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Solubility studies of silver sulfonamides.

The solubilities of silver sulfapyridine, silver sulfamethazine, and silver sulfamethizole as a function of pH were determined in nitric acid-potassium nitrate, acetate, and sulfonic acid buffers. All silver sulfonamides showed an increase in solubility with increasing hydrogen-ion concentration, a behavior which closely paralleled the protonation of the p-amino function of the sulfonamide. A silver-ion selective electrode was used to measure silver-ion concentration in solution and the methods of known subtraction and known addition were used to measure total silver. Both silver sulfamethizole and silver sulfamethazine were ionized completely in solution. Silver sulfapyridine was ionized completely only in the more acidic pH 2-3 range. A comparison of the physical properties of the silver salts for which mortality studies were available revealed a unique set of properties for silver sulfadiazine.

Hydrogen-Ion Concentration↗

Accumulation of silver from drinking water into cerebellum and musculus soleus in mice.

In spite of the general toxicity, ecotoxicity and sparsely known metabolism of silver, WHO allows silver ions (Ag) up to 0.1 mg/l in drinking water disinfection. In order to determine the accumulation and distribution of silver in a mammalian body, mice were given for 1 and 2 weeks drinking water containing a 3-fold lower concentration, namely 0.03 mg/l silver ions as silver nitrate labelled with 110mAg. The silver concentrations in different tissues were analysed by gamma radioactivity. The saturation of tissues with silver seems to occur quickly, as there were no statistical differences between silver contents of mice tissues in spite of the study design that mice were administered silver for 1 or 2 weeks. The highest concentrations were found in musculus soleus (m. soleus), cerebellum, spleen, duodenum, and myocardial muscle in the rank order. Concentrations of silver in musculus gastrocnemius (m. gastrocnemius) were found to correlate negatively with cerebrum and positively with blood and kidneys. The accumulation of silver into organs and tissues important in motor functions may be of relevance especially in emergency and catastrophe situations in which accurate motor functions may be critical. A re-evaluation of the present recommendations on the use of silver salts for disinfection of drinking water might be necessary.

Animals↗

Comparison of adhesion of the food spoilage bacterium Shewanella putrefaciens to stainless steel and silver surfaces.

AIMS: To compare the number of attached Shewanella putrefaciens on stainless steel with different silver surfaces, thus evaluating whether silver surfaces could contribute to a higher hygienic status in the food industry. METHODS AND RESULTS: Bacterial adhesion to three types of silver surface (new silver, tarnished silver and sulphide-treated silver) was compared with adhesion to stainless steel (AISI 316) using the Malthus indirect conductance method to estimate the number of cfu cm(-2). The number of attached bacteria on new silver surfaces was lower than on steel for samples taken after 24 h. However, this was not statistically significant (P > 0.05). The numbers of attached bacteria were consistently lower when tarnished silver surfaces were compared with stainless steel and some, but not all, experiments showed statistical significance (P < 0.05). Treating new silver with sulphide to reproduce a tarnished silver surface did not result in a similar lowering of adhering cells when compared with steel (P > 0.05). CONCLUSIONS: New or tarnished silver surfaces caused a slight reduction in numbers of attached bacteria; however, the difference was only sometimes statistically significant. SIGNIFICANCE AND IMPACT OF THE STUDY: The lack of reproducibility in differences in numbers adhering to the different surfaces and lack of statistical significance between numbers of adhered viable bacteria do not indicate that the tested silver surfaces can be used to improve hygienic characteristics of surfaces in the food industry.

Bacterial Adhesion↗

Justifying the need to prescribe limits for toxic metal contaminants in food-grade silver foils.

