2014 Nanod õhus TA seminar täitsa final valik … Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 2014 Our ‘zoo’ Test organisms at various levels of biological

Nanoparticles & nanotechnologiesAnne Kahru, PhD. Head of the Laboratory of Environmental Toxicology

National Institute of Chemical Physics and Biophysics

1Anne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 2014

E-mail: [email protected]

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National Institute of Chemical Physics and Biophysics (NICPB)

• established at 1980 • An independent research institution tightly cooperating with Estonian

universities. • Founder: E. Lippmaa• Current director: R. Stern• Not providing MSc or PhD degrees (co‐supervision)• NICPB is divided into 5 laboratories:

– Environmental Toxicology (A. Kahru)– Chemical physics (U. Nagel)– Bioenergetics (T. Käämbre)– High energy physics (M. Raidal)– Bio‐organic chemistry (J. Siigur)

• website: www.kbfi.ee

Anne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 2014

• Nanotechnology• Novel properties at nanoscale• Nanoparticles: classification• Nanorevolution• Nanoproducts, production volume• Nanoparticles: health risks• Nanoparticles: dual properties due to nanoscale,

toxicity mechanisms• Nanoparticles: LCA, fate in the environment• Nanosafety information available• Nanosafety projects in NICPB• Let’s talk about air• Sustainability of nanotechnologies

Outline of my talk

Anne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 2014 3

Nanotechnology

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Nanotechnology is science, engineering & technology conducted at the nanoscale

1-100 nm


How big is nano?• Sheet of paper ‐100 000 nm• Red blood cells – 8000 nm• Bacteria– 1000 nm• Antibodies‐ 10 nm• Cell membrane and membrane pore : 6–10 nm• Glucose molecule– 1 nm• Gold atom and H2O molecule – 0.3 nm• H atom ‐ 0.1 nm

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Au Au Au

1 nm

Glc


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Nano‐materials

Nanoparticles

NANOTECHNOLOGY

INNOVATIVE APPLICATION


Nanotechnological applications

NanotechApps

Energetics

Medicine

Biotech

Optics

Defence

Cosmetics

Textiles

Sensors


Synthetic = man‐made = engineered NPs

C‐based (fullerenes, C‐nanotubes, graphene)

Metal‐based (ZnO, TiO2, CuO, CeO2, CdSe etc)


1-100 nm• Natural• Antropogenic• Synthetic

Classification

China will soon outcompete USA in nanotechAnne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 2014 9

USA

China

NPs in consumer products: 2005‐2011

10

1015

603

580

356

54

2006 2009

Almost 4-fold increase in 5 years

1317

2011

>1300 consumer products containing ‘nano’ (2011)

_________________

- Nano-Ag – in 311 products

- carbon - 91

- TiO2 - 59


Nanosilver– first commercialized NPs ‐mostly in biocidal nanomaterials

• to protect surfaces–Food contact surfaces and materials–Hospitals (surfaces, textiles)

• to avoid biofilms (catheters, prosthesis, heart valves)

• biocidal textiles (silver socks, sportsware)



CNTs are 100x stronger than steel

Nanosilver kills bad microbes

Nanotitania & zinc protect the skin from UV

B&W drawings: A. Käkinen

The 10 leading causes of death in US: 1900 vs 1997

http://www.cdc.gov/mmwr/PDF/wk/mm4829.pdf



• Nanosilver is more toxic than microsize silver particles

• Nanosilver has to be toxic (to be efficient antimicrobial)

• What about the rest of NPs?

• New physico‐chemical properties

• Increased bioavailability?• Increased toxicity?

Dual novel properties at nanolevel: high function but also high risk

0.64 m2/g 25.5 m2/g

The same nominal concentration

• increased SSA• increased surface display of ingredient

atoms• higher surface reactivity

• display of new • electronic, • optic, • quantum mechanical etc

properties

15Anne Kahru, Nano-Workshop in Academy of

Sciences, Tallinn, May 29, 2014

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Agglomeration, adsorption

Possible toxicity mechanisms of metallic nanoparticles

Dissolution of the material

Toxicity caused by ions

Cu2+, Zn2+, Ag+, Cd2+etc

Toxicity caused by ROS

.OH .O2- .OOR

Catalytic/active sites exposed on the surface

High surface energyHigh surface to volume ratio

Enhanced contact area


TOXICOLOGICAL (prediction to HUMANS)

ECOTOXICOLOGICAL (prediction to ECOSYSTEM)

Tests on mice, rabbits, guinea pigs, etc

Tests on algae, daphnids, fish, etc

The main aims of REACH: to evaluate all industrial substances on the European market for hazardous effects to humans and environment by the year 2018

REACH ‐ Registration, Evaluation, Authorisationand Restriction of Chemicals

Existing and new substances

Classification and Labelling

Safety Data Sheets(toxicological data!)

