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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Study meets minimum scientific standards for a dermal irritation study and provides sufficient information regarding the irritation potential of the test substance. Exposure longer (24 h) than current guideline standard (4 h).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Federal Hazardous Substances Labelling Act Regulations, Section 191.11, Federal Register: 29, 13009 (1964)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White

Test system

Type of coverage:
occlusive
Preparation of test site:
other: half abraded/half intact
Vehicle:
not specified
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
up to 72 hrs
Number of animals:
6
Details on study design:
Six NZ White rabbits were restrained in stocks and the fur removed by  clipping.Half of the exposed area was abraded and the other half  remained intact. 0.5 ml (vol) of test compound was applied to the shaved  intact and abraded skin sites and covered with surgical gauze. The area  was then wrapped with impervious tape measuring 2.5 x 2.5 cm² and a stockinette sleeve.  Test  material remained in contact for 24 hrs and then removed.  Irritation  scores were determined at 24 and 72 hours after patch removal.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
mean
Time point:
other: mean 24+72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean 24+72 h
Score:
1.34
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
animal: #1, #5
Time point:
other: mean 24+72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal: #2,#4
Time point:
other: mean 24+72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
erythema score
Basis:
animal: #3, #6
Time point:
other: mean 24+72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal: #1, #5
Time point:
other: mean 24+72 h
Score:
0.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: mean 24+72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24+72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: mean 24+72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24+72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. CLP criteria
Irritant / corrosive response data:
Either slight or well defined erythema and from barely perceptible to  moderate edema of the skin at 24 hrs. 
Evidence of irritation persisted  at 72 hrs.

Any other information on results incl. tables

Reevaluated according CLP criteria

Shaved skin:

 

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

1

-

0

0.5

1

-

0

0.5

2

2

-

1

1.5

2

-

2

2

3

2

-

2

2

3

-

3

3

4

2

-

1

1.5

2

-

3

2.50

5

1

-

0

0.5

1

-

0

0.50

6

2

-

2

2

1

-

2

1.5

 

Comparison with CLP criteria:

Remark: Exposure time was higher than 4 hours, observation time only 72 hours.

Two scores were > 2.3 but observation time too short. The highest mean erythema score is 2 for 3/6 animals. The highest edema score is 3 for 1/6 animals. The observation time was too short to demonstrate reversibility.

 

Shaved and scarifized skin (not used for evaluation):

 

 

Animal Nr.

Erythema

24 h

Erythema

48 h

Erythema

72h

Mean

Erythema

Edema

24 h

Edema

48 h

Edema

72 h

Mean

Edema

1

1

-

0

0.5

1

-

0

0.5

2

2

-

1

1.5

2

-

2

2

3

2

-

2

2

3

-

3

3

4

2

-

1

1.5

2

-

3

2.50

5

1

-

1

1

1

-

1

1

6

2

-

2

2

1

-

2

1.5

 

Reevaluated acc. DSD criteria

 

2 h Exposure, shaved skin, occlusive

Erythema

Edema

24h

72h

24h

72h

Animal 1

1

0

1

0

Animal 2

2

1

2

2

Animal 3

2

2

3

3

Animal 4

2

1

2

3

Animal 5

1

0

1

0

Animal 6

2

2

1

2

Mean 

1.67

1

1.67

1.67

Overall mean 

1.34

1.67

Erythema

Edema

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Conclusions:
Classification: irritating
Executive summary:

In a primary dermal irritation study according to “Federal Hazardous Substances Labelling Act Regulations, Section 191.11, Federal Register: 29, 13009 (1964), 6 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of EMA for 24 hours to 2.5x 2.5 cm body surface area of the shaved/scarified skin. Animals then were observed for 3 days. Irritation was scored by the Draize method. This scoring system is similar to OECD guideline 404.

Only animals with the shaved intact skin were evaluated for C&L purposes.

24 h after application 2 animals showed very slight (score1) and 4 animals well defined (score 2) signs of erythema and 3 animals very slight (score 1), 2 animals slight (score 2) and 1 animal moderate (score 3) edema. 72 h after application 2 animals showed no erythema (score 0), 2 animals very slight (score 1) and 2 animals well defined erythema (score 2). No edema were observed after 72 h in 2 animals, slight edema (score 2) in 2 animals and moderate (score 3) in 2 animals. Acc. CLP criteria in 2/6 animals mean edema scores (24 +72h) were > 2.3. As observation time was only 72 h and reversibility could not be observed EMA is considerd as irriating to skin.