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

During a two year experiment, local sarcomas developed in 5 of 20 rats injected intramuscularly (i.m.) with 120 mumol of nickel(II)hydroxide air-dried gel (DRY), in 3 of 20 rats similarly injected with 120 mumol of crystalline industrial nickel(II)hydroxide (CRST) and in 16 of 20 rats injected i.m. with 40 mumol of nickel subsulfide (Ni3S2). I.m. injections of 120 mumol 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 mumol of nickel(II)sulfate (NiSO4) (total dose equalled 66 mumol/rat) or sodium sulfate (Na2SO4; controls). Statistical analysis ranked the tumor yields as follows: Ni3S2 greater than CRST = DRY greater than 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 less than CRST less than DRY less than COL. Hence, an inverse relation may exist between the tumor yield and rate of solubilization of the compounds tested.