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Safety concerns over tungsten

Mouse study provides insights into how the metal accumulates in bone tissue

Published: 17 April 2018
New research shows how and where tungsten accumulates in bones of mice exposed to the element through drinking water. The findings, by a team of chemists and biologists at 91社区, could add to doubts over the once-universal assumption that tungsten poses little or no health risk to the general human population.

With the highest melting point of any metal, tungsten鈥檚 remarkably high density and hardness make it a prized ingredient in a range of industrial, military and medical applications. Used in cutting tools, ammunition, medical devices and even some medications, tungsten has become part of our daily lives.

While many regulatory agencies have set limits on exposure to airborne tungsten dust 鈥 primarily to protect workers who mine and process the metal 鈥 there are very few officially mandated limits on water-soluble tungsten compounds, to which a broader cross-section of the community are at risk of exposure.

The issue came to prominence in the early 2000s when scientists investigated a possible link between a cluster of childhood leukemia cases in Fallon, Nevada, and high levels of tungsten in the groundwater from which the town drew its supply. The case prompted the US Centers for Disease Control and Prevention to nominate tungsten for toxicology and carcinogenesis studies.

IMAGE:聽 In mice exposed to tungsten in drinking water, the element accumulated in porous tissue near the end of bones (left). Using synchrotron-based x-ray absorption techniques, researchers produced an image (center) mapping the presence of tungsten in a form resembling the chemical catalyst phosphotungstate (P=phosphorus, W= tungsten, O=oxygen).聽CREDIT: Cassidy VanderSchee

Mixed results from previous toxicity studies

To date, research into tungsten鈥檚 toxicity and possible role as a carcinogen has produced mixed results. Some studies have shown that other communities exposed to tungsten levels comparable to those in Fallon were not affected by a higher-than-normal incidence of cancer 鈥 a finding that appeared to exonerate tungsten. But subsequent research has revealed that in subjects exposed to both tungsten and cobalt, tungsten appears to augment the toxicity of the other substance. These findings pointed to a need to better understand how tungsten accumulates in the body and in what form, and to what extent the body is capable of eliminating tungsten following exposure.

The 91社区 team鈥檚 study on tungsten exposure in mice, published in Communications Chemistry, used powerful x-ray spectroscopy techniques to find answers to these questions. The results raise a number of concerns.

While tungsten has previously been shown to accumulate in bone, the 91社区 researchers found that the element didn鈥檛 accumulate uniformly across bones; rather, it was concentrated in certain hot spots.

鈥淲e found that tungsten, once thought to be non-toxic and inert, does in fact accumulate heterogeneously in bone,鈥 said Cassidy VanderSchee, lead author of the study and doctoral student in the Department of Chemistry at 91社区. 鈥淣ot only that, we found that it accumulated in a chemically different form to that in which it was administered, which confirmed that tungsten is chemically active in the body.鈥

Accumulation in bone tissues

The study showed that in mice exposed to high levels of tungsten through drinking water, the element accumulated in specific regions 鈥 bone marrow and porous (or 鈥榗ancellous鈥) bone tissue 鈥 to a degree 10 times greater than background levels. The deposition of tungsten in cancellous bone suggests the element is incorporated during bone growth and remodelling, indicating that young, growing individuals are particularly susceptible.

The researchers also found that tungsten was retained in the bone鈥檚 hard outer layer 鈥 the cortex 鈥 even after the mice were given tungsten-free water for a period of eight weeks after initial exposure. With the body unable to clear tungsten from this tissue, the bone effectively becomes a source of chronic exposure.

Of even greater concern was the finding that tungsten was changing form in the body. The results showed that the element was accumulating in a form resembling phosphotungstate, a known chemical catalyst with significant potential to intervene in the biological processes that occur in bone marrow and cancellous bone 鈥 immune cell formation and bone growth among them.

鈥淲e believe that many of the biological effects of tungsten we鈥檝e been investigating will be traced back to changes in the bone,鈥 says Koren Mann, associate professor of oncology at 91社区 and a co-author of the study. 鈥淭his includes the effects on the immune system, stem cells, and cancer.鈥

鈥淲hile research continues into the health risks posed by human exposure to tungsten, our study provides important insights into how the element accumulates in the body 鈥 findings that are crucial to developing effective therapies for removing it,鈥 says 91社区 chemistry professor and senior author Scott Bohle.

The research was conducted in collaboration with scientists at the Canadian Light Source synchrotron in Saskatoon, Saskatchewan, and the U.S. Department of Energy鈥檚 National Synchrotron Light Source II facility at Brookhaven National Laboratory in Upton, NY.

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Funding for the research was provided by the Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, and the Canada Research Chairs Program.

鈥淎ccumulation of persistent tungsten in bone as in situ generated polytungstate,鈥 Cassidy R. VanderSchee et al. Communications Chemistry, published online Mar. 8, 2018. doi:10.1038/s42004-017-0007-6

Contacts:

Cassidy VanderSchee
cassidy.vanderschee [at] mail.mcgill.ca

Prof. Scott Bohle
Scott.Bohle [at] 91社区.CA

Chris Chipello
91社区, media relations office
christopher.chipello [at] mcgill.ca
514-398-4201

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