Tag Archives: Frank A. Witzmann

You probably can’t poison yourself by eating too many nanoparticles

Researchers, Ingrid Bergin in the Unit for Laboratory Animal Medicine, at the University of Michigan in Ann Arbor and Frank Witzmann in the Department of Cellular and Integrative Physiology, at Indiana University School of Medicine, in Indianapolis, have stated that ingesting food and beverage (translated by me from the more scientific description) with nanoparticles (at today’s current levels) is unlikely to prove toxic. A June 26, 2013 Inderscience news release on EurekAlert describes the researchers’ research and their conclusions,

Writing in a forthcoming issue of the International Journal of Biomedical Nanoscience and Nanotechnology, researchers have compared existing laboratory and experimental animal studies pertaining to the toxicity of nanoparticles most likely to be intentionally or accidentally ingested. Based on their review, the researchers determined ingestion of nanoparticles at likely exposure levels is unlikely to cause health problems, at least with respect to acute toxicity. Furthermore, in vitro laboratory testing, which often shows toxicity at a cellular level, does not correspond well with in vivo testing, which tends to show less adverse effects.

Ingrid Bergin in the Unit for Laboratory Animal Medicine, at the University of Michigan in Ann Arbor and Frank Witzmann in the Department of Cellular and Integrative Physiology, at Indiana University School of Medicine, in Indianapolis, explain that the use of particles that are in the nano size range (from 1 billionth to 100 billionths of a meter in diameter, 1-100 nm, other thereabouts) are finding applications in consumer products and medicine. These include particles such as nano-silver, which is increasingly used in consumer products and dietary supplements for its purported antimicrobial properties. Nanoparticles can have some intriguing and useful properties because they do not necessarily behave in the same chemical and physical ways as non-nanoparticle versions of the same material.

Nanoparticles are now used as natural flavor enhancers in the form of liposomes and related materials, food pigments and in some so-called “health supplements”. They are also used in antibacterial toothbrushes coated with silver nanoparticles, for instance in food and drink containers and in hygienic infant feeding equipment. They are also used to carry pharmaceuticals to specific disease sites in the body to reduce side effects. Nanoparticles actually encompass a very wide range of materials from pure metals and alloys, to metal oxide nanoparticles, and carbon-based and plastic nanoparticles. Because of their increasing utilization in consumer products, there has been concern over whether these small scale materials could have unique toxicity effects when compared to more traditional versions of the same materials.

Difficulties in assessing the health risks of nanoparticles include the fact that particles of differing materials and shapes can have different properties. Furthermore, the route of exposure (e.g. ingestion vs. inhalation) affects the likelihood of toxicity. The U.S. researchers evaluated the current literature specifically with respect to toxicity of ingested nanoparticles. They point out that, in addition to intentional ingestion as with dietary supplements, unintentional ingestion can occur due to nanoparticle presence in water or as a breakdown product from coated consumer goods. Inhaled nanoparticles also represent an ingestion hazard since they are coughed up, swallowed, and eliminated through the intestinal tract.

Based on their review, the team concludes that, “Ingested nanoparticles appear unlikely to have acute or severe toxic effects at typical levels of exposure.” Nevertheless, they add that the current literature is inadequate to assess whether nanoparticles can accumulate in tissues and have long-term effects or whether they might cause subtle alterations in gut microbial populations. The researchers stress that better methods are needed for correlating particle concentrations used for cell-based assessment of toxicity with the actual likely exposure levels to body cells. Such methods may lead to better predictive value for laboratory in vitro testing, which currently over-predicts toxicity of ingested nanoparticles as compared to in vivo testing.

The researchers focused specifically on ingestion via the gastrointestinal tract which I take to mean that they focused largely on nanoparticles in food (eaten) and liquid (swallowed).

Here’s a link to and citation for the paper,

Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps by Ingrid L. Bergin; Frank A. Witzmann.  Int. J. of Biomedical Nanoscience and Nanotechnology, 2013 Vol.3, No.1/2, pp.163 – 210.  DOI: 10.1504/IJBNN.2013.054515

I think the abstract further helps to understand the research focus,

The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures.

The article is behind a paywall.

I last mentioned Frank Witzmann here in a May 8, 2013 posting titled, US multicenter (Nano GO Consortium) study of engineered nanomaterial toxicology.

US multicenter (Nano GO Consortium) study of engineered nanomaterial toxicology

Nano Go Consortium is the name they gave a multicenter toxicology study of engineered nanomaterials which has pioneered a new approach  in the US to toxicology research. From the May 6, 2013 news item on Azonano,

For the first time, researchers from institutions around the country have conducted an identical series of toxicology tests evaluating lung-related health impacts associated with widely used engineered nanomaterials (ENMs).

The study [on rodents] provides comparable health risk data from multiple labs, which should help regulators develop policies to protect workers and consumers who come into contact with ENMs.

The May 6, 2013 North Carolina State University news release, which originated the news item, describes the results from one of two studies that were recently published by the Nano GO Consortium in Environmental Health Perspectives,

The researchers found that carbon nanotubes, which are used in everything from bicycle frames to high performance electronics, produced inflammation and inflammatory lesions in the lower portions of the lung. However, the researchers found that the nanotubes could be made less hazardous if treated to remove excess metal catalysts used in the manufacturing process or modified by adding carboxyl groups to the outer shell of the tubes to make them more easily dispersed in biological fluids.

