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Diss Factsheets

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
In Vitro Characterization of Borneol Metabolites by GC–MS Upon Incubation with Rat Liver Microsomes
Author:
Zhang R
Year:
2008
Bibliographic source:
Journal of Chromatographic Science, Vol. 46, May/June 2008, pp 419-423

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
- Principle of test: Study of metabolism of Borneol by the analysis of incubations of in vitro-prepared rat liver microsomes
- Short description of test conditions: see description below
- Parameters analysed / observed: Metabolites of Borneol in rat liver microsomes.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
DL-borneol
EC Number:
208-080-0
EC Name:
DL-borneol
Cas Number:
507-70-0
Molecular formula:
C10H18O
IUPAC Name:
1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Experimental Animal Center of Guangdong Province, P.R. China
- Age at study initiation: ca. 50 days
- Weight at study initiation: 230–250 g
- Housing: steel cages
- Diet (e.g. ad libitum): control diet
- Water (e.g. ad libitum): control diet
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22–26°C
- Humidity (%): 50–60%

Administration / exposure

Route of administration:
other: In vitro incubation with rat liver microsomes
Details on exposure:
A typical incubation mixture consisted of 2.5 mg/mL rat liver microsmal protein, 0.1M potassium phosphate buffer (pH 7.4), 1mM Nicotinamide-adenine dinucleotide phosphate (NADPH), and 325μM Borneol with a final volume of 1 mL. Borneol was dissolved in methanol (final concentration in the reaction medium of < 1.0%).
The reaction was initiated by the addition of the NADPH, and then the oxygen was quickly added with a syringe needle going into the middle of the mixtures for 40 s.
Control incubations were performed using inactivated microsomes, which were boiled in 90°C water for 45 min.
After incubation in a shaking water bath at 37°C for 30 min, the reaction was terminated by adding 2 mL ethyl acetate. The mixture was extracted for 10 min by shaking vigorously and then centrifuged at 15,000 × g for 10 min.
The organic phases were directly injected into the Gas chromatography (GC)–Mass spectrometry (MS) for analysis.
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: rat liver microsomes
- Method type(s) for identification: GC-MS

Results and discussion

Main ADME results
Type:
metabolism
Results:
Four metabolites (M1, M2, M3, and M4) were observed in the incubation mixture, which were not present in the control incubations

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Borneol was rapidly metabolized to four metabolites:
M1 (m/z 152): molecular weight of two mass units less than Borneol. M1 was confirmed as camphor by comparison with the standard mass spectrum library (NIST library, 95% similarity).
M2 (m/z 122): molecular weight of 32 mass units less than Borneol. It was proposed that this is the de-methylated and de-hydrated metabolite of Borneol. Although, further investigation is required to positively identify this metabolite.
M3 (m/z 170) and M4 (m/z 170): molecular weight of 16 mass units more than Borneol. it was proposed that M3 and M4 are probably hydroxylated metabolite(s) of borneol, although these will require further study to be certain.

Applicant's summary and conclusion

Conclusions:
Borneol was rapidly metabolized to four phase I metabolites in incubations with normal rat liver microsomes in the presence of NADPH.
Executive summary:

The metabolism of borneol was studied by the analysis of incubations of in vitro-prepared rat liver microsomes. Male Sprague-Dawley rats, aged approximately 50 days and weighing 230–250 g, were used for the study. A typical incubation mixture was performed in a shaking water bath at 37°C for 30 min and consisted of 2.5 mg/mL rat liver microsmal protein, 0.1M potassium phosphate buffer (pH 7.4), 1mM NADPH, and 325μM Bornel with a final volume of 1 mL. Gas chromatography (GC)–mass spectrometry (MS) method was developed for the identification of Borneol and its metabolites. Four phase I metabolites were detected: M1 (m/z 152) confirmed as camphor, M2 (m/z 122) proposed as the de-methylated and de-hydrated metabolite, M3 (m/z 170) and M4 (m/z 170) both proposed as the hydroxylated metabolites.