Paniculate Ni5As2has been shown to be highly cytotoxic and carcinogenic. By measuring the solubility of Ni5As2particles in a variety of aqueous solutions, we have determined that particulate Ni5As2that might be produced during oil‐shale retorting could be mobilized to the environment and made available to the cells of living organisms, including humans. Ni5As2was five times more soluble in ground water taken from aquifers surrounding a major oil‐shale source in Colorado, U.S.A., than in distilled water. It was also two times more soluble in oil‐shale product water from an above‐ground retort than in distilled water. Thus, it is possible that Ni5As2could be solubilized and mobilized to the environment by the flooding of abandoned in situ retorts with ground water or by the disposal of oil‐shale product water by spraying it on spent shale beds. Particulate Ni5As2was found to be 12 times more soluble in culture growth medium than in distilled water, and much more soluble in solutions of amino acids, inorganic salts, organic constituents of culture medium, and 75% calf serum. These observations suggest Ni5As2particles in airborne dust would be dissolved when they came in contact with the biological fluids of the lung and gastrointestinal tract. The availability to cells of the soluble products of NisAs2was demonstrated by measuring its effects on cell proliferation. As little as 1 ppm soluble NisAs2retarded Chinese hamster (CHO) cell proliferation in culture, and 4 ppm resulted in cell death. Flow cytometry measurements indicated there was a preferential cytotoxic effect on S‐phase cells. Despite this, many cells survived to form colonies, causing concern that Ni5As2might cause genetic damage that could be passed on to future cell generations. This did not appear to be the case, however, for no mutations could be detected at the hypoxanthine‐guanine phosphoribosyl transferase (HCPRT) locus in cells that survived the cytotoxic effects. This suggests that Ni5As2carcinogenesis might be caused by epigenetic rather than mutagenic mechanisms.