Cineole

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards with acceptable restrictions.

Data source

Reference

Reference Type:

publication

Title:

Biotransformation of 1,8-cineole by human liver microsomes.

Author:

Miyazawa M & Shindo M.

Year:

2001

Bibliographic source:

Natural Product Letters 15 (1) 49 - 53.

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The biotransformation of 1,8-cineole was investigated using human liver microsomes.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1,8-cineole

IUPAC Name:

1,8-cineole

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): 1,8-cineole

Radiolabelling:

not specified

Test animals

Species:

human

Strain:

other: Not applicable

Sex:

not specified

Administration / exposure

Route of administration:

other:

Vehicle:

not specified

Duration and frequency of treatment / exposure:

30 minutes

Doses / concentrations

Remarks:

Doses / Concentrations:
200 µM

No. of animals per sex per dose / concentration:

Not applicable

Control animals:

not specified

Details on study design:

A standard reaction mixture containing human liver microsomes (0.025 mg/mL) with the test substance was incubated in a final volume of 0.50 mL of 100 mM potassium phosphate buffer (pH 7.4) containing NADPH. Incubtations were carried out at 37 °C for 30 minutes and terminated by adding ethyl acetate. The mixtures were stirred vigorously and the extracts (organic layer) were collected by centrifugation at 3000 rpm for 10 min. The organic phase was transferred to an insert for analysis by GC-MS.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The formation of the 2-exo-hydroxylated metabolite was suggested by the GC chromatogram. The molecular weight of the metabolite increased from 154 to 170 by introduction of oxygen atom. A dehydration peak changed from 126 to 108 indicting that a hydroxyl group was introduced into the molecule. The position and relative stereochemistry of a hydroxyl group were determined by relative abundance of mass fragments and retention time of GC. Their values were consistent with those of authentic sample which 2-exo-hydroxy-1,8-cineole was obtained from biotransformation of 1,8-cineole by microorganism. From the above results, the metabolite was established as 2-exo-hydroxy-1,8-cineole.
The incubation time, P450 contents and the 1,8-cineole concentration in the metabolism of 1,8-cineole by liver microsomes was investigated. On incubation with human liver microsomes in the presence of NADPH, the metabolite was found to be formed with the increase of incubation time, P450 levels and substrate concentration. 1,8-cineole 2-hydroxylation activity was shown to be high for a short incubation time, a small quantity of P450 levels in liver microsomes at low concentration. Therefore, 1,8-cineole 2-hydroxylation cataysed by human liver microsomes was found to be efficiently conducted.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The biotransformation of 1,8-cineole was investigated using human liver microsomes. The metabolite was established as 2-exo-hydroxy-1,8-cineole. 1,8-cineole 2-hydroxylation cataysed by human liver microsomes was found to be efficiently conducted.