still people use toxic Silver in wound dressing!

1. RISK IN THE USE OF SILVER NANOPARTICLES
ON HUMAIN: SILVER TOXICITY AND ITS
EFFECTS ON HEALTH
PIERRE BASMAJI
CENTRE FOR RESEARCH AND DEVELOPMENT
BIOTECHNOLOGY - INNOVATECS , 9 ST JULY 1312,
SP 13560-042 SAO CARLOS –BRAZIL
Nanomaterials have many potential benefits to society with their development and
deployment in science, engineering and technology. Its benefits however, need to
be taken into account considering the potential risks to the public health and to the
environment.
Nanotechnology a nanoparticle is defined as a small object or particle that behaves as
a whole unit in terms of transport and properties. Nanotechnology takes advantage of
the fact that when a solid material becomes too small, increasing its specific surface
area, which leads to an increase in surface reactivity and is related quantum effects.
The physical and chemical properties of nanomaterials can be very different from
those of the same material as a larger mass. Nanomaterials (such as nanotubes and
nanorods) and Nanoparticles are particles that have at least one dimension in the
range 1 to 100nm. Nanoparticles are classified only on the basis of its size and may or
may not exhibit size-related properties that differ significantly from those observed in
bulk materials (ASTM 2006; Buzea et al, 2007). Due to the properties of nanoscale
silver, nanosilver is now used in an increasing number of consumer products and
medicaldevices, medicines, etc
Nanomaterials are nanoparticles that have special physicochemical properties as a
result of their small size (Buzea et al, 2007) .
Silver has been known to be an antibacterial, antifungal and a powerful antiviral agent
. But in recent years, the use of silver as a biocide solution, suspension and especially
in the form of nano-particles has experienced a dramatic revival. Due to the properties
of silver in nanolevels , nanosilver is currently used in an increasing number of
consumer products and medicines . The remarkably strong antimicrobial activity is a
major reason for the recent increase in the development of products containing
nanosilver. Examples of consumer products containing nanosilver include food
packaging, food supplements, textiles, electronics, appliances, cosmetics, medical
devices, disinfectants, water sprays , environmental materials , etc . There is a need for
the development of methods for measuring the nanosilver concentration, size, shape,
surface charge, the crystal structure, and surface chemistry transformations. Some
important questions to answer :
Nanosilver is toxic?
What are the mechanisms of toxicity?

2. Which conditions those occur in the mechanisms?
There is evidence that silver and nanosilver in particular, is toxic to aquatic and
terrestrial organisms, a variety of mammalian cells in vitro and can be harmful to
human health.
While undoubtedly nanosilver and silver have useful applications in the medical field
(for example, as coatings for medical devices such as wound healing or for the Victims
of severe burns), their use may need to be strictly controlled. Bacterial resistance to
antibiotics is a growing problem in the world and indiscriminate use of biocidal silver in
countless consumer products is not only unnecessary but may further increase
bacterial resistance to a dangerous level (Mühling et al . , 2009). There are preliminary
indications that in the form of nanoparticles, the toxicity of ionic silver increases or
that the nanoparticles can exert their own toxicity.
Nano silver can dissociate to form silver ions in the presence of moisture.
It is Also possible that nanoparticles of silver ions from shielding such interactions by
delivering silver ions to the membranes which are free of organisms or cells. In this
case, anaccentuation of the health risks would be expected apart from being
associated with a similar mass of silver itself.
The most common health effects associated with chronic exposure to silver are
apermanent gray or blue-gray discoloration of the skin (argyria; .1 and Figure 2) and
other organs (ATSDR, 1990; Drake & Hazelwood 2005;. White et al, 2003 . Lower level
of exposure also results in the silver to be deposited on the skin and other parts of
body such as liver, brain, muscle and kidneys and may cause changes in blood
cells (Fung and Bowen, 1996; Venugopal & Luckey, 1978). Exposure to high levels of
silver in the air can result in breathing problems, lung and throat irritation and
stomach pain. Skin contact with silver can cause mild allergic reactions including rash,
swelling and inflammation in some people.

3. Figure 1 : Systemic argyria of the skin by drinking colloidal silver (underside) when
compared with normal pigmentation (upper side) (Wadhera & Fung , 2010) .

