Pulmonary effects and clearance of intratracheally instilled Ni/sub 3/S/sub 2/ and TiO/sub 2/ in mice

The effects and clearance of intratracheally instilled nickel subsulfide (Ni/sub 3/S/sub 2/) and titanium dioxide (TiO/sub 2/) were compared. Instilled Ni/sub 3/S/sub 2/ was acutely toxic to mice. Blood was recovered from the lungs during lavage, pulmonary polymorphonuclear leukocyte cell levels were increased, body weights decreased, and mice appeared clinically sick. These effects were in contrast to TiO/sub 2/-instilled animals, which appeared similar to phosphate-buffered saline-instilled controls. The clearance of instilled particles from the lungs was examined for both Ni/sub 3/S/sub 2/- and TiO/sub 2/-exposed mice. Particles were rapidly cleared to the gastrointestinal (GI) tract within 15 min; this clearance was nonspecific for Ni or Ti and appeared to be due to the coughing reflex. Significantly less Ni was present compared with TiO/sub 2/ in mouse lungs at 3 and 7 days postexposure, with halflifes for the later clearance phase of 119 and 462 hr, respectively. Much of the early Ni lung burden was cleared to the GI tract, and Ni levels in the kidney and blood peaked at 1 hr. Longer-term Ni clearance rate constants were similar for lung, kidney, and blood and were consistent with the hypothesis that /sup 63/Ni was first solubilized in the lung then transportedmore » through the blood.« less