Avermectin A1a, 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-

Phototransformation in water

Link to relevant study record(s)

Reference

Endpoint:

phototransformation in water

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 10 Nov 1993 to 02 May 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP.

Study type:

other: Photodegradation

Qualifier:

according to guideline

Guideline:

other: U.S. Food and Drug Administration, Environmental Assessment Technical Assistance Document 3.10, Photodegradation

Deviations:

no

GLP compliance:

yes

Radiolabelling:

yes

Analytical method:

high-performance liquid chromatography

Details on sampling:

- Sampling intervals for the parent/transformation products: 0, 6, 24, 48, and 72 hours for preliminary study and 0, 1, 2, 3, 3.5, 5, 6, 6.5, 7, 7.5, 8, and 24 hours for the definitive study
- Sampling intervals/times for pH measurements: at time 0 and at test completion
- Sampling intervals/times for sterility check: at time 0 and at test completion
- Sample storage conditions before analysis: transferred to amber bottles for storage (1-9℃)

Light source:

Xenon lamp

Light spectrum: wavelength in nm:

290 - 800

Relative light intensity:

578

Details on light source:

The intensity of the xenon lamp during the study was 578 watts/m2 over the range 290 to 800 nm or 49.7 watts/m2 over the UV range 290 to 385 nm.

Details on test conditions:

Test solution preparation:
Since the test article was not very soluble in water (25±5.2 μg/L at 25 ℃), the stock solution of the test article was provided as a water, methanol, and acetonitrile mixture by the Sponsor at a concentration of 0.8 mg/mL. The concentration of the test article required for the study was 1 ppm which was equivalent to 1.28 mL of 14C-test substance stock solution in 1000 mL of water. A working stock solution was prepared by adding 896 μL of the original stock solution 7.104 mL ACN. The test solution of 14C-test substance was prepared by adding an aliquot (7 mL) of the working stock solution aseptically to a 1000 mL volumetric flask were mixed thoroughly by inverting and shaking. The final concentration of the test solution was approximately 1 ppm (~ 0.7 mg test article in 700 mL Millipore water).

Test system:
In the definitive study, three quartz test vessels (two for 14C-test substance and one for actinometer) containing approximately 150 mL of test solution were placed in a Hereaus Suntest system equipped with a xenon lamp.
Concurrently, three quartz test vessels (two for 14C-test substance and one for actinometer) containing approximately 150 mL test solution were wrapped in aluminum fail and were placed in an incubator in the dark at 25.0 ± 2.0 ℃.

Duration:

24 h

Temp.:

25 °C

Initial conc. measured:

1 mg/L

Reference substance:

yes

Remarks:

p-nitro acetophenone-pyridine

Dark controls:

yes

Preliminary study:

Approximately 43-54% of 14C-test substance was degraded in irradiated samples in 6 hours. In 24 hours, 100% of 14C-test substance was degraded under simulated sunlight. Dark controls (0 hours and 24 hours) and the samples designated for irradiation at 0 hour showed that 14C-test substance was intact.

Parameter:

max lambda

Value:

244 nm

% Degr.:

59

Sampling time:

5 h

Test condition:

Irradiating

% Degr.:

100

Sampling time:

24 h

Test condition:

Irradiating

Rate constant (for indirect photolysis):

0.16 other: hour-1

DT50:

4.45 h

Test condition:

~ 1 ppm solution of 14C-test substance continuously exposed to simulated sunlight

Transformation products:

not specified

Details on results:

The major photoproducts were polar materials that eluted close to the void volume of the isocratic HPLC method. Using an alternate HPLC method with gradient elution, the polar peak was resolved into at least six components (by UV detection at 244 nm) that eluted between 2.0 to 5.0 minutes and collectively accounted for 11% of the detected radioactivity. Although no major UV peaks were detected between 5 and 35 minutes, peaks detected by radioscan during this time period accounted for 28% of the detected radioactivity. The low UV response of radiolabel photoproducts implied these compounds did not contain the macrolide ring chromophore characteristic of test substance. From the combination of the UV and 14C radiochromatograms, the region between 0 and 45 minutes contained at least 10 components, none of which accounted for more than 10% of the applied radioactivity. Therefore, minor photodegradates were not further characterized. No degradation was observed in the 14C test substance or in the actinometer dark controls. The absence of absorption of light in the 290-800 nm range by test substance, as demonstrated by its UV-VIS absorption, suggested that 14C test substance was photodegraded by indirect mechanisms rather than by a direct absorption of photons.

Results with reference substance:

The dark controls (0 and 24 hours) and samples designated for irradiation at 0 hour showed that actinometer was intact. However, at the 5 hour sampling interval, a decrease in p-nitro acetophenone in irradiated samples was observed compared to 5-hour dark control. Approximately 27% of the actinometer was photodegraded in 5 hours. Furthermore, at the 24 hour sample interval, decrease of p-nitro acetophenone in irradiated samples was pronounced compared to the 5 hour irradiated sample. The degradation was 79% within 24 hours of irradiation.

Validity criteria fulfilled:

yes

Conclusions:

The test article 14C-test substance degraded rapidly under simulated sunlight with a half-life of 4.45 hours.

Description of key information

The test article 14C-test substance degraded rapidly under simulated sunlight with a half-life of 4.45 hours.

Key value for chemical safety assessment

Half-life in water:

4.45 h

Additional information

A Photodegradation study was conducted according to FDA Environmental Assessment Technical Assistance Document 3.10 under GLP (Fernando, 1994). The test article 14C-test substance degraded rapidly under simulated sunlight with a half-life of 4.45 hours.