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A Review of Destructive Effect of Nano Silver on Human Health, Environment and Animals

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Abstract

Silver nanoparticles (AgNPs) are gaining attention from the academic and regulatory communities, not only because of their antimicrobial effects and subsequent product applications, but also because of their potential health and environmental risks. Nano-silver is used in an increasing number of products. Some of the applications have resulted in the concern of governments and the public, since little is known about the potential risks of nano-silver. It is hypothesized that the toxic effects of nano-silver are due to a combination of the specific properties of silver nanoparticles and the generation of ions from them. The main issue for future investigation is confirmation of our ‗0-hypothesis‘ that toxic effects of nano-silver are proportional to the activity of free silver ions which are released by the nanoparticles.

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... Human health effects from AgNP exposure have been reported following dermal or oral administration (Gavanji et al. 2013); however, to the best of our knowledge, there are currently no published peer-reviewed studies that discuss the effects of AgNP inhalation in humans. Inhalation studies with animals demonstrated deposition of Ag in the lung and translocation of these nanoparticles to other organs Braakhuis et al. 2014;Genter et al. 2012;Ji et al. 2007;Sung et al. 2009). ...
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Commercial nanometer sized silver is widely used for its antibacterial effect; however, nanoparticles may also have ecotoxicological effects after being discharged into water. Nanometer sized silver can flow into aquatic environments, where it can exert a variety of physiologically effects in living organisms, including fish. The present study aimed to investigate the effect of nanometer sized silver on the development of zebrafish embryos, analyze the properties of commercial nanometer sized silver and define the toxicity relationship between embryogenesis and hatched flies. The commercial nanometer sized silver was analyzed in the ion form. The hatch rate decreased in the nano-silver exposed groups (10 and 20 ppt); furthermore, the hatched flies had an abnormal notochord, weak heart beat, damaged eyes and curved tail. The expression of the Sel N1 gene decreased in the nano-silver exposed groups, and the catalase activities of the exposed groups increased relative to those in the control group. Therefore, the ions in commercial nanometer sized silver could accumulate in aquatic environments and seriously damage the development of zebrafish embryos.
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In this study 1-[4-(2-methoxy benzyl)-6-aryl-pyridazin-3(2H)-ylidene] hydrazines were used for the synthesis of new heterocyclic systems such as thiazolidine, phthalazine, pyrazolo, tetrazolo, hydrazide and new pyridazine derivatives to explore the effect of silver nanoparticles on their biological activity efficiency. Structures of the new heterocycles were characterized by the aid of several analytical techniques including; 1 H-NMR, FTIR and mass spectra. Silver nanoparticles were synthesized by a simple methodology and the formation of silver nanoparticles was confirmed by transmission electron microscopy (TEM) and UV studies. Most of the new prepared heterocycles were evaluated in vitro as new antimicrobial agents. Combination effects of the silver nanoparticles on the antimicrobial activity of the new heterocycles were investigated using the disk diffusion method. Compound 10a exhibited the strongest enhancing effect of silver nanoparticles solution against Aspergillus flavus and Candida albicans.
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This paper deals with the antibacterial efficacy of nanosized silver colloidal solution on the cellulosic and synthetic fabrics. Two kinds of Bacteria; Gram-positive and Gram-negative, were used. TEM observation of silver nanoparticles showed their shape, and size distribution. The particles were very small (2–5 nm) and had narrow distribution. SEM images of treated fabrics indicated silver nanoparticles were well dispersed on the surfaces of specimens. WAXS patterns did not show any peak of silver as the fabric had very small quantity of silver particles. However, ICP-MS informed the residual concentration of silver particles on fabrics before/after laundering. The antibacterial treatment of the textile fabrics was easily achieved by padding them with nanosized silver colloidal solution. The antibacterial efficacy of the fabrics was maintained after many times laundering.
