Registration Dossier

Administrative data

Description of key information

Skin Corrosivity: The purpose of the study was to investigate whether the test material was acutely toxic via the dermal route, however the study included irritation and corrosion observations. Signs of dermal irritation noted were very slight erythema, light brown discolouration of the epidermis, blanching of the skin, small superficial scattered scabs, hardened light brown coloured scab, hardened dark brown/black coloured scab, scab cracking, scab lifting at edges to reveal dried blood, scab lifting to reveal glossy skin, scab undulating and glossy skin.  The scab/damaged tissue at the test site of one animal has sloughed off revealing a crater (ulcer) over the majority of the test site.
Eye irritancy: The purpose of the study was to assess the potential for occular irritancy (and corrosion) of the test material in vivo in a suitable animal model. The test material was administered to the eyes of two New Zealand White rabbits, and assessed for effects. The test item produced a maximum group mean score of 39.0 and was classified as a severe irritant (Class 6 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

All data available to the registrant have been conducted on structurally analogous substances. This is considered justifiable on the basis of avoiding additional animal testing and the fact that the registrant is classifying the substance on the basis of these data.

Skin:

The study Sanders, 2010 (Acute Dermal Toxicity) was included as the key study for this endpoint. The study was performed in compliance with the guideline OECD 402 and in compliance with GLP. The study was assigned a reliability score of 1 in line with the criteria for reliability of toxicological data as set out in Klimisch, 1997. A dermal toxicity study was selected as the key study ahead of the in vitro studies because according to the guideline OECD 404:

In the interest of both sound science and animal welfare,in vivotesting should not be undertaken until all available data relevant to the potential dermal corrosivity/irritation of the substance have been evaluated in a weight-of-the-evidence analysis. Such data will include evidence from existing studies in humans and/or laboratory animals, evidence of corrosivity/irritation of one or more structurally related substances or mixtures of such substances, data demonstrating strong acidity or alkalinity of the substance (2)(3), and results from validated and acceptedin vitro or ex vivo tests (4)(5)(6). This analysis should decrease the need forin vivotesting for dermal corrosivity/irritation of substances for which sufficient evidence already exists from other studies as to those two endpoints.”

 

In light of this, the OECD 402 acute dermal toxicity study was presented as the key study for this endpoint, having included dermal corrosion observations. Although the exposure period included in a toxicity test is rather extended in comparison to an in vivo skin irritation/corrosion study, the effects continue to worsen after removal of the test material, as only light scabbing was observed at 24 hours after administration (the point at which the test material was removed).

Two further in vivo studies (Kiplinger 1994 and Schöbel 1989) conducted on two other structural anologues support the conclusion that the substance should be considered corrosive to skin.

One in vitro study is included as supporting information.

Warren, 2010 assesses skin irritancy according to a validated in vitro method following the EPISKINTM reconstituted human epidermis model.

A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997 as this was conducted to a validated in vitro method and GLP.

Eye: The study, Sanders, 2010 was assigned as the key study assessment of this endpoint. The study was performed in vivo in New Zealand White rabbits, in compliance with GLP and the OECD guideline 405. The study was assigned a reliability score of 1 according to the criteria outlined by Klimisch, 1997. Warren, 2010, was provided as a supporting study to the endpoint. The study was performed using an in vitro method using RHC tissues A reliability score of 2 was assigned to the study according to the criteria outlined in Klimisch, 1997.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin corrosivity:

According to Regulation No. 1272/2008, the substance is considered corrosive to the skin and classified H314 skin corrosion 1C (Causes severe skin burns and eye damage) with the signal word "Danger".

Eye:

According to the results of the in vivo study in line with Regulation (EC) No 1272/2008, the substance is considered irritating to the eyes and classified as H319 (Causes serious eye irritation) with the signal word "warning".

In accordance with Annex 1 of the CLP regulation, section 3.3.2.3 states skin corrosive substances shall be considered as leading to serious damage to the eyes as well (Category 1). Thus the more severe classification is considered applicable to this substance.