Abstract  The attention of the Council was repeatedly called to certain claims made by the firm of Schering and Glatz for the substance collargolum. These claims were of a most unusual character. If true, they would place the substance in the front rank of therapeutic agents; if unfounded, they would constitute a most reprehensible abuse of the confidence of the medical profession. In view of the importance of the matter, the Council wished to proceed with especial thoroughness. It was decided, therefore, to appoint a committee to consider the question whether exaggerated statements are contained in the pamphlets on collargol that have been distributed by the above-mentioned firm, the agents of the preparation in this country. The undersigned, being four of the five members of the committee thus appointed, beg to submit the following report:

Abstract  The effects of several sub-lethal combinations of the metallic salts Ag2SO4, CuCl2, HgCl2 and ZnCl2 with the organic compounds Image -cysteine and albumin upon the heterotrophic activity of the microflora of a natural water are studied. This heterotrophic activity technique is based upon the uptake and mineralization of a radioactivity labelled metabolite by the indigenous microflora of the Simon Fraser University reflecting pool water. Data analysis by Michaelis—Menten enzyme kinetics equations allows the estimation of the maximum rate of heterotrophic activity as well as a determination of the turnover time of the nutrient in question. The addition of a sub-lethal combination of Cu2+ and Zn2+ to a sample of the pool water decreases heterotrophic activity to approximately the same extent as the additive decrease caused by these two cations added separately to samples of this water. Cu2+ and Zn2+ treated water samples do not recover the pre-metallic salt treatment activity following a 3-day incubation. Both Image -cysteine and albumin have no protective effect upon heterotrophic activity inhibition caused by Hg2+ and Ag+ respectively, at the concentrations used.

Abstract  The evolution in time of a nanoparticle (NP) aerosol released into a simulated workplace environment was investigated for different starting scenarios including (i) NP release into a particle-free atmosphere and (ii) release in presence of a pre-existing background aerosol. In each case, particle number distributions and total number concentrations in a 2 m(3) aerosol chamber were monitored over several hours. On the time scale and under the conditions relevant for workplace exposure, collisions between NP within their own size class and, if present, with the background aerosol were identified as the most important mechanism driving the change in particle size and number concentration. A model has been formulated on the basis of well-known aerosol dynamic principles to predict the evolution of NP number concentration for a defined source and a defined environment (a given background aerosol concentration). A dimensionless number is introduced to scale the rate of NP concentration change relative to background aerosol concentration and particle size, which scales inversely with the concentration of free NP in the atmosphere. Beyond the physical change, the emergence of binary agglomerates constitutes a change in chemical composition of the aerosol. It is shown that the NPs are still chemically present in the aerosol after becoming attached to background particles, thus remaining airborne while being invisible in the size distribution.

Abstract  Ultrafine particles (UFP, particles <100 nm) are ubiquitous in ambient urban and indoor air from multiple sources and may contribute to adverse respiratory and cardiovascular effects of particulate matter (PM). Depending on their particle size, inhaled UFP are efficiently deposited in nasal, tracheobronchial, and alveolar regions due to diffusion. Our previous rat studies have shown that UFP can translocate to interstitial sites in the respiratory tract as well as to extrapulmonary organs such as liver within 4 to 24h postexposure. There were also indications that the olfactory bulb of the brain was targeted. Our objective in this follow-up study, therefore, was to determine whether translocation of inhaled ultrafine solid particles to regions of the brain takes place, hypothesizing that UFP depositing on the olfactory mucosa of the nasal region will translocate along the olfactory nerve into the olfactory bulb. This should result in significant increases in that region on the days following the exposure as opposed to other areas of the central nervous system (CNS). We generated ultrafine elemental 13C particles (CMD = 36 nm; GSD = 1.66) from [13C] graphite rods by electric spark discharge in an argon atmosphere at a concentration of 160 microg/m3. Rats were exposed for 6 h, and lungs, cerebrum, cerebellum and olfactory bulbs were removed 1, 3, 5, and 7 days after exposure. 13C concentrations were determined by isotope ratio mass spectroscopy and compared to background 13C levels of sham-exposed controls (day 0). The background corrected pulmonary 13C added as ultrafine 13C particles on day 1 postexposure was 1.34 microg/lung. Lung 13C concentration decreased from 1.39 microg/g (day 1) to 0.59 microg/g by 7 days postexposure. There was a significant and persistent increase in added 13C in the olfactory bulb of 0.35 microg/g on day 1, which increased to 0.43 microg/g by day 7. Day 1 13C concentrations of cerebrum and cerebellum were also significantly increased but the increase was inconsistent, significant only on one additional day of the postexposure period, possibly reflecting translocation across the blood-brain barrier in certain brain regions. The increases in olfactory bulbs are consistent with earlier studies in nonhuman primates and rodents that demonstrated that intranasally instilled solid UFP translocate along axons of the olfactory nerve into the CNS. We conclude from our study that the CNS can be targeted by airborne solid ultrafine particles and that the most likely mechanism is from deposits on the olfactory mucosa of the nasopharyngeal region of the respiratory tract and subsequent translocation via the olfactory nerve. Depending on particle size, >50% of inhaled UFP can be depositing in the nasopharyngeal region during nasal breathing. Preliminary estimates from the present results show that ~20% of the UFP deposited on the olfactory mucosa of the rat can be translocated to the olfactory bulb. Such neuronal translocation constitutes an additional not generally recognized clearance pathway for inhaled solid UFP, whose significance for humans, however, still needs to be established. It could provide a portal of entry into the CNS for solid UFP, circumventing the tight blood-brain barrier. Whether this translocation of inhaled UFP can cause CNS effects needs to be determined in future studies.

