Nanoparticles and nanotechnology

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Nanoparticles and nanotechnology

• Dr Martin Cosgrove
• MB ChB FRCGP MFOM
• Consultant Occupational Physician

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Warning!

• Personal account
• The more I know,
• the more I realise I dont know anything
• I am likely to be wrong about some things,
• but not possible to know what or how much by
• If all you ask is questions
• More uncertainty

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Overview

• Cell biology
• Existing knowledge base
• Nano materials Carbon nanotubes
• HS

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The Cell
Credit STEVE GSCHMEISSNER
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Mitochondrion
500nm x 2 to 5000 nm
Credit BILL LONGCORE
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Cell Microtubules
25 nm diameter
Credit THOMAS DEERINCK, NCMIR
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The biological scale
10µm 1 µm 100nm 10nm
Nucleus 3-14 µm diameter Cilia 5-15
long Mitochondrion 0.5x 2 to 5 µm
Centriole 150nm x 300 to 500 nm Cell membranes
7.5 to180 nm thick Ribosomes 15-25 nm
diameter Microtubules 25 nm diameter
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Cell division
Credit DR ALEXEY KHODJAKOV
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Deposition of particles in the lung
Total body deposition
1 0.5 0
Deposition fraction
Alveolar deposition
0.001 0.01 0.1 1 10
100 Particle size µm
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Fate of UFPs in the lungs

• Soluble particle dissolved in mucus, absorbed
  into circulation
• Slowly dissolving and insoluble particles
• on airway wall coughed up
• in alveolus phagocytosis by macrophages
• Remains in lung
• Transported into circulation small

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Cell uptake

• Pinocytosis
• Biodistribution
• Localisation in tissues
• Lung, liver, spleen,
• bone marrow,
• brain and lymph nodes

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Particulate air pollution

• PM10 Course particles 2.5 10 µm diameter
• PM2.5 Fine particles lt2.5 µm diameter
• PM1 Ultrafine particles lt100 nm diameter

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Air pollution in the West

• Burning three rings of domestic gas
• 50 x 103 UFP / cm3
• London 10 - 50 x 103 UFP/cm3
• European cities 15 -18 x103 UFP/cm3
• USA 106 UFP / cm3 in busy road area

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Effects of air pollution

• For every increase of 10µg/m3 in PM2.5
  ?mortality by 6
• Cardiovascular disease
• Chronic lung disease
• But not a problem in welders or kitchen staff
  despite UFP exposure

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Asbestos

• Serpentine
• Chrysotile
• Fibrous amphiboles
• Actinolite
• Amosite
• Anthophyllite
• Crocidolite
• Tremolite

long curved flexible fibres, break easily
stiffer fibres, do not break so easily
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Crocidolite SEM false colour
CreditDR JEREMY BURGESS Magnification x60
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Asbestos fibre with macrophages impaled
macrophage
Credit PHOTO INSOLITE REALITE
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Effects of asbestos

• Lung cancer
• Increased in asbestos workers
• Multiplicative effect of smoking and asbestos
  exposure
• Asbestosis
• Mesothelioma

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Mesothelium

• Internal skin surrounding the lung and the
  abdominal organs
• Occasionally becomes malignant mesothelioma
  2000 cases/year UK
• Much more likely to become malignant if exposed
  to asbestos, particularly amphiboles
• Long lag time between exposure and cancer

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Mesothelioma
Credit science photo library
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Hazardous asbestos fibre

• Thinner than 3 µm
• Longer than 15-20 µm
• Bio-persistent in the lungs does not dissolve
  or break into smaller fibres
• Must reach a concentration level to cause chronic
  inflammation, genotoxicity, fibrosis and cancer
  in target cells

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Nanoparticles

• Nanos Greek, a dwarf
• Nano Scientific term, a billionth
• Particle up to 100 nm in at least one dimension
  created by engineering
• Below 50nm subject to quantum rather than
  Newtonian physics
• With decreasing size, more atoms are at the
  surface

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Examples of nanoparticles

• Fullerenes
• Nanotubes
• Nanowires
• Quantum dots
• Plasmons

• Aim is N3
• nMeters
• nJoules
• nSeconds

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The Market
Nano medicine
Nano metrology
Nano materials / nano particles
Nano fabrication
2007 value US 1,1000,000,000,000
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The scale of nanoparticles
Eukaryotes gt5 µm Bacteria 0.5-3 µm Herpes virus
100 nm Adenovirus 70-90 nm Parvovirus 18-26 nm
10µm 1 µm 100nm 10nm 1nm 0.1nm 0.01nm
Atomic size 0.2 nm Distance between two H atoms
in Hydrogen molecule 0.07nm
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Physico chemical properties

• Size and shape
• Solubility
• Chemical composition
• Lattice structure

• Surface chemistry
• Surface charge
• Surface area
• Aggregation state
• Biopersistence

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The new nano-world

• The function of engineered nanoparticles cannot
  necessarily be predicted from their chemistry and
  physical properties alone
• Its not a size thing!
• It what it does that matters
• What do we measure as regards dose?

