2,2'-bipyridyl

Neurotoxicity

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

Test material information

Constituent 1

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'-bipyridine

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.