Marketing & Use DirectivesMarketing & Use DirectivesMarketing & Use DirectivesMarketing & Use Directives

TOXICITY TESTING


Production volumes

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• The most produced is TiO2 ‐ close to 10 000 t/year

• CeO2, FeOx, AlOx, ZnO, carbon nanotubes 1000 t/year •• Ag, quantum dots and fullerenes <10 t/year



B&W drawing: A. Käkinen

Number of publications (per year) in ISI WoSSearch: October 23, 2011.

• Nanotoxicology lags ca 10 years behind nanomaterial research

• Nanoecotoxicological research lags ca 20 years behing nanotoxicological research


2Kahru and Ivask. Acc. Chem. Res., 2013, 46 (3), pp 823–833

Information registered in ISI WoS on various types of nanomaterials since 1980. Search was performed on October 16, 2011.

TOP 5 NMS:• CNTs• QDs• Nanogold• Nanosilver• Fullerenes


1000:10:1

Anne Kahru, Nano-Workshop in Academy of Sciences, Tallinn,

May 29, 2014



Scheme from:http://blog.taigacompany.com/blog/sustainability‐business‐life‐environment/sustainability‐cant‐do‐it‐without‐the‐supply‐chain

Life Cycle Analysis: from cradle to grave

Invention

Material

ProductionTransport

Distribution& use Deposition

of waste

Re-use


Waste streams

Occupational exposure


Nanotoxicological studies in theLaboratory of Environmental Toxicology of the

National Institute of Chemical Physics and Biophysics


Laboratory of Environmental Toxicology

Current activities:

• Toxic or not?• How toxic? Toxic to whom?• Why toxic? mechanistic toxicity safe by design

toxic by designUnderstanding on nano-bio interactions is essential!!

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Our ‘zoo’

Test organisms at various levels of biological and environmental organization:

• Design of (bio) assays/test batteries for rapid and cost‐efficient nanotoxicity testing and nanosafety analysis

Mammalian cell cultures

Yeast

Toxicological test systems:

waterflea protozoa algae bacteria

Test systems for environmental toxicity testing:

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Our test systems, to study the mechanisms of action of NPs

Recombinant luminescent sensor bacteria reporting on:

• Bioavailable metals (e.g., Zn, Cd, Ag, Cu, As, Cr)

• ROS• DNA damage

Mutant luminescent E. coli:

• sod1, sod2, sod3 & combinations

Mutant S. cerevisiae • different single gene

mutants, from EUROSCARF

metal

ROS

ROS


Nanotechnology Forum, Tartu, 2013 28

Nanotoxicology‐related projects of theLaboratory of Environmental Toxicology of the National Institute of Chemical

Physics and BiophysicsHead of the lab: Dr. Anne Kahru

IUT “Nano(eco)toxicology and beyond”, Estonia Research Council´s Institutional Research Grant (2014‐2019)

EU FP7 “Nanovalid” project (EU Nanosafety cluster) (2012‐2015)

EU FP7 “Modern” project (EU Nanosafety cluster) (2013‐2015)

“Terikvant” Estonian Research Council’s ‘Environmental Conservation and Environmental Technology R&D Program (KESTA) project (2012‐2014)

“Pharmaceutical’s residues and engineered nanoparticles: effect on the wastewater treatment and antibiotic resistance gene transfer in the environment”, Estonian Research Council’s ‘Environmental Conservation and Environmental Technology R&D Program (KESTA) project (2012‐2015)

SMaCell, project in Materials technology R&D program of SA Archimedes (2012‐2014)

FP7 NanoValid

> 40 partners, Coordinator: R. Reuther (Sweden). NICPB’s PI: Anne KahruAnne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 201429

Anne Kahru, Nano‐Workshop in Academy of Sciences, Tallinn, May 29, 2014

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NICPB’s PI: Anne Kahru

Coordinator: F. Giralt (Spain). NICPB’s PI: Anne Kahru


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Let’s talk about air

"Our task was to evaluate the air everyone breathes rather than focus on specific air pollutants," The predominant sources of outdoor air pollution were transport, power generation, emissions from factories and farms, and residential heating and cooking, the agency said.

Oct 17, 2013The World Health Organisation :outdoor air pollution is a leading cause ofcancer in humans.


After 24 h ca 10%translocated into organs (liver, spleen, kidneys, heart, brain, reproductive organs. 80 nm NPs 10x less translocated

ca 2% translocated

ca 0.2% translocated

Depends on size, material, exposure (inhalation, instillation)Anne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29,

201433

Anne Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29,

201434

Production volumes of nanoparticlescarbon nanotubes account for a 28% market share of overall nanomaterials demand

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Asbesthos – once miracle material

1962‐1994: ca 2.2 million tons of eternit (10‐15% chrysotile asbesthos) was produced in Kunda.

Currently asbesthos is banned in EU causes lung diseases and lung cancer

Asbesthos fiber similar to carbon nanotubes pulmonary effects?