Abstract  The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 Ág EAg m3 (3 * 106 cm3, 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 Ág Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 ÁL aqueous solution of 7 Ág silver nitrate (AgNO3) (4.4 Ág Ag) or 150 ÁL aqueous suspension of 50 Ág agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO3 from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO3, and entered systemic pathways.

Abstract  National Institute of Environmental Health Sciences. INTRODUCTION: Efficient elimination of inhaled soluble and insoluble particulate compounds deposited in the respiratory tract is necessary to keep its mucosal surfaces clean and functionally intact. In addition, the characteristic clearance processes and kinetics prevailing in different regions of the respiratory tract determine the retained dose of an inhaled substance in structures of the respiratory system. Thus, whether deposition and subsequent retention of inhaled particles is considered in clinical situations involving diagnostic or therapeutic aerosols or in toxicology with occupational or environmental pollutant aerosols, knowledge of the clearance of these substances is crucial in understanding their respiratory tract dosimetry. Clearance mechanisms are not only different for different regions of the respiratory tract, but also depend on physico-chemical characteristics of the deposited particulate material. Several recent review articles provide detailed descriptions and discussions of different processes governing the removal of inhaled solid and solute particles after deposition in the respiratory tract (Lauweryns and Baert, 1977; Morrow, 1977; Camner, 1980; Jones et al., 1982; Effros and Mason, 1983; Jones, 1984; Pavia, 1984; Morrow and Yu, 1985; Schlesinger, 1985; Brain, 1985, 1986; Cuddihy and Yeh, 1988). Because of the multitude and complexity of the diverse respiratory tract clearance processes, the present article will selectively review aspects of soluble and insoluble particle removal from tracheobronchial and deep lung regions. In addition, the article emphasizes clinical and toxicological implications of these removal processes and considers some unresolved issues related to lung clearance.

Abstract  A sensitive and rapid technique for directly measuring silver in blood, using electrothermal atomization atomic absorption spectrophotometry (ETAAS) is described. The method can be used to analyse precisely up to 40 blood samples a day in duplicate. Well-mixed, whole blood samples, collected in EDTA, were diluted 1 + 4 with a diluent containing 40 g l.-1 ammonium dihydrogen orthophosphate and 0.5 ml l.-1 Triton X-100. Aliquots of diluted blood were then analysed by ETAAS using wall atomization with a pyrolytically coated tube. The coefficient of variation for within-run precision was 4.55% at 10 micrograms 1.-1 and 5% at 25 micrograms 1.-1 Between-run variation, it was 4.1% at 25 micrograms l.-1 The analytical recovery for the method was 98% +/- 3% at both 8 and 30 micrograms 1. -1 The detection limit of the method was 0.1 microgram 1. -1, which was sufficiently sensitive to distinguish exposed from non-exposed individuals. Blood silver levels in unexposed subjects were found to be between < 0.1 and 0.2 micrograms 1. -1. Blood silver levels were determined in 98 occupationally exposed workers involved in bullion production, cutlery manufacture, chemical manufacture, jewelery production and silver reclamation. Blood silver levels ranged from 0.1 to 23 micrograms 1.-1, with some of the highest levels found in silver reclaimers.

