Abstract  A critical review of studies examining exposures to the various forms of silver was conducted to determine if some silver species are more toxic than others. The impetus behind conducting this review is that several occupational exposure limits and guidelines exist for silver, but the values for each depend on the form of silver as well as the individual agency making the recommendations. For instance, the American Conference of Governmental Industrial Hygienists has established separate threshold limit values for metallic silver (0.1 mg/m3) and soluble compounds of silver (0.01 mg/m3). On the other hand, the permissible exposure limit (PEL) recommended by the Occupational Safety and Health Administration and the Mine Safety and Health Administration and the recommended exposure limit set by the National Institute for Occupational Safety and Health is 0.01 mg/m3 for all forms of silver. The adverse effects of chronic exposure to silver are a permanent bluish-gray discoloration of the skin (argyria) or eyes (argyrosis). Most studies discuss cases of argyria and argyrosis that have resulted primarily from exposure to the soluble forms of silver. Besides argyria and argyrosis, exposure to soluble silver compounds may produce other toxic effects, including liver and kidney damage, irritation of the eyes, skin, respiratory, and intestinal tract, and changes in blood cells. Metallic silver appears to pose minimal risk to health. The current occupational exposure limits do not reflect the apparent difference in toxicities between soluble and metallic silver; thus, many researchers have recommended that separate PELs be established.

Abstract  Experimental conditions that mimic likely scenarios of manufactured nanomaterials (MNs) introduction to aquatic systems were used to assessthe effect of nanoparticle dispersion/solubility and water chemical composition on MN-toxicity. Aqueous suspensions of fullerenes (C60), nanosilver (nAg), and nanocopper (nCu) were prepared in both deionized water and filtered (0.45 microm) natural river water samples collected from the Suwannee River basin, to emphasize differences in dissolved organic carbon (DOC) concentrations and solution ionic strengths (I). Two toxicity tests, the Ceriodaphnia dubia and MetPLATE bioassays were used. Results obtained from exposure studies show that water chemistry affects the suspension/solubility of MNs as well as the particle size distribution, resulting in a wide range of biological responses depending on the type of toxicity test used. Under experimental conditions used in this study, C60 exhibited no toxicity even when suspended concentrations exceeded 3 mg L(-1). MetPLATE results showed that the toxicity of aqueous suspensions of nCu tends to increase with increasing DOC concentrations, while increasing I reduces nCu toxicity. The use of the aquatic invertebrate C. dubia on the other hand showed a tendency for decreased mortality with increasing DOC and I. MetPLATE results for nAg showed decreasing trends in toxicity with increasing DOC concentrations and I. However, C. dubia exhibited contrasting biological responses, in that increasing DOC concentrations reduced toxicity, while the latter increased with increasing I. Overall, our results show that laboratory experiments that use DI-water and drastic MN-suspension methods may not be realistic as MN-dispersion and suspension in natural waters vary significantly with water chemistry and the reactivity of MNs.

Abstract  Silver sulfadiazine (SSD) cream is a potent agent for the treatment of burns. In a patient with end-stage renal disease, we observed a marked elevation in serum silver concentration in the course of 2 weeks of SSD cream therapy (200 g/d). Serum concentration of silver reached a maximum of 291 ng/mL in association with a rapid deterioration of mental status. SSD therapy was discontinued, and hemodialysis, hemofiltration, or plasma exchange was continually performed. Four months later, the patient died. At autopsy, profoundly elevated levels of silver were found in brain tissues of this patient (617.3, 823.7 ng/g wet tissue weight in the cerebrum and cerebellum, respectively). To determine the most efficient therapy to remove silver from serum, we compared hemodialysis (HD), hemofiltration (HF), and plasma exchange (PE). Both plasma exchange and hemofiltration were effective in decreasing serum silver, and their effects were additive. By contrast, HD was ineffective in reducing serum silver. This case illustrates that, on SSD cream therapy, burn patients with disturbed renal function are at risk of accumulating silver in serum and tissue to the level that may cause neuralgic decompensation. Removal of serum silver can best be effected by PE, particularly when combined with HF. In contrast, HD per se does not appear efficacious. None of these blood purification modalities improves deterioration of neurological status potentially attributable to silver deposition in brain tissues.

