Introduction to nanomaterials safety: predicting the chronic effects by in vivo studies
Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan
Some multi-wall carbon nanotubes (MWCNT) are similar to asbestos in length distribution and we showed their potential to induce mesothelioma by intraperitoneal injection model using p53 eterozygous mice based on the knowledge of “fiber carcinogenesis” established by asbestos and the alternative fibers in the 1970s and 80s.
Histologically, non-granulomatous persistent chronic inflammatory microlesions accompanying single fibers in macrophages were considered to be important for the development of mesothelioma, whereas granulomas formed against aggregates/agglomerates were considered not directly involved in the process.
In general, acute toxicity of a biopersistent nanomaterial (NM) is transient and mild, and therefore not considered as a predictor of its chronic toxicity.
And when there is no pre-existing knowledge on its toxicity, whole body inhalation toxicity study is a default approach, along with oral and dermal toxicity studies. The most challenging part of the inhalation study is to generate well-dispersed aerosol. Here we report some data using the “Taquann” dispersion method and direct injection system using a MWCNT (Mitsui MWNT-7) as a case study sample.
In addition, using our original and literature data, the nature of the long-term nanomaterial toxicity wil l be discussed in terms of its shape and size of primary particles, characteristics of secondary particles including the status of agglomeration/aggregation and dispersion, crystalline and amorphous, biopersistency and solublility, and the nature of induced microlesions.
(Studies supported by Grants from MHLW, Japan.)