5-(methoxymethyl)-2-furaldehyde

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 October, 2010 - 20 October, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD guideline 437 “Bovine corneal opacity and permeability (BCOP) test method for identifying ocular corrosives and severe irritants” (2009)

Deviations:

no

Principles of method if other than guideline:

- The Ocular Toxicity Working Group (OTWG) of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Interagency Centre for the Evaluation of Alternative Toxicological Methods (NICEATM), Background Review Document (BRD): current status of in vitro test methods for identifying ocular corrosives and severe irritants: The Bovine Corneal Opacity and Permeability (BCOP) Test Method, March 2006.
- In Vitro Techniques in Toxicology Database (INVITTOX) protocol 124. Bovine Opacity and Permeability Assay - SOP of Microbiological Associates Ltd., 1999.
- Gautheron P., Dukic M., Alix D. and Sina J.F., Bovine corneal opacity and permeability test: An in vitro assay of ocular irritancy. Fundam Appl Toxicol 18:442-449, 1992.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-(methoxymethyl)furan-2-carbaldehyde

EC Number:

700-511-5

Cas Number:

1917-64-2

Molecular formula:

C7H8O3

IUPAC Name:

5-(methoxymethyl)furan-2-carbaldehyde

Details on test material:

- Name of test material (as cited in study report): MMF
- Description: Clear yellow liquid (determined at NOTOX)
- CAS Number: 1917-64-2

Test system

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 750 µL per cornea

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount(s) applied (volume or weight with unit): 750 µl per cornea
Concentration (if solution): 10% (w/v) Benzalkonium Chloride

Duration of treatment / exposure:

10 minutes

Details on study design:

TEST SITE
- Isolated bovine cornea (obtained from the slaughterhouse, Vitelco, 's-Hertogenbosch) at 32 ± 1°C. Three corneas were selected at random for each treatment group.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 10 minutes
- Post inbubation period: 120 minutes

SCORING SYSTEM:
- After exposure the cornea is thoroughly rinsed to remove the test substance followed by immediate opacity measurement and permeability evaluation of the cornea.

- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).


TOOL USED TO ASSESS SCORE:
- opacitymeter and microplate reader

DATA EVALUATION:
A test substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant

Results and discussion

In vivo

Results

Irritation parameter:

other: In vitro irritancy score (IVIS)

Basis:

mean

Time point:

other: 10 minutes

Score:

35 - 52

Max. score:

55.1

Any other information on results incl. tables

The corneas treated with MMF showed opacity values ranging from 41 to 43 and permeability values ranging from 0.118 to 1.602. The corneas were turbid after the 10 minutes of treatment with MMF. No pH effect of the test substance was observed on the rinsing medium. Hence, the in vitro irritancy scores ranged from 45 to 67 after 10 minutes of treatment with MMF.

 

Since one out of three corneas induced an in vitro irritancy score above 55.1, an additional experiment was performed to verify this severe irritancy score.

 

In the second experiment, the individual in vitro irritancy scores for the negative controls ranged from -0.1 to 0.2. The individual positive control in vitro irritancy scores ranged from 106 to 142 for Benzalkonium Chloride. The corneas treated with the positive control substances were turbid after the 10 minutes of treatment.

 

The corneas treated with MMF showed opacity values ranging from 32 to 35 and permeability values ranging from 0.043 to 0.131. The corneas were turbid after the 10 minutes of treatment with MMF. No pH effect of the test substance was observed on the rinsing medium. Hence, the in vitro irritancy scores ranged from 33 to 36 after 10 minutes of treatment with MMF.

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

MMF is not a severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test.

Executive summary:

The in vitro eye irritation test was conducted according to OECD 437 guideline and GLP principles. The ocular irritation properties of the test substance was tested on isolated bovine cornea through topical application for 10 minutes.

In the first experiment, the meanin vitroirritancy score was 51.8 after 10 minutes of treatment with MMF, in which the individual in vitro irritancy scores ranged from 45 to 67. Since one out of three corneas induced an in vitro irritancy score above 55.1, an additional experiment was performed to verify this severe irritancy score. In the second experiment, the mean in vitro irritancy score was 35.3 after 10 minutes of treatment with MMF, in which the individual in vitro irritancy scores ranged from 33 to 36.

The negative control responses of the opacity and permeability values were less than the upper limits of the laboratory historical rangeindicating that the negative control did not induce irritancy on the corneas in both experiments.The mean in vitro irritancy scores of the positive control (10% (w/v) Benzalkonium Chloride) were 144 and 119 in the first and second experiment, respectively and were within the historical positive control data range.It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

Since in both experiments, MMF induced a mean IVIS ≤ 55.1, it is concluded that MMF is not corrosive or severe irritant in the Bovine Corneal Opacity and Permeability test under the experimental conditions described.