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Reference
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
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
Radiolabelling:
yes
Species:
rat
Strain:
other: Dondryu
Sex:
male
Route of administration:
intraperitoneal
Vehicle:
propylene glycol
Dose / conc.:
15 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Three
Control animals:
no
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.
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.
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.
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.

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
80

Additional information

From CLH report:

All the toxicokinetic data available were obtained from rat studies.

Absorption: Rapidly absorbed from gastrointestinal tract after single oral administration of 10

mg/kg bw of 8-hydroxyquinoline in all animals at 8 h (>80%) based on urinary excretion. Excretion: Most of the radioactivity was eliminated by urine (80.0-79.6%) and faeces (3.7-

4.0%) at 8 h after a single oral administration of 10 mg/kg bw in males-females respectively. At 120 h recovery for both sexes was almost complete. The administered radioactivity was excreted with a half-life of 28 min after oral administration and of 34 min after intravenous administration. After intravenous administration of 15 mg/kg bw of 8-hydroxyquinoline to male rats with bile fistula, 82.8% of the test material was eliminated in urine and 8.7% in bile within 8 h.

Distribution: Radioactivity in the tissues was observed at marginal levels only at 72 h after oral administration. The greatest concentration found in tissues was in spleen (0.152%),

kidneys (0.055%) and liver (0.033%). Mean plasma radioactivity concentrations was observed in all animals after single oral and intravenous administrations of 10 mg/kg bw at 15

min and at 5 min respectively. All available data indicate that there was no accumulation in tissues. The systemic bioavailability of plasma radioactivity following oral administration of [14C]-8- hydroxyquinoline was 63.4% of that following intravenous administration.

Metabolism: 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. Enterohepatic circulation of 8-hydroxyquinoline was confirmed when the bile of one rat was infused to the duodenum of another one and both main metabolites were present in urine showing reabsorption of glucuronide conjugate. 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.