The use of silver foils in various food preparations is a common practice in Middle Eastern and South East Asian countries. The FAO/WHO Joint Expert Committee on Food Additives (JECFA) has included silver in the list of food additives, but specifications were not prepared. Indian food legislation has included food-grade silver foil and laid down a purity requirement of 99.9%. This leaves an unspecified margin of 0.1% or 1000 microg g(-1) for contaminants. Therefore, a study to investigate the levels of metallic contaminants in food-grade silver foil was undertaken. Of 178 foils analysed, 161 (90%) contained silver, whilst 10% were fraudulently made up of aluminium. In the case of silver foils, 46% of the samples adhered to the desired purity requirement of 99.9%, while 54% had a lower silver content. Copper was present in 86.3% of the silver foils, while chromium, nickel and lead contamination was found in over 54% of samples. Cadmium levels were detected in 28% of the silver foils and manganese was present in 6.8% of samples. In silver foils showing metal contaminants, average levels were found for nickel (487 microg g(-1)), lead (301 microg g(-1)), copper (324 microg g(-1)), chromium (83 microg g(-1)), cadmium (97 microg g(-1)) and manganese (43 microg g(-1)), which being appreciable justify the need to prescribe limits for some metals in food-grade silver foil as well as for silver powder used in confectioneries and medicinal preparations. The work reported here should encourage manufacturers to use high-purity raw materials and take suitable precautions to reduce unwarranted exposure of consumers to toxic metal contaminants.

Aluminum↗

Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I) to Daphnia magna. Part 2: toxicity results.

The protective effect of reactive sulfide against AgNO3 toxicity to Daphnia magna neonates was studied. Acute (48-h) toxicity tests were performed in the absence (<5 nM) and presence of low (approximately 25 nM) and high (approximately 250 nM) concentrations of zinc sulfide clusters under oxic conditions. In both the presence and the absence of sulfide, lower mean lethal concentration (LC50) values were observed when measured as opposed to nominal silver concentrations were used in calculations. This reflected the fact that measured total silver concentrations were lower than nominal concentrations due to losses of silver from solution observed during the experiment. High concentration (approximately 250 nM) of sulfide completely protected against toxicity up to the highest silver concentration tested (2 microg/L [19 nM]) with measured silver data. In the presence of environmentally realistic levels of sulfide (approximately 25 nM) in receiving waters, acute silver toxicity was reduced by about 5.5-fold. However, when filtered (0.45 microm) silver concentrations alone were considered, toxicity (48-h LC50) was similar in the absence (0.22 microg/L) and presence (0.28 microg/L) of sulfide. The difference between measured total and filtered silver was attributed to chemisorption of the metal sulfide onto the membrane filter and provides evidence that the toxic fraction of silver is that which is unbound to sulfide. Accumulation of silver was greater in daphnids exposed to silver in the presence of sulfide than in its absence, even though a toxic effect was not observed under these conditions. In this case, silver appears to be incorporated by daphnids rather than merely adsorbed on the surface. Our results point out the need to incorporate sulfide into the acute biotic ligand model and to assess its potentially large role in preventing chronic toxicity.

Adsorption↗

Opposite staining effect of two silver-staining techniques on sister chromatids.

Opposite differential staining between sister chromatids was obtained by two silver-staining techniques on chromosomes replicated twice in medium containing 5-bromodeoxyuridine (BrdU) and pretreated with Hoechst plus black light. Both silver-nitrate and silver-carbonate staining were affected by chemical extraction and enzyme digestion of chromosomal proteins. Prestaining of silver nitrate or silver carbonate also blocked the fluorescences of protein dyes. However, removal of chromosomal DNA affected the silver-carbonate but not the silver-nitrate staining; the fluorescences of DNA dyes were blocked by the prestaining of silver carbonate but not silver nitrate. Chromosomal protein labelling was released only slightly and its relative amount between BrdU bifilarly substituted and unifilarly substituted chromatids was unchanged during pretreatment of Hoechst plus black light. We speculate that chromosomal non-histones are the targets for silver-nitrate stain, and DNA-non-histone complexes for silver-carbonate stain.

Animals↗

Silver-doped sol-gel film as a surface-enhanced Raman scattering substrate for detection of uranyl and neptunyl ions.

A surface-enhanced Raman scattering (SERS) substrate containing silver particles was prepared by an acid-catalyzed sol-gel method. Silver nitrate was first doped into the sol-gel film followed by chemical reduction of the silver ions with sodium borohydride to produce silver particles. This silver-doped sol-gel substrate exhibits strong enhancement of Raman scattering from adsorbed uranyl ions with a detection limit of 8.5 x 10(-8) M, which is comparable to existing methods of uranyl detection such as spectrophotometry, fluorometry, and a SERS method based on ligand-modified solution silver colloids. However, in the present method, no preconcentration steps, chromogens, or complexing ligands are needed. Compared with the SERS method using Ag colloidal sols, the silver-doped sol-gel film has the advantage that the silver particles trapped in the sol-gel matrix are much more stable than Ag colloids in liquid media. Furthermore, porous silica sol-gel materials are known to have affinities toward many inorganic and organic molecules. The enhanced adsorption affinities could also lead to the increased SERS sensitivity. The performance of the new silver-doped sol-gel substrate was evaluated with uranyl ions and compared to that of a SERS substrate based on silver-coated silica beads prepared by vacuum deposition. The detection limit for the silver-doped sol-gel film was 104 times lower than that for the silver-coated silica beads. The sol-gel substrate was further used to obtain, for the first time, the surface-enhanced Raman spectrum of neptunyl ions in dilute aqueous solutions.

