Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
neurotoxicity
Remarks:
acute
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Significant methodological deficiencies

Data source

Reference
Reference Type:
publication
Title:
Zur tremorigenen Wirkung des alpha,alpha-Dipyridyl an der Ratte
Author:
Staib AH, Funk KF, Westermann KH
Year:
1975
Bibliographic source:
Acta biol med germ. 1975, 34: 1433-5

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female albino rats received intracranial injections of 2,2'-bipyridine into the substantia nigra or into the nucleus caudatoputamen. In parallel, mixtures of 2,2'-bipyridine with ammonium iron(II) sulfate were tested. Tremor resulting from these injections was assessed after 0.5, 1, 3, and 5 h after injection using a 4-stage rating system. Dopamine content of the striatum was also quantified.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-bipyridyl
EC Number:
206-674-4
EC Name:
2,2'-bipyridyl
Cas Number:
366-18-7
Molecular formula:
C10H8N2
IUPAC Name:
2,2'-bipyridyl
Details on test material:
- Name of test material (as cited in study report): alpha,alpha-Dipyridyl, alpha,alpha-D

Test animals

Species:
rat
Strain:
other: albino
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 140-160 g

Administration / exposure

Route of administration:
other: intracranial injection
Vehicle:
unchanged (no vehicle)
Details on exposure:
The test item was applied bilaterally into the substantia nigra or into the nucleus caudatoputamen. Injection volume was 1 µL/side.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Single exposure
Frequency of treatment:
Single exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
10 µg
Basis:
actual ingested
No. of animals per sex per dose:
Test group: 35-48 animals
Control group: 20-29 animals
Dopamine measurement: 7 animals/group in both groups
Control animals:
yes

Results and discussion

Any other information on results incl. tables

Female rats, when injected 2,2'-bipyridine (alone or in combination with ammonium iron(II) sulfate) into the substantia nigra showed slight but significant tremor compared to control animals (Table 1). No effect occurred when the test item was injected into the nucleus caudatoputamen. The dopamine content of the striatum remained unchanged upon injection (Table 2).

 

Table 1: Tremor after injection of 10 µg 2,2’-bipyridine (alone or in combination with ammonium iron(II) sulfate) into the substantia nigra (SN) or the nucleus caudatoputamen (NC); mean ± SD from 3 x 30 min measurements 1-5 h after injection; in parentheses: number of animals

Substance injected

SN

NC

0.9% NaCl (control)

8±0.9 (29)

-

2,2'-bipyridine

15±1.3 (48) **

8.8±0.5 (35

2,2'-bipyridine-Fe(II) complex

13±1.5 (16) **

9.3±2.1 (16)

Significant change to control (t-test): ** p<0.01

 

 

Table 2: Dopamine content in the striatum 3 and 24 h after injection of 10 µg 2,2’-bipyridine (alone or in combination with ammonium iron(II) sulfate) into the substantia nigra; mean ± SD; in parentheses: number of animals

Substance injected

3 h after injection

24 h after injection

Control (untreated)

6.0±0.44 (4)

Control (0.9% NaCl)

7.2±0.35 (7)

6.3±0.81 (3)

2,2'-bipyridine

7.6±0.44 (7)

6.1±0.47 (3)

2,2'-bipyridine-Fe(II) complex

6.9±0.28 (7)

5.7±0.34 (3)

 

Applicant's summary and conclusion

Conclusions:
When rats are given 2,2'-bipyridine (alone or in combination with ammonium iron(II) sulfate) as injection into the substantia nigra, tremor is induced. Influence on striatal dopamine content has not been found.
Executive summary:

Female albino rats received intracranial injections of 2,2'-bipyridine into the substantia nigra or into the nucleus caudatoputamen. In parallel, mixtures of 2,2'-bipyridine with ammonium iron(II) sulfate were tested. Tremor resulting from these injections was assessed using a 4-stage rating system. Dopamine content of the striatum was also quantified.

Injection of 2,2'-bipyridine (alone or in combination with ammonium iron(II) sulfate) into the substantia nigra showed slight but significant tremor compared to control animals; no effect was seen after injection into the nucleus caudatoputamen. The dopamine content of the striatum remained unchanged upon treatment.

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