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Buckminsterfullerene C60

• Uses
• Bowling balls,
• Tennis rackets,
• Clothing,
• Materials science,
• Pharmaceuticals,
• Resin coatings to improve controllability

0.7nm diameter
Credit David Taylor
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Single Walled Carbon Nanotubes

• Capped or uncapped
• Tend to aggregate
• Like graphite
• Defects in hexagonal tiling
• High surface area
• Width 0.7 3nm
• High aspect ratio

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Manufacture of CNTs
Arc discharge, laser, chemical vapour deposition
Catalyst
Carbon source
Purification
High pressure or temperature
Functionalisation
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Interactions with CNTs

• Filling of inside of tube
• Proteins bind strongly
• Able to cross cell membranes
• Bond with halogens, polymers, metals
• SWCNTs joint together to form MWCNTs

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MWCNTs and macrophages

• Hirano S Multiwalled carbon nanotubes injure the
  plasma membrane of macrophages. Toxicology and
  Applied Pharmacology 2008 232 244-51
• Porter AE. Direct imaging of single walled carbon
  nanotubes in cells. Nature nanotechnology 2007
  713-7

MWCNTs or Crocidolite
macrophage
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MWCNTs and mesothelioma

• Tagaki

Monitored until 100 mortality in one group
MWCNT Fullerene Crocidolite control solution
Intra-peritoneal injection into asbestos
sensitive mice
Tagaki A, Induction of mesothelioma in p53/-
mouse by intraperitoneal application of
multi-wall carbon nanotube. J Toxicol Sci 2008
33 105-15
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MWCNT and mesothelioma
Autopsy findings
Tagaki A, Induction of mesothelioma in p53/-
mouse by intraperitoneal application of
multi-wall carbon nanotube. J Toxicol Sci 2008
33 105-15
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The Big Question

• Could CNTs reach the mesothelium
• in a normal working environment?

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Final thought on carbon nanotubes

• For the moment, it would be no
• bad thing if they were treated by
• those making and using them if
• they were asbestos.
• Antony Seaton

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The future

• Fast, dynamic
• Inadvertent exposure from imported goods
• Overwhelming number of articles
• Difficult to sift out what matters
• Difficult to keep up
• Regulation needed - but time lag
• Nano materials are not uniform
• Review risk assessment regularly with updated
  information

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Actions

• Nanotechnology safety group
• Work out what nanomaterials you have
• Share information
• Make sure that the company knows that the group
  exist
• Risk assess procedure
• Control on basis of the risk assessment
• Consider the environmental impact
• End of life actions
• Make assumptions on the basis of what is already
  known

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Risk assessment

• Due to the developmental nature of much of
  nanotechnology. your information may be
  incomplete.your risk assessment..should be
  suitably cautious providing higher levels of
  protection as the significance and level of
  uncertainty about the risk increases.
• HSE Information Sheet - Nanotechnology

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Risk assess

• Chemistry
• Physics
• Surface attributes
• Exposures at different phases of life cycle

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Exposure potential

• Amount of material
• Dry powder
• Degree of containment
• Duration of use

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COSHH hierarchy of control

• Elimination
• Substitution
• Enclosure
• Engineering Control
• Procedural Control
• PPE

• Binding powder in liquid or solid media
• Local exhaust ventilation
• Limit people exposed,
• train staff,
• clean work wear,
• clean workplace

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Procedure

• Resources
• USA Department of Energy Nanoscale Science
  Research Centers
• Approach to Nanomaterial ESH
• British Standard PD6699-22007
• Nanotechnologies Part 2
• Guide to safe handling and disposal of
  manufactured nanomaterials

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Health Monitoring - the options

• No action
• Document the presence of free unbound
  nanoparticles
• Identify and record individual workers
• Handles particles with potential to become
  dispersed in air
• Routinely exposed
• Works on equipment that might be contaminated
  with nano materials that could be released during
  servicing or breakdown
• General medical check up
• Targeted medical testing cardio respiratory

Schulte P et al. Options for occupational health
surveillance of workers potentially exposed to
engineered nanoparticles state of the science.
J Occup Environ Med 2008 50 517-26
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Health promotion

• What do we do about smoking?

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The big five challenges

• Develop
• Instruments to assess exposure
• Methods to evaluate toxicity
• Models for predicting the potential health and
  environmental impact
• Robust systems for evaluating the health and
  environmental impact over entire life of product
• Strategic programmes to enable risk focussed
  research

Maynard AD, Nature 444 267-9
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Sources of information

• www.hse.gov.uk/
• www.cdc.gov/niosh/topics/nanotech/ default.html
• www.nanotechproject.org
• www.nano.org.uk
• www.oecd.org

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References - Articles

• Whatmore RW. Nanotechnology what is it? Should
  we be worried? Occupational Medicine 2006 56
  295-9
• Aitken RJ, et al Manufacture and use of
  nanomaterials current status in the UK and
  global trends. Occupational Medicine 2006 56
  300-6
• Garnett MC, Kallinteri P. Nanomedicines and
  nanotoxicology some physiological principles.
  Occupational Medicine 2006 56 307-11
• Seaton A. Nanotechnology and the occupational
  physician. Occupational Medicine 2006 56 312-6
• Schulte P et al. Occupational risk management of
  engineered nanoparticles. J Occup Environ Hyg
  2008 239-49

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General References

• Royal Commission on Environmental Pollution.
  Novel Materials in the environment the case of
  nanotechnology
• HSE information note Nanotechnology
• Nanotechnologies part 2 guide to safe handling
  and disposal of manufactured nanomaterials BSI
  PD6699-22007
• Workplace atmospheres ultrafine, nanoparticle
  and nanostructured aerosols inhalation exposure
  characterisation and assessment BSI PD 276282007
• Aitken RJ et al. Nanoparticles an occupational
  hygiene review. HSE research report 274. HSE
  Books 2004
• Journal of Nanobiotechnology
• Nature Nanotechnology
• ISO/TR 128852008

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