nanomaterials: potential impact on human health paul j.a. borm paris- oecd- june 7 th 2005
TRANSCRIPT
![Page 1: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/1.jpg)
Nanomaterials:Nanomaterials:Potential impact on human health Potential impact on human health
Paul J.A. Borm
Paris- OECD- june 7th 2005
![Page 2: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/2.jpg)
0 200 400 600 800 1000
SiO2
TiO2
Al2O3
Metals
Various
All
Nanoparticles-already a bulk market
Doubling from 493 € to 900Mi in 2005
Biggest increase SiO2 expected
Millions USD
![Page 3: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/3.jpg)
Estimated global Production rates forNanomaterials
![Page 4: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/4.jpg)
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
![Page 5: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/5.jpg)
Porous Polymer
Magnetite
Inductive
Heating
Engineered NP
Drug in Matrix
200-
1000
0 nm
Drug Release
Shrinkage
For inductive drug release
![Page 6: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/6.jpg)
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?
![Page 7: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/7.jpg)
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
![Page 8: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/8.jpg)
What are nanoparticles?
to a toxicologist
![Page 9: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/9.jpg)
0.01 0.1 1 10m
NanoparticlesParticles in traditional dusty trades
10 100 1000 10,000nm
![Page 10: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/10.jpg)
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
![Page 11: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/11.jpg)
Protein binding by NP mayhave different consequences
Borm and Kreyling (2004)J. Nanotech & NanoSci
![Page 12: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/12.jpg)
0,001
0,01
0,1
1
10
100
0 200 400 600 800 1000 1200
Diameter (nm)
Su
rfac
e/V
olu
me
per
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
![Page 13: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/13.jpg)
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.
![Page 14: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/14.jpg)
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).
![Page 15: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/15.jpg)
Combustion NP
Engineered NPBulk industrial NP
Epidemiology
Toxicology?
?
A Bermuda Triangle
![Page 16: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/16.jpg)
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.
![Page 17: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/17.jpg)
0
10
20
30
40
50
60
70
80
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:
![Page 18: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/18.jpg)
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)
?
![Page 19: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/19.jpg)
Hazard = Riskx exposure
![Page 20: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/20.jpg)
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
![Page 21: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/21.jpg)
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
![Page 22: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/22.jpg)
Producers and Users of Nanomaterials
Research Institutes
State of the art: Little exchange between companies or between companies and
Toxicological research institutes.
![Page 23: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/23.jpg)
Needed: networks to enable communication
and data exchange between nanoscience and
Toxicology.
![Page 24: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/24.jpg)
NANOTECHNOLOGY
HYPE
ScienceFiction
Hazardousarea
![Page 25: Nanomaterials: Potential impact on human health Paul J.A. Borm Paris- OECD- june 7 th 2005](https://reader035.vdocuments.us/reader035/viewer/2022062715/56649da95503460f94a96c4c/html5/thumbnails/25.jpg)
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)