4-tert-butylbenzonitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

january - march 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylbenzonitrile

EC Number:

224-137-2

EC Name:

4-tert-butylbenzonitrile

Cas Number:

4210-32-6

Molecular formula:

C11H13N

IUPAC Name:

4-tert-butylbenzonitrile

Details on test material:

- Name of test material (as cited in study report): 4-tert-Butylbenzonitril
- Physical state: liquid
- Apperance: brown solution
- Analytical purity: > 94.2 %
- Impurities (identity and concentrations): 3-tert-Butylbenzonitiril
- Lot/batch No.: FHI/TVT 281098
- Storage condition of test material: refigerator (2-8 °C), in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: J. Schitkovits, A-2620 Natschbach
- Weight at study initiation: animal No. 71: 3.0 kg; animal No.72: 2.5 kg; animal No.73: 3.5 kg.
- Housing: individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 com x 59 cm x 35 cm.
- Diet (e.g. ad libitum): Altromin 2023 diet for rabbits, ad libitum. Random samples of the feed are analysed for contaminats by Altromin, D-32791 Lage.
- Water (e.g. ad libitum): tap water from an automatical watering system, ad libitum.
- Acclimation period: 11 days (animal No. 71) and 17 days (animal No. 72 and No. 73).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 20 °C
- Humidity (%): average of 59 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of 4-tert-Butylbenzonitrile
- Lot/batch no. (if required): FHI/TVT 281098
- Purity: > 94.2 %

Duration of treatment / exposure:

0.1 mL of the test substance was administered into the conjunctival sac of the right eye after gently pulling the lower lid away from the eyeball. After instillation, the eyes were held closed for about one second to prevent a loss of test substance.
The left eyes remained untreated and served as negative controls.

Observation period (in vivo):

Eye examination: 1, 24, 48 and 72 h after the administration (p. a.) of the test substance.

Number of animals or in vitro replicates:

three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
CORNEA:
Opacity: degree of density (area most dense area is taken for reading).
0 No ulceration or opacity.
1 Scattered or diffuse areas of opacity (except for slight dulling of normal lustre), details of iris clearly visible.
2 Easily discernible translucent area, details of iris slightly obscured.
3 Nacreous area, no details of iris visible, size of pupil barely discernible.
4 Opaque cornea, iris not discernible through the opacity.

IRIS:
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection; any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive).
2 No reaction to light, haemorrhage, gross destruction (any of all these or all together).

CONJUNCTIVAE:
Redness: (refers to the most severe effect of palpebral and bulbar conjuctivae in comparison to the control eye).
0 Blood vessels normal.
1 Some blood vessels defintitely hyperaemic (injected).
2 Diffuse crimson colour, individual vessels not easily discernible.
3 Diffuse beefy red.

Chemosis: lids and/or nictating membranes.
0 No sweling.
1 Any swelling above normal (includes nictating membranes).
2 Obvious swelling with partial eversion of lids.
3 Swelling with lids about half closed.
4 Swelling with lids more than half closed.


TOOL USED TO ASSESS SCORE: an otoscope lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: # 71, 72 and 73

Time point:

other: 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

animal: # 71, 72 and 73

Time point:

other: 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 3

Irritation parameter:

other: redness

Basis:

animal: # 71

Time point:

other: 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 4

Irritation parameter:

other: redness

Basis:

animal: # 72 and 73

Time point:

other: 1 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 5

Irritation parameter:

other: redness

Basis:

animal: # 71, 72 and 73

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 6

Irritation parameter:

chemosis score

Basis:

animal: # 71

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 7

Irritation parameter:

chemosis score

Basis:

animal: # 72 and 73

Time point:

other: 1 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 8

Irritation parameter:

chemosis score

Basis:

animal: # 71, 72 and 73

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

Cornea, Iris: Only scores of "0", i.e. normal, were noted in all animals at all examination terms.
Conjunctivea, redness and chemosis: 2/3 animals were affected 1 h p.a., with a score of "1". No changes were observed later on.

Other effects:

No other effects were observed.

Any other information on results incl. tables

Table 1: Scores of the test eyes. Individual data and means.

Time after instillation (p.a.)	Cornea			Iris			Conjunctivae
							Redness			Chemosis
	animal No.			animal No.			animal No.			animal No.
	71	72	73	71	72	73	71	72	73	71	72	73
1 h	0	0	0	0	0	0	0	1	1	0	1	1
24 h	0	0	0	0	0	0	0	0	0	0	0	0
48 h	0	0	0	0	0	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0	0	0	0	0	0
Mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this test the test material 4-tert-Butylbenzonitrile is not considered to be an eye irritant.

Executive summary:

In an acute eye irritation study according to OECD Guideline 405, 0.1 mL of 4 -tert-Butylbenzonitrile was instilled into the right eye of three female albino rabbits (New Zealand White strain). The eyes were not washed afterwards and the left eyes remained untreated and served as negative controls. The animals then were observed 1, 24, 48 and 72 hours after the treatment. Irritation was scored and recorded by a scoring system concerning cornea, iris and conjunctivae.

Under the testing conditions cornea and iris were not affected in all of the test animals. Some injected blood vessels and a very slight swelling were observed in 2/3 animals 1 h p.a. Nevertheless this effect was fully reversible and no lesions were observed at the other examination terms. Therefore no classification for eye irritation of 4 -tert-Butylbenzonitrile is derived from the results of this study.