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This study presents the case of a man who developed a temporary and asymptomatic blue tongue. The dyschromia occurred following topical contact with gelato that contained Food, Drug, and Cosmetic (FD&C) blue dye no. 1. The etiology of a blue tongue is either congenital (in individuals with blue rubber bleb nevus syndrome) or acquired. Acquired blue dyschromia of the tongue results from either endogenous conditions or exogenous agents. The endogenous conditions include not only benign (angioleiomyoma, hemangioma, melanocytic macule, and varicosities) and malignant (ovarian carcinoma) tumors but also reactive lesions (intravascular papillary endothelial hyperplasia and mucocele) and systemic disorders (argyria, cyanosis, methemoglobinemia, primary adrenal insufficiency, and thrombocytosis). Exposure to the exogenous agents can either be systemic (ingestion of medications such as haloperidol, metoclopramide, minocycline, prochlorperazine, and risperidone), traumatic (tattoo resulting from the implantation of dental amalgam), or topical (contact with FD&C blue dye no. 1). Clinical clues to the topical exogenous etiology in the reported individual included not only the fact that the dyschromia spared both the lateral aspects and the tip of the tongue but also the observation that the blue color focally appeared on his upper lip.

Argyria is a rare but cosmetically distressing and difficult-to-treat condition for which quality-switched (Q-switched) lasers have been most commonly employed. However, at least one previous report suggests that the picosecond alexandrite laser may also serve as a successful treatment modality. Herein, we present a side-by-side comparison of a picosecond 755-nm alexandrite laser and a Q-switched 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser in the treatment of argyria. Our results reveal an equivalent success of the picosecond alexandrite when compared to the more commonly employed Q-switched Nd:YAG, suggesting that the picosecond 755-nm alexandrite laser is equally effective in the treatment of argyria.

Colloidal silver used as a suspension for (alternative) therapeutic purposes or silver exposure due to environmental or working conditions can lead to irreversible deposits of silver granules in the skin (bluish-gray hue of the skin), mucosa, cornea, retina and internal organs. Silver-induced discoloration of the conjunctiva should therefore be taken into account when a bluish-gray discoloration raises the suspicion of conjunctival melanoma.

Silver is used as a water disinfectant in hospital settings as well as in purifiers for potable water. Although there are no strict regulations on the concentration of silver in water, adverse effects such as argyria and respiratory tract irritation have been correlated to excess silver consumption. Based on this, the levels of silver in water are recommended to be maintained below 100 ppb to ensure safety for human consumption. In this work, we present a silver sensor for use in aqueous media that utilizes bathocuproine, a silver selective chromophore, adsorbed onto few-layer graphene (FLG) flake networks for the chemiresistive detection of silver. Complexation of silver to bathocuproine modulates the conductivity of the FLG film, which can be probed by applying a small voltage bias. The decrease in resistance of the film correlates with the concentration of silver in solution between 3 ppb and 1 ppm. Exposing the sensor to a lower pH resets the sensor, allowing it to be reused and reset multiple times. This sensor demonstrates a new pathway to chemiresistive cation sensing using known selective complexing agents adsorbed onto graphitic thin films. This concept can be expanded to the detection of other relevant analytes in domestic, industrial and environmental water sources.

Silver is used in a wide range of products, and during their production and use, humans may be exposed through inhalation. Therefore, it is critical to know the concentration levels at which adverse effects may occur. In rodents, inhalation of silver nanoparticles has resulted in increased silver in the lungs, lymph nodes, liver, kidney, spleen, ovaries, and testes. Reported excretion pathways of pulmonary silver are urinary and faecal excretion. Acute effects in humans of the inhalation of silver include lung failure that involved increased heart rate and decreased arterial blood oxygen pressure. Argyria—a blue-grey discoloration of skin due to deposited silver—was observed after pulmonary exposure in 3 individuals; however, the presence of silver in the discolorations was not tested. Argyria after inhalation seems to be less likely than after oral or dermal exposure. Repeated inhalation findings in rodents have shown effects on lung function, pulmonary inflammation, bile duct hyperplasia, and genotoxicity. In our evaluation, the range of NOAEC values was 0.11–0.75 mg/m3. Silver in the ionic form is likely more toxic than in the nanoparticle form but that difference could reflect their different biokinetics. However, silver nanoparticles and ions have a similar pattern of toxicity, probably reflecting that the effect of silver nanoparticles is primarily mediated by released ions. Concerning genotoxicity studies, we evaluated silver to be positive based on studies in mammalian cells in vitro and in vivo when considering various exposure routes. Carcinogenicity data are absent; therefore, no conclusion can be provided on this endpoint.

The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles particles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or non-silver matrix constituents.

