Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study carried out in accordance with method C7 of commission directive 92/69/EEC and in accordance with GLP. The test material was well characterised

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
1997

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
424-660-8
EC Name:
-
Cas Number:
224631-15-6
Molecular formula:
Hill formula: C18H26N4O5S CAS formula: C18H26N4O5S
IUPAC Name:
(S)-2,5-dioxopyrrolidin-1-yl 2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoate

Study design

Analytical monitoring:
yes
Details on sampling:
A known hydrolysis product of A-133816, 2,4-WING acid was detected chromatographically, confirming that the test materia had ben present in the initial samples and that hydrolysis had occurred

samples were taken at 30 min, 1 h, 2.4 h and 4 h
Buffers:
(i) pH4:m 4.92 g acetic acid + 1.44 g sodium acetate, made up to 1 litre with Milliq water (measured pH = 3.99)
(ii) pH 7: 0.1 N sodium hydroxide, 296.3 ml + 6.8 g potassium dihydrogen phosphate, made up to 1 litre wit Milli-q water (measuredpH = 7.1)
(iii) pH 9: 0.1 N sodium hydroxide, 426 ml + 0.1 M boric acid in 0.1 M potassium chloride, 1000 ml, made up to 2 litres with Milli-Q water. (measured pH=9.02)
Details on test conditions:
performed at 50 C and pH 4,7,9
performed at 20oC and pH 4,7,9
Number of replicates:
3 at each pH

Results and discussion

Test performance:
@ 50 oC:
samples from all pH environments, at all analytical time points, were also taken and chromatographed for the presence of 2,4 wing acid ( aknown hydrolysis product of A-133816.0). As the rate of hydrolysis was so rapid, no qunatifiable data could be determinded from the chromatography, i.e. established levels were outiwth the standard curve prepared.

20 oC:

The results at this temperature for all buffer solutons also show a very rapid degradation.

pH 4: no quantifiable peak established

ph 7 & 9: very rapid degradation. analysis of samples show that degradation occurs with a 1 h period
Transformation products:
not specified
Dissipation DT50 of parent compoundopen allclose all
pH:
4
Temp.:
50 °C
DT50:
< 1 h
pH:
4
Temp.:
20 °C
DT50:
< 1 h
pH:
7
Temp.:
50 °C
DT50:
< 1 h
pH:
7
Temp.:
20 °C
DT50:
< 0.5 h
pH:
9
Temp.:
50 °C
DT50:
< 1 h
pH:
9
Temp.:
20 °C
DT50:
< 0.5 h

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
The hydrolysis rate constant could not be determined becasue hydrolysis was very fast or virtually instantaneous.

The abiotic hydrolysis for A-1338196.0 could not be readily established. the investigations undertaken showed that A-133816.0 could not exist in its ready state in an aquatic environment with complete breakdown of the material to its beakdown products with 1 h (at 20oC)