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Humanity has serendipitously used nanotechnology for hundreds of years. In the Greco-Roman period, the mixing of lead oxide and slaked lime with water resulted in the creation of lead sulfite nanocrystals (5 nm), which blackened hair when allowed to accumulate in the hair cuticle and cortex.293 Gold nanoparticles produce the striking color of ruby glass present in the Roman Lycurgus cup and in later church stained glass windows.107 Carbon nanotubes (CNTs) and cementite (Fe3C) nanowires found in 17th century Damascus steel sword blades explain its high-quality mechanical properties.240 In 1959, the physicist Richard Feynman proposed the theoretical framework for "manipulating and controlling things" all the way down to the atomic level in "There's Plenty of Room at the Bottom."83 Norio Taniguchi is generally credited with coining the term "nano-technology"—"the processing of separation, consolidation and deformation of materials by one atom or one molecule"—in 1974.270

In practical terms, the invention of the scanning tunneling microscope (STM) in 1981 enabled the visualization of individual atoms and allowed the direct physical manipulation of atomic surfaces.139 In 1985, Kroto and colleagues reported on a novel minute crystalline allotropic form of carbon, apparently conceived of some 15 years previously.55,154,213 These now-familiar soccer ball—shaped carbon-60 structures were named "buckminsterfullerenes" after Buckminster Fuller. The discovery of CNTs followed in 1991.123 The 2003 Congress enacted the "21st Century Nanotechnology Research and Development Act" to create a National Nanotechnology Program with a mandate to establish the goals, priorities, and metrics for evaluation of federal nanotechnology research, development, and other activities; to invest in federal research and development programs in nanotechnology and related sciences to achieve those goals; and to provide for federal interagency coordination.196

The health and safety impact of nanotoxicology came to fore during the first consumer recall of a purported nano-based invention.301 In 2006, the bathroom cleaning product "Magic-Nano" was released in Germany. Within days, more than 110 cases of illness were reported, and several patients were hospitalized with severe respiratory complaints, including acute lung injury. No further episodes of illness occurred after product recall only 3 days after introduction.135 Although it was ultimately determined that "Magic-Nano" contained no nanoparticles, the incident raised many questions about nanotechnology development, regulation, and health risks.20,21 There are now more than 600 consumer xenobiotics incorporating nanotechnology, with approximately three to four new ones reaching the market weekly.272 Exposure to nanoparticles is anticipated through a variety of mechanisms that must be considered from a toxicologic perspective.

Nanotechnology is defined as the "understanding, control, and use of matter at dimensions of roughly 1 to 100 nm, where unique characteristics enable novel applications."238 The American Society for Testing and Materials (ASTM) International defines an ultrafine particle as a particle ranging in size from approximately 0.001 μm (1 nm; 10 Å) to 0.1 μm (100 nm; 1000 Å) and a nanoparticle as an ultrafine ...

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