Registration Dossier

Administrative data

Description of key information

The test article not irritating to both skin and eyes.

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:
04.02. - 12.03.1986
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:
adopted May 12, 1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Füllinsdorf, Switzerland
- Weight at study initiation: 2030 - 2560 g
- Housing: individually in metal cages
- Age at study initiation: approx. 12 - 14 weeks old
- Diet: standard rabbit pellet - Nafag No. 814, Gossau, Switzerland, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Photoperiod: 12 hours dark/12 hours light

IN-LIFE DATES: from 04 to 11 February 1986
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the test item were applied (unchanged).
Duration of treatment / exposure:
4 hours
Observation period:
7 days; the skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches. The observation period was extended to 7 days to determine the reversibility of the skin reactions.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm² on the flanks
- Type of wrap if used: The gauze patch was loosely covered with an aluminium foil (approx. 36 cm² ) and held in place for 4 hrs by an adhesive tape.

SCORING SYSTEM:
The skin reactions were evaluated 1, 24, 48, 72 hours and on day 7 after removing the gauze patches according to the OECD scoring system.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Minimal erythema was observed in all animals, reversible within 7 days the latest. One animal displayed a minimal edema reactions 1 hour after removal of the dressing, this effect was reversible within 24 hours. All other scores for edema were zero.
Other effects:
A severe loss of weight was observed in one animal caused by rejection of food. The other two gained weight normally.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the test article only caused minimal reactions of the skin below the regulatory significance and is therefore regarded as not irritating to the rabbit skin.
Executive summary:

The primary skin irritation potential of the test substance was investigated in a GLP compliant study according to OECD test guideline no. 404. The test item was applied by topical occlusive application of 0.5 ml to the intact flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches. The observation period was extended to 7 days to determine the reversibility of the skin reactions. The animals were checked daily for systemic symptoms and mortality. A severe loss of weight was observed in one animal caused by rejection of food. The other two gained weight normally. The individual mean scores for erythema for each of the three animals were 0.66, 1.0 and 0.33, respectively. One animal displayed an edema reaction 1 hour after removal of the dressing (score = 1), this effect was reversible within 24 hours. All other scores for edema were zero. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals. Thus, the test item did not induce significant irreversible damage to the skin and is therefore not regarded as a skin irritant.

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:
04.03. - 03.04.1986
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:
adopted May 12, 1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Füllinsdorf, Switzerland
- Weight at study initiation: 2140 - 2280 g
- Housing: individually in metal cages
- Age at study initiation: approx. 12 - 14 weeks old
- Diet: standard rabbit pellet - Nafag No. 814, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Photoperiod: 12 hours dark/12 hours light

IN-LIFE DATES: from 04 to 11 March 1986
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
single instillation
Observation period (in vivo):
7 days; examination of the eyes after 1 hour and 1, 2, 3, 7 days after instillation of the test item.
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OD TEST SUBSTANCE:
- Washing: no washing performed

SCORING SYSTEM:
According to the grading system given in the OECD guideline 405

TOOL USED TO ASSESS SCORE:
hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Instillation of the test article into the conjunctival sac of three rabbit eyes caused minimal redness in 2/3 animals. The average conjunctivae score for all three animals was 0.44 and reversed back to normal within 7 days. One animal displayed chemosis at the one hour time point, this finding reversed to normal within 24 hours. No other ocular reactions were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions employed the test article induced minimal irritation of the conjunctiva below the threshold of significance, and is therefore classified as non-irritating to the rabbit eye.
Executive summary:

The primary eye irritation potential of the test article was investigated in a GLP compliant study according to OECD test guideline No. 405. The test item was applied by instillation of 0.1 ml into the right eye of each of three young adult New Zealand White rabbits. The left eyes remained untreated and served as controls. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours and 7 days after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity, iris and chemosis were 0.00 for all three animals. One animal displayed chemosis at the one hour time point, this finding reversed back to normal within 24 hours. The individual mean scores for conjunctival redness were 0.33, 0 and 1, respectively. This effect was reversible and was no longer evident 7 days after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye and is regarded as not irritating.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The test article's potential to cause dermal irritation was assessed in a GLP-compliant study following OECD guideline 404 (CIBA-GEIGY Ltd., 851157, 1986). An amount of 0.5 ml of the test substance was applied topically to the intact skin of three male New Zealand white rabbits for 4 hours under occlusive dressing. The skin reactions were evaluated 1, 24, 48 and 72 hours after removing the gauze patches according to the OECD scoring system. One animal showed an edema reaction at 1 hour after removal of the dressing, reversible after 24 hours. All animals displayed minimal erythema reactions, reversible after 7 days the latest. The individual mean erythema scores (24 - 72 hours) for each animal were 0.66, 0.33 and 1. Overall, the reaction was only minimal and below the threshold of toxicological and regulatory significance. Therefore, under the test conditions chosen, the test substance is not considered to be irritating to the skin.

Eye irritation

To assess the acute eye irritation potential of the test substance in vivo, a GLP-compliant study with three male New Zealand white rabbits was performed according to OECD guideline 405 (CIBA-GEIGY Ltd., 851156, 1986). An amount of 0.1 ml of the test substance was placed into the conjunctival sac of the right eye and the ocular reactions were evaluated 1, 24, 48, and 72 hours and 7 days after instillation. One animal displayed chemosis at the one hour time point, this finding reversed to normal within 24 hours. All animals showed minimal redness of the conjunctiva, reversible after 7 days the latest. The individual mean scores for conjunctival redness (24 - 72 hours) for each animal were 0.33, 0 and 1. No reactions were observed regarding the cornea and iris. Overall, the observed effects were only minimal and below the threshold of toxicological and regulatory significance. Therefore, under the test conditions chosen and considering the present data, the test article is classified as not irritating.

Respiratory Irritation

No data

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, the test substance has not to be classified as skin or eye irritant.