Registration Dossier

Administrative data

Description of key information

the test item is not irritating to the skin and severely damaging the eyes of rabbits

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:
1998
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
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CHR. Fred Leuschner & Co., 24601 Löhndorf/Post Warendorf, Germany
- Age at study initiation: 4-6 months
- Weight at study initiation: 2.3 - 2-4 kg
- Acclimation period: at least 20 days

IN-LIFE DATES: From: 1998-01-29 To: 1998-02-01
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Remarks:
pasted with water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg per patch
Duration of treatment / exposure:
4 hour(s)
Observation period:
Scores were taken 60 min, 24, 48, and 72 hours after patch removal. Skin reactions were monitored until the changes observed have completely subsided, however not for more than 14 days after application.
Number of animals:
3
Details on study design:
The fur was removed by shaving the dorsal area of the trunk of 3 rabbits 24 hours prior to use. Only animals with healthy skin were used.
A dose of 500 mg was applied to the test sits (pulverized test substance moistened with water) and then covered with a gauze patch held in place with a semi-occlusive dressing. After 4 hours, the patches were removed and each site was assessed; the severity of the reaction was recorded 60 min, 24, 48, and 72 hours after patch removal.

- Scoring system: score range 0 - 4 for erythema and eschar formation; score range 0-4 for oedema formation; if other lesions occur, they will be listed


Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No redness or swelling was observed on the skin of any of the 3 rabbits 60 min, 24, 48, and 72 hours after exposure to the test material. Therefore, the primary irritation score was 0.0.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was classified as not irritating to rabbit's skin on the basis of the scores which were 0.0 out of a possible 4.
Executive summary:

In a skin irritation test performed according to OECD 404 none of the three rabbits exposed for 4 hours under semi-occulsive conditions to the test substance showed any skin reaction (score 0.0 for erythema and edema). Thus, the test substance is not irritating to the skin of 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
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
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1992
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Chr. Fred Leuschner & Co., 24601 Lohndorf/Post Wankendorf, Germany
- Age at study initiation: approx. 6.5 months
- Weight at study initiation: 2.9 - 3.0 kg
- Acclimation period: at least 20 days

IN-LIFE DATES: From: 1998-02-02 To: 1009-02-24
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
after administering the test item into the conjunctival sac of the right eye of 3 rabbits the lid was then gently held together for about one second in order to prevent loss of the test material
Observation period (in vivo):
up to 21 days post-instillation
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and also 1, 24, 48, 72 hours and 4 to 21 days after the administration. The eye reactions were observed and registered.
24 hours, 7, 14, and 21 days after administration the eyes were treated additionally with fluorescein and examined.
Eyes are monitored until the changes obsered have completely subsided, however for not more than 21 days after application.

SCORING SYSTEM:
Cornea opacity: score range 0-4
Iris: score range 0-2
conjunctivae redness: score 0-3
conjunctivae chemosis: score 0-4
any further lesions are listed.

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: up to day 21
Score:
> 4
Max. score:
4
Reversibility:
not reversible
Remarks:
within 21 days
Remarks on result:
probability of severe irritation
Remarks:
in the first 9 days score 1-2, increasing to score 3 at days 10-14 and to score 4 at days 15-19; thereafter the cornea appeared destroyed
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: up to day 21
Score:
> 2
Max. score:
2
Reversibility:
not reversible
Remarks:
within 21 days
Remarks on result:
probability of severe irritation
Remarks:
in the first 9 days score 1, increasing to score 2 at days 10-19; thereafter the cornea appeared destroyed
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Time point:
other: up to day 21
Score:
>= 0 - <= 1
Max. score:
3
Reversibility:
not reversible
Remarks:
within 21 days
Remarks on result:
probability of severe irritation
Remarks:
in the first 3 days score 0; on days 4-19 whitish deposits were seen in the conjunctival sac (probably pus) with temporarily slight reddening; thereafter the cornea appeared destroyed
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
other: up to day 21
Score:
>= 2
Max. score:
4
Reversibility:
not reversible
Remarks:
within 21 days
Remarks on result:
probability of severe irritation
Remarks:
score 2-3 on days 1-19; thereafter the cornea appeared destroyed
Irritant / corrosive response data:
Severity of eye irritation increasing with time after exposure with maximal scores of 4 for erythema, 2 for iritis, 1 for redness (with whitish deposits in the conjunctival sac, probably pus), and 3 for edema. At day 20 the cornea appeared destroyed and evaluation was not possible any more.
Other effects:
There were no systemic intolerance reactions.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance severely damages the eye of rabbits.
Executive summary:

In an eye irritation study performed according to OECD 405 on three rabbits the severity of eye irritation increased with time after exposure. Maximal scores of 4 for erythema, 2 for iritis, 1 for redness (with whitish deposits in the conjunctival sac, probably pus), and 3 for edema. At day 20 the cornea appeared destroyed and evaluation was not possible any more. The effects showed no reversibility within the observation period of 21 days. The test substance is thus severely damaging the eyes of rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a skin irritation test performed according to OECD 404 none of the three rabbits exposed for 4 hours under semi-occulsive conditions to the test substance showed any skin reaction (score 0.0 for erythema and edema). Thus, the test substance is not irritating to the skin of rabbits.

In an eye irritation study performed according to OECD 405 on three rabbits the severity of eye irritation increased with time after exposure. Maximal scores of 4 for erythema, 2 for iritis, 1 for redness (with whitish deposits in the conjunctival sac, probably pus), and 3 for edema. At day 20 the cornea appeared destroyed and evaluation was not possible any more. The effects showed no reversibility within the observation period of 21 days. The test substance is thus severely damaging the eyes of rabbits.

Justification for classification or non-classification

Based on a study on rabbits following OECD 404 no irritation is warranted for skin irritation.

Based on a study on rabbits following OECD 405 the test substance should be regarded as severely damaging the eye (Eye Damage 1, H319) according to EC 1272/2008.