Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
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:
The pharmacokinetic study on the fate of 8-hydroxyquinoline in rat
Author:
Kiwada H
Year:
1977
Bibliographic source:
Chem. Phar. Bull. 25: 1566-1573

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Propylene glycol solution for 8-hydroxyquinoline was administered intravenously through the femoral vein. Bile and urine samples were collected at approproate time intervals until 8 hr through polyethylene tubes set into bile duct, i.e bile fistula, and bladder, respectively. After 14C-8-hydroxyquinoline in propylene glycol solution 4.86 mg containing 10.1 uCi per head was administered intravenously, blood samples were collected from femoral artery through polyethylene cannula at appropriate time intervals until 4 hr.
GLP compliance:
no

Test material

Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: Dondryu
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
propylene glycol
Doses / concentrations
Dose / conc.:
15 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Three
Control animals:
no

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Intraperitoneal administration of 8-hydroxyquinoline showed rapid absorption in all animals at 8 h (>80%) based on urinary excretion.
Type:
metabolism
Results:
Glucuronide about 65% of dose and suphate about 25% of dose. No hydrolysis of the 8- hydroxyquinoline main metabolites occurred in vivo.
Type:
excretion
Results:
82.8% of the test material was eliminated in urine and 8.7% in bile within 8 h.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Intraperitoneal administration of 8-hydroxyquinoline showed rapid absorption in all animals at 8 h (>80%) based on urinary excretion.
Details on excretion:
82.8% of the test material was eliminated in urine and 8.7% in bile within 8 h.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Glucuronide about 65% of dose and suphate about 25% of dose. No hydrolysis of the 8- hydroxyquinoline main metabolites occurred in vivo.

Applicant's summary and conclusion

Executive summary:

Two metabolites were found in male rat urine and bile after intravenous administration of 15 mg/kg bw of 8-hydroxyquinoline within 8 hours. 8-hydroxyquinoline glucuronide conjugate was collected in urine (59.9%) and bile (8.7%) and 8-hydroxyquinoline sulphate accounted for only in urine (22.9%). Unmetabolized 8-hydroxyquinoline was hardly detected both in urine and bile.

The fate of the in vivo glucuronide conjugate was followed after intravenous administration to rats and about 90% and 10% of the dose were excreted in urine as the same conjugate. In the same way the sulphate metabolite was administered intravenously in vivo and 95% was detected in urine but not in bile. These results showed that no hydrolysis of the 8- hydroxyquinoline main metabolites occurred in vivo.