nanotechnology m hofmann
TRANSCRIPT
Particles:Particles:Nanoparticles, Fullerenes Nanoparticles, Fullerenes and Carbon Nano Tubes and Carbon Nano Tubes
Margarethe HofmannMargarethe HofmannMAT SEARCH, PullyMAT SEARCH, Pully
President SVMTPresident SVMT
Topics of the WorkshopTopics of the Workshop
« Environmental Aspects » – latest research « Environmental Aspects » – latest research activitiesactivities
« Material Safety Standards » - required for « Material Safety Standards » - required for safety of producers and consumerssafety of producers and consumers
nearly or insoluble particlesnearly or insoluble particles
Properties of Nanoparticles (< 100 nm)
Zimmermann
K arg
Cyrys
Behrendt/Allessandrini
S chulz
Peters
Wolff
Schramm
Maier
AndraeWittmaa ck
Zimmermann
K arg
Cyrys
Behrendt/Allessandrini
S chulz
Peters
Wolff
Schramm
Maier
AndraeWittmaa ck
Aerosol formation processes:
• Heterogeneous + homogeneous nucleationHeterogeneous + homogeneous nucleation
• Combustion, photochemical reactions; etc.Combustion, photochemical reactions; etc.
• Growth by coagulation, shrinkageGrowth by coagulation, shrinkage
Chemical formation processes:
• Polymerization (Emulsion)
• Precipitation, Crystallization
• Growth by coagulation, shrinkage
After: Wolfgang G. Kreyling, GSF – Forschungszentrum für Umwelt und Gesundheit, München
Investors, Industrials, ScientistsInvestors, Industrials, Scientists U.S. venture capital firm Draper Fisher Jurvetson: „It would not invest
in a nanotech business unless the products had already been proven safe“.
Germany-based Munich Re Group: „Up to now, losses involving dangerous products were on a relatively manageable scale, whereas, taken to extremes, nanotechnology products can even cause ecological damage which is difficult to contain” .
Patricia Pineau, a L’Oreal research adviser: “At each step of the product development – from the raw materials to the final formula – we evaluate the safety in vitro and then, only if the previous test is negative, in vivo on human volunteers” .
Ken Donaldson of the University of Edinburgh Medical School: „A new way of classifying nano-particles needs to be created, that takes more than size into account, but also the “full spectrum of toxicities“ that might arise from nanoparticles of different compositions“.
http://www.smalltimes.com/document_display.cfm?document_id=7608http://www.smalltimes.com/document_display.cfm?document_id=7608
Regulation Regulation
Currently, dosage of particles for regulation purposes is defined by Currently, dosage of particles for regulation purposes is defined by mass per unit volumemass per unit volume, however this does not take into account , however this does not take into account particle size. Hence it is clear that agglomeration, particle size and particle size. Hence it is clear that agglomeration, particle size and surface reactivity will now have to be taken into account when surface reactivity will now have to be taken into account when deciding the regulation of nanoparticles. deciding the regulation of nanoparticles.
The point was made however that there are many types of The point was made however that there are many types of nanoparticles and that they should not be treated as a nanoparticles and that they should not be treated as a general casegeneral case when deciding regulation. To resolve this issue, further toxicological when deciding regulation. To resolve this issue, further toxicological studies must be performed in order to effectively inform regulators. studies must be performed in order to effectively inform regulators.
The point was also made that regulations may The point was also made that regulations may differ between localesdiffer between locales e.g. in the USA sun creams are categorised as drugs for regulation, e.g. in the USA sun creams are categorised as drugs for regulation, while in the UK they are regulated as cosmetics. while in the UK they are regulated as cosmetics.
Nanotechnology: views of Scientists and Engineers
Report of a workshop held as part of the Nanotechnology study (http://www.nanotec.org.uk/)
Insoluble or nearly insoluble nano- or ultrafine Insoluble or nearly insoluble nano- or ultrafine particlesparticles
Research for developing standards together with Research for developing standards together with industryindustry Example 3R Foundation – reducing animal Example 3R Foundation – reducing animal
experimentsexperiments
SummarySummary
SummarySummary
Define the hot spots of danger coming from Define the hot spots of danger coming from nanoparticles – risk assessmentnanoparticles – risk assessment Road map – amount of particles on the market, exposure, Road map – amount of particles on the market, exposure,
uptakeuptake Road map for particles in research – nanotubes, CdSe etc.Road map for particles in research – nanotubes, CdSe etc.
