PowerPointPrsentation

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Properties of ultrafine particles
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Properties of ultrafine particles
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Retention of Nanoparticles
particle density 1 g cm-3 respiratory flow rate
300 cm3 s-1 breathing at rest cycle period 5 s
ICRP 66 (1994) MPPDep (2000) based on
experimental data
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Health effects of ultrafine particles
Influx of neutrophils (PMN) indicator of
inflammation Instillation of ultrafine TiO2 (20
nm) or fine TiO2 (250 nm) into the rat lungs
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Particle-size dependent retention sites in lungs
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Ultrafine 13C Particle Inhalation by Rats Lung
and CNS Tissue Concentrations
Oberdörster et al., 2002

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Cardio-vascular effects of ultrafine particle
Particles in the lung
Effects on electrical activity of the heart
Effects on blood supply to the heart
plaque destabilization blood coagulation deformabi
lity haemostasis
direct action of particles autonomic
control conductance-signaling
Fatal arrhythmias
Ischemia
Death of host with pre-existing disease
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Ultrafine particles in the brain?
From Kandel, Schwartz and Jessel Principles of
Neural Science, 2000

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UFP and CNS / brain
1941 Bodian and Howe Olfactory axonal
transport of Polio-virus (30 nm) after intranasal
instillation in chimpanzee. Transport velocity
2.4 mm/h 1970 de Lorenzo Olfactory axonal
transport of 50 nm colloidal gold after
intranasal instillation in squirrel monkey
reached olfactory bulb 30-60 min after
inoculation. Transport velocity 2.5
mm/h 1983 Katz et al. Axonal transport of
micro-injected rhodamine labelled microspheres
(20 200nm) in cortical neurons of rats and
cats. (optimal size 30nm?) 2002 Oberdörster
et al. Inhaled 13C-UFP (25 nm) translocated into
the olfactory bulb, cerebelum and cerebrum of rat
brains during the following week.

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Air pollution and brain damage
L. Calderón-Garciduenas et al. Tox. Path. (30)
2002 Healthy stray mongrel dogs daily exposed
to high levels of ambient air pollutants (PM10 ,
ozone, etc.) in Mexico City a control city

• Results
• Persistent pulmonary inflammation,
• deteriorating olfactory and respiratory barriers,
  
• brain neuropathology damage of
  blood-brain-barrier, degeneration of neurons
  glial cells, plaques.

Comparison Findings observed in exposed dogs
were similar to disorders observed in Alzheimer
and Parkinson patients

• Neurodegenerative disorders such as Alzheimers
  may begin early in life with air pollutants
  playing a crucial role?

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Cellular uptake

• Because of small size, all mechaniams of
  endocytosis are theoretically possible
• Options of transport phagocytosis, endocytosis
  via caveolae or clathrin-coated pits,
  pinocytosis, or unspecific, non-endocytic
  mechanism

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Cellular uptake

• Known so far
• Nanoparticles from physiological material such as
  human serum albumin phagocytic uptake
• Non-phygocytic route taken by poly(N-isopropylacry
  lamide-co- methacrylic acid) nanoparticles
• However, different surface characteristics
  promote phagocytosis
• First evidence that lung inhaled particles may be
  taken up by alveolar epithelial cells via
  caveolae
• Uptake has been shown to depend on the
  temperature, coating, cell type, and time of
  incubation!

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Interactions of ultrafine particles and proteins
mediated by UFP surface properties
Hypothesis Since UFP are similar sized as
large proteins, they may form complexes with
proteins which determine their biokinetic fate

• Coupled UFP-protein-complex
• protein function unchanged
• reactive UFP surface area
• less likely protein-mediated translocation across
  membranes

• Masked UFP-protein-complex
• protein function unchanged
• covered UFP surface
• possible protein-mediated translocation across
  membranes

• Nicked UFP-protein-complex
• degraded or denatured protein ? protein
  mal-function
• reactive UFP surface area
• less likely protein-mediated translocation across
  membranes

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Safety Aspects

• Public Health
• Overall air pollution (e.g. cigarettes, diesel
  soot,industrial contamination)
• How far does nanotech 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
• Challenges and requirements for research
• Support and requirements for industry?

• Material Safety Standards
• Create new or use existing ones?

Production New technologies, new particle
formulation (Production in clean rooms? Filters?
Health aspects of employees?)

• Environment
• Influence on biota internalization of
  particles
• Influence on the biosphere
• Recycling, waste/material combustion

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Safety at LTP