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

M.Sc. Lic. Eng. Klara MidanderInger 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

Particles in the society

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)

Men+

Men+

Men+

Men+

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

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

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

High particle concentration in air

exacerbation of asthma

Health effects of particles

What causes toxicity?

-material properties / released metal?

-particle itself / surface reactivity?

-is it possible to extrapolate toxicity from particle size?

Study of particle toxicity

Exposure of cultivated Exposure of cultivated lung cells to particleslung cells to particles

DNA damageDNA damagecomet assaycomet assay(single cell gel electrophoresis)(single cell gel electrophoresis)

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

street

subwayComposition of subway particles

(SEM-EDS)

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

Can bioaccessibility data (metal release) reflect the toxic effect

of metallic particles?

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).

Cultivated lung cells Metal release

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 solution pH 7.4 (neutral) simulates a normal

health condition within the lungOther simulated biological media:

PBS (phosphate buffered saline) pH 7.2 - 7.4

Artificial Sweat pH 6.5 Artificial gastrid fluid pH 1.6

Experimental procedure

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

Separation:centrifugation,

3000 rpm, 10 min

Analysis:Atomic Absorption

Spectroscopy – graphite furnace

The type of material influences metal release from particles

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).

Gamble’s (168h) Gamble’s (48h), note log-axis!

17Cr11Ni3Mo stainless steel Cu-materials

passive!

pure/oxide/product!

The environment influences metal release from particles

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 particle size influences metal release from particles

Fe >> Cr, Ni

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

Increasing particle size

< 4 µm 50 µm

Decreasing surface area

0.7 m2/g 0.07 m2/g

Sub-micron and nanosized Sub-micron and nanosized metallic particlesmetallic particles

metals, alloys, metal compoundsmetals, alloys, metal compounds

Particle/aerosol

generationSurface

reactivity

Toxicology

On-going cross-disciplinary research collaboration

KTH KI SU

Industry (REACH)Industry (REACH)Downstream usersDownstream users

General General publicpublic

LegislatorsLegislators