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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:
key study
Study period:
1991-10-25 to 1991-11-2
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study with 24 hour exposure and termination at 72 hours without evidence of reversibility

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
skin was not abraded
Principles of method if other than guideline:
Group 1:
One intact site per rabbit treated with pure (100%) test material.
Group 2:
4 intact sites per rabbit treated with four single applications of the test material at concentrations of 50, 25, 12.5 and 6.25% in light, white mineral oil.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 100%
- Physical state: brown liquid
- Stability under test conditions: Considered stable under normal storage conditions
- Storage condition of test material: Sealed container at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products Inc., Denve, Pennsylvania, USA
- Age at study initiation: Young adult
- Weight at study initiation: 2715 - 3176 g
- Housing: Individual suspended wire mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 66 - 70°F
- Humidity (%): 43 - 72%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 1991-10-25 To: 1991-11-02

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: light white mineral oil
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site
- Concentration (if solution): 100%

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 50, 25, 12.5 and 6.5%
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
12 rabbits (3 male, 9 female)
2 x group of 6 rabbits
Details on study design:
TEST SITE
Group 1
- Area of exposure: back, 1" x 1" patch, one site only
- % coverage: not specified
Group 2
- Area of exposure: back, 1" x 1" patch, 4 sites per rabbit
- % coverage: not specified

- Type of wrap if used: 2 ply gauze patch overwrapped with a gauze binder and secured with Dermiform tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, disposal paper towels moistened with tepid tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 hour
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 100% test material
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2.5
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 100% test material
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 50% test material
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3.4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 50% test material
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2.9
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 25% test material
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 25% test material
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 12.5% test material
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.5
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 12.5% test material
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.5
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 6.25% test material
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0.58
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 6.25% test material
Irritant / corrosive response data:
Dermal observations (See Table 1)

In Group 1, neat (100%) test material induced severe erythema and slight to moderate oedema. Eschar was present on all sites. Exfoliation and necrosis were noted on two sites each. There were no other dermal findings.

In Group 2, the 6.25% w/v concentration induced very slight to slight erythema and oedema on six and three sites respectively. Desquamation was noted on one site. There were no other dermal findings

In Group 2, the 12.5% w/v concentration induced slight to moderate erythema and very slight to slight oedema. Desquamation was present on one site. There were no other dermal findings.

In Group 2, the 25% w/v concentration induced slight to severe erythema and oedema. Eschar was noted on two sites. There were no other dermal findings.

In Group 2, the 50% w/v concentration induced severe erythema and moderate to severe oedema. Eschar was present on all sites. Blanching was noted on one site.
Other effects:
Mortality:
None of the rabbits died.

Body weights:
There were no treatment related effects on bodyweight

Any other information on results incl. tables

Table 1: Observations

Rabbit Number

Erythema

Oedema

24 h

72 h

24 h

72 h

100%

1

4e

4e

3

3

2

4e

4e

3

2

3

4e

4ex

2

2

4

4e

4en

3

2

5

4e

4en

3

2

6

4e

4ex

2

3

Mean Total

4.0

2.5

50%

1

4e

4e

3

3

2

4e

4e

4

3

3

4e

4e

4

3

4

4e

4e

4

3

5

4be

4be

4

4

6

4e

4e

3

3

Mean Total

4.0

3.4

25%

1

4e

4e

4

4

2

2

2

2

2

3

3

3

3

3

4

2

2

2

2

5

3

4e

3

3

6

3

3

2

2

Mean Total

2.9

2.67

12.5%

1

3

2

2

2

2

2

1d

1

0

3

2

2

2

2

4

2

2

1

1

5

2

2

2

2

6

2

2

1

2

Mean Total

2.0

1.5

6.25%

1

2

2

2

1

2

2

2

1

1

3

2

2

1

1

4

1

1

0

0

5

1

1d

0

0

6

1

1

0

0

Mean Total

1.5

0.58

e = eschar

n = necrosis

x = exfoliation

d = desquamation

b = blanching

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive)
Remarks:
Migrated information Pure test material Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the pure test material induced necrosis in 2 out of 6 animals by the 72 hour observation period and at the 50% w/v concentration, blanching was seen in one out of 6 animals. In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is required for skin corrosivity/irritation.
Erythema and oedema scores for the 12.5% w/v concentration would preclude the classification as a skin irritant at this dose level. However in the absence of observations beyond the 72 hour time point the potential for reversibilty of these effects is unknown. Therefore classification as Cat 2: Irritant is applicable at this concentration level.
Executive summary:

Test Guidance

Skin irritation study performed by a similar method to US OPP 81-5.

Method and Material

Group 1:

Six New Zealand White rabbits were shaved and a 0.5 mL portion of the test material was applied to an intact skin site. A gauze patch was placed over each application site and an impervious material was wrapped around the trunk of the animal to hold the patches. The wrapping was removed after 4 hours and washed .

Group 2:

Six New Zealand White rabbits were shaved and 4 intact sites per rabbit treated with four single applications of 0.5 mL each of the test material at concentrations of 50, 25, 12.5 and 6.25% in light, white mineral oil. A gauze patch was placed over each application site and an impervious material was wrapped around the trunk of the animal to hold the patches. The wrapping was removed after 4 hours and washed .

Treated areas were examined for erythema and oedema using the Draize method of scoring at 24 and 72 hours.

Results

In Group 1, neat (100%) test material induced severe erythema and slight to moderate oedema. Eschar was present on all sites. Exfoliation and necrosis were noted on two sites each. There were no other dermal findings.

In Group 2, the 6.25% w/v concentration induced very slight to slight erythema and oedema on six and three sites respectively. Desquamation was noted on one site. There were no other dermal findings In Group 2, the 12.5% w/v concentration induced slight to moderate erythema and very slight to slight oedema. Desquamation was present on one site. There were no other dermal findings.

In Group 2, the 25% w/v concentration induced slight to severe erythema and oedema. Eschar was noted on two sites. There were no other dermal findings.

In Group 2, the 50% w/v concentration induced severe erythema and moderate to severe oedema. Eschar was present on all sites. Blanching was noted on one site.

The only evidence of reversibility over the limited timeframe of the study was for oedema responses at the 6.25% test concentration.

Conclusion

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is required for skin corrosion/irritation.