4-methylpyrazole

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

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 report): 4-Methylpyrazol
- Description: pale yellow liquid
- Storage conditions: room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: aprroximately 8 weeks
- Weight at study initiation: mean 259 ± 7 g for males, and 227 ± 8 g for females
- Housing: during the acclimatization period animals were housed 1-7 animals per cage, in polycarbonate cages (48 cm x 27 cm x 20 cm); during the treatment animals were housed individually, in polycarbonate cages (35.5 cm x 23.5 cm x 19.3 cm); each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France)
- Diet: ad libitum, A04C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France)
- Water: ad libitum, filtered water by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 30 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure and preparation: on the day before treatment, the dorsal area (6 cm x 8 cm) of each animals was clipped.
- % coverage: it was placed on an area representing 10% (5 cm x 6 cm for the females, and 5 cm x 7 cm for the males) of the body surface of the animals
- Type of wrap if used: a hydrophylic gauze pad, which was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and restraining bandage.

REMOVAL OF TEST SUBSTANCE
- No residual test substance was observed at removal of the dressing.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 0.41, 1, 2.02 mL/kg (based on a specific gravity of 0.993 g/mL)

Duration of exposure:

24 hours

Doses:

400, 1000, 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

other: historical control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed frequently during the hours following administration. Thereafter, observation of the animals was made at least once a day until day 15. From day 2, only local cutaneous reaction was recorded. Animals were weighed individually just before administration on day 1, and on days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- No mortality was observed in animals exposed to 400 and 1000 mg/kg.
- All animals exposed to 2000 mg/kg died between day 2 and day 13 following treatment.

Clinical signs:

other: - 400 mg/kg dose group: Sedation was recorded in all animals on days 1 and 2. Ocular secretion was noted in 2 out of 5 females on day 2. No clinical signs persited on day 3. - 1000 mg/kg dose group: Sedation was observed in all animals on days 1 and 2, an

Gross pathology:

Macroscopic examination of the main organs revealed no apparent abnormalities.

Other findings:

No cutaneous reactions were recorded in all exposed animals.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information