Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is well described.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Objective of study:
metabolism
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, code Crl: CD(SD)BR VAF/Plus (Marget, Kent,  England)
- Age at study initiation: 7-8 weeks old (males), 9-10 weeks old (females)
- Weight at study initiation: 198-215 g
- Fasting period before study: 15 to 20 hours
- Housing: maximum 6 per cages during acclimatisation period. After  dosing, rats were housed in glass metabowls equipped with urine/faeces 
 separators.
- Individual metabolism cages: yes/no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days before the start of the treatment.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 40 to 60% relative humidity
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12h / 12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): dosing solutions were freshly prepared on the day of administration.

VEHICLE
- Justification for use and choice of vehicle (if other than water): frequently used as the dose  vehicle in metabolism studies of compounds with limited water solubility as it is well tolerated by rats, is water miscible, and has a high solvent capacity.
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 100 and 200 mg/kg
No. of animals per sex per dose:
56 animals were used (28 males and 28 females) during the study.
Control animals:
not specified
Details on study design:
- Dose selection rationale: these dose levels were selected to model those used during a 2-week dietary administration toxicokinetic study.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The test compound was therefore essentially completely absorbed
Details on excretion:
excretion was effectively complete at 5 days post-administration

Metabolite characterisation studies

Details on metabolites:
no data. However, ethylvanillin is rapidly metabolised

Any other information on results incl. tables

The test compound was therefore essentially completely absorbed and excretion was effectively complete at 5 days post-administration. Unchanged material was not detected in plasma by  radio HPLC,which demonstrated  that the test compound was subjected to rapid metabolism. Similary, no free ethylvanillin was detected  in urine, demonstrating its complete biotransformation prior to excretion.

Clinical signs/mortality:
No adverse reactions to treatment were observed in any of the rats dosed orally with ethyl 14C-vanillin at 50, 100 or 200 mg/kg.

Applicant's summary and conclusion