Registration Dossier

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Test item: finasteride saturated lactam
Batch No.: M4A001N
Physical state: crystalline powder
Colour: White
Storage: at 15-30 °C, protected from light and moisture

Test animals / tissue source

Species:
other: Chicken eyes
Details on test animals or tissues and environmental conditions:
Chicken heads collection and transport:
Species of chicken: COBB 500
Source: TARAVIS KFT., Hungary
Head collection was performed by a slaughter house technician. Heads were removed immediately after sedation of the chickens (sedation was happened by electric current). The heads were transported to TOXI-COOP ZRT. at the earliest convenience for use approximately within 2 hours from collection. The ambient temperature was optimal (20.2 ºC to 21.1 ºC) during the transport. All eyes used in the assay were from the same groups of eyes collected on one specific day.
After collection, the heads were inspected for appropriate quality and wrapped with paper moistened with saline, then placed in a plastic box that can be closed (4-5 heads/box).
Eyes selection:
After removing the head from the plastic box, it was put on soft paper. The eyelids were carefully cut away with scissors, avoiding damaging the cornea. If the cornea was in good condition, the eyeball was carefully removed from the orbit.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
The three test item were treated with 0.03 g/eye FINASTERIDE SATURATED LACTAM.
The three positive control eyes were treated in a similar way with 0.03 g Imidazole.
One negative control eye was treated with saline solution (9 g/L).
Duration of treatment / exposure:
The time of application was monitored, then after an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with 20 mL saline solution at ambient temperature, while taking care not to damage the cornea but attempting to remove all the residual test item if possible.
Observation period (in vivo):
The control and test eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse. Minor variations within ±5 minutes were considered acceptable.
The cornea thickness and cornea opacity were measured at all time points. Fluorescein retention was determined at baseline (t=0) and 30 minutes after the post-treatment rinse.
Number of animals or in vitro replicates:
Three test item treated eyes, three positive control eyes and one negetaive control eye were used in this study.
Details on study design:
The purpose of this Isolated Chicken Eye Test (ICET) was to evaluate the potential ocular corrosivity or severe irritancy of the test item FINASTERIDE SATURATED LACTAM by its ability to induce toxicity in enucleated chicken eyes. Each eye which was used in this study was collected in the slaughterhouse, eliminating the need for laboratory animals. The test compound was applied in a single dose onto the cornea of isolated chicken eyes in order to potentially classify the test compound as ocular corrosive and/or severe irritant. The damage by the test substance was assessed by determination of corneal swelling, opacity, fluorescein retention and morphological effects. These parameters were evaluated pre-treatment and starting at approximately 30, 75, 120, 180, and 240 minutes after the post-treatment rinse. The endpoints evaluated were corneal opacity, swelling, fluorescein retention, and morphological effects. All of the endpoints, with the exception of fluorescein retention (which was determined only at pre-treatment and 30 minutes after test substance exposure) were determined at each of the above time points.
The FINASTERIDE SATURATED LACTAM and Imidazole (positive control) were ground before use in the study. They were applied in an amount of 0.03 g/eye by powdering the entire surface of the cornea attempting to cover the cornea surface uniformly with the test substance or positive control. Three test item treated eyes and three positive control eyes were used in this study.
One negative control eye was treated with 30 μL saline solution.
After an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with ~20 mL saline solution at ambient temperature and this procedure was repeated for each eye.
In this ICET, FINASTERIDE SATURATED LACTAM did not cause ocular corrosion or severe irritation in the enucleated chicken eyes.
Positive and negative controls showed the expected results. The experiment was considered to be valid.

Results and discussion

In vivo

Irritant / corrosive response data:
In this ICET, FINASTERIDE SATURATED LACTAM did not cause ocular corrosion or severe irritation in the enucleated chicken eyes.
Positive and negative controls showed the expected results. The experiment was considered to be valid.

Any other information on results incl. tables

Observation

Value

ICEClass

Mean maximum corneal swelling at up to 75 min

1 %

I

Meanmaximumcorneal swelling at up to240 min

2 %

I

Mean maximum corneal opacity

0.5

I

Mean fluorescein retention

1.0

II

Other Observation

None

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
In this in vitro eye corrosives and severe irritants study, using the Isolated Chicken Eye model with finasteride saturated lactam, no ocular corrosion or severe irritation potential was observed. According to the guideline OECD 438, finasteride saturated lactam has been categorized as “No Category”.