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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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
-Observations at 1 hr and on Day 2 were not reported, occlusive dressing was used instead of semi-occlusive dressing
GLP compliance:
no
Remarks:
Study pre-dates GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): diacetone alcohol (DAA)
- Physical state: Stated in the report as a "widely used solvent"
- Analytical purity: Not reported
- Lot/batch No.: Reference PER 47657/2
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley, Sussex
- Age at study initiation: 4 to 5 months
- Weight at study initiation: Not reported
- Housing: Housed individually in cages
- Diet (e.g. ad libitum): rabbit food (SG1 with vitamin C supplement, Grain Harvesters Ltd.) was replenished daily
- Water (e.g. ad libitum): Filtered but untreated water from the public supply was automatically replenished
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature, 22 ± 2
- Humidity (%): 55 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
other: shorn with fine electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL or 500 mg
- Concentration (if solution): undiluted

Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6 (3 animals/sex)
Details on study design:
TEST SITE
- Area of exposure: After the dorsal hair between shoulders and hindquarters was closely shorn, 2 test sites located lateral to the midline were selected. One of the test sites was abraded using a fine hypodermic needle giving injuries deep enough to disturb the stratum corneum without bleeding.
- % coverage: 2 x 2 cm
- Type of wrap if used: To each test site, a 2 x 2 cm lint patch was applied and 0.5 mL or 500 mg of the test material applied. The patches were occluded by an impervious polythene sheet held in place by means of an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The wrappings and patches were removed and the residual test material washed from the skin with warm dilute detergent solution.
- Time after start of exposure: After 24 hours

SCORING SYSTEM: The intact and abraded test sites were examined and scored for erythema and oedema on a graded scale of 0 to 4 at 24 hours, 72 hours, and 7 days after application as detailed below:

Erythema scale: Score
No erythema: 0
Very slight erythema (barely perceptible, area not defined): 1
Well defined erythema (pale red, area well defined): 2
Moderate to severe erythema (bright red, area well defined): 3
Severe erythema (beet or crimson red): 4

Oedema scale: Score
No oedema: 0
Very slight oedema (barely perceptible, edges of area not defined): 1
Slight oedema (edges of area defined by raising): 2
Moderate oedema (area well defined, raised 1 mm): 3
Severe oedema (area raised more than 1 mm, extends beyond exposure area): 4

Injury in depth: Score
Escharosis, necrosis: 8

On the basis of the mean scores for erythema and oedema of the intact and abraded skin after 24 and 72 hours, the number of animals showing the responses and the persistence of the responses at 7 days, the irritation was transcribed into a grade and descriptive rating as follows:
1 = Non-irritating
2 = Minimally irritating
3 = Slightly irritating
4 = Mildly irritating
5 = Moderately irritating
6 = Severely irritating
7 = Extremely irritating

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
erythema scorenon-abraded skin
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
edema score non-abraded skin
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
edema score non-abraded skin
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4

Applicant's summary and conclusion

Interpretation of results:
other: minimally irritating (not classified)
Remarks:
Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
A single 24 h application of the test material to occluded rabbit skin was minimally irritating.
Executive summary:

A skin irritation study on diacetone alcohol has been conducted in which no guidelines were followed; however, the study design was similar to OECD Guidelines for the Testing of Chemicals No. 404 with deviations.  In this study, 6 New Zealand White rabbits (3 animals/sex) were exposed to 0.5 mL of undiluted diacetone alcohol on the shorn dorsal region (intact and abraded) under occlusive conditions.  Animals were exposed to the test compound for 24 hours and observations were recorded at 24 and 72 hours, and 7 days after application of the test substance.  Skin reactions were scored according to a prescribed numerical system.  Very slight transient erythema was observed in 3 animals with abraded skin, which was fully reversible by Day 3 in all 3 animals.  The other rabbits with abraded skin did not display any dermal reactions.  No irritation was observed in animals with intact skin.  Based on the results of this study, the authors stated that diacetone alcohol was "minimally irritating to rabbit skin". However, the substance is considered to be non-irritating to intact skin.