Develop models (in-vitro and in-vivo) for interaction Develop models (in-vitro and in-vivo) for interaction with the human bodywith the human body toxicity, biodistribution, allergiestoxicity, biodistribution, allergies
Life Cycle assessment for chemicals Life Cycle assessment for chemicals adapted to nanoparticlesadapted to nanoparticles Define component by nanoparticle relevant Define component by nanoparticle relevant
featuresfeatures
SummarySummary
SummarySummary
Further detailed recommendationFurther detailed recommendation Need more information from responsibles in Need more information from responsibles in
industry and related researchers, toxicologists, risk industry and related researchers, toxicologists, risk assessmentassessment
Workshop SVMT-SATW-TOP NANO 21 on Workshop SVMT-SATW-TOP NANO 21 on « Safety aspects of nanoparticles » « Safety aspects of nanoparticles » November 2004November 2004
ParticlesParticles
Ultrafine- or nanoparticles, colloids, aerosolsUltrafine- or nanoparticles, colloids, aerosols are are smaller than 100 nm. smaller than 100 nm.
In comparison with their source materials, such In comparison with their source materials, such nanoparticles have different optical, electrical, nanoparticles have different optical, electrical, mechanical, and chemical properties. mechanical, and chemical properties.
They are not only unique to this field of hi-tech; They are not only unique to this field of hi-tech; they are present in our everyday lives and at they are present in our everyday lives and at various conventional workplaces. various conventional workplaces.
After BIA-Report 7/2003
Nanoparticle Application 2003Nanoparticle Application 2003
Established commercial Established commercial nanoparticle applicationsnanoparticle applications Tires, Other Rubber Products Catalytic Converters Photographic Supplies Inks and Pigments Coatings and Adhesives Ultrafine Polishing Compounds UV Absorbers for Sun Screens Synthetic Bone Ferrofluids Optical Fiber Cladding
Launch-Phase Nanoparticle Launch-Phase Nanoparticle ApplicationsApplications Fabrics and Fabric Treatments Filtration Systems Dental Products Surface Disinfectants Diesel Fuel Additives Fuel and Explosive Additives Hazardous Chemical Neutralizers
Developmental Nanoparticle Developmental Nanoparticle Applications Applications Recharg. Lithium Ion Batteries Antioxidants Dental-Care Products
http://www.mindbranch.com
Nanotube Application 2003Nanotube Application 2003 Commercial Nanotube ApplicationsCommercial Nanotube Applications
Automotive Components Electronics Production/Clean-Room Equipment Scanning Microscope Tips Sports Equipment
Launch-Phase Nanotube ApplicationsLaunch-Phase Nanotube Applications Field Emission Devices X-Ray Devices Flat-Panel Displays Other Field Emission Applications
Developmental Nanotube ApplicationsDevelopmental Nanotube Applications Semiconductors Drug-Delivery Systems Fuel Cells
http://www.mindbranch.com
Field of Concern in the EnvironmentField of Concern in the Environment Behaviour and influence of nanoparticles in the biota?Behaviour and influence of nanoparticles in the biota?
Nanoparticles may influence the biosphereNanoparticles may influence the biosphere Structural transition by liquids like water (biogenic nanoparticles)Structural transition by liquids like water (biogenic nanoparticles) Chemical/physical transition by recycling (combustion)Chemical/physical transition by recycling (combustion)
Behaviour and influence of nanoparticles in the food chain? Behaviour and influence of nanoparticles in the food chain? Filter-feeding organisms such as plankton regulate the intake and Filter-feeding organisms such as plankton regulate the intake and
distribution of these nanoparticles? distribution of these nanoparticles? Further uptake by fishes, birds, large animalsFurther uptake by fishes, birds, large animals
Biodistribution of nanoparticles in the body?Biodistribution of nanoparticles in the body? Lung, liver, blood, etc. Lung, liver, blood, etc.
