Occupational exposure to nanofibers: in vitro characterization of their cytotoxic and genotoxic effects

Nanofibers are nano-objects with two similar dimensions in the nanoscale (size range from approximately 1nm to 100nm) and the third dimension significantly larger (ISO 2011). According to this definition, the most widespread group of nanofibers is the one of carbon nanotubes, a group of compounds consisting of graphite sheets with a cylindrical arrangement, displaying various lengths, and with a diameter at the nanoscale. Carbon nanotubes have unique properties. They are mechanically strong, flexible, lightweight, heat resistant, and have high electrical conductiv¬ity. They are being currently used in several industrial and biomedical applications, and many novel applications are expected to be developed in the following years. Nanofibrillar cellulose is a recent nanofiber that holds great expectations in the forest industry, but which is still very poorly characterized. Cellulose is the most common biopolymer in nature and besides being completely renewable and cheaper to produce, also exhibits exceptional high resistance, softness and low density at the nano-scale. Chemically pre-treated nanocellulose can be regarded as interconnected webs of tiny nanofibrils with diameters typically of less than 20 nm and lengths in the micrometer scale. Although great benefits are expected from nanofibers, the same properties which are intentionally exploited may have a detrimental effect from unintentional exposure and interaction with the biological systems. The main human exposure route to nanofibers is inhalation and the respiratory system is the first to be attained. Inhaled nanofibers can reach the distal regions of the lung, deposit in the alveolar epithelium, interact with macrophages and be eliminated or they may reach the interstitium, fibroblasts and endothelial cells, and even the pleura. Several in vivo and in vitro toxicological studies have shown an association between nanofiber exposure and development of acute or persistent pulmonary inflammation, interstitial fibrosis with granulomatous lesions, and bronchiolar or bronchioloalveolar hyperplasia. Also, given the fiber-like shape similarity of some nanofibers with tiny asbestos, there have been concerns about their fibrogenic and carcinogenic potential in the mesothelium. In this study, we analyse and compare the cytotoxic, genotoxic and immunotoxic effects of a needle-like carbon nanotube (NRCWE-006), a nanofibrillar cellulose produced from industrial bleached Eucalyptus globulus kraft pulp and crocidolite on a co-culture of A549 lung epithelial cells and THP-1 monocyte-derived macrophages. Our results highlighting the impact of these nanofibers as an emerging occupational hazard.N/