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Nanomaterials: Potential impact on human health. Paul J.A. Borm. Paris- OECD- june 7 th 2005. Nanoparticles-already a bulk market. All. Various. Doubling from 493 € to 900 Mi in 2005 Biggest increase SiO 2 expected. Metals. Al 2 O 3. TiO 2. SiO 2. 0. 200. 400. 600. 800. 1000.

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Nanomaterials: Potential impact on human health

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Nanomaterials potential impact on human health

Nanomaterials:

Potential impact on human health

Paul J.A. Borm

Paris- OECD- june 7th 2005


Nanomaterials potential impact on human health

Nanoparticles-already a bulk market

All

Various

Doubling from 493 € to 900

Mi in 2005

Biggest increase SiO2 expected

Metals

Al2O3

TiO2

SiO2

0

200

400

600

800

1000

Millions USD


Nanomaterials potential impact on human health

Estimated global

Production rates for

Nanomaterials


Life sciences and nanomaterials

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


Nanomaterials potential impact on human health

Engineered NP

Porous Polymer

Shrinkage

Magnetite

Inductive

Heating

200-10000 nm

Drug Release

Drug in Matrix

For inductive drug release


Nanomaterials potential impact on human health

Intravenous delivery of engineered NP

Needs 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?


Nanomaterials potential impact on human health

  • Intentionally produced NP

  • already on the market

  • Newly engineered

  • Unintentionally produced NP

  • Combustion

  • Nucleation

New products, applications

High added value

Negligible exposure (CNT, CB)

Low risk

No added value, extra cost

Considerable health risks


What are nanoparticles

What are nanoparticles?

to a toxicologist


Nanomaterials potential impact on human health

Particles in traditional dusty trades

Nanoparticles

0.01 0.1 1 10mm

10

100

1000

10,000nm


Nanomaterials potential impact on human health

Smaller size means different interactions and distribution

Cilia 0.25µm diameter

.

1.0µm

0.1µm

10µm 1 µm 0.1µm

.

.

N

Mit

Bronchial epithelium


Nanomaterials potential impact on human health

Protein binding by NP may

have different consequences

Borm and Kreyling (2004)

J. Nanotech & NanoSci


Nanomaterials potential impact on human health

Nanosize has physical implications

  • High Surface/volume ratio:

  • Suitable for catalysis,

  • More soluble.

  • More particles at similar mass.

  • Not subject to gravity

Nanosize has implications for surface reactivity and chemistry

  • Size does not allow stoichiometry,

  • Cluster Irregularities.

  • quantum effects

  • Electron holes, reactive surface

TiO2 TiO2 Ti0.99O1.95


Toxicological hazards of nanoparticles what do we know

Toxicological hazards of Nanoparticleswhat do we know?

Have an active and large surface that can interact with

many 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

However:

Most of the evidence for human effects is generated

using unintentionally produced combustion

Nanoparticles.

Effects of manufactured Nanoparticles have mainly

been studied with a small set of particles already

on the market for decades (carbon black, TiO2, FexOy)

Little data on occupational exposure to manufactured

Nanoparticles. Available data suggest negligible

Inhalation exposure (= background).


Nanomaterials potential impact on human health

A Bermuda Triangle

Combustion NP

Epidemiology

Toxicology

?

Bulk industrial NP

Engineered NP

?


Scenario s to consider for testing and regulation of np

Scenario’s to consider for testing and regulation of NP

  • Differences with fine particles merely quantitative (depends on effect)

  • Important qualitative differences in toxicity

  • Regulation driven by application.

  • Find means to extrapolate findings and build conceptual understanding

  • Invest in studies on environmental distribution, accumulation and effects.


Nanomaterials potential impact on human health

Summary of inhalation (o)

and instillation studies (●)

With fine and ultrafine

particles

0.2-0.3 m2/rat

Ad 1:

The carcinogenic response in the rat is driven by surface dose.

This means that regulation of all particles could be done using

A surface dose concept.

Borm et al (2004) Int J cancer


Nanomaterials potential impact on human health

Ad2: qualitative differences: Uptake of NP in the brain

Activation of inflammatory

Cascade 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)

?

Oberdorster et al, 2004

Carbon, Au, MnO


Nanomaterials potential impact on human health

Hazard

x exposure

= Risk


What do we need to know about nanomaterials

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

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


Nanomaterials potential impact on human health

State of the art: Little exchange between companies or between companies and Toxicological research institutes.

Producers and Users of Nanomaterials

Research Institutes


Nanomaterials potential impact on human health

Needed: networks to enable communication

and data exchange between nanoscience and

Toxicology.


Nanomaterials potential impact on human health

NANOTECHNOLOGY

Hazardous

area

HYPE

Science

Fiction


Current and recent initiatives on sustainable nanomaterials

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)


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