Drugs Down the Drain

Many years ago a study out of England reported the discovery of mixed-sex fish (primarily male fish with eggs). Although nothing new now, this was one of the first reports of feminized fish. What I remember most about that study, was how we laughed (I was working with some fish physiologists) at some of their possible explanations, which included hormones from the pill or just every-day urine that had been flushed down the toilet.

Years later, the USGS routinely measures drugs, or the remnants of drugs flushed after passing through our bodies, or intentionally flushed by folks wanting to discard old or unused drugs. Scientists are increasingly concerned about the impacts of pharmaceuticals not only on aquatic creatures (imagine swimming in a sea of heart medication, pain killers and birth control pills) but in some cases on drinking water.

Now the American Pharmaceuticals Association (APhA) has teamed up with the U.S. Fish and Wildlife service to educate the public about proper drug disposal through a campaign called SMARxT DISPOSAL.

I don’t have the numbers on how much is estimated to come from intentional disposal and how much is excreted, (although either way – giving drugs a proper burial as described in the disposal guidelines has got to be better than ditching them down the tube – and some, they actually suggest you do flush), but it will be interesting to monitor the impact of this program.

New Journal, Nanotoxicology

For those interested in nanotoxicology, there is a new journal called Nanotoxicology, published by Informa Healthcare. It’s a quarterly and you can review the first issue (just published March 2007) for free, which allows you to access to the first issue. The first article, Toxicology of nanoparticles: A Historical Perspective, by Gunter Oberdorster, Vicki Stone and Ken Donaldson, provides an excellent review. They include some early studies of particles such as viruses and combustion particles that were around well before the age of intentionally manufactured nanomaterials but which fit the nano description, and provided scientists with insights into the movement and fate of very small particles in living systems.

I’d expect an explosive growth in our understanding of how nanoparticles interact with the environment and with living bodies, but it seems there is a long ways to got and an urgency to get there quickly. Notes Oberdorster and others, “There have been many conferences, meetings, and workshops….with as many calls for developing testing strategies, with only few proposals, followed through by far less action.”

This first sample issue is worth a read and the few moments it takes to register for your month-long free access. Other articles include: “Assessing exposure to airborne nanomaterials: Current abilities and future requirements” by Andrew D. Maynard; Robert J. Aitken; Characterization of the size, shape, and state of dispersion of nanoparticles for toxicological studies by Kevin W. Powers; Maria Palazuelos; Brij M. Moudgil; Stephen M. Roberts; and Cellular responses to nanoparticles: Target structures and mechanisms by Klaus Unfried; Catrin Albrecht; Lars-Oliver Klotz; Anna Von Mikecz; Susanne Grether-Beck; Roel P. F. Schins.

Stumbling Through Nanoparticle Definitions

I am still trying to understand the nano-world. It’s a big world and there are many different kinds of very small particles. But I’ve had some trouble finding good definitions of the inhabitants of this new world. What, for example, are quatum dots? And what makes metallic
nanoparticles different from other kinds of nanoparticles?

As discussed earlier down in Whoville, we know that not all nanoparticles (particles smaller than 100 nanometers) are created equally, and, even better -- or worse, depending on your viewpoint and the material -- many nanoparticles aren’t even equal to their larger counter parts. And that really, is just the point, or one of the points at least, of all this technology.

Fortunately for me, the EPA, in their recent Nanotechnology White Paper, organizes nanoparticles into four categories, and though there may be other ways to categorize nanomaterials I found these groupings helpful in understanding the different kinds of nanoparticles that might one day enter our world – if they haven’t already.

Below are EPA's catagorizes for nanomaterials along with some brief examples.

Carbon Based:

Carbon-based nanomaterials include things like fullerenes (cage-like carbon structures) which make up the single walled carbon nanotubes (those are the SWNTs I’ve referred to before) and buckyballs. All are made carbon. Just carbon. When there are 60 carbons involved, a sphere is formed, its a Buckyball. When there are more, the structure is tube – or cage-like, and is made of a single layer of carbons, almost like a tube of chicken wire, it’s a SWNT.

