Biomedical Engineering Reference
In-Depth Information
did not imagine that particles might affect tissues at the systemic level. The
nanotoxicology field is also considering the interaction between insoluble
NPs and biological systems (e.g., body fluids, proteins, and cells).
We recognize now that NPs, ranging from 1 to 100 nm, can cross the bio-
logical membrane and they can be translocated inside of cell organelles or
entities such as the mitochondria, lysosome, and nucleus. Therefore, the
potential health risk will depend on the magnitude and nature of the expo-
sures with NPs, and on the physical behavior of this particle related to dis-
persion, translocation, and deposition. The NPs have posed a new dilemma
because they can migrate to body compartments away from the application
site or deposition sites. In particular, because of their low uptake by macro-
phages, NPs are absorbed by endothelial cells, and they have access to cells
in the epithelium, the interstitium, and the vascular endothelium [3]. The
ability of low and toxic poorly soluble particulates such as carbon black and
titanium dioxide (TiO
2
) to induce chronic inflammation, fibrosis, neoplastic
lesions, or lung tumors in rats has been well established [4]. Considering
these challenges, it is important to understand the route taken by this new
xenobiotic particulate structure (e.g., NPs). We are between the curative and
toxicity impact with this new technology. Many of the exposure assessments
related to a nanomaterial can be approached as a logical subset of tradi-
tional exposure assessment for chemical hazards in the workplace and the
environment [5].
The objectives of this chapter are to highlight some limiting steps related
to nanotoxicokinetics, and to emphasize the difficulty of finding pertinent
information because there is a lack of data in toxicology. To respond to
these objectives, our effort focused on the ADME steps. The absorption step
explored the different routes by which NPs can reach the systemic circula-
tion, and then target tissue in the organism. The major ways of exposure
were oral, inhalation, and the cutaneous routes. Following absorption, NPs
are distributed in the organism, are free to bind to proteins, and are incorpo-
rated in specialized cells. Biotransformation will only be briefly mentioned
because commercial NPs are not easily degraded unless they are functional-
ized with a long-chain peptide or an unstable group of NPs. Section 9.4 will
discuss excretion, or externalization of the NPs, and the impact of this action.
9.2 Absorption
Absorption is the procedure by which a xenobiotic can cross the biological
barrier from the environment into the organism. Absorption of NPs can occur
via the oral route from the gastrointestinal tract (GIT), in the lung (inhala-
tion), and across the skin (cutaneous). These routes have different properties
and degrees of penetration depending on the characteristics of the NPs.
