This review is presented as a common foundation for scientists interested in nanoparticles, their
origin, activity, and biological toxicity. It is written with the goal of rationalizing and informing
public health concerns related to this sometimes-strange new science of ‘nano’, while raising
awareness of nanomaterials’ toxicity among scientists and manufacturers handling them. We show
that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other
natural processes, and that our bodily systems are well adapted to protect us from these potentially
harmful intruders. The reticuloendothelial system in particular actively neutralizes and eliminates
foreign matter in the body, including viruses and non-biological particles. Particles originating from
human activities have existed for millennia, e.g. smoke from combustion and lint from garments,
but the recent development of industry and combustion-based engine transportation has profoundly
increased anthropogenic particulate pollution. Significantly, technological advancement has also
changed the character of particulate pollution, increasing the proportion of nanometer-sized
particles - “nanoparticles” and expanding the variety of chemical compositions. Recent
epidemiological studies have shown a strong correlation between particulate air pollution levels,
respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of
nanoparticles on human health depend on individual factors such as genetics and existing disease,
as well as exposure, and nanoparticle chemistry, size, shape, agglomeration state, and
electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less
efficiently removed than larger particles by the macrophage clearance mechanisms in the lung,
causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and
nervous systems to many tissues and organs, including the brain. The key to understanding the
toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows
them to penetrate these basic biological structures, disrupting their normal function. Examples of
toxic effects include tissue inflammation, and altered cellular redox balance toward oxidation,
causing abnormal function or cell death. The manipulation of matter at the scale of atoms,
“nanotechnology”, is creating many new materials with characteristics not always easily predicted
from current knowledge. Within the near-limitless diversity of these materials, some happen to be
toxic to biological systems, others are relatively benign, while others confer health benefits. Some
of these materials have desirable characteristics for industrial applications, as nanostructured
materials often exhibit beneficial properties, from UV absorbance in sunscreen to oil-less
lubrication of motors. A rational science-based approach is needed to minimize harm caused by
these materials, while supporting continued study and appropriate industrial development. As
current knowledge of the toxicology of ‘bulk’ materials may not suffice in reliably predicting toxic
forms of nanoparticles, ongoing and expanded study of ‘nanotoxicity’ will be necessary. For
nanotechnologies with clearly associated health risks, intelligent design of materials and devices is
needed to derive the benefits of these new technologies while limiting adverse health impacts.
Human exposure to toxic nanoparticles can be reduced through identifying creation-exposure
pathways of toxins, a study that may some day soon unravel the mysteries of diseases such as
Parkinson’s and Alzheimer’s. Reduction in fossil fuel combustion would have a large impact on
global human exposure to nanoparticles, as would limiting deforestation and desertification. While
‘nanotoxicity’ is a relatively new concept to science, this review reveals the result of life’s long
history of evolution in the presence of nanoparticles, and how the human body in particular has
adapted to defend itself against nanoparticulate intruders.