m-tolyl isocyanate

Endpoint summary

Description of key information

Skin Irritation:

K2, occlusive patch-test on rabbits, Schreiber FhG (1980) Corrosive 

S2, semi-occlusive plaster patch, 1 hour-test on rabbit,Thyssen (1980) 

 

Eye Irritation:

K2, rabbits, Schreiber FhG (1980) Irritating

S2, rabbits, Thyssen (1980)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 16, Section 1500.41

Principles of method if other than guideline:

500 µl of the m-tolylisocyanate was applied on a 2.5 x 2.5 cm² area at the shaved (one side) and sacrificed (other side) trunk of 6 rabbits and fixed for 24 h. Reading was carried out 24 and 72 h after start of application.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

24 hours

Observation period:

8 days

Number of animals:

6 animals

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 72 h

Score:

>= 3.8

Max. score:

8

Reversibility:

not fully reversible within: 8 d

Remarks on result:

probability of severe irritation

Irritation parameter:

edema score

Basis:

animal: 1 to 6

Time point:

other: 24h / 72h

Score:

0

Max. score:

8

Reversibility:

not specified

Remarks on result:

not determinable

Irritation parameter:

erythema score

Basis:

animal: 1 to 6

Time point:

other: 24h/72h

Score:

0

Max. score:

8

Reversibility:

not specified

Remarks on result:

not determinable

Irritant / corrosive response data:

White discoloration of the skin within 24 hours. Dryness, folding and red-brownish discoloration of the skin after 72 hours. dry eschar formation after 8 days and beginning of ablation. Beginning of reparation and cicatrisation

m-tolylisocyanate is corrosive to the skin

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

The test item was found to be corrosive to the skin, Category 1C, according to Regulation (EC) No 1272/2008 (CLP).

Executive summary:

500 µl of the m-tolylisocyanate was applied on a 2.5 x 2.5 cm² area at the shaved (one side) and sacrificed (other side) trunk of 6 rabbits and fixed for 24 h. Reading was carried out 24 and 72 h after start of application.

Within 24 hours a white discoloration of the skin occurs, followed by dryness, folding and red-brownish discoloration of the skin after 72 hours. A dry eschar formation after 8 days and beginning of ablation was observed, with a beginning of reparation and scarring.

The primary irritation index was > 3.8. m-tolylisocyanate was regarded as corrosive to the skin, category 1C, in accordance with Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Remarks:

other: Code of Federal Regulations, Title 16, Section 1500.42

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documented

Principles of method if other than guideline:

100 µl m-tolylisocyanate was applied into the conjunctival sac of the right eye of 6 rabbits. Reading was carried out 24, 48 and 72 h after start of application of the test substance.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

8 days (eye was not washed after application of the test substance)

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

6 animals

Irritation parameter:

other: primary irritation index

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

54.1

Max. score:

110

Reversibility:

not fully reversible within: 8 d

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Eight days after application of the test substance, a slow repair of the cornea damage was observed. The condition of the chemosis and the inflamation of the conjunctiva were unchanged, no repair was visible.

 

Irritation	24h						48h						72h
I.Cornea: A-Opacity B-Area   Max (80)	1	2	3	4	5	6	1	2	3	4	5	6	1	2	3	4	5	6
	2	1	1	1	1	2	1	2	1	2	1	2	1	2	1	3	2	2
	4   40	4   20	4   20	4   20	4   20	4   40	4   20	4   40	4   20	4   60	4   40	4   40	4   20	4   40	4   20	4   60	4   40	4   40
II.Iris: Max (10)	0 0	1 5	0 0	0 0	0 0	0 0	0 0	1 5	2 10	1 5	1 5	1 5	1 5	2 10	1 5	1 5	1 5	1 5
III.Conjunctive: A-Redness B-Chemosis C-Discharge   Max (20)	2 4 2   16	2 4 3   18	2 4 2   16	2 4 2   16	2 4 3   18	2 4 3   18	2 4 3   18	2 4 3   20	3 4 3   20	3 4 3   20	3 4 3   20	3 4 3   20	3 4 3   18	2 4 3   20	3 4 3   20	3 4 3   20	3 4 3   20	3 4 3   20
Max (110)	56	43	36	36	38	58	43	70	45	65	45	65	43	70	45	85	65	65

