Reaction mass of 2-ethylhexyl (3-isocyanato-4-methylphenyl)carbamate and 2-ethylhexyl (5-isocyanato-2-methylphenyl)carbamate and 2-ethylhexyl (3-isocyanato-2-methylphenyl)carbamate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed to a recognised guideline in accordance with generally accepted scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: FHSA Procedure - Draize Scoring Method (Federal Register Vol. 38, No. 187, Section 1500.42, September 27, 1973.)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2-Ethylhexyl N-(5-isocyanato-2-methylphenyl)carbamate and 2-Ethylhexyl N-(3-isocyanato-4-methylphenyl)carbamate and N,N'-(4-Methyl-1,3-phenylene)bis(carbamic acid) C,C'-bis(2-ethylhexyl) ester

EC Number:

937-955-6

Molecular formula:

components with the molecular formulae C25H42N2O4 and C17H24N2O3

IUPAC Name:

Reaction mass of 2-Ethylhexyl N-(5-isocyanato-2-methylphenyl)carbamate and 2-Ethylhexyl N-(3-isocyanato-4-methylphenyl)carbamate and N,N'-(4-Methyl-1,3-phenylene)bis(carbamic acid) C,C'-bis(2-ethylhexyl) ester

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Diet (e.g. ad libitum): Appropriate Wayne diet, ad libitum.
- Water (e.g. ad libitum): ad libitum.

Test system

Controls:

other: The animal's other eye remains untreated as a control.

Amount / concentration applied:

Single instillation of 0.1 mL.

Duration of treatment / exposure:

Once the test material has been instilled into the conjunctival sac, the lids are gently held together for one second to prevent loss of the material.

Observation period (in vivo):

72 hours.

Number of animals or in vitro replicates:

6

Details on study design:

No data is given, however the guideline is included: Federal Register Vol. 38, No. 187, Section 1500.42, September 27, 1973; Test for eye irritants.

(a)
(1) Six albino rabbits are used for each test substance. Animal facilities for such procedures shall be so designed and maintained as to exclude sawdust, wood chips, or other extraneous materials that might produce eye irritation. Both eyes of each animal in the test group shall be examined before testing and only those animals without eye defects or irritation shall be used.
The animal is held firmly but gently until quiet. The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released. The other eye, remaining untreated, serves as a control. For testing liquids, 0.1 millilitre is used.
(2) The eyes are examined and the grade of ocular reaction is recorded at 24, 48 and 72 hours. Reading of reactions is facilitated by use of a binocular loupe, hand slit-lamp or other expert means. After the recording of the observations at 24 ours, any or all eyes may be further examined after applying fluorescein. For this optional test, one drop of fluorescein sodium ophthalmic solution U.S.P. or equivalent is dropped directly on the cornea. After flushing out the excess fluorescein with sodium chloride solution U.S.P. or equivalent, injured areas of the cornea appear yellow; this is best visualised in a darkened room under ultraviolet illumination. Any or all eyes may be washed with sodium chloride solution U.S.P or equivalent after the 24 hour reading.

(b)
(1) An animal shall be considered as exhibiting a positive reaction if the test substance produces at any of the readings ulceration of the cornea (other than a fine stippling), or opacity of the cornea (other than a slight dulling of the normal luster), or inflamation of the iris (other than a slight deepening of the folds (or rugae) or a slight circumcorneal injection of the blood vessels), or if such substance produces in the conjunctivae (excluding the cornea and iris) an obvious swelling with partial eversion of the lids or a diffuse crimson-red with individual vessels not easily discernible.
(2) The test shall be considered positive if four or more of the animals in the test group exhibit a positive reaction. If only one animal exhibits a positive reaction, the test shall be regarded as negative. If two or three animals exhibit a positive reaction, the test is repeated using a different group of six animals. The second test shall be considered positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the in the second test exhibit a positive reaction, the test shall be repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if any animal exhibits a positive response.


SCORING SYSTEM: Draize Scale for Ocular Lesions

1. CORNEA
(A) Degree of Opacity (most dense area used)
No opacity.........................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible..................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity..............................................................................4

(B) Area of Cornea Involved
One quarter (or less) but not zero........................................................................................................1
Greater than one quarter but less than half..........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.....................................................................................4

THE TOTAL SCORE = (A x B) x 5 MAXIMUM TOTAL = 80

2. IRIS
(C) Values
Normal.............................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these orcombination of any thereof) iris still reacting to light
(sluggish reaction is positive).........................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = C x 5 MAXIMUM TOTAL = 10

3. CONJUNCTIVAE
(D) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal..................................................................................................................................0
Vessels definitely injected above normal..........................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red..............................................................................................................................3

(E) Chemosis
No swelling........................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids...................................................................................2
Swelling with lids about half closed...................................................................................................3
Swelling with lids half closed to completely closed...........................................................................4

(F) Discharge
No discharge.................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)............................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids.............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye..................3

THE TOTAL SCORE = (D + E + F) x 2 MAXIMUM TOTAL = 20
The total score for the eye is the sum of all scores obtained for the cornea, iris and conjunctivae.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: Score/Max. score not reported. 3/6 eyes positive for corneal injury

Results 2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: Score/Max. score not reported. 3/6 eyes positive for conjunctival redness

Results 3

Irritation parameter:

iris score

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: Score/Max. score not reported. 2/6 eyes positive for irridial injury

Results 4

Irritation parameter:

chemosis score

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: Score/Max. score not reported. 1/6 eyes positive for chemosis

Any other information on results incl. tables

3/6 eyes positive for corneal injury and for conjunctival redness.

2/6 eyes positive for iridial injury.

1/6 eyes positive for chemosis.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test substance produced some eye irritation.

Executive summary:

A test was performed to assess the eye irritation potential of the test material to the eye of the New Zealand White rabbit.

It was administered to the eyes of six animals, producing a positive reaction for corneal injury and conjunctival redness in three of the six; two eyes exhibited a positive response for iridial injury and one eye showed chemosis.