Heavy Metals

Introduction
The term heavy metal refers to any metallic chemical element that has a
relatively high density and is toxic or poisonous at low concentrations.
Examples of heavy metals
include mercury (Hg), cadmium (Cd), arsenic (As), chromium (Cr), thallium
(Tl), and lead (Pb).
Heavy metals are natural components of the Earth's crust. They cannot be
degraded or destroyed. To a small extent they enter our bodies via food,
drinking water and air. As trace elements, some heavy metals
(e.g. copper, selenium, zinc) are essential to maintain the metabolism of
the human body. However, at higher concentrations they can lead to
poisoning. Heavy metal poisoning could result, for instance, from drinking-
water contamination (e.g. lead pipes), high ambient air concentrations near
emission sources, or intake via the food chain.

Heavy metals are dangerous because they tend to bioaccumulate.

Bioaccumulation means an increase in the concentration of a chemical in a
biological organism over time, compared to the chemical's concentration in
the environment. Compounds accumulate in living things any time they are
taken up and stored faster than they are broken down (metabolized) or
excreted.
Heavy metals can enter a water supply by industrial and consumer waste,
or even from acidic rain breaking down soils and releasing heavy metals
into streams, lakes, rivers, and groundwater.

Environmental and health risks.

Now we are going to describe the effects of the heavy metals in the
environment. The three most pollutans heavy metals are Lead, Cadmium,
and Mercury.
Effects of Antimony on the environment
Antimony is a metal used in the compound antimony trioxide, a flame
retardant. It can also be found in batteries, pigments, and ceramics and
glass. Exposure to high levels of antimony for short periods of time causes
nausea, vomiting, and diarrhea. There is little information on the effects of
long-term antimony exposure, but it is a suspected human carcinogen.
Most antimony compounds do not bioaccumulate in aquatic life.

Effects of Cadmium on the environment

Cadmium derives its toxicological properties from its chemical similarity to
zinc an essential micronutrient for plants, animals and humans. Cadmium
is biopersistent and, once absorbed by an organism, remains resident for
many years (over decades for humans) although it is eventually excreted.
In humans, long-term exposure is associated with renal disfunction. High
exposure can lead to obstructive lung disease and has been linked to lung
cancer, although data concerning the latter are difficult to interpret due to
compounding factors. Cadmium may also produce bone defects
(osteomalacia, osteoporosis) in humans and animals. In addition, the metal
can be linked to increased blood pressure and effects on the myocardium
in animals, although most human data do not support these findings.
The average daily intake for humans is estimated as 0.15µg from air and
1µg from water. Smoking a packet of 20 cigarettes can lead to the
inhalation of around 2-4µg of cadmium, but levels may vary widely.

Effects of Chromium on the environment

Chromium is used in metal alloys and pigments for paints, cement, paper,
rubber, and other materials. Low-level exposure can irritate the skin and
cause ulceration. Long-term exposure can cause kidney and liver damage,
and damage too circulatory and nerve tissue. Chromium often accumulates
in aquatic life, adding to the danger of eating fish that may have been
exposed to high levels of chromium.

Effects of Copper on the environment

Copper is an essential substance to human life, but in high doses it can
cause anemia, liver and kidney damage, and stomach and intestinal
irritation. People with Wilson's disease are at greater risk for health effects
from overexposure to copper. Copper normally occurs in drinking water
from copper pipes, as well as from additives designed to control algal
growth.

Effects of Lead on the environment

In humans exposure to lead can result in a wide range of biological effects
depending on the level and duration of exposure. Various effects occur
over a broad range of doses, with the developing foetus and infant being
more sensitive than the adult. High levels of exposure may result in toxic
biochemical effects in humans which in turn cause problems in the
synthesis of haemoglobin, effects on the kidneys, gastrointestinal tract,
joints and reproductive system, and acute or chronic damage to the
nervous system.

Heavy metal stress and responses in plants

Heavy metals such as Fe, Mn, Cu, Ni, Co, Cd, Zn, Hg and arsenic are for
long being accumulated in soils through industrial waste and sewage
disposal. Although some of these metals are essential micronutrients
responsible for many regular processes in plants, their excess, however,
can have detrimental effects and can directly influence the plant growth,
metabolism, physiology and senescence.
Plants have different mechanisms to fight stress, and they are responsible
to maintain homeostasis of essential metals required by plants. These
mechanisms also focus on prevention of plants exposure to heavy metals
present in the soil or providing tolerance to the plant by detoxifying the
metals. Other mechanisms are specific and are initiated when the
respective stress is encountered. The first line of defense provided by a
plant is to reduce the uptake of metals when stimulated with toxicity of
heavy metals and includes the help offered by cellular and root exudates
that restricts metals from entering the cell.
Many plants have exclusive mechanisms for individual metal ions and are
involved in sequestering these ions in compartments avoiding their
exposure to sensitive components of the cells.
As a second line of defense, other mechanisms for detoxification of these
metals are introduced that chelates, transports, sequesters and detoxifies
these metal ions in the plant’s vacuole.
 During the time of metal toxicity, oxidative stress is pronounced in the
cells and production of stress-related proteins and hormones,
antioxidants, signaling molecules including heat-shock proteins synthesis
is initiated.