Journal Article↗

Formation process of silver-polypyrrole coaxial nanocables synthesized by redox reaction between AgNO3 and pyrrole in the presence of poly(vinylpyrrolidone).

We have recently demonstrated a one-step process to fabricate silver-polypyrrole (PPy) coaxial nanocables (Chen, A.; Wang, H.; Li, X. Chem. Commun. 2005, 14, 1863). The formation process of silver-PPy coaxial nanocables is discussed in this article. It was found from the results of TEM and SEM images that large numbers of silver atoms were formed when AgNO3 was added to a pyrrole solution. Then silver atoms transform to silver-PPy nanosheets with regular morphology, which will connect together to be more stable. Silver-PPy nanocables will be able to grow at the expense of the silver-PPy nanosheets. Poly(vinylpyrrolidone) (PVP) plays crucial roles in this process: as a capping agent to form silver nanowires, and as a dispersant of pyrrole monomers, which can influence the site at which pyrrole monomer exists. On the basis of experimental analysis, the possible mechanism was proposed. Because of the effect of PVP, silver ions and pyrrole monomers are apt to be adsorbed at the [111] and [100] facets of silver nanosheets, respectively. Obvious polymerization will take place on the boundary of the [111] and [100] facets. The PPy layer stays stable on the [100] facets. Meanwhile, newly formed silver atoms and silver nanosheets will further ripen and grow on the [111] facets. In a word, the morphology of final products and the formation process are determined by the reaction site between AgNO3 and the pyrrole monomer, which is influenced by PVP.

Journal Article↗

Do burn patients have a silver lining?

Silver-containing pharmacological preparations have been used for many years in the prophylaxis and management of burn wound sepsis and, more recently, 1 per cent silver sulphadiazine cream (SSD) has been the treatment of choice for such problems. A prospective clinical study has been undertaken to determine the absorption and effects of the silver ion from SSD, with particular reference to hepatic and renal function. Twenty-two patients were studied. The silver assay was done by atomic absorption spectrophotometry with an attached graphite furnace. The detection level was 0.5 micrograms/l. The precision at 3.5 micrograms/l was 4.8 per cent and at 8.5 micrograms/l was 2.8 per cent. Silver was rapidly absorbed through the burn wound and serum silver levels were elevated in 20 patients. Silver was found to be deposited biochemically and electronmicrographically in the liver and kidneys of the only patient who died in the study group. Early hepatic dysfunction was present in all burns greater than 10 per cent total body surface area. Liver and renal function tests did not correlate with serum silver levels. A urinary threshold to silver excretion was seen at a serum silver level of 100 micrograms/l. This study demonstrates that silver is rapidly absorbed through burn wounds, is deposited in large amounts throughout the body but appears safe when used in the treatment of moderate burns. Whether the very high levels recorded in the subject who died were inherently detrimental will remain a matter for speculation.

Absorption↗

Effects of ligand-bound silver on Ceriodaphnia dubia.

In aqueous media, ionic silver concentrations are low and transport occurs in the colloidal phase. In the aquatic environment, silver forms 1:1 complexes with thiol-containing compounds such as cysteine and glutathione. In order to quantitatively characterize the risk associated with silver in aquatic ecosystems, the bioavailabilities and toxicities of silver cysteinate and silver glutathionate were characterized. Static renewal bioassays were conducted with Ceriodaphnia dubia to estimate chronic toxicity, using mortality and reproduction as endpoints. Silver nitrate was the most lethal compound, with a median lethal concentration (8-d LC50) of 0.32 microg Ag/L (95% confidence interval [CI] = 0.19-0.54). The 48-h LC50 for AgNO3 was 0.5 microg/L and did not change significantly through 8 d. The presence of food in the bioassay did not change the 48-h LC50 for AgNO3. Silver glutathionate (AgGSH) and silver cysteinate (AgCys) induced less mortality during the 8-d bioassay. Silver cysteinate appeared to have the greatest effect on fecundity, with a no-observable-effect concentration (NOEC) less than 0.001 microg/L. Silver nitrate and AgGSH had lowest-observable-effect concentration (LOEC) values (nominal concentrations) of 0.01 and 0.6 microg/L, respectively. Results indicate that the ligand-bound silver in these laboratory studies is bioavailable and impairs reproduction of C. dubia at low aqueous concentrations.