Abstract  To help extend the freshwater based biotic ligand model for silver (Ag) into brackish and saltwater conditions, 50g Gulf toadfish (Opsanus beta) were acclimated to 2.5%, 5%, 10%, 20%, 40%, 80%, or 100% salt water and exposed for 6d to 1.0microM AgNO(3), with or without 10mg C/L organic matter. Suwannee River natural organic matter collected by reverse osmosis was used. Silver accumulation in toadfish gills and plasma decreased as salinity increased, indicating low bioavailability of AgCl complexes. Complexation of Ag by organic matter, normally important in freshwater conditions, was less important as salinity increased. Although relatively little intestinal Ag uptake was observed, both liver and bile accumulated Ag from water imbibed past the isosmotic salinity point ( approximately 1/3 salt water). Toadfish also produced intestinal carbonate pellets, minerals which did not influence Ag accumulation. Our results further stress the importance of Ag speciation, physiological mechanisms, and intestinal Ag uptake when modelling Ag uptake and toxicity beyond freshwater conditions.

Abstract  The increasing use of nanomaterials in consumer products has led to increased concerns about their potential environmental and health impacts. To better understand the transport, fate, and behavior of nanoparticles in aquatic systems, it is essential to understand their interactions with different components of natural waters including natural organic matter over a broad range of physicochemical conditions. Fluorescence correlation spectroscopy was used to determine the diffusion coefficients of TiO2 nanoparticles having a nominal size of 5 nm. The effects of a various concentrations of the Suwannee River Fulvic Acid (SRFA) and the roles of pH and ionic strength were evaluated. Aggregation of the bare TiO2 nanoparticles increased for pH values near the zero point of charge. At any given pH, an increase in ionic strength generally resulted in increased aggregation. Furthermore, conditions which favored adsorption of the SRFA resulted in less aggregation of the TiO2 nanoparticles, presumably due to increased steric repulsion. Under the conditions studied here, nanoparticle dispersions were often stable for environmentally relevant conditions of SRFA, pH, and ionic strength, suggesting that in the natural environment, TiO2 dispersion might occur to a greater extent than expected.

Abstract  Metals play a vital role in human, animal and plant physiology, and important research, past and ongoing, is directed towards exploring the interrelated mechanisms that govern their penetration through skin. Much insight has been gained through these efforts, but our understanding of the process is still incomplete, mainly due to the failure to allow for the effects of chemical speciation of metallic elements, especially the transition metals. Also, the skin as target organ presents imponderable and wide margins of variability. In vivo permeability is subject to homeostasis regulating the overall organism; in vitro, the sections of skin used for diffusion experiments are likely to present artifacts. Endeavors to define rules governing skin penetration to give predictive quantitative structure–diffusion relationships for metallic elements for risk assessment purposes have been unsuccessful, and penetration of the skin still needs to be determined separately for each metal species, either by in vitro or in vivo assays. Phenomena observed by us and other investigators, which appear to determine the process of skin permeation for a number of metals, are reviewed, separating the exogenous factors from the characteristics of the skin or other endogenous factors.

Abstract  Journal article.

Abstract  There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 microg/cm2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm(-2) (range

Abstract  This Dredging Operations and Engineering Research (DOER) Technical Note (TN) is a tutorial with examples of the PTM, developed jointly by the Coastal Inlets Research Program (CIRP) and DOER Program. This note is applicable to Version 1.0 of PTM. Demirbilek et al. (2005a) describe the PTM interface, and an overview of features and capabilities of the PTM is presented in Demirbilek et al. (2005b). The theoretical formulation and implementation of the PTM are given in a technical report (MacDonald and Davies, in preparation). The PTM is a Lagrangian particle-tracking model that is part of the U.S. Army Corps of Engineers (USACE) Surface Water Modeling System, SMS (Zundel 2005, Zundel et al. 1998). It employs a Lagrangian method of tracking particle pathways to estimate migration of sediment particles as influenced by waves and currents. For its input, the PTM requires a geometric surface defining the bottom elevation (depth) over which water level, current velocity vectors, and waves are available at each point in the modeling domain. The user specifies sediment sources and model parameters to perform a PTM simulation within the SMS for a given set of hydrodynamic input (waves, water levels, and currents). The SMS includes commands for layout of the sediment sources, specification of the numerical parameters, and management of the Eulerian quantities (water depth, surface elevation, current velocity).

