Lung clearance and retention of toner, utilizing a tracer technique, during chronic inhalation exposure in rats

Male and female F-344 rats were exposed to 6 hr/day, 5 days/week for up to 24 months to a special test toner at 0, 1, 4, and 16 mg/m3, TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3 by the inhalation route. 59Fe-labeled iron oxide and 85Sr-labeled polystyrene particles were periodically inhaled by the nose-only route and used to measure alveolar clearance rates during the course of the study. This method was used to describe a maximum functionally tolerated dose (MFTD). Pulmonary retention of toner and control materials (TiO2 and SiO2) was measured after 3, 9, 15, 21, and 24 months of exposure. The quantity of all three materials retained in the lungs and lung-associated lymph nodes increased with exposure duration and level. The final pulmonary burdens of toner at the three exposure levels were 0.22, 1.73, and 15.6 mg/lung, respectively. Alveolar clearance of both tracers was substantially impaired at the toner high-exposure level, and moderately slowed at the toner middle-exposure level. The excessive quantity of toner retained and the substantially retarded clearance in the toner high-exposure group are indicative of "lung overloading." Alveolar clearance of 85Sr-polystyrene particles was slightly slowed in the TiO2-exposed group and substantially impaired in the SiO2-exposed group. The alveolar clearance of the unexposed rats decreased about 30% during the study, a change ascribed to aging. For a general description of the toxicokinetics of the various dusts, a semiempirical kinetic model was developed, which could generally be useful for the extrapolation of lung retention of insoluble particles from a subchronic to a chronic inhalation study. Both the maximum tolerated dose (MTD) and the MFTD were exceeded at the toner high-exposure level during the study in rats.