: Morrow, P.; Kilpper, R.; MacKenzie, J.; Mermelstein, R.; Bellmann, B.; Creutzenberg, O.; Fuhst, R.; Koch, W.; Mohr, U.; Muhle, H.; Takenaka, S.

Abstract
A subchronic inhalation study of a special test toner was conducted by exposure of groups of F-344 SPF rats for 6h/day, 5 days/wk for 13 wk. The test material was a special 9000 type xerographic toner, enriched in respirable size particle compared to commercial toner, such that it was about 35% respirable according to the ACGIH criteria. The nominal aerosol exposure concentrations were 0, 1.0, 4.0, 16.0 and 64.0 mg/cbm. Body weight, clinical chemistry values, food consumption, and organ weight were normal except for a 40% increase in lung weight for the highest exposure group. Histopathological examination of the lungs indicated an exposure-related accumulation of particle-laden alveolar macrophages. A very slight degree of thickening of the alveolar structure was noted in the highest exposure group. Clearance results for the test material and a superimposed spike of 59Fe2O3 were essentially unchanged at exposure concentrations of 0, 1 and 4 mg/cbm. At 16 mg/cbm, some indications of re tareded clearance were noted and at 64 mg/cbm, no appreciable toner clearance was observed. The pulmonary changes observed at the two highest exposure levels are interpreted on the basis of the "lung overloading" concept. Based upon the above observations, as well as the increase in lung weight, both the maximum tolerated dose and the maximum functionally tolerated dose of test toner in this subchronic study were exceeded at the 64 mg/cbm exposure level.