Dialuminium nickel tetraoxide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Additional information:

There are no skin sensitisation data available for nickel aluminate. However, there are reliable data available for the structurally related substances nickel oxide and nickel sulphate. Thus, read-across was conducted based on an analogy approach.

Data characterizing sensitization were limited to two skin sensitization studies; no studies evaluating respiratory sensitization were identified. No relevant or reliable human studies were identified for skin irritation. Two skin sensitization studies conducted according to OECD Guideline Test #406 – Skin Sensitization indicated that nickel oxide was not a contact sensitizer in guinea pigs. Both studies relied on an initial sensitization phase followed by a challenge phase, and collectively evaluated skin sensitization following both dermal and intradermal exposures.

The most recently conducted study (EPSL, 2009d) used the Buehler Methods to evaluate the sensitization potential of repeated topical applications of a nickel oxide sinter (composed of 98% Nickel oxide and 1.5% Cobaltous oxide), also described as dark grey nickel oxide green, in a preliminary test and a main test (induction, challenge and rechallenge). For the preliminary test, the highest non-irritating concentration (HNIC) of 68% w/w was determined following a single 6-hour exposure of 0.4 g of 90%, 68%, 45% or 23% w/w mixture, and thus was used as the challenge dose in the main test. During the induction phase of the main test, a 90% w/w mixture of the test substance in mineral oil (0.4 g) was topically applied to 20 healthy test guinea pigs, once each week for a three-week induction period. Twenty-seven days after the first induction dose, a challenge dose (0.4 mL of 68% w/w mixture in mineral oil) was applied to a naive site on each surviving guinea pig. Approximately 24 and 48 hours after each induction and challenge dose, the animals were scored for erythema. Three and five animals, of twenty, had positive responses (incidence) at 24 and 48 hours, respectively; the severity was 0.53 and 0.50, respectively. However, because of higher than expected irritation scores in the naive control animals after the challenge dose, study authors could not determine if a sensitization response had occurred and thus conducted a rechallenge phase using a lower concentration. Seven days after the primary challenge, 0.4 ml of a 45% w/w mixture of the test substance in mineral oil was applied to a naïve site in the test animals; a new group of naive control animals (n=10) was also exposed. In the rechallenge phase, no test animals had an incidence of positive response at 24 or 48 hours, and severity was 0.15 and 0.10, respectively. Thus, the study report concluded that under the current test conditions, this nNickel oxide green was not considered to be a contact sensitizer. It should be noted that the Buehler Method, as with other animal models for evaluating potential dermal sensitizers, may not be sufficient for assessing nickel-containing compounds. Therefore, the results of this study should be interpreted with caution.

Similar findings were also reported by the Food & Drug Research Laboratories (1986) several years prior. In this evaluation using the guinea pig maximization test (GPMT), guinea pigs were sensitized to nickel via intradermal injection with 0.1 mL 1% (w/v) nickel sulfate in distilled water and 0.1 mL Freund’s complete adjuvant. Eight days later, each site was further sensitized by a topical exposure to nickel sulfate (0.3 mL 5% w/v) and occluded for 48 hr. On day 22 after the initial sensitization injections, virgin sites and original injection sites were challenged and occluded for 24 hr with nickel sulphate, 0.2 g NiO moistened with propylene glycol, or propylene glycol. The challenge sites were scored for erythema and edema via the Draize method at 24 and 48 hr after removal. The erythema scores in animals challenged with NiO were 0 at 24 and 48 hr for animals previously sensitized with nickel sulfate or vehicle controls. The authors concluded that under the conditions of this study, NiO failed to cause sensitization in female albino guinea pigs while nickel sulfate did cause dermal contact sensitization.

Collectively, these two studies provide sufficient data to characterize skin sensitization potential following dermal or intradermal exposure to nickel oxide. The available data indicate that nickel oxide does not present a skin sensitization health hazard in guinea pigs under the conditions evaluated.

In a modified guinea pig maximization test (GPMT), nickel sulphate produced positive reactions in all tested animals at an induction concentration of 1% and challenge concentrations of 5, 2 and 1% (Ikarashi et al., 1996). The same authors performed a sensitive mouse lymph node assay with nickel sulphate. In this assay, the intradermal treatment with a 2% solution and the topical application of a 5% solution resulted in a total stimulation index of 24.08 (Ikarashi et al., 1996).

Migrated from Short description of key information:
Nickel aluminate is currently classified as a dermal sensitizer (R43) according to the CLP Regulation.

Read across from nickel oxide and nickel sulphate:
Nickel oxide is currently classified as a dermal sensitizer (R43) according to the 1st ATP to the CLP Regulation. However, a recent study evaluating the bioaccessibility of a series of Ni compounds in synthetic sweat indicated very low nickel ion release from nickel oxide suggesting very low or no sensitization potency. This is supported by earlier results in a Guinea pig GMPT test that were positive for nickel sulfate and negative for nickel oxide. While no change to the existing classification is proposed within this registration file, a complete summary of the testing program including results and discussion are provided in the Appendix in the CSR.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no skin sensitisation data available for nickel aluminate. However, there are reliable data available for the structurally related substance nickel oxide. Thus, read-across was conducted based on an analogue approach.

No animal or human studies were identified characterizing respiratory sensitization following exposure to nickel oxide. While there is some evidence from exposure to indicate that some more water-soluble nickel compounds are a respiratory sensitiser in humans, the available data are not considered sufficient for classification of nickel oxide.

Migrated from Short description of key information:
Read across from nickel oxide:
The available data are not considered sufficient for classification as a respiratory sensitizer.

Justification for classification or non-classification

Nickel aluminate as well as the structurally related substance nickel oxide are currently classified as a dermal sensitizer (category 1) according to the CLP Regulation. However, a recent study evaluating the bioaccessibility of a series of nickel compounds in synthetic sweat indicated very low nickel ion release from nickel oxide suggesting very low or no sensitization potency. This is supported by earlier results in apig GMPT test that were positive for nickel sulfate and negative for nickel oxide. While no change to the existing classification is proposed within this registration file, a complete summary of the testing program including results and discussion are provided in Appendix in the CSR.