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Administrative data

Description of key information

Skin: EEC Directive 93/21, Annex VI; no skin irritation was observed in rabbits; reliability = 2; NOT CLASSIFIED.
Eye: OECD 405; eye irritation was observed in rabbits; reliability = 2; CLASSIFIED: Cat 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Guide to Labeling of Dangerous Substances published in the Official Journal of European Communiites (EEC Directive 93/21, Annex VI).
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Source: Hare Marland, Hewitt, New Jersey.
Housing: Single, in suspended, stainless steel, wire-mesh cages.
Food: Purina Certified High Fiber Rabbit Chow #5325, ad libitum, except during exposure.
Water: Ad libitum except during exposure.
Weight: 2074-2162 g
Light/Dark Cycle: 12/12
Temperature: 20ºC ± 1
Humidity: 50% ± 10%
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: other areas on test animals' body was used for comparison (control)
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, and 48 hours
Number of animals:
6
Details on study design:
On the day prior to treatment, the hair of 6 male rabbits was closely shaved to expose the skin from the scapular to the lumbar region of the back. Each rabbit was placed into a stock which had been fitted with a piece of rubber sheeting, approximately 8" x 18". The rabbits remained in the stocks throughout the exposure period and during that time did not have access to food or water. Approximately 0.5 g of the test substance, moistened with deionized water prior to dosing, was applied directly to the test site and was covered with a 2" gauze square. The gauze square was held in place with non-irritating tape. The rubber sheeting was then wrapped around the animal and secured with clips to retard evaporation and to keep the test substance in contact with the skin without undue pressure. Approximately 4 hours after application of the test substance, the rubber sheeting was loosened, and the skin at the corners of the gauze squares was marked with a waterproof pen. Wrappings and gauze squares were then removed. The test sites were gently washed with soap and warm water to remove excess test substance. The skin was gently patted dry and the animals were returned to their cages. Approximately 1, 24, and 48 hours after removal of the test substance, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according to the Draize scale. The adjacent areas of the untreated skin were used for comparison. Additionally, the rabbits were examined for clinical signs of toxicity at each dermal evaluation.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48 h
Score:
1.5
Max. score:
4
Reversibility:
other: not reversible in 48 hours
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48 h
Score:
1.5
Max. score:
4
Reversibility:
other: not reversible in 48 hours
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Evaluations made up to 48 hours
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: Evaluations made up to 48 hours
Irritant / corrosive response data:
The test substance produced slight erythema in 3 rabbits and mild erythema in 3 rabbits at 1 hour after the test substance was removed. No edema was observed. By 24 hours, 2 rabbits exhibited slight erythema but no edema and 4 rabbits exhibited mild erythema and slight edema. Four rabbits were clear of all dermal irritation and 2 rabbits exhibited slight erythema but no edema by 48 hours after removal of the test substance.
See results tables 1 and 2 for further details.
Other effects:
In addition, the test sites of 2 rabbits were stained gray by the test substance. No clinical signs of toxicity were observed during the study.

TABLE 1:

Summary of Skin Response to the test substance

 

 

 

 

 

 

 

 

Erythema

Edema

Response

1 hr

24 hr

48 hr

1 hr

24 hr

48 hr

None

0/6

0/6

4/6

6/6

2/6

6/6

Slight

3/6

2/6

2/6

0/6

4/6

0/6

Mild

3/6

4/6

0/6

0/6

0/6

0/6

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TABLE 2:

Individual Skin Irritation Scores
Skin Response Observed in Rabbits

 

 

 

 

 

 

 

Rabbit

Erythema

Edema

Number

1 hr

24 hr

48 hr

1 hr

24 hr

48 hr

30374

1

2

1

0

1

0

30383

1(x)

1(x)

0(x)

0

0

0

30384

2

2

0

0

1

0

30385

2(x)

2(x)

0(x)

0

1

0

30386

2

2

1

0

1

0

30392

1

1

0

0

0

0

 

 

 

 

 

 

 

(x) = skin stained gray

 

 

 

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance produced slight erythema in 3 rabbits and mild erythema in 3 rabbits at 1 hour after the test substance was removed. No edema was observed.  By 24 hours, 2 rabbits exhibited slight erythema but no edema and 4 rabbits exhibited mild erythema and slight edema.  Four rabbits were clear of all dermal irritation and 2 rabbits exhibited slight erythema but no edema by 48 hours after removal of the test substance.
Executive summary:

The irritation potential of the test substance was studied in rabbits. The test substance produced slight erythema in 3 rabbits and mild erythema in 3 rabbits at 1 hour after the test substance was removed. No edema was observed.  By 24 hours, 2 rabbits exhibited slight erythema but no edema and 4 rabbits exhibited mild erythema and slight edema.  Four rabbits were clear of all dermal irritation and 2 rabbits exhibited slight erythema but no edema by 48 hours after removal of the test substance.  