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In this study the cytotoxic effect of commercially available silver (Ag) nanoparticle was evaluated using human dermal and cervical cancer cell lines. Prior to the cellular studies a full particle size characterisation was carried out using Dynamic Light Scattering (DLS), Transmission Electron Microscopy and Scanning Electron Microscopy in distilled water and cell culture media. The Zeta Potential (ZP) associated with the Ag nanoparticle was also determined in order to assess its stability in the solutions and its possible interaction with the media. The DLS and ZP study have suggested interaction of Ag nanoparticles with the media, which can lead to secondary toxicity. The toxic effects of Ag nanoparticles were then evaluated using different cytotoxic endpoints namely the lysosomal activity, mitochondrial metabolism, basic cellular metabolism, cellular protein content and cellular proliferative capacity. The cytotoxic effect of Ag nanoparticle was dependant on dose, exposure time and on the cell line tested. Further investigation was carried out on HeLa and HaCaT cell lines to elucidate the mechanism of its cytotoxicity. The Ag nanoparticle was noted to induce elevated levels of oxidative stress, glutathione depletion and damage to the cell membrane as found from the adenylate kinase assay and that leads to the apoptosis. Overall, significant differences were observed between the sensitivity of the two cell lines which can be understood in terms of their natural antioxidant levels.
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Oysters (Crassostrea virginica) from 50 to 69 locations (sites) along the Gulf of Mexico coastline, collected annually in 1986, 1987 and 1988, have been analyzed for 13 trace metals, including most of the metals of concern from an environmental quality perspective. Essentially the entire U.S. Gulf coastline was sampled, from far south Texas to far south Florida. Pooled samples of 20 oysters from three different stations at each site were analyzed by atomic absorption spectrophotometry. The concentrations found were generally less than or equal to literature values from other parts of the world thought to be uncontaminated by anthropogenic trace metal inputs. A few sites did, however, show apparent trace metal pollution and other sites gave anomalous values that cannot readily be explained by either known anthropogenic or natural causes. The range of values for the overall data set (maximum/minimum) varied from 15-fold for Mn to 624-fold for Pb, whereas the coefficient of variation (standard deviation/mean) was generally in the 50-60% range for most metals. Variations were much greater between stations than between years at a given station. Enrichments usually occurred in suites of three to four elements with Ag, Cd, Cu and Zn being the most common suite, thus several strong inter-element correlations were found. There was, however, little correlation between metal levels in oysters and in sediments from the collection sites even when sediment data were rationed to Al (sediment data are not given here). There was likewise little correlation between oyster metal levels and size, sex or reproductive stage of the oysters (data given elsewhere). Geographically, appreciably elevated (greater than 3 times average) metal levels were generally restricted to single sites within bays or estuaries, implying local control. On the other hand, regionally, Ag, Cd and Se levels were somewhat higher in Texas oysters than in those from Florida, whereas the reverse was true for As and Hg. Concentrations were lower than average for several metals in oysters from central Louisiana, especially Ag, Cd and Cu. Thus, the Mississippi River outflow and extensive offshore oil development do not seem to enrich oysters in trace metals.
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Wound care is painful for the patient with a burn injury and tedious for the burn unit staff but necessary to remove exudates and debris and to limit infections. In an effort to circumvent daily dressing changes while ensuring optimal wound protection, Sildimac (Marion Laboratories, Kansas City, Mo.), a new drug delivery system for silver sulfadiazine, was developed. When silver sulfadiazine, a topical antimicrobial commonly used for the treatment of burns, is incorporated into the delivery system, the drug is released in a sustained fashion. We report here the results of a multicenter evaluation of the safety and efficiency of Sildimac for treatment of full-thickness burn wounds. Sildimac, when left in place for up to 4 days, appears to be as effective as twice-daily wound cleansing and application of Silvadene cream 1% (Marion Laboratories, Kansas City, Mo.) for the treatment of full-thickness burns.
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Topical antimicrobial agents can prevent or minimize burn infections and should be used from the outset in all patients who are at significant risk from sepsis--either because of their wound severity or associated comorbid factors. All of the currently available topical agents have shortcomings; some of them have appreciable toxicity. The recent shift in emphasis toward early surgical closure of extensive deep burns in great part has resulted from appreciation of the inadequacies of currently available topical agents. Topical agents cannot substitute for timely and comprehensive physiologic support of burned patients.
