Chinese researchers link nanoparticle exposure to pulmonary fibrosis in workers

Toxicity from nanoparticulates has been the topic of increasing research effort for several years. For some nanoparticles and nanomaterials, toxicity has already been established in animals. For example, mice were found to develop symptoms of inflammation and pulmonary fibrosis following application of carbon nanoparticles to the trachea (Lam et. al, 2004).However, until now no cases have been reported in humans. The work of a Beijing-based group of scientists to be published in the European Respiratory Journal (ERJ) this week linking exposure to nanoparticles in adhesive paint to severe pulmonary fibrosis in a group of young female workers therefore breaks new ground in the area, providing fascinating new evidence for consideration in the debate on the dangers of nanotechnologies.

The study, by a team led by Yuguo Song, of the Occupational Disease and Clinical Toxicology Department at Chaoyang Hospital in Beijing, involved seven healthy young women employed in a print plant. Over the course of a few months, all of the women were hospitalised for respiratory problems, accompanied by itchy eruptions of the skin on the face and arms. On examination, the patients were found to have liquid effusion around the heart and lungs, which proved resistant to all treatments. Comprehensive investigation led to a diagnosis, in all cases, of pulmonary fibrosis with consequent impairment of lung function.

The Chinese team's link between the symptoms and nanoparticle exposure was based on the results from electron microscopy of the chemical used, lung biopsy tissue and pleural effusion liquid, all three of which were found to contain round nanoparticles with a diameter of approximately 30 nanometres. Yuguo Song, the lead scientist, claims that these particles were likely to originate in the polyacrylate-based adhesive paints used by the women daily in the course of their work.However, he emphasises that despite repeated efforts, the group has not at this stage been able to obtain precise data on the composition of the paint in question. Likewise, the researchers have not been able to determine the workers' level of exposure through measurement of airborne particles, since the workshop was closed down several months before their investigation began.

Via investigation of the women's working conditions, and analysis of lung biopsy tissue and pleural effusion liquid, researchers at Beijing Chaoyang Hospital, together with the Chinese Centre for Disease Control, attempted reconstruct the probable sequence of events that led to the onset of the womens’ poisoning illness.

Before their respiratory symptoms led them to consult a doctor, the seven young women had been working for between 5 and 13 months in the same workshop, where white paint was sprayed onto polystyrene slabs. The spraying, and the heating and drying of the polystyrene slabs, were part of an automatic process; the workers' task was, using a large scoop, to load the machine with adhesive paint, made up of polyacrylic esters, and handle the slabs. The researchers learned that, in the months leading up to the workers' illness, the 70 m2 workshop had been very poorly ventilated. It was windowless, the door remained closed because of the cold, and the ventilation system had broken down five months earlier.

"The workers, of peasant origin, were also completely unaware of workplace health and safety regulations and of the potential toxicity of the materials they were handling", explains Yuguo Song. "Their only protection, used sporadically, was cotton gauze masks."

When interviewed, the women mentioned that flecks were often present in the air and this seemed to cause itching on their face and arms.

Despite the unfavourable working conditions, the authors of the ERJ article maintain that this was not simply a case of intoxication by paint vapour as a result of poor ventilation; but rather that the illness was caused by the inherent toxicity of the nanoparticles, which entered the body either through the airways or through the skin, or perhaps through both.

"It is clear that the symptoms, the examination results and the progress of the disease in our patients differ markedly from respiratory pathologies induced by paint inhalation", Yuguo Song emphasises.

By way of evidence, he points to the fact that, within two years, two of the women died and the other patients' pulmonary fibrosis continued to develop slowly even once the exposure had stopped.

As the machine was shut down after the workers became ill, no further cases were identified, and the Chinese researchers admit many questions remain unanswered. Importantly, this includes the precise nature of the particles involved. The researchers insist, however, that the study serves to highlight the need for urgent assessment of the risks of nanoparticles, and development of effective protection systems.

Given the increasing enthusiasm for nanotechnologies, the authors urge that priority be given to protecting the public and the workforce. "We call on scientists throughout the world to work together and address this new challenge", Yuguo Song concludes in the ERJ.

Clearly, the paper’s findings are set to have a huge impact on the nanotoxicology field, and potentially on the public acceptance of nano in general. However, there are a number of issues with the evidence presented in the paper, which are causing leading nanotoxicologists to question the causal link implicated between the nanoparticle exposures and the consequent illness.

The paper is available from the ERJ - click here to access the journal.

SAFENANO has prepared a special feature on this paper, which provides an impartial breakdown & appraisal of the study's findings in order to assist readers in forming their own opinion on its importance & implications. To read it, click here.

SAFENANO guest expert Dr Andrew Maynard has provided a fascinating  three-part opinion piece on the paper, featuring not only his thoughts, but those of key nanotoxicologists from around the globe. Included is input from:

• Ken Donaldson - Professor of Respiratory Toxicology specializing in workplace lung diseases, University of Edinburgh, UK. Professor Donaldson is one of the world’s leading authorities on the health impacts of inhaling airborne nanoparticles.  His group at the University of Edinburgh have led research into the potential health impacts of inhaling carbon nanotubes and other nanomaterials.
• Gunter Oberdorster - Professor of environmental medicine, Rochester University, USA. Prof. Oberdorster is considered by many to be the father of modern toxicology research into the potential health impacts of inhaling nanoparticles.  His research group at the University of Rochester has led global research in this area for over two decades.
• Vicki Stone - Professor of toxicology, Edinburgh Napier University,  SAFENANO’s Director of Toxicology & Editor of the journal Nanotoxicology). Prof. Stone is a foremost expert on the mechanisms by which nanoparticles potentially interact with the body and cause harm.
• Kristen Kulinowski - a Director of the International Council On Nanotechnology (ICON) at Rice University, and a global leader in developing safe and responsible nanotechnology applications.
• Rob Aitken - Director of Strategic Consulting, IOM UK & Director of SAFENANO. Dr Aitken has a wealth of experience addressing workplace safety and health.  He is a leading international expert in developing safe practices for working with engineered nanomaterials - including nanoparticles.
• Anthony Seaton - a distinguished clinical physician, specializing in occupational health, and a highly regarded expert on the potential health impacts of inhaling airborne nanoparticles. He is currently emeritus professor in the Department of Environmental and Occupational Medicine at the University of Aberdeen.

Reference:

Chiu-wing Lam, John T. James, Richard McCluskey, Sivaram Arepalli, Robert L. Hunter (2006), A Review of Carbon Nanotube Toxicity and Assessment of Potential Occupational and Environmental Health Risks, Critical Reviews in Toxicology 36:3, 189-217Source: Safenano