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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with GLP and appropriate OECD Guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test substance, Iso-PROPYL BROMIDE, used in the study was supplied by Elf Atochem S.A.
Documentation supplied by the Sponsor identified the test substance as follows:
· denomination: Iso-PROPYL BROMIDE
· batch number: 1-302-1
· labelling: ISO-PROPYL BROMIDE
lot 1-302-1
description: colourless liquid
· quantity and container: 1 glass flask
· date of receipt: 7.5.93
· storage conditions: room temperature and protected from light
· purity> 99%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

Sex, species, strain: Male New Zealand White rabbits.
Reason for this choice: species commonly requested by the international regulations for this type of study.
Breeder: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
Number of animals and identification: 3 animals were used, as recommended by the international regulations and taking into account that a good correlation of results can be obtained with either 3 or 6 animals. The animals were identified individually with a metal tag in the ear.
Weight: on the day of treatment, the animals had a mean body weight of 3.0 ± 0.4 kg.
Acclimatization: at least 5 days before the beginning of the study.
Selection of the animals: the day before treatment, the eyes of each animal were examined in order to use only animals without any signs of ocular irritation. Animals showing signs of ocular irritation, ocular defects or pre-existing corneal injury were not used.


ENVIRONMENTAL CONDITIONS

During the acclimatization period and during the main test, the environmental conditions in the animal room were as follows:
temperature: 18 ± 3°C
relative humidity: 50 ± 20%
light/dark cycle: 12 h / 12 h
The animals were housed individually in polystyrene cages (35 x 55 x 32 cm or 48.2 x 58 x 36.5 cm). Each cage was equipped with a food container and a water bottle.

FOOD AND WATER

All the animals had free access to 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France).
Drinking water filtered by a F.G. Millipore membrane (0.22 micron) and contained in bottles was provided ad libitum.
There were no contaminants in the diet or water at levels likely to have influenced the outcome of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml of iso-propyl bromide (undiluted and > 99% purity) in a single dose installed into the conjunctival sac of the left eye
Duration of treatment / exposure:
Single treatment and eyes were not rinsed after administration of the test substance.
Observation period (in vivo):
Animals were observed for ocular reactions for 72 hours following administration.
Number of animals or in vitro replicates:
3
Details on study design:
TREATMENT

Preparation of the animals

The day before treatment, the animals' eyes were checked for abnormalities. Only animals without ocular defects were used for the study.

Administration of the test substance

A single dose of 0.1 ml of the test substance in its original form was instilled into the conjunctival sac of the left eye of 3 animals after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test substance. The right eye, which remained untreated, served as a control. The eyes were not rinsed after administration of the test substance.

OCULAR EXAMINATIONS

The eyes were examined approximately 1, 24, 48 and 72 hours after administration of the test substance. As there was no evidence of irritation after 72 hours, the study was ended. Any change in the animals' behaviour was noted.

DESCRIPTION AND EVALUATION OF OCULAR REACTIONS

Ocular reactions were evaluated for each animal according to the following numerical scale:

Conjunctival lesions and discharge

Chemosis (lids and/or nictitating membranes)
no swelling 0
any swelling above normal (includes nictitating membranes) 1
obvious swelling with partial eversion of lids 2*
swelling with lids about half-closed 3*
swelling with lids more than half-closed 4*
* indicates positive effect

Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
blood vessels normal 0
a number of blood vessels definitely hyperaemic (injected) 1
diffuse, crimson colour, individual vessels not easily discernible 2*
diffuse, beefy red 3*

Discharge
absence of discharge 0
slight discharge (does not include small amounts normally found in inner canthus) 1
discharge with moistening oflids and hairs adjacent to lids 2
discharge with moistening of lids and hairs on wide area around the eye 3

Iris lesions
normal 0
markedly deepened rugae, congestion, swelling, moderate circum-corneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1*
no reaction to light, haemorrhage, gross destruction (any or all of these) 2*

Corneal lesions

Cornea (direct examination or, if necessary, with an Ultra Violet lamp)
To determine the presence or absence of corneal opacification and to evaluate the affected area, 1 or 2 drops of 0.5% sodium fluorescein solution can be instilled into the eye (however, this must be performed after a period of 24 hours). If corneal opacification is difficult to determine, the eye can be examined under a U.V. lamp (a clear fluorescence is visible in the areas of opacification).

Opacity (degree of intensity: area most dense taken for reading)
no ulceration or opacity 0
scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible 1*
easily discernible translucent area, details of iris slightly obscured 2*
nacrous areas, no details of iris visible, size of pupil barely discernible 3*
opaque cornea, iris not discemible through the opacity 4*

Area of opacity
one quarter (or less) but not zero 1
greater than one quarter but less than a half 2
greater than one half but less than three quarters 3
greater than three quarters up to whole area 4

Any other lesions observed were noted.
* indicates positive effect

INTERPRETATION OF RESULTS AND CLASSIFICATION OF SUBSTANCES

The results obtained were evaluated taking into consideration the nature and the reversibility or irreversibility of the findings observed. Classification of the test substance is based on the criteria laid down in: Directive 91/325/E.E.C. Commission Directive of 1st March 1991 adapting to
technical progress for the twelfth time Council Directive 67/548/E.E.C. on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances.

All the scores obtained for each reading (24, 48 and 72 hours) of a reaction were used to calculate the respective mean values.

Irritant substances and preparations

An ocular lesion must be considered as marked when the test is performed on 3 animals, if at least 2 of them reaches one of the following values:
opacity of the cornea >= 2, but lower than 3,
lesion of the iris >= 1, but lower than 2,
redness of the conjunctivae >= 2.5,
oedema of the conjunctivae (chemosis) >= 2.

Ocular lesions must be considered as severe if at least 2 of the 3 animals showed lesions equal to one of the following values:
opacity of the cornea >= 3,
· iridiac lesion equal to 2.

Results and discussion

Any other information on results incl. tables

One hour after the instillation of the test substance, marked reactions of the conjunctiva (chemosis and redness) in all 3 animals and slight iris congestion in 1 animal were noted. On day 2, slight chemosis and/or redness persisted in the 3 animals. On day 3, slight redness of the conjunctiva was noted in 1 animal. On day 4, no ocular reactions were observed.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions described in this study report, iso-propyl bromide was considered as non-irritant when administered by ocular route in rabbits.
Executive summary:

In a CoR 1 primary eye irritation study, 0.1 ml of undiluted iso-propyl bromide (>99% a.i.) was instilled into the conjunctival sac of the left eye of three male New Zealand White rabbits. The eyes were not rinsed following administration. Animals were then observed for 72 hours. Irritation was scored consistent with E.E.C. Directive 91/325.

 

In this study, iso-propyl bromide is not an eye irritant when administered in rabbits.