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To observe the effect of 40 microA direct current (DC) on plasma albumin extravasation after burn injury. Silver-nylon wound dressings were used as anodes (-) on anesthetized male Sprague-Dawley rats with 20% total body surface partial-thickness scald burns. Burned rats with no treatment, or treated with silver-nylon dressing without current, were used as controls. Quantitative analysis of fluorescein isothiocyanate (FITC)-albumin leakage and accumulation in the wound tissue was performed using confocal fluorescence microscopy. In controls, the rate of albumin leakage was maximal at 1 hour postburn (PB) and then decreased, but remained higher than normal for 48 hours PB. The accumulation of FITC-albumin was maximal 4 to 6 hours PB and substantial for 48 hours. When DC was applied, leakage was reduced by 30 to 45% and approached normal control rates by 8 hours PB. FITC-albumin concentration peaked 4 hours PB, was 18 to 48% less then in burned control, and approached the level observed in unburned control by 18 hours PB. DC has a beneficial effect in reducing plasma protein extravasation after burn injury.
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Pseudomonas aeruginosa . Even so, effective topical antimicrobial chemotherapy and early burn wound excision have significantly reduced the overall occurrence of invasive burn wound infections. Individual patients, usually those with extensive burns in whom wound closure is difficult to achieve, may still develop a variety of bacterial and nonbacterial burn wound infections. Consequently, the entirety of the burn wound must be examined on a daily basis by the attending surgeon. Any change in wound appearance, with or without associated clinical changes, should be evaluated by biopsy. Quantitative cultures of the biopsy sample may identify predominant organisms but are not useful for making the diagnosis of invasive burn wound infection. Histologic examination of the biopsy specimen, which permits staging the invasive process, is the only reliable means of differentiating wound colonization from invasive infection. Identification of the histologic changes characteristic of bacterial, fungal, and viral infections facilitates the selection of appropriate therapy. A diagnosis of invasive burn wound infection necessitates change of both local and systemic therapy and, in the case of bacterial and fungal infections, prompt surgical removal of the infected tissue. Even after the wounds of extensively burned patients have healed or been grafted, burn wound impetigo, commonly caused by Staphylococcus aureus , may occur in the form of multifocal, small superficial abscesses that require surgical débridement. Current techniques of burn wound care have significantly reduced the incidence of invasive burn wound infection, altered the organisms causing the infections that do occur, increased the interval between injury and the onset of infection, reduced the mortality associated with infection, decreased the overall incidence of infection in burn patients, and increased burn patient survival.
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Antibiotic-resistant bacteria represent an increasing concern in wound infections. Wound colonization with these organisms normally results in aggressive management of the wound complicated by a greatly limited choice of therapeutic antibiotics. Silver and other noble metals are recognized as potential allies in combating these organisms in wounds. Three types of topical silver applications were tested to determine their bactericidal efficacies against clinical isolates of antibiotic-resistant organisms. The silver-based applications represent 3 methods of applying silver to wounds: as a liquid (silver nitrate), incorporated in a cream (silver sulfadiazine) and as a dressing coating (silver-coated dressings). The reduction in the viable bacterial population recovered from test articles after exposure to silver provided a comparative measure of the bactericidal efficacies of these silver applications. All of the products demonstrated an ability to reduce the number of viable bacteria. However, the methods varied in their efficacy against antibiotic-resistant bacteria, with the silver-coated dressing being the most efficacious and silver nitrate the least efficacious. Silver was demonstrated to be effective at killing the antibiotic-resistant strains tested. The silver-coated dressing was particularly rapid at killing the tested bacteria and was effective against a broader range of bacteria. Silver may be a useful prophylactic or therapeutic agent for the prevention of wound colonization by organisms that impede healing, including antibiotic-resistant bacteria.
Article
One mechanism of silver resistance in microorganisms is accumulation of the metal ions in the cell. Here, we report on the phenomenon of biosynthesis of silver-based single crystals with well-defined compositions and shapes, such as equilateral triangles and hexagons, in Pseudomonas stutzeri AG259. The crystals were up to 200 nm in size and were often located at the cell poles. Transmission electron microscopy, quantitative energy-dispersive x-ray analysis, and electron diffraction established that the crystals comprise at least three different types, found both in whole cells and thin sections. These Ag-containing crystals are embedded in the organic matrix of the bacteria. Their possible potential as organic-metal composites in thin film and surface coating technology is discussed.