Metal Based:

Metal-base nanomaterials include quantum dots, metal oxides and pure metal nanoparticles. Quantum dots are structures so small that their properties are susceptible to the removal of a single electron. Every living creature depends on a kind of quantum dot for energy production, as electrons are moved around by proteins so the cell can store or use energy.

Manufactured quantum dots can contain a small number of atoms, for example, from tens of atoms to a few hundred. Some manufactured quantum dots are nanosized crystals of various elements (silicon and germanium or cadmium and selenium are a couple of examples), and emit light when excited. What most interesting is that the color of the light, which is based on wavelength, will vary with the size of the crystal or the type of crystal, with smaller particles of a particular crystal emitting light of shorter wavelengths (towards the blue end of the visible light spectrum) and larger particles emitting light of longer wavelengths (towards the red end.)

Titanium dioxide, which you can find in your sunblock lotion, is an example of a metal oxide that is now manufactured as a nano-metal oxide. As explained in an earlier article, it's the nano formulation of this material that allows us to smear the sunblock but avoid looking like a clown.

Metals can also exist as single ions, or larger bulkier structures think gold, or silver. But, as with many nanomaterials, it seems that when metals occur as nanoparticles they may exhibit different properties than their larger counterparts. Nanoized silver (or silver ions), for example, is a potent antimicrobial, but apparently aggregates of silver particles tend to loose their antimicrobial ability.

Dendrimers:

Dendrimers are branched polymers (a polymer is made up of repeating units or monomers. Monomers are molecules that can combine – or polymerize - with similar or identical molecules.) These can be manufactured so that they can carry other molecules within them, such as certain drugs.

Composites:

Composites refer to combinations of nanomaterials with other materials, for example DNA molecules may be combined with various nanomaterials to make a nanosized biocomposite.

These examples just scratch the surface of the world of nanomaterials. But this revolutionary technology is sure to present those charged with protecting human health and the environment a future filled with both opportunity, (providing new materials to clean up and reduce distribution and use of hazardous materials, and new drug formulations) and challenges as health and environmental scientists race to understand the impact of materials that play by new rules.

Length Matters: Nanotoxicity

Obviously size matters for nanoparticles, or the world wouldn’t be making such a big deal of them. Size also matters when it comes to toxicity of nanoparticles. A recent study published in Advanced Materials (Length-Dependent Uptake of DNA-Wrapped Single-Walled Carbon Nanotubes) by Matthew Becker and others, emphasizes that size (such as length and diameter of particles) matters particularly when deciphering toxicity studies. One source of size variation suggests the authors is dispersion of single-walled carbon nanotubes (SWNT) used in toxicity testing.

According to the article:

“Given a constant dosage, differences in dispersion ranging from macroscopic aggregates to micrometer-scale clusters bundles of multiple nanotubes or individually dispersed nanotubes will dramatically affect the absolute size and amount of nanotube surface area to which the cells will be exposed.”

Surfactants are materials used to increase water solubility and in some cases dispersion of a material, and are commonly used in studies of nanoparticle toxcity. Becker’s group used DNA as a surfactant, because they noted,

“These dispersions, in the case of DNA, are even stable enough to allow for the separation of the dispersed material into well-defined subpopulations of the SWNTs.”

Using this method to test the toxicity of SWNTs of varying length to muscle cells, the authors concluded that, “The assays determined an approximate uptake threshold of approximately (189+17) nm. Indicating that nanotubes shorter than this are consumed and likely induce more toxicity.”

Though they note that identifying an upper threshold for toxicity of nanoparticles is nothing earth-shattering or new, they do suggest that such behavior is likely to be a “general phenomenon,” though the actual size threshold is likely to vary depending on the type of cell.

For more information check out: Length-Dependent Uptake of DNA-Wrapped Single-Walled Carbon Nanotubes, by Becker et al, Vol 19:939-945.