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Administrative data

Description of key information

The test substance was found to cause minimal irritation when applied to intact and abraded rabbit skin. The treatment resulted in very slight transient erythema and very slight transient edema. The test item is therefore regarded as non-irritating to the skin. Irritative effects to the eye were partially not reversible.

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:
12.07.82 - 19.07.82
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The animals were exposed under occlusion for 24 hours (instead of 4 hours under semi-occlusion: OECD404). This represents a worst case situation.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: male/female
- Source: Kleintierfarm Madoerin AG, CH4414, Fuellinsdorf
- Age: not indicated
- Weight at study initiation: 2-3 kg
- Housing: individually in metal cages.
- Diet: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
7 days
Number of animals:
3/sex
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm on the back
The shaven skin on one side was slightly scarified with the help of a "Schroepfschnaepper", Aesculap, Switzerland.
- Type of wrap if used: The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not indicated

SCORING SYSTEM: similar to OECD404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
other: intact skin
Irritant / corrosive response data:
Minimal erythema formation were observed (maximum score of 1) in 4/6 animals, reversible within 72 hours the latest. Minimal edema formation were observed (maximum score of 1) in 2/6 animals, reversible within 48 hours the latest. Exposure of the abraded skin gave similar results.
Other effects:
none reported
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating
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:
January 19, 1984 - February 13, 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414, Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2070-2180 g
- Housing: individually in metal cages
- Diet: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
Observation times: 1, 24, 48 and 72 hours, 7 days and 21 days after instillation
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: according to OECD guideline 405

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: corrosion observed in 2/3 animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: corrosion was reversed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
48 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
48 h
Score:
1.7
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
1.3
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
1.7
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
21 d
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
48 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
Irritation response was already observed 1 hour after instillation of the test article (mean scores of 2.3, 3.3, 2 and 0.7 for conjunctivae, chemosis, cornea and iris, respectively). After 72 hours corrosion of conjunctiva was observed in 2 animals which was no longer recorded at the 7 days observation point. All effects were reversible within 21 days except for cornea effects in 2/3 animals, which was still available at scores of 1 and 2, respectively.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Serious eye damage
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In the key study the test substance was investigated for skin irritation in rabbits in a test similar to OECD testing guideline 404. The protocol differed by additional testing of abraded skin versus intact skin and a prolonged exposure time of 24h was used. Observation was terminated after 7 days which is acceptable as no indication of erythema or erythema was observed during the observation period. Only minimal erythema and edema reactions well below the threshold of significance were observed. Based on the results of this study, the test article is considered to be not irritating to the rabbit skin. This result is confirmed by additional supporting studies showing the same result.

Eye irritation

An acute eye irritation study following OECD guideline 405 was performed using three New Zealand White Rabbits. An amount of 0.1 g of the test article was placed into the conjunctival sac of the right eye of each animal, the left eye remained untreated and served as the control. The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period by means of a slit-lamp. Under the conditions of the present experiment the test article was found to be irritating and corrosive when applied to the rabbit eye mucosa. All effects were reversible within 21 days except for cornea effects in 2/3 animals, which was still available at scores of 1 and 2, respectively on day 21. In three supporting studies the test substance showed a similar ocular irritation potency.

Justification for classification or non-classification

There are conclusive but not sufficient data for classification of the test item with regard to skin irritation

The test item is not classified for this endpoint in accordance to Directive 67/548/EEC or the CLP Regulation (EC) No 1272/2008 as well as GHS regulations. However, the test substance has to be classified as eye damaging.