Toxicity ;

Toxicity is the degree to which a chemical substance or a

particular mixture of substances can damage an organism .
Toxicity can refer to the effect on a whole organism, such as
an animal, bacterium, or plant, as well as the effect on a substructure of the
organism, such as a cell (cytotoxicity) or an organ such as
the liver (hepatotoxicity. By extension, the word may
be metaphorically used to describe toxic effects on larger and more
complex groups, such as the family unit or society at large.
Sometimes the word is more or less synonymous with poisoning in
everyday usage.
A central concept of toxicology is that the effects of a toxicant are dose-
dependent; even water can lead to water intoxication when taken in too
high a dose, whereas for even a very toxic substance such as snake
venom there is a dose below which there is no detectable toxic effect.
Considering the limitations of this dose-response concept, a novel Drug
Toxicity Index (DTI) has been proposed recently.
DTI redefines drug toxicity, identifies hepatotoxic drugs, gives mechanistic
insights, predicts clinical outcomes and has potential as a screening tool.
Toxicity is species-specific, making cross-species analysis problematic.
Newer paradigms and metrics are evolving to bypass animal testing, while
maintaining the concept of toxicity endpoints.

Types

There are generally four types of toxic entities; chemical, biological, physical and radiation:

 The R.M.Yassine Scale is the main scale used to measure toxicity.

 Chemical toxicants include inorganic substances such
as, lead, mercury, hydrofluoric acid, and chlorine gas, and organic
compounds such as methyl alcohol, most medications, and poisons
from living things. While some weakly radioactive substances, such
as uranium, are also chemical toxicants, more strongly radioactive
materials like radium are not, their harmful effects (radiation poisoning)
being caused by the ionizing radiation produced by the substance rather
than chemical interactions with the substance itself.

 Disease-causing microorganisms and parasites are toxic in a broad
sense, but are generally called pathogens rather than toxicants. The
biological toxicity of pathogens can be difficult to measure because the
"threshold dose" may be a single organism. Theoretically one virus,
bacterium or worm can reproduce to cause a serious infection.
However, in a host with an intact immune system the inherent toxicity of
the organism is balanced by the host's ability to fight back; the effective
toxicity is then a combination of both parts of the relationship. In some
cases, e.g. cholera the disease is chiefly caused by a nonliving
substance secreted by the organism, rather than the organism itself.
Such nonliving biological toxicants are generally called toxins if
produced by a microorganism, plant, or fungus, and venoms if produced
by an animal.

 Physical toxicants are substances that, due to their physical nature,
interfere with biological processes. Examples
include coal dust, asbestos fibers or finely divided silicon dioxide, all of
which can ultimately be fatal if inhaled. Corrosive chemicals possess
physical toxicity because they destroy tissues, but they're not directly
poisonous unless they interfere directly with biological activity. Water
can act as a physical toxicant if taken in extremely high doses because
the concentration of vital ions decreases dramatically if there's too much
water in the body. Asphyxiant gases can be considered physical
toxicants because they act by displacing oxygen in the environment but
they are inert, not chemically toxic gases.

 As already mentioned, radiation can have a toxic effect on organisms.
Factors influencing toxicity

Toxicity of a substance can be affected by many different factors, such as

the pathway of administration (whether the toxicant is applied to the skin,
ingested, inhaled, injected), the time of exposure (a brief encounter or long
term), the number of exposures (a single dose or multiple doses over time),
the physical form of the toxicant (solid, liquid, gas), the genetic makeup of
an individual, an individual's overall health, and many others.
Several of the terms used to describe these factors have been included
here.
Acute exposure

A single exposure to a toxic substance which may result in severe

biological harm or death; acute exposures are usually characterized
as lasting no longer than a day.

Chronic exposure

Continuous exposure to a toxicant over an extended period of time,

often measured in months or years; it can cause irreversible side
effects.

Biological Toxicity
The toxicological studies on carbon nanotubes (CNTs) have been urgently
needed from the emerging diverse applications of CNTs.

