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Description of key information

The test substance caused skin irritation on rabbit skin. Erythema and edema with a score of 2 - 3 were evident in all 6 animals. Only very slight effects in the rabbit eye were caused by the substance (Ciba Geigy Ltd.; reliability score: 2).

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:
August 3, 1981 - August 10, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited documentation, no data on test substance purity, occlusive conditions, 24 h exposure)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(limited documentation, occlusive treatment, 24 h exposure)
Qualifier:
according to guideline
Guideline:
other: (Proposed Guidelines of the United States Environmental Agency (EPA), §163.81-5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978).
Principles of method if other than guideline:
Gauze patches of 2.5 x 2.5 cm laden with 0.5 mL of the test material were applied to the prepared abdraded and intact skin for 24 hours. Scoring was recorded 24 h, 48 h, 72 h, 4 d and 7 d after application.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: bred and raised in Ciba-Geigy premises
- Age at study initiation: adult
- Weight at study initiation: 2-3 kg
- Housing: housed individually in metal cages
- Diet (e.g. ad libitum): standard rabbit food (NAFAG, No. 814, Gossau SG); ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10%
- Photoperiod (hrs dark / hrs light): 12/ 12
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of test material on gauze patches of 2.5 x 2.5 cm
Duration of treatment / exposure:
24h
Observation period:
7 days
Number of animals:
6 (3 males and 3 females)
Details on study design:
TEST SITE
- Site of exposure: back and flank of the rabbits
- Area of exposure: 2.5 x 2.5 cm²
- Type of wrap if used: gauze patches covered with an impermeable material, fastened to the body of the rabbits with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24h

SCORING SYSTEM:
- Evaluation was performed according to the Draize Scoring System.
- Calculation of the primary skin irritation index: the scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4.
- Assessment of irritation:
0
0.0-1.0 : minimal
1.1-2.0 : slight
2.1-4.0 : moderate
4.1-6.0 : marked
6.1-8.0 : extreme
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: mean over 24, 48 and 72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: mean over 24, 48 and 72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days

Results of Skin irritation (intact skin, 24 h exposure):

Observation time

Rabbit no.

1

2

3

4

5

6

Ery.

Edema

Ery.

Edema

Ery.

Edema

Ery.

Edema

Ery.

Edema

Ery.

Edema

24 h

2

3

2

3

2

3

2

3

2

1

2

1

48 h

2

3

4

3

3

3

2

3

2

2

2

1

72 h

2

3

4

3

3

3

4

3

3

2

3

1

4 d

2

3

4

3

3

2

4

2

2

2

3

2

7 d

2

3

3

3

3

2

3

3

3

2

3

2

Mean value 24 + 48 + 72 h

2.00

3.00

3.33

3.00

2.67

3.00

2.67

3.00

2.33

1.67

2.33

1.00

Mean value 24 + 48 + 72 h all animals

2.55

2.44

-

-

-

-

-

-

-

-

-

-

Ery.: Erythema

 

Mean reaction scores:

 

Mean reaction score

 

Time after exposure (hours)

Erythema

Edema

Total

Intact skin

Abraded skin

Intact skin

Abraded skin

24

2.0

2.3

2.3

2.7

 

72

3.2

3.3

2.5

2.7

 

Total

5.2

5.6

4.8

5.8

21

Primary irritation index = 21.0 / 4 = 5.3

The test substance caused a marked irritation when applied to intact and abraded rabbit skin.

Up to 4 days after application, the surface of the erythema was greater than the site of application.

Slightly ischaemic areas were observed after 48 hours in 4/12 and after 3 and 4 days in 10/12 application sites.

After 7 days, practically all animals had cracked skin.

Both erythema and edema were observed with an average score between 2 and 3 (24 to 72h). The skin condition did not improve on day 4 and only barely improved on day 7, which was the last observation time point. The results for abraded skin were not considered for classification.

Interpretation of results:
irritating
Remarks:
Migrated information
Conclusions:
The test article was found to cause a marked irritation when applied to intact and abraded rabbit skin.

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:
August 3, 1981 - August 10, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited documentation, inadequate characterization of the test subtsubstance, e.g. purity not given)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(limited documentation)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2 - 3 kg
- Housing:individually in metal cages, numbered by ear tags
- Diet: NAFAG, No. 814, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated right eye served as a control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
one single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM:
Evaluation of the eye reactions according to the Draize Scoring System.

