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Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-05-02 to 2018-08-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: EU method, OECD , GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
4-amino-5-methyl-1,2-dihydropyridin-2-one
EC Number:
682-818-3
Cas Number:
95306-64-2
Molecular formula:
C6 H8 N2 O
IUPAC Name:
4-amino-5-methyl-1,2-dihydropyridin-2-one
Test material form:
solid
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Details on sampling:
Preliminary Test (Tier 1)
Test Duration: The incubation was terminated after 5 days.
Sampling of the Test Samples: pH 4, 7 and 9: 0, 3.5, 24, 120 h
At each sampling point, samples were taken in duplicate.
Buffers:
Sterile aqueous solutions buffered at pH 4, 7 and 9.
The pH of each buffer solution was measured with a calibrated pH meter.
pH 4: 0.05 M acetat buffer
410 mL acetic acid (0.1 M) was added to 90 mL sodium acetat (0.1 M). The solution was filled up to 1000 mL with pure water.
pH 7: 0.05 M phosphate buffer
296 mL NaOH (0.1 M) was added to 500 mL potassium dihydrogenphosphate (0.1 M). The solution was filled up to 1000 mL with pure water.
pH 9: 0.05 M boric acid buffer
213 mL NaOH (0.1 M) was added to 500 mL of a solution of boric acid (0.1 M) in potassium chloride (0.1 M). The solution was filled up to 1000 mL with pure water.
Details on test conditions:
Temperature: Preliminary test (Tier 1): 50°C ± 0.3°C
Anoxic Conditions: To avoid oxidation the buffer solutions were purged with inert gas (nitrogen) prior to sterilisation.
Sterile Conditions: Degased buffer solutions and the used glassware were sterilised using an autoclave (20 min at 121°C) prior to application.
Duration of testopen allclose all
Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
ca. 50 mg/L
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
ca. 50 mg/L
Duration:
5 d
pH:
9
Temp.:
50 °C
Initial conc. measured:
ca. 50 mg/L
Number of replicates:
Preliminary test (Tier 1): 8 samples per pH level
pH 4, 7 and 9: 0, 3.5, 24, 120 h
At each sampling point, samples were taken in duplicate.
Positive controls:
no
Negative controls:
no

Results and discussion

Preliminary study:
Samples were incubated at three different pH-values and at one temperature. The test was carried out for 5 days. During incubation the concentration of the test item remained stable at each tested pH-value of 4, 7 and 9. Recoveries (mean) were in the range of 97.0-100.2% of the applied concentration. Thus the test item can be stated as hydrolytically stable. The main test (Tier 2) was not performed.
Test performance:
The main test (Tier 2) was not performed.
Transformation products:
not measured
Total recovery of test substance (in %)open allclose all
% Recovery:
97
St. dev.:
0.3
pH:
4
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
97.5
St. dev.:
0.1
pH:
7
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
97.9
St. dev.:
0.3
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:
Validity of the Study
Accuracy of the Applied Concentration: Immediately after application (0 h) recoveries of the samples were as follows:
Replicate A: 124.3-124.9% of the nominal applied concentration.
Replicate B: 104.7-105.7% of the nominal applied concentration.
Recoveries of the applied concentration were considered acceptable for replicate B. In case of replicate A, values were out of the desired range. However, determinations of the hydrolysis properties were feasible with the prepared samples. For result evaluation, values refer to the applied concentration after application (mean of 0 h).
Validity of Sample Preparation and Analysis
Specificity: Specificity was confirmed.
Limit of Detection (LOD) and Limit of Quantification (LOQ): LOD: 0.02 mg/L
LOQ: 5 mg/L
Linearity: The correlation coefficient (r) was at least 0.9995
Interference: No interference was observed
Accuracy and Precision:
50 mg/L (100% Level)
Mean recoveries (n=5) were 105.0% (pH 4), 105.6% (pH 7) and 105.6% (pH 9) with RSD of 0.5% (pH 4), 0.8% (pH 7) and 0.8% (pH 9).
5 mg/L (10% Level)
Mean recoveries (n=5) were 105.1% (pH 4), 105.6% (pH 7) and 105.3% (pH 9) with RSD of 0.6% (pH 4), 0.3% (pH 7) and 0.8% (pH 9).
Test Parameters and Conditions
Temperature: Preliminary test (Tier 1): 50°C ± 0.3°C pH-Value:
Preliminary test (Tier 1, mean): 4.0 (pH 4), 7.0 (pH 7), 9.0 (pH 9)
Sterility of the Test Solution: Sterility was confirmed. No colonies were observed.
Results of the Preliminary Test (Tier 1)
Samples were incubated at three different pH-values and at one temperature. The test was carried out for 5 days. During incubation the concentration of the test item remained stable at each tested pH-value of 4, 7 and 9. Recoveries (mean) were in the range of 97.0-100.2% of the applied concentration. Thus the test item can be stated as hydrolytically stable. The main test (Tier 2) was not performed.
Summary and Conclusion
The present study investigated the hydrolytic behaviour of 4-Amino-5-Methylpyridon in aqueous solutions buffered at pH 4, 7 and 9 at 50°C. Samples were incubated in the dark. The test was carried out for 5 days. At the end of incubation, 97.0-97.9% of the applied concentration were found and thus the test item can be stated as hydrolytically stable (t0.5 > 1 year at 25°C).

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Remarks:
Immediately after application the recovery was 105 - 125% of the nominal applied concentration.
Conclusions:
The present study investigated the hydrolytic behaviour of 4-Amino-5-Methylpyridon in aqueous solutions buffered at pH 4, 7 and 9 at 50°C. Samples were incubated in the dark. The test was carried out for 5 days. At the end of incubation, 97.0-97.9% of the applied concentration were found and thus the test item can be stated as hydrolytically stable (t0.5 > 1 year at 25°C).
Executive summary:

Title: 4-Amino-5-Methylpyridon: Hydrolysis as a Function of pH [OECD 111]

Test Item: 4-Amino-5-Methylpyridon

Guidelines/Recommendations: This study was based on the procedures indicated by the following internationally accepted guidelines and recommendations:

-OECD Guideline for Testing of Chemicals No. 111: "Hydrolysis as a function of pH", adopted April 13, 2004.

GLP: Yes (certified laboratory)

Purpose: The purpose of the study was to determine the rate of hydrolysis of 4-Amino-5-Methylpyridon at different environmentally relevant pH-values and at different temperatures.

Test Setup: Test Vessels:

Glass flasks (10 mL) were used for the test.

Aqueous Solution:

Sterile aqueous solutions buffered at pH 4, 7 and 9.

Test Conditions: In the dark at,

Preliminary test (Tier 1): 50°C ± 0.3°C

Treatment Rate:          Preliminary test (Tier 1): 50 mg/L (two individual replicates)

 

Results:           

The present study investigated the hydrolytic behaviour of 4-Amino-5-Methylpyridon in aqueous solutions buffered at pH 4, 7 and 9 at 50°C. Samples were incubated in the dark. The test was carried out for 5 days. At the end of incubation, 97.0-97.9% of the applied concentration were found and thus the test item can be stated as hydrolytically stable (t0.5 > 1 year at 25°C).

 This study is classified acceptable and satisfies the guideline requirements for hydrolysis studies.