Registration Dossier

Administrative data

Description of key information

The test item was found to be irritating to skin but not 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:
03.10. - 11.11.1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
OECD Guideline study before 2002, GLP. In deviation from the current OECD 404 guideline the test substance was applied to an area of 12-16 cm² and not 6 cm² as recommended, further, no information on removal of residual test substance after the exposure period is available.
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: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: 2470 to 2620 g
- Housing: individually in metal cages
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From: 22.10. to 01.11.1991
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:
0.5 mL of the test substance were applied (unchanged)
Duration of treatment / exposure:
4 hours
Observation period:
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches. The observation period was extended to 10 days to determine the reversibility of the skin reactions.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: right flank, approx. 12-16 cm²
- 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 and day 10 after removing the gauze patches according to the OECD scoring system.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24-72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Erythema Score 1 and scaling after 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24-72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Erythema Score 1 and scaling after 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Erythema Score 1 and scaling after 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Edema Score 1 after 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Edema Score 1 after 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Erythema and edema were observed already at the 1 hour time point. From the reading one hour up to 72 hours after patch removal the erythema reaction was extending beyond the application area in all animals. The skin reactions observed were reversible until the end of the observation period on day 10.
Other effects:
Scaling was seen on day 7 in all animals. A loss of body weight was recorded in one animal on day 3.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the experimental conditions employed the test article induced erythema and edema reactions when applied to the clipped albino rabbit skin at levels above the threshold of significance and must therefore be classified as irritant to the skin.
Executive summary:

In an acute dermal irritation study following OECD guideline 404 and in compliance with GLP, three rabbits were exposed to 0.5 ml of the test substance for 4 hours. The test substance was applied unchanged to a gauze patch (12 -16cm²) which was applied to the shaved right flank of each animal. The gauze patch was loosely covered with an aluminium foil (approx. 36 cm²) and held in place for 4 hrs by an adhesive tape. A control gauze patch moistened with distilled water was applied to the contralateral flank. Observations were made 1, 24, 48 and 72 hours after removal of the gauze patches. Erythema and edema were observed already at the 1 hour time point. From the reading one hour up to 72 hours after patch removal the erythema reaction was extending beyond the application area in all animals. Scaling was seen on day 7 in all animals. A loss of body weight was recorded in one animal on day 3. The skin reactions observed were reversible until the end of the observation period on day 10. Based on the results the test article is regarded as irritating to the rabbit skin and has to be classified.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
03.10. - 19.11.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute 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: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: between 2660 to 2760 g
- Housing: individually in metal cages
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From: October 29, 1991 To: November 12, 1991
Vehicle:
unchanged (no vehicle)
Controls:
other: The right 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):
Examination of the eyes after 1 hour and 1, 2, 3, 7 days after instillation of the test substance.
Number of animals or in vitro replicates:
3 male NZW rabbits
Details on study design:
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:
other: mean (24+48+72h)
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean (24+48+72h)
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean (24+48+72h)
Score:
0.89
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean (24+48+72h)
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
See table 1 below.
Other effects:
None.

Table 1: Eye irritation scores of the test substance

 

time

animal 1

animal 2

animal 3

corneal opacity

24 h

0

0

0

48 h

0

0

0

72 h

0

0

0

iris

24 h

0

0

1

48 h

0

0

0

72 h

0

0

0

conjunctivae

24 h

1

1

1

48 h

1

1

1

72 h

0

1

1

chemosis

24 h

0

0

1

48 h

0

0

0

72 h

0

0

0

All ocular reactions were reversible within 7 days.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions employed the test article, when instilled into the conjunctival sac of albino rabbits' eyes, induced irritation of the conjunctiva below the threshold of significance and does therefore not require classification for eye irritation.
Executive summary:

In an acute eye irritation/corrosion study according to OECD guideline 405 and in compliance with GLP, 0.1 ml of the undiluted test item was instilled into one eye of each of three male New Zealand White rabbits. Observations were made 1, 24, 48, 72 hours and 7 days after instillation. Irritation of the conjunctivae was seen as redness and chemosis, reversible within 7 days. The average scores (24 -72 hours) for each animal were 0.67, 1 and 1 for redness and 0, 0 and 0.33 for chemosis, respectively. Based on these results and according to the EC criteria for classification and labeling requirements the test substance does not need to be classified.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In an acute dermal irritation study following OECD guideline 404 and in compliance with GLP (Ciba-Geigy, 1991), three rabbits were exposed to 0.5 ml of the test substance for 4 hours. The test substance was applied unchanged to the shaved right flank of each animal for four hours. A control gauze patch moistened with distilled water was applied to the contralateral flank. Observations were made 1, 24, 48 and 72 hours after removal of the gauze patches. Erythema and edema were observed already at the 1 hour time point. From the reading one hour up to 72 hours after patch removal the erythema reaction was extending beyond the application area in all animals. Scaling was seen on day 7 in all animals. A loss of body weight was recorded in one animal on day 3. The skin reactions observed were reversible until the end of the observation period on day 10. Based on the results the test article is regarded as irritating to the rabbit skin and has to be classified.

In a second study performed by the same method (Ciba-Geigy, 1989), the observed skin reactions were similar but slightly less severe, reaching the level of significance only in 1 out of three animals. Nevertheless, the substance is considered to be irritating to the skin and classified accordingly.

Eye irritation

In an acute eye irritation/corrosion study according to OECD guideline 405 and in compliance with GLP (Ciba-Geigy, 1991), 0.1 ml of the undiluted test item was instilled into one eye of each of three male New Zealand White rabbits. Observations were made 1, 24, 48, 72 hours and 7 days after instillation. Irritation of the conjunctivae was seen as redness and chemosis, reversible within 7 days. The average scores (24 -72 hours) for each animal were 0.67, 1 and 1 for redness and 0, 0 and 0.33 for chemosis, respectively. Based on these results and according to the EC criteria for classification and labeling requirements the test substance does not need to be classified.

In a second study following the same method (Ciba-Geigy, 1989), similar reactions were observed. The ocular reactios were limited to the conjunctiva and the iris, reversible within 14 days and 24 hours, respectively. The observed reaction scores remained below the threshold of significance in all animals, supporting the findings of the key study.


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

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

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for skin irritation but not for eye irritation is warranted under Directive 67/548/EEC.

 

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, classification for skin irritation but not for eye irritation is warranted under Regulation (EC) No.1272/2008.