2-fluoro-6-trifluoromethylpyridine

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:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

428-100-3

EC Name:

-

Cas Number:

94239-04-0

Molecular formula:

C6H3NF4

IUPAC Name:

2-fluoro-6-(trifluoromethyl)pyridine

Details on test material:

- Purity: 99.7%

Specific details on test material used for the study:

Substance ID: F6TF
Lot #: 8922/16
Purity: 99.7%

Test animals

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Males weighed 291-430 g and the females weighed 238-248 g
- Fasting period before study: Fasted overnight immediately prior to dosing
- Housing: A maximum of 5 rats was housed per cage, sexes separately
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 30-70%
- Air changes (per hr): A minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): Artificial, giving 12 hours light, 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

DOSAGE PREPARATION: Dose levels were altered by adjusting the concentration of the dosing preparations. The volume of the dose was calculated for each animal according to its weight at the time of dosing. A standard volume of l0 mL/kg of the dosing preparation was administered by oral gavage using a stomach tube.

Doses:

Sighting phase: 500 and 2000 mg/kg
Main Study: 50 and 500 mg/kg

No. of animals per sex per dose:

Sighting phase: 1 female per dose
Main study: 5 per sex at 500 mg/kg; 5 males at 50 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: Main study up to day 15; Sighting phase up to day 7
- Frequency of observations and weighing: The animals were observed for signs of systemic toxicity twice following dosing on day 1. Subsequent observations were made daily. The animals were weighed prior to fasting on the day before dosing (day -1), immediately before dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

discriminating dose

Effect level:

50 mg/kg bw

Based on:

test mat.

Mortality:

Sighting Phase: Following a dose of 500 mg/kg, the animal survived and showed signs of slight, but evident, toxicity. Following a dose of 2000 mg/kg, the animal was killed in extremis on day 2. At examination post mortem this animal had a dark liver.

Main Study: Following a dose of 500 mg/kg to male and female rats, three males were killed in extremis on day 2. Surviving animals showed signs of evident toxicity, with complete recovery by day 5. No animals died following a dose of 50 mg/kg.

Clinical signs:

other: There were signs of evident toxicity in the surviving animals, with complete recovery by day 5.

Body weight:

other body weight observations

Remarks:

With the exception of one female, which showed a slight weight loss, all surviving animals showed an overall bodyweight gain during the study.

Gross pathology:

Distension of the stomach was seen in the three males dosed with 500 mg/kg which were killed in extremis. This finding is considered to be treatment-related. In the males dosed with 50 mg/kg, one animal had only one testis (congenitally absent) and two males had speckling of the thymus. These are spontaneous or non-specific findings and are considered to be unrelated to treatment.

Applicant's summary and conclusion

Conclusions:

The highest fixed dose of the test substance administered in this test without causing any lethality (i.e., the overall discriminating dose-level) was 50 mg/kg.

Executive summary:

A group of 5 male and 5 female rats was dosed with 500 mg/kg of the test substance and assessed daily for 14 days for any signs of systemic toxicity. A further group of 5 male rats was similarly treated, but dosed with 50 mg/kg. Bodyweights were recorded at intervals throughout the study. Animals in extremis and those surviving to the end of the study were killed and subjected to a macroscopic examination post mortem.

 

Following a dose of 500 mg/kg to 5 male and 5 female rats, 3 males were killed in extremis on day 2. Surviving animals showed signs of evident toxicity, with complete recovery by day 5. Distension of the stomach was seen in the 3 males killed in extremis. This finding is considered to be treatment-related. No mortality was observed following a dose of 50 mg/kg to 5 male rats, and there were no signs of toxicity. The highest fixed dose of the test substance administered in this test without causing any lethality (i.e., the overall discriminating dose-level) was 50 mg/kg.