2,6-difluorobenzonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A non-GLP study performed in accordance with generally accepted scientific principles with a sufficient level of detail to assess the quality of the submitted data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A single dose of test material was orally administered by gavage to groups of 5 mice and rats, of each sex, at 2.15 µL/kg to 2150 µL/kg of bodyweight in the mice experiment and 100 µL/kg to 2150 µL/kg of bodyweight in the rat experiment. All dose levels were brought to a volume of 10 ml/kg of bodyweight with 1% aqueous gum tragacanth. Following dose administration all animals were observed for a period of 14 days and any sign of intoxication ascertained by observation and manipulation was recorded.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-difluorobenzonitrile

EC Number:

217-589-7

EC Name:

2,6-difluorobenzonitrile

Cas Number:

1897-52-5

Molecular formula:

C7H3F2N

IUPAC Name:

2,6-difluorobenzonitrile

Details on test material:

Code No.: Postmus 74-85-01

Test animals

Species:

other: mice and rats

Strain:

other: Swiss (mice); SPF Wistar (rats)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 16-20 g (mice); 200-220 g (male rats); 120-150 g (female rats)
- Fasting period before study: mice and rats were fasted overnight (18 hours) prior to dosing
- Housing: 5 per cage according to species, sex and dose level
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (ºC): 24 ºC
- Humidity (%): 60-75%
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: gum tragacanth

Details on oral exposure:

DOSE VOLUME APPLIED:
10 ml/kg bodyweight administered as a standard dose volume

Doses:

Mice (dose levels in µL/kg): 2.15, 4.64, 10.0, 21.5, 46.4, 100, 215, 464, 1000, 2150
Rats (dose levels in µL/kg): 100, 215, 464, 2150

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Observations: following treatment any sign of intoxication which could be ascertained by observation and manipulation of the animals was recorded

Animal source: TNO., Zeist, The Netherlands

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 153.8 mg/kg bw

Based on:

test mat.

95% CL:

792.5 - 1 682.1

Remarks on result:

other: Mice experiment. Minimum symptomatic dose: 578 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 345.7 mg/kg bw

Based on:

test mat.

95% CL:

923.3 - 1 956

Remarks on result:

other: Mice experiment. Minimum symptomatic dose: 578 mg/kg bw

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

727.7 mg/kg bw

Based on:

test mat.

95% CL:

535.8 - 989.3

Remarks on result:

other: Rat experiment. Minimum symptomatic dose: 267.9 mg/kg bw

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

848.5 mg/kg bw

Based on:

test mat.

95% CL:

578.1 - 1 246

Remarks on result:

other: Rat experiment. Minimum symptomatic dose: 267.9 mg/kg

Mortality:

MICE EXPERIMENT
Following a single oral dose of 2150 µL/kg all five male and female animals died within 24 hours following dose administration. At the dose level of 1000 µL/kg three male and 2 female animals died within 48 hours following dose administration. All animals at all other dose levels survived the 14 day observation period.

RAT EXPERIMENT
At the dose level of 2150 µL/kg all dosed animals died between 24 and 48 hours following dose administration. At the dose level 464 µL/kg one male animal dies 72 hours after treatment.

Clinical signs:

other: MICE EXPERIMENT Dose level 2150 µL/kg: Animals showed slowed down respiration rate, abnormal body posture and abnormal gait, loss of righting reflexes, mydriasis, loss of pinna and cornea reflexes, marked loss of body tone and grip strength, slight increa

Any other information on results incl. tables

Table 1: Mortality Results - Mice Study

Dose level (mg/kg bw)	No. Dead/ No. Treated (male)	No. Dead/ No. Treated (female)
2678.9	5/5	5/5
1246.0	3/5	2/5
578.1	0/5	0/5
267.9	0/5	0/5
124.6	0/5	0/5
57.8	0/5	0/5
26.8	0/5	0/5
12.5	0/5	0/5
5.8	0/5	0/5
2.7	0/5	0/5

Table 2: Mortality Results - Rat Study

Dose level (mg/kg bw)	No. Dead/ No. Treated (male)	No. Dead/ No. Treated (female)
2678.9	5/5	5/5
2678.9	5/5	5/5
578.1	1/5	0/5
267.9	0/5	0/5
124.6	0/5	0/5

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the condutions of the study, the highest fixed dose of the test material administered without causing any lethality was 578 mg/kg in the mice experiment and 267.9 in the rat experiment.The LD50 values were determined to be > 300 < 2000 in all cases.

Executive summary:

The acute oral toxicity of the test material was investigated by administering a single dose of test material orally, by gavage, to groups of 5 mice and rats, of each sex, at dose levels of 2.15 µL/kg to 2150 µL/kg bodyweight in the mice experiment and 100 µL/kg to 2150 µL/kg bodyweight in the rat experiment. All dose levels were brought to a volume of 10 ml/kg of bodyweight with 1% aqueous gum tragacanth. Following dose administration all animals were observed for a period of 14 days and any sign of intoxication ascertained by observation and manipulation was recorded.

Under the conditions of the study, the highest fixed dose of the test material administered without causing any lethality was 578 mg/kg in the mice experiment and 267.9 mg/kg in the rat experiment. The LD₅₀ values were determined to be > 300 < 2000 in all cases.

In accordance with the criteria for classification as defined in Annex I, Regulation No. 1272/2008, the test material meets the criteria for classification as 'Acute toxicity oral: Category 4' with the associated hazard phrase 'Harmful if swallowed (H302)'. This is equivalent to Xn (Harmful) with the associated risk phrase 'Harmful if swallowed (R22)' under Directive 67/548/EEC.