Cobalt Nickel Manganese Oxide

Endpoint summary

Description of key information

The substance pNMC oxide is a grey powder, with melting point in excess of 500°C. Most of the material is in the form of large particles, with the majority of particles below 20 µm (D90 of 11.8 µm).

Only limited amount of toxiclogical information is available on pNMC oxide. The substance is essentially non-toxic when given as a single dose (oral) to rat, is neither a skin irritant nor a skin sensitiser. It is also negative in two in vitro genotoxicity tests

No chronic or sub-chronic mammalian studies have been performed with pNMC oxide as testing material. The potential adverse effects of such exposures are therefore based on the known toxicological profiles of the main constituents of this iUVCB, i.e. Cobalt and Nickel (oxide).

The National Toxicology Program Technical Report on the toxicity and carcinogenesis studies of cobalt sulphate heptahydrate (CAS no 10026-24-1) in F344/N rats and B6C3F1 mice (inhalation studies) (NTP TR471, August 1998) states that “'Krasovskii and Fridyland (1971) administered 0.5 or 2.5 mg/kg cobalt by gavage to rats six times per week for 7 months. These investigators found polycythemia and a suppression of leucocyte function”.

 

Absorption

When ingested in sufficient amounts, adverse effects may be observed. Bioelution tests demonstrated that the element-specific release in gastric fluid ranged between 6% (Mn) and 82% (Ni), and was around 100% for all elements in lysosomal fluids.

 

Distribution

The substance is a complex insoluble mixed metal oxide. It is unlikely to be absorbed unchanged. It is likely that, if absorbed, the substance is not distributed widely.

 

Metabolism

The substance is a complex insoluble mixed metal oxide. It is unlikely to be absorbed unchanged. Given that nickel, cobalt and manganese are considered essential elements, absorbed ions are likely to enter appropriate metabolic pools.

 

Excretion

Overall, most of the complex will be excreted, unabsorbed, in faeces. Absorbed material (probably as metal ions) will be excreted mainly in urine.

 

The following information is taken into account for any hazard / risk assessment:

The substance does appear to dissociate to some extent in the acid conditions of the stomach to render some material available for absorption. It is not expected that the solid material will be absorbed following dermal administration, however a dermal absorption value of 1 % is adopted for risk assessment

Additional information

A generic hazard assessment of inorganic UVCBs (such as pNMC oxide) for the purpose of classification and derivation of safe effect thresholds (i.e. DN(M)EL) is a cumbersome and complex process. Due to the intrinsic variability of the composition of most UVCBs, it is often difficult to select a sample that would unambiguously be representative for the toxicological hazard profile of the specific UVCB and could subsequently be used for testing. Instead of direct testing, a precautionary approach can be taken where the UVCB is treated as a complex metal containing substance containing a number of discrete constituents (metals, metal compounds, non-metal inorganic compounds etc.).

For pNMC oxide specifically, test data were generated with a representative worst-case sample of pNMC oxide for the assessment of acute and local hazards of pNMC oxide (acute toxicity, skin/eye irritation, sensitization, mutagenicity). The starting point for other endpoints is the hazard profile for the relevant constituents. These are used for the derivation of classification of the UVCB (using the mixture rules) and/or for the derivation of the DN(M)ELs of the constituent (forwarded to the risk assessment). Using the DN(M)EL of all individual constituents circumvents indirectly the issue of varying composition of an UVCB as it implicitly assumes that each time the UVCB substance consists of the pure substance, i.e. that each constituent would be present and bioavailable at a 100% concentration in the UVCB substance. This can be considered a conservative approach. A main outcome of the constituents’ based assessment is the selection of all the constituents for which any human health hazard is identified. This selection defines the scope of the further exposure and risk assessment (CSR, Ch. 9&10).

The actual hazard profile of the inorganic UVCB substance and the individual constituents is dependent on the speciation of each and every constituent and hence this information needs to be collected in order to obtain a robust classification or DNEL value used for risk assessment purposes. Different scenarios can be encountered.

• When the speciation of a constituent is known, this is used as such for the human health hazard assessment (i.e. the oxide forms of the critical metal constituents).
• When the speciation is unknown or few metal species co-exist, the worst-case speciation for the purpose of human health hazard assessment is selected, i.e. the speciation that would lead to the most severe effects and thus the lowest DN(M)EL

Please note that dependent on the exercise (i.e., classification versus risk assessment) different speciation forms could be utilized.

Selection of the toxicological information for the purpose of classification

As previously indicated, toxicity data were generated with a representative worst-case sample of pNMC oxide for the assessment of acute and local hazards of pNMC oxide (acute toxicity, skin/eye irritation, sensitization, mutagenicity).

For systemic hazard endpoints, the UVCB classification is calculated by applying the CLP mixture rules based on the classification of the oxide speciation form for each constituent and worst-case constituent concentration in the UVCB (i.e. maximum of the legal entity typical value), using the MeClas tool. Depending on the availability of information, the classification can be refined following MeClas Tiered approach.

 

Selection of the toxicological information for the purpose of risk assessment

For the purpose of the human health risk assessment for the UVCB, the hazards of each constituent will be assessed and DNEL/DMEL values for all the constituents for which a hazard has been identified are compiled. As indicated above, workers can be exposed on the work floor to different speciation forms than those present in the mineralogical composition of the UVCB. Hence the information on the intrinsic properties of the UVCB constituents relevant for the hazard assessment (classification) can be refined if it is known which chemical speciation is present in the workplace.

The quantitative assessment of pNMC oxide is predominantly based on the Ni and Co constituents because other constituents, do not significantly add to the systemic hazard properties of this UVCB (see classification and labelling). It should be noted that the comparison between the MeClas-based assessment on one hand, and a direct testing-based assessment on the other hand, clearly demonstrated that a MeClas-based assessment resulted in a worst-case hazard profile