Registration Dossier

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 August 2010 - 29 September 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions and OECD Guideline 437

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 437: Bovine corneal opacity and permeability (BCOP) test method for identifying occular corosives and severe irritants (adopted September 7, 2009)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MTDID 21721, TFEE-5
- Substance type: clear colorless liquid
- Physical state: liquid
- Lot/batch no.: TFEE5-276/12/09-1
- Expiration date of the lot/batch: 12 Dec 2012
- Stability under test conditions: stable
- Storage condition of test material: room temperature in the dark under nitrogen

Test animals / tissue source

Species:
other: bovine
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: eyes were obtained from Vitelco, s'Hertogenbosch, The Netherlands

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: 3 corneas were treated with physiological saline (negative control) and three were treated with 10% benzalkonium chloride in physiological saline (positive control)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 uL per cornea
- Concentration (if solution): undiluted
VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
10 +/- 1 min
Observation period (in vivo):
corneas were incubated for 120 +/- 10 min following exposure
Number of animals or in vitro replicates:
3 corneas per treatment group
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:
SCORING SYSTEM:
TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vitro

Results
Irritation parameter:
in vitro irritation score
Run / experiment:
Mean of three exposures
Value:
ca. 0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: High IVIS: 1, Low IVIS: -1

In vivo

Irritant / corrosive response data:
The mean in vitro irritancy score for TFEE-5 was 0.0.
Other effects:
none

Any other information on results incl. tables

Mean laboratory historical control irritancy scores for the negative and positive controls were 0.5 and 152, respectively.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the study, TFEE-5 is not considered an ocular irritant.
Executive summary:

OBJECTIVE: The corneal irritation and damage potential of TFEE-5 (MTDID 21721, lot TFEE5-276/12/09-1) was tested in the Bovine Corneal Opacity and Permeability assay (BCOP).

METHODS: This study was conducted in compliance with the OECD GLP (1997). The study method was based on OECD 437 (2009), Background Review Document (BRD) prepared by ICCVAM and NICEATM (2006), INVITTOX (UK) protocol no. 124 SOP of Microbiological Associates Ltd. (1999) and Gautheron, P, et al (1992). TFEE-5 was tested as received. Bovine corneas (3 per group) were prepared in cMEM medium, supplemented with 1% FBS and 1% L-glutamine. The corneas were mounted in an O-ring holder and incubated for at least 1 hour at 32 C prior to exposure. Corneas (3 per group) were treated with 0.75 mL of TFEE-5, 10% benzalkonium chloride (positive control) or physiological saline (negative control) and incubated for a 10 minute exposure period at 32 C. At the end of the exposure period, the corneas were rinsed with media and they were then incubated for approximately 120 minutes. Opacity was evaluated prior to treatment and 120 minutes after the exposure period. Permeability was evaluated at 120 minutes after exposure using a fluorescein method. The mean in vitro irritation scores (IVIS) were calculated and a score greater than or equal to 55.1 indicates an ocular corrosive or severe ocular irritant.

RESULTS: The positive and negative controls were within the historical range which indicates the test was valid. The IVIS for TFEE-5 was 0.0.

CONCLUSION: Based on the results of this study, TFEE-5 is not considered an ocular irritant.