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Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-08-05 to 2002-08-22
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
yes
Principles of method if other than guideline:
At pH values where more than 10 % degradation was observed under the conditions of the preliminary test (5 days at 50 °C), experiments at elevated temperatures were necessary in order to extrapolate from the hydrolysis rate constants determined at elevated temperatures to the hydrolysis rate constant at 25 °C. Those experiments were conducted only at one elevated temperature instead of two elevated temperatures. This is justified since acceptable results were obtained. At pH 9, only one insted of two experiments were conducted.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
7 beta-Hydroxy-3 beta,15 alpha-dipivaloyloxy-5-androsten-17-one
EC Number:
617-708-6
Cas Number:
85390-94-9
Molecular formula:
C29 H44 O6
IUPAC Name:
7 beta-Hydroxy-3 beta,15 alpha-dipivaloyloxy-5-androsten-17-one
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Duration of testopen allclose all
Duration:
190.1 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
0.45 mg/L
Duration:
6 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
0.432 mg/L
Duration:
16.2 h
pH:
4
Temp.:
80 °C
Initial conc. measured:
0.45 mg/L
Duration:
2.08 h
pH:
7
Temp.:
80 °C
Initial conc. measured:
0.432 mg/L
Duration:
8.5 h
pH:
9
Temp.:
25 °C
Initial conc. measured:
0.309 mg/L

Results and discussion

Transformation products:
not measured

Any other information on results incl. tables

The rate of hydrolysis increases with pH. The half-life at 25 °C decreases from 50 days at pH 4

to 1.9 hours at pH 9. The hydrolysis is therefore base-catalyzed.

Two ester functions are present in the molecule leading to three possible hydrolysis products by

cleavage of one of the ester functions or of both of them. One of the products can be identified

by a peak at 3.3 min in the chromatograms of the hydrolysis solutions at pH 7. This peak

appears to be the final hydrolysis product ZK 91535 since its area increases steadily with

hydrolysis time.

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Executive summary:

The rate of hydrolysis of ZK 92136 was determined at pH 4, 7 and 9.

The rate constants and half-lives at 25 °C are:

 pH  k [1/h]  95 % confidence intervalsfor k [1/h]  half-life  95 % confidenceintervals for half-life
 4  5.803 E-04  5.061 E-04 to 6.545 E-04  50 d  44 to 57 d
 7 1.182 E-02  7.760 E-03 to 1.588 E-02  58.6 h  43.6 to 89.3 h
 9  0.3668  0.2837 to 0.4498  1.9 h  1.5 to 2.4 h