Article
In 1965, Moyer revived interest in silver nitrate solution. He concluded on the basis on in vitro and in vivo studies that a 0.5% solution represented the lowest concentration at which antibacterial action (against Staphylococcus aureus, haemolytic streptococci and generally against Pseudomonas aeruginosa and E. coli) was obtained. Mafenide acetate was introduced a short time after the reintroduction of silver nitrate, followed a few years later by silver sulphadiazine. Thus, in a short period of time three medicaments appeared on the market which represented a radical change in the topical treatment of burns. The action of silver sulphadiazine has been intensively studied. Since silver sulphadiazine does not offer sufficient protection to prevent or retard the growth of gram-negative bacteria in patients with burns covering more than 50% of body surface, Monafo introduced the combined preparation silver sulphadiazine and cerium nitrate. Although various attempts have been made to develop more effective silver compounds, so far silver sulphadiazine still remains the most widely used substance of this type.
Article
Evaluation of the healing and persistence of a meshed composite skin graft applied without immunosuppression. The contraction of wounds grafted with 9:1 split-thickness autograft/1.5:1 allodermal mesh composite skin grafts (auto/allo MCSGs) was investigated. No immunosuppressive agent was applied. Male ACI rats and female Lewis rats reciprocally served as allodermis graft donors and recipients. Autograft/dermal autograft and allograft/dermal allograft MCSGs were the controls. AT 3 months after grafting, when epithelized auto/allo MCSG wounds were measured by computerized morphometric analysis, the silver nylon (SN) dressing group displayed less contraction than the Vaseline (petroleum jelly) dressing group (p < 0.003), and direct current treatment (SNDC) was more effective than SN (p < 0.005). The histologic structures of the hair follicles appear to confine the rejection process to the allogeneic follicles of the graft. The focal nature of the rejection process and the relatively low antigenicity of the dermal matrix allowed the survival of the allodermis layer. Although direct current significantly enhanced MCSG healing, SN and SNDC were not the immunosuppressive agents that were confirmed. This type of MCSG can heal without immunosuppressive treatment.
Article
Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-binding protein (SilE) and two efflux pumps (a P-type ATPase (SilP) plus a three-protein chemiosmotic RND Ag(I)/H+ exchange system (SilCBA)). The same genes were identified on five of 19 additional IncH incompatibility class plasmids but thus far not on other plasmids. Of 70 random enteric isolates from a local hospital, isolates from catheters and other Ag-exposed sites, and total genomes of enteric bacteria, 10 have recognizable sil genes. The centrally located six genes are found and functional in the chromosome of Escherichia coli K-12, and also occur on the genome of E. coli O157:H7. The use of molecular epidemiological tools will establish the range and diversity of such resistance systems in clinical and non-clinical sources. Silver compounds are used widely as effective antimicrobial agents to combat pathogens (bacteria, viruses and eukaryotic microorganisms) in the clinic and for public health hygiene. Silver cations (Ag+) are microcidal at low concentrations and used to treat burns, wounds and ulcers. Ag is used to coat catheters to retard microbial biofilm development. Ag is used in hygiene products including face creams, "alternative medicine" health supplements, supermarket products for washing vegetables, and water filtration cartridges. Ag is generally without adverse effects for humans, and argyria (irreversible discoloration of the skin resulting from subepithelial silver deposits) is rare and mostly of cosmetic concern.
