Page 221 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

206 Principles and Methods

to be taken up and travel through the body, deposit in target organs,
penetrate cell membranes, lodge in mitochondria, and trigger injurious
responses.
Against this background, it should be our goal to develop appropriate
methods to assess the safety of NM and, by so doing, help to safeguard
the future of nanotechnology without the fear of negative public per-
ception, government overregulation, and potentially costly litigation. It
is essential that we adopt standardized test methods to assess NM safety
and to generate an online databank that is accessible to all users and pro-
ducers of NM. In this chapter, we propose an approach to the assessment
of NM toxicity that uses a test paradigm proven useful for studying the
toxicity of ambient air particles. This approach attempts to predict which
NM are dangerous based on the material characteristics that predis-
pose them to ROS production and the generation of oxidative stress. We
propose that this test paradigm be developed into a high throughput
screening system that can be used to predict NM toxicity in vivo.

Paradigms for Assessing NM Toxicity
Air pollution and mineral dust particles have been implicated in a
number of adverse biological effects and disease outcomes. Major dis-
ease outcomes include the exacerbation of airway inflammation, asthma,
interstitial pulmonary fibrosis, atherosclerosis, ischemic cardiovascular
events, and cardiac arrhythmias. Fortunately, no clinically recogniza-
ble disease outcomes have so far been reported for manufactured NM
to date. Although a household-cleaning product Magic Nano was recently
implicated in respiratory symptoms, closer investigation failed to reveal
a link to NM. However, we are just entering the nano-revolution and it
is quite possible that clinically relevant NM toxicity could emerge. While
such outcomes will no doubt launch intensive investigations into NM
toxicity, a retroactive approach could be disastrous in terms of public per-
ception and possibly harm the nanotechnology industry. It makes far
more sense to instigate preventative measures to avert such a disaster.
Is it possible to formulate a preemptive approach to the potential
danger(s) of NM? In our opinion the answer is yes, since the potential mech-
anism(s) of injury can be studied by a science-based approach. One of the
key mechanisms by which ambient particulate matter (PM) causes tissue
injury and cardiopulmonary disease is through the generation of the reac-
tive oxygen species (ROS) and oxidative stress. Since the oxidative stress
paradigm has evolved into a comprehensive disease model, it illustrates
the type of approach that could be used to develop a predictive paradigm
for the NM toxicity testing.
Biological systems are generally able to integrate multiple pathways
of injury into a limited number of pathological outcomes, including