Carcinogenicity of nickel compounds in animals

A total of 18 nickel compounds were tested for carcinogenicity in male Fischer rats by a single i.m. injection at equivalent dosages (14 mg Ni/rat). Within two years, the following incidences of sarcomas occurred at the injection site: nickel subsulfide (alpha Ni3S2), 100%, crystalline nickel monosulfide (beta NiS), 100%; nickel ferrosulfide (Ni4FeS4), 100%; nickel oxide (NiO), 93%; nickel subselenide (Ni3Se2), 91%; nickel sulfarsenide (NiAsS), 88%; nickel disulfide (NiS2), 86%; nickel subarsenide (Ni5AS2), 85%; nickel dust, 65%; nickel antimonide (NiSb), 59%; nickel telluride (NiTe), 54%; nickel monoselenide (NiSe), 50%; nickel subarsenide (Ni11AS8), 50%; amorphous nickel monosulfide (NiS), 12%; nickel chromate (NiCrO4), 6%; nickel monoarsenide (NiAs), 0%; nickel titanate (NiTiO3), 0%, ferronickel alloy (NiFe1.6), 0%; 84 vehicle controls, 0%. Distant metastases were found in 109 of 180 sarcoma-bearing rats (61%). The nickel-induced sarcomas included rhabdomyosarcomas, 52%, fibrosarcomas, 18%, undifferentiated sarcomas, 13%, osteosarcomas, 8%, and miscellaneous and unclassified sarcomas, 9%. Kendall's rank-correlation test showed that the carcinogenic activities of the compounds were correlated (p = 0.02) with their nickel mass-fractions, but not with dissolution half-times in rat serum or renal cytosol, or with phagocytic indices by rat peritoneal macrophages in vitro. Rank-correlation (p less than 0.0001) was found between the carcinogenic activities and the potencies of the compounds to induce erythrocytosis in rats. The discovery that the carcinogenic activities of particulate nickel compounds are correlated with a physical property, namely the nickel mass-fraction, may help to elucidate the mechanisms of nickel carcinogenesis; the observation that nickel stimulation of erythropoiesis is correlated with carcinogenic activity provides a new in vivo screening test for use in determining the carcinogenic risk of nickel compounds.