Animals↗

Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat.

Incisional wounds 15 mm long were induced surgically in the back skin of young adult Wistar rats. They were sutured and used as an experimental model in the therapeutic evaluation of daily applications of 0.5 mL of silver nitrate (SN) at 0.01, 0.1 or 1.0% w/v aqueous solution, or 0.5 g silver sulphadiazine (SSD) over a 10-day period. Control wounds received deionized water only. The silver preparations were not toxic but SN did stain the hair and superficial layers of the stratum corneum. The wounds remained microbiologically clean. Wounds exposed to SN (0.1 or 1.0%) or SSD healed more rapidly than controls. From about the fourth day of treatment, we noted a more rapid exteriorization of sutures, improved wound closure and an earlier loss of scabs and wound debris. Silver treatment appeared to reduce the inflammatory and granulation tissue phases of healing and enhance epidermal repair. Silver from SN was deposited as silver sulphide in extrafollicular hair shafts and superficial aspects of the skin and wound debris but not at deeper levels. Silver uptake was four-fold higher in damaged skin than in intact tissue. SSD was absorbed by intact and wounded skin but the silver did not precipitate as silver sulphide and its localization in the tissue is not known. Uptake of silver from SN or SSD was associated with changes in the concentrations of zinc and calcium in the skin. Zinc levels were depressed during the inflammatory and proliferative phases of healing and then increased. Zinc concentrations had normalized by 10 days when wound healing was achieved. Calcium levels remained higher than normal throughout the observation period. The mechanism of action of silver in advancing wound healing in the rat is unclear. Its ability to reduce the inflammatory and granulation phases of healing, and to invoke metallothionein production and influence metal ion binding are possibly important.

Animals↗

Effect of increasing silver content in phosphate-based glasses on biofilms of Streptococcus sanguis.

Silver is a powerful antibacterial ion that may be useful for dealing with localized infections, such as periodontitis. However, the use of silver in this role could be significantly improved by the development of an effective means of delivery. Phosphate-based glasses may provide a means of delivering the ions in a controlled manner. In our study, we have examined the effect of increasing silver content in phosphate-based glasses on biofilms of Streptococcus sanguis. Glasses of nominally the same dissolution rate were doped with silver at 1, 5,10, and 15 mol % and the number of colony-forming units (CFUs) determined after 6 and 24 h in a constant depth film fermenter (CDFF). The 1 mol % silver showed little change between 6 and 24 h. However, only 0.5 log CFUs were present on the glass containing 5 mol % at 6 h, and this reduced to virtually zero at 24 h. Few viable bacteria were found on the 10 mol % glass at both 6 and 24 h. The 15 mol % glass was investigated in this experiment, but no viable counts were detected. In a second set of experiments, glasses with 10 and 15 mol % silver were tested in the CDFF for up to 192 h. For the 10 mol % silver glass, there was approximately 0.8 log CFUs on this glass, which dropped to almost zero at 50 h. This was approximately 1.5-2.0 log reduction in CFUs compared to controls, and this difference was maintained for the first 50 h. After 50 h, there was a slow increase in the CFUs on all samples. However, CFUs on the 10 mol % silver glass were still suppressed up to 192 h compared to the controls. However, both controls also exhibited a decrease in viable counts at 50 h; this may have been due to carryover of silver into the control sample holders. However, this was minimized by the specimen layout in the CDFF and by having gaps between specimen sets. For the 15 mol % silver glass, counts for both this glass and the controls decreased to virtually zero between 24 and 48 h, but the numbers slowly increased up to 170 h, but the number of CFUs was suppressed compared to the 10 mol % glass at the same time point. The decrease seen is clearly the effect of the silver ions; however, the slow increase in CFUs may be accounted for by the biofilms forming thick layers on top of the glass discs inhibiting the release of ions from the glass by forming a "sacrificial layer" through which further ions have to diffuse.