About 80% of our older buildings still contain harmful asbesthos materials


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From the report ‘Nano‐Regulation’ (issued at 2005 by various Swiss ‘nano’ stakeholders)

The protection of health and environmental safety aspects has to be guaranteed and potential risks must be reduced.

The future social value of nanotechnology should be maximized

versus

SUSTAINABILITY OF NANOTECHNOLOGIES

Nanosafety to regulate emerging nanotechnology:

It is all about striking the right balance between precautionand venture



....’ Nanotechnology and its myriad applications have the potential for enormous benefits (in particular in the field of “nanomedicine”), but also for serious harm. As with most emerging technologies, many risks, both to public health and to the environment, are as yet poorly understood...’/...’ In the context of the current knowledge (and lack of it) on the potential hazard nanotechnologies present both to human health and the environment, it thus seems evident to me that the precautionary principle needs to be applied in this field...’

Parlamentary Assembly of the Council of Europe (PACE), discussed for the recommendation, April 26, 2013)


Until we do not have enough scientific evidence on biological effects of synthetic NPs, it is wise

to apply the precautionary principle, i.e.,

BETTER SAFE THAN SORRY

PAREM KARTA KUI KAHETSEDA (in Estonian)

Additional information


• Chapter in a recent book: ‘Research in Estonia’ (2011)

2011 J. Engelbrecht (editor‐in‐chief), G.Varlamova


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Anne Kahru, Nano-Workshop in Academy of Sciences,

Tallinn, May 29, 2014

Our most recent scientific nanosafety papers


43Anne Kahru, Nano‐Workshop in Academy of Sciences, Tallinn, May 29, 2014

Ivask, A; Kurvet, I., Kasemets, K., Blinova, I., Aruoja, V.; Suppi, S., Vija, H., Käkinen, A., Titma, T., Heinlaan, M., Visnapuu, M., Koller, D., Kisand, V., Kahru, A. Size‐dependent toxicity of silver nanoparticles to bacteria, yeast, algae, crustaceans and mammalian cells in vitro. PLOS One, in revision.

Ivask, A.; Juganson, K.; Bondarenko, O.; Mortimer, M.; Aruoja, V.; Kasemets, K.; Blinova, I.; Heinlaan, M.; Slaveykova, V.; Kahru, A. (2014). Mechanisms of toxic action of Ag, ZnO and CuO nanoparticles to selected ecotoxicological test organisms and mammalian cells in vitro: a comparative review. Nanotoxicology.doi:10.3109/17435390.2013.855831

Käkinen A., Ding F., Chen P., Mortimer M., Kahru A. and Ke PC. (2013) Interaction of firefly luciferase and silver nanoparticles and its impact on enzyme activity. Nanotechnology 24 (34) 345101, 9 page

Bondarenko, O., Juganson, K., Ivask, A., Kasemets, K., Mortimer, M., Kahru, A. (2013) Toxicity of Ag, CuO and ZnO nanoparticles to selected environmentally relevant test organisms and mammalian cells in vitro: a critical review. Archives of Toxicology, 87 (7): 1181‐1200.

Mortimer, M., Kahru, A., Slaveykova, V. Uptake, localization and clearance of quantum dots in ciliated protozoa Tetrahymena thermophila. Environ Pollut.;190:58‐64.

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Bondarenko O, Ivask A, Käkinen A, Kurvet I, Kahru A (2013) Particle‐Cell Contact Enhances Antibacterial Activity of Silver Nanoparticles. PLoS ONE, 8(5):e64060. doi:10.1371/journal.pone.0064060;

Blinova I, Niskanen J, Kajankari P, Kanarbik L, Käkinen A, Tenhu H, Penttinen OP, Kahru A. (2013) Toxicity of two types of silver nanoparticles to aquatic crustaceans Daphnia magna and Thamnocephalus platyurus. Environ Sci Pollut Res (2013) 20(5):3456‐63. doi: 10.1007/s11356‐012‐1290‐5.

Kahru, A. and Ivask, A. (2013) Mapping the Dawn of NanoecotoxicologicalResearch. Accounts of Chemical Research. Acc. Chem. Res., 2013, 46 (3), pp 823 833; DOI: 10.1021/ar3000212

Kasemets, K., Suppi, S., Ku ̈nnis‐Beres, K., Kahru, A. (2013) Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild‐type and its nine isogenic single‐gene deletion mutants. Chemical research in toxicology 26 (3), 356‐367

Juganson, K., Mortimer, M., Ivask, A., Kasemets, K., Kahru, A. Extracellular conversion of silver ions into silver nanoparticles by protozoan Tetrahymena thermophilaEnvironmental Science: Processes & Impacts 15 (1), 244‐250


Documents

2014 Nanod õhus TA seminar täitsa final valik … Kahru, Nano-Workshop in Academy of Sciences, Tallinn, May 29, 2014 Our ‘zoo’ Test organisms at various levels of biological