2,6-difluorobenzonitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 April 1992 to 17 April 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed to GLP and was conducted in compliance with the standard test guideline OECD 405 with no deviations thought to affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(see "Principles of method if other than guideline" for more information)

Principles of method if other than guideline:

Deviations from the protocol, which do not affect the quality of the relevant results are as follows:
- The test animals were obtained from a supplier other than stated in the protocol.
- Due to malfunction of the thermeohygrograph the temperature and the relative humidity in the animal room were not recorded on 12 April 1992.
- Due to the low melting point it was not possible to weigh the filled syringes, before the test material solidified.
- The lot number was not given on the test material container but confirmed by an internal memorandum. It therefore was not specified on the raw data.

GLP compliance:

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: white paste
Storage condition of test material: prior to dosing the test material was stored in a refrigerator

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan CPB, Zeist, The Netherlands (bred at the R.I.V.M., Bilthoven, The Netherlands
- Weight at study initiation: 2.5-3.0 kg
- Housing: individually in stainless steel wire cages
- Diet: standard laboratory diet LKK-20, Hope Farms, Woerden, The Netherlands ad libitum
- Water: ad libitum
- Acclimation period: 5 days prior to study initiation

ENVIRONMENTAL CONDITIONS
- Temperature (ºC): 20-21 ºC
- Humidity (%): 20-60%
- Air changes (per hr): approximately 16
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark

IN-LIFE DATES: From 14 April 1992 to 17 April 1992

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

test material was melted prior to application

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

- Dose administration: test material was placed (via syringe) in the conjunctival sac of the left eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test material was added. The lids were then gently held together for a few seconds after which the animal was released and returned to its cage. The right eye, remaining untreated, served as a control.

Observation period (in vivo):

Animals were observed for 72 hours following treatment.

Number of animals or in vitro replicates:

Three male rabbits were used in the study.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): irrigation was not performed

SCORING SYSTEM
The reactions observed were scored in accordance with the criteria of Draize (1944), presented as Table 1 in the field " Any other information on materials and methods incl. tables".

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hr readings

Score:

0

Max. score:

80

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hr readings

Score:

0

Max. score:

10

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hr readings

Score:

0

Max. score:

20

Irritant / corrosive response data:

At 24 hours after application of the test material a fold of the cornea across the whole eye was observed in one rabbit. No adverse effects were observed hereafter. The numerical grades awarded to the eye reactions elicited by the test material are given in Table 2 in the field "Any other information on results incl. tables".

Any other information on results incl. tables

Table 2: Scores of the Irritation Reactions after Application of 0.1 ml diflubenil to the Eye of Three Rabbits

Animal No.	Region of the eye				Hours (h) after treatment				Mean
				Pretest	1 h	24 h	48 h	72 h
1	Cornea	Opacity		0	0	0	0	0	0
		Area involved		0	0	0	0	0	0
	Iris			0	0	0	0	0	0
	Conjunctiva	Redness		0	0	0	0	0	0
		Chemosis		0	0	0	0	0	0
		Discharge		0	0	0	0	0	0
2	Cornea	Opacity		0	0	0	0	0	0
		Area involved		0	0	0	0	0	0
	Iris			0	0	0	0	0	0
	Conjunctiva	Redness		0	0	0	0	0	0
		Chemosis		0	0	0	0	0	0
		Discharge		0	0	0	0	0	0
3	Cornea	Opacity		0	0	0a	0	0	0
		Area involved		0	0	1	0	0	0
	Iris			0	0	0	0	0	0
	Conjunctiva	Redness		0	0	0	0	0	0
		Chemosis		0	0	0	0	0	0
		Discharge		0	0	0	0	0	0

^aA fold of the cornea across the whole eye

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 test, the test material caused no significant eye irritation in any of the animals and the test material does not require classification as an eye irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The irritation of the test material to the rabbit eye was investigated following standard test guideline OECD 405. 0.1 ml of test material was placed into the conjunctival sac of one eye of each of three male rabbits. The eyes of the rabbits were examined and the ocular reactions graded at 24 hour intervals up to and including 72 hours post treatment. At 24 hours after application of the test material a fold of the cornea across the whole eye was observed in one rabbit. No adverse effects were observed hereafter.

The test material caused no significant eye irritation in three rabbits. The test material is therefore classified as a non-irritant to the eye and does not require classification for eye irritation in line with Regulation No. 1272/2008.