Abstract  BACKGROUND: Contaminated surfaces can act as a reservoir for pathogenic microorganisms and potentially exacerbate the risk of infection. Surface disinfection and decontamination provide temporary amelioration against bacterial colonization. Disinfected surfaces eventually become contaminated, thus, mitigating the benefit of the initial disinfection. It is hypothesized that to improve on the current state of the art, a disinfectant should not only immediately disinfect a surface but also provide persistent antimicrobial action after the product has been applied. We describe here a silver-based disinfectant technology designed to provide long-lasting sanitization and disinfection to treated surfaces as evaluated on hard surfaces after repeated environmental insults. METHODS: A comparative evaluation of 6 disinfectant formulations for residual antimicrobial activity after water rinsing was performed. Log reduction of bacterial populations on disinfectant-treated substrates were measured after 30 minutes to 8 hours of exposure and compared with an untreated control. In a similar study, the residual antimicrobial activity of a silver disinfectant was evaluated against antibiotic- and biocide-resistant bacteria also after water rinsing. Further, residual antimicrobial activity of the silver disinfectant was measured after 5 cycles of rinsing, abrasion, and contamination against representative household and nosocomial pathogens (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter aerogenes, Enterococcus faecium, or Salmonella choleraesuis) after 10-minute exposure times. RESULTS: In the comparative assay, only the silver disinfectant and a persistent quaternary ammonium compound disinfectant demonstrated significant residual activity (> or =3.0 log(10) reduction to control) against S aureus whereas only the silver disinfectant demonstrated activity against Pseudomonas. No residual activity (< or = 0.5 log reduction to untreated control) was observed for the other disinfectant products. The silver-based disinfectant also showed significant and equivalent efficacy against antibiotic- and silver-resistant bacteria. In addition, the silver disinfectant was able to achieve significant residual activity in 10 minutes against all organisms tested after 1, 3, and 5 cycles of water rinse, abrasion, and microbial contamination. CONCLUSIONS: The findings show the ability of a new silver-based disinfectant to reduce bacterial populations that contact treated surfaces within minutes, highlight the potential to interrupt cross-contamination from environmental surfaces, and reduce the risk of infection within the home and health care settings.

Abstract  Every cell has a silver lining! The toxicity of Ag nanoparticles is investigated using a panel of recombinant bioluminescent bacteria. The presence of the nanoparticles leads to the production of a superoxide radical (see figure). Furthermore, the Ag nanoparticles damage the cellular membranes, causing a disruption in the ion efflux system. Thus, the cells cannot effectively extrude the Ag ions and, hence, Ag nanoparticles cause more damage than do Ag ions.

Abstract  Little is known about the impact manufactured nanoparticles will have on aquatic organisms. Previously, we demonstrated that toxicity differs with nanoparticle type and preparation and observed behavioral changes upon exposure to the more lethal nanoparticle suspensions. In this experiment, we quantified these behavioral and physiological responses of Daphnia magna at sublethal nanoparticle concentrations. Titanium dioxide (TiO2) and fullerenes (nano-C60) were chosen for their potential use in technology. Other studies suggest that addition of functional groups to particles can affect their toxicity to cell cultures, but it is unknown if the same is true at the whole organism level. Therefore, a fullerene derivative, C60HxC70Hx, was also used to examine how functional groups affect Daphnia response. Using a high-speed camera, we quantified several behavior and physiological parameters including hopping frequency, feeding appendage and postabdominal curling movement, and heart rate. Nano-C60 was the only suspension to cause a significant change in heart rate. Exposure to both nano-C60 and C60HxC70Hx suspensions caused hopping frequency and appendage movement to increase. These results are associated with increased risk of predation and reproductive decline. They indicate that certain nanoparticle types may have impacts on population and food web dynamics in aquatic systems.

Abstract  We have adapted an "in vitro" toxicity test using zebrafish embryos for a toxicogenomics approach. Our goal is to develop a rapid toxicity assay for nanoparticles to be used in food and other applications. We incubated fertilized fish eggs for 48 h in the presence of a solution of purified MWCNT (1 ppb to 10 ppm) or with nanosilver solutions (1 ppb to 5 ppm). We could not detect effects on development or timing. We have used quantitative RT-PCR to analyze the expression patterns of Cyp1A1, Ahr2, Cpt1, iNOS, Ncf1, NudT1, c/EBP- and MafT. These genes are involved in detoxification patterns, in the protection against oxidative stress or code for regulatory factors involved in the immune response. At these concentrations, nanosilver had clear effects on the expression of most of the genes in a dose dependant manner. Induction was maximum in the case of regulatory factors. On the contrary, changes in gene expression induced by MWCNTs were much lower, suggesting a reduced toxicity at the tested concentrations.

