Lifetime effects of intratracheally instilled nickel subsulfide on B6C3F1 mice

A nickel subsulfide (Ni3S2) lung tumor model for the study of metal carcinogenesis was evaluated using intratracheally dosed B6C3F1 mice. A preliminary study of the survival of mice 14 days after a single intratracheal dose of Ni3S2 displayed an LD50 of 4 mg/kg. A lifetime study was then initiated using five graded doses of Ni3S2 or saline alone, administered once a week for 4 weeks. Animals which survived more than 60 days after the final dose were evaluated by histopathology. The study was terminated 27 months after initiation when approximately 50% of the control animals had died. There was no increase in neoplastic or nonneoplastic lesions observed in animals treated with Ni3S2 nor was there evidence of damage to the organs of the respiratory tract from this treatment. The lack of significant biological response appears to be the result of relatively low tolerated dose, efficient lung clearance, and repair of early lung lesions.