Abstract  The rapid advancement of nanotechnology has created a vast array of engineered nanomaterials (ENMs) which have unique physical (size, shape, crystallinity, surface charge) and chemical (surface coating, elemental composition and solubility) attributes. These physicochemical properties of ENMs can produce chemical conditions to induce a pro-oxidant environment in the cells, causing an imbalanced cellular energy system dependent on redox potential and thereby leading to adverse biological consequences, ranging from the initiation of inflammatory pathways through to cell death. The present study was designed to evaluate size-dependent cellular interactions of known biologically active silver nanoparticles (NPs, Ag-15 nm, Ag-30 nm, and Ag-55 nm). Alveolar macrophages provide the first defense and were studied for their potential role in initiating oxidative stress. Cell exposure produced morphologically abnormal sizes and adherence characteristics with significant NP uptake at high doses after 24 h. Toxicity evaluations using mitochondrial and cell membrane viability along with reactive oxygen species (ROS) were performed. After 24 h of exposure, viability metrics significantly decreased with increasing dose (10-75 microg/mL) of Ag-15 nm and Ag-30 nm NPs. A more than 10-fold increase of ROS levels in cells exposed to 50 microg/mL Ag-15 nm suggests that the cytotoxicity of Ag-15 nm is likely to be mediated through oxidative stress. In addition, activation of the release of traditional inflammatory mediators were examined by measuring levels of cytokines/chemokines, including tumor necrosis factor (TNF-alpha), macrophage inhibitory protein (MIP-2), and interleukin-6 (IL-6), released into the culture media. After 24 h of exposure to Ag-15 nm nanoparticles, a significant inflammatory response was observed by the release of TNF-alpha, MIP-2, and IL-1beta. However, there was no detectable level of IL-6 upon exposure to silver nanoparticles. In summary, a size-dependent toxicity was produced by silver nanoparticles, and one predominant mechanism of toxicity was found to be largely mediated through oxidative stress.

Abstract  Mice were fed either 13 nm silver nanoparticles or 2–3.5 μm silver microparticles. The livers were then obtained after 3 days and subjected to a histopathological analysis. The nanoparticle-fed and microparticle-fed livers both exhibited lymphocyte infiltration in the histopathological analysis, suggesting the induction of inflammation. In vitro, a human hepatoma cell line (Huh-7) was treated with the same silver nanoparticles and microparticles. The mitochondrial activity and glutathione production were hardly affected. However, the DNA contents decreased 15% in the nanoparticle-treated cells and 10% in the microparticle-treated cell, suggesting a more potent induction of apoptosis by the nanoparticles. From a microarray analysis of the RNA from the livers of the nano- and micro-particle-fed mice, the expression of genes related to apoptosis and inflammation was found to be altered. These gene expression changes in the nanoparticle-treated livers lead to phenotypical changes, reflecting increased apoptosis and inflammation. The changes in the gene expression were confirmed by using a semi-quantitative RT-PCR.

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 Models Knowledge Base is an inventory of the computational models that are developed, used or supported by EPA's offices. For each model, the Models Knowledge Base provides information on: its development; its conceptual basis, scientific detail and evaluation; technical requirements and how to use it; information on the its inputs and outputs; and directions for downloading it and links to further information.

