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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:
1995-07-18 until 1995-07-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Test material form:
liquid
Specific details on test material used for the study:
Stabilizer: hydrocarbon

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: on the day of treatment, the animals had a mean body weight (and standard deviation) of 2.3 (0.1) kg
- Housing: The animals were housed individually in polystyrene cages
- Diet: All the animals had free access to 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France)
- Water: Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Photoperiod: 12 h/12 h

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated skin served as control
Amount / concentration applied:
A single dose of 0.5 mL of the test substance was applied
Duration of treatment / exposure:
3 minutes and 4 hours
Observation period:
1, 24, 48, 72 hours after application. One animal was observed after 96 hours.
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'Hygiène, 21300 Chenove, France) and a restraining bandage (Laboratoires 3M Santé, 92245 Malakoff, France).
No residual test substance was noted at removal of the dressing.

SCORING SYSTEM:
Erythema and eschar formation:
no erythema...0
very slight erythema (barely perceptible)...1
well-defined erythema...2
moderate to severe erythema...3
severe erythema (beet redness) to slight eschar formation (injuries in depth)...4

Oedema formation:
no oedema...0
very slight oedema (barely perceptible)...1
slight oedema (edges of area well-defined by definite raising)...2
moderate oedema (raised approximately 1 millimetre...3
severe oedema (raised more than 1 millimetre and extending beyond area of exposure)...4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 96 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After a 3-minute application: in one rabbit, very slight erythema (grade 1) was noted on days 2 and 3.
After a 4-hour application: in 2/3 rabbits, very slight erythema (grade 1) was observed for 24 or 48 hours after treatment. In one of these two rabbits, slight oedema (grade 2) was noted only one hour after treatment. In 1/3 animals, very slight to slight erythema (grade 1 or 2) was noted up to 72 hours.
Mean scores over 24, 48 and 72 hours for individual animal were 1.7, 0.7 and 0.3 for erythema, and 0.0 for oedema.
Other effects:
None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study experimental conditions, the test substance was considered non-irritant when administered by cutaneous route in rabbits.
Executive summary:

The potential of the test substance to induce dermal irritation was evaluated in rabbits according to the OECD 404 and EU method B4 guidelines. The test substance was applied in a first assay for a period of 3 minutes and 4 hours in one male New Zealand White rabbit.

Since the test substance was not strongly irritant in this first assay, it was applied for 4 hours in two other males in a second assay. A single dose of 0.5 mL of the test substance was applied to the closely-clipped skin of the flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately one hour, 24, 48 and 72 hours after removal of the dressing and then at 96 hours only for one rabbit.

Very slight to slight erythema was observed in the three animals until day 2, 3 or 4, respectively. In one rabbit, slight oedema was noted only one hour after treatment. Mean scores over 24, 48 and 72 hours for individual animal were 1.7, 0.7 and 0.3 for erythema and 0.0 for oedema.

Under our experimental conditions, the test substance was considered non-irritant when administered by cutaneous route in rabbits.