(3S,6S,7R,8R)-8-Benzyl-3-{[(3-hydroxy-4-methoxypyridin-2-yl)carbonyl]amino}-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Phototransformation in water

Administrative data

Endpoint:

phototransformation in water

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Study type:

other: surface and solution phase photolysis

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

For surface phase photolysis, 10 µg of compound was applied to a PTFE surface and exposed in a UV chamber for various time points along with dark controls. The freeze dried mycelium (X633974) powder containing the active ingredient X642188 (UK-2A) was also evaluated for surface photolysis stability. Additionally the photostability of X642188 (UK-2A) was evaluated in solution (10 ppm in pH 4 buffer). In addition, X642188 was evaluated for hydrolytic stability under neutral (pH 7), acidic (pH 4) and basic (pH 10) conditions.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

(3S,6S,7R,8R)-8-benzyl-3-(3-hydroxy-4-methoxypyridine-2-amido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Cas Number:

167173-85-5

Molecular formula:

C26H30N2O9

IUPAC Name:

(3S,6S,7R,8R)-8-benzyl-3-(3-hydroxy-4-methoxypyridine-2-amido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Specific details on test material used for the study:

Substance name: X642188 (UK-2A)
Purity: Not specified

Study design

Radiolabelling:

no

Analytical method:

high-performance liquid chromatography

Light source:

other: UV chamber

Duration of test at given test condition

Initial conc. measured:

10 other: µg

Dark controls:

yes

Results and discussion

Dissipation half-life of parent compound

Dissipation half-life of parent compound 1

Key result

DT50:

30.6 d

Test condition:

X642188 (UK-2A) (surface phase photolysis)

Dissipation half-life of parent compound 2

DT50:

22 h

Test condition:

X642190 (UK-2C/2D) (surface phase photolysis)

Dissipation half-life of parent compound 3

DT50:

15 h

Test condition:

X650872 (UK-3A) (surface phase photolysis)

Dissipation half-life of parent compound 4

DT50:

10.6 d

Test condition:

freeze dried mycelium (X633974) powder containing the active ingredient X642188 (UK-2A) (surface photolysis stability)

Dissipation half-life of parent compound 5

Key result

DT50:

1.2 h

Test condition:

X642188 (UK-2A) was evaluated in solution (10 ppm in pH 4 buffer)

Dissipation half-life of parent compound 6

Key result

DT50:

5.1 h

Test condition:

X642188 at pH 4

Dissipation half-life of parent compound 7

Key result

DT50:

6.9 h

Test condition:

X642188 at pH 7

Dissipation half-life of parent compound 8

Key result

Test condition:

X642188 at pH 10

Remarks on result:

other: hydrolysis appeared to be instantaneous. No X642188 was detectable even at the initiation of the experiment.

Applicant's summary and conclusion

Conclusions:

Several of the picolinamides investigated in this study have limited stability in sunlight on surfaces such that care will need to be taken to minimize its effect. More importantly however, is the hydrolytic instability of the primary candidate X642188. When diluted for application from the formulated material, the solution pH should be maintained acidic or neutral. From these studies it is apparent that X642188 has an extremely limited life-time under basic aqueous conditions. Additionally, UV screening of the application solution will also be necessary to maintain a consistent application due to the photolysis of X642188 in solution.

Executive summary:

Several naturally derived picolinamides received from Meiji Company were evaluated for surface and solution phase photostability. For surface phase photolysis, 10 µg of compound was applied to a PTFE surface and exposed in a UV chamber for various time points along with dark controls. Samples were exposed in triplicate for each time point. Samples were removed at predetermined intervals, extracted with acetonitrile and analyzed by HPLC to determine the extent of photodegradation. Half-lives for each compound were determined as follows: X642188 (UK-2A) 30.6 days, X642190 (UK-2C/2D) 22 hours, and X650872 (UK-3A) 15 hours. The freeze dried mycelium (X633974) powder containing the active ingredient X642188 (UK-2A) was also evaluated for surface photolysis stability. The half-life for the mixture was slightly faster than the pure isolate at 10.6 days due to the differing application technique used to apply the test solution to the PTFE disks.

Additionally the photostability of X642188 (UK-2A) was evaluated in solution (10 ppm in pH 4 buffer). Photolysis was extremely rapid in solution with an estimated half-life of 1.2 hours. In addition, X642188 was evaluated for hydrolytic stability under neutral (pH 7), acidic (pH 4) and basic (pH 10) conditions. Hydrolysis appeared to be base catalyzed. At pH 4 X642188 was relatively stable with a half life of 5.1 hours. At pH 7 the half life was determined to be 6.9 hours.

Under basic pH conditions however, hydrolysis appeared to be instantaneous. No X642188 was detectable even at the initiation of the experiment. The hydrolytic stability of the mycelium powder X633974 was evaluated as well at pH 4, 7 and 10. The half-lives for the active ingredient X642188 in the mycelium powder were somewhat longer than seen for the pure material at 11 and 16 hours for pH 4 and 7, respectively. As with the pure material at pH 10, the half-life could not be determined due to the rapid nature of the hydrolysis.