Anti-Bacterial Agents↗

Exogenous silver in dorsal root ganglia, peripheral nerve, enteric ganglia, and adrenal medulla.

Following intraperitoneal (i.p.) or oral administration of silver salts, the anatomic distribution of silver in the peripheral nervous system (PNS) has been studied. The structures examined were dorsal root ganglia, peripheral nerve (N. ischiadicus), enteric ganglia, and adrenal medulla. Four days after an i.p. injection of silver lactate, silver deposits were found in these structures. The silver content remained stable during the observation period (45 days). The localization of silver deposits in the orally treated animals was independent of the administered silver salt (silver nitrate or silver lactate). The silver deposits in neurons and chromaffin cells were located in the cytoplasm. In all organs silver was present in large amounts in connective tissue membranes, macrophage-like cells, vascular basal laminae, and supporting cells. Satellite cells of the dorsal root ganglia were always heavily stained, while less stain was present in Schwann cells of the peripheral nerves. Intracellular deposits were invariably located in lysosomes, whereas extracellular grains were found in connective tissue fibers and basement membranes.

Adrenal Medulla↗

Autointerference in silver accumulation in macrophages without affecting phagocytic, migratory or interferon-producing capacity.

Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 microM to 20 microM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon-producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/phagosome system is suggested as a basis for the phenomenon.

Animals↗

Silver accumulation in Daphnia magna in the presence of reactive sulfide.

Previously, we demonstrated a higher silver body burden when Daphnia magna were exposed to silver in the presence of environmentally relevant concentrations (25 nM) of reactive sulfide, but the explanation was unclear. In the present study, D. magna were exposed to AgNO3 (0.93 microg Ag/L=8.6 nM as a mixture of cold Ag and (110m)Ag) in synthetic water in either the presence or absence of 25 nM sulfide as zinc sulfide clusters. After 1-h exposure, daphnids were transferred to clean water for up to 5-h depuration. At different times of Ag exposure and depuration, daphnids were randomly sampled for whole body silver burden. Also, after 1 h, daphnids were sampled for silver accumulation in "gills" (small organs on the thoracic appendages), digestive tract, and carcass. Other groups were exposed to the same silver and sulfide concentrations for 1 h and then sampled for whole-body autoradiography. Silver body burden was about two-fold higher in the presence of sulfide. A two-fold increase in silver burden in "gills" and digestive tract, but not in carcass, was also observed in the presence of sulfide. Absolute differences due to sulfide were greatest in digestive tract and explained most of the difference in whole body burden. Transfer to clean water caused a significant drop in silver concentration in whole body and all compartments to similar levels in the two groups after 5-h depuration. These results indicate that the higher silver body burden observed in the presence of sulfide is mainly due to sulfide-bound silver in the digestive tract of the daphnids. This conclusion is supported by autoradiography, which showed a high concentration of silver in the digestive tract of daphnids exposed to Ag/sulfide.

Animals↗

Effects of water hardness on the physiological responses to chronic waterborne silver exposure in early life stages of rainbow trout (Oncorhynchus mykiss).

Early life stages of rainbow trout were exposed to 0, 0.1 and 1 microg/L Ag (as AgNO(3)) in very soft water (2mg/L CaCO(3)), moderately hard water (150 mg/L CaCO(3)) and hard water (400mg/L CaCO(3)) of low dissolved organic carbon concentration (0.5mg C/L) from fertilization to swim-up (64 days) under flow-through conditions, and monitored for whole embryo/larval silver accumulation, Na(+) and Cl(-) concentrations, Na(+) uptake and Na(+)K(+)-ATPase activity. The objective of the study was to investigate potential protective effects of water hardness on the physiological responses to chronic silver exposure. In the absence of silver, there was little effect of hardness on the ionoregulatory parameters studied, though higher hardness did improve survival post-hatch. At all three water hardness levels, whole embryo/larval Na(+) uptake was low and relatively constant prior to 50% hatch, but dramatically increased following 50% hatch, whereas Na(+)K(+)-ATPase activity steadily increased over development. Whole embryo/larval Na(+) and Cl(-) concentrations were low and constant prior to 50% hatch, but following 50% hatch Na(+) concentration increased, while Cl(-) concentration decreased. Following 50% hatch, exposure to 0.1 and 1 microg/L Ag resulted in a decrease in whole embryo/larval Na(+) concentration, Cl(-) concentration, Na(+) uptake and Na(+)K(+)-ATPase activity, indicating that the mechanism of chronic silver toxicity involves an ionoregulatory disturbance, and is similar to the mechanism of acute silver toxicity. An increase in water hardness reduced or eliminated the effect of silver on these parameters while enhancing survival, suggesting that the nature of the protective effect of hardness involves effects on the ionoregulatory disturbance associated with silver exposure. An increase in water hardness did not fully protect against the accumulation of silver associated with silver exposure. These results suggest that it may be possible to model chronic silver toxicity using a biotic ligand type model, and that a physiologically based model may be more appropriate because Na(+)K(+)-ATPase activity or Na(+) uptake is an endpoint for prediction rather than whole embryo or larval silver accumulation.

