(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:

13 October 1997 to 19 October 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

413-110-2

EC Name:

-

Cas Number:

135861-56-2

Molecular formula:

C24H30O6

IUPAC Name:

1-[2,6-bis(3,4-dimethylphenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Gel All DX
- Substance type: white powder
- Physical state: solid
- Storage condition of test material: room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.54 to 2.75 kg
- Housing: animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16- 19 °C
- Humidity (%): 55- 74 %
- Air changes (per hr): 15 changes per hr
- 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): volume 0.1 mL , which was found to weigh approximately 41 mg

Duration of treatment / exposure:

Single application lasting 72 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

One rabbit was initially treated. A volume of 0.1 mL of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about 1 s immediately after application, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, 2 additional animals were treated.

Assessment of ocular damage/irritation was made approximately 1 h and 24, 48 and 72 h following treatment, according to the Draize scale for scoring ocular irritation.

Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects at any observation in any animal

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No iridial effects at any observation in any animal

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 1 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 14 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 15 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 1 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 14 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 15 - male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Tables 1 and 2 (attached background material). The individual means scores are presented in Table 3 (attached background material).

Residual test material was noted around 1 treated eye at the 1-hour observation but did not prevent an evaluation of the ocular responses.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes 1 h after treatment with minimal conjunctival irritation at the 24-hour observation. Minimal conjunctival persisted in 1 treated eye at the 48-hour observation.

Treated eyes appeared normal at the 48 or 72-hour observations.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The eye irritancy potential of the test material was assessed according to OECD guideline 405.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce postive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48 or 72-hour observations.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).