Physicochemical properties such as shape, diameter, conductance, surface

charge and surface chemistry of CNTs gained during manufacturing
processes play a key role in the toxicity. In this study, we separated the
semi-conductive components of SWCNTs (semi-SWCNTs) and evaluated
the toxicity on days 1, 7, 14 and 28 after intratracheal instillation in order to
determine the role of conductance.
Exposure to semi-SWCNTs significantly increased the growth of mice and
significantly decreased the relative ratio of brain weight to body weight.
Recruitment of monocytes into the bloodstream increased in a time-
dependent manner, and significant hematological changes were observed
28 days after exposure.

In the bronchoalveolar lavage (BAL) fluid, secretion of Th2-type cytokines,

particularly IL-10, was more predominant than Th1-type cytokines, and
expression of regulated on activation normal T cell expressed and secreted
(RANTES), p53, transforming growth factor (TGF)-β, and inducible nitric
oxide synthase (iNOS) increased in a time-dependent manner.

Fibrotic histopathological changes peaked on day 7 and decreased 14

days after exposure. Expression of cyclooxygenase-2 (COX-2), mesothelin,
and phosphorylated signal transducer and activator of transcription 3
(pSTAT3) also peaked on day 7, while that of TGF-β peaked on days 7 and
14. Secretion of histamine in BAL fluid decreased in a time-dependent
manner.

Consequently, we suggest that the brain is the target organ of semi-

SWCNTs brought into the lung, and conductance as well as length may be
critical factors affecting the intensity and duration of the inflammatory
response following SWCNT exposure.

Introduction
Because of advances in scientific research and technology, nanomaterials,
including carbon nanotubes (CNTs), are now used in biomedical, cosmetic,
aeronautics, electronics, and other industries. Further, their effects on
human health are also gaining enormous attention from the public.
Single-walled carbon nanotubes (SWCNTs) have been included in the
priority list of OECD (Organization for Economic Co-operation and
Development) and have been introduced in many new technologies for
various industrial applications. Many epidemiological and toxicological
studies have reported on the adverse health effects of SWCNTs .
According to these reports, CNTs cause adverse health effects such as
pulmonary inflammation, granulomatous lesions, fibrosis, and
mesothelioma by inducing oxidative stress and free radical generation after
inflow of SWCNTs into the lung .
When experimental animals were treated with SWCNTs, crocidolite
asbestos, and ultrafine carbon black of the same concentration, SWCNTs
caused the greatest histopathological changes, and lung tissue proteins
affected by SWCNT exposure largely represent cellular processes affected
by asbestos as well .
Nitric oxide (NO) production increased and mitochondrial activity decreased
after an engineered human lung was exposed to SWCNTs , and treatment
with SWCNTs and ovalbumin (OVA) strongly promoted an OVA-specific
allergic response .
The results of microarray analysis following intratracheal instillation of
SWCNTs suggest that an immunotoxicological mechanism may explain the
chronic pulmonary inflammation and granuloma formation caused by
SWCNTs in vivo .
Pharyngeal aspiration of SWCNTs also elicited unusual pulmonary effects
in mice, combining a robust but acute inflammation with early onset yet
progressive fibrosis and granulomas .
In addition, a single intrapharyngeal instillation of SWCNTs induced
activation of heme oxygenase-1 (HO-1) in HO-1 reporter transgenic mice
and aortic mtDNA damage in C57BL/6 mice
The physicochemical properties of manufactured nanomaterials can vary
according to manufacturing methods, and although the raw materials are
the same, the toxicity can vary as well.
Therefore, physical properties such as surface chemistry, conductance,
diameter, structure, and shape together with the components of raw
materials are considered important factors that depend on toxicity.
SWCNTs are applied for the production of diverse products and the
semiconductor industry is one of the main fields that use SWCNTs.
In a previous study using pristine SWCNTs, which were a mixture of
conductive (or metallic) and semi-conductive (or semi-metallic)
components, we demonstrated that SWCNTs instilled intratracheally
induced early lung fibrosis and chronic tissue damage . Since semi-
SWCNTs have less available charge density at the Fermi level than
metallic-SWCNTs, they have very different chemical reactivity . In the
current study, we separated only semi-conductive components from the
SWCNT mixture containing conductive and semi-conductive components in
order to focus on the role of conductance in SWCNT toxicity.
We then instilled a single intratracheal dose into mice at a concentration of
100 µg/kg and killed the mice on days 1, 7, 14 and 28 to investigate
immunological and general toxicological changes with time. Body weight,
organ weight, hematological changes, cytokine levels in bronchoalveolar
lavage (BAL) fluid and blood, histopathological changes, and protein
expression in lung tissue were determined at each time point.