Wednesday, June 21, 2006

Who’s afraid of nanoparticles?

Lots of people, it seems. They have the potential to become the new DDT or dioxins or hormone mimics, the invisible ingredients of our environment and our synthetic products that are suspected of wreaking biochemical havoc. I don’t say the notion is ridiculous, but we need to keep it in proportion. The Royal Society/RAE report on the hazards and ethics of nanotechnology did a good job of giving some perspective on the concerns: we shouldn’t take it for granted that nanoparticles are safe (even if their bulkier counterparts are), but neither are we totally ignorant about exposure to such particles, and it is unlikely that we can make many generalizations about their health risks. Certainly, we need legislation to stop these tiny grains from slipping through current health & safety regulations.

My recent article on the damaging effects that titania nanoparticles apparently have on mouse microglia, the defensive cells of the brain, will probably be welcomed as ammunition by those who want a moratorium on all nanoparticle research. It does not give grounds for that – this research is a long way from establishing actual neurotoxocity – but it does give pause for thought about nanoparticle sun creams. I rather suspect this stuff is not going to be a major hazard, but we can’t be sure of that, and I confess that I’ll prefer to avoid them this summer.

For various mundane reasons, some comments by the EPA researchers involved in this work didn’t make it into the article. But they help to put the implications in perspective, and so I’m posting them here:
Responses from Dr. Bellina Veronesi
Question: Apart from sun creams, which consumer products that involve contact with the human body currently use titania nanoparticles?
Answer: Cosmetics, prosthetics (artificial joints, for example)
Question: You mention toothpaste and cosmetics - do you know of specific examples of these?
Answer: Most product labels would probably not note if a given chemical concentration was in the “nano” range. Often times, the titanium oxide is listed in the ingredients, but is not identified as "nano-." More specific information might be considered to be confidential business information (CBI) and not available.
Question: I'm finding it hard to see from the paper exactly how long the production of ROS tended to continue for after the microglia were exposed.
Answer: Over a 120 minute period, which was the extent of our measurements.
Question: It seems that the worry is not about the response per se, but that it is sustained.
Answer: The concern from the neurobiology/neurotoxicology point of view is that a cell type (the microglia), whose job it is to react to offending foreign stimuli in the brain by releasing free radicals (ROS), is doing just that in response to nanosize Titanium dioxide. If those free radicals are not neutralized by anti-oxidants present in the brain (Vitamin C, Vitamin E, super oxide dismutase), they can damage neurons.
But remember, these measurements were made in isolated microglia, so we can't yet say if it is neurotoxic. Rather, the next step would be to examine the consequences of ROS release in a more complex culture system consisting of mixtures of brain cells, including microglia and neurons. Based on those findings, we would then test in animals.
Question: What do we know about how such nanoparticles might get transported around the body? Can you say anything about the chances of them reaching the brain?
Answer: Experts such as Dr. Wolfgang Kreyling (GSF Institute for Inhalation Biology (Munich)) have shown that nanosize particles, such as TiO2, can leave the lungs of exposed animals and distribute to other organs. However, it is still undetermined whether TiO2 can cross the blood brain barrier and enter the brain.
Question: Can you say anything about whether the concentrations you studied might be realistic in terms of exposure levels?
Answer: It is not “good science” to extrapolate in vitro data to whole animal/human response. There are many obligatory steps/test models that must be tested first. Similarly, our study was not designed to assess whether the test concentrations used in the cell culture studies have relevance to those found in consumer products.
Question: How worrying are the results at this point, given that they are not in vivo studies?
Answer: This was a carefully designed study that followed a format prescribed in the nanoparticle scientific literature ((Nel et al., Science 2006) That format entails moving from cell culture to animal testing in a tiered fashion. We are examining further the possibility that TiO2 may be neurotoxic in culture. If these results prove positive, we will adhere to the format and next test in more complex culture models that use neurons or dissociated whole brain to determine. Results of these studies will determine if animal studies should be pursued.
Question: What are the major uncertainties about how the findings might translate to humans, and what are the next steps?
Answer: This study exposed TiO2 to isolated, brain cells taken from a mouse. Within the confines of this model, it would be speculative to say what the effects would occur in human cells, let alone a human being. Such a prediction requires an extremely lengthy course of testing, involving successively more complicated experimental models. As I noted in my previous answer, we will follow a format that allows for such sequential research.
Question: How do you feel about the fact that titania nanoparticles are currently in use in consumer products? Would you want to use such products yourself?
Answer: Nano-size TiO2 has been in commercial use/multiple routes of human exposure for several years, providing great benefits without incident. Numerous already published studies give TiO2 (nanosize, larger size) a clean bill of health.
The uniqueness of this study is that we are looking at the response of cells with very high resolution, state-of-the-art measurements. Again, this is the initial stage of a very lengthy experimental process the findings of which will provide better insight and guidance related to the use of such products.


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