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

Endpoint summary

Description of key information

Reaction mass of Carbamic acid, N-(5-isocyanato-2-methylphenyl)-, 2-ethylhexyl ester and Carbamic acid, N-(3-isocyanato-4-methylphenyl)-, 2-ethylhexyl ester and N,N'-(4-Methyl-1,3-phenylene)bis(carbamic acid) C,C'-bis(2-ethylhexyl) ester (EC: 937-955-6) Read-across data:

Skin irritation / corrosion: primary irritation score equal to 1.2.

Eye damage / irritation: 3/6 eyes positive for corneal injury and for conjunctival redness. 2/6 eyes positive for iridial injury. 1/6 eyes positive for chemosis.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin 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.

Qualifier:

according to guideline

Guideline:

other: FHSA Procedure - Draize Scoring method (Federal Register, Vol. 38, No. 187, Sept. 27, 1973, §1500.41)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

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

Type of coverage:

occlusive

Preparation of test site:

other: both intact and abraded sited clipped free of hair.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

No further detail on the study design is given, but the guideline is quoted: Federal Register, Vol. 38, No. 187, Sept. 27, 1973, §1500.41: Method of testing primary irritant substances

Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of the albino rabbit, clipped free of hair. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch, such as surgical gauze measuring 1 inch by 1 inch and two single layers thick, 0.5 millilitre (in the case the of liquids) or 0.5 gram (in the case of solids and semisolids) of the test substance. Dissolve solids in a appropriate solvent and apply the solution as for liquids.
The animals are immobilised with patches secured in place by adhesive tape. The entire trunk of the animal is then wrapped with an impervious material such as rubberised cloth for the 24 hour period of exposure. This material aids in maintaining the test patches in position and retards the evaporation of volatile substances.
After 24 hours of exposure, the patches are removed and the resulting reactions evaluated on the basis of the designated values in the following table.

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptable) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Readings are again made at the end of a total of 72 hours (48 hours after the first reading). An equal number of exposures are made on areas of skin that have been previously abraded. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding. Evaluate the reactions of the abraded skin at 24 hours and 72 hours. Add values for erythema and eschar formation at 24 and 72 hours for intact skin to the value son abraded skin at 24 and 72 hours.
Similarly, add the values for oedema formation at 24 and 72 hours for intact and abraded skin (four values). The total of the eight values is divided by four to give the primary irritation score.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: Overall score

Time point:

24/48/72 h

Score:

1.2

Irritation parameter:

erythema score

Basis:

animal: mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Not specified

Irritation parameter:

edema score

Basis:

animal: mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not fully reversible within:

Remarks on result:

other: Not specified

Interpretation of results:

GHS criteria not met

Conclusions:

Primary Irritation Score equal to 1.2.

Executive summary:

The skin irritation potential of the test material was assessed in New Zealand White rabbits according to the FHSA Procedure - Draize Scoring method (Federal Register, Vol. 38, No. 187, Sept. 27, 1973, §1500.41)

The material was applied to the clipped intact and abraded skin of 6 animals and occluded for 24 hours. Skin reactions were observed and evaluated after 24 and 72 hours, resulting in a primary irritation score equal to 1.2.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See Justification attached under Section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: overall score

Time point:

24/48/72 h

Score:

1.2

Irritation parameter:

erythema score

Basis:

animal: mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Not specified

Irritation parameter:

edema score

Basis:

animal: mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Not specified

Interpretation of results:

GHS criteria not met

Conclusions:

The read across for Trixene AS; is based upon the analogous substances to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of skin irritation/corrosion. Based on the information available for the read across substances, the substance is not expected to be irritating or corrosive to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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.

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

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.

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.

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

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

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

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

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

2/6 eyes positive for iridial injury.

1/6 eyes positive for chemosis.

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.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

1 study available for read-across

Adequacy of study:

key study

Justification for type of information:

See Justification attached under section 13.

Reason / purpose for cross-reference:

read-across source

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

Irritation parameter:

iris score

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: 2/6 eyes positive for iridial injury

Irritation parameter:

conjunctivae score

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: 3/6 eyes positive for conjunctival redness.

Irritation parameter:

chemosis score

Basis:

other: overall positive results

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: 1/6 eyes positive for chemosis

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The read across for Trixene AS; is based upon the analogous substances to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of eye damage/irritiation. Based on the information available for the read across substances, the substance would meet the criteria for eye irritation category 2.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion (in vivo)

The skin irritation potential of the test material was assessed in New Zealand White rabbits according to the FHSA Procedure - Draize Scoring method (Federal Register, Vol. 38, No. 187, Sept. 27, 1973, §1500.41)

The material was applied to the clipped intact and abraded skin of 6 animals and occluded for 24 hours. Skin reactions were observed and evaluated after 24 and 72 hours, resulting in a primary irritation score equal to 1.2.

Eye damage / irritation (in vivo)

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.

Justification for classification or non-classification

Based on the information available from the read-across substance, the substance would be expected to meet the classification criteria for eye irritation category 2.