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Bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems. M.Sc. Lic. Eng. Klara Midander Inger Odnevall Wallinder, Jinshan Pan, Christofer Leygraf Div. Corrosion Science, Dept. Chemistry, KTH Hanna Karlsson, Pontus Cronholm Dept. Biosciences and Nutrition, KI

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slide1

Bioaccesibility of nano- and micron-sized metallic particles in simulated lung systems

  • M.Sc. Lic. Eng. Klara Midander
  • Inger Odnevall Wallinder, Jinshan Pan, Christofer Leygraf
  • Div. Corrosion Science, Dept. Chemistry, KTH
  • Hanna Karlsson, Pontus Cronholm
  • Dept. Biosciences and Nutrition, KI
  • MITF-seminar, Oct. 18, 2007
slide3

Inhalation of airborne particles

Combustion particle in lung alveolar

Iron particle from subway

Photo: Lennart Nilsson (dn.se, Chem. Res. Toxicol., Vol. 18, No. 1, 2005)

slide4

Men+

Men+

Men+

Men+

What causes toxicity?

-material properties / released metal?

-particle itself / surface reactivity?

-is it possible to extrapolate toxicity from particle size?

Health effects of particles

1952: ”The London Fog”  4000-12000 premature deaths

90ies: air pollution/particles  cardiovascular diseases, lung cancer

High particle concentration in airexacerbation of asthma

Particles cause inflammation?Particles can form radicals oxidize DNA (oxidative stress)

slide5

subway

street

Study of particle toxicity

Exposure of cultivated lung cells to particles

DNA damagecomet assay(single cell gel electrophoresis)

Subway particlesCombustion particles (wood and pellets)Particles from tiresCommersial nanoparticles

Composition of subway particles(SEM-EDS)

Karlsson et al., Chem. Res. Toxicol., Vol. 18, No. 1, 2005)

slide6

The metal release is influenced by particle size (surface area), shape, reactivity and material type (passive/non-passive, pure/alloy/oxide) as well as the exposure environment (within the lung).

Can bioaccessibility data (metal release) reflect the toxic effect of metallic particles?

Metal release

Cultivated lung cells

slide7

Metal release studies of metallic particles

in-vitro

Simulated lung conditions:

ALF (artificial lysosomal fluid)

pH 4.5 - 5 (agressive) simulate conditions

following an immunologic reaction in the body

Gamble’s solutionpH 7.4 (neutral) simulates a normal

health condition within the lung

  • Other simulated biological media:
  • PBS (phosphate buffered saline) pH 7.2 - 7.4Artificial SweatpH 6.5Artificial gastrid fluidpH 1.6
slide8

Exposure:37C, darkness, gentle agitation, 10 min - 1 week

Analysis:Atomic Absorption Spectroscopy – graphite furnace

Separation:centrifugation, 3000 rpm, 10 min

Experimental procedure

slide9

The type of material strongly influences metal release from particles.

Chemical and compositional material properties are crucial for the metal release mechanism (chemical dissolution and/or corrosion process).

The type of material influences metal release from particles

17Cr11Ni3Mo stainless steel

Cu-materials

passive!

pure/oxide/product!

Gamble’s (168h)

Gamble’s (48h), note log-axis!

slide10

The metal release rate increases with decreasing pH of the test media.

At comparable pH, the release rate may vary due to differentcomposition of the test media.

The environment influences metal release from particles

slide11

Increasing particle size

50 µm

< 4 µm

Decreasing surface area

0.07 m2/g

0.7 m2/g

The particle size influences the metal release process. Metal releaseincreases with decreasing particle size mainly due to a larger surface area.

The particle size influences metal release from particles

Fe >> Cr, Ni

slide12

On-going cross-disciplinary

research collaboration

KTH  KI SU

Sub-micron and nanosized metallic particles

metals, alloys, metal compounds

Toxicology

Particle/aerosol generation

Surface

reactivity

General public

Industry (REACH)Downstream users

Legislators