By staff reporter Xu Chao

(Caijing Magazine) The deaths of two women who worked with few safety precautions at a Beijing paint shop have contributed to an international controversy over the suspected labor health hazards of ultra-fine nanoparticles.

The victims, ages 19 and 29, were among seven women employed by the shop hospitalized between January 2007 and April 2008 at the vocational medicine and clinical toxicology department of Beijing's Chaoyang Hospital.

Doctors said they suffered from shortness of breath, pleural and pericardial fluid effusions, and rashes with intense itching on their faces, hands and arms. One died a few weeks after surgery, another succumbed after 21 months of treatment.

The case was described in the September issue of European Respiratory Journal in an article written by the lead physician, Dr. Song Yuguo, and his colleagues at the hospital's vocational medicine and poisons department. The article entitled Exposure to Nanoparticles Is Related to Pleural Effusion, Pulmonary Fibrosis and Granuloma may be the world's first report on clinical toxicity in humans linked to nanoparticles.

The authors wrote that the patients, ages 18 to 47, appeared to suffer from "a nanomaterial-related disease." They based the conclusion on surveys of the paint shop, clinical observations and patient exams.

Their report triggered a tsunami in international medical circles at a time when nanoparticles are undergoing intense research worldwide. A nano length is one billionth of a meter, and nanoparticles measure between 1 and 100 nanometers.

Several internationally acclaimed nanotechnology researchers expressed reservations about Song's results during interviews with Caijing at a recent nanotechnology conference in Beijing. Skeptics argued that nanoparticles could be just one of several causes of the women's health problems.

Experts acknowledge that workplace safety is a major concern in China. And Caijing has learned that U.S. and European scientists plan to conduct research in China to explore the issue of the sick workers. 

A lack of information about increasingly popular use of nanomaterials for industrial uses leaves open the possibility of new risks to workers, consumers and the environment. These materials offer a wide variety of applications in the fields of biomedicine, optics and electronics.

M.C. Roco, a senior adviser to the U.S. National Science Foundation, estimated in a 2005 report that a nanotechnology economy could be worth more than US$ 1 trillion by 2012.

Nanoparticle research enjoys generous public funding in the United States and Europe. So far, though, government support for nanotechnology safety research has been limited in China, said Zhao Yuliang, chief nanotechnologist for a program launched by the Ministry of Technology. Less than a score of nano materials have undergone safety tests in the country.

But nanotechnology safety research is catching up with industrial developments in China. The Chinese Academy of Sciences opened a Nano Biological Effect and Security Lab in 2001, and Zhao is working on a five-year, 25 million yuan research program for the technology focusing on the biological safety of manmade nanomaterials.

Moreover, the article written by Song and colleagues about the sick workers has contributed to the ongoing debate over future of implications of nanotechnology. Epidemiologists from the national Center for Disease Control (CDC) and the Beijing CDC joined the Chaoyang Hospital doctors in investigating the paint shop.

Song and his colleagues reported that nanoparticles measuring 30 nanos in diameter were found in the women's lungs and chest fluids. Neither other workers in separate areas of the shop nor the women's relatives suffered similar ailments.

The women came from farm families living near the factory, received no safety training, and were protected only by cotton face masks, worn occasionally. The report said they handled paint materials in the factory for eight to 12 hours every day, and were exposed to nanoparticles for five to 13 months.

The women worked in a 70 square meter workshop. Every day, they put about 6 kilos of polyacrylic paste into a pressure sprayer and sprayed it on polystyrene boards or glass. The boards were heated to between 75 to 100 degrees Celsius, and emissions vented.
Accumulated dust particles were found in the exhaust vent.

The workshop has a door but no windows. For five months before the women fell sick, the sprayer's vent was broken and the door kept closed to conserve heat.

The report said an ivory-colored polyacrylite found at the workshop is a widely used, low toxicity adhesive. Investigators found it contained butanoic acid, acetic acid, toluene and ethylene dioxide – none of which were likely causes of the women's severe health problems.

But sometimes nanoparticles are added to make materials stronger and more resistant to abrasion. They may be added by manufacturers to make silicon nanoparticles, thin zinc oxide, titanium dioxide, nanoscale silver cluster, and other nanomaterials.

Some of the nano materials, such as titanium dioxide, have been proved toxic in animal experiments, according to another article by Song published on the Chinese-language newspaper Health, or Jiankangbao, on Aug. 31.  But he said animal experiment results may not be true for humans. 

Electron microscopy focusing on the polyacrylic paste used by the women and dust particles found in the shop -- nanoparticles 30 nanos in diameter -- matched those found in the pleural fluid and lung tissues of the patients.

After seven months of clinical observation, three patients had severe and four moderate to mild lung damage. Pleural effusions recurred repeatedly, and traditional treatments were ineffective.

The 19-year-old died 16 days after thoracic surgery at the hospital. The 29-year-old died of respiratory failure 21 months after the symptoms appeared.

Pathological examinations of lung tissue showed pulmonary inflammation, pulmonary fibrosis, and foreign-body granulomas of pleura – symptoms consistent with damage caused by nanoparticles in experiments with animals.

After excluding infections, malignant tumors, immune system disorders and other diseases, Song and his colleagues concluded that long-term exposure through inhalation of and skin contact with some nanoparticles -- without protective measures -- may be linked to human lung damage.

"It is the nanomaterials containing nano-size particles that appear to produce the toxicities seen in the exposed workers," said the report.

Song and colleagues noted it is impossible to remove nanoparticles that penetrate cells, so worker safety measures are critical.

"Effective protective methods appear to be extremely important in terms of protecting exposed workers from illness caused by nanoparticles," they wrote.

Although the study may be the first "on the clinical toxicity in humans due to long-term exposure to nanoparticles," the doctors admitted the limitations of their findings. For example, they lacked environmental monitoring data from the workplace, and failed to determine the composition of the nanoparticles, despite efforts to contact the product manufacturer for details.

For this reason, Song and his colleagues have called for more study of the possible mechanisms, diagnosis, treatment and prevention of the ‘‘nanomaterial-related disease.''

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Full article in Chinese: http://magazine.caijing.com.cn/2009-09-13/110248536.html