Registration Dossier

Administrative data

Description of key information

In two primary skin irritation tests, no skin effects were observed (BASF SE, 2013; American Cyanamid Company 1990)

Two primary eye irritation studies are available. In one study no irritation potential was observed (BASF SE, 2013). In the other study, cornea opacities were still observed until the end of the 21 day observation period (American Cyanamid Company, 1990).

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:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

key study

A primary dermal irritation study has been performed according to OECD guideline 404 (BASF SE, 18H0141/04X051, 2013). The potential of the test substance to cause acute dermal irritation or corrosion was assessed by a single topical application of an amount of 0.5 g of the test item for 4 hours to the intact skin of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch. No signs of systemic toxicity or skin effects were observed in all three animals. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema. Considering the absence of cutaneous reactions as well as the average score for irritation, the test substance does not show a skin irritating potential under the test conditions chosen.

supporting study

A primary dermal irritation study has been performed according to 43 FR 37336, Part 163, guideline no. 81-5 (American Cyanamid Company, T-0229, 1990). Six male albino rabbits (New Zealand White strain) were used for the study. The rabbits were dosed with 0.5 g of the test substance as received, applied to a 1 inch-square gauze pad, moistened with tap water, and applied to the intact skin. The application sites were examined at the following intervals after removal of the test material for irritation: 1 hour, 24 hours, 48 hours, and 72 hours. The application sites were scored using the Draize scale for the evaluation of skin irritation. A barely perceptible erythema was present in 1/6 animals at the 1 hour observation. All signs of irritation had resolved by the 24-hour observation. No overt signs of toxicity were observed during the study period and all animals survived the experimental period. It was concluded that the test substance was not irritating to the rabbit skin.

Eye irritation (WoE)

BASF SE, 11H0141/04X052, 2013

The potential of the test substance to cause damage to the conjunctiva, iris or cornea was assessed according to OECD guideline 405. A single ocular application of 0.1 mL bulk volume (about 29 mg) of the test item was applied to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application in two out of three animals and in a weekly interval until day 7 in a third animal. The following test item-related clinical observations were recorded during the course of the study:

· Slight conjunctival redness (grade 1)

· Slight to moderate conjunctival chemosis (grade 1-2)

· Slight to obvious discharge (grade 1-2)

· Additional findings like injected scleral vessels in a circumscribed or circular area were noted in all three animals from hour 1 until hour 48 after application. In two animals the ocular reactions were reversible within 72 hours and in one additional animal within 7 days after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity, 0.0, 0.0 and 0.0 for iris lesions, 1.0, 0.7 and 0.7 for redness of the conjunctiva and 0.7, 0.3 and 0.3 for chemosis. Considering the described ocular reactions as well as the average score for irritation, the test substance does not show an eye irritating potential under the test conditions chosen.

American Cyanamid Company, IZ-415 -001, 1990

 The eye irritating potential was assessed in a primary eye irritation test according to EPA guideline OPP 81-4. Six male albino rabbits (New Zealand White strain) were used for the study. The rabbits were dosed with 0.1 g of the test substance instilled into the conjunctival sac of the left eye.The eyes were examined at the following intervals: pretreatment (-4 hours), 1 hour, 24 hours, 48 hours, 72 hours, 4 days, 7 days, 10 days, 14 days, 17 days, and 21 days.The eyes were scored using the Draize scale for the evaluation of eye irritation. Eye irritation at one hour after dosing was characterized by slight redness of the conjunctivae (6/6), moderate chemosis (6/6), and a slight ocular discharge (6/6). Diffuse areas of corneal opacity were observed in 6/6 animals with mild-moderate conjunctival irritation (6/6), moderate chemosis (6/6), and a slight-moderate ocular discharge (6/6) at 24 hours postdosing. At 48 hours postdosing, diffuse corneal opacities were still present in 6/6 animals. Conjunctival irritation at 48 hours consisted of slight-to-moderate redness, moderate chemosis, and a mild ocular discharge. At 72 hours postdosing, corneal opacities were still present in 5/6 animals. Conjunctival irritation at 72 hours consisted of mild-to-moderate redness, mild to moderate chemosis, and a slight ocular discharge (4/6). Irritation observed at 4 days postdosing was similar to the 72-hour observation with the exception that 1/6 animals now exhibited translucent areas of corneal irritation. At the 7-day observation, corneal opacities persisted in 3/6 animals with 1/6 animals exhibiting slight vascularization of the cornea. Conjunctival irritation at 7 days consisted of slight redness in 5/6 animals and moderate chemosis in 1/6 animals. One of six animals had completely recovered at the 7-day observation. Corneal opacities were still present in 3/6 animals with all 3 animals exhibiting slight-moderate vascularization of the cornea. A slight redness of the conjunctivae (4/6) and mild chemosis (2/6) was still present at 10 days. At the 14-day observation only 2 animals still exhibited corneal opacities and vascularization. Conjunctival irritation had completely resolved in the remaining animals. Corneal opacities persisted in the remaining 2 animals for the remainder of the 21-day observation period. It was concluded that the test substance was irreversibly irritating to the rabbit eye.

Conclusions

Both eye irritation tests show an equal validity with regards to GLP and guideline compliance. The purity of the tested substance in both studies is also similar (97.7 % vs. 99.5 %) as well as the study performance. Only the number of test animals differs in both tests (3 vs. 6 animals). Therefore the worst case was regarded for local effects considering the test substance to be eye irritating with irreversible effects.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled as skin irritating. The test substance needs to be classified as eye damaging cat. 1 (H318) under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation EC No 2016/1179.