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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Rabbit enucleated eye test
Version / remarks:
ICCVAM, 2006 and 2009
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

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

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals were 12 to 20 weeks old. Rabbits that have previously been used in skin or eye irritation studies at the test facility may be used as eye donors. If the donor animals have been used in an eye irritation study, only the untreated eyes were used.

Test system

Vehicle:
physiological saline
Controls:
yes
Amount / concentration applied:
A volume of 0.1 mL of the test item, which was found to weigh approximately 91 mg
Duration of treatment / exposure:
After 10 seconds the test item was washed off the cornea using a minimum of 20 mL of saline solution (approximately 32 °C).
Immediately following washing of the corneal surface, the treated eye was returned to the superfusion chamber and the saline drip repositioned to irrigate the eye.
Number of animals or in vitro replicates:
3
Details on study design:
Assessment of corneal cloudiness was made pre-enucleation, post equilibration and approximately 60, 120, 180 and 240 minutes following treatment.
Measurements for corneal thickness were carried out pre-enucleation, post equilibration and approximately 60, 120, 180 and 240 minutes following treatment.
The condition of the corneal epithelium was assessed approximately 60, 120, 180 and 240 minutes following treatment.
The uptake of fluorescein by the corneal epithelium was assessed pre-enucleation, post equilibration and approximately 240 minutes following treatment

Results and discussion

In vitro

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Run / experiment:
1A
Value:
0
Irritation parameter:
cornea opacity score
Run / experiment:
3A
Value:
0
Irritation parameter:
cornea opacity score
Run / experiment:
5A
Value:
0
Irritation parameter:
fluorescein retention score
Run / experiment:
1A
Value:
0
Irritation parameter:
fluorescein retention score
Run / experiment:
3A
Value:
0
Irritation parameter:
fluorescein retention score
Run / experiment:
5A
Value:
0
Irritation parameter:
percent corneal swelling
Remarks:
% Mean corneal swelling 1 hour following treatment
Run / experiment:
mean of 3 test eyes
Value:
12.2
Irritation parameter:
percent corneal swelling
Remarks:
% Mean corneal swelling 2 hour following treatment
Run / experiment:
Mean of 3 test eyes
Value:
11.4
Irritation parameter:
percent corneal swelling
Remarks:
Mean corneal swelling 4 hours following treatment
Run / experiment:
mean of 3 test eyes
Value:
6.6
Irritation parameter:
percent corneal swelling
Remarks:
60 min
Run / experiment:
mean of 2 control eyes
Value:
7.2
Irritation parameter:
percent corneal swelling
Remarks:
120 min
Run / experiment:
mean of 2 control eyes
Value:
7.4
Irritation parameter:
percent corneal swelling
Remarks:
240 min
Run / experiment:
mean of 2 control eyes
Value:
5.3
Irritation parameter:
morphological effects
Remarks:
Condition of Corneal Epithelium
Run / experiment:
3 runs
Remarks on result:
no indication of irritation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Following assessment of the data for all endpoints the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.
Executive summary:

A study was performed to assess the ocular irritancy potential of the test item in the rabbit following application onto the cornea of the enucleated eye. The results of the study are believed to be of value in predicting the ocular irritation potential of the test item in man.

0.1 mL of the test item, which was found to weigh approximately 91 mg, was applied onto the cornea of each of three enucleated eyes which had been maintained at a temperature of 32 ±1.5 °C within the superfusion chamber. A further two enucleated eyes remained untreated for control purposes.

Maximal ocular irritation observations recorded for the test eyes were as follows: Corneal Opacity (score 0), Fluorescein Uptake (score 0), Corneal Swelling (60 mins 12.2% test eyes mean of 3 runs vs 7.2% control eyes mean of 2 runs, 120 mins 11.4% test eyes mean of 3 runs vs 7.4% control eyes mean of 2 runs, 240 min 6.6% test eyes mean of 3 runs vs 5.3% control eyes mean of 2 runs), condition of corneal Epithelium (normal).

Following assessment of the data for all endpoints the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.