3,5-bis(difluoromethyl)-1H-pyrazole

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Mar - 26 Apr 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

adopted in 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted in 2002

GLP compliance:

yes (incl. QA statement)

Remarks:

OQYEI National Institute of Pharmacy and Nutrition, Budapest, Hungary

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,5-bis(difluoromethyl)-1H-pyrazole

EC Number:

814-072-3

Cas Number:

77614-79-0

Molecular formula:

C5H4F4N2

IUPAC Name:

3,5-bis(difluoromethyl)-1H-pyrazole

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Doses:

55, 175 and 550 mg/kg bw
Starting dose: 55 mg/kg bw
Dosing schedule: 55, 175, 55, 175, 550 and 175 mg/kg bw

No. of animals per sex per dose:

1 female per step (6 steps in total)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Individually after dosing at 30 minutes, then 1, 2, 3, 4, and 6 h and
once daily for 14 days thereafter or until death. Additional body weight measurements were made for the 4th animal (dosed 175 mg/kg bw) on Day 4, based on the clinical signs of the animal.
- Frequency of weighing: Before treatment, on Days 7 and 14 (at necropsy) and on the day of death.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

175 mg/kg bw

Based on:

test mat.

95% CL:

29.03 - 714

Mortality:

55 mg/kg bw: 0/2 animals died
175 mg/kg bw: 2/3 animals died (Day 1 or 2)
550 mg/kg bw: 1/1 animals died (Day 1)

Clinical signs:

other: 55 mg/kg bw: Slightly decreased activity, hunched back and piloerection in 2/2 animals, starting from the day of treatment up to Day 3 or 4, fully reversible within 5 days. 175 mg/kg bw: Decreased activity (slight, moderate or severe) in 3/3 animals, hunc

Gross pathology:

55 mg/kg bw: Necropsy and histopathological examination revealed no substance-related findings.
175 mg/kg bw:
- animals found dead: Non-collapsed lung in 2/2 dead animals.
- animals sacrificed at termination: Necropsy and histopathological examination revealed no substance-related findings.
550 mg/kg bw:
- animals found dead: Diffuse red discoloration of all lobes of non-collapsed lungs and multifocal red discolouration of the glandular mucosa of the stomach in 1/1 dead animals.

Applicant's summary and conclusion

Interpretation of results:

other: Acute Oral 3, H301 according to Regulation (EC) No. 1272/2008.

Conclusions:

Oral administration of the test substance according to OECD guideline 425 with the three dose levels 55, 175 and 550 mg/kg bw induced mortality at ≥ 175 mg/kg bw. Clinical signs of toxicity were observed in all animals and comprised decreased activity, hunched back and piloerection at ≥ 55 mg/kg bw and incoordination, reddish discharge from the nose and cold appearance at touch at ≥ 175 mg/kg bw. There was no impairment of body weight development. Gross necropsy of animals found dead revealed diffuse red discoloration of all lobes of non-collapsed lungs and multifocal red discolouration of the glandular mucosa of the stomach at 550 mg/kg bw and non-collapsed lungs at 175 mg/kg bw. Gross necropsy of surviving animals revealed no abnormalities. A LD50 value of 175 mg/kg bw was derived. The substance requires classification as Acute Oral 3, H301 according to CLP/EU GHS criteria.