Nanomaterials: Potential impact on human health

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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.
Nanomaterials:Potential impact on human health Paul J.A. Borm Paris- OECD- june 7th 2005Nanoparticles-already a bulk marketAllVariousDoubling from 493 € to 900Mi in 2005Biggest increase SiO2 expectedMetalsAl2O3TiO2SiO202004006008001000Millions USDEstimated global Production rates forNanomaterialsLife 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 toolboxEngineered NPPorous PolymerShrinkage MagnetiteInductiveHeating200-10000 nmDrug ReleaseDrug in MatrixFor inductive drug releaseIntravenous 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 valueNegligible exposure (CNT, CB)Low riskNo added value, extra costConsiderable health risksWhat are nanoparticles? to a toxicologistParticles in traditional dusty tradesNanoparticles0.01 0.1 1 10mm 10 100 100010,000nmSmaller size means different interactions and distributionCilia 0.25µm diameter.1.0µm0.1µm10µm 1 µm 0.1µm..NMitBronchial epitheliumProtein binding by NP mayhave different consequencesBorm and Kreyling (2004)J. Nanotech & NanoSciNanosize 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 Ti0.99O1.95Toxicological hazards of Nanoparticleswhat do we know?Have an active and large surface that can interact withmany targets in the bodyBad recognition by our immune system and even Enhance response to antigensCan 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 unintentionally 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).A Bermuda TriangleCombustion NPEpidemiologyToxicology?Bulk industrial NPEngineered 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.
  • Summary of inhalation (o)and instillation studies (●)With fine and ultrafineparticles0.2-0.3 m2/ratAd 1: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.Borm et al (2004) Int J cancerAd2: qualitative differences: Uptake of NP in the brainActivation of inflammatoryCascade in brain Caldwell et al, 2005Relation to Alzheimer?Calderon-Garciduenas, et al, 2004Relation to systemic effects such as heart rate, blood pressure changes (Brook et al, 2002; Lippman et al, 2005)?Oberdorster et al, 2004Carbon, Au, MnOHazardx exposure= RiskWhat 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
  • State of the art: Little exchange between companies or between companies and Toxicological research institutes.Producers and Users of NanomaterialsResearch InstitutesNeeded: networks to enable communication and data exchange between nanoscience andToxicology. NANOTECHNOLOGYHazardousareaHYPEScienceFictionCurrent 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)
  • Related Search
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