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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: GLP 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:
(1987)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
425-240-7
EC Name:
-
Molecular formula:
C28H42O8Cl2Co2N12Zn4
IUPAC Name:
Zinc hexacyanocobaltate(III), tertiary butyl alcohol/polypropylene glycol complex

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Crl:NZW/Kbl.BR
- Sex: males
- Source: Charles River Ltd., Margate, UK
- Age at study initiation: approx. 11-14 weeks
- Weight at study initiation: 2.74-3.09 kg
- Housing: singly in floor-pens with minimum floor area of 0.6 m².
- Diet and water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22°C
- Humidity (%): within the range 40-80%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 10/14

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and served as a control.
Amount / concentration applied:
22 mg (weight equivalent to compacted volume of 0.1 ml)
Duration of treatment / exposure:
After instillation the eyelids were held closed for a few seconds to prevent loss of the dose.
Observation period (in vivo):
As ocular changes persisted, further observations were recorded daily until resolution of the changes occurred or until Day 22.
Number of animals or in vitro replicates:
3
Details on study design:
One dose consisting of the above specified amount of powdered test substance, dispensed from a spatula, was instilled into the left conjunctival sac of a single rabbit. The lower eyelid was gently prised away from the eyeball to create a receptacle for the dose. After instillation the eyelids were held closed for a few seconds to prevent loss of the dose. The condition of the treated eye of the rabbit was assessed for a period of not less than three days to ensure the test article did not cause marked ocular damage. Subsequently, two further rabbits were subjected to a single instillation of the test article into the left conjunctival sac as described above.

Further details on study: Any clinical signs of ill health or systemic toxicity was maintained. The weight of each rabbit was determined on the day before dosing commenced. Ocular changes were assessed and recorded immediately, one half hour, one and four hours after treatment on Day 1 and 24, 48 and 72 hours after treatment.

TOOL USED TO ASSESS SCORE: pencil-beam torch. At examinations carried out 24 hours after treatment, and on subsequent daily examinations, the cornea was subject to application of 2% aqueous fluorescein solution followed by irrigation with water for irrigation. The corneal surface was then illuminated by an ultraviolet source.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 12 days
Remarks on result:
other: mean score after 72 h: 1.3
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 22 days
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: mean score after 72 h: 1.7
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score after 72 h: 0.7
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 20 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: mean score after 72 h: 1.3
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
>= 0 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score after 72 h: 0.7
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: mean score after 72 h: 1.7
Irritant / corrosive response data:
The treated eye of one animal showed corneal damage (circa 10% of corneal surface affected) which persisted for three weeks after instillation of the test article.
Other effects:
There was virtually no initial sting response. No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of the study.

Applicant's summary and conclusion

Executive summary:

An acute eye irritation/ corrosion test according to OECD TG 405 was performed on three male rabbits. Ocular reactions were assessed for up to 21 days after treatment.

Within 24, 48 and 72 hours after instillation of the test substance areas of corneal opacity, conjunctival reactions and chemosis affected all rabbits (at maximum score 2). All conjunctival irritation resolved before completion of the observation period, but corneal changes persisted in one rabbit until the end of the study. There were no signs indicative of systemic toxicity or ill health noted during the course of the study.