Lung clearance and retention of toner, TiO2, and crystalline silica, utilizing a tracer technique during chronic inhalation exposure in Syrian golden hamsters

Male and female Syrian golden hamsters were exposed 6 h/day, 5 days/wk for up to 18 months to a special test loner, TiO2, and crystalline silica. The mass median aerodynamic diameters (MMAD) were about 4.0 mu m for loner, 1.1 mu m for TiO2, and 1.4 mu m for silica. The target test aerosol exposure concentrations during the first 5 mo were 1.5, 6, and 24 mg/m(3) (called loner low, toner medium, and toner high) for the test toner, 40 mg/m(3) for TiO2, and 3 mg/m(3) for SiO2. They were changed to 4, 16, and 64 mg/m(3) for toner and 30 mg/mg for TiO2 after 5 mo in order to achieve the desired lung burdens. Alveolar lung clearance was measured following inhalation of Sr-85-labeled polystyrene particles by the nose-only route at 3, 9, and 15 mo of the study. The results of these measurements were used to confirm the maximum functionally tolerated dose (MFTD) previously defined for rats. Clearance half-times of the polystyrene particles were substantially retarded at the loner high (males only) and in the TiO2 and SiO2 exposure groups. Pulmonary retention of toner and reference materials (TiO2 and SiO2) was measured after 3, 9, 15, and 18 mo and additionally after a 3-mo postexposure period. The quantity of all three materials retained in the lungs and lung-associated lymph nodes increased with exposure duration and level. The pulmonary burdens of toner at the three exposure levels and of TiO2 and SiO2 after 18 mo of exposure were 0.15, 0.87, 9.32, 19.6, and 1.7 mg/lung, respectively. In satellite groups, postexposure effects after 9 mo of exposure were followed in the female toner medium, toner high, and TiO2 group during a 6-mo clean air period. The clearance half-times were increased slightly in the toner medium group, moderately to strongly in the toner high group, and strongly in the TiO2 group calculated both for test materials and for [Sr-85]polystyrene particles. These data are consistent with an overload concept on a volumetric basis for toner and TiO2. The excessive quantity of retained toner and the substantially retarded clearance in the toner high exposure group are indicative of "lung overloading." Both the maximum tolerated dose (MTD) and the maximum functionally tolerated dose (MFTD) were exceeded at the toner high and the TiO2 exposure level during the study in hamsters.