).

Light source:

Xenon lamp

Light spectrum: wavelength in nm:

300 - 800

Relative light intensity:

432

Details on light source:

Light intensity measurement (290 to 400 nm): 47.57 W/m2
Filter used to limit the emission wavelength spectrum: UV filter
Similar spectra distribution as natural sunlight
Continuous irradiation for 20 days
Dark controls included

Details on test conditions:

Test apparatus: borosilicate glass cuvettes with quartz lids
Test system: sterile pH 4.0 buffer (sterilised by autoclave)
Test concentration: 23 μg/L
Number of replicates 2 irradiated, 2 dark controls
Traps for CO2 and organic volatiles: one ethylene glycol (organic volatiles) and one 2M NaOH (CO2) per sample, foam bungs were placed at the outlet of the 2M NaOH trap on all irradiated samples.
Solvent: acetonitrile
Test temperature: 25 ± 1 °C

Duration:

20 d

Temp.:

25 °C

Initial conc. measured:

0.024 mg/L

Reference substance:

no

Dark controls:

yes

Computational methods:

The rate of degradation of 14C-labelled test substance for irradiated samples, based on experimental days, was calculated using single first-order (SFO) kinetics (CAKE v. 3.2) by fitting data for the MP-, HP- and OXO-labels together. As the substance did not degrade in the dark control samples, no compensation for degradation in the dark controls was made for this compound.

Key result

DT50:

72.4 d

Test condition:

Half-life recalculated for summer sunlight at 30 to 50° N

Key result

DT50:

233.9 d

Test condition:

Half-life recalculated for Tokyo spring light at 35° N

DT50:

38.4 d

Test condition:

24 μg, 25 ± 1 °C, continuous irradiation for 20 days

Transformation products:

yes

No.:

#1

Details on results:

Mass balance (sum of activity in the treated solution, vessel rinse and trapped as 14CO2 in the traps)

Recovery at start of experiment (irradiated vessels and dark controls)
MP label: 97.6 to 101.0% of applied radioactivity (mean 99.3%)
HP label: 101.6 to 105.1% of applied radioactivity (mean 103.3%)
Oxo label: 100.7 to 104.3% of applied radioactivity (mean 102.5%)

Overall recovery (irradiated samples)
MP label: 96.1 to 107.1% of applied radioactivity (mean 100.8%)
HP label: 90.9 to 105.1% of applied radioactivity (mean 97.1%)
Oxo label: 90.3 to 104.3% of applied radioactivity (mean 96.2%)

Overall recovery (dark controls)
MP label: 93.3 to 106.3% of applied radioactivity (mean 100.7%)
HP label: 96.2 to 107.8% of applied radioactivity (mean 102.7%)
Oxo label: 93.8 to 106.1% of applied radioactivity (mean 100.1%)

14C carbon dioxide evolved at the end of experiment (irradiated)
MP label: 3.8% of applied radioactivity
HP label: 5.8% of applied radioactivity
Oxo label: 1.6% of applied radioactivity

14C carbon dioxide evolved at the end of experiment (dark control)
MP label: <0.1% of applied radioactivity
HP label: <0.1% of applied radioactivity
Oxo label: <0.1% of applied radioactivity

Other volatiles (all labels, all samples)
<0.7% for all labels

The substance degraded slowly in pH 4 buffer under continuous irradiation. In the irradiated samples, the mean amount of substance decreased from initially 97.3% - 102.3% AR (all labels) at the start of the experiment to 70.8, 70.4 and 67.3% AR for MP, HP and OXO labels respectively, after 20 days of continuous irradiation. In the dark control samples, the substance remained stable, representing 100.2%, 102.4% and 95.3% of AR after 20 days for the MP, HP and OXO label, respectively.
Following analysis using a HPLC method, the only major (≥10% AR) degradation product observed in the MP and HP samples was 4-[5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzamide, which reached maximum mean levels of 30.7% AR at 10 DAT and 29.2% AR at 15 DAT in the MP and HP test systems, respectively. The degradation product then decreased to 18.4% and 17.0% AR at the final interval in the MP and HP samples, respectively. No other significant (>5% AR) degradates were observed.
In the OXO samples, polar degradation products, eluting between 0 and 10 minutes in the HPLC method, reached a total maximum of 24.2% AR. The nature of these polar degradation products was further investigated by 2D-TLC, following (a) isolation of the polar region (0-10 minutes) and (b) re-generation and analysis of an additional 20 OXO sample. However, analysis of the entire 20 DAT OXO samples (replicates A and B) using 2D-TLC demonstrated that this polar region consisted of multiple components, none of which individually exceeded >10% AR (with the largest individual component equating to 4.8% AR). Therefore analysis of the isolated fraction from the original and regenerated samples is not discussed.

