Dr. John Morris, SOT Vice President-Elect, introduced Dr. Günter Oberdörster, the 2015 winner of the SOT Merit Award, with a most amusing story. Apparently, one of Dr. Oberdörster’s early experiences with dust toxicity involved a road-trip in a convertible, with the loss of a windshield, necessitating the wearing of goggles for the duration of a trip somewhere between Turkey and Germany. We all have to start somewhere!
Dr. Oberdörster, University of Rochester, is a pioneer and highly esteemed researcher in the field of particle inhalation toxicology. He presented some recent observations that reflect our naiveté regarding nanoparticles. On one hand, nanoparticles are readily available for purchase as ingested health supplements, but Dr. Oberdörster has also been asked by a consumer whether a razor with blades containing polished nanoparticles on the surface was “safe.” He also commented on a recent publication that demonstrated that intranasal administration of TiO2 nanoparticles caused inflammation in the brain, at a dose that is inconceivable for human exposure.
An overriding theme of the Merit Lecture was that in particle research, several issues must be considered: particle dose, size, volume, surface area, solubility, and surface properties. Measurements of such endpoints as reactive oxygen species, or better, the interpretation thereof, depends on how the data are normalized (e.g., mass vs. surface area).
Dr. Oberdörster commented on several current issues in particle toxicology. First, are carbon nanotubes (CNTs) the next asbestos—i.e., risk for inducing mesothelioma? He showed data on the differences in toxicity of multi-walled carbon nanotubes (MWCNTs) vs. single-walled carbon nanotubes (SWCNTs) vs. nitrogen “doped” MWCNT. This issue is timely, as the International Agency for Research on Cancer (IARC) recently classified MWCNT-7 as “possibly carcinogenic (Group 2B), whereas evidence for carcinogenicity was “inadequate” for other MWCNT and for SWCNT (Group 3). This issue is addressed in detail in a 2014 IARC Monograph.
Dr. Oberdörster also commented on poorly soluble particles (PSPs) and particle overload effects. He summarized data related to macrophage clearance of PSP in the context of particle size. He then summarized the recent work of Baisch et al., 2014, which examined the effect of dose rate of TiO2 nanoparticles on lung inflammation. A caution arising from this work is that high dose studies can help rank materials with respect to their relative toxicity, but are unsuitable for quantitative risk assessment.
Dr. Oberdörster also presented data on respiratory tract exposure to nanoparticles and their subsequent distribution to most organs in the body. Inhalation of some nanomaterials can clearly result in translocation to the brain via the olfactory and trigeminal nerves. Perhaps the most fascinating data presented in this part of the talk, which was an issue I had not previously considered, is the in vivo processing of nanoparticles. To summarize some beautiful chemical analysis and electron microscopy data related to SiO2 nanoparticles, the particles do not just sit wherever they are deposited, but undergo reduction in size, major changes in shape, and even dissolution and disappear.
At the conclusion of Dr. Oberdörster’s prepared comments, Dr. Morris asked if he had any advice for young inhalation toxicologists. His response was simple: know the literature (much of what was previously known is still the topic of present investigations and publications, in his view), and relate your work to risk assessment.
When the floor was opened for questions, the audience raised some interesting issues:
With regards to e-Cigarettes, and the particles that they generate, what should be the approach to their characterization? Dr. Oberdörster responded that size distribution and chemistry should be evaluated. A follow-up question related to whether nanoparticles could be liquids, and Dr. Oberdörster commented that soluble particles would likely instantly dissolve when put into a moist environment.
Another question was about particle build-up and the problem of the lack of data about clearance kinetics. Dr. Oberdörster commented that particles smaller than 1 nm were excreted in the urine, but those larger undergo hepatobiliary excretion into the gastrointestinal track. He also indicated that research regarding clearance of particles from the brain is a work in progress at the University of Rochester. He also stated that about 11% of inhaled nanoparticles are deposited in the brain.
A clinician raised the issue of nanoparticles as ingredients in dermatological products and whether she should recommend sunscreens containing nano-sized zinc or titanium to pregnant women or children. Dr. Oberdörster responded that sunscreen use should not be discouraged, as that there is no compelling evidence that nanoparticles penetrate intact skin in an amount of concern. He also pointed out that if a small amount of zinc was to penetrate across the skin into the blood, that zinc is an essential metal and the body has mechanisms to handle it properly.
A final question was about testing of nanomaterials using alternative models systems (i.e. not in whole animals). Dr. Oberdörster stated that the critical issue is to take into account the dose that cells would see in vivo—i.e., pay attention to in vitro dosimetry. He also pointed out that currently it is very difficult to extrapolate from acute in vitro exposures and effects to possible chronic in vivo effects.
One of my take home messages from the lecture was that inhalation studies should be designed to be useful for risk assessment, not merely to find high-dose toxic effects. The other take home message was that Dr. Oberdörster is truly a giant role model, outstanding researcher, and resource for particle researcher, regardless of the size of the particle.
This blog discusses highlights from the SOT Annual Meeting and ToxExpo Merit Award Lecture: Chronicles of Particles: From Micro- to Nano-Particles