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 ?

• ISO/TS 27687 Nanoobjects ≥ 1 nanodim

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

Incidental

Combustion

(motors)

Smelting

Incinerators

Fuming, …

Welding fumes

Intentional (engineered)

Metallic NP

Carbon NP,

nanotubes,

graphene

Complex NP

Anthropogenic

Vulcans

Forrest fires

Virus

Air pollution : ultrafines particles

Respiratory, cardio-vascular toxicity , allergy…

Nanotechnology

• 2014 : >1/10th of the global manufacturing workforce employed in nanotechnology-related processes (Lux Research 2004)

INDUSTRIAL SECTOR EXAMPLES OF APPLICATIONS

Automobile, aeronautics, aerospatial 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

Industrial applications of nanomaterials (1)

INRS, 2012

INDUSTRIAL SECTOR EXAMPLES OF APPLICATIONS

Cosmetics 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 Detection, monitoring

Guiding

Light, self-reparing fabrics

Manufacturing Microscopes and precision tools

Industrial applications of nanomaterials (2)

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 throughout resp. tract

• Digestive (primary), secondary

• Cutaneous liquids, powders abraded skin (irritation, allergy)

• Olfactive 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

Elder et al, 2006

MnO 30 nm

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, …)

Ctl

CNT-7

Asb 2

SiO LPS

0

5

10

15

***

***

Pro

port

ion (

%)

Monocytic MDSC

Huaux et al. 2016

1 2 4 81

63

26

4 1 2 4 81

63

26

4 1 2 4 81

63

26

4 1 2 4 81

63

26

4

0

50

100

150

§ §

§

§

#

*

§ §§

§

§*

§§

§

§

§

§ §

§

§

1 day

% o

f co

ntr

ols

7 days 15 days 30 days

His48

CD

11

bc

Engineered nanoparticles

Nanoparticles in food

Nanoparticles in food

Systemic toxicity

Local toxicity ?

Microbiota ?

2. Microbiota (Ag NP)

Modifications at phyla level

trend : p < 0.0001 % all phyla

0 46 460

4600

0

20

40

60

80

100

bacteroidetes

firmicutes

other phyla

Ag NP (ppb)

% o

f to

tal b

ac

teri

a

van den Brule et al. 2016

Modifications at genus level

% all genera

0 46 460

4600

0

20

40

60

80

100

Coprococcus

Dorea

Mucispirillum

Odoribacter

Oscillospira

Ruminococcus

other genera

unidentified Bacteroidetes

unidentified Firmicutes

[Prevotella]

Bacteroides

Blautia

Ag NP (ppb)

% o

f to

tal b

ac

teri

a

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