Article
Using mainly United Kingdom estuaries as examples, various factors governing the bioavailability, bioaccumulation and biological effects of heavy metals in sediment-dominated estuaries are reviewed. Estuaries and metals primarily discussed include the Mersey (Hg, methylmercury; Pb, alkyllead), the Loughor (Cr, Sn), the Severn (Ag, Cd), the Fal (As, Cu, Sn, Zn), Poole Harbour (Cd, Hg, Se, tributyltin) and Southampton Water (tributyltin). Concentrations and bioavailabilities of metals in estuarine sediments depend on many different processes. Examples include (1) mobilisation of metals to the interstitial water and their chemical speciation, (2) transformation (e.g. methylation) of metals including As, Hg, Pb and Sn (3) the control exerted by major sediment components (e.g. oxides of Fe and organics) to which metals are preferentially bound, (4) competition between sediment metals (e.g. Cu and Ag; Zn and Cd) for uptake sites in organisms, and (5) the influence of bioturbation, salinity, redox or pH on these processes. Under field conditions, identification of dominant processes can be achieved by observing the goodness of fit between metal concentrations in ubiquitous deposit-feeding species and levels in various types of sediment extract over a wide spectrum of sediment types. Factors of more local importance are often indicated by the marked deviation of some points from otherwise excellent relationships. For example, points lying above the line relating tissue Sn concentrations in the clam Scrobicularia plana to those in 1 n HCl extracts of sediments were found to reflect the accumulation of tributyltin, a more readily bioavailable form of Sn. In the same species, unexpectedly high tissue-Cu concentrations were characteristic of very anoxic in sediments and tissue And As and Pb concentrations were suppressed in sediments having high concentrations of Fe oxides. Under field conditions, examples of deleterious effects on benthic organisms that can be attributed to specific metallic pollutants are comparatively rare. Effects of tributyltins from antifouling paints on oysters and neogastropods have been documented and their toxicity has undoubtedly led to environmental degradation in many UK estuaries and coastal areas. In estuaries contaminated with metal-mining wastes, the effects of Cu and Zn on species distribution can be observed, but they are generally less obvious than would be predicted from experimental data. Effects are ameliorated by the induction of metal tolerance mechanisms in some species and in others by the appearance of tolerant strains. The induction of metal detoxification systems involving the formation of granules or metal-binding proteins leads in some species to tissue concentrations that are orders of magnitude higher than normal. For example, high concentrations of Cd and Ag have been found in some species from the Severn Estuary, although there is no unequivocal evidence that either metal has caused deleterious effects on benthic populations. On the other hand, experimental studies with Ag, Cd, Cr, Cu, Hg and Zn show that they are toxic to some species at environmentally realistic levels. Since pollutants rarely occur singly, it is likely that in many moderately contaminated estuaries metals contribute to the stress to organisms caused by substances requiring detoxification. There has been much speculation over the years concerning the biomagnification of metals with increasing trophic levels along food chains. Whilst animals having higher metal concentrations than their prey are sometimes found, the only consistent evidence of biomagnification concerns methylmercury. When estuarine birds are considered, there are relatively few instances in which deleterious effects can unequivocally be attributed to metals or their compounds. However, the Mersey bird kill was attributable to alkyllead pollution from industry. Among other organometals, methylmercury has proved toxic to birds but, so far, no evidence for the toxicity of tributyltin has been reported. However, the compound may have affected bird populations through its effects on the abundance of prey organisms, particularly estuarine molluscs. Of the inorganic forms of metals, Pb in the form of shot has caused problems in many areas and Cd, Hg and Se are suspected of causing toxic effects. There is little field evidence that birds have been affected by Ag, As, Cr, Cu or Zn individually. On the other hand, it is difficult to exclude the possibility that, additively, these metals may produce a significant effect. In part, the lack of evidence reflects the fact that relatively little research has been done. There is scope for more work on metals and organometals in estuarine birds, particularly with regard to their metabolism and their effects on juveniles and individuals subjected to stresses such as starvation.
Article
The anti-inflammatory activity of topical nanocrystalline silver cream was assessed and compared with the effects of topical steroids and currently available immunosuppressants using a guinea pig model of allergic contact dermatitis. Dermatitis was induced with dinitrochlorobenzene and treated with different concentrations of nanocrystalline silver, medium and high potency steroids, tacrolimus and pimecrolimus, or appropriate vehicles once daily for 5 days. Erythema was evaluated daily (on a score of 0 to 4, from absent to very severe) and histopathology of the skin biopsies was evaluated after 5 days of treatment. Prior to treatment, the average scores of erythema in all the groups were in the range of 3(+) to 4(+). In the no treatment and vehicles groups these scores remained at about this level for the subsequent 5 days of the study. Nanocrystalline silver reduced erythema within 1 day of treatment in a concentration-dependent manner with significant reduction at silver concentrations of 0.5% and 1% (P < 0.05) and this reduction progressed throughout the study period. Steroids and immunosuppressants produced similar decreases in erythema, with no significant differences compared to 0.5% and 1% nanocrystalline silver. In skin biopsies scored for degree of inflammatory response, effects of treatments mirrored erythema results. This study suggests that nanocrystalline silver cream may have therapeutic potential for topical treatment of inflammatory skin diseases.
