Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
Although nanotechnology has vast potential in uses such as fuel cells, microreactors, drug delivery devices, and personal care products, it is prudent to determine possible toxicity of nanotechnologyderived products before widespread use. It is likely that nanomaterials can affect wildlife if they are accidentally released into the environment. The fullerenes are one type of manufactured nanoparticle that is being produced by tons each year, and initially uncoated fullerenes can be modified with biocompatible coatings. Fullerenes are lipophilic and localize into lipid-rich regions such as cell membranes in vitro, and they are redox active. Other nano-sized particles and soluble metals have been shown to selectively translocate into the brain via the olfactory bulb in mammals and fish. Fullerenes (C 60 ) can form aqueous suspended colloids (nC 60 ); the question arises of whether a redox-active, lipophilic molecule could cause oxidative damage in an aquatic species. The goal of this study was to investigate oxyradical-induced lipid and protein damage, as well as impacts on total glutathione (GSH) levels, in largemouth bass exposed to nC 60 . Significant lipid peroxidation was found in brains of largemouth bass after 48 hr of exposure to 0.5 ppm uncoated nC 60 . GSH was also marginally depleted in gills of fish, and nC 60 increased water clarity, possibly due to bactericidal activity. This is the first study showing that uncoated fullerenes can cause oxidative damage and depletion of GSH in vivo in an aquatic species. Further research needs to be done to evaluate the potential toxicity of manufactured nanomaterials, especially with respect to translocation into the brain. Two separate trials were performed using the same cohort of juvenile bass and the same batch of nC 60 . A total of 28 fish were randomly assigned to either exposure or control tanks over the course of the two trials (Table 1). Fish were exposed in groups of three or four in 10-L aquaria. The smaller trial consisted of fish in one aquarium each of control [reconstituted hard water (RHW), U.S. Environmental Protection Agency (EPA) protocol (U.S. EPA 1978), containing 192 mg/L sodium bicarbonate, 120 mg/L gypsum (CaSO 4 -2H 2 O), 120 mg/L magnesium sulfate, and 8 mg/L potassium chloride, pH 8.5] and 0.5 ppm nC 60 in RHW. The larger trial consisted of fish in two aquaria each of control, 0.5 ppm nC 60 , and 100 µM hydrogen peroxide (positive control for oxidative damage) and fish in one aquarium of 1 ppm nC 60 . Because of the high cost of production and limited quantities of nC 60 , I exposed fish in groups of either three larger fish (control and 0.5 ppm nC 60 ) or four smaller fish (1 ppm nC 60 ) per 10-L aquarium containing 7 L exposure water. To avoid aggressive interactions, I used smaller fish in the 1-ppm exposure aquaria to allow more space for individual fish. For aquaria with three fish, the fish were physically separated from one another with glass dividers. Vigorous aeration assured that water flowed freely between all three compartment...
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