Manipulation of of cells and/or genes by nanoparticles?Manipulation of of cells and/or genes by nanoparticles? TransfectionTransfection Formation/initiation of tumour cellsFormation/initiation of tumour cells Misfunction of proteins after adsorptionMisfunction of proteins after adsorption
Lung Smoking, diesel soot, tires, rubber products
Smoke and exhaust of welding, soldering, foundaries, injection molding, grinding and polishing
Nanoparticles based ceramics, quantum dots
Nanoparticles based medical products (aerosols)
Skin Cosmetics, pharmaceutics, paintings
Intravenious, intraarticular, systemic Drugs, diagnostic agents, food
Way of assimilation and incorporation
Modes of action and mechnisms Lymphatic system Blood system Nervous systems Cells - cell interaction Uptake in the cells and the nucleus
Way of assimilation and incorporation
Material Safety StandardsMaterial Safety Standards
No standards exist for nanoparticlesNo standards exist for nanoparticles FDA list “Generally Recognized As Safe”
(GRAS) – applicable to nanosized particles? MAK not applicable for nanoparticles? In-vivo-solubility of nanoparticles – no method Nanopathology ?
Strategy for sustainable risk assessment
Classical tests not sufficiently specific and not adequate for a comprehensive risk assessment of multiple interactions of NP with biological systems
Deleterious effects (inflammation,
cytotoxicity, muta- + cancerogenesis)
Genomic screening
(gene array)
Proteomic verification
(RT-PCR)Secondary
target organ Risk
assessment
Regulation
Organ of intake
Cells, proteins, fluids, tissues
NP
After W. G. Kreyling, GSF - Forschungszentrum für Umwelt und Gesundheit, Institut für Inhalationsbiologie, Neuherberg
Material StandardsMaterial Standards
Physical standards for surface roughness, subsurface properties, form (flatness, sphericity, asphericity) glass, ceramics and metals are urgently needed.
Besides those standards, made of anorganic materials, equivalent standards are very desired for nanotechnology in all kind of processes (manufacture, monitoring, measurement) of organic materials including living cells in special cases.
Position paper on „The need for measurement and testing in nanotechnology“ Compiled by the High Level Expert Group on Measurement and Testing, Under the European Framework Programme for Research and Development 2002 - HLEG_nanotech_full_final_11/3/02
Analytic AspectsAnalytic Aspects AnalyticsAnalytics (measurement and test engineering) (measurement and test engineering)
– air, surface, liquid, body Particle concentration
Particles size and form, particle agglomerates
Particle surface charge,
coating after synthesis, within the environment
Dissolution and recombination
Safety AspectsSafety Aspects
Production Production New technologies, new particle formulationNew technologies, new particle formulation
Production in clean rooms? Filter? Health aspects of employees?
Classic production routesClassic production routes Learn from already existing safety standards?
Safety AspectsSafety Aspects
EnvironmentEnvironment Functionalized particles Functionalized particles
Influence on biota: internalization of particles Influence on the biosphere
Nanoparticles in a matrixNanoparticles in a matrix Recycling, waste/material combustion
Pollution, smoke, dustPollution, smoke, dust Reduced size and size distribution, higher
internalization
Safety AspectsSafety AspectsPublic HealthPublic Health Overall air pollution (e.g. cigarettes, diesel soot, tires, industrial Overall air pollution (e.g. cigarettes, diesel soot, tires, industrial
contamination)contamination) How far does nanotechnology boost danger? Need for more epidemiologic research?
Daily life body exposure (cosmetics, paint, clothing, nutrition)Daily life body exposure (cosmetics, paint, clothing, nutrition) Information of customers? Future requirements for industry? Challenges and requirements for research (medical, basic, engineering)
Future tailored particles (e.g. in life sciences, transport, etc.)Future tailored particles (e.g. in life sciences, transport, etc.) Challenges and requirements for research (medical, basic, enginering) Support and requirements for industry? Information of customers?
Properties of Nanoparticles to be determined
Chemistry Surface chemistry, surface charge
Combination of elements (transition metals)
Dissolution and recombination
Adsorption, desorption, catalytic activity ….
Physics (Quantum) size and form effect
Volume - Surface properties
Transport …..
Biology Uptake: histospecific, cellular, subcellular (nucleus)
Blood compatibility, rheological effects …..
