tert-butyl peroxyisobutyrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-07-25 until 1995-07-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl peroxyisobutyrate

EC Number:

203-650-5

EC Name:

tert-butyl peroxyisobutyrate

Cas Number:

109-13-7

Molecular formula:

C8H16O3

IUPAC Name:

tert-butyl 2-methylpropaneperoxoate

additive 1

Reference substance name:

2,2,4,6,6-pentamethylheptane

EC Number:

236-757-0

EC Name:

2,2,4,6,6-pentamethylheptane

Cas Number:

13475-82-6

Molecular formula:

C12H26

IUPAC Name:

isododecane

Test material form:

liquid

Specific details on test material used for the study:

Stabilizer: hydrocarbon

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: mean body weight of 2.4 (+/- 0.1) kg
- Housing: The animals were housed individually in polystyrene cages (35 cm x 55 cm x 32 cm or 48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- Diet: 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France)
- Water: drinking water filtered by a F.G. Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least five days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 30 to 70%
- Photoperiod: 12 h/12 h

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: a single dose of 0.1 mL of the test item

Duration of treatment / exposure:

A single dose of 0.1 mL of the test substance was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball.

Observation period (in vivo):

The eyes were examined approximately one hour, 24, 48, 72 and 96 hours after administration of the test substance.

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
The test item was not washed out.

SCORING SYSTEM:
Ocular reactions were evaluated for each animal according to the following numerical scale:
2.5.1 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*
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 of lids and hairs adjacent to lids - 2
. discharge with moistening of lids and hairs on wide area around the eye - 3
2.5.2 Iris lesions
. normal - 0
. markedly deepened rugae, congestion, swelling, moderate circum-corneal hyper-aemia, 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*
2.5.3 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, one or two drops of 0.5% sodium fluorescein solution can be instilled into the eye (however, this must be performed before the 24-hour reading).
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 discernible 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

*indicates positive effect

TOOL USED TO ASSESS SCORE: Cornea lesions by direct examination or, if necessary, with an Ultra-Violet lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 96 hours

Irritant / corrosive response data:

Very slight chemosis and conjunctival redness were noted in 2/3 animals one hour after treatment only.
In the remaining animal, slight chemosis and very slight conjunctival redness were noted one hour after treatment and persisted for 24 hours; in addition, slight corneal opacity was noted 48 and 72 hours after treatment; reversibility of this latter ocular lesion was achieved after 96 hours.
The mean scores calculated over 24, 48 and 72 hours were 0.0, 0.0 and 0.7 for chemosis, 0.3 for conjunctival redness, 0.0 for iris lesions and 1.3 for corneal opacity.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under our experimental conditions, the test substance was considered non-irritant when administered by ocular route in rabbits.

Executive summary:

The potential of the test substance to induce ocular irritation was evaluated in rabbits according to OECD 405 and EC method B.5.

As no irritant effects were anticipated, a single dose of 0.1 mL of the test substance was introduced into the left conjunctival sac of three male New Zealand White rabbits. The right eye served as control. The test substance was used in its original form and the eyes were not rinsed after administration of the test substance. Ocular reactions were observed approximately one hour, 24, 48, 72 and 96 hours after the administration.

In 2/3 animals, a very slight conjunctival irritation (chemosis and redness) was noted only one hour after treatment.

In the remaining animal, a very slight or slight conjunctival irritation was noted one hour after treatment and persisted for 24 hours; in addition, a slight corneal opacity was observed only 48 and 72 hours after treatment.

The mean scores calculated over 24, 48 and 72 hours were 0.0 0.0 and 0.7 for chemosis, 0.3 for conjunctival redness, 0.0 for iris lesions and 1.3 for corneal opacity. Under our experimental conditions, the test substance was considered non-irritant when administered by ocular route in rabbits.