1-[2-fluoro-6-(trifluoromethyl)benzyl]-5-iodo-6-methylpyrimidine-2,4(1H,3H)-dione

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6th September 2018 to 18th September 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The Guidelines for the Testing of Chemicals No. 111 'Hydrolysis as a function of pH (MEP, 2013|)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-5-iodo-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

EC Number:

687-893-6

Cas Number:

1150560-54-5

Molecular formula:

C13H9F4IN2O2

IUPAC Name:

1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-5-iodo-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

Test material form:

solid: particulate/powder

Study design

Analytical monitoring:

yes

Buffers:

- pH: 4.0, 7.0 and 9.0

- Composition of buffers:
pH 4.0 - 500ml of 0.1 mol/L Potassium Dihydrogen Citrate + 90ml 0.1 mol/L of NaOH, made up to 1000ml with pure water
pH 7.0 - 500ml of 0.1 mol/L KH2PO4 + 296.3 of 0.1 mol/L of NaOH, made up to 1000ml with pure water
pH 9.0 - 500ml of 0.1 mol/L Boracic Acid(dissolved in 0.1 mol/L KCl + 213ml 0.1 mol/L of NaOH, made up to 1000ml with pure water

All buffer solutions and glassware were sterilised for 20mins at 121oC.

Details on test conditions:

100μL of stock solution of 2000mg/L was added to 100ml of the buffer solutions of pH 4.0, 7.0 and 9.0 to generate a test solution of 2.0mg/L. The solutions were divided in 3 and placed at 50± 0.5oC in the dark. The residual concentration was measured on Day 5.

Duration of test

Duration of test 1

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

1.934 mg/L

Duration of test 2

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

2.042 mg/L

Duration of test 3

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

2.052 mg/L

Number of replicates:

Three

Positive controls:

no

Negative controls:

no

Results and discussion

Preliminary study:

Tier 1-preliminary test: The average initial concentration of pH4, pH7, and pH9 was 1.934 mg/L, 2.042 mg/L, and 2.052 mg/L, respectively. And hte residual percentage of pH4, pH7, and pH9 on the 1st day was 97.1%, 93.5%, and 94.6%, respectively. While the residual percentage of pH4, pH7, and pH9 on the 5th day was 102.3%, 99.3%, and 96.2%, respectively. In orther words, the hydrolysis rate was less than 10% on the 5th day under 50 +/-0.5 degrees C, so the definitive test was terminated. The DT50 can't be calculated (but estimated to be >1 year at 25 degrees C based on test guideline MEP 111).

Transformation products:

not specified

Total recovery of test substance (in %)

Total recovery of test substance (in %) 1

% Recovery:

102.3

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Total recovery of test substance (in %) 2

% Recovery:

99.3

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Total recovery of test substance (in %) 3

% Recovery:

96.2

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Dissipation DT50 of parent compound

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

The DT50 cannot be calculated but is estimated to be >1 year at 2.5oC

Applicant's summary and conclusion

Conclusions:

The test item Methyl iodouracil is hydrolytically stable. The DT50 cannot be calculated but is estimated to be >1 year at 2.5oC based on Test Guideline MEP 111. 

Executive summary:

HPLC was employed to determine the Test Item Methyl iodouracil. The recovery test in buffer solution used two concentrations, 0.2mg/L and 2mg/L. The mean recovery rate was in the range 82.8- 98.7% with RSD in the range of 0.7 -6.3%. The analytical method used met the quality criteria. The hydrolysis rate at pH 4.0, 7.0 and 9.0 were all less than 10% on the 5th day at 50^oC ± 0.5^oC so the definitive test was terminated. 

The test item Methyl iodouracil is hydrolytically stable. The DT₅₀ cannot be calculated but is estimated to be >1 year at 2.5^oC based on Test Guideline MEP 111.