Abstract  The widespread use of silver nanoparticles (Ag-NPs) in commercial products, especially textiles, will likely result in an unknown spread of Ag into the environment. The quantification and characterization of the Ag released from nano-Ag-products is an important parameter needed to predict the effect of Ag-NPs on the environment. The aim of this study was to determine the amount and the form of Ag released during washing from nine fabrics with different ways of silver incorporation into or onto the fibers. The effect of pH, surfactants, and oxidizing agents was evaluated. The results show that little dissolution of Ag-NPs occurs under conditions relevant to washing (pH 10) with dissolved concentrations 10 times lower than at pH 7. However, bleaching agents such as hydrogen peroxide or peracetic acid (formed by the perborate/TAED system) can greatly accelerate the dissolution of Ag. The amount and form of Ag released from the fabrics as ionic and particulate Ag depended on the type of Ag-incorporation into the textile. The percentage of the total silver emitted during one washing of the textiles varied considerably among products (from less than 1 to 45%). In the washing machine the majority of the Ag (at least 50% but mostly >75%) was released in the size fraction >450 nm, indicating the dominant role of mechanical stress. A conventional silver textile did not show any significant difference in the size distribution of the released silver compared to many of the textiles containing nano-Ag. These results have important implications for the risk assessment of Ag-textiles and also for environmental fate studies of nano-Ag, because they show that under conditions relevant to washing, primarily coarse Ag-containing particles are released.

Abstract  Research has demonstrated that metallic nanoparticles produce toxicity in aquatic organisms that is due largely to effects of particulates as opposed to release of dissolved ions. The present research examined the interplay of nanoparticle composition and dissolution on response of the zebrafish gill following exposure to toxic (nanocopper or nanosilver) or nontoxic (nano-TiO2) nanometals. Female zebrafish were exposed to 48-h no observable effects concentration of nanocopper and nanosilver or to soluble Cu and Ag that matched the concentration of dissolved metals released during nanoparticle exposure. Both nanocopper and nanosilver exposures increased metal content associated with gill tissue, though silver concentrations were much higher following nanosilver exposures suggesting that intact silver nanoparticles are associated with the gill. Morphological and transcriptional responses of the gills differed among various nanomaterials and between nanoparticulate and soluble species. Nanocopper increased mean gill filament width by three to fourfold between 24 and 48 h, whereas nanosilver did not alter gill filament width at either time point. Global gene expression analysis demonstrates that the exposure to each nanometal or soluble metal produces a distinct gene expression profile at both 24 and 48 h, suggesting that each exposure is producing biological response by a different mechanism. The differences in responses among the exposures indicates that each particle is having a distinct biological effect that does not appear to be driven solely by release of soluble metal ions into the water column. Based on these results, care should be taken when inferring toxicity of nanomaterials from data on a different material.

Abstract  Exposure to elevated waterborne silver as AgNO3 (4.07 µM=448 µg l-1) in seawater resulted in osmoregulatory disturbance in the lemon sole (Parophrys vetulus). The main effects were increased plasma Na+ and Cl- concentrations which translated into increased plasma osmolality. Plasma Mg2+ levels were also slightly increased after 96 h exposure. Using radio-isotopic flux measurements, a 50% reduction in branchial unidirectional Na+ extrusion was observed after 48 h silver exposure. By applying an intestinal perfusion approach, we were able to separate and thus quantify the intestinal contribution to the observed silver-induced physiological disturbance and internal silver accumulation. This analysis revealed that the intestinal contribution to silver-induced ionoregulatory toxicity was as high as 50-60%. In marked contrast, internal silver accumulation (in liver and kidney) was found to be derived exclusively from uptake across the gills. Drinking of silver-contaminated seawater resulted in substantial silver accumulation in the intestinal tissue (but apparently not silver uptake across the intestine), which probably explains the intestinal contribution to silver-induced physiological disturbance.

