Registration Dossier

Administrative data

Endpoint:
neurotoxicity
Remarks:
acute
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: Only partial examination of the neurotoxicity but the study is relevant for the target effect. Comparative study performed with only 1 dose.

Data source

Reference
Reference Type:
publication
Title:
Intracerebral microdialysis neurotoxicity studies of quinoline and isoquinoline derivatives related to MPTP/MPP+
Author:
Booth RG, Castagnoli N, Rollema H
Year:
1989
Bibliographic source:
Neuroscience Letters 100: 306-312

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
It's an in vivo dopaminergic neurotoxicity study in rats using an intrastriatal microdialysis technique that measures the release of dopamine.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
From commercial source, no further detail.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
No data

Administration / exposure

Route of administration:
other: perfusion
Vehicle:
other: Ringer's solution
Details on exposure:
U-shaped cannulae equipped with cellulose dialysis membranes were implanted into the corpus striatum of male Sprague-Dawley rats with the aid of a stereotaxic frame. All experiments were performed one day after surgery. The striata were perfused with Ringer's solution and the perfusate was delivered to an HPLC-EC system for measurement of dopamine (DA) and DOPAC (3,4-dihydroxyphenylacetic acid). Once the basal levels of DA and DOPAC stabilized, the striatum was perfused with a Ringer's solution of the test compound for 15 min to 10 h. Dialysate concentrations of DA and DOPAC were measured at 20 min intervals. One day after the end of the drug perfusion (Day 2), the new basal striatal levels of DA and DOPAC were measured. The extent of nerve terminal damage caused by the initial drug treatment was then assessed the same day by perfusing the brain with 10 mM MPP + (1-methyl-4-phenylpyridinium ) for 15 min and measuring once again DA and DOPAC levels.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
See above
Frequency of treatment:
See above
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mM
Basis:
no data
No. of animals per sex per dose:
no data
Control animals:
yes

Examinations

Observations and clinical examinations performed and frequency:
not relevant
Specific biochemical examinations:
not relevant
Neurobehavioural examinations performed and frequency:
not relevant
Sacrifice and (histo)pathology:
not relevant
Other examinations:
not relevant
Positive control:
1-methyl-4-phenylpyridinium (MPP+)
Statistics:
no data

Results and discussion

Effect levels

Dose descriptor:
dose level:
Effect level:
10 other: mM
Sex:
male
Basis for effect level:
other: Negative
Remarks on result:
other:

Applicant's summary and conclusion

Conclusions:
Quinoline has no neurotoxic properties in this test.
Executive summary:

The in vivo dopaminergic neurotoxicity of quinoline was assessed in rats using an intrastriatal microdialysis technique that measures the release of dopamine.

Quinoline has dopamine-releasing properties but no dopaminergic neurotoxicity.