4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-09-08 to 1996-01-09

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:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31. July 1992

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

EC Number:

421-750-9

EC Name:

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

Cas Number:

57280-22-5

Molecular formula:

C7H12O3

IUPAC Name:

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Age at study initiation: adults
- Weight at study initiation: males: 2.7 - 2.8 kg; females: 2.6 - 2.8 kg
- Housing: individually in conventional metal cages
- Diet (e.g. ad libitum): pell. Altromin® K ad libitum
- Water (e.g. ad libitum): demineralized water ad libitum
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 64-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100% a.i.

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: 6 cm² each site of the spine
- Type of wrap if used: Both sites (treated and untreated) were covered with a piece of gauze (semi-occlusive) fixed on the skin with Leukoflex®.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure the gauze was removed and the treated and untreated skin areas were wiped carefully with lukewarm tap water and cotton wool.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): Clinical observations were performed 30-60 minutes and 24 hours after end of exposure and thereafter daily until day 7 of the test and findings were recorded. Deviating from the method referred to in the study protocol the interval between daily clinical observations between days 4-5 for animal no. 548 and days 2-3 for the other animals was only 16 hours instead of 24 hours. This deviation is not considered to have influenced the result of the study since the animals were without findings on the respective days. Body weights were recorded on day 1 and day 7 of the test. Necropsy was not performed.

SCORING SYSTEM: According to guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

erythema score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The test item provoked on the intact skin of the rabbit after single application only very slight to slight reddening in two males and one female animal only on the appl!ication day. No other findings were observed during the observation period of 7 days.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to the system of evaluation recommended by EEC (1 ), the mean values of findings relevant for classification as ".irritant" (reddening· and scab formation, swelling) at the time points 24, 48 and 72 hours after application were 0. Also based to the classification criteria of Regulation (EU) No. 1272/2008 (CLP) the test item does not need to be classified with respect to skin irritation.

Executive summary:

In a primary dermal irritation study according to Annex to EEC directive 92/69/EWG, dated 31 Jul. 1992, for the 17th adaption of the EEC directive 67/548/EWG, 8.4. Acute Toxicity (Skin lrritation), young adult New Zealand White rabbits (4 animals) were dermally exposed to 500 µL of Trioxabicyclooctan (100 % a.i.) for 4 hours to 6.5 cm² skin. Animals then were observed for 7 days.  Irritation was scored by the method recommended by the guideline.

Trioxabicyclooctan provoked on the intact skin of the rabbit after single application only very slight to slight reddening in two males and one female animal only on the application day. No other findings were observed during the observation period of 7 days. According to the system of evaluation recommended by EEC (1 ), the mean values of findings relevant for classification as ".irritant" (reddening· and scab formation, swelling) at the time points 24, 48 and 72 hours after application were 0.

Based on the test results described above, the test item is not considered to be irritating to the skin according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).