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EC number: 231-445-0 | CAS number: 7554-65-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: other routes
Administrative data
- Endpoint:
- short-term repeated dose toxicity: other route
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Animal experimental study, published in peer reviewed literature.
Data source
Reference
- Reference Type:
- publication
- Title:
- Normal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis)-a possible new treatment of methanol poisoning.
- Author:
- Blomstrand R.
- Year:
- 1 984
- Bibliographic source:
- Drug Alcohol Depend. 1984 Jan;13(1):9-20.
Materials and methods
- Principles of method if other than guideline:
- Four male Macaca fascicularis monkeys per dose were injected intramuscular with the test substance once a day, 5 times/week for 6 weeks. Ophthalmoscopic examinations and ERG recordings were performed, haematology and clinical chemistry were examined, and clinical signs recorded. After an observation period of an additional 72 hours animals were necropsied.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- 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 (4-MP)
Constituent 1
Test animals
- Species:
- monkey
- Strain:
- Macaca fascicularis
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2.1 - 3 kg
- Diet: ad libitum
- Water: ad libitum
Administration / exposure
- Route of administration:
- intramuscular
- Vehicle:
- physiological saline
- Details on exposure:
- Injection in 2-10% solutions
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 6 weeks
- Frequency of treatment:
- Once a day, 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
- Group 2: 20 mg/kg
- Group 3: 100 mg/kg for 5 weeks, and 200 mg/kg in the last week
- No. of animals per sex per dose:
- 4
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: 72 h after the last injections
Examinations
- Observations and examinations performed and frequency:
- - DETAILED CLINICAL OBSERVATIONS: Animals were carefully observed for clinical signs of intoxication during the course of the experiment.
- OPHTHALMOSCOPIC EXAMINATION: It was performed after 3 weeks and repeated 72 hours after the last injection at the end of the study.
- HAEMATOLOGY: Before the start of the experiment and at the end of the experiment blood samples were collected for determination of hemoglobin, number of erythrocytes, leucocytes and platelets, and blood cell microscopy.
- CLINICAL CHEMISTRY: Before the start of the experiment and at the end of the experiment blood samples were collected for determination of aminotransferases ASAT and ALAT, alkaline phosphatase, bilirubin, N-urea and glucose.
- CONCENTRATION IN BLOOD: From the second week and once a week afterwards, blood samples were taken for analysis of the serum levels of 4-MP in group 3. In group 2 the serum levels were checked only after 6 weeks.
- ERG: During the ERG recording, the heads and bodies of the naimals were held by means of plastic support. Pupils were dilated (by Mydriacyl® and 10% Neosynephrine®), photographs were taken from the left eye and ERG was recorded on the right eye. 45 min before the ERG animals were dark-adapted. The ERG was elicited with a strobe lamp connected to a pulse generator (Grass model PS 22). The signal was displayed on storage oscilloscope and photographed. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes. Tissue samples were taken from the brain, spinal cord, sciatic nerve, eyes, heart, liver, kidney and the spleen.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
In the third week, one monkey from group 3 died during anaesthesia. No test substance related clinical toxic reactions were observed in all exposed animals. All animals were in good shape, well nourished, alert, strong and showed a normal behavioural pattern.
OPHTHALMOSCOPIC EXAMINATION
No changes during the course of the experiments were observed.
HAEMATOLOGY and CLINICAL CHEMISTRY
No effects were observed in comparison with animals in the control group in all parameters.
GROSS PATHOLOGY and HISTOPATHOLOGY
No gross and microscopic morphological effects were observed.
CONCENTRATION
Animals in group 3 had very high and rather constant serum levels for the first 5 weeks, the range being between 204 and 1154 µM/L, then the values increased considerably (range 1742 – 2353 µM/L) the last week when the dose levels were doubled. Serum levels in group 2 were only taken at the end of the study. In three animals is was roughly similar (37 – 45 µM/L), but in one animal is much higher (425 µM/L).
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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