 

 

Irritation	After 8 days
I.Cornea: A-Opacity B-Area Max (80)	1	2	3	4	5	6
	2	2	1	3	2	2
	4	3	3	3	2	4
II.Iris: Max (10)	2	2	1	1	1	1
III.Conjunctive: A-Redness B-Chemosis C-Discharge Max (20)	3 4 3	3 4 3	3 4 3	3 4 2	3 4 3	3 4 3
Max (110)

 

The total sum is divided by 18 and gives the degree of primary irritation on the eye.

 

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, classified as GHS category 1.

Executive summary:

100 µl m-tolylisocyanate was applied into the conjunctival sac of the right eye of 6 rabbits. Reading was carried out 24, 48 and 72 h after start of application of the test substance.

Eight days after application of the test substance, a slow repair of the corneal damage was observed. The condition of the chemosis and the inflamation of the conjunctiva were unchanged, no repair was visible.

A primary irritation index of 54.1 was found. The test-substance m-tolylisocyanate is highly irritating (R 41) to the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin Irritation:

Schreiber (1980): 500 µl of the m-tolylisocyanate was applied on a 2.5 x 2.5 cm² area at the shaved (one side) and sacrificed (other side) trunk of 6 rabbits and fixed for 24 h. Reading was carried out 24 and 72 h after start of application.  Within 24 hours a white discoloration of the skin occurs, followed by dryness, folding and red-brownish discoloration of the skin after 72 hours. A dry eschar formation after 8 days and beginning of ablation was observed, with a beginning of reparation and scarring.  The primary irritation index was > 3.8. m-tolylisocyanate was regarded as corrosive to the skin.

Thyssen (1980): 500 µl/animal of m-tolylisocyanate was applied to the inner surface of one ear per animal; exposure time was one hours. The test-substance was fixed by a plaster.After the removal of the plaster bandage, for 2 days aslight and afterwards a very strong redness was observed.Until the second observation day, the skin was slightly and afterwards strong swollen. The symptoms were persistent until the end of the observation period (7 days). The post exposure observation time was 7 days.

 

Eye Irritation:

Schreiber (1980): 100 µl m-tolylisocyanate was applied into the conjunctival sac of the right eye of 6 rabbits. Reading was carried out 24, 48 and 72 h after start of application of the test substance.  Eight days after application of the test substance, a slow repair of the corneal damage was observed. The condition of the chemosis and the inflamation of the conjunctiva were unchanged, no repair was visible.  A primary irritation index of 54.1 was found. The test-substance m-tolylisocyanate is highly irritating (R 41) to the eyes.

Thyssen (1980): 100 µl test substance was applied into the conjuctival sac of 2 rabbits. Post exposure time was 7 days. The treated eye was not washed. Eyes were examinated after application of test substance up to 7 days.  Immediately after application of the test substance a moderate reddening and a moderate to strong edema of the conjunctivae were observed. beginning with the 3rd observation day a slight to moderate reddening and a slight to moderate edema was evident which persists until the end of the observation period. The iris was slightly reddened and swollen for 2 days. The cornea was slightly diffus opaque during the whole observation time.  Result: m-tolylisocyanate is highly irritating to the eyes.

Justification for classification or non-classification

Harmonised classification:

The substance does not have a harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP). 

 

Self-classification:

Based on the available information on the registered substance, self-classification is proposed according to GHS and CLP:

GHS classified as Skin Corr. 1C as result of the corrosive effects on the skin.

GHS classified for Eye Damage 1, justified as a result of severe effects on the eye.

Several studies reported respiration irritational effects. Therefore STOT-SE Category 3 is applicable for respiratory irritation.