NANOPARTICULES : USAGES ET EFFETS SANITAIRES Dominique Lison Louvain centre for Toxicology and Applied Pharmacology (Bruxelles)
nanomaterials nano = dwarf, 10-9 solids (particles, fibres, rods,...) produced by manipulating @ atomic level at least one dimension < 100 nm quantum physics unique physico-chemical properties (compared to bulk) also. unique toxicological hazards? Nanoobjects 1 nanodim ISO/TS 27687 Nanoplates 1 dim Nanofibres Nanotubes 2 dim Nanoparticles 3 dim
Nanomaterials a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50 % (1-50%) or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm - 100 nm or if the specific surface area by volume of the material is greater than 60 m² / cm³ fullerenes, graphene flakes and single wall carbon nanotubes with one or more external dimensions below 1 nm should be considered as nanomaterials. EC definition, Oct 2011
Different types of nanomaterials Natural Anthropogenic Vulcans Forrest fires Virus Incidental Combustion (motors) Smelting Incinerators Fuming, Welding fumes Intentional (engineered) Metallic NP Carbon NP, nanotubes, graphene Complex NP Air pollution : ultrafines particles Respiratory, cardio-vascular toxicity, allergy
Nanotechnology 2014 : >1/10th of the global manufacturing workforce employed in nanotechnologyrelated processes (Lux Research 2004)
Industrial applications of nanomaterials (1) INDUSTRIAL SECTOR Automobile, aeronautics, aerospatial EXAMPLES OF APPLICATIONS Reinforced and lighter materials Paints : color, brightness, antiscratch, antidirt Sensors optimizing engine performances Ice sensors on aircraft wings Diesel additives Tyres : performances, durability, recycling Electronics and communications High density storage miniprocessors Solar cells e-book readers Computers Wireless technologies Flat screens Chemistry and materials Pigments Ceramic powders Corrosion inhibitors Catalysts Dirt-resistant and self-cleaning windows, paints Antibacterial and resistant fabrics Water treatment Thermal insulation Pharmaceutics, biomedicine, biotechnology Drugs (delivery, targeting) Anti-allergy surface Biocompatible surfaces, implants Tissue regeneration (bone) Heat destruction of tumors Gene therapy Diagnostic kits INRS, 2012
Industrial applications of nanomaterials (2) INDUSTRIAL SECTOR Cosmetics EXAMPLES OF APPLICATIONS Sun creams Toothpastes (abrasive) Make-up, lipsticks (long lasting) Moisturisers (healing, anti-oxidant) Energy Photovoltaic cells Batteries Smart windows Insulation Artificial photosynthesis Hydrogen storage Ecology, environment Water purification Pesticides, fertilisers Sensors Recovery, cleaning Chemical analysers Defence Manufacturing Detection, monitoring Guiding Light, self-reparing fabrics Microscopes and precision tools INRS, 2012
Some occupational scenarios Liquid vs powder Sampling, transfer, weighing, shaking, mixing, drying, filling Drilling, cutting, polishing Packing, packaging, storage Cleaning Maintenance Waste treatment Recycling Accident
Exposure routes Inhalation Digestive Cutaneous Olfactive throughout resp. tract (primary), secondary liquids, powders abraded skin (irritation, allergy) CNS
What makes nanos different in terms of toxicity? The same physico-chemical properties that make nanos so attractive for technological applications may be a source of concern for health : Surface area (dose) Surface reactivity (oxidative stress?) Tissular/cellular distribution
MnO 30 nm Elder et al, 2006
Assessing the toxicity of nanos Solid material Distinct from bulk material Different biological targets Different modes of action Several nanos for same compound (ZnO)
Massive funding, mainly in vitro studies, a lot of noise, relatively little progress
3 selected new horizons
1. Cancer and Immunosuppression Great diversity Experimental data only (>200 in vivo studies) Lung inflammation granulomas fibrosis Genotoxic (in vitro, in vivo) Lung cancer (Mitsui) Mesothelioma (Mitsui, )
CD11bc 1 2 4 8 16 32 64 1 2 4 8 16 32 64 1 2 4 8 16 32 64 1 2 4 8 16 32 64 % of controls Proportion (%) Monocytic MDSC 15 *** *** 10 5 0 Ctl CNT-7 Asb SiO 2 LPS 150 * 100 # * 50 0 1 day 7 days 15 days 30 days His48 Huaux et al. 2016
2. Microbiota (Ag NP) Engineered nanoparticles Nanoparticles in food Nanoparticles in Systemic food toxicity Local toxicity? Microbiota?
% of total bacteria Modifications at phyla level 100 80 60 40 % all phyla trend : p < 0.0001 other phyla bacteroidetes firmicutes 20 0 0 46 460 4600 Ag NP (ppb) van den Brule et al. 2016
% of total bacteria Modifications at genus level % all genera 100 80 60 40 20 0 0 46 460 Ag NP (ppb) 4600 unidentified Bacteroidetes other genera Ruminococcus Oscillospira Odoribacter Mucispirillum Dorea Coprococcus Blautia Bacteroides [Prevotella] unidentified Firmicutes van den Brule et al. 2016
3. Transgenerational toxicity (DEP) Valentino et al. 2016
Valentino et al. 2016
Valentino et al. 2016
Valentino et al. 2016
Thank you for your attention