Reaction mass of (2R*,4R*,4aR*,9bS*)-2,4-dimethyl-4,4a,5,9b-tetrahydroindeno[1,2-d][1,3]dioxine and (2R*,4R*,4aS*,9bR*)-2,4-dimethyl-4,4a,5,9b-tetrahydroindeno[1,2-d][1,3]dioxine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Feb - 02 Mar 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

yes

Remarks:

several test substance concentrations were applied on one animal

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Jan 1997

Deviations:

yes

Remarks:

several test substance concentrations were applied on one animal

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dimethyl-2H,4H,4aH,5H,9bH-indeno[1,2-d][1,3]dioxine

EC Number:

944-528-8

Molecular formula:

C13H16O2

IUPAC Name:

2,4-dimethyl-2H,4H,4aH,5H,9bH-indeno[1,2-d][1,3]dioxine

Test animals

Species:

rabbit

Strain:

other: SPF albino rabbits

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.8 - 3.0 kg
- Housing: individually in PPO cages
- Diet: Altromin 2123 (Altromin, Lage, Germany), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to ph 2.5, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: for test substance concentrations of 1, 10, 25 and 50% ethanol/diethylphthalat (1:1) was used as vehicle

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentrations: 1, 10, 25, 50 and 100%

Duration of treatment / exposure:

4 hours

Observation period:

72 hours
Reading time points: 1, 24, 48 and 72 hours

Number of animals:

4 females

Details on study design:

TEST SITE
- Area of exposure: 10 x 10 cm on the back (divided into six fields)
- Type of wrap: The test substance or vehicle was applied to 16-layer gauze patches (2.5 x 2.5 cm) and the patches placed on the appropriate test sites on the back of each rabbit. The gauze patches were secured with adhesive Gothaplast tape (2.5 cm wide) and fixed with Gothaplast tape (5 cm wide) loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: After application the skin sites were cleaned with mild soap and lukewarm water.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: test concentration: 100%

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: test concentration: 100%

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: test concentration: 100%

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: test concentration: 100%

Results 5

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversiblitiy: not applicable

Remarks on result:

other: test concentration: 100%

Irritant / corrosive response data:

One hour after termination of exposure none of the 4 animals showed skin reactions at any concentration. 24 hours after termination of exposure a very slight erythema (score 1) was observed in all animals at 100%. 48 hours after termination of exposure a very slight erythema (score 1) was observed in one animal at 100%. The other animals were free of any signs of skin irritation after 48 hours at 100%. No skin reactions were observed at 1, 10 and 50% test substance concentration at any reading time point. Only very slight erythema (score 1) was observed in one animal 24 hours after removal of the patch at 25% test substance concentration. The animal was free of signs after 48 hours.

Any other information on results incl. tables

Table 1: Individual skin examination scores with the undiluted test substance

Skin effect	Erythema				Edema
Scoring	24h	48h	72h	Mean^a	24h	48h	72h	Mean^a
Animal 1	1	1	0	0.67	0	0	0	0
Animal 2	1	0	0	0.33	0	0	0	0
Animal 3	1	0	0	0.33	0	0	0	0
Animal 4	1	0	0	0.33	0	0	0	0

^aMean of 24, 48 and 72 h scores

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this skin irritation study in rabbits the undiluted test substance (100%) was not irritating to the skin. Also the test substance concentrations of 1, 10, 25 and 50% in ethanol/diethylphthalat (1:1) did not show an irritation potential.