Results with reference substance:

Not applicable

Validity criteria fulfilled:

yes

Conclusions:

Photo-degradation of the substance in pH 4.0 buffer solution was slow as a result of direct photolysis. A half-life of 233.9 days for Tokyo spring sunlight at 35° N and of 72.4 days for summer sunlight at 30 to 50° N was determined.

Executive summary:

The photolysis of the substance was investigated under GLP to OECD TG 316 in sterile pH 4 buffer solution (direct photolysis). The substance was 14C-radio-labelled at three separate positions, methylphenyl (MP), halophenyl (HP) and oxoisoxazolidinyl (OXO), and applied at a concentration of 23 μg/L to the buffer solution in photolysis vessels made of borosilicate glass. The treated solutions were irradiated using light from a xenon arc lamp, which was filtered to give a spectral distribution close to that of natural sunlight at a mean intensity of 47.57 W/m2 (290 – 400 nm). The samples were maintained at 25 °± 1 °C and were continuously irradiated for periods up to 20 days, equivalent of 37.9 days of summer sunlight at 30-50° N. Treated samples were also incubated under similar conditions, but in the dark as controls.
Duplicate samples per radio-label were taken for analysis at seven intervals during irradiation. Correspondingly, duplicate dark control samples were taken for analysis at intervals equivalent to the irradiation test. Aqueous samples were radioassayed using liquid scintillation (LSC) and analysed by HPLC to determine the amount (% of applied radioactivity) of parent and significant photodegradates in each sample. The chromatographic results obtained by HPLC were confirmed by 2D-TLC and LC-MS for selected samples. Additionally, samples from all radio-labels were collected at the start and end of the experiment and analysed by chiral LC-MS to determine the isomer ratios of the substance and its major degradate.
Mass balance values in individual samples ranged from 90.3 to 107.8% of applied radioactivity (AR). In sterile buffer, the substance degraded slowly with 70.8%, 70.4% and 67.3% AR remaining after 20 days of continuous irradiation for MP, HP and OXO radiolabelled samples, respectively. There was no evidence of isomer interconversion or stereo-selective metabolism of the substance. The only significant degradate observed in the MP and HP samples was metabolite 1, resulting from direct photolysis of the substance via cleavage of the oxoisoxazolidinyl ring. This metabolite reached maximum mean levels of 30.7% AR at 10 DAT in the MP-labelled samples and 29.2% AR at 15 DAT in the HP-labelled samples. Subsequently, it decreased to 18.4% and 17.0% AR by the final interval (20 DAT) in the MP and HP samples, respectively. No significant (>10% AR) degradates were observed in OXO-labelled samples.
Carbon dioxide was a minor product of photolysis in all samples reaching a maximum of 5.8% AR (HP label) by the end of the irradiation period.
Negligible degradation was apparent in the dark control samples, indicating that degradation in irradiated samples was due to photodegradation only.
The degradation rate of the substance was determined using non-linear regression and a single first order kinetic model (SFO, CAKE software version 3.2). A half-life of 233.9 days for Tokyo spring sunlight at 35° N and of 72.4 days for summer sunlight at 30 to 50° N was determined.

Description of key information

Direct photolysis of the substance was studied under GLP in a study following OECD TG 316, using sterile pH 4 buffer solution. The molecule was separately radio-labelled at the methylphenyl, halophenyl or oxoisoxazolidinyl positions, and applied at a concentration of 23 μg/L to the buffer solution in photolysis vessels. These solutions were irradiated using light from a xenon arc lamp, which was filtered to give a spectral distribution close to that of natural sunlight. Furthermore, vessels with test solutions were kept in the dark under similar conditions as dark controls. A degradation half-life of 233.9 days was determined for Tokyo spring sunlight at 35° N and of 72.4 days for summer sunlight at 30 to 50° N. Only one significant degradation product was observed, which resulted from the cleavage of the oxoisoxazolidinyl ring. Carbon dioxide was a minor product of photolysis. No degradation occurred in the vessels serving as dark controls showing that the observed degradation of the test substance was due to direct photolysis alone.

Key value for chemical safety assessment

Half-life in water:

72.4 d