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
Study period:
04 June 1998 to 12 June 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-isopropyl-9H-thioxanthen-9-one
EC Number:
226-827-9
EC Name:
2-isopropyl-9H-thioxanthen-9-one
Cas Number:
5495-84-1
Molecular formula:
C16H14OS
IUPAC Name:
2-isopropyl-9H-thioxanthen-9-one
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: yellow powder

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:NZW/KbI.BR
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 11 to 14 weeks old
- Weight at study initiation: 2.05 to 2.41 kg
- Housing: Rabbits were housed in floor-pens, each accommodating one animal throughout the acclimatisation and experimental phases of the study. Each pen had a minimum floor area of 0.6 square metres. The partitions between pens were constructed of slotted laminate board 1.0 m high. Wood chips were provided as floor litter. Each batch of wood chips was analysed for specific contaminants.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 8 to 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16 to 22 °C
- Humidity: 40 to 80 % (expected range)
- Air changes: 10 air changes per hour
- Photoperiod: The room was illuminated by fluorescent strip-lights for twelve hours daily.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
3 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 30 x 20 mm area on the clipped dorsum
- Type of wrap if used: After moistening with approximately 0.1 mL of water, the dose was spread uniformly over the designated area and then each site was covered by a dense gauze patch (30 x 20 mm) on Day 1. This in turn was covered by a larger gauze patch (40 x 40 mm) and an open weave elasticated adhesive bandage which was wrapped firmly around the torso to secure the applied dose and patch in the correct position. The dressing was considered to be semi-occlusive.

REMOVAL OF TEST SUBSTANCE
- The test patch was removed after four hours and the treated skin was lightly brushed clean of any solid residues and swabbed with moist cotton wool. The location of the test site was marked on the dorsum with indelible ink after completion of the cleansing process.

OBSERVATION TIME POINTS
- The condition of the treated skin of the sentinel was assessed for a period of at least three days to ensure the test material did not cause severe dermal changes. Subsequently, two further rabbits were subjected to a single, four hour, semi-occluded topical application of 500 mg of test material to moistened skin.
- Clinical signs: A detailed account of any clinical signs of ill health or systemic toxicity was maintained.
- Body weights: Each rabbit was weighed on the day before dosing (Day -1).
- Dermal reactions: The conditions of the dermal test sites were recorded immediately after removal of the patches and dressings from the sentinel animal. The condition of all dermal test sites was recorded approximately one hour, 24. 48 and 72 hours after removal of the patch and dressing. Inflammatory skin reactions were graded according to the following scheme:

Erythema and eschar:
- No erythema = 0
- Very slight erythema = 1
- Well-defined erythema = 2
- Moderate erythema = 3
- Severe erythema (beet redness) or eschar preventing reading of erythema = 4

Oedema:
- No oedema = 0
- Very slight oedema (barely perceptible) = 1
- Slight oedema (edges of area well-defined by definite raising) = 2
- Moderate oedema (edges raised approximately 1 mm) = 3
- Severe oedema (raised >1 mm and extending beyond area of exposure) = 4

TERMINAL PROCEDURES
- All rabbits were killed by intravenous injection of an overdose of sodium pentobarbitone, following confirmation that the condition of the dermal test sites was normal, on Day 4. No tissue preservation or histopathological assessment of tissues was undertaken.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Dermal responses
- No dermal change or response to treatment was observed in any animal throughout the observation period.

Other effects:
Clinical signs
- There were no signs of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study the test material was determined to be non-irritating to the skin.
Executive summary:

A study was performed to investigate the potential of the test material to cause dermal irritation in accordance with the standardised guidelines OECD 404 and EU Test Method B.4 under GLP conditions.

The test article (500 mg) was applied to a 30 x 20 mm area on the clipped and moistened dorsum of each of three New Zealand White rabbits on Day 1. The treated area of skin was covered by a semi-occlusive bandage for four hours. Dermal reactions to treatment were assessed for up to three days after removal of the dressings.

No dermal changes were observed following a single semi-occluded application of the test material to intact rabbit skin for four hours.

Under the conditions of this study the test material was determined to be non-irritating to the skin.