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Toxicological information

Eye irritation

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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

Constituent 1
Chemical structure
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

Resultsopen allclose all
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
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
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
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
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
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
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
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
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
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