nanomaterials: potential impact on human health paul j.a. borm paris- oecd- june 7 th 2005
TRANSCRIPT
Nanomaterials:Nanomaterials:Potential impact on human health Potential impact on human health
Paul J.A. Borm
Paris- OECD- june 7th 2005
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SiO2
TiO2
Al2O3
Metals
Various
All
Nanoparticles-already a bulk market
Doubling from 493 € to 900Mi in 2005
Biggest increase SiO2 expected
Millions USD
Estimated global Production rates forNanomaterials
Life Sciences and Nanomaterials
• Imaging and microscopy, contrast fluids• Diagnostics and analysis (research)• Production of bio-active compounds (Lab-on-a-Chip)• Transport and dosing of drugs.• Intervention in biological processes (cell growth).• Nutrition (bioavailability, stability, optics).• Cosmetics (UV-filter).• Sensors ( MEMS)- nanorobots• Biomolecules for ICT (DNA computing).
Nanoparticles and nanotubes are important parts in this toolbox
Porous Polymer
Magnetite
Inductive
Heating
Engineered NP
Drug in Matrix
200-
1000
0 nm
Drug Release
Shrinkage
For inductive drug release
Intravenous delivery of engineered NPNeeds to study a series of questions:
• what happens to the particles after release of drugs and coatings?
• Is the surface active to bind endogenous proteins?
• Are NP being degraded, excreted and/or cumulated?
Intentionally produced NP-already on the market
-Newly engineered
Unintentionally produced NP-Combustion-Nucleation
New products, applicationsHigh added value
Negligible exposure (CNT, CB)Low risk
No added value, extra costConsiderable health risks
What are nanoparticles?
to a toxicologist
0.01 0.1 1 10m
NanoparticlesParticles in traditional dusty trades
10 100 1000 10,000nm
Smaller size means different interactions
and distribution
Smaller size means different interactions
and distribution
10µm 1 µm 0.1µm ..0µm
0.1µm
Cilia 0.25µm diameter
Bronchial epithelium
N
Mit
Protein binding by NP mayhave different consequences
Borm and Kreyling (2004)J. Nanotech & NanoSci
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0,01
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Diameter (nm)
Su
rfac
e/V
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cen
tag
e
High Surface/volume ratio: • Suitable for catalysis, • More soluble. • More particles at similar mass. • Not subject to gravity
Nanosize has physical implications
Nanosize has implications for surface reactivity and chemistry
TiOTiO22 TiO TiO22 Ti Ti0.990.99OO1.951.95
• Size does not allow stoichiometry, • Cluster Irregularities.• quantum effects• Electron holes, reactive surface
Toxicological hazards of Nanoparticles
what do we know?Have an active and large surface that can interact withmany targets in the body
Bad recognition by our immune system and even Enhance response to antigens
Can cause acute inflammation with secondary effects such As cancer.
Combustion nanoparticles cause worsening of heart disease, atherosclerosis and asthma.
Are in the size of proteins and can interfere with normal cellular signaling pathways.
However:
Most of the evidence for human effects is generated using unintentionallyunintentionally produced combustion Nanoparticles.
Effects of manufactured Nanoparticles have mainlybeen studied with a small set of particles alreadyon the market for decades (carbon black, TiO2, FexOy)
Little data on occupational exposure to manufactured Nanoparticles. Available data suggest negligibleInhalation exposure (= background).
Combustion NP
Engineered NPBulk industrial NP
Epidemiology
Toxicology?
?
A Bermuda Triangle
Scenario’s to consider for testing and regulation of NP
1. Differences with fine particles merely quantitative (depends on effect)
2. Important qualitative differences in toxicity
3. Regulation driven by application.4. Find means to extrapolate findings and
build conceptual understanding5. Invest in studies on environmental
distribution, accumulation and effects.
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0.001 0.01 0.1 1 10 100
surface (m2/lung)
% l
un
g t
um
ou
rs
Summary of inhalation (o)and instillation studies (●)With fine and ultrafineparticles
0.2-0.3 m2/rat
Borm et al (2004) Int J cancer
The carcinogenic response in the rat is driven by surface dose.This means that regulation of all particles could be done usingA surface dose concept.
Ad 1:
Ad2: qualitative differences: Uptake of NP in the brain
Oberdorster et al, 2004Carbon, Au, MnO
Activation of inflammatoryCascade in brain Caldwell et al, 2005
Relation to Alzheimer?Calderon-Garciduenas, et al, 2004
Relation to systemic effects such as heart rate, blood pressure changes (Brook et al, 2002; Lippman et al, 2005)
?
Hazard = Riskx exposure
What do we need to know about Nanomaterials?
•Toxicity data in relevant models•Uptake and distribution•Measurement and Detection methods•Worker Protection and Industrial
Hygiene•Environmental distribution and effects
How can we achieve this?
• Bridging studies• Communication and exchange of
data between area’s of application • Communication between disciplines• Develop and validate toxicicological
testing protocols for nanoparticles
Producers and Users of Nanomaterials
Research Institutes
State of the art: Little exchange between companies or between companies and
Toxicological research institutes.
Needed: networks to enable communication
and data exchange between nanoscience and
Toxicology.
NANOTECHNOLOGY
HYPE
ScienceFiction
Hazardousarea
Current and recent initiatives on sustainable nanomaterials.
• Meetings DG-SANCO (march 04) HSI (oct 04), Royal Society (july 04), ICON (dec 04)
• EU research programs (e.g. NANOSAFE)
• HESI-ILSI working groups (jan, feb 05)• ECETOC-White Paper (May 2005) and
workshop (nov 05)