159 Keynote: An Overview of Carbon Nanotube Carcinogenesis from Mouse Inhalation Data

Abstract There were “miracle materials” at the time that were later banned. Most of them were “biopersistent” and had “mild acute toxicity but nasty chronic toxicity”. This toxicity gap had given time to allow for mass use before ban. Most carbon-based nanomaterials are taught to be biopersistent and therefore we investigated their chronic inhalation toxicity as a part of particulate matter toxicology. We developed a universal dispersion method and a small-scale cheap and easy inhalation system named “Taquann”. The first sample was Mitsui-7 multiwall carbon nanotube (MWCNT) donated by the company. Based on its size and shape, we referred to the asbestos and performed the intraperitoneal injection studies. Meanwhile, we started monitoring the inhaled mouse lung for the mechanism of lung fibrosis and carcinogenesis. The responses against inhaled particles were monitored in three studies (A) 2hr/day x 5days of inhalation (Mitsui-7) with monitoring at 0, 13w, 26w, 52w, (B) 2hr/day/week x 5weeks (Mitsui-7, TiO2 , MWCNT-N) at 0, 1w, 4w, 8, and (C) 6hr/day/4weeks x 104weeks (Mitsui-7) at 26w, 52w, 104w. There were responses common and different among rigid fiber, tangled fiber and non-fiber particles. Alveolar macrophages tend to phagocytize at its full capacity and relocate to a certain position in the lung, and/or die off, releasing the particles to be re-phagocytized. Type II cell proliferation and interstitial fibrosis may be related to the level of “frustrated phagocytosis” which may be maximized by rigid fibers. More detail including immune responses and lymphatics will be presented. (Health and Labour Science Research Grants).