Inhaled multiwalled carbon nanotubes modulate the immune response of trimellitic anhydride-induced chemical respiratory allergy in brown norway rats

Abstract

Introduction: Comprehensive data on the carcinogenicity of airborne nanoparticles are lacking. CeO 2 and BaSO 4 are currently being tested in a chronic and carcinogenicity inhalation study (OECD TG 453), within the EU-project NanoREG. Materials and Methods: Rats were exposed to 0.1, 0.3, 1 and 3 mg/ m 3 CeO 2 and 50 mg/m 3 BaSO 4 for 6 h/day for 2 years. Interim results after 13 and 52 weeks and results of previous studies with 1 and 4 weeks of exposure to 0.5, 5 and 25 mg/m 3 CeO 2 are available. Examinations included burdens and histopathology of the respiratory tract and bronchoalveolar lavage fluid (BALF) analysis. Results: Inhaled CeO 2 is deposited in the lung and cleared with a half-time of 40 days; the clearance was retarded by exposure to higher concentrations (25 mg/m 3 ). Lung burden after 13 weeks of exposure to 3 mg/m 3 was 1.4 mg/lung. Pulmonary inflammation was observed with neutrophils in BALF after 1 and 4 weeks of exposure to 5 and 25 mg/m 3 and after 13 weeks of exposure to 1 and 3 mg/m 3 CeO 2 . The slope of the dose-response curve was steeper after shorter exposure times. Granulomatous inflammation was observed by histopathology after 4 weeks exposure to 5 and 25 mg/m 3 CeO 2 . BaSO 4 is rapidly cleared from the lung (half-time 7 days); lung burdens were 1.7 mg/lung after 13 weeks exposure. Neutrophils in BALF were not increased after 4, but slightly increased after 13 weeks. Conclusions: The time course of particle burdens and effects in the lung are described. A link between retarded clearance and inflammation in the lung driven by neutrophils and macrophages and subsequent granulomatous inflammation was observed.