Combustion generated nickel species aerosols: Role of chemical and physical properties on lung injury

Systematic manipulation of furnace temperature, residence time, and dilutio n air was used to study the formation of submicrometer nickel oxide (NiO) o r nickel sulfate hexahydrate (NiSO4) particles in a horizontal, laminar flo w tube reactor. Chemical speciation, morphological changes, and aerosol siz e distributions were measured using x-ray diffraction, transmission electro n microscopy, and diffusion mobility analysis, respectively. A technique wa s developed to use these submicrometer nickel species aerosols in animal in halation studies. Representative aerosols were administered to C57BL/6J mic e by intratracheal instillation or whole-body inhalation to study the effec t of submicrometer particles on pulmonary injury. For instillation, NiO par ticles having a geometric mass mean diameter (d(pg)) of 40, 300, and 1000 n m were generated by pyrolysis of nickel nitrate hexahydrate aerosol suspend ed in physiological saline and administered at a dose corresponding to 3, 3 0, 300, or 3000 mug Ni/kg body weight. Bronchoalveolar lavage fluid was collected 18 hr after instillation and ana lyzed for total and differential cell counts, cell viability, and total pro tein. For inhalation experiments, an acute, whole-body exposure was conduct ed, exposing mice to 6, 24, 48, or 72 hr of continuous submicrometer NiO ae rosol (d(pg) = 50 nm; 340 mug Ni/m(3)) or 24, 48, or 72 hr of NiSO4 aerosol (d(pg) = 60 nm; 420 mug Ni/m(3); d(pg) = 250 nm; 480 mug Ni/m(3)). Exposur e to NiO produced no significant lung injury when either instilled or inhal ed, whereas inhaled NiSO4 caused significant increases in protein content a nd