TOOL USED TO ASSESS SCORE: hand-slit lamp

Eyes of 3/6 animals were rinsed after approx. 30 seconds.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of 6 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 3/6 rinsed
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of 6 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: 3/6 rinsed
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: rinsed
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: rinsed
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: rinsed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: rinsed
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: rinsed
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: rinsed

Results: Eye irritation

 

Eye treatment

not rinsed

rinsed (after 30 s)

Animal no.

1

2

3

4

5

6

24 h

Cornea

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

1

1

2

1

1

1

Chemosis

0

1

1

1

1

1

Discharge

0

0

0

0

0

0

48 h

Cornea

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

1

0

1

1

0

0

Chemosis

0

0

1

1

1

0

Discharge

0

0

0

0

0

0

72 h

Cornea

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

0

1

1

1

0

0

Chemosis

0

0

1

1

1

0

Discharge

0

0

0

0

0

0

4 d

Cornea

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

0

1

1

1

1

0

Chemosis

0

0

1

1

1

0

Discharge

0

0

0

0

0

0

7d

Cornea

0

0

0

0

0

0

Area

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

0

1

1

0

0

1

Chemosis

0

0

0

0

1

1

Discharge

0

0

0

0

0

0

Mean value 24, 48, 72 h

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

0.67

0.67

1.33

1.00

0.33

0.33

Chemosis

0

0.33

1.00

1.00

1.00

0.33

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Under the conditions of this experiment the test material was found to cause a minimal irritation below the level of regulatory significance when applied to the rabbit eye mucosa.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation

In a primary dermal irritation study, performed using a method identical to that described in the Federal Register, Vol. 43, No. 163, August 22, 1978, 0.5 mL of the test substance (no data on purity) was applied under occlusive conditions to the intact and abraded skin of 6 Albino rabbits. Treatment was terminated 24 hours following application and the animals were observed for 7 days. Irritation was scored according to the Draize method 24, 48 and 72 hours after application.

5/6 animals had an average erythema score (24 h – 72 h) ≥ 2.3 (maximal score = 4). 4/6 animals had an average edema score (24 h – 72 h) ≥ 3 (maximal score = 4). None of the observed effects was reversible within the observation period in any animal.

Results from the abraded skin are not included in the final judgment for skin irritation of the test substance because of its lack of scientific justification and gross deviation from today's acceptable standardized procedures for the appraisal of skin irritation. In this study, the test substance is a skin irritant (Ciba Geigy Ltd. 1981).

 

This study is suitable for assessment of dermal irritation as it was performed using a protocol which is similar and equivalent to the OECD guideline. The conditions are even harsher (occlusive, extended exposure) than that described by the actual OECD guideline.

 

 

Eye irritation

The eye irritation potential of the test substance (no data on purity) was determined in a procedure similar and equivalent to the Test Guideline OECD 405. 0.1 mL of the test substance was applied to the conjunctival sac of the left eye of each of 6 Albino rabbits. The other eye remained untreated and served as control. Irritation was recorded after 24, 48 and 72 hours. Appraisal of eye irritation was performed according to the method of Draize. Average Draize scores (24, 48 and 72 hours) were calculated per animal for corneal opacity, iritis, conjunctivae redness and chemosis. Average values (24 h – 72 h) for cornea and iris score were 0 (maximal score = 4 and 2, respectively) in all animals. Effects on conjunctivae redness were seen in all animals. The average scores were between 0.33 (2/6) and 1.33 (1/6) (maximal score = 3) and were not fully reversible within the observation period in 3/6 animals. The average values for chemosis were between 0 (1/6) and 1 (3/6) and were not fully reversible within 7 days in 2/6 animals. These values are beneath the threshold for classification, hence the test substance is not an eye irritant in this study (Ciba Geigy Ltd. 1981).

 

This study is suitable for assessment of eye irritation as it was performed using a protocol which is similar and equivalent to the OECD guideline.


Justification for selection of skin irritation / corrosion endpoint:
Study comparable to guideline.

Justification for selection of eye irritation endpoint:
Study comparable to guideline.

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Dangerous substance Directive (67/548/EEC)

The available experimental test data are considered reliable and suitable for the purpose of classification. Based on the criteria for classification of skin irritants of Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC, R38 is warranted due to its skin irritant potential. Classification for eye irritation is not warranted.

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

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the 2nd time in Directive EC 286/2011, category 2 is warranted due to its skin irritant potential. Classification for eye irritation is not warranted.