4. Figure 2 Paul Karason Blue Men
Even though silver is generally not available in high enough concentrations to pose a
risk to human health and the environment ; nanosilver in contrast has physical and
surface properties that could pose a threat to human and environmental health (Lee
et al, 2007). Due to the different physico-chemical properties and biological activities
of nanosilver when compared with normal metal , it cannot be excluded that the
increase in reactivity of nanosilver (due to the large surface area) leads to increased
toxicity due to the activity of the silver ions released very easily by the nanoparticles.
Some nanoparticles can penetrate the lungs or skin and enter the circulatory and
lymphatic systems of humans and animals, reaching the tissues and organs of the body
and potentially disrupting cellular processes , cause diseased cells and cause disease.
Silver nanoparticles were found in blood of patients suffering from the diseases of
the blood and in the colon of patients with colon cancer (Gatti, 2004; Gatti et al,
2004). Silver is known to have a lethal effect on bacteria but the same property that
makes it an antibacterial makes it toxic to human cells as well . The silver
concentration that is lethal to the bacterium is also lethal to both keratinocytes and
fibroblasts (Poon & Burd, 2004). In vitro studies have shown that nanosilver effects
reproduction & development and has an effect on DNA, among others. A recent
survey of 12nm silver nanoparticles in highly purified zebra - fish showed that the early
development of fish embryos was affected (Lee et al, 2007). Silver nanoparticles have
the potential to cause chromosomal aberrations and DNA damage and are capable of
inducing proliferation arrest in cell lines of zebra -fish (Asharani et al . 2007).
In addition, toxicity studies were performed in mammalian species have shown that
silver nanoparticles are able to enter cells and cause cellular damage (Hussain et al,
2005; Ji et al, 2007). The toxicity of nanosilver causes oxidative stress induction or cell
dysfunction) or a mixture of both (El- Ansary & Al - Daihan, 2009; Oberdörster et al,
2005b). The nanoparticles were found to be distributed to the colon, lung, bone
marrow, liver, spleen and lymph after intravenous injection (Hagens et al. , 2007).
Distribution in the human body is usually followed by a fast clearance from the
systemic circulation predominantly by the action of the liver and spleen macrophages
(Moghimi et al, 2005) to causegastrointestinal problems. Some systems of
nanoparticles may accumulate in the liver during first-pass metabolism (El- Ansary
Daihan & al, 2009; Oberdörster et al, 2005a).

5. A case study was published regarding liver enzymes after topical use of nanosilver
preparation for a young burn victim (Trop et al, 2006). Six days after treatment, the
patient developed blue-gray discoloration on lips (argyia).
Respiratory Tract Toxicity:
Human exposure to inhalation of environmental particle including nanosilver, may
have adverse effects on health (Buzea et al, 2007 effects; Dockery, 2005; Donaldson
et al, 2004; Lippmann et al, 2003; Shah, 2007; Vermylen et al 2005).Cardiovascular and
pulmonary diseases can result when inhaled particles interfere with the normal
function of bodily systems (Peters et al, 1997, 2001 and 2005).
Dermal Toxicity: Although based on nanosilver , dressings and surgical sutures have
received approval for clinical application ; it is important to make a good control of
infection of the wound, it's skin toxicity . And that is still a topic of concern. Despite
clinical and laboratory studies confirm the biocompatibility of dermal dressings based
nanosilver, several other researchers demonstrated cytotoxicity of these materials
(Chen et al , 2006 & El- El- Ansary Daihan 2009; Limbach et al, 2007; Muangman et al,
2006. Oberdörster et al, 2005b. Supp et al, 2005; Wright et al, 2002). Shovel-Ledinek et
al. (2006). Acticoat ® is a dressing consists of a polyethylene mesh coated with nanosilver (average size 15 nm). There is one case of silver poisoning after the use of
Acticoat ® for the treatment of severe burns to the legs (Trop et al, 2006. Wijnhoven et
al, 2009). On day 6 of post-injury, the patient developed a grayish color in the treated
area, complained of being tired and had no appetite. On the day 7, silver levels in
urine and blood were found to be elevated (28 and 107 mg/kg, respectively).
Kidney toxicity :
Kim et al. (2008 ) reported gender differences in the accumulation of silver
nanoparticles in rat kidneys. In a study by Kim et al. ( 2009), the tissue distribution of
silver nanoparticles showed a dose-dependent accumulation of silver in all tissues
examined, including the testis, kidney, liver, brain, lungs and blood. The gender
difference in the accumulation of silver was observed in the kidneys, with
a largest concentration in female and male kidneys compared after subacute exposure
of silver nanoparticles through inhalation or oral ingestion. Silver nanoparticles were
detected in the cytoplasm and nucleus of interstitial cells in the inner medulla of
kidney.
Conclusions on nanosilver toxicity:
Silver nanoparticles are used because of the antibacterial activity of silver. It has been
suggested that the main mechanism of action is the death of cells due to uncoupling of
oxidative phosphorylation (Holt & Bard, 2005) or inducing the formation of free
radicals (Kim et al, 2007). Interference with the respiratory chain, cytochrome c levels,
and/or components of microbial electrons transport system has also been reported
(Muangman et al, 2006). Interactions with membrane bound enzymes and thiol groups
of proteins that may result in compromised integrity of the cell wall have been
postulated (Bragg & Rainnie, 1974, Lok et al, 2006. Silver, 2003; Wijnhoven et al,

6. 2007;et Zeiri. al, 2004). It has also been suggested that the silver ions bind to DNA and
can cause DNA strand breaks in DNA replication and (ATSDR, 1990. Russell & Hugo
1994 toxicity of silver nanoparticles is mainly determined in vitro with particles ranging
in size from 1-100nm. potential target organs for nanosilver toxicity may involve the
liver, kidneys and the immune system. Accumulation and histopathological effects
were observed in the liver of mice systemically exposed to silver nanoparticles 10-15
nm (Ji et al, 2007), whereas an effect on the liver enzymes was observed in a study of
the case of human dermal exposure to an average particle size of the same (Trop et al,
2006). More studies are needed to better characterize the risk of the use of silver
nanoparticles on humans
.
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