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Description of key information

Skin irritation: OECD Guideline 404 and EU Method B.4. GLP study. The test item was determined to be not irritating to the skin. Test performed with 3 New Zealand White rabbits for which the observed effects were: mean 24 -72 erythema scores of 1.7, 0.0 and 0.0 and mean 24 -72h oedema scores of 0.0, 0.0, 0.0.

Eye irritation: OECD Guideline 405 and EU Method B.5. GLP study. The test item was determined to be not irritating to eye. Test was performed with 3 New Zealand Whithe rabbits for which the observed effects were: mean 24 -72h scores of corneal opacity, iris and chemosis of conjuctiva as 0.0 for all three animals; mean 24 -72h scores of redness of conjuctiva was 0.0 for one animal and 0.3 for the other two (fully reversible after 48 hour).

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:
15 March 1994 - 25 March 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K. Thomae. 88400 Biberach.
- Age at study initiation: About 3-5 months.
- Weight at study initiation: 2.6-2.7 kg
- Housing: In fully air-conditioned rooms, separate cages.
- Diet (e.g. ad libitum): Ad libium
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 ºC
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: PEG 400
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 0.5 g test item in 0.1 mL PEG 400 (5 g/mL)
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Application: Cellulose patch on a piece of surgical plaster.
- Type of wrap if used: Semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With warm tap water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
30-60 minutes, 24, 48 and 72 hours after removal and after 7 days.

SCORING SYSTEM:
- Method of calculation: Eythema, eschar formation and oedema were evaluated numerically according to the technique of DRAIZE. All other changes of the skin were recorded.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
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:
24/48/72 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:
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:
From 30 minutes up to 72 hours after removal of the patches one animal showed a very slight to well-defined erythema, which was fully reversible after 7 days. 30 minutes after removal all the patches a barely perceptible erythema was noted at the skin of another animal 24 hours p.a. the irritation was reversible. No irritation was observed at the skin of the 3rd animal.
Other effects:
- Other adverse local effects: No.
- Other adverse systemic effects: No.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was determined to be not irritating to the skin.
Executive summary:

An in-vivo skin irritation test was performed according to OECD Guideline 404 and EU Method B.4 (GLP study). About 24 hours before the start of the study the hair in the dorsal region of the body of 3 New Zealand White rabbits was removed with an electric clipper. Each animal was treated with 0.5 g test item pasted with 0.1 mL PEG 400. The substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area and the covered with a semi-occlusive bandage. After 4 hour of exposure, all remmanents were carefully removed from the skin with warm tap water. Examinations of the skin took place after 30 -60 minutes, 24, 48 and 72 hours and 7 days after removal. Erythema and oedema were evaluated numerically according to the technique of DRAIZE. From 30 minutes up to 72 hours after removal of the patches one animal showed a very slight to well-defined erythema (24 -72h mean erythema score of 1.7 and oedema score of 0.0), which was fully reversible after 7 days. 30 minutes after removal all the patches a barely perceptible erythema was noted at the skin of another animal 24 hours p.a. the irritation was reversible (24 -72h mean erythema and oedema score of 0.0). No irritation was observed at the skin of the 3rd animal. Based on the results of this study, the test item was not irritating to the skin.

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:
19 April 1994 - 29 April 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K. Thomae. 88400 Biberach.
- Age at study initiation: About 3-5 months
- Weight at study initiation: 2.8-3.3 kg
- Housing: In fully air-conditiones rooms, separate cages.
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 ºC
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg test item.
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): With isotonic saline at approx. 37 ºC.
- Time after start of exposure: 24 hours.

SCORING SYSTEM: The eyes were examined 1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after installation of one drop of 0.01% fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded.

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:
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
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
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:
One hour p.a. the conjuctiva of the animals showed slight swelling as well as up to 24 hours p.a. definitely injected blood vessels to diffuse deeper crimson red colour. 48 hours p.a. the irritations were reversible. Additional a clear colourless discharge was observed.
Other effects:
- Lesions and clinical observations: No.
- Effects of rinsing or washing: No.
- Other effects: A clear colourless discharge was observed.
Interpretation of results:
GHS criteria not met
Conclusions:
Testing of test item for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.
Executive summary:

An in-vivo eye irritation test was performed according to OECD Guideline 405 and EU Method B.5 (GLP study). 100 mg of test item was applied once to the conjuctival sac of the left eye of tree rabbits. 24 hours after application and at all the other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out throughly with isotonic saline at approx. 37 ºC. The eyes were examined 1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours the eyes were also examined for corneal lesiones under UV light after installation of one drop of 0.01% fluorescein-sodium solution. Lesions in cornea, iris or conjuctivae were graded numerically. One hour p.a. the conjuctiva of the animals showed slight swelling as well as up to 24 hours p.a. definitely injected blood vessels to diffuse deeper crimson red colour. 48 hours p.a. the irritations were reversible (mean 24 -72h scores of corneal opacity, iris and chemosis of conjuctiva as 0.0 for all three animals; mean 24 -72h scores of redness of conjuctiva was 0.0 for one animal and 0.3 for the other two). Additional a clear colourless discharge was observed. Based on these results, the test item was determined to be not irritating to the eye.

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

Skin irritation: Based on the available data (mean scores of < 2,3 for erythema/eschar or for oedema), the substance is not classified for skin irritation according to the CLP Regulation (EC) no. 1272/2008.

Eye irritation: Based on the available data (mean scores of <1 for corean opacity or iritis and <2 for conjunctival redness or oedema), the substance is not classified for eye irritation according to the CLP Regulation (EC) no. 1272/2008.

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