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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March to June 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 February 1987

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Age at study initiation: adults
- Weight at study initiation: male: 2.6 kg; females: 3.1 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: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%):52-58
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100 % a.i.

Duration of treatment / exposure:

single exposure and observation 0.5, 1 and 2 h after application and once daily afterwards until day 16

Observation period (in vivo):

16 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: According to OECD test guideline 405

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: not specified

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal: #2 #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 16 days

Results 2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 16 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: #2 #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 16 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 16 days

Results 5

Irritation parameter:

iris score

Basis:

animal: #1 - #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 16 days

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal: #2 #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 16 days

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 16 days

Any other information on results incl. tables

Test substance/ Calculation for EEC classification
Location (finding)	Time point after end of exposure time	690M	702F	704F
Cornea (opacity	24 h	1.0	1.0	1.0
	48 h	2.0	1.0	1.0
	72 h	2.0	1.0	1.0
Individual mean values		1.67	1.0	1.0
iris	24 h	1.0	1.0	1.0
	48 h	1.0	1.0	1.0
	72 h	1.0	1.0	1.0
Individual mean values		1.0	1.0	1.0
Conjunctivae (reddening)	24 h	2.0	3.0	3.0
	48 h	3.0	3.0	3.0
	72 h	3.0	3.0	3.0
Individual mean values		2.67	3.0	3.0
Conjunctivae (swelling)	24 h	2.0	3.0	3.0
	48 h	1.0	3.0	3.0
	72 h	1.0	2.0	2.0
Individual mean values		1.3	2.67	2.67

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

On the whole, a single application of Trioxabicyclooctan into the conjunctival sac of the rabbit eye provoked severe irritation which lasted for several days after application and which only very slowly normalized over a period of up to 16 days.
Although the rabbit eye reacts more sensitively than the human eye due to anatomical and physiological. differences, similar effects have to be expected on the human eye. Therefore, inadvertent contact of the human eye with this substance should be strictly avoided.

Executive summary:

In a primary eye irritation study according to OECD test guideline 405 (1987), 100 µL Trioxabicyclooctan (100 % a.i.) were instilled into the conjunctival sac of one eye of 3 young adult New Zealand White rabbits. Animals then were observed for 16 days. Irritation was scored by the method recommended by the test guideline.

After application of 100 µL of the test sample into the conjunctival sac, there were slight reactions in the cornea and initially strong changes in the conjunctivae, which are completely reversible within 16 days. According to Regulation (EU) No. 1272/2008 (CLP) the test item is classified as Category 2 (irritating to eyes) based on the results obtained under the conditions described.