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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: Study conducted to OECD guidelines and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Between 12 and 24 weeks old
- Weight at study initiation: At least 1.5 kg
- Housing: Individually housed in labelled cages with performated floors and shelters.
- Diet (e.g. ad libitum): Pelleted diet for rabbits at approximately 100g per day. Hay and wooden sticks were also available.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days before the start of treatment, under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25°C
- Humidity (%): 40 to 70%
- Air changes (per hr): At least 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light, 12 hour dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Instillation on average of 82.9 mg (range 82.3 to 83.2 mg) of the test substance (a volume of approximately 0.1 mL).


Duration of treatment / exposure:
No test substance was observed on the eye at the first one hour observation check. This indicates it would have been removed by physiological mechanisms. Remnants of the test substance were noticed on the outside of the eyelid in one animal on Day 1.

If the test substance wasn't removed from the eye by physiological mechanisms at the first observation period of approximately 1 hour, the eye was rinsed with saline or distilled water.
Observation period (in vivo):
14 day observation period in surviving animals.
Number of animals or in vitro replicates:
3 (Study conducted in a stepwise manner and was started by treatment of a single rabbit (sentinel)). The two remaining animals were treated in a similar manner up to 3 weeks later, after considering the degree of eye irritation observed in the first animal.
Details on study design:
Eye irritation was assessed using the standard approach in the OECD 405 guidelines, which looks at corneal irritation (including the area of the cornea involved), Iris irritation, conjunctival irritation, chemosis, and evidence of discharge.

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.

Green staining after fluorescein treatment was used to determine the % of total corneal area effects.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of animals 1 and 2.
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
0.3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
of animals 1 and 2
Time point:
other: 24, 48 and 72 hours
Score:
0.15
Max. score:
0.3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of animals 1 and 2
Time point:
other: 24, 48 and 72 hours
Score:
2.15
Max. score:
2.3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Remarks:
of animals 1 and 2.
Time point:
other: 24, 48 and 72 hours
Score:
1.65
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Two animals showed similar eye irritation effects in the cornea, iris and conjunctivae approximately 1 hour after instillation.
Cornea: The corneal injury consisted of opacity and epithelial damage and resolved within 7 days.
Iris: Iridial irritation was observed and resolved within 24 hours in one of the animals, and within 48 hours in the other.
Conjunctivae: The irritation of the conjunctivae consisted of redness, chemosis, and discharge and completely resolved within 14 days in both animals.

There was no evidence of ocular corrosion.
Other effects:
One animal was found undergoing severe spasms followed by a comatose appearance approximately 45 minutes after instillation of the test substance. After this, the animal was sacrificed for humane reasons. Post mortem examination showed eye effects similar to the surviving rabbits.

As this effect was not seen in the two remaining rabbits (which both showed similar eye irritation effects and full reversibility) and that the sacrificed animal had mostly slightly lesser eye irritation findings, this effect is not considered to be evidence of systemic toxicity and was most likely a stress response of a potentially (prior to treatment) compromised animal.

Any other information on results incl. tables

Mean value eye irritations scores:

Animal

Mean 24, 48 and 72 hours

Corneal Opacity

Iris

Conjunctivae

Redness

Chemosis

1

0.3

0.3

2.0

1.3

2

0.3

0.0

2.3

2.0

3

-

-

-

-

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance showed eye irritation effects in two animals which were fully reversible by Day 14 of the observation period. One animal that was sacrificed for humane reasons had effects not attributed directly to treatment and systemic toxicity of the test substance.