Z-85

Endpoint summary

Description of key information

Skin irritation was observed in a reliable in vivo study in the rabbit. Irritation responses were all reversible within the 7 day observation period but slight desquamation persisted at the 7-day observation. Classification under EU CLP Regulation (EC) No. 1272/2008 is not required as the acute dermal and the LLNA studies did not demonstrate any clinical effects such as erythema or edema following exposure to the test article and can provide weight of evidence that the test substance will not cause skin irritation..
Eye irriration was observed in a reliable ex vivo study in the rabbit.  The substance is classifed for damage to eyes under EU CLP Regulation (EC) No. 1272/2008.

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 (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read-across to properties of an analog is applicable based on the similarity in structure and physico-chemical properties.The justification for read-across is presented in Section 13 Assessment reports- Read-across justification.

Skin

In a key study performed to OECD Guideline No. 404 and EU Method B4 undiluted test substance was applied to New Zealand white rabbits. Initially, one rabbit was used and three patches of 0.5 ml test substance/site was applied on a 2.5 cm x 2.5 cm cotton guaze patch. One patch was removed following 3 minutes, 1 hour and 4 hours after application. After consideration of the skin reactions observed in animal 1, two additional animals were used for the study. For the second 2 animals, the test substance was administered once and the patch remained in contact with the skin for 4 hours and then followed by removal of the patch containing the test article. A 0.5 ml dose of the test article was applied to the clipped, unabraded skin at the test site. Following the exposure periods, the bandages were removed and the application sites were evaluated in accordance with the method of Draize at approximately 24, 48, and 72 hours after patch removal and daily through day 7.

The mean total scores for erthema and oedema were 1.1 and 0.33 respectively. All erythema and oedema was reversible within 7 days. Slight desquamation persisted in two animals at the 7-day observation period.

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for dermal irritation i.e. although there was slight desquamation in 2 animals on Day 7, the primary effects, erythema and edema, were reversed by the end of the observation period. Furthermore, the acute dermal and the LLNA studies did not demonstrate any clinical effects such as erythema or edema following exposure to the test article and can provide weight of evidence that the test substance will not cause skin irritation.

Eye

The Rabbit Enucleation Eye Test (REET) was completed prior to an in vivo testing in accordance with OECD Guideline 405 as a step-wise procedure in the interest of animal welfare.

This study was completed to ascertain any ocular irritancy potential of the test material in the rabbit following application onto the cornea of the enucleated eye. The REET was completed to confirm information that the test material may cause irritation in a rabbit eye.

For the REET, 0.1 mL of test material was applied onto the cornea of three separate enucleated eyes. The enucleated eyes have been stored at 32 +/- 1.5 degrees C within a superfusion chamber. The superfusion chamber, a water heating circulator, gave a stable temperature. Also, a persistaltic pump was used to supply saline solution at a flow rate of 0.15 - 0.4 ml/minute into the reat of each chamber of the apparatus in order to irrigate the surface of the cornea.

The removed eyes were allowed acclimate for 30 minutes. Three eyes were treated with test material and two eyes were untreated and were controls. For test eyes, 0.1 mL of undiluted test substance was applied to the cornea and allowed to remain for 30 seconds. Then the test material was washed away using 20 mL of saline solution. Immediately following the saline wash, the treat eye was returned to the chamber and continued to be flushed wth saline.

Endpoints included corneal opacity, condition of corneal epithelium, fluorescein uptake, and percentage change of corneal thickness. Following 4 hours of treatment, all test eyes had scores > or = to 1 for corneal opacity. All other endpoints were increased as compared with that of the control eyes. After analysis of REET results, it was determined that the test material has the potential to cause severe ocular irritancy ex vivo. Therefore, the acute in vivo eye irritation study is not required.

The test material has the potential to cause severe ocular irritancy ex vivo. In accordance with EU CLP Regulation No. 1272/2008 classification of this substance as Eye Dam. Category 1 is required for eye irritation.

Effects on eye irritation: irritating

Justification for classification or non-classification

Under the conditions of the studies, the test material is not irritating to the skin of rabbits but was shown to have the potential to cause severe ocular irritancy ex vivo .

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for dermal irritation effects, but it is classified for eye irritation as Eye Damage Category 1.