Registration Dossier

Administrative data

Description of key information

Based on the results obtained from testing the substance was not considered to be irritating to skin or eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-07-18 until 1995-07-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Stabilizer: hydrocarbon
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: on the day of treatment, the animals had a mean body weight (and standard deviation) of 2.3 (0.1) kg
- Housing: The animals were housed individually in polystyrene cages
- Diet: All the animals had free access to 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: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Photoperiod: 12 h/12 h
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated skin served as control
Amount / concentration applied:
A single dose of 0.5 mL of the test substance was applied
Duration of treatment / exposure:
3 minutes and 4 hours
Observation period:
1, 24, 48, 72 hours after application. One animal was observed after 96 hours.
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'Hygiène, 21300 Chenove, France) and a restraining bandage (Laboratoires 3M Santé, 92245 Malakoff, France).
No residual test substance was noted at removal of the dressing.

SCORING SYSTEM:
Erythema and eschar formation:
no erythema...0
very slight erythema (barely perceptible)...1
well-defined erythema...2
moderate to severe erythema...3
severe erythema (beet redness) to slight eschar formation (injuries in depth)...4

Oedema formation:
no oedema...0
very slight oedema (barely perceptible)...1
slight oedema (edges of area well-defined by definite raising)...2
moderate oedema (raised approximately 1 millimetre...3
severe oedema (raised more than 1 millimetre and extending beyond area of exposure)...4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 96 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After a 3-minute application: in one rabbit, very slight erythema (grade 1) was noted on days 2 and 3.
After a 4-hour application: in 2/3 rabbits, very slight erythema (grade 1) was observed for 24 or 48 hours after treatment. In one of these two rabbits, slight oedema (grade 2) was noted only one hour after treatment. In 1/3 animals, very slight to slight erythema (grade 1 or 2) was noted up to 72 hours.
Mean scores over 24, 48 and 72 hours for individual animal were 1.7, 0.7 and 0.3 for erythema, and 0.0 for oedema.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study experimental conditions, the test substance was considered non-irritant when administered by cutaneous route in rabbits.
Executive summary:

The potential of the test substance to induce dermal irritation was evaluated in rabbits according to the OECD 404 and EU method B4 guidelines. The test substance was applied in a first assay for a period of 3 minutes and 4 hours in one male New Zealand White rabbit.

Since the test substance was not strongly irritant in this first assay, it was applied for 4 hours in two other males in a second assay. A single dose of 0.5 mL of the test substance was applied to the closely-clipped skin of the flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately one hour, 24, 48 and 72 hours after removal of the dressing and then at 96 hours only for one rabbit.

Very slight to slight erythema was observed in the three animals until day 2, 3 or 4, respectively. In one rabbit, slight oedema was noted only one hour after treatment. Mean scores over 24, 48 and 72 hours for individual animal were 1.7, 0.7 and 0.3 for erythema and 0.0 for oedema.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Stabilizer: hydrocarbon
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
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
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
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
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

- Key study

The potential of the test substance to induce dermal irritation was evaluated in rabbits according to the OECD 404 and EU method B4 guidelines. The test substance was applied in a first assay for a period of 3 minutes and 4 hours in one male New Zealand White rabbit.

Since the test substance was not strongly irritant in this first assay, it was applied for 4 hours in two other males in a second assay. A single dose of 0.5 mL of the test substance was applied to the closely-clipped skin of the flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately one hour, 24, 48 and 72 hours after removal of the dressing and then at 96 hours only for one rabbit.

Very slight to slight erythema was observed in the three animals until day 2, 3 or 4, respectively. In one rabbit, slight oedema was noted only one hour after treatment. Mean scores over 24, 48 and 72 hours for individual animal were 1.7, 0.7 and 0.3 for erythema and 0.0 for oedema.

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

 

- Disregarded study

The potential of the test item to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 mL of the test material to the closely-clipped dorsum of one New Zealand White rabbit for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours and six, nine, twelve and fifteen days after removal of the dressings.

Severe oedema was observed one hour after bandage removal. At the 24 hour examination, very slight erythema and slight oedema were observed, continuing to the 72 hour examination. On the sixth day, well-defined erythema and very slight oedema and loss of elasticity and flexibility were observed. The skin of the test site appeared to be thickened from the ninth day.

The animal was killed after the last examination and subjected to a post mortem examination; the skin of the test site was approximately twice the thickness of the control site. As only one animal was investigated, this study is not suitable for hazard assessment and classification and labelling and was not considered.

 

Eye irritation

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

 

Respiratory irritation

TBPIB did not cause local irritancy in the respiratory tract (see acute inhalation study, IUCLID section 7.2.2).

Justification for classification or non-classification

Based on the results obtained from testing tert-butyl peroxyisobutyrate was not classified according to Regulation (EC) No 1272/2008 (CLP).