This article was originally published by the National Nanomanufacturing Network’s "InterNano" project (  It is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported.

A recent study published in the well-known medical journal, the European Respiratory Journal, has been receiving significant publicity as the authors have claimed their findings support an apparent linkage between workplace exposures to nanoparticles and severe respiratory disease. Specifically, in this study, investigators at China’s Capital University of Medical Science related unusual and progressive lung disease in seven Chinese workers, two of whom died, to nanoparticle exposures in a print plant where a polyacrylic ester paste containing nanoparticles was used. This linkage was made by the study investigators despite a general lack of exposure data for the workers. 

The complete review is after the jump . . .

Reviewed by Christopher M. Long, Sc.D., and Barbara D. Beck, Ph.D., DABT, FATS, Gradient

While there are cellular and laboratory animal studies that suggest the enhanced toxicity of some engineered nanoparticles (ENP) relative to larger sized particles of the same chemical composition (e.g., carbon nanotubes versus graphite, nano-sized titanium dioxide versus conventional titanium dioxide), there remains no direct human evidence of the health risks posed by ENP. The absence of any epidemiology or medical case studies examining potential ENP exposures and adverse health effects among either workers or consumers is likely a result of several factors. These factors include the fairly recent intensification in ENP manufacturing and commercial application, as well as the fact that relatively small amounts are typically manufactured and handled. The Song et al. (2009) study is a medical case report that claims to provide the first human evidence of "nanomaterial-related disease" following long-term nanoparticle exposure.

This study attributed unusual and progressive lung disease in seven Chinese workers, two of whom died of respiratory failure, to workplace nanoparticle exposures in a print plant where a polyacrylic ester paste containing nanoparticles was sprayed onto a polystyrene substrate, with subsequent heat-curing. For 5 to 13-month durations, all seven employees worked in the same department of the print plant, specifically, in a room with little to no ventilation due to the failure of the mechanical ventilation system. Lacking any measurement data of actual worker exposures, study investigators concluded, based on the detection of 30-nm nanoparticles in the paste material as well as in accumulated dust in the workplace, that these workers were exposed to polyacrylate nanoparticles. Reporting the presence of similarly-sized nanoparticles in the chest fluid and lung cells of the diseased workers, Song et al. highlighted the emerging body of nanotoxicological evidence from animal and in vitro studies to support their conclusion that the observed health effects were due to polyacrylate nanoparticle exposures.

While highly tragic and certain to create a stir among regulators, the media, and the general public, it is important to recognize that this study does more to highlight the critical need to follow well-established industrial hygiene practices than to provide direct evidence in humans of any unique health risks posed by ENPs. This study has several key limitations, including a general lack of information on the exposures experienced by the workers. Given the spraying of a chemical paste and the heating of a plastic material in an enclosed space lacking any mechanical ventilation, it is clear that these workers were exposed to a complex cocktail of chemicals and fumes, in addition to any nanoparticle exposures.

Based on the identification of nanoparticles in the paste, in accumulated dust in the workplace, and in lung tissues and cells of the workers, it is likely that these workers were exposed to nanoparticles in their workplace. However, Song et al. do not provide the necessary materials characterization data to demonstrate that the observed nanoparticles are indeed engineered nanoparticles (i.e., nanoscale particles intentionally created to have nano properties) and to confirm that the nanoparticles observed in the paint paste are the same nanoparticles identified in the workplace dust and in biological samples. Incidental nanoparticles are ubiquitous in indoor and outdoor air from a variety of anthropogenic and natural sources (engine exhaust, metal fumes, secondary organic aerosols), and characterization data are thus needed to confirm that the nanoparticles observed in the dust and in biological samples are indeed polyacrylate nanoparticles.

Given the lack of chemical analysis of the nanoparticles and the workers’ co-exposures to a variety of other toxic substances, it remains highly uncertain to what extent workplace nanoparticle exposures, compared to other workplace exposures, may have contributed to the observed health effects. Further, toxicological evidence cited by the investigators as linking ENP such as carbon nanotubes and zinc oxide with toxic responses in animals and cell cultures is of dubious relevance to polyacrylate nanoparticles, which are unlikely to exhibit similar biological activity due to important differences in toxicologically-relevant properties, in particular chemical composition. Scientific evidence is quite clear that toxicological properties differ greatly among different nanoparticles.

Regardless of the actual role of nanoparticles in the observed health effects, there are important lessons that can be learned from this study. In particular, given the limited knowledge regarding the health and safety risks posed by ENPs, it is imperative that best management practices for workplace exposures be followed to control and minimize potential exposures. It is clear that occasional use of cotton gauze masks, as reported by Song et al. for the Chinese workers, is not an adequate practice for controlling workplace exposures. Fortunately, a number of good resources are available for identifying state-of-the-art nano practices, including the ICON GoodNanoGuide . This study also highlights the critical need for robust exposure assessments to support health effects studies, providing data to characterize key nanoparticle properties and to differentiate ENPs from incidental nanoparticles.

In summary, this study highlights the importance of continued vigilance for any signs of ENP-related illnesses in exposed human populations. However, it lacks the essential materials characterization, exposure, and toxicity data for both the ENP and the other chemicals to which the workers were exposed. Thus, the study is not supportive of the authors’ conclusions that ENP exposures underlie the observed health effects among the Chinese workers and that these findings are of relevance to all commercially available ENPs.