A
new study just published in the European Respiratory Journal links
workplace nanoparticle exposure to seven cases of serious and
progressive lung disease in China - leading to two patient deaths - and
presses a number of "hot" buttons when it comes to the safety of
emerging nanotechnologies. To help place the study in context, I have
posted separately the following pieces on 2020 Science, and also on the
SAFENANO blog:
Nanoparticle exposure and occupational lung disease – six expert perspectives on a new clinical study
Observations from six leading experts on the study, and it's significance
Is nanotechnology posed for the ride of its life?
A caution against overlooking the study's true relevance in the rush
to use it to justify pre-existing positions on nanotechnology
Further links to useful resources are included at the end of this blog.
Study Overview
In
brief, the paper by Song et al. that appears in the European
Respiratory Journal is a clinical study of 7 female Chinese workers who
were diagnosed with unusual and progressive lung damage. Two of the
women died as a result of the damage. All had been working for some
months in a facility spraying a polyacrylic ester paste onto a
polystyrene substrate that was subsequently heat-cured. The work was
carried out in an enclosed space with little natural ventilation. Five
months before the lung disease was identified, the local exhaust
ventilation in the facility broke down - and from the account given was
never mended.
All
seven patients were suffering from shortness of breath, and pleural
effusions (an excess of liquid in the cavity surrounding the lungs).
Lung tissue samples showed non-specific inflammation, pulmonary
fibrosis, and foreign-body granulomas of the pleura - the membrane
surrounding the lungs. Five of the patients were found to have
pericardial effusions - an excess of liquid around the heart.
On
examination, investigators found ~30 nm diameter particles in fluid
surrounding the lungs of the patients, and in the cytoplasm and
nucleoplasm of cells lining the inside and outside of the patients'
lungs. They also found evidence of similar sized nanoparticles in the
polyacrylic ester paste, and in the (defunct) workplace ventilation
system. There were accounts of smoke being produced as the coated
polystyrene was heat-cured.
Based
on the presence of the nanoparticles in the workplace and the patients,
the nature of the disease observed and previously published cell
culture and animal exposure studies on the impacts of nanoparticles,
the authors speculated that the lung disease - and the two deaths -
were a direct result of the nanoparticle exposure. They conclude that
this
may be the first study on the clinical toxicity in humans due to
long-term exposure to nanoparticles, and so many questions need to be
answered, more studies on the possible mechanisms, diagnosis, treatment
and prevention of the 'nano material-related disease' are needed. These
cases arouse concern that long-term exposure to some nanoparticles
without protective measures may be related to serious damage to human
lungs. It is impossible to remove nanoparticles that have penetrated
the cell and lodged in the cytoplasm and caryoplasm of pulmonary
epithelial cells, or that have aggregated around the red blood cell
membrane.
In the
press release accompanying the paper from the European Respiratory
Journal, more explicit associations with the safety of nanotechnology
are drawn:
While nanoparticles' diminutive size means they have
unprecedented physical properties (such as diffusion, resistance or
flexibility of use) that are invaluable in industrial applications, it
also raises the question of their toxicity for consumers and the
workforce. Their tiny diameter means that they can penetrate the body's
natural barriers, particularly through contact with damaged skin or by
inhalation or ingestion. Moreover, their toxicity has already been
established in animals: mice were found to develop symptoms of
inflammation and pulmonary fibrosis following application of carbon
nanoparticles to the trachea. But until now no cases had been reported
in humans. The revelations to be published in the ERJ by a Beijing team
will thus break new ground and relaunch the debate on the dangers of
nanotechnologies.
Given
the buttons this paper and the associated press release hit - including
nanoparticle safety, worker deaths and (in the press release) parallels
with asbestos, this is a paper that could garner a lot of attention. I
suspect that it will refocus attention on what is and isn't known about
the safe use of nanomaterials. Even though the logic is suspect from a
purely scientific perspective, the two deaths and their association
with nanoparticle exposure will most likely lead to some tough
questions being asked by consumers and others on the safety of other
nanomaterials. This may not be a bad thing, but at the same time it is
important to understand the limitations of the study:
This is a clinical study and not a toxicology study: The
investigators did not have the luxury of conducting controlled and
well-designed experiments, but were placed in the position of
detectives piecing together a series of events after the fact.
Inevitably, this leaves gaps in the information presented, but does not
necessarily detract from the usefulness of the study.
The
paper adds to the general knowledge base of how nanoparticle exposures
might impact on human health. In this respect, it is an important
addition to the literature.However, in isolation it tells us very
little beyond this particular incident, and great care should be taken
in extrapolating the findings to the handling of nanoparticles in
general. It is not possible to draw any general conclusions on the
safe use of nanotechnologies from the study.
Interpretation of the study is hampered by a lack of exposure
data. Nothing concrete is known about the nature or magnitude of the
workplace exposures. It can be speculated (reasonably up to a point)
that the workers were exposed to high airborne concentrations of a
cocktail of materials that probably contained nanometer-scale particles
in some form. What is not known is what the particles were made of of,
whether they were inhaled as single particles or as large agglomerates
or aggregates, or whether there was anything unusual about their
surface--including the presence of adsorbed chemicals. All of these
pieces of information are important in making sense of the health
effects seen.
There
are no electron microscope images of the nanoparticles found in the
workplace. The researchers note the presence of ~30 nm particles in the
polyacrylate paste and the ventilation system. But without images,
this information isn't much help in working out whether the presence of
these particles was significant.
There
is no chemical analysis of the particles found in the workplace or
biological samples. This is a critical data gap - the information is
needed to link the workplace material to the material found in the
patients, and to establish whether these were polyacrylic particles, an
inorganic additive to the paste, or something else.
There
is no assessment of other plausible causes of the symptoms seen. The
authors are quick to dismiss other possible causes (such as other fumes
and vapors from the polyacrylic paste or the polystyrene substrate) and
focus in on the nanoparticles. But without further research, it is
difficult to rule out the possibility of other factors playing a role
here.
In
discussing the relevance of the study, no distinction is made between
different types of nanomaterials and their potential impacts. The
authors cite the in vitro and in vivo behavior of a
range of nanomaterials observed in previous studies and relate these
findings to their own observations,. But they fail to recognize that
different nanoparticles behave in very different ways. For instance,
they refer to lung damage associated with inhaling carbon nanotubes in
animals as being similar to some of the symptoms observed in their
patients, without acknowledging that the particles they observe bear no
resemblance to carbon nanotubes. As a result, the authors propagate
the idea that nanoparticles are a generic class of material - which
research suggests they are not.
Despite these limitations, this is a strong clinical study, and if
viewed appropriately, will most likely help avoid similar incidents in
the future.
And as a final observation, it is worth noting that the illnesses
and deaths observed would most likely not have occurred if
long-accepted occupational practices had been followed. The tragedy
here is that, irrespective of the presence of nanoparticles, the
illnesses and deaths could have been prevented if simple steps had been
taken to reduce exposures.
Additional resources:
GoodNanoGuide
A community resource for working safely with engineered nanomaterials
SAFENANO
Further information on the Song study
ICON Blog
Further comments on the study on the ICON blog
This post also appears on the 2020 Science blog