Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

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:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
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:
MCP 968 is a straw colored homogenous liquid. The MEHSL CRU number is 90163. This substance is stable for 6 month at 20C with an expiration date of 8/30/1990.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three male and three female young adult New Zealand White rabbits obtained form Hazleton Research Products, Inc. (Denver, Pa) were used in this study. The animals were identified by individual ear tags and cage cards. The temperature of the study room was maintained at 68-71F with a relative humidity of 44-66%

Test system

Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5ml
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).
Details on study design:
Three 1 sq. in. test sites were selected on both the left and right flank of each animal and designated as anterior (4-hour, occlusion), middle (24-hour occlusion), and posterior (24-hour, no occlusion). All sites on the right flank were abraded prior to administration prior to administration of the test substance. 0.5mls of the test substance was applied to the anterior and middle test sites under Webril patches. The patches were secured with an occlusive rubber dam followed by a non-irritating surgical tape. 0.5mls of the test substance was also applied to the posterior test sites without occlusion. Elizabethan style collars were fitted to each animal after administration of the test substance. Following a 4 hour exposure the anterior sites were unwrapped and evaluated fro dermal corrosion. The residual test substance was wiped from the test sites and the sites reevaluated fro corrosion 48 hours post-dosing. The test sites were also evaluated for dermal irritation at 4.5, 28, 52, 76 hours according to the Draize method.

Following a 24 hour exposure period the middle test sites were unwrapped and the residual test substance wiped from both the middle and posterior test sites. These sites were evaluated for dermal irritation at 26 and 72 hours according to the Draize method. Clinical observations were recorded at approximately 1 and 4 hours post-dosing and daily thereafter. T he condition of each animal (live, dead, moribund) was checked daily in the morning.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h
Score:
0
Remarks on result:
other: 4hr occluded exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Remarks:
combined mean
Basis:
mean
Time point:
other: 24/48/72 hr average
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0.2
Reversibility:
fully reversible
Remarks:
by 48 hours
Remarks on result:
other: 4 hour occluded exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hrs
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Remarks:
combined mean
Basis:
mean
Time point:
other: 24/48/72 hr average
Score:
ca. 0.07
Max. score:
0.2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Score:
1
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #5
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
48 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
0
Remarks on result:
other: 4 hr occluded exposure
Other effects:
4 hour exposure of abraded skin under occlusive conditions resulted in a combined erythema mean of 0.2 and a combined edema mean of 0.23. Evidence of erythema and edema were reported at all time points. Neither edema nor erythema were fully reversible within the 72 hour timepoint.

24 hour exposure under occluded conditions of unabraded skin resulted in erythema scores of 0.3 and 0 at 24 and 72 hours respectively, and edema scores of 0.5 and 0 at 24 and 72 hours respectively. Under semiocclusive conditions, 24 hour exposure to unabraded skin resulted in erythema and edema scores of 0 at 24 and 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 test material were 0 and 0.07 (4 hour occluded).This finding does not warrant classification of the test material 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 test material 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 test 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. Soft stool, decreased fecal output, and decreased food consumption were observed in one or more animals. The mean erythema and edema scores for the test material on unabraded skin were 0 and 0.7 (4 hour occluded), 0.15 and 0.25 (24 hour occluded), and 0 and 0 (24 hour non-occluded), respectively.This finding does not warrant classification of the test material 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.