Transcript Hope, Danger and Generalization of Nanotechnology
Particles: Nanoparticles, Fullerenes and Carbon Nano Tubes
Margarethe Hofmann MAT SEARCH, Pully President SVMT
Topics of the Workshop
« Environmental Aspects » – latest research activities « Material Safety Standards » - required for safety of producers and consumers
nearly or insoluble particles
Properties of Nanoparticles (< 100 nm) Chemical formation processes:
• Polymerization (Emulsion) • Precipitation, Crystallization • Growth by coagulation, shrinkage
Aerosol formation processes:
• Heterogeneous + homogeneous nucleation • Combustion, photochemical reactions; etc.
• Growth by coagulation, shrinkage After:
Wolfgang G. Kreyling, GSF – Forschungszentrum für Umwelt und Gesundheit, München
Current and Emerging Applications for Nanoparticles
Investors, Industrials, Scientists
U.S. venture capital firm Draper Fisher Jurvetson: safe“. „It would not invest in a nanotech business unless the products had already been proven 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: negative, in vivo on human volunteers” .
“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 Ken Donaldson of the University of Edinburgh Medical School: that might arise from nanoparticles of different compositions“.
„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“ http://www.smalltimes.com/document_display.cfm?document_id=7608
Nanotechnology: views of Scientists and Engineers
Regulation
Currently, dosage of particles for regulation purposes is defined by
mass per unit volume
, however this does not take into account particle size. Hence it is clear that agglomeration, particle size and surface reactivity will now have to be taken into account when deciding the regulation of nanoparticles. The point was made however that there are many types of nanoparticles and that they should not be treated as a
general case
when deciding regulation. To resolve this issue, further toxicological studies must be performed in order to effectively inform regulators. The point was also made that regulations may
differ between locales
e.g. in the USA sun creams are categorised as drugs for regulation, while in the UK they are regulated as cosmetics. Report of a workshop held as part of the Nanotechnology study (http://www.nanotec.org.uk/)
Summary
Insoluble or nearly insoluble nano- or ultrafine particles Research for developing standards together with industry Example 3R Foundation – reducing animal experiments
Summary
Define the hot spots of danger coming from nanoparticles – risk assessment Road map – amount of particles on the market, exposure, uptake Road map for particles in research – nanotubes, CdSe etc.
Develop models (in-vitro and in-vivo) for interaction with the human body toxicity, biodistribution, allergies
Summary
Life Cycle assessment for chemicals adapted to nanoparticles
Define component by nanoparticle relevant features
Summary
Further detailed recommendation Need more information from responsibles in industry and related researchers, toxicologists, risk assessment Workshop SVMT-SATW-TOP NANO 21 on « Safety aspects of nanoparticles » November 2004
Particles
Ultrafine- or nanoparticles, colloids, aerosols smaller than 100 nm. are In comparison with their source materials, such nanoparticles have different optical, electrical, mechanical, and chemical properties. They are not only unique to this field of hi-tech; they are present in our everyday lives and at various conventional workplaces. After BIA-Report 7/2003
Nanoparticle Application 2003
Established commercial nanoparticle 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 Applications
Fabrics and Fabric Treatments Filtration Systems Dental Products Surface Disinfectants Diesel Fuel Additives Fuel and Explosive Additives Hazardous Chemical Neutralizers
Developmental Nanoparticle Applications
Recharg. Lithium Ion Batteries Antioxidants Dental-Care Products http://www.mindbranch.com
Nanotube Application 2003
Commercial Nanotube Applications Automotive Components Electronics Production/Clean-Room Equipment Scanning Microscope Tips Sports Equipment Launch-Phase Nanotube Applications Field Emission Devices X-Ray Devices Flat-Panel Displays Other Field Emission Applications Developmental Nanotube Applications Semiconductors Drug-Delivery Systems Fuel Cells http://www.mindbranch.com
Field of Concern in the Environment
Behaviour and influence of nanoparticles in the biota?
Nanoparticles may influence the biosphere Structural transition by liquids like water (biogenic nanoparticles) Chemical/physical transition by recycling (combustion) Behaviour and influence of nanoparticles in the food chain? Filter-feeding organisms such as plankton regulate the intake and distribution of these nanoparticles? Further uptake by fishes, birds, large animals Biodistribution of nanoparticles in the body?
Lung, liver, blood, etc. Manipulation of of cells and/or genes by nanoparticles?
Transfection Formation/initiation of tumour cells Misfunction of proteins after adsorption
Way of assimilation and incorporation
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
Material Safety Standards
No 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 NP Organ of intake Cells, proteins, fluids, tissues Genomic screening (gene array ) Proteomic verification (RT-PCR) Secondary target organ Risk assessment Deleterious effects (inflammation, cytotoxicity, muta- + cancerogenesis) Regulation
After W. G. Kreyling, GSF - Forschungszentrum für Umwelt und Gesundheit, Institut für Inhalationsbiologie, Neuherberg
Material 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 Aspects
Analytics (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 Aspects Production
New technologies, new particle formulation Production in clean rooms? Filter? Health aspects of employees?
Classic production routes Learn from already existing safety standards?
Safety Aspects Environment
Functionalized particles Influence on biota: internalization of particles Influence on the biosphere Nanoparticles in a matrix Recycling, waste/material combustion Pollution, smoke, dust Reduced size and size distribution, higher internalization
Safety Aspects
Public Health
Overall air pollution (e.g. cigarettes, diesel soot, tires, industrial contamination) How far does nanotechnology boost danger?
Need for more epidemiologic research?
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.) 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 …..
Material Safety Standards 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
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 Nanoparticles
After W. G. Kreyling, GSF - Forschungszentrum für Umwelt und Gesundheit, Institut für Inhalationsbiologie, Neuherberg
Translocation of Nanoparticles
After David B. Warheit in Materialstoday February 2004
Ten Toxic Warnings
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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. March 2002 – „…
engineered nanoparticles
accumulate in the organs of lab animals and are taken up by cells…“ Dr. Mark Wiesner March 2003 - „.. studies on effects of 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)
nanotubes
on the lungs of rats 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 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 Warnings
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7.
8.
9.
10.
January 2004 - Dr. Günter Oberdörster: from the nasal passageway to the brain.
nanoparticles
are able to move easily 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) January 2004 - Nanotox 2004: Dr. Vyvyan Howard presents initial findings that
gold nanoparticles
can move across the placenta from mother to fetus.
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) March 2004 - Dr. Eva Oberdörster: 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.
buckyballs (fullerenes)
cause brain http://online.sfsu.edu/~rone/Nanotech/nanobraindamage.htm
Material Safety Standards 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