Silver nanoparticles (AgNPs) are effective antimicrobial agents however excess release of silver causes argyria and argyrosis. An strategy to avoid these detrimental side effects is immobilization of AgNPs on several organic and inorganic substrates. Herein, we propose immobilization of AgNPs on TiO

Silver cutlery and serving dishes are a potential source of exposure of humans that was never quantified. Release of silver was assessed in vitro in an acidic solution mimicking food fluid in two conditions: i] the JRC guidelines for hot fill conditions with stable high temperature over a 2 hour-period of time, and ii] a more realistic condition with spontaneous progressive decline from 90̊C to ambient temperature over the same period of time. Massive silver 95% strips were exposed to a 5% citric acid solution: i) cooling down from 90̊C to ambient or ii) 70̊C maintained, during 2 hours. Spectrometry with optical emission was used to measure silver in solution. In the spontaneous cooling down study, the time-course of temperature was close to the Newton's law of cooling and the released quantities were detected but too low to be measured. The 70̊C exposition resulted in a non-linear release that became quantifiable after one hour of heating up to an apparent plateau at 120 min with a mean concentration [extreme] of 24.6 [22.3-26.8] μg/L. The results of the present study allow concluding that 95% silver used for cutlery and serving dishes may be released in foods. However, the extent of release depends on the condition of use. At a stable 70̊C temperature over a 2 h-period of time, silver is released in a non-linear model up to a mean concentration of 24.6 μg/L. In contrast, in conditions fitting with the routine recommendations of use, infinitesimal detectable amounts of silver were released.

An 84-year-old woman was referred to our clinic with grey discolouration of her face. She had a history of hypertension that was managed with amlodipine and olmesartan. She reported that she had ingested an ionic silver solution (1 mg/mL), which she purchased from a naturopathic practitioner, every

Recent studies have shown that silver is no longer restricted to just being found in soil and natural waters. The metal and its various forms are used in medicine as nanoparticles for various applications. After assimilating and reviewing a considerable volume of literature, it can be safely stated that silver displays different extents of bioaccumulation depending on the ecosystem involved. Aquatic ecosystems were revealed to be less prone to the toxic effects of the metal due to the buffering capacity of water and its dissolved contents. Evidence suggests that even though bioaccumulation is possible in terrestrial animals, biomagnification is not. Humans are more prone to bioaccumulation due to the use of silver nanoparticles in medicine. The toxic effects of silver are attributed to the formation of free silver (I) ions (Ag + ). Biochemical effects are brought about by interactions with proteins, deoxyribonucleic acid (DNA) and intracellular signalling pathways. Physiological effects are manifestations of biochemical effects in different regions of the body. Literature has shown that by means of physiological and biochemical effects, silver bioaccumulation gives rise to both benign and harmful disease, namely argyria, cardiovascular disease and respiratory disease.

International audience; BACKGROUND:Silver-containing dressings are considered to be safe even though there have been some reports of complications, including argyria and various organ system dysfunctions. Despite the widespread use of silver dressings, little research has been done regarding the absorption and toxicity of silver.OBJECTIVE:We aimed to study the systemic absorption of silver in patients with chronic inflammatory wounds and to determine associated factors of systemic silver absorption and evaluated its association with silver toxicity.PATIENTS AND METHOD:Prospective, longitudinal, observational, multicentre, open-label pilot study. Patients from the Dermatology Departments of Lorraine (France) with the following inclusion criteria: (i) a chronic wound of more than 6 weeks and (ii) an ulcer needing silver-containing dressing were included. Before and after 28 days of treatment, clinical characteristics of the wound were recorded; hemogram, hepatic and renal functions, albumin sera and serum silver level were measured.RESULTS:Half of the cases displayed raised levels of silver after 1 month of treatment. Predictive factors for systemic silver absorption were wound area, anaemia and malnutrition with anaemia and malnutrition confirmed on multivariate analysis. Wound vascularization may also play a role, as a higher absorption was observed in cases of wound granulation without arterial components. No toxicity was detected. This work has also emphasized the slow elimination of silver from the body.CONCLUSION:Both long-term application and iterative treatments with silver dressings should be discouraged, especially in the elderly, who often suffer from malnutrition and anaemia to avoid potential cumulative toxicity.

Skin hyperpigmentation results from increased number of epidermal melanocytes, increased synthesis of melanin, or both. Occasionally, deposition of melanin or other exogenous pigments in the deeper dermis causes changes of skin color. Facial pigment disorders include various dermatologic entities; they may also reflect organ dysfunction or metabolic conditions (e.g., pellagra, porphyria), result from deposition of metals (argyria, mercury intoxication), or be a side effect of chemicals and drugs. Postinflammatory hyperpigmentations of different origin may occur and overlap.

This chapter shows endophytic fungus Aspergillus niger that was isolated from leaves of Ficus panda for the synthesis of silver nanoparticles and to study the antibacterial activity against clinical human pathogenic microbial strains. The Ficus panda is from the family Moraceae and needs more light to have a vigorous growth. Different types of nanomaterials like copper, zinc, titanium, magnesium, gold alginate and silver have come up but silver nanoparticles have proved to be most effective because of antimicrobial efficacy against bacteria, viruses and other eukaryotic micro-organisms. Silver nanoparticles are used as drug disinfectant and have some risks as the exposure to silver can cause agyrosis and argyria also; and are toxic to mammalian cells. The first evidence of bacteria synthesizing silver nanoparticles was established using the Pseudomonas stutzeri strain that was isolated from silver mine. Nanoparticles showed significant antibacterial activity against Enterococcus sp., E. coli, Staphylococcus albus and Klebsiella pneumonia.

This report details the natural history of corneal argyrosis over 3 years using in vivo confocal microscopy to document regression of hyperreflective deposits, as well as effects on corneal nerves and endothelial cell morphology.To report the in vivo confocal microscopic features and clinical characteristics of a case of bilateral corneal argyrosis.A 52-year-old man referred to us 3 months following cautery of the palpebral conjunctiva of both eyes with a silver nitrate stick was observed over the course of 3 years, during which slit-lamp photography and in vivo confocal microscopy were performed. At the first visit, slit-lamp examination showed a light blue-green discoloration and a thick, yellow, oval discoloration in the right and left cornea, respectively. One year later, under slit-lamp examination, the right cornea appeared nearly transparent, and the discoloration in the left cornea had remarkably regressed. In vivo confocal microscopy done at that time showed highly reflective deposits in Descemet membrane of the right cornea and throughout Bowman layer, the stroma, and Descemet membrane of the left cornea. Three years later, no accumulation of silver was observed during slit-lamp examination of either eye. In vivo confocal microscopy of the right cornea did not reveal any silver deposits, and the corneal structure appeared normal. In the left cornea, some silver deposits were still evident in Descemet membrane, and alterations of corneal nerve and endothelial cell morphology were also evident.This report reviews the 3-year natural history of a patient with corneal argyrosis. In vivo confocal microscopy demonstrates that over time the corneal argyrosis gradually resolves without any treatment. However, the presence of silver in the cornea may impact the corneal nerves and endothelial cells.

A biopsy specimen from the nasal mucosa of a 37-year-old man disclosed a subepithelial accumulation of black granules mainly running parallel to the surface in the absence of any inflammatory infiltrate. Since the mucosal pigment was negative with Perls’ stain and resisted to melanin bleach, an exogenous pigmentation was suspected. The biopsy specimen had been taken because of a diffuse steel-blue pigmentation of the nasal mucosa, incidentally discovered during routine clinical examination. A diagnosis of occupational argyria of the nasal mucosa was finally made since the patient was a silver cleaner. Argyria is a rare cause of nasopharyngeal mucosal pigmentation; it is not a precancerous condition, but it can be mistaken for a melanosis or a melanocytic tumor both clinically and histopathologically. Clinicopathological correlation is mandatory, since the final diagnosis is based on a history of chronic silver exposure.

Minocycline is a derivative of tetracycline. It has been widely used in dermatology for the treatment of acne and rosacea. One of its adverse effects is pigmentation of various body tissues. Clinically, 3 main distinct types of hyperpigmentation by minocycline have been distinguished: type I, with blue-gray to black pigment on the face in areas of scarring or inflammation; type II, with blue-gray pigment on normal skin of the legs, forearms and on the shins; and type III, with a diffuse muddy-brown discoloration in areas of sun exposure. In the current report, we present the case of a 50-year old man with a history of severe acne treated with minocycline in the past, who currently complained about discoloration of his face. He had also taken colloidal silver supplements for "good health" about 16 years ago. Physical examination revealed gray-blue discoloration on the face, sclera, hard palate and back. Histologic examination showed intracellular pigment deposits in macrophages of the superficial dermis in a perivascular and an interstitial distribution. The pigment stained with Fontana-Masson and von Kossa, whereas it was Perls' iron negative. This case does not fit well into any of the previously described patterns of minocycline-related hyperpigmentation.

Medical and non-medical uses of silver are increasing. While the health benefits of silver therapy are widely claimed, few studies address the possible side effects of resistance, allergy, or skin discoloration. In this manuscript, a review of silver absorption, mechanism of action, allergy, microbial resistance and skin changes is presented. The ideal silver-delivery system is unknown. Most studies of side effects are animal or laboratory studies, which may not correlate with human experience. There is little correlation between serum silver levels, end-organ deposition and cytotoxic effects. The multiple mechanisms of antimicrobial action make true resistance unlikely. In microbes, genotypic resistance does not necessarily confer phenotypic resistance. Most cases of argyria occur from occupational exposure or from ingestion of colloidal silver rather than from topical application. Although toxicity, resistance and chronic skin changes are a theoretic concern, the lack of reported side effects despite widespread silver use is reassuring.