Abstract  The Nanoparticle Occupational Safety and Health (NOSH) consortium of international industrial, academic, government and non-governmental organizations has focused research since the beginning of 2006 upon obtaining information on occupational safety and health associated with aerosol nanoparticles and workplace exposure monitoring and protocols. The three main technical goals of the consortium are 1) the development of a method to generate a well-characterized aerosol of solid nanoparticles and to measure aerosol behavior as a function of time; 2) the development of an air sampling method that can be used on a day-to-day basis toconduct worker exposure assessments in workplace settings; and 3) the ability to measure barrier efficiency of filter media with respect to specific engineered aerosol nanoparticles. Since one stated objective of the NOSH consortium is the wide dissemination of all findings, including nanoparticle synthesis methods, behavior of aerosol nanoparticles as a function of time, and barrier efficiency of commercially available filter media to aerosol nanoparticles, this talk will serve as one method to present data and findings from the consortium. This consortium continues work towards developing knowledge of workplace exposure monitoring capabilities and strategies through the design and development of portable aerosol monitoring instrumentation for conducting assessments of worker exposure to airborne engineered nanoparticles. Additionally the consortium continues to conduct studies to obtain knowledge of the barrier performance characteristics of commercially available filter media to aerosol nanoparticles. To accomplish these objectives, multiple aerosol synthesis and characterization systems have been designed and optimized to generate well-characterized aerosol nanoparticles of various chemistries in the 3 – 100 nm size range. These aerosol nanoparticles are transported to one of three enclosed aerosol test chambers in which the concentration and particle size distribution of the incoming aerosol nanoparticles are controlled to examine aerosol behavior as a function of time, including rate of dispersion, aggregation, and particle loss for both charged and uncharged aerosol nanoparticles. These well-controlled and well-characterized aerosol nanoparticle studies form the basis for the development of a portable nanoparticleaerosol monitoring instrument which will be field tested in a wide variety of workplace environments. Good handling techniques, which isolate the potential hazard at the source, and effective containment and control measures includingengineering controls, respiratory protective devices and protective clothing fabricsare generally considered to provide adequate protection for exposures to fine-sized particulates. However, prior to the consortium inception, the available methodologies utilized in industrial hygiene practices to measure particle exposures were typically not sufficiently sensitive to measure occupational or ambient nanoparticle aerosol concentrations, whether in terms of particle mass, particle numbers, or surface area. Through this effort, the consortium has developed the instrumentation and protocols required to assess the barrier effectiveness of filter media to charged and uncharged aerosol nanoparticles as a function of particle chemistry, particle size distributions, and number concentration. The consortium continues to focus on identifying appropriate filter media that can be used as effective barriers for aerosol nanoparticles and establishing a knowledge baseon determining specificationsfor using those filter media given a set of known properties about a specific nanoparticle aerosol.

Abstract  Silver nanoparticles (Ag NPs) have recently received much attention for their possible applications in biotechnology and life sciences. Ag NPs are of interest to defense and engineering programs for new material applications as well as for commercial purposes as an antimicrobial. However, little is known about the genotoxicity of Ag NPs following exposure to mammalian cells. This study was undertaken to examine the DNA damage response to polysaccharide surface functionalized (coated) and non-functionalized (uncoated) Ag NPs in two types of mammalian cells; mouse embryonic stem (mES) cells and mouse embryonic fibroblasts (MEF). Both types of Ag NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and phosphorylated-H2AX expression. Furthermore both of them induced cell death as measured by the annexin V protein expression and MTT assay. Our observations also suggested that the different surface chemistry of Ag NPs induce different DNA damage response: coated Ag NPs exhibited more severe damage than uncoated Ag NPs. The results suggest that polysaccharide coated particles are more individually distributed while agglomeration of the uncoated particles limits the surface area availability and access to membrane bound organelles.

