Nanomaterial toxicity assessment

Despite the considerable attention that in vitro systems have received and their growing application to nanomaterial toxicity assessment (Braydich-Stolle et al., 2005 Hussain et al., 2005), little attention has been devoted to a critical examination of their suitability, particularly when it comes to particle solution dynamics and dosimetry (Teeguarden et al., 2007). In contrast to soluble chemicals, particles can settle, diffuse, and aggregate differentially according to their size, density, and surface physicochemistry... 

Jones, C.F. and Grainger, D.W. (2009) In vitro assessments of nanomaterial toxicity. Advanced Drug Delivery Reviews, 61 (6), 438-456. 

Challeng es for assessing carbon nanomaterial toxicity to the skin. Carbon, 44 (6), 1070-1078. 

CNCs are becoming an important class of renewable nanomaterials with many applications in different areas, including biomedicine. A number of reviews on the bioapplications of CNCs can be found in the literature. The U.S. Food and Drug Administration (FDA) has listed CNCs as a Generally Regarded As Safe (GRAS) material. The toxicity assessment of CNCs in the microvascular endothelial cells of human brain was conducted and CNCs were found to be non-toxic to cells and therefore could be used as carriers in the targeted delivery of therapeutics. The non-toxicity of CNCs has been confirmed by interactions with rainbow trout hepatocytes and microvascular endothelial cells. The biocompatibility of CNCs has also been verified in a recent study. " ... 

As we will see later in this chapter, not only is one able to alter a nanostructure by the types of atoms and their stoichiometries, but also their 3-D arrangement. With such profound nanostmctural variety, it is no wonder that standardized toxicokinetics studies i.e., absorption, distribution, metabolism, and excretion characteristics) are still greatly lacking. For this to occur, there is a need for reference nanomaterials that would allow a systematic structure V5. toxicity assessment for various classes of nanostructures. To date, the only commercially-available reference materials are spherical nanoparticles that are used to calibrate particle-size analyzers. Such reference materials will only be possible once we have standardized protocols for the synthesis and characterization of various types of nanomaterials, an active area of investigati(Mi at the National Institute of Standards and Technology (NIST). 

Degradability is an important factor in the assessment of the toxicity of nanomaterials [71]. Nondegradable nanomaterials may in fact accumulate in organs and/or intracellularly, where they would exert toxic effects. 

CNTs have been studied for cancer therapies despite the fact that these have been shown to accumulate to toxic levels within the organs of diverse animal models and different cell lines (Fiorito et al., 2006 Tong and Cheng, 2007). The molecular and cellular mechanisms for toxicity of carbon nanotubes have not been fully clarified. Furthermore, toxicity must be examined on the basis of multiple routes of administration (i.e., pulmonary, transdermal, ocular, oral, and intravenous) and on multiple species mammals, lower terrestrial animals, aquatic animals (both vertebrates and invertebrates), and plants (both terrestrial and aquatic). A basic set of tests for risk assessment of nanomaterials has been put forward (Nano risk framework). 

CNTs are of importance as useful bio-nanomaterials for pharmaceutical applications and biomedical engineering. However, despite the contribution of CNTs to bio-nanomaterials for pharmaceutical applications, the potential risks of CNTs about the exposure to human health have not been adequately assessed. Toxicology issues associated with CNT inhalation, dermal toxicity, pulmonary, biodistribution, biocompatibility, blood compatibility, and elimination need to be addressed prior to their pharmacological application in humans. 

For nanomaterials this is especially true if the exposure scenarios used in the test system are not representative of those likely to be found in the field [91, 92]. For example, the degree of toxicity observed in aquatic invertebrates exposed to multi-walled nanotubes (MWNTs) in water and sediment was influenced by the functional groups on the MWNTs and their preparation for dispersal into the test systems [93]. As noted, even the concept of what constitutes nanomaterials is not fixed [87], so these emerging materials will likely require a rethinking of how their toxicity is assessed and the hazards and risks they might pose to ecosystems [90]. For more information on nanomaterials, including application of life-cycle concepts to their design, see Chapter 8. 

Research is needed to explore the impacts of nanomaterials and nanomaterial production on the environment and public health. One framework for assessing these impacts is that of comparative risk assessment. Applied to an assessment of the production, use, and disposal of nanomaterials, a risk assessment typically considers both the potential for exposure to a given material and (once exposed) potential impacts such as toxicity or mutagenicity. The need to elucidate both of these components of risk in assessing the consequences of nanomaterials on the environment and public health is essential. 

Bello D, Hsieh SF, Schmidt D, Rogers E (2009) Nanomaterials properties vs. biological oxidative damage implications for toxicity screening and exposure assessment. Nanotoxicology 3(3) 249-261... 

Monteiro-Riviere N, Cunningham M J (2006). Screening methods for assessing skin toxicity of nanomaterials. Toxicol. Sci. 90(1-S) 5. 

Thus, the distinction between the hazard (an inherent toxic property of a chemical that may or may not be manifested, depending on exposure potential) and risk (the consequences of being exposed to a hazardous chemical at a particular exposure level) is critical (Purchase, 2000). Each component of a risk assessment—hazard identification, dose-response evaluation, and exposure assessment—is essential for evaluating the potential risks associated with the use of a substance such as a nanomaterial. The components of a risk assessment are universal in their application for assessing the hazards and risks of chemicals or products for a variety of industries or environmental exposures, regardless of the types of chemicals of interest (such as solvents, fibers, particulates and nanomaterials). 

Determining anticipated route and magnitude of exposure is an important component in the overall assessment of safety and must be done on a nanomaterial-by-nanomaterial basis, with secondary exposures taken into consideration when necessary. The estimated exposure levels for a nanomaterial may then be compared with the calculated safe dose derived from the hazard identification evaluation. The procedures and factors considered in the exposure assessment process are not expected to be any different for nanomaterials than for larger particles or chemicals. The degree of hazard associated with exposure to any chemical or substance, regardless of its physicochemical characteristics, depends on several factors, including its toxicity, dose-response curve, concentration, route of exposure, duration and/or frequency of exposure. However, depending on the route of anticipated exposure (dermal, inhalation, oral) and types of associated toxicities (local or systemic), a chemical may not pose any risk of adverse effects if there is no... 

Landsiedel, R., Ma-Hock, L, Hofmann, T, Wiemann, M., Strauss, V, Treumann, S., Wohlleben, W, Groters, S., Wiench, K. Van Ravenzwaay, B. 2014. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Particle and Fibre Toxicology, 11, 16. 

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