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:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 2490 or 2536 grams
- Housing: The rabbits were housed singly in suspended, stainless steel, wire-mesh cages.
- Diet (e.g. ad libitum): The rabbits were offered approximately 125 grams of Purina Certified High Fiber Rabbit Chow daily during the study.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Rabbits were quarantined, weighed, and observed for general health for approximately 2 weeks.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye of each rabbit served as the control (untreated)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approximately 0.01 g
- Concentration (if solution): N/A
Duration of treatment / exposure:
approximately 20 seconds
Observation period (in vivo):
7 days
Rabbits were observed during exposure and for approximately 30-60 seconds, 1 and 4 hours, and 1, 2, 3, and 7 days after administration of the test substance.
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes. Both eyes of the rabbit one rabbit were rinsed for approximately one minute with room temperature water. The eyes of the other rabbit were not washed.
- Time after start of exposure: Approximately 20 seconds

SCORING SYSTEM:
- Draize scale
- Eyes were also observed for any unusual responses to treatment such as pannus, blistering of the conjunctiva, ulceration, or other effects indicative of corrosive action.
- Control eyes were not scored. These untreated eyes were used for comparison and were considered "normal" relative to the treated eye.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
- illumination and magnification
Irritation parameter:
cornea opacity score
Basis:
other: range
Time point:
other: 1 hour to 7 days
Score:
0 - 3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: See Tables 1 and 2 in IUCLID section 7.3.2 for complete individual rabbit scores
Irritation parameter:
iris score
Basis:
other: range
Time point:
other: 1 hour to 7 days
Score:
0 - 1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: See Tables 1 and 2 in IUCLID section 7.3.2 for complete individual rabbit scores
Irritation parameter:
conjunctivae score
Basis:
other: range
Time point:
other: 1 hour to 7 days
Score:
0 - 4
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: See Tables 1 and 2 in IUCLID section 7.3.2 for complete individual rabbit scores

 

Table 1: Eye Irritation Reactions Observed in the Unwashed Rabbit Eye

Rabbit No. 30418

Cornea

Iritis

Conjunctiva

Opacity

Area

Redness

Chemosis

Discharge

1 Hour

3A

2

1

2

3B

3

4 Hours

3A

1

1

2

3B

3

1 Day

0

0

0

3H

2

3

2 Days

2A

2

0

3H

2B

1

3 Days

0

0

0

2H

2B

0

7 Days

0

0

0

0

0

0

A = Epithelial sloughing

B = Blistering of the conjunctiva

C = Hemorrhaging of the nictitating membrane

 

 

Table 2: Eye Irritation Reactions Observed in the Washed Rabbit Eye

Rabbit No. 30419

Cornea

Iritis

Conjunctiva

Opacity

Area

Redness

Chemosis

Discharge

1 Hour

3

3

1

2

3B

3

4 Hours

3

3

1

2

3B

3

1 Day

3A

3

1

3H

4B

3

2 Days

3A

3

1

3H

2B

2

3 Days

3A

3

1

2H

2B

2

7 Days

0

0

0

0

0

0

A = Epithelial sloughing

B = Blistering of the conjunctiva

H = Hemorrhaging of the nictitating membrane

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Under the conditions of this study, the test substance produced severe conjunctival redness, moderate corneal opacity, moderate iritis, copious discharge, hemorrhaging of the nictitating membrane, blistering of the conjunctiva, and epithelial sloughing of the cornea in both treated rabbit eyes. In addition, severe chemosis was observed in the treated unwashed rabbit eye. Both treated rabbit eyes were normal by 7 days following treatment.
Executive summary:

The test substance was evaluated for acute eye irritation potential in two young adult New Zealand white rabbits. Approximately 0.01 grams of the test substance was instilled into the lower conjunctival sac of the right eye of each animal. Approximately 20 seconds after instillation, the treated and control eyes of 1 rabbit were washed. The treated and control eyes of the remaining rabbit were not washed. The untreated eye served as a control. The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according to a numerical scale approximately 1 and 4 hours, and 1, 2, 3 and 7 days following administration. Under the conditions of this study, the test substance produced severe conjunctival redness, moderate corneal opacity, moderate iritis, copious discharge, hemorrhaging of the nictitating membrane, blistering of the conjunctiva, and epithelial sloughing of the cornea in both treated rabbit eyes. In addition, severe chemosis was observed in the treated unwashed rabbit eye. Both treated rabbit eyes were normal by 7 days following treatment. No adverse clinical signs of toxicity were observed during the study. One rabbit pawed its treated eye after instillation of the test substance.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

After 4 hours of exposure to 0.5 g of wetted test substance to the skin, slight erythema was seen in 2 of 6 rabbits and no erythema was observed in 4 of 6 rabbits 48 hours after the test substances was removed. Furthermore, no edema was seen in any rabbit 48 hours after removal of the test substance. 

After instillation of 0.01 g of test substance into the lower conjunctival sac of the right eye of two rabbits for approximately 20 seconds, severe conjunctival redness, moderate corneal opacity, moderate iritis, copious discharge, hemorrhaging of the nictitating membrane, blistering of the conjunctiva, and epithelial sloughing of the cornea in both treated rabbit eyes was observed. In addition, severe chemosis was observed in the treated unwashed rabbit eye. Both treated rabbit eyes were normal by 7 days following treatment. No adverse clinical signs of toxicity were observed during the study.


Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the reversible eye damage resulting from eye exposure, the substance is classified as Irritation Category 2 (Causes serious eye irritation) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.