[Research strategy for evaluation methods of the manufactured nanomaterials in NIHS and importance of the chronic health effects studies].

Manufactured nanomaterials are one of the most important substances for the nanotechnology. The nanomaterials possess different physicochemical properties from bulk materials. The new properties may lead to novel biological effects and also may or may not cause unknown adverse effects. However, the toxicological evidences are very limited, and there are no standardized evaluation methods at present. Some domestic and international activities are ongoing, in order to share the information or to standardize the methods. In 2005, our institute launched the research on the establishment of health risk assessment methodology of manufactured nanomaterials by funding from the research grants of the Japanese Ministry of Health, Labour and Welfare. The project contains four themes. The first is development of measurement methods of nanomaterials from biological samples. The second is development of dispersion methods in in vitro systems. The third is development of inhalation exposure systems. And the last is development of in vivo systems for evaluating long-term health effects. As evaluation materials, fullerene, titanium oxide and multi-walled carbon nanotubes were chosen because of their high production volumes. In the course of the research project, we revealed that the nanomaterials were competent to cause chronic effects, by analyzing intraperitoneal administration studies and carcinogenic promotion studies. These studies suggested that even aggregated nanomaterials were crumbled into nano-sized particles inside the body during the long-term, and the particles were transferred to other organs. Additionally, long lasting particles/fibers in the particular tissues may cause chronic adverse effects. The phsyco-chemical properties or toxicity mechanism related with these chronic effects were considered to be different from those properties or mechanism related to acute toxicity. Therefore, we suggested that the toxicological characterization of chronic effects by nanomaterials would be important for the future research. Also, investigations of the toxicokinetic properties and biological interaction with nanomaterials are important to predict the chronically targeted tissues after exposure.