Registration Dossier

Administrative data

Description of key information

The substance was found to cause mild transient irritating effects on skin and eyes in rabbits, as tested in GLP and OECD testing guideline compliant studies. Effects were below the threshold of classification and labelling.

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:
From June 13th, 1989 to June 16th, 1989.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to the OECD TG 404 and to GLP, however with following deviation: testing was conducted under occlusive conditions instead of semiocclusive as recommended by the guideline.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(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 Fuellinsdorf
- Age at study initiation: approximately 12-14 weeks
- Weight at study initiation: 2290-2380 g
- Housing: individually in metal cages (and identified by individually numbered ear tags)
- Diet (e.g. ad libitum): standard rabbit pellet (Nafag No. 814, Gossau, Switzerland) ad libitum
- Water (e.g. ad libitum): fresh water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h / 12h

All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer.
The drinking water quality fulfilled the critical parameters in the specification of the "Schweizerisches Lebensmittelbuch" (Edition 1972).
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: A control gauze patch moistened with distilled water was applied to the contralateral flank.
Amount / concentration applied:
A gauze patch (approx. 12-16 cm ) bearing 0.5 mL of the test substance was applied to the right flank of each animal. The patches were loosely covered with an aluminum foil and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).
Duration of treatment / exposure:
4 hours
Observation period:
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches; skin reaction was assessed according to the OECD scoring system. Moreover, the animals were checked daily for systemic symptoms and mortality.
Number of animals:
3 male animals.
Irritation parameter:
erythema score
Remarks:
(mean)
Basis:
animal: 1, 2 and 3
Time point:
other: 24-48-72 h
Score:
0.1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Erythema graded 1 was seen in all 3 animals at reading time point 1 hour and persisted until 24 hours in only one case. After 48 hours, recovery was complete.
Irritation parameter:
edema score
Remarks:
(mean)
Basis:
animal: 1, 2, 3
Time point:
other: 24-48-72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: None of the animals showed edema
Irritant / corrosive response data:
The substance applied for 4 hours to the skin of rabbit under occlusive conditions induced very slight erythema in all 3 animals but no edema. Erythema was seen at reading time point 1 hour following removal of the dressing and was graded 1(max. 4). At reading time point 24 hour, very slight erythema persisted in one of the 3 animals. At reading time point 48 hour, reversibility was completed in all 3 animals.
Other effects:
None
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU 67/548/EEC and EC/1271/2008
Conclusions:
Under the experimental conditions employed the test article induced minimal erythema reactions well below the threshold of significance when applied to the clipped albino rabbit skin.
Executive summary:

The substance was applied for 4 hours to the skin of 3 male rabbits according to the OECD TG 404, but under occlusive conditions. The treatment induced very slight erythema in all 3 animals but no edema. Erythema was seen at reading time point 1 hour following removal of the dressing and was graded 1(max. 4). At reading time point 24 hour, very slight erythema persisted in one of the 3 animals. At reading time point 48 hour, reversibility was completed in all 3 animals. Based on the scoring of the skin findings as recommended by the OECD guideline, the test item was not irritating to the skin of rabbit.

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:
From June 20th, 1989 to June 27th, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
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 Fuellinsdorf
- Age at study initiation: approximately 12-14 weeks
- Weight at study initiation: 2500 to 2700 g
- Housing: individually in metal cages (and identified by individually numbered ear tags)
- 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 (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h / 12h

