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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD 404. GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
multiple test sites per animal, including abraded test sites and occluded sites. 4h exposure was occluded
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MCP 917
- Physical state: colorless homogeneous liquid
- Expiration date of the lot/batch: 04/01/1994
- Stability under test conditions: stable for 5 years at room temperature
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, PA
- Age at study initiation: young adult
- Weight at study initiation: ~ 2.0-4.0 kg

Test system

Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4-hour (occluded) and 24 hours (occluded and non-occluded)
Observation period:
Following the 4 hour exposure, the test sites were evaluated for dermal irritation at 4.5, 28, 52, and 76 hours. Following the 24 hour exposure, clinical observations were recorded at approximately 1 and 4 hours post-dosing and the sites were evaluated for dermal irritation at 26 and 72 hours post-exposure.
Number of animals:
6 animals (3/sex).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
male
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
male
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
male
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
female
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
female
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
female
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
male
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
male
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
male
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
female
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
female
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
female
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
male
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
male
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
male
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
female
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
female
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
female
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure effects were fully reversible within 72 hours for all but one animal
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
male
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
male
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
male
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
female
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
female
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
female
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
male
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
male
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
male
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
female
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
female
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
female
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
male
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
male
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
male
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
female
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
female
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin, 4 hour occlusive exposure
Other effects:
4 hour exposure of abraded skin under occlusive conditions resulted in a combined erythema mean of 0.47 and a combined edema mean of 0.067. Erythema was not fully reversible within 72 hours whereas edema was fully reversible within 48 hours.

24 hour exposure of non-abraded skin under non-occlusive conditions resulted in a combined erythema mean score of 1.0 at 26h and 0.2 at 72h; and a combined edema mean score of 1.0 at 26h and 0 at 72 hours after onset of exposure.

24 hour exposure of intact skin under occlusive conditions resulted in a combined erythema mean of 1.0 and the combined edema mean was 0.75; both the erythema and edema were not fully reversible within 72 hours. 24 hour exposure of abraded skin under occlusive conditions resulted in a combined erythema mean of 1.0 and a combined edema mean of 0.65; both erythema and edema were not fully reversible within 72 hours.

24 hour exposure of intact skin under non-occlusive conditions resulted in a combined erythema mean of 0.6 and the combined edema mean was 0.55; the edema, but not the erythema, was fully reversible within 72 hours. 24 hour exposure of abraded skin under occlusive conditions resulted in a combined erythema mean of 0.85 and a combined edema mean of 0.5; the edema, but not the erythema, was fully reversible within 72 hours.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean erythema and edema scores for the study substance were 0.36 and 0.1 (4 hour occluded), 1.0 and 0.75 (24 hour occluded), and 0.6 and 0.5 (24 hour non-occluded), respectively.This finding does not warrant classification of the study substance as a dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) nor as an R38 skin irritant under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

The study substance was administered to the skin of New Zealand White rabbits. Test sites were selected on both the left and right flank of each animals and designated as anterior (4-hour, occluded), middle (24-hour, occluded), and posterior (24-hour, non-occluded). All sites of the right flank were abraded. 0.5 ml of the study substance was applied to each test site. Following the 4 hour exposure, the test sites were evaluated for dermal irritation at 1/2, 24, 48, and 72 hours according to the Draize method. Following the 24 hour exposures, both test sites were evaluated at 26 and 72 hours. Clinical observations were recorded at approximately 1 and 4 hours post-dosing. Slight to moderate erythema and edema were noted at each test site. Soft stool, decreased fecal output, and decreased food consumption were observed in one or more animals. The mean erythema and edema scores for the study substance were 0.36 and 0.1 (4 hour occluded), 1.0 and 0.75 (24 hour occluded), and 0.6 and 0.5 (24 hour non-occluded), respectively.This finding does not warrant classification of the study substance as a dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) nor as an R38 skin irritant under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.