抄録
Toxicity assessment of nanomaterials (NMs) faces difficulties by its purity/ununiformity, lag in measuring technique, unpredictable/unknown ADME, and hence unpredictable toxicologic endpoints. At least, we know that many of the NMs are biopersistent and chemically stable and therefore chronic toxicity may be more significant than acute toxicity. Although limited in number, there is useful toxicity information of particulate matters (PM) that meets the size definition of nanoparticles. They are the asbestos (mesothelioma/ lung adenocarcinoma) and thorotrast (3-10 nm-sized thorium dioxide emulsion; reticuloendothelial system (RES) deposition with in vivo half life of over 20 years). Some multi-wall carbon nanotubes are 10 to 20 micrometers long and 0.1 micrometer wide and induce mesothelioma when administered intraperitoneally to p53 heterozygous mice. A low dose study suggested non-granulomatous chronic inflammatory microlesions as primary foci for atypical mesothelial proliferation. Fullerene molecules form micrometer-sized aggregates by van der Waals force. Phagocytic cells seem to "digested" the aggregates down to sub-micrometer granules and bring them to RES. Currently these two responses are the initial checkpoints for chronic toxicity of a new nanomaterial. In addition to this, information such as pulmonary fibrosis and/or systemic distribution without overt acute or chronic inflammatory reactions is accumulating. In general, acute responses may not be the direct predictors of chronic toxicity. NMs in an available form should be tested for their chronic pathology, possibly at submicroscopic levels, in a case-by-case approach at least for a while until the elements of the difficulties indicated above resolve. (supported by Grants from MHLW, Japan.)
