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Description of key information

In an in vivo skin irritation assay conducted in accordance with OECD test guideline 404, the target substance OO-tert-butyl monoperoxymaleate (98% purity) was applied to the skin of young adult White New Zealand male rabbits for 4 hours. The target substance was non-irritating to the skin.

The eye irritation potential of OO-tert-butyl monoperoxymaleate was examined in an in vivo study conducted in accordance with OECD 405. In this study, the target substance (98% purity) was applied into the conjunctival sac of one eye of young adult White New Zealand rabbits (three males) for 24 hours. In this study, OO-tert-butyl monoperoxymaleate induced irreversible damage to the eye and must be therefore considered as corrosive to the eye.

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:
1993-01-12 to 1993-05-28
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:
Version from May 12, 1981
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
EEC Publication No. L251, September 1984
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
The powdery test substance was moistened with distilled water, immediately before application, to ensure close contact to the animal's skin.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren , The Netherlands
- Age at study initiation: Approx. 12 weeks
- Weight at study initiation: 2312 - 2533 grams
- Housing: Individually in label led cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen , The Netherlands)
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm , Hope Farms, Woerden , The Netherlands) approx. 100 gram per day.
- Water (e.g. ad libitum): Free access to tap-water dil uted with decalcified water .
- Acclimation period: Seven days before start of treatment under test conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21.5°C
- Humidity (%): 25-50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
The powdery test substance was moistened with distilled water, immediately before application
Controls:
yes, concurrent negative control
Amount / concentration applied:
0.5 gram of the test substance
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal fur, exposing area of approx. 150 square centimeters
- Type of wrap if used: Scotchpaknon-woven patch (2x3 cm, 3M, St.Paul, U.S.A.) mounted on Micropore tape (3M, St. Paul, U.S.A .).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 4 hours, the dressing was removed and the remaining test substance removed using a tissue moistened with tap-water and subsequently a dry tissue

OBSERVATION TIME POINTS
-1, 24, 48 and 72 h after removal of the dressings and remaining test substance

SCORING SYSTEM:
- Scoring system: see table 1 in "Any other information on materials and methods incl. tables"
- Method of calculation: A primary irritation index was calculated by combining the average skin, the degree of irritation can be obtained by the primary irritation index (see table 2 in "Any other information on materials and methods incl. tables) as well as irritation scores for erythema and oedema after 24 and 72 hours . Using the table of primary irritation index (see table 2, chapter "Any other information on materials and methods incl. tables), the degree of irritation was obtained (Draize, J.H. , Woodard, G. and Calvery, H.O., 1944) .

Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
No skin irritation and corrosion was caused by the test substance after a 4 h dermal application. No staining of the treated skin by the test substance was observed.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Table 3: Individual skin irritation scores

Animal No.1, Skin Irritation Scores Post-Application after
Observation 24 h 48 h 72 h average score (24, 48 and 72 hours)
Erythema 0 0 0 0
Oedema 0 0 0 0
Animal No.2, Skin Irritation Scores Post-Application after
Observation 24 h 48 h 72 h average score (24, 48 and 72 hours)
Erythema 0 0 0 0
Oedema 0 0 0 0
Animal No.3, Skin Irritation Scores Post-application after
Observation 24 h 48 h 72 h average score (24, 48 and 72 hours)
Erythema 0 0 0 0
Oedema 0 0 0 0
Interpretation of results:
GHS criteria not met
Conclusions:
In an in vivo acute skin irritation/corrosion study in rabbits according to OECD 404, OO-tert-butyl monoperoxymaleate did not produce any irritating effects.
Executive summary:

In a primary dermal irritation study (OECD 404), young adult White New Zealand male rabbits were dermally exposed to 0.5 gram OO-tert-butyl monoperoxymaleate (98% purity) moistened with distilled water for 4 hours to 150 square centimetres body surface. 4 hours after application, the dressing and the remaining substance has been removed from the skin. Animals then were observed for 72 h. Irritation was scored by the method of Draize. No skin irritation nor corrosion was caused by the test substance after a 4 h dermal application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Under the condition of the present study, no skin irritation or corrosion was caused by OO-tert-butyl monoperoxymaleate after a 4 h dermal application. In this study, OO-tert-butyl monoperoxymaleate is not irritating to the skin according to CLP criteria.

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:
1993-01-18 to 1993-05-28
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:
Version 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Directive 84/449/EEC
Version / remarks:
EEC Publication No. L. 251, September 1984
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the powdery test substance was instilled as delivered by the sponsor
Species:
rabbit
Strain:
New Zealand White
Remarks:
SPF Quality
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 13 weeks
- Weight at study initiation: 2419 - 2732 grams
- Housing: Individually labelled cages with perforated floors and equipped with an automatic drinking system. Standard laboratory conditions
- Diet (e.g. ad libitum): standard laboratory rabbit diet (LKK-20 pellet diameter 4 mm)
- Water (e.g. ad libitum): free access to tap-water diluted with decalcified water
- Acclimation period: 14 days before start of treatment under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 55%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h dark, 12 h light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 48 mg

Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): in day 2 after fluorescein examination, both eyes of all three animals were rinsed with approx. 50 ml tap-water per eye, using a velocity of flow which did not affect the eyes, to remove residual test substance.

