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Metal hydride – Zirconium hydride (CAS 7704-99-6; EC 231-727-3)


Background:To induce sensitization, metal ions need to penetrate through the outer stratum corneum barrier layer of the skin and reach the underlying viable epidermis. It is generally believed that to be immunologically reactive, metal ions must bind to macromolecules such as proteins to form a hapten complex. Antigen presenting cells display this hapten complex on their cell surfaces and when the hapten is recognized as foreign by naïve T-lymphocyte cells, these cells undergo differentiation to form hapten-specific effector and memory helper T-cells (i.e., a person becomes sensitized). Upon repeated contact with the offending metal, at exposure levels that result in sufficient metal ion release and stratum corneum penetration, memory T-cells are recruited to the site of skin contact and elicit an inflammatory reaction (Stefaniak et al., 2014; Gibbs et al., 2018).

Regarding skin sensitization of zirconium hydride as requested under REACH regulation1907/2006, no data are currently available. To meet the skin sensitization endpoint requirement, read-across strategy with zirconium salts has been used.

Zirconium salts:

Testing of potential sensitizers of metals is traditionally carried out by applying the metal test chemical in the form of salt to the skin of animals or reconstructed skin under standard conditions. Preferably the salt should dissolve to form metal ions. In that respect, a couple of papers publicly available have been found.

Ikarashi et al., 1996

Sensitization potency of a zirconium salt (ZrCl4) was studied using the guinea-pig maximization test (GPMT) and adjuvant and patch test (APT). In addition, a sensitive mouse lymph node assay was also ran (SLNA). As result, ZrCl4 did not show any sensitization responses in all tests made.

Turk and Parker, 1977

Guinea pigs (Outbred Hartley-strain) were injected intradermally with 5 mg, 0.5 mg, and 0.05 mg of zirconium carbonate (ZrC03). No increase in skin thickness was detected. While ZrCO3 induced no measurable granulomas, the injection site usually contained a small collection of macrophages that had ingested crystalline material. There was no evidence of fibrosis and the macrophages remained undifferentiated with no other cellular infiltrate. At no time epithelioid cells were seen.


Conclusion: According to the papers found in the literature and publicly available, zirconium salts would not be classified as dermal sensitizer. On this basis, the non-sensitization of zirconium hydride has been extrapolated. In addition, water solubility of zirconium hydride at various pH was assessed and showed that the test item is insoluble (<0.08 mg/L) in water at pH which maximises the solubilisation (pH 5.8). This argument strengthens the non-allergic property of zirconium dihydride.

Key value for chemical safety assessment

Justification for classification or non-classification