Registration Dossier

Administrative data

Description of key information

Skin irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.
No skin irritation was observed.
Eye irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.
According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to 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:
December 4, 1984 - December 7, 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
(Ciba-Geigy Limited, Experimental Toxicology GU 2.1, 4332 Stein/Switzerland)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Haedorin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in metal cages
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: December 4, 1984 - December 7, 1984
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: the patches were moistened with water
Controls:
other: The contralateral flank treated with a control gauze patch served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
3 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: flank
- Type of wrap if used: gauze patch covered with an occlusive membrane and held in place by an adhesive tape.

SCORING SYSTEM: according to the grading scheme given in OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Reversibility:
fully reversible within: 24 hours (2/3 animals), 48 hours (1/3 animals)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Irritant / corrosive response data:
Minimal formation of erythema was observed in all three animals (score = 1), reversible within 48 hours the latest. All scores for edema were zero at all time points.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions employed the test substance induced erythema reactions below the regulatory threshold of significance, therefore, the test article is considered to be 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards. Similar to OECD guideline 405. Non-GLP study.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
other: Draize JH et al. J. Exp. Pharmacol. Ther., 83, 377-390, 1944. Draize JH Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, 36-45, Ass. of Food and Drug Officials of the United States, Topeka, Kansas, 1965
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data reported
- Age at study initiation: no data reported
- Weight at study initiation: no data reported
- Housing: no data reported
- Diet (e.g. ad libitum): no data reported
- Water (e.g. ad libitum): no data reported

ENVIRONMENTAL CONDITIONS: no data reported
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of finely powdered AN-703 instilled onto one eye.
Observation period (in vivo):
Observation were made at 24, 48, 72 and 168 hours after application
Number of animals or in vitro replicates:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE: No removal of the test substance

SCORING SYSTEM: Draize score system used to report result in the report. Raw data of the observations were available in the report, therefore, EU scoring has been reported in the results section for Cornea - Opacity, Iris - Inflammation, Conjunctivae - Redness and Chemosis.

TOOL USED TO ASSESS SCORE: Not reported in the report.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
(after 168 hours - score: 1)
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1.66
Max. score:
2
Reversibility:
fully reversible within: 168 hours
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 168 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1.66
Max. score:
2
Reversibility:
fully reversible within: 168 hours
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 168 hours
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Conjunctiva Chemosis score:
* Animal 1 - 24, 48 and 72 hours - 1.66 max: - 2 - fully reversible within: 168 hours
* Animal 2 - 24, 48 and 72 hours - 0
* Animal 3 - 24, 48 and 72 hours - 1 max: 2 - fully reversible within: 72 hours
* Animal 4 - 24, 48 and 72 hours - 1 max: 2 - fully reversible within: 72 hours
* Animal 5 - 24, 48 and 72 hours - 2 max: 3 - fully reversible within: 168 hours
* Animal 6 - 24, 48 and 72 hours - 0
Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.
Executive summary:

0.1 ml of the test item was applied into the conjunctival sac of one eye in each of 6 New Zealand white rabbits. The eye reactions were scored after 24, 48, 72 and 168 h. All effects were fully reversible within the observation period with the exeption of corneal opacity in one animal that however showed signs of reversibility. Mild irritation effects were observed at grades that are borderline for classification. According to the ECHA guidance on application of CLP criteria, 2009 a classification as category 2 eye irritant (H319) is proposed based on the fact that 4 of 6 rabbits had cornea scores at or above 1 for the 24, 48, 72 h average. Based on Dir. 67/548/EEC however, no classification as eye irritant (R36) would be attributed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

No skin irritation was observed.

 

Eye irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.


Justification for selection of skin irritation / corrosion endpoint:
Klimisch 1. Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

Justification for selection of eye irritation endpoint:
Klimisch 2. Similar to OECD guideline 405. Non-GLP study.

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the available data, the substance is classified as an eye irritant:

Skin irritation: No skin irritation was observed.

Eye irritation: According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.