Nanoparticle toxicity doesn't get wacky at the smallest sizes

Feb 16, 2009

(PhysOrg.com) -- The smallest nano-sized silica particles used in biomedicine and engineering likely won't cause unexpected biological responses due to their size, according to work presented today. The result should allay fears that cells and tissues will react unpredictably when exposed to the finest silica nanomaterials in industrial or commercial applications.

Nanotoxicologist Brian Thrall and colleagues found that, mostly, size doesn't matter, by using total surface area as a measure of dose, rather than particle mass or number of particles, and observing how cultured cells responded biologically.

"If you consider surface area as the dose metric, then you get similar types of responses independent of the size of the particle," said Thrall, a scientist at the Department of Energy's Pacific Northwest National Laboratory in Richland, Wash. "That suggests the chemistry that drives the biological responses doesn't change when you get down to the smallest nanoparticle."

Nanoparticles are materials made up of spherical particles that are on average 100 to 1,000 times smaller than the width of a human hair. They are being used in tires, biomedical research, and cosmetics. Researchers are exploring these tiny spheres because their physical and chemical properties at that size offer advantages that standard materials don't, such as being able to float through blood vessels to deliver drugs.

But whether these materials are safe for human consumption is not yet clear. Previous work suggested, in some cases, nanoparticles become more toxic to cells the smaller the particles get.

Thrall presented this toxicology data on amorphous silica nanoparticles today at the 2009 American Association for the Advancement of Science's annual meeting. He also presented data on which cellular proteins the nanoparticles use to get inside cells.

One difficulty in measuring toxicity is that not everyone agrees which kind of dose unit to compare. Some researchers measure the dose by total weight, some by the number of particles. Neither method distinguishes whether a nanomaterial's toxicity is due to the inherent nature of the material or the particle size under scrutiny.

"Different dose metrics give different impressions of which particles are more toxic," he said.

To find out, Thrall and his colleagues at PNNL measured the dose at which the particles caused a biological response. The biological response was either death of the cell, or a change in which genes the cell turned on and off. They found that when calculating doses by particle number or mass, the amount needed to generate a biological response was all over the map.

They found that the best way to pinpoint how toxic the particles are to cells was to calculate the dose based on the total surface area of the nanomaterial. Only when they considered the surface area of the dose could they predict the biological response.

And the biological response, they found, was very similar regardless of the size of the nanoparticles. Inside cells, some genes responded to nanoparticles by ramping up or down. More than 76 percent of these genes behaved the same for all nanoparticle sizes tested. This indicated to the researchers that, for these genes, the nanoparticles didn't pick up weird chemical properties as they shrunk in size.

"The big fear is that you'd see unique biological pathways being affected when you get down to the nanoscale. For the most part, we didn't see that," said Thrall.

However, the team found some genes for which size did matter. A handful of genes, these fell into two categories: smaller particles appeared to affect genes that might be involved in inflammation. The larger particles appeared to affect genes that transport positively charged atoms into cells. This latter result could be due to metals contaminating the preparation of the larger particles, Thrall suggested.

Overall, the results contribute to a better understanding of what goes on at the nanoscale.

Provided by Pacific Northwest National Laboratory

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User comments : 3

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holmstar
5 / 5 (2) Feb 16, 2009
Wow... not only a misleading title, but the results of the research are even skewed to suggest that there is no danger, but in fact the opposite was found:

The research shows that the reaction is based on surface area. For the same mass, smaller particles have a higher surface area, thus the create a bigger reaction for the same amount of mass than larger particles.

In other words, the small particles are more dangerous than an equivalent amount of large particles.
gopher65
not rated yet Feb 16, 2009
Right holmstar. But at least this research could help determine the optimal dose for nanoparticle delivered drugs, and the maximum safe limits for nanoparticle environmental containments.
superhuman
5 / 5 (1) Feb 22, 2009
They did find that nanopoarticles enter cells and affect gene expression which is very worrying and enouth to show they pose serious health risks. Last thing you want is random particles entering your cells and getting in the way of what those cells are trying to do.

Microparticles OTOH can't enter cells due to their size, so the problem IS due to size, besides the research shows the effect depends on surface area which means the smaller the particles for a given weight the higher the danger.

Nanoparticles pose very serious risk to human health and they should be avoided unless there is some very good reason to use them. Especially chronic exposure should be avoided. In time the regulatory agencies will wake up to the problem and ban them but it will most likely take quite some time, especially with industry lobbing against it.

I really support nanotechnology and believe materials assembled with molecular precision will soon (within the next 10 years) revolutionize technology and research but adding nanoparticles to consumer products like cosmetics is definitely NOT the way to go. Not only public health but also public attitude towards nanotechnology is at stake here. It is very important for future nanotechnology to have proper safety regulations in place before the greed of those trying to cash on "nano fashion" irreversibly damages public reception of nanotechnology.

Article abstract:
Concerns about the potential adverse health effects of engineered nanoparticles stems in part from the possibility that some materials display unique chemical and physical properties at nanoscales which could exacerbate their biological activity. However, studies that have assessed the effect of particle size across a comprehensive set of biological responses have not been reported. Using a macrophage cell model, we demonstrate that the ability of unopsonized amorphous silica particles to stimulate inflammatory protein secretion and induce macrophage cytotoxicity scales closely with the total administered particle surface area across a wide range of particle diameters (7%u2013500 nm). Whole genome microarray analysis of the early gene expression changes induced by 10- and 500-nm particles showed that the magnitude of change for the majority of genes affected correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were particle size-specific were also identified. However, the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Direct comparison of the cell processes represented in the 10- and 500-nm particle gene sets using gene set enrichment analysis revealed that among 1009 total biological processes, none were statistically enriched in one particle size group over the other. The key mechanisms involved in silica nanoparticle-mediated gene regulation and cytotoxicity have yet to be established. However, our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.

http://toxsci.oxf...t/kfn250

Some groups are petitioning FDA about nanoparticles but so far without result, here is some info on the subject:
http://newstandar...ems/3756