2-fluoro-6-trifluoromethylpyridine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

yes

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: 99.56%

Specific details on test material used for the study:

Substance ID: F6TF
Purity: 99.56%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 12 weeks
- Weight at study initiation: approximately 200-250 g
- Fasting period before study: No
- Housing: Plastic cages and numbered individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25°C
- Humidity (%): 40-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Prescribed amounts of the test substance were mixed with distilled water according to the prescribed doses at the time of administration.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Not reported

Duration of treatment / exposure:

Days 6 to 15 of gestation

Frequency of treatment:

Daily

Duration of test:

20 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

200 mg/kg bw/day

No. of animals per sex per dose:

A minimum of 15 pregnant rats/dose were examined

Control animals:

yes, concurrent vehicle

other: A positive control group was included, but the positive control material was not reported.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Every 3 days, including the day of dissection

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No data

Statistics:

T-test method was used for body weight growth of pregnant rats, body length, tail length, and body weights of foetuses. Χ2-test method was used for absorptivity, mortality, and teratogenic rate of foetuses.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:

mortality observed, non-treatment-related

Description (incidence):

Three rats in 100 mg/kg dose group and six rats in 200 mg/kg dose group died during the test period.

Body weight and weight changes:

no effects observed

Maternal developmental toxicity

Pre- and post-implantation loss:

no effects observed

Changes in number of pregnant:

no effects observed

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Three rats died at 100 mg/kg and 6 rats died at 200 mg/kg during the test period.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Fetal body weight changes:

effects observed, non-treatment-related

Changes in sex ratio:

no effects observed

Skeletal malformations:

effects observed, treatment-related

Description (incidence and severity):

Delayed sternebral ossification was observed at 200 mg/kg.

Visceral malformations:

no effects observed

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
A slight increase in resorptions was observed at 200 mg/kg, without adverse effects on mean litter size. Reduced mean tail length and fetal weight were observed at 100 and 200 mg/kg. Delayed sternebral ossification was observed at 200 mg/kg.

Effect levels (fetuses)

Key result

Basis for effect level:

other:

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The test substance has toxic effects on parents and may cause delay of fetus growth at doses above 100 mg/kg but no teratogenic effects.

Executive summary:

Sprague Dawley (SD) rats were used as test animals. Three dose groups (50, 100, and 200 mg/kg body weight/day) were set based on the results of the preliminary test. A negative control and a positive control were used synchronously. Pregnant rats were administered daily by oral gavage on the 6^th to 15^th day of gestation and were sacrificed at the 20^th day of gestation. At necropsy, the uteri were removed and weighed. The number of corpora lutea, live foetuses, early dead foetuses, late dead foetuses, and resorptions were recorded. The sex, body weight, body length, tail length of each live foetus and the weight of the placenta were recorded as well. External, skeletal, and visceral examinations were conducted. All data were processed.

The test substance has toxic effects on parents and delayed foetal growth at 100 and 200 mg/kg by oral administration. At 200 mg/kg, it also delayed the skeletal growth of the foetus. No teratogenic effects were found at 50, 100, or 200 mg/kg. Based on the findings of the study, the test substance would be considered to be a toxicant at dose levels greater than or equal to 100 mg/kg, based on decreased total number of pregnant rats, delayed foetus growth, and delayed skeletal growth. No teratogenic effects were observed at 200 mg/kg (the highest dose tested).