Registration Dossier

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:
other: Study was conducted in compliance with OECD GLP (1997), FDA GLP, and EPA GLP regulations. Study was performed in compliance with OECD 437 (2013).

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 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Viscous liquid
Details on test material:
- Name of test material (as cited in study report): MTDID 15655
- Substance type: Mono-constituent
- Physical state: Viscous liquid
- Analytical purity: 91.4%
- Purity test date: 11 May 2015
- Lot/batch No.: 565093
- Expiration date of the lot/batch: 27 August 2017

Test animals / tissue source

Species:
other: NA: in vitro method
Strain:
other: NA: in vitro method
Details on test animals or tissues and environmental conditions:
Not applicable: in vitro method.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: None: in vitro method. Negative and positive control tissues were utilized.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 mL

VEHICLE: None
Duration of treatment / exposure:
Corneas were incubated at 32C with the test article or appropriate control for 10 minutes then washed with MEM solution containing phenol red.
Observation period (in vivo):
After exposure and washing, the tissue holders were filled with MEM solution and opacity measurements were made following the 10-minutes exposure and MEM solution refill.
Number of animals or in vitro replicates:
None: in vitro method
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The tissues were washed with MEM with phenol red after a 10 minute exposure to the test article or appropriate control.
- Time after start of exposure: 10 minutes.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

TOOL USED TO ASSESS SCORE: Fluorescein

All substances (test article and controls) were applied using the closed chamber method.

Results and discussion

In vivo

Results
Irritation parameter:
other: In Vitro Irritation Score (IVIS)
Basis:
mean
Time point:
other: 10 Minute
Score:
ca. 1.21
Irritant / corrosive response data:
The corrected mean opacity score was 1.00. The corrected mean optical density (permeability) score was 0.014. The in vitro irritancy score (IVIS) was calculated as 1.21.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the test article is expected to cause no significant irritation to the cornea (IVIS=1.21).
Executive summary:

The corneal irritation and damage potential of the test article (Viscous liquid, Lot # 565093, Purity: 91.4%) was tested in the Bovine Corneal Opacity and Permeability test (BCOP). The study was performed in compliance with EPA GLP 40 CFR 160 and 792, FDA GLP 21 CFR 58, and OECD GLP (1997). The test method was based on OECD Guideline 437 (2013). Corneas (3/group) were prepared in cell culture media. The corneas were mounted in specially designed holders and incubated at 32 C for at least 1 hour prior to exposure. Corneas were treated with 0.75 mL of the test article or appropriate control (Positive: 100% ethanol, Negative: MEM) using the closed chamber method and incubated for an approximate 10 minute exposure period at 32 C. At the end of the exposure period, the corneas were rinsed with cell culture media and incubated for 2 hours in cell culture solution. Opacity was evaluated prior to treatment and immediately following the 2 hour incubation. Immediately following the opacity measurement, the cell culture media was replaced with 0.4% sodium fluorescein solution in Dulbecco’s Phosphate Buffered Saline (DPBS) and incubated for another 90 minutes. Following the 90 minute incubation, permeability was evaluated using a fluorescein method. The mean in vitro irritation score (IVIS) was calculated and the scores were classified according to protocol defined categories. For the test article, the IVIS= 1.21. The corrected mean opacity score was 1.00 (range -1 to 1), and the mean permeability score was 0.014 (range 0.002 to 0.02). Controls performed as expected. Based on the results of the test, the test article is expected to cause no significant irritation to the cornea (IVIS = 1.21).