Registration Dossier

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 May 2014 to 28 May 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted in compliance with OECD GLP (1997) and OECD Guideline 437 (2013).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
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

Constituent 1
Reference substance name:
MTDID 13999
IUPAC Name:
MTDID 13999
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): MTDID 13999
- Substance type: Pure active substance
- Physical state: Liquid
- Analytical purity: 99.0%
- Purity test date: 11 March 2014
- Lot/batch No.: Batch 529783
- Expiration date of the lot/batch: 23 September 2016

Test animals / tissue source

Species:
other: Not applicable
Strain:
other: No applicable
Details on test animals or tissues and environmental conditions:
No applicable: in vitro test on Bovine corneas.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Corneas were exposed to negative and positive controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 uL
Duration of treatment / exposure:
The corneas were exposed to the test article for 10 minutes at 32 degrees C.
Observation period (in vivo):
After exposure, the corneas were observed for possible pH effects. They were then incubated for 120 minutes. After the incubation period, the opacity of the
Number of animals or in vitro replicates:
0
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The corneas were washed with Minimum Essential Medium after exposure.
- Time after start of exposure: 10 minutes

SCORING SYSTEM: The opacity and permeability of each cornea was measured.

TOOL USED TO ASSESS SCORE: An opacitometer was utilized to measure the opacity of each cornea and sodium fluorescein was used to determine permeability.

Results and discussion

In vivo

Results
Irritation parameter:
other: In Vitro Irritation Score (IVIS)
Basis:
mean
Time point:
other: 10 minutes
Score:
ca. 12
Max. score:
13
Reversibility:
other: Not applicable
Irritant / corrosive response data:
The mean opacity score was 7 (range 6-7) and the mean permeability score was 0.300 (range 0.252-0.376). The mean in vitro irritation score (IVIS) was 12.0 after 10 minutes.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Irritating to eyes (CLP Category 2A) Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the test and OECD 437 (2013), MTDID 13999 is a possible eye irritant, but is not corrosive to eyes (IVIS = 12.0).
Executive summary:

The ocular corrosion potential of MTDID 13999 (clear yellowish liquid, Purity 99.0% CASRN 4303-67-7, Batch 529783) was tested in the Bovine Corneal Opacity and Permeability test (BCOP test). The study was performed in compliance with OECD GLP (98) 17 (1997). The test method was based on OECD no. 437 (2013), EC No. 440/2008 B. 47 (2010), OTWG- ICCVAM-NICEATM (2006), INVITTOX 127 (2006), and Gautheron, P. et al. 18: 442-449 (1992). Corneas were prepared in cell culture medium and incubated at 32 C for at least 1 hour prior to exposure. Corneas (3/group) were treated with 0.75 mL of undiluted MTDID 13999 test material and incubated in a horizontal position for 10 minutes at 32 C. A positive control (10% w/v Benzalkonium Chloride) and a negative control (physiological saline) were tested in parallel with the test material. At the end of the exposure period, the corneas were rinsed and incubated in fresh cell culture medium for 120 +/- 10 minutes at 32 C. Opacity was evaluated using an opacitometer after the 2 hour post-exposure incubation. Following opacity readings, the cell culture medium was replaced with Na-fluorescein medium and incubated for approximately 90 minutes at 32 C. Following the 90 minute Na-fluorescein exposure, permeability was measured. The mean in vitro irritation score (IVIS) was calculated and the scores were classified according to OECD 437 (2013). For MTDID 13999, the mean IVIS = 12 after 10 minutes. The mean opacity score was 7 (range 6-7) and the mean permeability score was 0.300 (range 0.252-0.376). The pH of the rinsing medium was not altered by the test substance. Based on the results of the test and OECD 437 (2013), MTDID 13999 is a possible eye irritant, but is not corrosive to eyes (IVIS = 12.0).