(2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(1981)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

EC Number:

406-850-2

EC Name:

(2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

Cas Number:

133855-98-8

Molecular formula:

C17 H13 Cl F N3 O

IUPAC Name:

1-{[(2R,3R)-3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach
- Mean weight at study initiation: 200g males, 192 g females
- Housing: In groups of 5 in steel wire mess cages Type DK-III
- Diet ad libitum: Kliba diet 343
- Water ad libitum: Tap water
- Acclimation period: 1 week
-Fasting period: Animals were withdrawn from food 16 h before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 % aqueous solution

Details on oral exposure:

DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

5000, 3160 and 1470 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
- Duration of observation period following administration: 21 days
- Frequency of observations for clinical symptoms: Several times on first day, afterwards once each workday.
- Frequency of observations for mortality: Several times on first day, afterwards twice on workday and once on holidays.
- Frequency of weighing: On first day, day 7, day 13 and day 20.
- Necropsy of survivors performed: Yes, at study termination all animals were sacrificed and subjected to gross pathology. Moribund animals were examined as early as possible.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 1/5 females was found dead at the highest dose group (5000 mg/kg bw)

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 3 160 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/5 males were found dead at the highest and the mid dose group (5000 and 3160 mg/kg bw).

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3/10 animals were found dead at the highest and 2/10 animals were found dead at the mid dose group (5000 and 3160 mg/kg bw, respectively).

Mortality:

1/5 females and 2/5 males were found dead at the highest dose group (5000 mg/kg bw).
0/5 females and 2/5 males were found dead at the mid dose group (3160 mg/kg bw).
No animal died at the lowest dose group (1470 mg/kg bw).

Clinical signs:

other: Clinical symptoms, like dyspnea, imbalance, excitation, staggering, spastic gait, piloerection, alopecia and a poor general state were seen in animals of both sexes at 5000 and 3160 mg/kg bw.

Gross pathology:

Animals that died:
In males that died, necropsy revealed general congestion at 3160 and 5000 mg/kg bw. In addition, the liver of males treated with 5000 mg/kg bw showed a yellow-brown tinge. The examination of 1 dead male at 3160 mg/kg bw and of 1 dead female at 5000 mg/kg bw was not possible due to decomposition.
Animals that were sacrificed at test ending:
No macroscopic findings were observed in animals sacrificed at study termination.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral median lethal dose of the test substance in rats is higher than 5000 mg/kg bw.

Executive summary:

The substance was tested for its potential acute hazard after single oral administration. The test method was based on EPA (FIFRA) and OECD 401 guidelines. GLP requirements were fulfilled. 5 male and 5 female Wistar rats per dose group were administered 1470, 3160 and 5000 mg/kg bw of the test substance by gavage. The observation period was 14 days. Unspecific clinical symptoms occurred in the two high dose group. Mortality occurred in the dosages of 3160 and 5000 mg/kg bw.

Necropsy findings in animals that died were: general congestion, yellow brown tinge of the liver. Thus, the LD50 (oral) in rats is > 5000 mg/kg bw.