(1R)-1-[(4R,4aR,8aS)-2,6-bis(3,4-dimethylphenyl)tetrahydro[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5th March 1993 to 16th June 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline studies with restrictions. Information relating to the test animals, exposure and test system were not described in the main body of the report but were given in the protocol only.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

Purity: 97.3 %
Batch No.: 9236-23

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS (information provided in study protocol)
- Source: E.S.D., Romans, 01400, Chatillon-sur-Chalaronne, FRANCE
- Age at study initiation: adult (about 3 months old)
- Weight at study initiation: 2.00 to 3.00 kg
- Housing: Individually housed in stainless steel cages (internal dimensions 500 x 600 x 400 mm)
- Diet (e.g. ad libitum): About 150 g/animal/day of pelleted complete rabbit diet (Diet reference 112 C - Usine d'Alimentation Rationnelle, Villemoisson, 91360 Epinay-sur-Orge, FRANCE)
- Water (e.g. ad libitum): Softened and filtered mains drinking water available ad libitum (via automatic system)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (information provided in study protocol)
- Temperature (°C): Maximum recorded: 22.2 °C
- Humidity (%): >= 45%
- Air changes (per hr): minimum 12 air changes per hour
- Photoperiod: 12 hours Ilght (artificial)/12 hours dark

IN-LIFE DATES: Not specified

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 mg per animal (quantity corresponding to a volume of 0.1 mL) was applied into the inferior conjunctival sac of the right eye.

VEHICLE
Not applicable

Duration of treatment / exposure:

Not applicable

Observation period (in vivo):

Up to 7 days

Number of animals or in vitro replicates:

6 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were not rinsed after applciation of the test material.
- Time after start of exposure: Not applicable

SCORING SYSTEM: In accordance with OECD Guideline 405

TOOL USED TO ASSESS SCORE: Fluorescein (acorrding to the protocol)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

other: Mean overall score for 24, 48 and 72 h

Time point:

24/48/72 h

Score:

0.56

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. duration: 72 h; Max. value at end of observation period (extended to day 7): 0

Remarks:

Mean overall score for 24, 48 and 72 h

Results 2

Irritation parameter:

chemosis score

Basis:

other: Mean overall score for 24, 48 and 72 h

Time point:

24/48/72 h

Score:

0.22

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0

Remarks:

Mean overall score for 24, 48 and 72 h

Results 3

Irritation parameter:

cornea opacity score

Basis:

other: Mean overall score for 24, 48 and 72 h

Time point:

24/48/72 h

Score:

0.06

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0

Remarks:

Mean overall score for 24, 48 and 72 h

Results 4

Irritation parameter:

iris score

Basis:

other: Mean overall score for 24, 48 and 72 h

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0

Remarks:

Mean overall score for 24, 48 and 72 h

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 7 days

Other effects:

None reported

Any other information on results incl. tables

Table 1: Mean values for ocular irritation

Readings	Chemosis	Enanthema	Congestion	Opacity
at 24 hours	0.67	1.00	1.00	0.17
at 48 hours	0.00	0.50	0.00	0.00
at 72 hours	0.00	0.17	0.00	0.00
Global average (24 h + 48 h + 72 h)	0.22	0.17	0.33	0.06

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

From the results obtained under the experimental conditions employed, application of the test article to the rabbit eyes provoked a weak irritation but the lesions observed at 72 h in one animal showed a total reversibility by Day 7.

Executive summary:

The test material, Millad®3988, was evaluated for its acute ocular irritation and reversibility potential in male rabbits. The results obtained under the experimental conditions employed demonstrated that application of this test article to the eyes provoked a weak irritation but the effects were fully reversible by 72 hours after treatment.