SCORING SYSTEM: Scoring system for ocular lesions see chapter "Any other information on materials and methods"

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
21 d
Score:
1
Max. score:
1
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
21 d
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
21 d
Score:
1
Max. score:
1
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
21 d
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
21 d
Score:
1
Max. score:
1
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
Corneal opacity, varying from grade 1-3, was observed in animals 2 and 3 during the study, which persisted up to termination of the study {day 22). From day 15 onwards pannus formation (neovascularisation of the cornea) was seen in these two animals. In animal 1 slight dulling of normal lustre of the cornea was observed from day 2 until day 8. Treatment of the eyes with 2% fluorescein, 24 hours after instillation, revealed corneal epithelial damage in all animals. At following treatments with fluorescein, signs of recovery were noted in all animals and the corneal epithelial damage had completely resolved within 14 days after instillation in animal 1. In animals 2 and 3 the epithelial damage had not resolved on day 22.
The iridic irritation had resolved within 7 days after instillation in all three animals.
Moderate to severe irritation of the conjunctivae was observed in all animals over the first week. Recovery was noted from day 15 onwards, but the irritation had not completely resolved at day 22. Reduced elasticity of the eyelids, a reduction of the size of the pupil in the treated eye and/or gray/white discoloration of the conjunctivae, as a sign of necrosis, were observed in animals 2 and 3 during the study.
For more detailed information on the individual response please see Table 2 in "Any other information on results.
Other effects:
After the 24 hour observation the eyes were rinsed with water to remove remnants of the test substance. However the test substance could only be partly removed, which might have influenced further effects.
No systemic toxicity were observed in the animals during the test period and no mortality occurred.

Table 2: Individual Irritation Scores

Animal No. 1 Eye Irritation Scores Post-Application after
Observation 24 h 48 h 72 h average score (24, 48 and 72 h) 21 days after administration
Cornea - opacity 0 0 0 0,0 0
Iris 1 1 1 1,0 0
Conjunctivae redness 2 3 3 2,7 1
Conjunctivae chemosis 4 3 3 3,3 0
Animal No. 2 Eye Irritation Scores Post-Application after
Observation 24 h 48 h 72 h average score (24, 48 and 72 h) 21 days after administration
Cornea - opacity 2 2 2 2,0 2
Iris 1 1 1 1,0 0
Conjunctivae redness 3 3 3 3,0 1
Conjunctivae chemosis 3 2 2 2,3 0
Animal No. 3 Eye Irritation Scores Post-Application after
Observation 24 h 48 h 72 h average score (24, 48 and 72 h) 21 days after administration
Cornea - opacity 2 1 1 1,3 2
Iris 1 1 1 1,0 0
Conjunctivae redness 3 3 3 3,0 1
Conjunctivae chemosis 3 2 2 2,3 0
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an in vivo acute eye irritation/corrosion study in rabbits according to OECD 405, OO-tert-butyl monoperoxymaleate produced corrosive effects.
Executive summary:

In a primary eye irritation study according to OECD 405, 48 mg of OO-tert-butyl monoperoxymaleate (98% purity) was instilled into the conjunctival sac of one eye of three male New Zealand White Rabbits (13 weeks old) for 24 h. Both eyes were washed with tap-water after 24 h of exposure. Animals were observed for 21 days with examination at 1, 24, 48, 72 h and 7, 14 and 21 days after test substance administration. Eye lesions were scored by the method of Draize.

Under the conditions of the present study, a single ocular application of the test item to rabbits produced adverse effects on cornea, iris and conjunctivae in all animals. The corneal injury persisted at termination of the study in two animals. The iridic irritation had resolved within 7 days after instillation in all three animals. The irritation of the conjunctivae had not resolved completely at termination of the study in all three animals. Neither mortalities nor clinical signs of toxicity were observed.

In this study, OO-tert-butyl monoperoxymaleate is corrosive to the eye and does warrant for classification as Eye Dam. Category 1 according to CLP criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an in vivo skin irritation assay conducted in accordance with OECD test guideline 404, the target substance OO-tert-butyl monoperoxymaleate (98% purity) was applied to the skin of young adult White New Zealand male rabbits for 4 hours. The target substance was non-irritating to the skin.

The eye irritation potential of OO-tert-butyl monoperoxymaleate was examined in an in vivo study conducted in accordance with OECD 405. In this study, the target substance (98% purity) was applied into the conjunctival sac of one eye of young adult White New Zealand rabbits (three males) for 24 hours. In this study, OO-tert-butyl monoperoxymaleate induced irreversible damage to the eye and must be therefore considered as corrosive to the eye.

Justification for classification or non-classification

The target substance did not cause any skin effects in an acute dermal irritating study conducted according to OECD test guideline 404. Therefore, the target substance does not warrant classification for skin irritation.

In contrast, the test item was severely irritating to the eyes of rabbits in an OECD 405 study. The application of the substance to the eye of rabbits led to an irreversible effect within the 21 days observation period. Therefore, the test item meets the classification criteria according to the CLP regulation. The target substance is classified for irreversible effects on the eye (Category 1, H318).