Registration Dossier

Administrative data

Description of key information

The test substance was found to be not irritating or corrosive to the skin and the eye.

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: Males: 15 weeks, Female: 16 weeks
- Weight at study initiation: Males: 2.6 - 2.8 kg, Female: 3.0 kg
- Housing: Individually in stainless steel cages equipped with an automatic cleaning and drinking system.
- Diet: Pelleted standard Kliba 341, batch 52/90 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum
- Water: Community tap water from Itingen ad libitum
- Acclimation period: Four days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
Test material was applied moistened in distilled water
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours
Number of animals:
3; 2 males and 1 female
Details on study design:
Approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm). The skin of the animals was observed 1 day prior to test article administration. On test day 1, 0.5 g of the test article was applied to approx. 6 cm2 of the intact skin of the shaved area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water. The skin reaction was assessed at 1, 24, 48 and 72 hours intervals after the removal of the dressing, gauze patch and test article.
Irritation parameter:
other: Primary Irritation Score
Basis:
mean
Time point:
other: Average 24, 48, and 72 hours
Score:
0
Max. score:
8
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hrs
Score:
0
Max. score:
4
Irritant / corrosive response data:
Irritation: FAT 40'400/A showed a primary Irritation score (24,48,72 hours) of 0.00 when applied to intact rabbit skin. Local signs (mean 1 hour to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.
Corrosion: No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Other effects:
Coloration: In the area of application yellowish staining of the treated skin by pigment or coloring of the test article was observed in all animals between 1 to 72 hours (termination).
Body weights: The body weight gain of all rabbits was similar.
Toxic symptoms/mortality: No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.
Executive summary:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the treated skin was flushed with water and observation were made for an additional 72 hours. The test substance showed a primary Irritation score (24,48,72 hours) of 0.00 and local signs (1 hour to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No corrosive effect was evident on the skin. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

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 compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: Males: 15 weeks, Female: 16 weeks
- Weight at study initiation: Males: 2.7 kg, Female: 2.5-2.7 kg
- Housing: Individually in stainless steel cages equipped with an automatic cleaning and drinking system (Dipl. Ing. W. Ehret GmbH, Versuchstiertechnik, D-7830 Emmendingen).
- Diet: Pelleted standard Kliba 341, batch 52/90 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum
- Water: Community tap water from Itingen ad libitum
- Acclimation period: Four days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
up to 72 hours
Number of animals or in vitro replicates:
3; 1 male, 2 females
Details on study design:
The eyes of the animals were observed one day prior to test article administration. The test article (0.1 g) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control. The eyes of each animal were examined 1, 24, 48 and 72 hours after administration. The irritation was assessed and the corrosive properties of the test article and the staining of the treated eye were described and recorded.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
other: Primary Irritation Score
Basis:
mean
Time point:
other: Average 1, 24, 48, 72 hours
Score:
0
Irritant / corrosive response data:
Irritation: FAT 40'400/A showed a primary irritation score of: 0.00 when applied to the conjunctival sac of the rabbit eye.
Corrosion: No corrosion of the cornea was observed at any of the measuring intervals.
Other effects:
Toxic symptoms/mortality: No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.
Coloration: Yellow staining of the eyelashes of the treated eyes by pigment or coloring of the test article was observed in all treated animals throughout the 72-hour observation period.
Body weights: The body weight gain of all rabbits was similar.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.
Executive summary:

In a GLP compliant eye irritation study, performed according to OECD guideline 405, the test substance (0.1 g) was placed in the conjunctival sac of the left eye of three New Zealand White rabbits. The eyes were examined for 72 hours. The test substance showed a mean chemosis, cornea, iris, and conjunctivae scores of 0.00 during the whole observation period. The primary irritation score was 0.00. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours (RCC 1990). After 4 hours, the treated skin was flushed with water and observation were made for an additional 72 hours. The test substance showed a primary Irritation score (24,48,72 hours) of 0.00 and local signs (1 hour to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No corrosive effect was evident on the skin. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

Eye irritation/corrosion:

In a GLP compliant eye irritation study, performed according to OECD guideline 405, the test substance (0.1 g) was placed in the conjunctival sac of the left eye of three New Zealand White rabbits (RCC 1990). The eyes were examined for 72 hours. The test substance showed a mean chemosis, cornea, iris, and conjunctivae scores of 0.00 during the whole observation period. The primary irritation score was 0.00. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.


Justification for selection of skin irritation / corrosion endpoint:
Only study available.

Justification for selection of eye irritation endpoint:
Only study available.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study the test substance does not need to be classified according to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008