Etching out a nanotoxicology

Three days after the U.S. House of Representatives renewed a 2003 bill that promotes exploration into the adverse health effects of nanoparticles, scientists convened to debate what form that assessment should take. The symposium, "Driving Beyond Our Nano-Headlights?", took place on 14 February at the AAAS meeting in Chicago.

Although researchers have manipulated matter at the atomic scale for nearly 20 years, and many consumer products now include nanoparticles, no clear model yet exists for understanding their toxicity.

At the symposium, nanotoxicologist Brian Thrall of Pacific Northwest National Laboratory presented data indicating that the sizes of nanoparticles have no discernable effect on their interactions with cells and tissues. The result flies in the face of past studies suggesting that the smaller the particle, the more danger it holds.

Thrall explained that rather than mass or number of particles, his team used an agglomerate's total surface area as the parameter that defines dose. This distinction made all the difference, he said.

Thrall studied the effect of silica nanoparticles on cell cultures. The particles ranged from 10 nanometers to 500 nanometers in diameter. (One nanometer is one-millionth of a millimeter.) His team discovered that cells responded no differently to the smallest of these particles than they did to the largest.

Nanoparticles are manufactured compounds whose sizes place them at the most elemental end of biology: as small as 1 nm, on the scale of proteins. Their size has made them a promising material for medicine, because of their ability to travel deeper into lungs and through the bloodstream to other vital organs.

However, some researchers have been concerned that nanoparticles could travel through the nervous system and penetrate easily into individual cells. There, they might tune into biological processes in a new way and pose new health hazards for people and wildlife.

However, Thrall's team believes that the reported effects of small manufactured particles were due not to a poison inherent to their size, but to an overlooked relationship in the dosage system itself.

Tests by Thrall's team showed that the only reliable measurement of dose was the total surface area of the particles. Total surface area increases for doses of the same mass or volume when they contain smaller sized particles, much as a box of tennis balls has more total fuzz than the same box would when stuffed with larger balls of similar coating. Greater total surface area leads to greater chemical reactivity, explaining the increased toxicity of nano-sized particles more directly than their smallness.

Thrall presented data showing that the 10 nm and 500 nm particles, though vastly different in size, had the same effect on surrounding cell culture when applied in doses measured by total surface area.

Thrall stressed that the superior relationship between dose and surface area was not limited to the cell death of macrophages, which he studied, but to all gene expressions.

"It's a fundamental principle we must keep in mind," he said. "Still, in the literature, this principle is ignored to some extent."

Other speakers at the symposium noted the hazards of nanoparticles in different contexts. For instance, asbestos toxicity expert Agnes Kane of Brown University reviewed the connections between asbestos fibers and carbon nanotubes, rolled sheets of graphite whose ends are capped at both sides. Kane explained that both fibers obstruct the ability of white blood cells to engulf and deliver them out of the system. She illustrated her point with an image of a tube sticking out of a macrophage like a spear.

Nanoparticles interact with biological systems on a scale so uncharted that researchers are still grappling with how to perform the science, said Sally Tinkle, cochair of the nanoscale science subcommittee of the National Science and Technology Council.

"Against which properties are we to analyze?" asked Tinkle. She read a list of features including shape, mass, solubility, surface area, surface charge, and newer ones such as crystal structure and surface defects. Other speakers questioned whether classifying nanoparticles by material is even possible.

Dose definitions are at the heart of any toxicity study, Thrall said. His team's finding comes at a time when the bias for basing toxicity and dose metrics on particle size is being questioned for larger particles as well: http://www.newswise.com/articles/view/548875/

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Zoe Macintosh studies English literature and physics at Smith College, and is a staff writer for the Smith Sophian. She's the founder of a school club called the Forum for Contemporary Media / Political Inquiry and is pursuing a career in science writing. Reach her at zmacinto@gmail.com