Article
The antimicrobial activity of silver nanoparticles against E. coli was investigated as a model for Gram-negative bacteria. Bacteriological tests were performed in Luria-Bertani (LB) medium on solid agar plates and in liquid systems supplemented with different concentrations of nanosized silver particles. These particles were shown to be an effective bactericide. Scanning and transmission electron microscopy (SEM and TEM) were used to study the biocidal action of this nanoscale material. The results confirmed that the treated E. coli cells were damaged, showing formation of "pits" in the cell wall of the bacteria, while the silver nanoparticles were found to accumulate in the bacterial membrane. A membrane with such a morphology exhibits a significant increase in permeability, resulting in death of the cell. These nontoxic nanomaterials, which can be prepared in a simple and cost-effective manner, may be suitable for the formulation of new types of bactericidal materials.
Article
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.
Article
Treatment of acute burn wounds with silver sulfadiazine (SSD) has raised concern about potential silver toxicity. Numerous adverse reactions and side effects have been reported and an increasing resistance to SSD, especially in Pseudomonas strains, have motivated researchers to search for an alternative wound dressing. Recently, a silver-coated wound dressing Acticoat (Smith & Nephew, Inc.) has become available for use in burn patients. It is a three-ply dressing, consisting of an inner rayon/polyester absorptive core between two layers of silver-coated, high-density polyethylene mesh. In a moist environment, the nanocrystals of silver are released and improve the microbial control in the wound. After 1 week of local treatment with Acticoat in a young, previously healthy 17-year-old boy with 30% mixed depth burns, hepatotoxicity and argyria-like symptoms, a grayish discoloration of the patient's face, appeared. The silver levels in plasma (107 microg/kg) and urine (28 microg/kg) were clearly elevated, as well as the liver enzymes. As soon as the local application of Acticoat was aborted, the clinical symptoms and liver enzymes returned to the normal values. This is the first report on silver toxicity in a patient with 30% burns who received Acticoat for local treatment. Due to substantial experiences with adverse SSD reactions and side effects, it is appropriate to keep the possibility of a toxic silver effect in burn patients treated with Acticoat silver-coated wound dressing in mind. The silver levels in plasma and/or urine should be monitored.
Article
This study deals with cytotoxicity assays performed on an array of commercially manufactured inorganic nanoparticulate materials, including Ag, TiO(2), Fe(2)O(3), Al(2)O(3), ZrO(2), Si(3)N(4), naturally occurring mineral chrysotile asbestos and carbonaceous nanoparticulate materials such as multiwall carbon nanotube aggregates and black carbon aggregates. The nanomaterials were characterized by TEM, as the primary particles, aggregates or long fiber dimensions ranged from 2nm to 20microm. Cytotoxicological assays of these nanomaterials were performed utilizing a murine alveolar macrophage cell line and human macrophage and epithelial lung cell lines as comparators. The nanoparticulate materials exhibited varying degrees of cytoxicity for all cell lines and the general trends were similar for both the murine and human macrophage cell lines. These findings suggest that representative cytotoxic responses for humans might be obtained by nanoparticulate exposures to simple murine macrophage cell line assays. Moreover, these results illustrate the utility in performing rapid in vitro assays for cytotoxicity assessments of nanoparticulate materials as a general inquiry of potential respiratory health risks in humans.
Article
Silver is a xenobiotic element with no recognized trace metal value in the human body. It is absorbed into the body through the lungs, gastrointestinal tract, mucus membranes of the urinogenital tract, and through the skin, mainly in the form of silver protein complexes. Although silver is metabolized throughout the soft tissues, available evidence from experimental animal studies and human clinical reports has failed to unequivocally establish that it enters tissues of the central nervous system or is a cause of neurotoxic damage. Argyria characterized by deposition of particles of silver sulfide or silver selenide is the principle contraindication for using silver in medical devices or occupationally. This presents discoloration of the skin but is not regarded as a health risk or manifestation of toxicity. No evidence is available to demonstrate the toxic risk of silver to the peripheral nervous system, although silver sulfide deposits have been identified in the region of cutaneous nerves. Transitory silver sulfide deposits seen in the tissues of the blood-brain and blood-CSF barriers are mostly lysosomally bound or deposited on basement membranes or collagen without toxic effect. Silver is mostly excreted from the body in the urine and feces. Further research is indicated to evaluate the role of metal binding proteins including metallothioneins as cytoprotectants for neurological tissue.