The researchers also found that titanium dioxide nanoparticles also caused inflammation in the lower regions of the lung. Belt-shaped titanium nanoparticles caused more cellular damage in the lungs, and more pronounced lesions, than spherical nanoparticles.

Here’s a link to and a citation for this study on rodents,

Interlaboratory Evaluation of Rodent Pulmonary Responses to Engineered Nanomaterials: The NIEHS NanoGo Consortium by James C. Bonner, Rona M. Silva, Alexia J. Taylor, Jared M. Brown, Susana C. Hilderbrand, Vincent Castranova, Dale Porter, Alison Elder, Günter Oberdörster, Jack R. Harkema, Lori A. Bramble, Terrance J. Kavanagh, Dianne Botta, Andre Nel, and Kent E. Pinkerton. Environ Health Perspect (): .doi:10.1289/ehp.1205693  Published: May 06, 2013

And the information for the other study which this consortium has published,

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS NanoGo Consortium by Tian Xia, Raymond F. Hamilton Jr, James C. Bonner, Edward D. Crandall, Alison Elder, Farnoosh Fazlollahi, Teri A. Girtsman, Kwang Kim, Somenath Mitra, Susana A. Ntim, Galya Orr, Mani Tagmount8, Alexia J. Taylor, Donatello Telesca, Ana Tolic, Christopher D. Vulpe, Andrea J. Walker, Xiang Wang, Frank A. Witzmann, Nianqiang Wu, Yumei Xie, Jeffery I. Zink, Andre Nel, and Andrij Holian. Environ Health Perspect (): .doi:10.1289/ehp.1306561 Published: May 06, 2013

Environmental Health Perspectives is an open access journal and the two studies are being offered as ‘early’ publication efforts and will be updated with the full studies at a later date.

Most interesting for me is the editorial offered by four of the researchers involved in the Nano GO Consortium, from the editorial,

Determining the health effects of ENMs presents some unique challenges. The thousands of ENMs in use today are made from an enormous range of substances, vary considerably in size, and take a diversity of shapes, including spheres, cubes, cones, tubes, and other forms. They are also produced in different laboratories across the world using a variety of methods. In the scientific literature, findings on the properties and toxicity of these materials are mixed and often difficult to compare across studies. To improve the reliability and reproducibility of data in this area, there is a need for uniform research protocols and methods, handling guidelines, procurement systems, and models.

Although there is still much to learn about the toxicity of ENMs, we are fortunate to start with a clean slate: There are as yet no documented incidences of human disease due to ENM exposure (Xia et al. 2009). Because ENMs are manmade rather than natural substances, we have an opportunity to design, manufacture, and use these materials in ways that allow us to reap the maximum benefits—and minimal risk—to humans.

With $13 million from the American Recovery and Reinvestment Act (2009), the National Institute of Environmental Health Sciences (NIEHS) awarded 13 2-year grants to advance research on the health impacts of ENMs (NIEHS 2013). [emphasis mine] Ten grants were awarded through the National Institutes of Health (NIH) Grand Opportunities program and three were funded through the NIH Challenge Grants program. One goal of this investment was to develop reliable, reproducible methods to assess exposure and biological response to nanomaterials.

Within the framework of the consortium, grantees designed and conducted a series of “round-robin” experiments in which similar or identical methods were used to perform in vitro and in vivo tests on the toxicity of selected nanomaterials concurrently at 13 different laboratories.

Conducting experiments in a round-robin format within a consortium structure is an unfamiliar approach for most researchers. Although some researchers acknowledged that working collaboratively with such a large and diverse group at times stretched the limits of their comfort zones, the consortium ultimately proved to be “greater than the sum of its parts,” resulting in reliable, standardized protocols that would have been difficult for researchers to achieve by working independently. Indeed, many participants reflected that participating in the consortium not only benefitted their shared goals but also enhanced their individual research efforts. The round-robin approach and the overall consortium structure may be valuable models for other emerging areas of science.

Here’s a link to and a citation for the Consortium’s editorial, which is available in full,

Nano GO Consortium—A Team Science Approach to Assess Engineered Nanomaterials: Reliable Assays and Methods by Thaddeus T. Schug, Srikanth S. Nadadur, and Anne F. Johnson. Environ Health Perspect 121(2013). http://dx.doi.org/10.1289/ehp.1306866 [online 06 May 2013]

I like the idea of researchers working together across institutional and geographical boundaries as that can be a very powerful approach. I hope that won’t devolve into a form of institutionalized oppression where individual researchers are forced out or ignored. In general, it’s the outlier research that often proves to be truly groundbreaking, which often generates extraordinary and informal (and sometimes formal) resistance. For an example of groundbreaking work that was rejected by other researchers who banded together informally, there’s Dan Shechtman, 2011 Nobel Laureate in Chemistry, famously faced hostility from his colleagues for years over his discovery of quasicrystals.