2-[(2-cyanoethyl)[4-[(6-nitrobenzothiazol-2-yl)azo]phenyl]amino]ethyl acetate

Endpoint summary

Description of key information

Not irritant to the skin of rabbits.

Not irritant to the eye of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Test sample used to assess skin and eye irritation potential of target substance contained 30 % dye, 69 % sodium lignosulphonate as dispersant and 1 % dedustant.

Skin and eye irritation potentials were tested in rabbits by topical application and instillation, respectively.

A skin irritation study was performed according to The Code of Federal Regulations, title 16, section 1500.41. Accordingly, 0.5 g of test substance were applied on both intact and abraded skin of 6 rabbits. Observations were done at 24 h and 72 after application; no signs of oedema and erythema were noted.

Such study protocol differs from currently accepted OECD guideline 404, since no 48 -hour observation is done, test substance is applied for 24 h instead of 4 h, application is also on abraded skin. However, based on the lack of response, such data were safely used for the assessment.

An eye irritation study was performed according to The Code of Federal Regulations, title 16, section 1500.42. Accordingly 59 mg of test substance were instilled in one eye of 6 rabbits, while the other eye served as control. No irritation of iris was noted; corneal opacity or dulling was seen in 4/6 rabbits and was fully reversible within 7 days; conjunctivae chemosis and redness were seen in all rabbits and had a clear tendency to decrease, if not to fully recover, within the 7 days observation period.

Compared to the currently accepted OECD guideline 405, significant differences in procedure are present. In particular, no rinse of treated eye was reported and observations were done up to day 7 instead of day 21. Based on available data, slight effects on conjunctivae (score 1) still present at day 1 were reasonably deemed to fully recover within the recommended 21 days period.

Furthermore, available data on a structural analogue, Similar Substance 01, confirmed the lack of a skin and eye irritation potential. Details on this substance are attached in section 13.

Justification for classification or non-classification

Skin Irritation

According to the CLP Regulation (EC 1272/2008), skin corrosion means the production of irreversible damage to the skin, and skin irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

A substance has to be classified as category 1 (corrosive) if it produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to a 4 hour duration.

 

A substance has to be classified as category 2 (irritant) if shows:

(1) mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

(2) inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

(3) in some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

 

As no effects in terms of erythema and oedema were reported, no classification within the CLP Regulation (EC 1272/2008) applied.

 

Eye Irritation

According to the CLP Regulation (EC 1272/2008), serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application .

Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

 

A substance has to be classified as category 1 (irreversible effects on the eye), if, when applied to the eye of an animal, a substance produces:

- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

- at least in 2 of 3 tested animals, a positive response of:

- corneal opacity ≥ 3 and/or

- iritis > 1,5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

 

A substance has to be classified as category 2 (irritating to eye) if, when applied to the eye of an animal, a substance produces:

at least in 2 of 3 tested animals, a positive response of:

- corneal opacity ≥ 1 and/or

- iritis ≥ 1, and/or

- conjunctival redness ≥ 2 and/or

- conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

In case of 6 tested animals, classification in category 1 or 2 applies when 4/6 (instead of 2/3) show effects on cornea, iris and conjunctivae above the threshold levels of the CLP Regulation (EC 12727/2008). As irritation scores of treated eyes were all below the thresholds and showed a clear tendency to decrease over the observation period, no classification applied.