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Administrative data

Description of key information

A valid skin irritation/corrosion study and 2 eye irritation studies are available. In the study from 1999 with a test substance of high purity (99.7%) no eye irritation potential was found. In the older study with a purity of the test substance of 86.3 %, an eye irritation potential was found. Due to the negative results of the study of 1999 which used a test substance of high purity, the positive results of the study from 1992 are judged as caused by the impurities of the test substance used (purity 86.3). The study of 1992 is regarded as not assignable.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions (e.g. rel. low purity of test substance 86.3%)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: 84/449/EWG, B.4
GLP compliance:
yes
Species:
rabbit
Strain:
other: Small white Russians, Chbb: HM, SPF
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach
- Age at study initiation:
- Weight at study initiation: healthy, adult animals 2-3 kg
- Housing: animals were kept individually in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 14 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr):
- Photoperiod: artificial light, 12 hours light/dark cylce


I
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Moistening of the surface with completely deionized water.
Controls:
not required
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2, covered with gauze
- % coverage:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm water
- Time after start of exposure:up to 72 h


SCORING SYSTEM:
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: score = 0 at any time point
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: score = 0 at any time point
Other effects:
No skin irritations were observed.

The study showed that dermal application of 0.5 g of the solid test substance, while being wetted with completely de-ionized water, to three animals for 4 hours under semi-occlusive conditions did not lead to any skin irritations.

Interpretation of results:
GHS criteria not met
Conclusions:
No skin irritations were observed after application of the test substance to 3 animals for 4 hours.
Executive summary:

In a OECD Guideline study (404) with rabbits, the dermal application of 0.5 g of the solid test substance to three animals for 4 hours did not lead to any skin irritations (Hüls AG 1992c).

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: GLP and OECD Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: 92/69/EWG, B.5
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
Source: CHR. FRED Leuschner & CO., D-24601 Löhndorf/Post Wankendorf
- Weight at study initiation: 2.0-2.3 kg
- Acclimation period: at least 20 adaptation days
- Housing: single, in special restrainers which allowed free movement of the head
- Diet: ad libitum
- Water: ad libitum




Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
1 test day and a follow-up period of 72 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
TOOL USED TO ASSESS SCORE: fluorescein, fluorescein SE Thilo eye drops (Alcon Pharma GmbH, D-79108 Freiburg).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: score = 0 at any time point
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: score = 0 at any time point
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: score = 0 at any time point
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 2 days
Other effects:
Weiße Ablagerungen (möglicherweise Eiter) im Augenlid.
"ENGLISH"
Withish deposits (probably jus) in the conjunctival sac.

A single application of 100 mg Vulcuren Trial product KA 9188 per animal into the conjunctival sac of the right eye of three rabbits caused the following changes:

Cornea opacity (grad 1) was observed in animal no. 1 and 2 at the examination time points 1 and 24 hours after instillation. The effect was fully reversible within 24 h.

The iris and conjunctivae were not affected by instillation of the test compound.

In addition, whitish deposits (probably pus) were observed in the conjunctival sac in animal no. 2 and 3 24 and 48 hours after instillation.

There were no systemic intolerance reactions.

Interpretation of results:
GHS criteria not met
Conclusions:
Vulcuren Trial product KA 9188 was not irritating to the eyes.
Executive summary:

A single application of 100 mg Vulcuren Trial product KA 9188 per animal into the conjunctiva sac of the right eye of three rabbits caused very slightly cornea opacity effects (grad 1) in 2/3 animals 1 and 24 h after instillation (mean score 0.3). The effect was reversible within 24 hours. Based on these findings, the author assessed the test material Vulcuren Trial product KA 9188 as not irritating to eyes (LPT 1999).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

Non-human information

In an OECD Guideline study (404) with rabbits, the dermal application of 0.5 g of the solid test substance Vulcuren (purity: 86.3%) to three animals for 4 hours did not lead to any skin irritations (Hüls AG 1992c).

Human information

There are no human data available.

Eye

Non-human information

In an OECD Guideline study with rabbits, a single application of 100 mg Vulcuren (purity: 99.7%) caused very slightly cornea opacity effects (grad 1) in 2/3 animals, 1 and 24 h after instillation (mean score 0.3). The effects were reversible within 24 hours. Based on these findings, the author assessed the test material Vulcuren (purity: 99.7%) as not irritating to eyes (LPT 1999).

Human information

There are no human data available.

Respiratory tract

Non-human information

There are no non-human data available.

Human information

There are no human data available.

Summary and discussion of irritation

In conclusion, Vulcuren (purity: 86.3%) showed no skin irritating potential in an OECD Guideline study with rabbits (Hüls AG 1992). In addition, only very slightly and transient eye irritating effects were seen after application of Vulcuren (purity: 99.7%) in the conjunctiva sac of rabbits (LPT 1999).

Corrosivity

Non-human information

The test substance is not corrosive (see above).

Human information

There are no human data available.

Summary and discussion of corrosion

The test substance is not corrosive (see above).


Justification for selection of skin irritation / corrosion endpoint:
key study is used

Justification for selection of eye irritation endpoint:
the study with the higher purity of the test substance (key study) is used.

Justification for classification or non-classification

Vulcuren (purity: 86.3%) showed no skin irritating potential in an OECD Guideline study with rabbits (Hüls AG 1992). In addition, only very slightly and transient eye irritating effects were seen after application of Vulcuren (purity: 99.7%) in the conjunctiva sac of rabbits (LPT 1999).

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Respiratory irritation: There are no data available.

Corrosion: The test substance is not corrosive (see above).