Abstract  Dissolution, translocation, and disposition have been shown to play a key role in the fate and effects of inhaled particles and fibers. Concepts that have been applied in the micron size range may be usefully applied to the nanoscale range, but new challenges are presented based on the small size and possible change in the dissolution:translocation relationship. The size of the component molecule itself may be on the nanoscale. Solute concentration, surface area, surface morphology, surface energy, dissolution layer properties, adsorbing species, and aggregation are relevant parameters in considering dissolution at the nanoscale. With regard to the etiopathology caused by these types of particulates, the metrics of dose (particle number, surface area, mass or shape) is not yet well defined. Analytical procedures for assessing dissolution and translocation include chemical assay and particle characterization. Leaching of substituents from particle surfaces may also be important. Compartmentalization within the respiratory tract may add another dimension of complexity. Dissolution may be a critical step for some nanoscale materials in determining fate in the environment and within the body. This review, combining aspects of particle toxicology, material science, and analytical chemistry, is intended to provide a useful basis for developing relevant dissolution assay(s) for nanoscale particles.

Abstract  #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 biokinetic 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.

Abstract  The increasing use of engineered nanoparticles (NP) in industrial and household applications will very likely lead to the release of such materials into the environment. Assessing the risks of these NP in the environment requires an understanding of their mobility, reactivity, ecotoxicity and persistency. This review presents an overview of the classes of NP relevant to the environment and summarizes their formation, emission, occurrence and fate in the environment. The engineered NP are thereby compared to natural products such as soot and organic colloids. To date only few quantitative analytical techniques for measuring NP in natural systems are available, which results in a serious lack of information about their occurrence in the environment. Results from ecotoxicological studies show that certain NP have effects on organisms under environmental conditions, though mostly at elevated concentrations. The next step towards an assessment of the risks of NP in the environment should therefore be to estimate the exposure to the different NP. It is also important to notice that most NP in technical applications are functionalized and therefore studies using pristine NP may not be relevant for assessing the behavior of the NP actually used.

Abstract  Rarely observed nanoparticle dissolution rate data have been collected and explained for an environmentally and industrially relevant nanomaterial (PbS, the mineral galena) as a function of its particle size and aggregation state using high-resolution transmission electron microscopy (HRTEM) and solution analysis. Under identical anoxic acidic conditions (pH 3 HCl), it has been determined that the dissolution rate of PbS galena varies by at least 1 order of magnitude simply as a function of particle size, and also due to the aggregation state of the particles (dissolution rates measured are 4.4 x 10(-9) mol m(-2) s(-1) for dispersed 14 nm nanocrystals; 7.7 x 10(-10) mol m(-2) s(-1) for dispersed 3.1 microm microcrystals; and 4.7 x 10(-10) mol m(-2) s(-1) for aggregated 14 nm nanocrystals). The dissolution rate difference between galena microparticles and nanoparticles is due to differences in nanotopography and the crystallographic faces present. Aggregate vs. dispersed dissolution rates are related to transport inhibition in the observed highly confined spaces between densely packed, aggregated nanocrystals, where self-diffusion coefficients of water and ions decrease dramatically. This study shows that factors at the nanometer scale significantly influence the release rate of aqueous, highly toxic and bioavailable Pb in natural or industrial environments during galena dissolution.

Abstract  To fully assess the impact of pollutant releases into the environment, it is necessary to determine both the concentration of chemicals accumulating in biota and the biological effects they give rise to. Owing to time, expertise, and cost constraints, this is, however, rarely achieved. Here, quick, simple to perform, and inexpensive biomarkers and chemical immunoassays were combined in a rapid assessment approach to measure exposure to and effects of organic and metal pollutants on the ribbed mussel (Geukensia demmissa) from New Bedford Harbor, MA. Significant differences in polychlorinated biphenyl (PCB) and polyaromatic hydrocarbon (PAH) tissue residue concentrations were detected among sites using RaPID immunoassay. Selected analyses were verified using GC/MS. No significant differences were observed in metal concentrations (Cu, Cd, Pb, As, Hg, Ni) throughout the area. While causality cannot be attributed, multivariate canonical correlation analysis indicated that PCB and PAH concentrations were strongly associated with the induction of biomarkers of genotoxicity (micronucleus formation), immunotoxicity (spontaneous cytotoxicity), and physiological impairment (heart rate). It is concluded thatthe incorporation of chemical immunoassays with biological monitoring tools into routine management procedures is clearly viable and valuable as a means of identifying toxic impacts of pollutants on biota in situ.