Article
The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. Thus, the exposed population continues to increase as the applications expand. Although previous studies on silver dust, fumes, and silver compounds have revealed some insights, little is yet known about the toxicity of nano-sized silver particles, where the size and surface area are recognized as important determinants for toxicity. Thus, the inhalation toxicity of silver nanoparticles is of particular concern to ensure the health of workers and consumers. However, the dispersion of inhalable ambient nano-sized particles has been an obstacle in evaluating the effect of the inhalation of nano-sized particles on the respiratory system. Accordingly, the present study used a device that generates silver nanoparticles by evaporation/condensation using a small ceramic heater. As such, the generator was able to distribute the desired concentrations of silver nanoparticles to chambers containing experimental animals. The concentrations and distribution of the nanoparticles with respect to size were also measured directly using a differential mobility analyzer and ultrafine condensation particle counter.
Article
A detailed accounting of environmental releases of silver is presented for the year 1997, based on data from Yale University's Stocks and Flows (STAF) project and other sources. The analysis is carried out for 64 countries, eight regions, and the world. From the chemical composition and receiving media of these different releases, each emission category is assigned an environmental impact score in accordance with the Indiana Relative Chemical Hazard (IRCH) ranking system. Flows are scaled by impact and land area to form an overall semiquantitative assessment of the environmental impact of silver. Of the 64 countries, the United States has the highest gross emissions for nearly all flows to the environment. On a regional basis, Asia is the largest emitter of silver directly to land and water. In major silver-producing countries, tailings tend to have the highest environmental impact of any emissions category; in nonproducing countries, it is dissipation to land (Hong Kong having the highest impact in this category). Globally, more than 13 Gg of silver are emitted annually to the environment, with that in tailings and landfills making up almost three-fourths of the total. The utility of this method for evaluating the environmental impact of other metals is explored.
Article
Increased production of industrial devices constructed with nanostructured materials raises the possibility of environmental and occupational human exposure with consequent adverse health effects. Ultrafine (nano) particles are suspected of having increased toxicity due to their size characteristics that serve as carrier transports. For this reason, it is critical to refine and improve existing deposition models in the nano-size range. A mathematical model of nanoparticle transport by airflow convection, axial diffusion, and convective mixing (dispersion) was developed in realistic stochastically generated asymmetric human lung geometries. The cross-sectional averaged convective-diffusion equation was solved analytically to find closed-form solutions for particle concentration and losses per lung airway. Airway losses were combined to find lobar, regional, and total lung deposition. Axial transport by diffusion and dispersion was found to have an effect on particle deposition. The primary impact was in the pulmonary region of the lung for particles larger than 10 nm in diameter. Particles below 10 nm in diameter were effectively removed from the inhaled air in the tracheobronchial region with little or no penetration into the pulmonary region. Significant variation in deposition was observed when different asymmetric lung geometries were used. Lobar deposition was found to be highest in the left lower lobe. Good agreement was found between predicted depositions of ultrafine (nano) particles with measurements in the literature. The approach used in the proposed model is recommended for more realistic assessment of regional deposition of diffusion-dominated particles in the lung, as it provides a means to more accurately relate exposure and dose to lung injury and other biological responses.
Article
Wound dressings containing silver have been in widespread use for many years. However, there are few quantitative data on the systemic absorption of silver or whether there is associated clinical risk. To assess systemic silver levels when Acticoat dressings containing nanocrystalline silver were used, and to determine whether increases in such levels were associated with haematological or biochemical indicators of toxicity. A prospective, single-centre, open-label study of 30 patients with relatively small burns that required skin grafting. Serum silver levels were measured before, during and at discontinuation of the use of the Acticoat dressings, and again at 3 and 6 months following completion of treatment. The median total postoperative wound size was 12% of the total body surface area. The median time to maximum silver levels was 9 days. The median maximum serum silver level was 56.8 microg/l. The median serum level at 6 months was 0.8 microg/l. There were no haematological or biochemical indicators of toxicity associated with the silver absorption observed in this study. This study has confirmed our view that Acticoat products are safe for use on burns and they remain a standard part of treatment at our centre.
