Metal carcinogenesis. II. A study on the carcinogenic activity of cobalt, copper, iron, and nickel compounds.

Nickel sulfide, nickel oxide, cobalt sulfide, and cobalt oxide were shown to be car cinogenic on single intramuscular injection in rats. The sulfide of each metal induced a significantly higher tumor incidence than did its oxide. Comparisons between average latent periods and between measures of tumor progression also indicated that the presence of the sulfide enhances the carcinogenic activity of these compounds. Nickel sulfate, iron and copper sulfides, and oxides failed to induce tumors in rats under these conditions. Both CSH and Swiss mice developed tumors from single intramuscular exposure to Ni@S2and to NiO; however, no tumors were induced with CoO in this species. Tumor response in mice was consistently lower than in rats, and no apparent enhancing effect of the sulfide was evidenced. In rats, almost all tumors examined histologically were rhabdomyosarcomas, with a few fibrosarcomas, particularly among those tumors induced with NiO. Difficulty was encountered in definitely classifying the mouse tumors; whereas most appeared to be fibrosarcomas, many of these were not typical, and a few were almost certainly myomas. It was concluded that nickel sulfide was probably the compound responsible for the carcinogenic activity of the sample of metallurgical dust originally investigated (col lected from the dust flue of a nickel refinery). The apparent specificity of nickel and cobalt compounds for striated muscle tumori genesis is discussed.