Octane-1,2-diol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to an internationally accepted technical guideline and in compliance with GLP in a recognized contract research organization.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

of 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Octane-1,2-diol

EC Number:

214-254-7

EC Name:

Octane-1,2-diol

Cas Number:

1117-86-8

Molecular formula:

C8H18O2

IUPAC Name:

octane-1,2-diol

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Species, Strain: Rabbits, New Zealand White (SPF Crl:NZW)
- Source: Charles River Wiga GmbH, D-97320 Sulzfeld, Germany
- Number and Sex: 2 males
- Age on day of dosing (Day 1): > ca. 3 months
- Weight prior to dosing (Day 1): Minimum 3790 g and 4545 g
- Housing: Individual housing in stainless steel cages (50 x55 x40 cm) with ovally peforated floor
- Bedding: ALTROMIN Type S8/15, granulated soft wood bedding
- Diet (ad libitum): Standard diet for rabbits (Brand: "ALTROMIN 2123"; Altromin, 32791 Lage/Lippe, Germany)
- Water(ad libitum): Tap water (municipal supply), in Makrolon® bottles, changed daily
- Acclimation period: Ca. 3 months prior to study start under laboratory conditions.

Routine analysis of the batch of diet used for nutrients and possible contaminants (heavy metals, aflatoxins, pesticides) and of the drinking water and bedding material for microbial contaminants, heavy metals and halogenated hydrocarbons were conducted or available at the testing facility.

ENVIRONMENTAL CONDITIONS

Air conditioned animal room set at:
- Temperature (°C): 21.5 to 22.5°C
- Relative Humidity (%): 40 to 70%
- Photoperiod: 12 hours artificial light, 12 hours dark per 24 hours

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL of the undiluted liquid test material was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.

Duration of treatment / exposure:

The treated eyes of both animals were carefully rinsed with deionised water at 1 hour after test material instillation, because of conjunctival redness and chemosis, grade 1 and 2, respectively. At 24 h after test material instillation, the treated eye of animal #1 was rinsed again, because of corneal opacity grade 2 in this eye.

Observation period (in vivo):

animal #1: 16 days
animal #2: 14 days

Number of animals or in vitro replicates:

2 male rabbits

Details on study design:

EYE EVALUATION:

Before treatment start both eyes of each animal were investigated after instillation of 2 or 3 drops of fluorescein sodium solution (0.5% in deionised water) into the conjunctival sac, to ensure that there were no pre-existing ocular defects. After 30 seconds the eyes were rinsed with deionised water.

One animal was initially treated and, in view of corneal opacity up to grade 2 and iridic swelling grade 1 for a number of days in this animal (#1), only one other animal (#2) was committed to the study for confirmation of the initial results 13 days afterwards.

Eyes were evaluated in both animals at approximately 1, 24, 48 and 72 hours after test material instillation adopting the numerical scoring system listed in Table 1 in the field below. Additional examinations were performed daily thereafter ending 16 and 14 days after test material instillation in animals #1 and #2, respectively. Grades attained at 48, 72 and 96 hours after instillation were included in the mean gradings of ocular lesions. Staining with fluorescein sodium solution supported the recognition of corneal lesions in animal #1 at 6 & 9 days after test material instillation and in #2 at 6, 8, 10 & 14 days after test material instillation.

Equipment used for eye evaluation: Hand slit-lamp (Heine OPTOTECHNIK)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: A lesion of the superficial epithelium of the cornea, ca. 3 mm diameter, was seen from Day 5 to Day 8 after test material instillation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: A lesion of the superficial epithelium of the cornea, ca. 3 mm diameter, was seen from Day 5 to Day 8 after test material instillation

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 11 days

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Corneal lesions, grade 1 or 2 in animal #1 and grade 1 in #2 were seen from 1 hour (Day 0) or 24 hours after test material instillation (Day 1) and had entirely disappeared by Day 16 in animal #1 and by Day 14 in animal #2. On a number of consecutive days, a lesion of the superficial epithelium of the cornea, ca. 3 mm in diameter, was recorded in each animal.

Swelling of the iris (grade 1) was evident in animal #1 from 48 hours until 11 days after test material instillation and in animal #2 from 1 hour until 8 days after instillation and associated with circumcorneal hyperaemia in the iris in animal #1 for 5 days and animal #2 for 4 days. The observation of an oval appearance of the pupil seen on a number of days in each animal was considered to be related to iris swelling.

In addition to the findings specified above and under "Overall irritation/corrosion results", conjunctival redness grade 1 and chemosis grade 2 followed by grade 1 were also seen in both animals at 1 and 24 hours after instillation, and on some occasions, mucous secretion from the eye was recorded.

All ocular findings seen in the present study were fully reversible. Control eyes (untreated) were without ocular findings throughout the observation period.

Other effects:

Mortality or signs of systemic toxicity were not evident and bodyweight was unaffected by treatment with the test material.

Applicant's summary and conclusion

Interpretation of results:

other: irritating to eyes