Exposure During manufacturing + processing at the workplace
Single nanoparticle product (aerosol, colloid)
Concentration (air, skin)
Exposure periods assessable
General population + population during use + application
Multiple products at low concentrations (exhaust, cosmetics, medical products)
Undefined exposure periods and concentration
Material Safety Standards
RISK = HAZARD + EXPOSURE (ASSESSMENT)
Too often, the ‘exposure’ part of this equation is omitted and hazard is equated with risk. This is an important oversight because there can be little risk to even hazardous materials provided there is no exposure. Thus, the exposure component of the risk equation is vital.
Example: recent toxicity studies have demonstrated that high-dose, intratracheally-instilled, single walled carbon nanotubes in the lungs of rats may produce unusual foreign-body tissue reactions.
Physiological relevance: occupational exposure assessment studies have indicated that aerosol exposure levels of carbon nanotubes in the workplace were, in this case, negligible.
After David B. Warheit in Materialstoday February 2004
Translocation of NanoparticlesTranslocation of Nanoparticles
After W. G. Kreyling, GSF - Forschungszentrum für Umwelt und Gesundheit, Institut für Inhalationsbiologie, Neuherberg
After David B. Warheit in Materialstoday February 2004
Translocation of NanoparticlesTranslocation of Nanoparticles
Ten Toxic WarningsTen Toxic Warnings1. 1997 - Titanium dioxide/zinc oxide nanoparticles from sunscreen are
found to cause free radicals in skin cells, damaging DNA. (Oxford University and Montreal University) Dunford, Salinaro et al.
2. March 2002 – „… engineered nanoparticles accumulate in the organs of lab animals and are taken up by cells…“ Dr. Mark Wiesner
3. March 2003 - „.. studies on effects of nanotubes on the lungs of rats produced more toxic response than quartz dust.“ „Scientists from DuPont Haskell laboratory present varying but still worrying findings on nanotube toxicity. Nanotubes can be highly toxic." - Dr. Robert Hunter (NASA researcher)
4. March 2003 - Dr. Howard: the smaller the particle, the higher its likely toxicity and that nanoparticles have various routes into the body and across membranes such as the blood brain barrier. ETC Group
5. July 2003 - Nature reports on work by CBEN scientist Mason Tomson that shows buckyballs can travel unhindered through the soil. "Unpublished studies by the team show that the nanoparticles could easily be absorbed by earthworms, possibly allowing them to move up the food-chain and reach humans" - Dr. Vicki Colvin, the Center's director.
http://online.sfsu.edu/~rone/Nanotech/nanobraindamage.htm
Ten Toxic WarningsTen Toxic Warnings6. January 2004 - Dr. Günter Oberdörster: nanoparticles are able to move easily
from the nasal passageway to the brain.
7. January 2004 - Nanosafety researchers from University of Leuven, Belgium in Nature: nanoparticles will require new toxicity tests: "We consider that producers of nanomaterials have a duty to provide relevant toxicity test results for any new material, according to prevailing international guidelines on risk assessment. Peter H. M. Hoet, Abderrrahim Nemmar and Benoit Nemery, University of Belgium(14)
8. January 2004 - Nanotox 2004: Dr. Vyvyan Howard presents initial findings that gold nanoparticles can move across the placenta from mother to fetus.
9. February 2004 - Scientists at University of California, San Diego discover that cadmium selenide nanoparticles (quantum dots) can break down in the human body potentially causing cadmium poisoning. "This is probably something the [research] community doesn't want to hear." - Mike Sailor, UC San Diego.(16)
10. March 2004 - Dr. Eva Oberdörster: buckyballs (fullerenes) cause brain damage in juvenile fish along with changes in gene function. "Given the rapid onset of brain damage, it is important to further test and assess the risks and benefits of this new technology before use becomes even more widespread." - Dr. Eva Oberdörster.
http://online.sfsu.edu/~rone/Nanotech/nanobraindamage.htm
Exposure to nanoparticles Smoking, diesel soot, tires, rubber products
Smoke and exhaust of welding, soldering, foundaries, injection molding, grinding and polishing
Nanoparticles based ceramics, quantum dots
Nanoparticles based medical products (aerosols)
Cosmetics, pharmaceutics, paintings
Drugs, diagnostic agents, food
Material Safety Standards