Abstract  Primary cells are ideal for in vitro toxicity studies since they closely resemble tissue environment. Here, we report a detailed study on the in vitro interactions of 7-20 nm spherical silver nanoparticles (SNP) with primary fibroblasts and primary liver cells isolated from Swiss albino mice. The intended use of silver nanoparticles is in the form of a topical antimicrobial gel formulation for the treatment of burns and wounds. Upon exposure to SNP for 24 h, morphology of primary fibroblasts and primary liver cells remained unaltered up to 25 microg/mL and 100 microg/mL SNP, respectively, although with minor decrease in confluence. IC(50) values for primary fibroblasts and primary liver cells as revealed by XTT assay were 61 microg/mL and 449 microg/mL, respectively. Ultra-thin sections of primary cells exposed to 1/2 IC(50) SNP for 24 h, visualized under Transmission electron microscope showed the presence of dark, electron dense, spherical aggregates inside the mitochondria, and cytoplasm, probably representing the intracellular SNP. When the cells were challenged with approximately 1/2 IC(50) concentration of SNP (i.e. 30 microg/mL and 225 microg/mL for primary fibroblasts and primary liver cells, respectively), enhancement of GSH (approximately 1.2 fold) and depletion of lipid peroxidation (approximately 1.4 fold) were seen in primary fibroblasts which probably protect the cells from functional damage. In case of primary liver cells; increased levels of SOD ( approximately 1.4 fold) and GSH ( approximately 1.1 fold) as compared to unexposed cells were observed. Caspase-3 activity assay indicated that the SNP concentrations required for the onset of apoptosis were found to be much lower (3.12 microg/mL in primary fibroblasts, 12.5 microg/mL in primary liver cells) than the necrotic concentration (100 microg/mL in primary fibroblasts, 500 microg/mL in primary liver cells). These observations were confirmed by CLSM studies by exposure of cells to 1/2 IC(50) SNP (resulting in apoptosis) and 2 x IC(50)) cells (resulting in necrosis). These results clearly suggest that although silver nanoparticles seem to enter the eukaryotic cells, cellular antioxidant mechanisms protect the cells from possible oxidative damage. This property, in conjunction with the finding that primary cells possess much higher SNP tolerance than the concentration in the gel (approximately 20 microg/g), indicates preliminary safety of the formulation and warrants further study for possible human application.

Abstract  The environmental genotoxic behavior of silver nanoparticles (nanoAg) combined with the detergent cetylpyridine bromide (CPB) was examined in vitro. The experimental results showed that the genotoxicity of nanoAg itself is weak, but nanoAg shows obvious genotoxicity after combined with CPB. The combined materials have a strong coeffect on calf thymus DNA (ctDNA) at a concentration of 3.3 × 10−6 g mL−1 nanoAg and 6.0 × 10−6 mol L−1 CPB. After the addition of ctDNA to the nanoAg–CPB system, the particles are scattered and the diameter decreases, which indirectly reveal that nanoAg–CPB has genotoxicity.

Abstract  Ecological and toxicological aspects of silver (Ag) and silver salts in the environment are briefly summarized with an emphasis on natural resources. Elevated silver concentrations in biota occur in the vicinities of sewage outfalls, electroplating plants, mine waste sites, and silver-iodide seeded areas; in the United States, the photography industry is the major source of anthropogenic silver discharges into the biosphere. Silver and its compounds are not known to be mutagenic, teratogenic, or carcinogenic. Under normal routes of exposure, silver does not pose serious environmental health problems to humans at less than 50 ug total Ag/L drinking water or 10 ug total Ag/m3 air. Free silver ion, however, was lethal to representative species of sensitive aquatic plants, invertebrates, and teleosts at nominal water concentrations of 1.2 to 4.9 ug/L; sublethal effects were significant between 0.17 and 0.6 ug/L. Silver was harmful to poultry at concentrations as low as 1.8 mg total Ag/kg whole egg fresh weight by way of injection, 100 mg total Ag/L in drinking water, or 200 mg total Ag/kg in diets; sensitive mammals were adversely affected at total silver concentrations as low as 250 ug/L in drinking water, 6 mg/kg in diets, or 13.9 mg/kg whole body.

Abstract  Silver nanoparticles (nano-Ag) are potent and broad-spectrum antimicrobial agents. In this study, spherical nano-Ag (average diameter = 9.3 nm) particles were synthesized using a borohydride reduction method and the mode of their antibacterial action against E. coli was investigated by proteomic approaches (2-DE and MS identification), conducted in parallel to analyses involving solutions of Ag(+) ions. The proteomic data revealed that a short exposure of E. coli cells to antibacterial concentrations of nano-Ag resulted in an accumulation of envelope protein precursors, indicative of the dissipation of proton motive force. Consistent with these proteomic findings, nano-Ag were shown to destabilize the outer membrane, collapse the plasma membrane potential and deplete the levels of intracellular ATP. The mode of action of nano-Ag was also found to be similar to that of Ag(+) ions (e.g., Dibrov, P. et al, Antimicrob. Agents Chemother. 2002, 46, 2668-2670); however, the effective concentrations of nano-Ag and Ag(+) ions were at nanomolar and micromolar levels, respectively. Nano-Ag appear to be an efficient physicochemical system conferring antimicrobial silver activities.