Carcinogenesis bioassays of nickel oxides and nickel-copper oxides by intramuscular administration to Fischer-344 rats.

Five nickel oxides and nickel-copper oxides, with chemical compositions, physicochemical properties, and biological characteristics that were previously reported, were tested for carcinogenicity by administration to groups of male Fischer-344 rats as a single im injection (20 mg Ni/rat). Two additional groups of rats received injections of the glycerol vehicle (Negative Controls) or nickel subsulfide (alpha Ni3S2, 20 mg Ni/rat, Positive Controls). Within the observation period of 2 yr post-injection, the following numbers of sarcomas developed at the injection site: Negative Controls, 0/15; Positive Controls, 15/15; Compound A (INCO black NiO, prepared at less than 650 degrees C), 6/15; Compound B (grey NiO, calcined at 735 degrees C), 0/15; Compound F (green NiO, calcined at 1,045 degrees C), 0/15; Compound H (oxidized Ni-Cu matte, Ni/Cu = 2.5:1, calcined at 850 degrees C), 13/15; Compound I (oxidized Ni-Cu matte, Ni/Cu = 5:1, calcined at 850 degrees C), 15/15. The Ni- and Ni/Cu-oxides that induced sarcomas (Compounds A, H, and I) had measurable dissolution rates in body fluids and were strongly positive in an erythrocytosis stimulation assay, demonstrating Ni bioavailability. Compound A contained detectable Ni[III] and Compounds H and I contained Cu, plus traces of Fe, Co and S, which may all promote oxygen free-radical reactions. In contrast, the compounds that did not induce sarcomas (Compounds B and F) were essentially insoluble in body fluids, did not stimulate erythrocytosis, and were practically devoid of Ni[III], Cu, Fe, Co, or S. Thus, the bioavailability of nickel and the presence of constituents that promote oxygen free-radical reactions evidently influence the carcinogenicity of nickel oxides and related compounds.