Carcinogenicity of nickel(II)hydroxides and nickel(II)sulfate in Wistar rats and its relation to the in vitro dissolution rates

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Abstract
During a two year experiment, local sarcomas developed in 5 of 20 rats injected intramuscularly (i.m.) with 120 μmol of nickel(II)hydroxide air-dried gel (DRY), in 3 of 20 rats similarly injected with 120 μmol of crystalline industrial nickel(II)hydroxide (CRST) and in 16 of 20 rats injected i.m. with 40 μmol of nickel subsulfide (Ni3S2). I.m. injections of 120 μmol of freshly precipitated colloidal nickel(II)hydroxide (COL) did not produce tumors. No tumors were found in animals which had been injected i.m. with 15 doses of 4.4 μmol of nickel(II)sulfate (NiSO4) (total dose equalled 66 μmol/rat) or sodium sulfate (Na2SO4 controls). Statistical analysis ranked the tumor yields as follows: Ni3S2 > CRST = DRY > COL = NiSO4. The in vitro solubilization rates of the hydroxides and nickel subsulfide in human blood serum, artificial lung fluid and ammonium acetate buffer, pH 7.4, were found to increase in the following order: Ni3S2 < CRST < DRY < COL. Hence, an inverse relation may exist between the tumor yield and rate of solubilization of the compounds tested.