Registration Dossier

Administrative data

Description of key information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP.
Qualifier:
according to guideline
Guideline:
other: EC directive 92/69, method B.4.
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Supplier: Charles River Wiga GmbH, D-97633 Sulzfeld.
Number and sex: 3 females.
Body weight (at the start and at the conclusion of the test): 2.4 to 2.7 kg, respectively 2.4 to 2.9 kg
Animal maintenance:
Hygiene: improved conventional conditions.
Room temperature: average of 19.5 °C.
Relative humidity: average of 50 %.
Air exchange: 12 per hour.
Light: artificial light from 6 a.m. to 6 p.m.
Cages: individual caging in metal wire cages.
Feed: Altromin 2023 diet for rabbits, ad libitum.
Water: tap water from an automatic watering system, ad libitum.
Acclimatization: 6 days.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
500 mg, soaked with 1.5 mL distilled water.
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h after patch removal.
Number of animals:
3
Details on study design:
Hair was clipped on the dorsal area of the trunk one day before the application of the test substance. An electric hair clipper with a 1 mm cutterhead was used. The test site was median on the dorsal thoracal region.
A cellulose patch with 0.5 g of the test substance (actual concentrations: 496, 504 and 498 mg), spread over an area of approximately 6 cm2 and soaked with 1.5 ml distilled water, was applied to the test site and held in place by fixing marginally with non irritating tape. The application site was covered by a dressing. Access by the animal to the application site was prevented by a plastic collar.
The duration of exposure was 4 hours.
At the end of the exposure period the dressing, the tape with the patch and the collar were removed. Residual test substance was wiped off using wet cellulose tissue.
Irritation parameter:
erythema 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:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 1 day
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
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:
edema score
Basis:
animal #2
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:
Reversibility of any observed effect: Changes fully reversible until 48 h p.a.
Other effects:
No other local or general findings were noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not classified as irritant.
Executive summary:

The test substance was applied to the intact skin of each of 3 rabbits. The animals were examined for local reactions and for general signs. Methods and investigations were performed according to the OECD Guideline 404 and the EC method B.4.

Only slight erythema were observed in one rabbit at 1 and 24 h p.a. The test substance is not classified as irritant.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Supplier: Charles River Wiga GmbH, D-97633 Sulzfeld.
Number and sex: 3 females.
Body weight (at the start and at the conclusion of the test): 2.5 to 2.8 kg, respectively 2.6 to 3.1 kg
Animal maintenance:
Hygiene: Optimal hygienic conditions.
Room temperature: average of 20 °C.
Relative humidity: average of 61 %.
Air exchange: 12 per hour.
Light: artificial light from 6 a.m. to 6 p.m.
Cages: individual caging in metal wire cages.
Feed: Altromin 2023 diet for rabbits, ad libitum.
Water: tap water from an automatic watering system, ad libitum.
Acclimatization: 5 to 12 days.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL equivalent.
Duration of treatment / exposure:
Test substance instillation
The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent a loss of test substance. The weighed amounts of the individual doses were 68, 68 and 66 mg.
The left eyes remained untreated and served as a control.

Observation period (in vivo):
Eye examinations
Both eyes of the animals were examined within 24 hours before the instillation and approximately I, 24, 48 and 72 hours p.a.. The whole eyes, especially the corneae, the irises and the conjunctivae were examined, using an otoscope lamp.
Number of animals or in vitro replicates:
3
Details on study design:
The test substance was dosed first to one animal. As no evidence for a serious damage to the eye of this animal was found until 72 h p.a. (no corrosive effect), the test substance was administered to the other two animals too.

The animals were observed for other than local changes at all observation times too.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
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:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 3 days
The untreated eyes were normal at each observation time.
Other effects:
No other local or general findings were noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not regarded as irritating to eyes.
Executive summary:

The test substance was applied to the intact test eye of each of 3 rabbits. The animals were examined for local reactions and for general signs. Methods and investigations were performed according to the OECD Guideline 405 and the EC method B.5.

Only slight redness was observed in one rabbit at 24 h and 48 h p.a. The test substance is not classified as irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

No classification is derived from the results.