4,4'-methylenebis[2-chloroaniline]

Eye irritation

Administrative data

Endpoint:

eye irritation

Remarks:

other: in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14-Jun-2010 to 15-Jun-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

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”

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): 4,4’-Methylene bis (2-chloroaniline)
- Substance type: Light yellow granules
- Physical state: Solid
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark

Test system

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 357 to 381 mg per cornea
- Concentration (if solution): 20% (w/w)

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): 20% (w/v) Imidazole

Duration of treatment / exposure:

240 minutes

Details on study design:

TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 240 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: 240 minutes

Score:

8.1

Other effects:

- The corneas were clear after the 240 minutes of treatment with 4,4’-Methylene bis (2-chloroaniline).
- No pH effect of the test substance was observed on the rinsing medium.

Applicant's summary and conclusion

Interpretation of results:

other: not severe irritant or corrosive

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The positive and negative controls were within the historical control data.

4,4’-Methylene bis (2-chloroaniline) did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 8.1 after 240 minutes of treatment.

Finally, it is concluded that this test is valid and that 4,4’-Methylene bis (2-chloroaniline) is not severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in the report.