Physicochemical characteristics and biological effects of nickel oxides

Ten nickel oxides and nickel-copper oxides, which all contained NiO (bunsenite) as the predominant crystalline phase, were assayed as follows: in vitro dissolution tests in water and body fluids; in vitro phagocytosis tests in Chinese hamster ovary and C3H-10T1/2 cells; morphological transformation and cytotoxicity tests in cultured Syrian hamster embryo (SHE) cells; erythropoiesis stimulation assay by intrarenal administration to Fischer-344 rats; and scoring the renal histopathologic responses in rats killed 3 months post-injection. The test compounds differed substantially in their biological effects when tested in the various experimental systems. Based upon highly significant concordance of ranked results in the assays (P less than 0.001), six colligative biological attributes of the compounds were identified: (i) dissolution half-times in rat serum and renal cytosol; (ii) phagocytosis by C3H-10T1/2 cells; (iii) morphological transformation of SHE cells; (iv) erythropoiesis stimulation in rats; (v) induction of tubular hyperplasia in rat kidneys; and (vi) induction of arteriosclerosis in rat kidneys. Strong rank correlation (P less than 0.01) between results of the cell transformation and erythropoiesis stimulation assays is especially notable, since the compounds were tested by blind protocols in independent laboratories. The presence of high surface area and demonstrable Ni(III) were two physicochemical characteristics that were associated with the greatest biological effects of nickel oxides.