2,6-difluorobenzonitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 May 1992 to 19 May 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

( the protocol described that the int. doc. no. of this study was 56645/13/92 rather than 56645/37/92) This deviation is not considered to have affected the integrity of the study or its results.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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:

- Physical state: a white paste

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/CPB, Zeist, The Netherlands
- Weight at study initiation (animal arrival): Male rats weighed 175-200g and females 150-175g
- Housing: Individually (application period); 2-3 animals per cage (all other times)
- Diet: ad libitum (standard laboratory diet RHM-TM, Hope Farms, Woerden, The Netherlands)
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (ºC): 19-23 ºC
- Humidity (%): 40-65%
- Air changes (per hr): approximately 16 changes
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs light (artificial)

IN-LIFE DATES: 5th May 1992 - 19th May 1992

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

test material was melted at 32 ºC prior to application

Details on dermal exposure:

TEST SITE
- Area of exposure: Hair from the back and flanks of the animals was removed with an electric clipper
- Type of wrap used: The test material was applied over a strip of gauze of about 15 cm². The patch was heated under an incandescent lamp to melt the test material so that it could be applied uniformly over the patch. The gauze was covered with an occlusive Blenderm tape of about 5 x 10 cm, on a wider strip of plaster. The total patch with test material was applied on the back and flanks of each animal and help in place with strips of plaster.
- Animal restraint during test material application: To prevent damaging of the patches, the rats were fitted with collars during the application period. After 24 hours the collars were removed.

REMOVAL OF TEST SUBSTANCE: After 24 hours of exposure the gauze patches were peeled off under light ether anaesthesia. The skin was wiped to remove any remaining test material.

TEST MATERIAL
- Amount(s) applied: The amount of test material was calculated for each animal according to its weight at the time of dosing. All animals were treated with 2000 mg/kg of test material.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observation and weighing: Prior to the start of the study, all rats were examined for any skin lesions. The animals were observed at 1, 3, 5, 25 and29 hours after application and thereafter once on each day until the end of the study. The animals were weighed one day before dosing (day -1), on the day of dosing (day 0), and at 2, 7 and 14 days after treatment.
- Necropsy of survivors performed: At the end of the study all animals were killed by ether inhalation and an autopsy was performed that included inspection of the external appearance, the cervical area, the thoracic and abdominal cavities.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 other: mg/kg

Based on:

test mat.

Mortality:

None of the animals dies over the course of the study.

Clinical signs:

other: During the application period, chromodacryorrhoea and dirty noses were noticed from 1 hour after start of the application up to 24 hours after treatment in both males and females. Upon removal of the collars these signs disappeared. In both males and fem

Gross pathology:

At autopsy 14 days after treatment, 4 male and 3 female rats had a few red spots on their lungs and thymus. These findings were considered not to be treatment-related. No macroscopic abnormalities were noted that could be considered to be treatment-related.

Any other information on results incl. tables

Table 1: Body Weights (g)

Sex	Animal No.	Day
		-1	0	2	7	14
M	1	203	216	209	236	259
	2	212	221	214	238	259
	3	212	229	202	236	267
	4	200	209	203	229	262
	5	197	210	196	211	232
	Mean	204.8	217.0	204.8	230.0	255.8
F	1	179	174	175	182	194
	2	183	191	173	190	208
	3	178	185	172	186	202
	4	185	194	179	188	190
	5	159	170	164	176	190
	Mean	176.8	182.8	172.6	184.4	196.8

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg in rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The acute dermal toxicity of the test material was determined in accordance with standard guideline EU Method B.3. During the study five male and five female rats received a single dermal application of 2000 mg/kg of the test material. Animals were assessed over a 14 day observation period for any signs of systemic toxicity. None of the animals died during the study and the clinical signs noted were mostly indicative of effects on motor coordination (abnormal gait and posture). In addition, signs indicative of effects on the autonomic nervous system were observed in one male and female and on the central nervous system in one female only. Time of onset of signs was between 5 and 25 hours after application. Signs were slight to moderate in intensity and had disappeared after 29 hours in males and 3 days in females. After dermal application of the test material the animals showed a decrease in body weights in the first few days of the study. Thereafter body weight gains appeared to be normal. There were no macroscopic abnormalities at examination post-mortem. The acute median lethal dose of the test material was estimated to be in excess of 2000 mg/kg in both male and female rats.