All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer.
The drinking water quality fulfilled the critical parameters in the specification of the "Schweizerisches Lebensmittelbuch" (Edition 1972).
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served for control
Amount / concentration applied:
0.1 mL was instilled into the conjunctival sac of the left eye of each animal. The right eye served as untreated control.
Duration of treatment / exposure:
0.1 mL was instilled into the conjunctival sac of the left eye of each animal, the lids were then held together for about one second in order to prevent loss of the test item. The treated eyes were not rinsed.
Observation period (in vivo):
72 hours, extended to 7 days because reactions were observed within 72 hours after instillation of the test item.
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation according to the OECD scoring system. A slit-lamp was used to facilitate the evaluation. Because reactions were observed within 72 hours after treatment, the observation period was extended to 7 days to determine the reversibility of the eye reactions.
Moreover, the animals were checked daily for systemic symptoms and mortality.
Irritation parameter:
cornea opacity score
Remarks:
(mean)
Basis:
animal: 1, 2, 3, respectively
Time point:
other: 24-48-72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Corneal opacity was seen in none of the 3 animals
Irritation parameter:
iris score
Remarks:
(mean)
Basis:
animal: 1, 2, 3, respectively
Time point:
other: 24 -48-72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Effect in the iris graded 1 was seen in 1/3 animals at reading time point 1 hour only.
Irritation parameter:
conjunctivae score
Remarks:
(mean)
Basis:
animal #1
Time point:
other: 24 -48-72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Conjunctival redness graded 1 was seen at reading time points 1 and 24 hrs but no more thereafter.
Irritation parameter:
conjunctivae score
Remarks:
(mean)
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Conjunctival redness graded 1 was seen at reading time points 1, 24 and 48 hours, and no more thereafter.
Irritation parameter:
conjunctivae score
Remarks:
(mean)
Basis:
animal #3
Time point:
other: 24 -48-72 h
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Conjunctival redness graded 1 was seen at reading time points 1, 24 and 48 hours, and no more thereafter.
Irritation parameter:
chemosis score
Remarks:
(mean)
Basis:
animal: 1, 2, 3, respectively
Time point:
other: 24- 48-72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Chemosis graded 1 was seen in each of the 3 animals at reading time point 1 h only.
Irritant / corrosive response data:
Under the experimental conditions employed, iritis, conjunctival redness and chemosis, all of them graded 1, were reported for all 3 animals at reading time point 1 hour; no corneal opacity was seen. Almost all findings disappeared within 24 to 48 hours, and complete reversibility was achieved at reading time point 72 hours.
Other effects:
None
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU 67/548/EEC and EC/1271/2008
Conclusions:
Under the experimental conditions employed the test article induced minimal irritation of the iris and conjunctiva well below the threshold of significance when instilled into the conjunctival sac of albino rabbits.
Executive summary:

The substance was instilled into the conjunctival sac of one eye in each of 3 female rabbits according to the OECD TG 405; the eyes were not rinsed. The treatment induced iritis, conjunctival redness and chemosis, all of them graded 1, in each of the 3 animals at reading time point 1 hour; no corneal opacity was seen. Almost all findings disappeared within 24 to 48 hours, and complete reversibility was achieved at reading time point 72 hours. Based on the scoring of the eye findings as recommended by the OECD guideline, the test item was not irritating to the eye of rabbit.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Two skin irritation studies are available, both showing the same result of transient erythema. Low grade Edema scores were observed only at the one hour reading in a single animal. In the key study erythema graded 1 was seen in all 3 animals at reading time point 1 hour and persisted until 24 hours in only one case. After 48 hours, recovery was complete (Ciba-Geigy, 1989). In the supporting study, erythema was seen in 2/3 animals at reading time point 1 hour and was graded 1 and 2, respectively. Erythema graded 2 persisted until 24 hours. At reading time point 48 hours, erythema had completely disappeared (Ciba-Geigy, 1987).

Eye irritation

Two studies are avaliable assessing the ocular irritation potential of the test article. In the key study, the substance was instilled into the conjunctival sac of one eye in each of 3 female rabbits according to the OECD TG 405; the eyes were not rinsed (Ciba-Geigy, 1989). The treatment induced iritis, conjunctival redness and chemosis, all of them graded 1, in each of the 3 animals at reading time point 1 hour; no corneal opacity was seen. Almost all findings disappeared within 24 to 48 hours, and complete reversibility was achieved at reading time point 72 hours. The study was performed under GLP.

In the supporting study, the substance was instilled into the conjunctival sac of one eye in each of 3 female rabbits according to the OECD TG 405; the eyes were not rinsed (Ciba-Geigy, 1987). Conjunctival redness and chemosis graded 1-2 were reported for all 3 animals at reading time point 1 hour; neither corneal opacity nor effects in the iris was seen. Complete reversibility was achieved at reading time point 72 hours.


Justification for selection of skin irritation / corrosion endpoint:
GLP-compliant guideline study

Justification for selection of eye irritation endpoint:
GLP-compliant guideline study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin or eye irritation under Directive 67/548/EEC.

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008.