2,2'-bipyridyl

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

insufficient documentation.

Data source

Reference

Reference Type:

publication

Title:

Acute and subacute toxicity in Sherman strain rats exposed to 4,4'- and 2,2'-dipyridyl

Author:

Groce DF, Kimbrough RD

Year:

1982

Bibliographic source:

J Toxicol Environ Health. 1982, 10(3):363-72; PMID: 7175967

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In a subchronic toxicity study, male and female Sherman rats received 2,2'-bipyridine at 0.01 or 0.05% in drinking water ad libitum over a period of 3 months. Water consumption was measured twice weekly and rats were weighed biweekly. At autopsy, selected tissues were removed, fixed in formalin and examined microscopically after H&E staining.

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): 2,2'-bipyridyl

Test animals

Species:

rat

Strain:

Sherman

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: U.S. Department of Health and Human Services, Center for Disease Control
- Fasting period before study: 24 h
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.01 and 0.05%

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

3 months

Frequency of treatment:

Drinking water was offered ad libitum, so continuous exposure can be assumed.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.01 other: %

Remarks:

Basis:
nominal in water

Doses / concentrations 2

Dose / conc.:

0.05 other: %

Remarks:

Basis:
nominal in water

No. of animals per sex per dose:

6 rats per dose group

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE AND DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: biweekly

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: twice weekly

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Details on results:

Rats given 0.01 or 0.05% 2,2'-bipyridine in drinking water had no symptoms of toxicity but did gain less weight and drink less water than control animals.
Microscopically, no lung changes were present. Kidney changes (table 1) included Ca concrements found in tubules of three rats and nephrosclerosis in one of six receiving 0.01% 2,2'-bipyridine. Bowman's capsule was thickened, and the tubular epithelium contained a brown pigment in one rat of each does group. The tubular epithelium had enlarged and atypical nuclei in 2 of 10 rats receiving 0.05% 2,2'-bipyridine .

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1:Mean water consumption, daily dose, and kidney pathologyforsubchronic exposure of rats to 2,2’-bipyridine.

Observation	Control ^a)	2,2’-Bipyridine
		0.01%	0.05%
Mean water consumption, [ml/d]	26.2	21.4	18.0
Mean daily dose, [mg/kg bw/day]	0.00	7.13	35.6
Hydronephrosis	1/15
Tubules containing Ca concrements		3/6
Nephrosclerosis		1/6
Bowman's capsule of glomeruli occasionally thickened			1/10
Tubular epithelium containing brown pigment			1/10
Tubular epithelium containing enlarged atypical nuclei			2/10
Normal	13/15	2/6	7/10

^a)Numbers are for two control groups (another study with 4,4’-bipyridine was run in parallel).

Applicant's summary and conclusion

Conclusions:

Oral administration of 2,2'-bipyridine at 0.01 or 0.05% in drinking water to rats caused no symptoms of toxicity than reduced weight gain and water consumption. Slight kidney changes were observed.
The administered doses were calculated to be 7.13 and 35.6 mg/kg bw/day based on mean food consumption data.

Executive summary:

Subacute oral toxicity of 2,2’-bipyridine was determined by administration of the test item to rats. Groups of male and female rats were treated with the test item as 0.01 or 0.05% solution in drinking water offered ad libitum over a period of 3 months. Water consumption was measured twice weekly and rats were weighed biweekly. At autopsy, selected tissues were removed, fixed in formalin and examined microscopically after H&E staining.

Treated rats showed no symptoms of toxicity than reduced weight gain and reduced water consumption. The administered doses were calculated to be 7.13 and 35.6 mg/kg bw/day based on mean food consumption data.

Microscopically, no lung changes were present. Kidney changes were slight and included Ca concrements in tubules and nephrosclerosis in one of six animals receiving 7.13 mg/kg bw/day 2,2'-bipyridine. Bowman's capsule was thickened, and the tubular epithelium contained a brown pigment in one rat of the high-dose group. The tubular epithelium had enlarged and atypical nuclei in 2 of 10 rats receiving 35.6 mg/kg bw/day 2,2'-bipyridine.