Registration Dossier

Administrative data

Description of key information

In vitro studies were performed on:
- skin corrosion and irritation, with the Reconstructed Human Epidermis (RHE) Model.
- eye irritation with the Bovine Cornea Opacity and permeability Assay (BCOP).
All the test are recent (2010) and were performed according to standard OECD Test Guidelines and GLP standards.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

As indicated in OECD 404 and 405 test guidelines, screening for existing data indicating irritation or corrosion potential shouldprecede testing. Screening for skin and eye corrosion/irritation potential by Toxtree (Cramer rule) analysis was performed for the major component Nickel arsenide (see attachment), but only resulted in no irritation potential; another components (copper sulfide) had a Cat. 2 classification for eye/skin irritation, but was only present at lower percentage. Testing of pH in 10% suspension was 6.99 (at 24,3°C), therefore in vitro testing was considered necessary. Based on Meclas, nickel speiss would not be classified for eye or skin corrosion/irritation.

A key in vitro  skin corrosion  study with a three- dimensional reconstructed human epidermis was conducted with Nickel speiss according to the GLP guidelines and the OECD 431 test guideline (Hey S., 2010). Two RHE cultures were topically exposed to 122.3 mg (±1.2 mg) Nickel speiss. Corrosive effects were determined after 3 min and 1 h exposure by determining cell viability using the standard MTT Assay. The viability of the negative control was set to 100%.Application of Nickel speiss on top of the stratum corneum resulted in a mean cell viability of 83.6 % (±10.7 %) after 3 min exposure period and 86.0 % (±0.2 %) after 1 h exposure period. Additionally, it was found that Nickel speiss itself did not reduce MTT. It is concluded that Nickel speiss was non corrosive to skin in the in vitro skin corrosion study using in vitro reconstructed human epidermis models is applied according to the international OECD Test Guideline 431.

A key in vitro   skin irritation  study with a three- dimensional reconstructed human epidermis (RHE) model) was conducted with Nickel speiss according to the GLP guidelines and OECD 439 test guideline (Heisler E., 2010). Three RHE cultures were topically exposed to 122.3 (±1.2 mg) Nickel speiss for a 60 min (±1 min) period time. The cell viability was determined after an additional 42h (±1 h) post incubation period. For the analysis of the tissue viability, the standard MTT Assay was used. The viability of the negative control was set to 100%. Application of Nickel speiss on top of the stratum corneum of the EpiDermTM cultures (each in triplicate) resulted in a mean cell viability of approximately 24 % after 60 min (±1 min) exposure. Additionally, it was found that Nickel speiss did not show any chemical reducing properties to the MTT reagent by itself. It is concluded that Nickel speiss was irritating to skin in the in vitro skin irritation study using in vitro reconstructed human epidermis models is applied according to the international OECD Test Guideline 439.

An in vitro study for   eye irritation   was conducted with Nickel speiss according to the GLP guidelines and OECD 437 test guideline (Hepperheimer A., 2010). After the background opacity of fresh bovine corneas (t0) was determined with an opacitometer, a 20% (w/v) suspension in saline [0.9% (w/v) NaCl in deionised water] of Nickel speiss was applied to corneas and incubated for 240 minutes at 32±1°C. After the incubation phase, Nickel speiss was rinsed from the corneas and opacity was measured again (t240). Thereafter, the permeability of the corneas was determined while application of 1ml of sodium fluorescein for 90 minutes at 32±1°C in a horizontal position. The concentration of sodium fluorescein that crossed into the posterior corneal chamber was measured spectrophotometrically. An in vitro score was calculated on basis of the results obtained on opacity and permeability.Nickel speiss slightly increased opacity of the corneas but did not cause permeability of the corneas compared with the results of the negative control. The calculation mean in vitro score was 10.47. According to the criteria mentioned in the report, Nickel speiss was classified as a mild irritant. But according to the OECD 437 guideline, Nickel speiss is considered as a non- irritant.

The acceptance criteria for the three studies with negative and positive controls were met and the studies are considered reliable, adequate and relevant.

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Effects on skin irritation/corrosion: irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Speiss, lead, nickel-contg does not fulfill the classification criteria for skin corrosion.

Speiss, lead, nickel-contg does fulfill the classification criteria for skin irritation.

Speiss, lead, nickel-contg does not fulfill the classification criteria for eye corrosion or severe eye irritation.