Molybdenum nickel tetraoxide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

No experimental data are available for Molybdenum nickel tetraoxide, but there are various sensitisation studies performed with the surrogate substance Nickel sulphate. Thus, read-across is performed. The endpoint summary information is adopted from the 2008/2009 EU Nickel sulphate risk assessment.

A number of studies on skin sensitisation in guinea pigs have been performed with nickel sulphate. The dose-response relationship for nickel sulphate hexahydrate has been studied in the guinea pig maximization test. Six intradermal (0.01%-3.0% solutions in water) and six topical (0.25%-10.0% pet.) concentrations were chosen for induction and nickel sulphate hexahydrate 1% in petrolatum was used for challenge in the first instance. At 48 h, a linear relationship was obtained between the intradermal induction dose (but not topical dose) and the response, resulting in a maximum sensitisation rate of 40% after intradermal induction with 3% nickel sulphate. The reactivity disappeared at re-challenge 1 week later. Following a booster closed patch on day 35, using 10% nickel sulphate in petrolatum, the animals were challenged with nickel sulphate 2% in petrolatum and statistical analyses of 72-h readings revealed a non-linear dose-response relationship, giving a maximum response frequency of 40% after initial induction with nickel sulphate 3% intradermally and 2% after topical application. (Rohold et al. 1991).

As the maximum response rate of 40%, found in the study cited above was found to be low, an open epicutaneous application method was tried, and found to be more efficient. Immediately after pre-treatment with 1% aqueous sodium lauryl sulphate, the upper back skin was treated daily for 4 weeks with 0.3%-3% nickel sulphate in either a 1% lanolin cream (Vaseline, pH 5 SAD cream) or hydroxypropyl cellulose. Weekly intradermal injections with aluminium potassium sulphate were used as adjuvant. The animals were challenged twice with a one-week interval, with nickel sulphate 2% in water and 1% in petrolatum, respectively. Considering both readings at both challenges concentrations, the frequency of sensitisation was 57-93% (8 /14 to 13/14 animals) in the group treated with 1% in the lanolin cream, 60-100% (9/15 to 15/15 animals) in the group treated with 3% in the lanolin cream, and 67-75% (8/12 to 9/12 animals) in the group treated with 1% in hydroxypropyl cellulose. Rechallenge of initially sensitised animals 10 weeks later confirmed that a lasting contact allergy had been obtained. (Nielsen et al. 1992). Basketter & Scholes (1992) tested nickel sulphate in the local lymph node assay (LLNA) in mice at concentrations of 0.5, 1 and 2.5%. Nickel sulphate was negative in the LLNA.

Several studies have demonstrated that immunological tolerance to nickel can be achieved in animals (Vreeburg et al., 1984; van Hoogstraten et al., 1992a and b; van Hoogstraten et al., 1993; Ishii et al., 1993; van Hoogstraten et al., 1994; Troost et al., 1995; and Artik et al. 1999). In a number of experiments on mice and guinea pigs, persistent immune tolerance to nickel was induced by oral dosing with nickel prior to cutaneous exposure (Ishii et al., 1993; van Hoogstraten et al., 1992; Vreeburg et al., 1984). It was observed that intragastric priming with nickel sulphate prior to sensitisation successfully reduced the cutaneous delayed type hypersensitivity response to cutaneous application of the same antigen in mice in a dose-dependent manner, as measured by ear swelling (van Hoogstraten et al., 1993). Although the objective of these studies was to investigate the possibility to induce immunological tolerance to nickel, indirectly they provide evidence that nickel sulphate can induce skin sensitisation in mice.

A number of studies using different protocols showed that nickel sulphate is a skin sensitiser in guinea pigs and mice.

Migrated from Short description of key information:
- GMPT, open epicutaneous test, epicutaneous skin painting: skin sensitising (RA Nickel sulphate)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Migrated from Short description of key information:
Some data suggest that soluble Nickel compounds are respiratory sensitisers in humans. No data regarding respiratory sensitisation in animals have been located.

Justification for classification or non-classification

Molybdenum nickel tetraoxide is classified as R42/43 “May cause sensitisation by inhalation and skin contact” according to the criteria of Directive 67/548/EEC (DSD) and as Skin Sens 1 "May cause an allergic skin reaction” and as Resp. Sens. 1 "May cause allergy or asthma symptoms or breathing difficulties if inhaled" according to the criteria of Directive 1272/2008/EC (CLP).