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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:
24th May to 7th June 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Similar to OECD guideline and conducted to 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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Composition data on the test material is held by the sponsor. The test material was received from the sponsor on May 16, 1988 and stored at ambient
temperature. In the opinion of the sponsor, the test material is stable under the recommended storage conditions.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: R and R Rabbitry, Stanwood, Washington
- Age at study initiation: The animals were 26-28 weeks old when dosed.
- Housing: The animals were housed individually in support bar-bottom cages in an air-conditioned room.
- Diet (e.g. ad libitum): The animals were fed a daily ration of Purina Certified High Fiber Rabbit Chow #5325
- Water (e.g. ad libitum): Free access to water.
- Acclimation period: Conditioning period of 18 weeks before dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22 °C
- Humidity (%): 58-83%
- Photoperiod (hrs dark / hrs light): The photoperiod was a 12-hour light/dark cycle.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: Animals were shaved and had 2 intact and 2 abraded sites
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 & 72 hours and then 7 & 14 days after treatment.
Number of animals:
6 females per dose
Details on study design:
TEST SITE
The fur on the backs of six rabbits was clipped the day before dosing. One-half milliliter of the test material was applied to each of two intact and two abraded sites on the back of each rabbit. Epidermal abrasions (cross-hatching) were made with a hypodermic needle penetrating the stratum corneum over areas of approximately one square inch. After application, each treated site was covered with a gauze patch secured by porous tape. The trunk of each animal was loosely wrapped in a sheet of plastic film, and paper towels were wrapped around the plastic to prevent tearing. A collar was also placed on each animal to protect the wrappings during the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After a four-hour exposure period, the wrappings and collars were removed, and the skin was wiped with gauze pads moistened with mineral oil, followed by dry gauze to remove any remaining test material.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Irritation was scored at 1, 24, 48, and 72 hours after removal of the test material and at 7 and 14 days, using a modified scoring method of Draize et al.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
3.4
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
2.8
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Intact skin
Irritation parameter:
primary dermal irritation index (PDII)
Score:
6.2
Irritant / corrosive response data:
The test material caused well-defined to severe erythema with no to moderate edema within one hour after unwrapping. Irritation increased to severe erythema and eschar formation with well-defined to severe edema at 24 through 72 hours. Cracking was observed on one animal at 72 hours. Severe erythema, eschar, cracking, a thin layer of light brown necrotic skin and thick light brown flakes were present on Day 7 with slight edema observed in one animal. At 14 days, well-defined to severe erythema, with eschar, a thin layer of light brown necrotic skin, thick light brown flakes, sloughing, alopecia and thin fur regrowth were present. There were no consistent differences between intact and abraded skin.
Other effects:
Microscopic findings included acanthosis, hyperkeratosis and subacute inflammation in all sites. Epidermal exudate was also observed. These findings are considered to be compound-related and indicate mild dermal irritation.

Any other information on results incl. tables

Based on the primary irritation score of 6.2, this test material is considered to be a severe skin irritant. Compound-related microscopic observations occurred at all treated sites.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on a primary irritation score of 6.2, the test material is considered to be a severe skin irritant. There were compound-related microscopic observations at all treated sites.
The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 3.5 and so will be classified as irritating according to the dangerous substances directive, 67/548/EEC.
Executive summary:

One-half milliliter of the test material was applied to two intact and two abraded areas on the back of each of six rabbits for four hours. The primary irritation score was 6.2. Erythema and edema were observed one hour after unwrapping. Severe erythema vas observed at 24 hours and persisted in some cases through Day 14; edema was present through Day 7.

Other signs of severe skin irritation were also observed; there were no significant differences between intact and abraded sites. Compound-related microscopic findings included acanthosis, hyperkeratosis and subacute inflammation in all sites. Epidermal exudate was also observed.

Based on a primary irritation score of 6.2, the test material is considered to be a severe skin irritant. There were compound-related microscopic observations at all treated sites. The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 3.5 and so will be classified as irritating according to the dangerous substances directive, 67/548/EEC.