Animals↗

Toxicity of silver to two freshwater algae, Chlamydomonas reinhardtii and Pseudokirchneriella sub-capitata, grown under continuous culture conditions: influence of thiosulphate.

In a test of the biotic ligand model (BLM), the uptake and toxicity of silver, in the absence or presence of the inorganic ligand, thiosulphate, were assessed for two freshwater green algae, Chlamydomonas reinhardtii and Pseudokirchneriella sub-capitata, using turbidostat continuous cultures. In the initial experiments, run in the absence of thiosulphate, the influent Ag concentration was varied from 0 to 75 nM in steps; for each influent concentration, silver uptake was calculated and the algal growth rate was determined. Silver uptake rates at low Ag concentrations were similar for both algae (e.g., 14-19 nmolm(-2)h(-1), for influent Ag(+) concentrations of approximately 9 nM) but at higher exposures uptake by P. sub-capitata exceeded that of C. reinhardtii. Despite this higher uptake rate, in the absence of thiosulphate P. sub-capitata was not more sensitive to free silver; 50% growth inhibition was reached at influent free Ag(+) concentrations of 15+/-7 and 22+/-13 nM for C. reinhardtii and P. sub-capitata, respectively. In the second series of experiments, the free Ag(+) concentration was held constant ( approximately 9 nM in the influent; 2-3 nM in the effluent) while the concentration of the silver thiosulphate complex, AgS(2)O(3)(-), was increased from 9 to 90 nM in steps. Under such conditions, the BLM would predict that silver uptake and toxicity should remain constant. On the contrary, both silver uptake and silver toxicity increased, indicating that the anionic silver thiosulphate complex enters the algal cells via a membrane-bound sulphate transporter and contributes to uptake and toxicity. However, for both algae there were indications that silver assimilated in this manner was somewhat less toxic to the algal cell than silver that entered via cation transport only. Physiological indicators of stress revealed possible different intracellular targets for these two freshwater algae, proteins and enzymes for C. reinhardtii and the photosynthetic apparatus for P. sub-capitata.

Animals↗

In vitro cytotoxity of silver: implication for clinical wound care.

In this study, we look at the cytotoxic effects of silver on keratinocytes and fibroblasts. We have assessed the viability of monolayer cultures using the MTT and BrdU assays. The composition of the culture medium and also the culture technique were modified to assess the effects of culture 'environment' on the susceptibility of the cells to the toxic action of silver. Further in vitro, experiments were performed using tissue culture models to allow cellular behavior in three dimensional planes which more closely simulated in vivo behavior. The silver source was both silver released from silver nitrate solution but also nanocrystalline silver released from a commercially available dressing. The results show that silver is highly toxic to both keratinocytes and fibroblasts in monolayer culture. When using optimized and individualized culture the fibroblasts appear to be more sensitive to silver than keratinocytes. However, when both cell types were grown in the same medium their viability was the same. Using tissue culture models again indicated an 'environmental effect' with decreased sensitivity of the cells to the cytotoxic effects of the silver. Nevertheless in these studies the toxic dose of skin cells ranging from 7 x 10(-4) to 55 x 10(-4)% was similar to that of bacteria. These results suggest that consideration of the cytotoxic effects of silver and silver-based products should be taken when deciding on dressings for specific wound care strategies. This is important when using keratinocyte culture, in situ, which is playing an increasing role in contemporary wound and burn care.

3T3 Cells↗