Acute oral toxicity of nickel compounds

Acute oral toxicity studies were conducted on samples of nine unique nickel compounds and two complex materials to comply with the data and classification requirements of the new Registration, Evaluation, and Authorization of Chemicals Regulation (REACH) in Europe. The samples tested in this study confirmed the overall low oral toxicity of nickel substances and demonstrated a wide range of LD50 values extending from 310 to >11,000 mg/kg. This variation highlights the differences in toxicological properties between various forms of nickel and underscores the importance of Ni(II) ion bioavailability in determining toxicity. The relative acute oral toxicity of the various nickel substances was found to be: nickel fluoride, nickel sulfate, nickel chloride, nickel acetate > nickel sulfamate > nickel hydroxycarbonate > nickel dihydroxide ≫≫ nickel subsulfide, nickel oxides, nickel ash, nickel mattes. Based on these data, four nickel compounds would receive a Category 4 acute toxicity classification according to the European Regulation on Classification, Labelling and Packaging of Chemical Substances and Mixtures (CLP), while the rest of the nickel substances tested fit the criterion for no classification. These data also provided the in vivo verification needed to perform read-across for additional oral toxicity endpoints and nickel substances.

► Acute oral toxicity studies with nickel-containing substances are reported.
► Relative toxicity determined for 11 substances (nine compounds, two complex materials).
► Four compounds warrant Category 4 CLP acute toxicity classification.
► Remaining nickel substances fit the criterion for no acute toxicity classification.
► In vivo data provide verification needed of an extensive read-across paradigm.