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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not reported.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with generally accepted scientific principles, with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
publication
Title:
Role of the Arene Oxide-Oxepin Systemin the Metabolism of Aromatic Substrates I. In Virto Conversion of Benzene Oxide to a Premercapturic Acid and a Dihydrodiol
Author:
Jerina D, Daly J, Witkop B, Zaltzman-Nirenberg P & Udenfriend S
Year:
1968
Bibliographic source:
Archives of Biochemistry and Biophysics, 128, 176-183

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test material was incubated with rabbit liver microsomes. Following incubation, the products were identified and purified by thin-layer chromatography.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Radiolabelling:
no

Test animals

Species:
other: administered in vitro to a microsomal liver preparation
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: administered in vitro to a microsomal liver preparation
Vehicle:
unchanged (no vehicle)
Details on exposure:
The test material was incubated with a microsomal liver preparation.
Details on study design:
The test material was incubated at 37º for 30 minutes with the following:
- 10ml of the rabbit liver microsomal preparation,
- 2ml of 0.5 M tris buffer (pH 8.0),
- 1 ml of 10-2 M EDTA,
- 10 mg Tween-80,
- 200 µmol of substrate (which was added to 0.2 ml of ethanol.

The mixture was extracted with ether, which was then dried over Na2SO4 and concentrated in vacuum.

The products were then separated by chromatography on silica gel: GF: ethyl acetate-benzene-chloroform in the ratio 1:1:1.

Results and discussion

Main ADME results
Type:
metabolism
Results:
by epoxy hydrase to 1,2-cyclohexanediol.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The liver enzyme, epoxide hydrase was reported to convert the test material to 1,2-cyclohexanediol.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The test material was determined to convert to 1,2-cycloheanediol in the presence of the liver enzyme, epoxide hydrase.
Executive summary:

The metabolism of the test material was determined by incubation with a microsomal preparation of rabbit liver. Under the conditions of the test it was determined that the test material is hydrolysed by the liver enzyme, epoxide hydrase and forms the metabolite 1,2-cyclohexanediol.