Pulmonary deposition, retention, and clearance of a pigmented polymer in rats

We have defined the Maximum Functionally Tolerated Dose (MFTD) of a material as the lung burden for which macrophage mediated lung clearance is not significantly impaired. In order to establish its value for the pigmented polymer, a 90-day subchronic inhalation study of a toner fraction was conducted by exposure of groups of F-344 rats for six hours/day, five days/week for 13 weeks. The test material used was specially prepared and characterized powder sample identical to 9000 type xerographic toner, except that its ACGIH respirable fraction was enriched about 10-fold to 35%. The exposure concentrations used were 0, 1.0, 4.0, 16.0, and 64.0 mg/cubic meter total mass. Clearance results for the test material and a superimposed spike of Fe59 iron oxide were essentially unchanged at exposure concentrations of 0, 1 and 4 mg/cubic meter when measured at different times during the exposure period. At 16 mg/cubic meter, some indications of slightly retarded iron oxide clearance were noted afte r 90 days of exposure. At 64 mg/cubic meter, some indications of slightly retarded iron oxide clearance were noted after 90 days of exposure. At 64 mg/cubic meter, no appreciable toner clearance was observed after 60 and 90 days of exposure, and clearance of the iron oxide tracer was significantly retarded after 30, 60 and 90 days. Based upon the above observations, as well as the increase in lung weight, the maximum functionally tolerated dose of test material in this subchronic study was exceeded at the 64mg/cubic m exposure level