Article
The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. However, while the population exposed to silver nanoparticles continues to increase with ever new applications, silver nanoparticles remain a controversial research area as regards their toxicity to biological systems. In particular, the oral toxicity of silver nanoparticles is of particular concern to ensure public and consumer health. Accordingly, this study tested the oral toxicity of silver nanoparticles (60 nm) over a period of 28 days in Sprague-Dawley rats following Organization for Economic Cooperation and Development (OECD) test guideline 407 with Good Laboratory Practice (GLP) application. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose group (30 mg/kg), middle-dose group (300 mg/kg), and high-dose group (1000 mg/kg). After 28 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathological examination and silver distribution study. The male and female rats did not show any significant changes in body weight relative to the doses of silver nanoparticles during the 28-day experiment. However, some significant dose-dependent changes were found in the alkaline phsophatase and cholesterol values in either the male or female rats, seeming to indicate that exposure to over more than 300 mg of silver nanoparticles may result in slight liver damage. There were no statistically significant differences in the micronucleated polychromatic erythrocytes (MN PCEs) or ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Therefore, the present results suggest that silver nanoparticles do not induce genetic toxicity in male and female rat bone marrow in vivo. Nonetheless, the tissue distribution of silver nanopaticles did show a dose-dependent accumulation of silver content in all the tissues examined. In particular, a gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in the female kidneys when compared with the male kidneys.
Article
The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. However, despite the continuing increase in the population exposed to silver nanoparticles, the effects of prolonged exposure to silver nanoparticles have not been thoroughly determined. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during 90 days of inhalation exposure to silver nanoparticles. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of 0.7 x 10(6) particles/cm(3) (low dose), 1.4 x 10(6) particles /cm(3) (middle dose), and 2.9 x 10(6) particles /cm(3) (high dose) for 6 h/day in an inhalation chamber for 90 days. The lung function was measured every week after the daily exposure, and the animals sacrificed after the 90-day exposure period. Cellular differential counts and inflammatory measurements, such as albumin, lactate dehydrogenase (LDH), and total protein, were also monitored in the acellular bronchoalveolar lavage (BAL) fluid of the rats exposed to the silver nanoparticles for 90 days. Among the lung function test measurements, the tidal volume and minute volume showed a statistically significant decrease during the 90 days of silver nanoparticle exposure. Although no statistically significant differences were found in the cellular differential counts, the inflammation measurements increased in the high-dose female rats. Meanwhile, histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, such as infiltrate mixed cell and chronic alveolar inflammation, including thickened alveolar walls and small granulomatous lesions. Therefore, when taken together, the decreases in the tidal volume and minute volume and other inflammatory responses after prolonged exposure to silver nanoparticles would seem to indicate that nanosized particle inhalation exposure can induce lung function changes, along with inflammation, at much lower mass dose concentrations when compared to submicrometer particles.
Environmental and Human Health Risks of Aerosolized Silver Nanoparticles Silver coated dressing acticoat caused raised liver enzymes and argyria-like symptoms in burn patient Effect on exposure to silver Vlachou E nanocrystalline silver dressings on burns: A study of systemic silver absorption
  • E Marina
  • Linsey
  • M Trop
  • M Novak
  • S Rodl
  • B Hellbom
  • W Kroell
  • W Goessler
  • E Chipp
  • E Shale
  • Yt Wilson
  • R Papini
  • Moiemen
Marina E, Linsey CM (2010). Environmental and Human Health Risks of Aerosolized Silver Nanoparticles . Journal of the Air & Waste Management Association, 60:770-781. Trop M, Novak M, Rodl S, Hellbom B, Kroell W, Goessler W (2006). Silver coated dressing acticoat caused raised liver enzymes and argyria-like symptoms in burn patient. Journal of Trauma-Injury Infection & Critical Care, 60: 648-652. Effect on exposure to silver Vlachou E, Chipp E, Shale E, Wilson YT, Papini R, Moiemen NS (2007). nanocrystalline silver dressings on burns: A study of systemic silver absorption. Burns, 33: 979-985
Topical therapy for burns Critical observations on the neurotoxicity of silver
  • Ww Monafo
  • Freedman
Monafo WW, Freedman B (1987). Topical therapy for burns. Surgical Clinics of North America, 67: 133-145. Lansdown AB (2007). Critical observations on the neurotoxicity of silver. Critical Reviews in Toxicology, 37:237-250