Tag Archives: Vincent Castranova

More from PETA (People for the Ethical Treatment of Animals) about nanomaterials and lungs

Science progress by increments. First, there was this April 27, 2016 post featuring some recent work by the organization, People for the Ethical Treatment of Animals (PETA) focused on nanomaterials and lungs. Now approximately one month later, PETA announces a new paper on the topic according to a May 26, 2016 news item on phys.org,

A scientist from the PETA International Science Consortium Ltd. is the lead author of a review on pulmonary fibrosis that results from inhaling nanomaterials, which has been published in Archives of Toxicology. The coauthors are scientists from Health Canada, West Virginia University, and the University of Fribourg in Switzerland.

A May 26, 2016 PETA news release on EurekAlert, which originated the news item, provides more detail (Note: Links have been removed),

The increasing use of nanomaterials in consumer goods such as paint, building materials, and food products has increased the likelihood of human exposure. Inhalation is one of the most prominent routes by which exposure can occur, and because inhalation of nanomaterials may be linked to lung problems such as pulmonary fibrosis, testing is conducted to assess the safety of these materials.

The review is one part of the proceedings of a 2015 workshop [mentioned in my Sept. 3, 2015 posting] organized by the PETA International Science Consortium, at which scientists discussed recommendations for designing an in vitro approach to assessing the toxicity of nanomaterials in the human lung. The workshop also produced another report that was recently published in Archives of Toxicology (Clippinger et al. 2016) and a review published in Particle and Fibre Toxicology (Polk et al. 2016) [mentioned in my April 27, 2016 posting] on exposing nanomaterials to cells grown in vitro.

The expert recommendations proposed at the workshop are currently being used to develop an in vitro system to predict the development of lung fibrosis in humans, which is being funded by the Science Consortium.

“International experts who took part in last year’s workshop have advanced the understanding and application of non-animal methods of studying nanomaterial effects in the lung,” says Dr. Monita Sharma, nanotoxicology specialist at the Consortium and lead author of the review in Archives of Toxicology. “Good science is leading the way toward more humane testing of nanomaterials, which, in turn, will lead to better protection of human health.”

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

Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs) by Monita Sharma, Jake Nikota, Sabina Halappanavar, Vincent Castranova, Barbara Rothen-Rutishauser, Amy J. Clippinger. Archives of Toxicology pp 1-18 DOI: 10.1007/s00204-016-1742-7 First online: 23 May 2016

This paper is behind a paywall.

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.

Multi-walled carbon nanotubes, cancer, and the US National Institute of Occupational Health and Safety’s (NIOSH) latest findings

A Mar. 11, 2013 news item on Nanowerk reveals some of the latest research performed by US National Institute of Occupational Health Safety (NIOSH) researchers into the question of whether or not multi-walled carbon nanotubes (MWCNT) cause cancer,

Earlier today, at the annual meeting of the Society of Toxicology, NIOSH researchers reported preliminary findings from a new laboratory study in which mice were exposed by inhalation to multi-walled carbon nanotubes (MWCNT). The study was designed to investigate whether these tiny particles have potential to initiate or promote cancer. By “initiate,” we mean the ability of a substance to cause mutations in DNA that can lead to tumors. By “promote,” we mean the ability of a substance to cause cells that have already sustained such DNA mutations to then become tumors.

It is very important to have new data that describe the potential health hazards that these materials might represent, so that protective measures can be developed to ensure the safe advancement of nanotechnology in the many industries where it is being applied.

The Mar. 11, 2013 posting (which originated the news item) by Vincent Castranova, PhD; Charles L Geraci, PhD; Paul Schulte, PhD  on the NIOSH blog provides details about the experimental protocols and the outcome of the experiments,

In the NIOSH study, a group of laboratory mice were injected with a chemical that is a known cancer initiator, methylcholanthrene.  Another group of mice were injected with a saline solution as a control group.  The mice then were exposed by inhalation either to air or to a concentration of MWCNT.   These protocols enabled the researchers to investigate whether MWNCT alone would initiate cancer in mice, or whether MWCNT would promote cancer where the initiator, methylcholanthrene, had already been applied.

Mice receiving both the initiator chemical plus exposure to MWCNT were significantly more likely to develop tumors (90% incidence) and have more tumors (an average of 3.3 tumors/mouse lung) than mice receiving the initiator chemical alone (50% of mice developing tumors with an average of 1.4 tumors/lung).  Additionally, mice exposed to MWCNT and to MWCNT plus the initiator chemical had larger tumors than the respective control groups.  The number of tumors per animal exposed to MWCNT alone was not significantly elevated compared with the number per animal in the controls.  These results indicate that MWCNT can increase the risk of cancer in mice exposed to a known carcinogen.  The study does not suggest that MWCNTs alone cause cancer in mice.

That last sentence is quite important because (from the NIOSH blog post),

Several earlier studies in the scientific literature indicated that MWCNT could have the potential to initiate or promote cancer. The new NIOSH study is the first to show that MWCNT is a cancer promoter in a laboratory experiment, and reports the growth of lung tumors in laboratory mice following inhalation exposure to MWCNT rather than injection, instillation, or aspiration.  Inhalation exposure most closely resembles the exposure route of greatest concern in the workplace. In the study, laboratory mice were exposed to one type of MWCNT through inhalation at a concentration of 5 milligrams per cubic meter of air for five hours per day for a period of 15 days.

Risk of occupational cancer depends on the potency of a given substance to cause or promote cancer and the concentration and duration of worker exposure to that substance.  This research is an important step in our understanding of the hazard associated with MWCNT, but before we can determine whether MWCNT pose an occupational cancer risk, we need more information about actual exposure levels and the types and nature of MWCNT being used in the workplace, and how that compares to the material  used in this study.

This study is part of a larger program designed to establish safety practices with regard to handling nanomaterials/nanoparticles (from the NIOSH blog post),

These laboratory studies are part of a strategic program of NIOSH research to better understand the occupational health and safety implications of nanoparticle exposure, and to make authoritative science-based recommendations for controlling exposures so that the technology is developed responsibly as the research advances, and the societal benefits of nanotechnology can be realized.  NIOSH has worked closely with diverse public and private sector partners over the past decade to incorporate occupational health and safety into practical strategies for safe development of this revolutionary technology. More information is available on the NIOSH nanotechnology topic page.

There is no mention in the blog post as to whether the MWCNTs in this latest work were long or short or a mixture of both. Unfortunately, the study has not yet been published in a journal, so it’s not yet available for reading purposes. I did mention carbon nanotubes and toxicity in a Jan. 16, 2013 posting about a recent study,

Researchers at the University College of London (UCL), France’s Centre national de la recherche scientifique (CNRS), and Italy’s University of Trieste have determined that carbon nanotube toxicity issues can be addressed be reducing their length and treating them chemically.

While I find this latest work from NIOSH interesting, it’s hard for me to understand why there’s no mention of length. Unless, the NIOSH work is focused on what happens when MWCNTs are inhaled along with known cancer initiators and they believe that length is not a factor.

ETA Mar. 15, 2013: I did find get some information about the length (long carbon nanotubes for the most part) as per this Mar. 14, 2013 posting or you can find the update in my Mar. 15, 2013 posting here.