4-methylpyrazole

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Animal experimental study, published in peer reviewed literature, restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

publication

Title:

Long term toxicity study with alcohol and 4-methylpyrazole in rat.

Author:

Kager L.

Year:

1974

Bibliographic source:

Acta Pathol Microbiol Scand A. 1974 Jul;82(4):534-8.

Materials and methods

Principles of method if other than guideline:

Twelve male Sprague-Dawley rats were exposed to the test substance continuously via drinking water for 12 weeks. During the exposure period clinical signs and fluid consumption were recorded. Animals were weighed once a week. After the exposure period blood was taken for haematology and clinical chemistry, and animals were necropsied.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-methylpyrazole

EC Number:

231-445-0

EC Name:

4-methylpyrazole

Cas Number:

7554-65-6

Molecular formula:

C4H6N2

IUPAC Name:

4-methyl-1H-pyrazole

Details on test material:

Name of test material (as cited in study article): 4-methylpyrazole

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: AB Anticimex (Sollentuna, Sweden)
- Age at study initiation: 5-6 weeks
- Weight at study initiation: mean 130 g
- Housing: individually
- Diet: ad libitum, Anticimex Mouse and Rat Food 201 (3.7% fat, 37.2% protein)
- Water: ad libitum

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

12 weeks

Frequency of treatment:

continuously

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0.13 ± 0.02 mmol/kg bw
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
14.8 ± 2.4 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

12 male animals

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

-CAGE SIDE OBSERVATIONS: were performed, frequency unknown
-BODY WEIGHT: once a week rats were weighed.
-WATER CONSUMPTION AND COMPOUND INTAKE: Amounts of fluid consumed were registered once a week.
-HAEMATOLOGY: At termination of the experiments, after 12 weeks, the aorta was catheterized under ether anaesthesia. Determinations of hemoglobin, leucocytes, differential white cell count.
-CLINICAL CHEMISTRY: At termination of the experiments, after 12 weeks, the aorta was catheterized under ether anaesthesia. Determination of serum creatinin, GPT, GOT and serum protein.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes; liver, kidneys, heart and spleen were weighed.
HISTOPATHOLOGY: Liver, pancreas, kidney, and heart were taken for microscopic examination.

Results and discussion

Results of examinations

Details on results:

In all animals treated with 4-methylpyrazole no clinical symptoms and no signs of toxicity occurred. Body weight gain and organ weights were comparable to the concurrent control. There were no changes in liver function and the results of the haematological investigations revealed no signs of damage to the bone marrow. There were no changes of gross pathology and histology.

Effect levels

Dose descriptor:

NOEL

Effect level:

14.8 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified