Journal of J. Appl. Biomed.

6: 117–129, 2008
APPLIED ISSN 1214-0287
BIOMEDICINE www.zsf.jcu.cz/jab

REVIEW

Silver or silver nanoparticles: a hazardous threat to the

environment and human health?
Nagender Reddy Panyala1, Eladia María Peña-Méndez2, Josef Havel 1,3
1
Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
2
Department of Analytical Chemistry, Nutrition and Food Chemistry, Faculty of Chemistry, University of La
Laguna, Tenerife, Spain
3
Department of Physical Electronics, Faculty of Science, Masaryk University, Brno, Czech Republic

Received 12th April 2008.

Revised .27th May 2008.
Published on line 23rd June 2008.

Summary
Nanotechnology is a rapidly growing science of producing and utilizing nano-sized particles that measure
in nanometers. These nanomaterials are already having an impact on health care. Now-a-days we are using
nanoproducts in various fields. Of these, silver nanoparticles are playing a major role in the field of
nanotechnology and nanomedicine.
Their unique size-dependent properties make these materials superior and indispensable as they show
unusual physical, chemical and biological properties. Silver nanoparticles have potential antimicrobial
activity towards many pathogenic microbes. Along with this antimicrobial activity, silver nanoparticles are
showing unacceptable toxic effects on human health and the environment. The chronic exposure to silver
causes adverse effects such as permanent bluish-grey discoloration of the skin (argyria) and eyes (argyrosis).
Besides argyria and argyrosis, exposure to soluble silver compounds may produce other toxic effects like
liver and kidney damage, irritation of the eyes, skin, respiratory and intestinal tract and changes to blood
cells. This review summarizes the hazardous effects of silver nanoparticles in the environment and their
toxic effects on human health.

Key words: silver nanoparticles – antimicrobial activity – argyria – argyrosis – silver toxicity

INTRODUCTION
few years has the technology existed to produce this
Only in the last few years has nano-technology begun cutting edge silver suspension. Only now has silver
to evolve into a valuable science. And only in the last arrived as the natural immune system assistant it was
in the early days of mankind when it was plentiful in
its metallic form in ground water. For the optimum
Josef Havel, Department of Chemistry, Faculty of function of body immunity, everyone needs
Science, Masaryk University, Kotlářská 2, 611 37 nano-silver circulating in their bloodstream
Brno, Czech Republic (http://www.nano-silver.com/).
 [email protected] Silver is a naturally occuring precious metal, most
 +420-549 494 114 often as a mineral ore in association with other
 +420-549 492 494 elements. It has been positioned as the 47th element
in the periodic table, having a atomic weight of 107.8
 Panyala et al.: Silver or silver nanoparticles

and two natural isotopes 106.90 Ag and 108.90 Ag Westhofen et al. (1986) observed that the affinity of
with abundance 52 and 48%. It has been used in a silver for membrane and neuronal structures and the
wide variety of applications as it has some special deposition of silver as an insoluble compound (Ag2S)
properties like high electrical and thermal induce the progression of clinical diseases like
conductivity (Nordberg and Gerhardsson 1988). generalized argyria. Argyrosis is a pathologic
Ancient civilizations used this precious metal in bluish-black pigmentation in a tissue resulting from
medicine, eating utensils, plates, cups, food the deposition of an insoluble albuminate of silver
containers, jewellery, money/coins, clothes, building (http://medical-dictionary.thefreedictionary.com/ar
materials, and as a disinfectant for water and human gyrosis).
infection. In the environment or in living organisms the
Silver metal and silver dressings, when used in silver can be present in different forms. The most
reasonable amounts, has no negative effects on the common is metallic silver, silver salts (ionic silver),
human body and it has a natural antimicrobial activity silver complexes and colloidal silver. Metallic silver
(Margaret et al. 2006, Sarkar et al. 2007) towards dissolves in acids and salts like e.g. silver nitrate is
many pathogens such as bacteria (Hill and Pillsbury formed. Aqueous solution of soluble silver nitrate
1939, Morones et al. 2005, Zhang and Sun 2007), contains silver in the form of hydrated silver cations
viruses, fungi, yeast etc. Silver salts have been used Ag(H2O)n+ which is typical “ionic silver”. However,
for the treatment of mental illness, nicotine addiction, silver cation can be complexed with various organic
gastroenteritis and infectious diseases like syphilis ligands and even if silver cation is still present in the
and gonnorrhea (Marshall and Schneider 1977, molecule, the overall charge of the complex can be
Shelley et al. 1987, Gulbranson et al. 2000, Drake et neutral. Furthermore, highly stable complexes are
al. 2005). New silver coated catheters are used known which are not dissociated at all in the solution
because they stop the infections that were common or biological liquids. Colloidal silver is a colloidal
place with the old ones (Samuel et al. 2004). To state of silver-containing particles in water with 1 nm
protect us from food poisoning, silver particles are to 1 micron silver or silver-containing particles. The
now being put in cutting boards, table tops, surface term “colloidal” was coined by English chemist
disinfectants, and refrigerators. Silver is woven and Thomas Graham (in 1800) who was later on called as
impregnated into fabrics to kill bacteria that cause “father of colloid chemistry”. Colloidal silver can be
body odor. in the form of super-fine metallic form or in the form
But ecologists have warned that widespread use of insoluble silver compounds, finally dispersed in
of such a powerful antimicrobial could have serious solution which shows small or high turbidity. Nano
negative consequences for bacteria in natural systems silver means usually nano-sized particles of
if nano-anti microbials are released in waste streams nanometre size and the term is connected to colloidal
etc. There is also growing evidence that as well as silver or identical. There are now many commercial
being toxic to bacteria, silver nanoparticles are also products, some are named as "NanoSilver". The term
highly toxic to mammalian cells (Braydich-Stolle et nano-silver refers to the nanoparticulate size of the
al. 2005, Wen et al. 2007, Gopinath et al. 2008). silver particles of 5–50 nm. Nanosilver has a more
Silver nanoparticles have been shown to damage active surface area and better porosity than
brain cells (Hussain et al. 2006), liver cells (Hussain commercial silver (Alt et al. 2004).
et al. 2005) and stem cells (Braydich-Stolle et al. The aim of this paper is to give an overview and
2005). Even with prolonged exposure to colloidal analyze the various toxic effects of silver or
silver or silver salt deposits of metallic silver under nanosilver on human health and the environment.
the skin cause skin diseases like argyria or argyrosis
(Chen et al. 2007).
Even in its bulk form, silver is extremely toxic to
fish (Hogstrand et al. 1996), algae, some plants, fungi
(Eisler et al. 1996), crustaceans and bacteria like WHAT IS NANOSILVER?
nitrogen fixing heterotrophic and soil forming
chemolithotrophic bacteria (Albright et al. 1974). NanoSilver is a commercial name for pure de-ionized
The toxicity of a metal is influenced by several water with superfine silver in suspension
factors like solubility, binding specificity to a (http://www.nano-silver.com). Nanoparticles size is
biological site, etc. The toxic effect or heavy metal from 5 to 50 nm. Most of the silver is in the form of
poisoning is defined as, “Any functional or metallic silver nano-particles. The remaining silver is
morphologic change in the body produced by an in ionic form. Because of the small size of the
ingested, injected, inhaled or absorbed drug, particles, the total surface area of the silver exposed
chemical, or biological agent”. In contrast, in solution is maximized, resulting in the highest

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 Panyala et al.: Silver or silver nanoparticles

possible effect per unit of silver (Alt et al. 2004). As irradiation, etc. (Sergeev et al. 1999, Sun and Xia
a result, a very small concentration of silver in 2002, Zhang et al. 2002, Pyatenko et al. 2004, Bogle
NanoSilver provides greater effectiveness inside the et al. 2006, Chen and Schluesener 2007). The
body than silver solutions in the colloidal form of literature (Elechiguerra et al. 2005, Jose et al. 2005,
many times greater concentration. Lok et al. 2006) demonstrated that silver
Nano-silver products are characterized by high nanoparticles with certain size ranges and shapes
percentage of silver metallic form. This is important have special interactions with bacteria and viruses.
because ionic silver becomes silver chloride in the Through all these basic physiochemical properties,
stomach or bloodstream. Solubility of silver chloride silver can easily be absorbed in cellular environments
is low. In addition, the silver chloride is less effective and it makes adhesive interactions with biological
than metallic silver. Only metallic particles survive macromolecules and can be translocated within the
the hydrochloric acid of the stomach to remain human body.
effective inside the body Silver can enter the human body through various
(http://www.nano-silver.com). portals like ingestion, inhalation of dusts or fumes
containing silver (Phalen and Morrow 1973, Furchner
et al. 1968), skin contact, contact with jewellery and
by the application of burn creams etc. Existing
SILVER CLUSTERS AND SILVER literature (Drake and Hazelwood 2005) demonstrated
NANOPARTICLES that silver also gains entry into the body through the
use of acupuncture needles (Sato et al. 1999),
Silver atoms can form under various conditions so catheters (Saint et al. 2000), dental amalgams
called clusters which can eventually further aggregate (Catsakis and Sulica 1978), or through accidental
forming silver nanoparticles. Silver clusters can be puncture wounds (Rongioletti et al. 1992).
formed e.g. by the action of laser during ablation of Silver ions may enter through various semi-open
metallic silver or silver salts. For example, charged poruses which are present in the human body, i.e.,
silver clusters like Ag2+, Ag3+ are formed by laser lungs, gastrointestinal tract, respiratory tract, mucous
desorption/ionisation of Ag(s) or Ag salts and Agn membranes of the urinogenital tract and skin mostly
clusters with n up to 50 – 60 were described (Staudt in the form of silver protein complexes (Chen et al.
et al. 2000). Due to the two isotopes of silver, in mass 2007). These silver nanoparticles can bind to
spectra characteristic isotopic envelopes are different proteins and causes phagocytosis.
developed. Although silver is absorbed in and metabolized in
An example of experimental and theoretical mass soft tissues, available experimental animal studies
spectrum for Ag2 cluster is given in Fig. 1. Evidently, and human clinical reports have shown that it enters
there are three combinations of the silver isotopes into tissues of the central nervous system or it causes
yielding three peaks in mass spectrum. Silver cluster neurotoxic damage. According to Cheng et al. (2004),
Ag8 can be stabilized in erionite channels. Erionite is Zhang and Sun (2007b), silver ions can also enter in
a kind of zeolite which shows cavities with diameter to the human body through the female genital tract.
0.63 nm and length 1.5 nm, such elongated cavities As per existing literature (Armitage et al. 1996),
are connected by small windows with a diameter 0.25 inhaled silver deposited in the lung can be absorbed
nm. The interconnections between the neighbouring through the wall of the alveolus. Some of the inhaled
channels are with twisted 8-member rings (with sizes particles are eliminated by mucocilliary action in the
0.36 × 0.52 nm) (Ogden et al. 1999). Mass spectrum lungs.
and the structure of this interesting Ag8 cluster are Nearly 10 – 20% of the ingested silver metal is
shown in Fig.2. Silver isotopes give rather rich absorbed in the gastrointestinal tract, mainly by the
isotopic pattern. duodenum and small intestine. Absorption of
ingested metal in the skin has also been reported, but
it may depend on damage to the epithelium layer
being present (Boosalis et al. 1987).
CHARACTERISTICS OF SILVER Silver and silver salts are distributed around the
NANOPARTICLES, THEIR UPTAKE, body and they accumulated mainly in the liver,
INTERACTIONS AND THEIR kidney and spleen. Chronic exposure of silver leads
CYTOTOXICITY IN VARIOUS ORGANS to irreversible deposition in subcutaneous and
AND CELL MEMBRANES mucous membranes. Through this deposition,
melanin production is enhanced, stimulated by the
There are many processes to synthesize silver presence of silver, leading to discoloration of the skin
nanoparticles e.g. electrochemical reduction, and/or (Armitage et al. 1996, Greene and Su 1987).

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TOXIC EFFECTS OF NANOSILVER OR As per the existing literature (Seung-heon et al.

SILVER ON HEALTH 2006), it has been demonstrated that silver
nanoparticles show intensive toxic effects on the
Silver has potentially toxic effects on human health proliferation and cytokine expression by peripheral
and it can enter into the human body through various blood mononuclear cells (PMBCs). At levels of over
portals. Previous literature (Kone et al. 1988) 15 ppm, nano-silver was found to have a significant
indicated that Ag+ causes early changes in the cytotoxic effect on PBMCs, and
permeability of the cell membrane to K+ and then to Phytohaemagglutinin-induced cytokine production
Na+ at concentrations that do not limit Na+, K+-ATP was significantly inhibited by nano-silver (Shin et al.
activity or mitochondrial function. 2007).

106.9
Ag108.9 Ag
Relative intensity(%)

100 215.7
80
A
108.9
60 Ag108.9Ag
213.7 217.8
106.9
40 Ag106.9 Ag
20
0
208 210 212 214 216 218 220
Relative intensity(%)

100
215.8
80 B
60 213.8
217.8
40

20
0
208 210 212 214 216 218 220

m/z
Fig. 1. Experimental (A) and theoretical (B) mass spectra of Ag2+cluster cation. Commercial MALDI-TOF MS instrument
(Axima-CFR, Schimadzu biotech, Japan) with a pulsed nitrogen laser of a wavelength of 337 nm was used for laser desorption
ionization of silver nitrate with addition of trifluoroacetic acid.
Conditions: the linear-positive mode.

Silver does not only cause dermal and cosmetic toxic In the literature of Burd et al. (2007), it was
effects, but also it causes death in animals. Soto et al. demonstrated that commercially available
(2005) have recently shown that silver nanoparticles silver-based dressings (Acticoat™, Aquacel® Ag,
can be nearly 50% more toxic than chrysolite Contreet® Foam, PolyMem® Silver, Urgotul®SSD)
asbestos. Nanoparticles, such as silver nanoparticles, are also showing potential cytotoxic effects. They
are showing severe toxic effects on the male assessed their cytotoxicity in various cultures such as
reproductive system. The identified research suggests in a monolayer cell culture, a tissue explants culture
that nanoparticles cross the blood-testes barrier and model and a mouse expurgated wound model. The
are deposited in the testes, and that there is potential results showed that Acticoat™, Aquacel® Ag, and
for adverse effects on sperm cells (McAuliffe et al. Contreet® Foam, when pre-treated with specific
2007). solutes, were likely to produce the most significant

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cytotoxic effects on both cultured keratinocytes and 1979, Sue et al. 2001). Silver ions show a high
fibroblasts, while PolyMem® Silver and Urgotul®SSD affinity for thiol in the liver (Baldi et al. 1988, Drake
demonstrated the least cytotoxicity. The cytotoxicity et al. 2005). Silver can accumulate and shows some
correlated with the silver released from the dressings toxic effects in organs and tissues. Venugopal and
as measured by the silver concentration in the culture Luckey (1978) noted that argyria can be considered
medium. a mechanism to detoxify silver by sequestering it in
the tissues as harmless silver-protein complexes or
silver sulphide.
Nanoparticles, such as silver nanoparticles, can
EFFECTS ON TISSUES AND ORGANS bind to different tissues and can cause potential toxic
effects like cell activation, producing reactive oxygen
By over-exposure, silver can be accumulated in the species, which are more toxic to tissue, inflammation
liver, skin, kidneys, corneas, gingival, mucous and finally all these processes gradually lead to cell
membranes, nails and spleen etc. (Rosenman et al. death (Xia et al. 2006).

Fig. 2. An example of Ag8 cluster structure and theoretical mass spectrum demonstrating rich isotopic envelope.

As a result of the experimental studies by nanoparticles can enter through the cardiovascular
Gopinath and Gogoi et al. (2008), it is known that system. In their experiments, they have studied
nanomaterials can pass through cell membranes pulmonary and systemic distribution of inhaled ultra
easily and cause severe toxic effects on human fine elemental silver nanoparticles in rats. They have
health. They have concluded that silver nanoparticles observed that Ag was found in the lungs immediately
in higher concentrations (> 44.0 µg ml-1) are necrotic after the end of exposure. They have found
to cells, leading to rapid cell membrane rupture. significant amounts of Ag in the blood, liver, kidney,
Recent studies have shown that nanoparticles can spleen, brain and heart. Importantly they have
easily pass through the blood-brain and blood-testes detected high Ag concentrations in nasal cavities,
barriers (Borm and Kreyling 2004) in mouse models. especially in the posterior portion and lung-associated
Through the experimental studies of Takenaka et lymph nodes. By these experiments, it is now known
al. (2001), it has been learned that elemental silver that after phagocytosis of inhaled silver nanoparticles

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by alveolar macrophages, there are Ag nanoparticles turning people's skin an ashen-grey colour, an
in the region of lungs, mostly on the alveolar walls. affliction known as argyria (irreversible pigmentation
of skin) and/or argyrosis (pigmentation of eyes)
Effects on central nervous system (CNS) (Marshall and Schneider 1977, Lee et al.1994,
The localization of exogenous silver is distributed Prescott et al. 1994, Fung et al.1996, Gulbranson et
heterogeneously in the central nervous system. It can al. 2000, Menaguale et al. 2003, Brandt and Park et
enter through the blood-brain barrier and accumulate al. 2005, Padlewska et al. 2007). As per the literature
in large motoneurones in the brain stem and spinal of Drake et al. (2005), argyria and argyrosis are
cord, neurons in cerebellar nuclei and glia. By the caused by the placement of silver-containing
usage of Ag in animal experiments, it is now known materials into the skin or body (Espinal et al. 1996),
that the biological half-life of silver in CNS is longer inhalation of silver particles (Rosenman et al. 1979),
than in other organs (Scott and Hamilton 1950, or by usage of silver-containing medicines (Fung and
Furchner et al. 1968, Phalen and Morrow 1973, Bowen 1996, Gulbranson et al. 2000, Tomi et al.
Rungby and Danscher 1983a, b). By prolonged 2004), dental materials (Watanabe 1989) etc.
administration of different silver compounds like Dietl et al. (1984) showed that manic depressive
silver lactate, silver nitrate and some silver proteins psychosis will develop at about the same time if not
like Protargol, silver accumulates in neurons and glia. a short time after cutaneous argyria has been
Prolonged exposure to silver shows toxic effects on diagnosed. It leads to a ruptured aortic aneurysm and
CNS such as cerebral ataxia (Aaseth et al. 1981). finally death. In this case they observed some
deposits of silver in the skin, mucous membranes,
Respiratory effects heart, kidney, liver, in the central nervous system and
The respiratory system is a major portal for in the leptomeninges and choroid plexus also.
nanoparticles. Actually larger sized particles than Even the usage of silver and silver creams can
nanoparticles will be seized by the microcilliary cause cutaneous side effects including
system which is present in the respiratory tract. But hypersensitivity reactions, allergic contact dermatitis,
ultra fine particles like nanoparticles can be deposited erythema multiforme and systemic argyria in humans
on the alveolar space. It has been proved that inhaled (Fisher et al. 2003).
silver nanoparticles do not interfere with the Generally argyria and argyrosis may be classified
microcilliary elimination process (Lippmann et al. into two major types, i.e., localized and generalized
1980). At the alveolar region these particles can be (Greene and Su 1987). Localized argyria is caused by
submersed into the surfactant lining of alveoli. By the direct contact of silver and silver-containing
this submersion, nanoparticles can produce surface substances. Small silver particles can enter the body
radicals and reactive oxygen species, which are more through sweat glands or through needle punctures
toxic to alveolar surfaces (Chen et al. 2007). Some (Buckley et al. 1965). In this case the most commonly
recent studies indicated that exposure to nanoparticles affected areas are mucous membranes, eyes and
can induce oxidative stress in lung epithelial cells hands (Breitstadt 1995). In this generalized argyria,
(Kaewamatawong et al. 2006, Limbach et al. 2007, silver granules are found most commonly around the
Sharma et al. 2007) and also in alveolar macrophage eccrine glands, in the walls of blood vessels, and
cells (Soto et al. 2008). These toxic effects are due to along elastic fibres (Robinson-Bostom et al. 2002).
their intensive catalytic activity (Limbach et al. Generalized argyria symptoms include
2007). So it can be said that having such a large pigmentation on the skin, eyes, face, ‘V of the neck´,
surface area and oxidative property, only silver waist, bald scalp, hands, nails and forearms (Legat et
nanoparticles can produce highly reactive species like al. 1998, Bouts 1999, Johnston et al. 1999, Graham et
reactive oxygen species at the intra-alveolar spaces al. 2004, Brandt et al. 2005, Bianchi et al. 2006, ).
(Chen et al. 2007). Through these interactions with Their light microscopical studies have revealed that
alveolar surfaces, silver nanoparticles can cause fine granules cluster in the periadnexal basement
irritation in the respiratory tract (Rosenman et al. membrane and dermal elastic fibres (White et al.
1987). By inhalation of silver dust or fumes, alveoli 2003).
and bronchial tissue will be stained. But this staining In generalized argyria, the degree of slate-grey
is not harmful to human health (Brooks 1981, Drake cutaneous discoloration varied from barely
et al. 2005). perceptible to pronounce. Silver-containing granules
deposit in and around cutaneous adnexal structures.
Argyria and argyrosis Histochemical studies suggested that the granules
It is known and acknowledged that long-term use of consisted of silver sulphide. Indiscriminate use of
colloidal silver or silver salts, like AgNO3, deposit currently available silver-containing medications can
metallic silver under the skin and abdominal viscera, result in generalized argyria (Pariser 1978).

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TOXIC EFFECTS OF SILVER OR the health of the estuarine system (Flegal et al. 2007).
NANO-SILVER ON THE ENVIRONMENT Silver causes lethal damage to hepatocytes in rats and
finally it leads to cell death (Baldi et al. 2002).
Silver, along with its potential antimicrobial activity,
also causes adverse effects not only in the human Case studies
body (Fung and Bowen 1996) but also it causes some Various forms of silver and silver-containing
toxic effects in aquatic systems and soil microbial compounds cause adverse effects in humans and
communities. animals. Most studies discuss the various toxic effects
of silver on the human body and the environment
Effects on soil communities following intensive ingestion and inhalation of silver
Silver has some potential toxic effects on beneficial compounds. A number of studies describe the effects
bacteria in soil, which play a major role in nitrogen of occupational exposure to metallic and soluble
fixation. For instance, according to the report of silver compounds.
Senjen (2007), it has been discovered that there is As discussed earlier, silver has a potential
currently very little research available regarding the antimicrobial activity towards many pathogens (Hill
effects of silver nanoparticles on soil microbial and Pillsbury 1939) and it has been used in the past
communities. Silver, with its potential bactericidal for medication purposes. According to the medical
activity, inhibits soil microbial growth at levels below literature citation, numerous cases of argyria were
the concentrations of other heavy metals (Murata et observed after colloidal silver ingestion. In a typical
al. 2005, Throback et al. 2007). It shows toxic effects case study by Chang et al. (2006), data from a 59-
on human-friendly microbes like heterotrophic year-old man who was suffering from skin colour
(nitrogen-fixing and ammonifying bacteria) and change was analyzed. It was revealed that he had
chemolithotrophic bacteria in soil communities. ingested colloidal silver two to three times a year for
Chemolithotrophic bacteria belong to the lithotrophic at least the previous two years, whenever he felt a
family of microbes and consume inorganic material. ´cold´ coming on. The patient believed that the
These organisms deliver many crucial nutrients colloid silver had antibiotic properties. Along with
which are most essential in soil formation this skin colour change, some other symptoms were
(http://en.wikipedia.org/wiki/Lithotroph). These soil also visible like hyperlipidemia, hypertension,
bacteria can play a key role in nitrogen fixing and the diabetes, gastroesophageal reflux disease, benign
breakdown of organic matter. These bacteria also prostatic hypertrophy, and post-traumatic stress
form symbiotic relationships with legumes plants, disorder. After a critical examination, it was reported
which provide a major source of fixed nitrogen for that he had a diffuse blue-grey appearance on his
both these and other plants. By showing potential face, mostly on his cheeks and nose with slight
toxic effects on denitrifying bacteria, silver disrupts sparing of the periorbital and paranasal areas. Finally,
denitrification processes leading to eco-system it was concluded that the ingestion of colloidal silver
disruption. Denitrification is a bacterium driven appears to be an increasing practice among patients
process in which nitrates are converted to nitrogen using ‘alternative health’ practices and can lead to
gas in some soils, wetlands and in some other wet specific pathological and clinical findings like
environments. Environmental denitrification is argyria.
important because excess nitrates can reduce plant In the literature of Drake et al. (2005), it was
productivity, which in turn can result in mentioned that colloidal silver protein had been used
eutrophication in rivers, lakes and marine as an allergy and cold medication (Bouts 1999,
ecosystems, and are a drinking water pollutant Gulbranson et al. 2000, Tomi et al. 2004), in eye
(Senjen 2007). drops to alleviate soreness (Loeffler and Lee 1987)
and for the treatment of various ailments (White et al.
Effects on aquatic systems 2003). Prolonged usage of this silver protein as a
Silver has some unexpected adverse toxic effects on medication caused discoloration in the fingernails,
aquatic systems like lakes, rivers etc. For instance, in ocular agyrosis and generalized argyria.
freshwater fish, the acute toxicity of Ag appears to be Silver nanoparticles can show a potential
caused solely by ionic Ag+ interacting at the gills, cytotoxic effect on mammalian germ line stem cells.
inhibiting basolateral Na+, K+-ATPase activity. In the experimental case study of Braydich-Stolle et
Disruption of this enzyme inhibits active Na+ and Cl- al. (2005), the cytotoxicity effects of silver
uptake and therefore osmoregulation by the fish nanoparticles on mammalian germ line stem cells
(Wood 1999). Recent toxicity studies with were investigated. In this study, the effect on cell
macro-invertebrates in the San Francisco Bay have morphology, mitochondrial function, membrane
indicated that silver may still be adversely affecting leakage etc. was taken into consideration. It was

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concluded that silver nanoparticles at 10 µg/ml and sulfadiazine cream to wounds and dermatitis, it
above concentration showed dramatic changes like causes some cutaneous side effects including
necrosis and apoptosis of cells. Silver nanoparticles hypersensitivity reactions, allergic contact dermatitis,
at 5–10 µg/ml, drastically reduced mitochondrial erythema multiforme and sytemic argyria.
function and cell viability. In the fourth case study, Rosenman et al. (1987),
In the second case study by White et al. (2003), a cross sectional study on workers engaged in
data from a 58-year-old man suffering from manufacturing precious metal powders was carried
worsening facial discoloration over 3 years. He drank out. Around 27 workers, 96% of the workers, had
colloidal silver protein solution for at least one year raised urine silver concentrations (range 0.5–52.0
but was unable to estimate his total consumption. He µg/l, mean 11.3 µg/l) and 92% of workers had raised
believed that this silver protein had properties to treat blood silver concentrations (range 0.05–6.2 µg/100
and prevent various diseases like dandruff and ml, mean 1.0 µg/100 ml). Most workers had
colonic cancer. On a critical examination, a symptoms of respiratory irritation and nose bleeds
deep-blue/grey discoloration of the skin, face, neck, were reported in eight (30%) of the 27 workers.
bald scalp, hands and forearms was observed. His Deposition of silver in the cornea of the eye in around
fingernails showed a blue discoloration extending five of eight (63%) workers was observed. Raised
from the lanulae to halfway along the nail plate. urinary enzyme N-acetyl-B-D glucosaminidase
Using a light microscope, they observed fine (NAG) was detected in four individuals and was
granules clustered in the periadnexal basement correlated with blood silver concentrations and age.
membranes and dermal elastic fibres. Electron It was noted that kidney function appeared to have
microscopic studies also revealed bright granules been adversely affected by exposure at work but it
below the dermal/epidermal junction. After all these has not been confirmed as, up to this study, it was not
studies, it was concluded that the precise mechanism known if exposure to silver causes any decrement or
of silver deposition in argyria is not fully understood, not in the kidney function.
but ingestion of silver is thought to cause deposition In our own cross sectional case study, we have
of silver-protein complexes. Elemental silver is analysed twenty six workers from an industrial plant
reduced to silver sulphide in the skin. This process is in Hyderabad, India which eliminates silver and silver
catalysed by sunlight in a process similar to that compounds like silver nitrate and silver oxide from
harnessed in photography. The process, combined industrial wastes. By the consumption of drinking
with melanocyte stimulation, causes the cutaneous water mixed with these silver containing industrial
discolouration (White et al. 2003). wastes, we have concluded that some people were
In the third case study (Tomi et al. 2004) data was suffering from cutaneous diseases like argyria and
analyzed from a 42-year-old non-smoking white man argyrosis.
complaining of skin discoloration. He had initially This cross sectional study revealed that five
noticed a slight blue-grey tinge to his skin some people had generalized argyria and fifteen had
months previously, but which had increased over argyrosis. Ten of the twenty six workers had
time. On clinical examination, they have found a complained of gastrointestinal irritation and some
peculiar slate, blue-grey discolouring of the entire allergic and hypersensitivity reactions. This symptom
tegument, sclera, mucosal surfaces and nails. He had was significantly associated with silver in the blood
applied one to two 10 ml bottles of a topical and deposition of silver in the periadnexal basement
vasoconstrictor, Coldargan (Sigmapharm, Vienna) membrane and dermal elastic fibres (White et al.
weekly to ameliorate the symptoms of allergic 2003). However, the permanent discoloration and
rhinitis. In microscopic studies they also observed potential effect of some allergic reactions suggest the
brownish-black perivascular pigment deposits in need to limit exposure to silver.
muscle, nerve, sweat glands and dermis. So finally it
was concluded that the person was suffering from
generalized argyria on the basis of above mentioned
clinical symptoms.
Along with this case study, we witnessed our own DISCUSSIONS AND CONCLUSIONS
case of argyria in an elderly Indian woman who, for
several years, had applied the silver sulfadiazine After reviewing the literature one fact is noticeable.
cream every day to heal her wound and contact Over the past decades, the usage of silver containing
dermatitis. After using the silver sulfadiazine cream, medications has become more prevailing because of
a scar-localized argyria developed within a post their potential antimicrobial and bactericidal activity
surgical wound and area of severe contact dermatitis. and people are choosing silver containing medicines
So it can be concluded that by applying this silver as an alternative health supplement. Earlier, we

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mentioned that silver has a natural antimicrobial According to the literature, it was reported that
activity (Margaret et al. 2006, Sarkar et al. 2007) many people are using silver and silver compounds as
towards many pathogens such as bacteria (Hill and medications for symptoms such as allergies and colds
Pillsbury 1939, Morones et al. 2005, Zhang and Sun (Bouts 1999, Gulbranson et al. 2000, Tomi et al.
2007), viruses, fungi, yeast etc. 2004) and eye diseases (Loeffler and Lee 1987).
Some people believe that silver has properties In conclusion, it has been reported that silver
such that it can protect them from diseases like nanoparticles can bind to proteins and enzymes in
colonic cancer and some skin diseases like dermatitis. mammalian cells. These silver nanoparticles can
The explanation of the protection effect is still not make adhesive interactions with cellular membranes
understood. It is suggested that silver can disrupt the and produce highly reactive and toxic radicals like
bacterial cell wall. At minimal and reasonable reactive oxygen species, which will cause
concentrations of silver, there are no side effects on inflammation and destroy cells like mitochondria.
human health. Even though it is has potential Subsequently they produce apoptogenic factors that
antimicrobial activity, prolonged exposure to silver cause cell death and necrosis in the cellular
causes intensive diseases like argyria and argyrosis. environment. Silver nanoparticles can show intensive
According to Drake et al. (2005), the uptake of toxic effects on the mitochondrial function and cell
silver into the human body is often much higher viability and they can produce lytic enzymes which
when it is administered orally as a medication than can cause apoptosis and necrosis. It has been reported
from occupational exposure like inhalation of silver that ingestion of colloidal silver (a suspension of
compounds. The majority of occupational exposure silver in microparticles and/or nanoparticles) has also
reports involve soluble silver compounds, which been linked with neurological problems, kidney
seem to cause toxic effects at lower concentrations damage, stomach upset, headache, fatigue and skin
than metallic and insoluble silver compounds. For irritation (Senjen 2007). Silver affects denitrification
example, blood-silver concentrations found by bacteria such strongly that, in reality, disrupts the
Williams and Gardner (1995) and Armitage et al. bacterium driven environmental denitrification
(1996), were considerably higher than that found in processes. As a consequence it results a great up to
workers exposed to metallic silver or insoluble silver catastrophic eutrophication in rivers, lakes and
compounds. marine ecosystems (Senjen 2007).
But in many of the studies we cannot say that Having a tremendous surface area and small
silver could definitely be associated with an adverse particle size, nanoparticles can make potential
health outcome. For example the study of Rosenman interactions with membrane surfaces and can easily
et al.(1987) was an attempt to investigate the effects translocate and become distributed throughout the
of silver on kidney function. It was found that human body. Taking into account their
creatinine clearance was depressed and urinary physicochemical and biological properties, it is likely
enzyme NAG levels were significantly raised in the that nanoparticles possess unique toxicity
exposed group. However, it was difficult to mechanisms. It remains to be determined whether
determine if silver caused any adverse effects on silver nanoparticles and other nanoparticles will
kidney function or not because the workers had also introduce new mechanisms of injury from which new
been exposed to many other nephrotoxic agents. pathologies may result. Finally for silver, whether
Several cross sectional studies were carried out nano-sized or not, there are always the problems of
and it was reported that argyria is the most frequent argyria and argyrosis in humans and eutrophication in
adverse outcome from exposure to silver. For the environment.
example even in a typical recent case study done by
Chang et al. (2006), it was reported that the
prolonged ingestion of silver containing medicines
causes colour changes to the skin and a blue-grey
appearance on the face. Along with these symptoms ACKNOWLEDGEMENTS
some other symptoms like hypertension, diabetes,
gastroesophageal reflux disease, benign prostatic Supports from theAcademy of Sciences of the Czech
hypertrophy and post-traumatic stress disorders were Republic, project KAN 101630651 (Nanotechnology
also observed. But in some cases, many of the for the Society) and of the Grant Agency of the Czech
workers complained of decreased vision at night. Republic, project No. 525/06/0663 are greatly
Many ophthalmologic studies have been conducted acknowledged. E.M.P-M. and J.H. acknowledge the
and they have concluded that decreased vision at partial support from University of La Laguna, La
night is associated with the deposition of silver in the Laguna, Spain.
cornea.

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