MERCURY TOXICITY

PAPER FOR ENVIRONMENTAL TOXICOLOGY

Afit Hendrawan 105096003152

Maidi Saputra 106096003239
Neki Oktapera 104096003091
Pipit Pitriani 106096003242

CHEMISTRY DEPARTEMENT
FACULTY OF SCIENCE AND TECHNOLOGY
ISLAMIC STATE UNIVERSITY SYARIF HIDAYATULLAH
JAKARTA
2010
Introduction

The health hazards of mercury compounds have been recognized for quite
sometime. In the early part of the 19th century, hat makers used a solution of
mercury salts to soften animal hairs in the production of felt. Hat makers were
known to exhibit bizarre behavior and terms such as "hatter's shakes" arose due to
the neurological symptoms of chronic (long-term) mercury poisoning.
Consequently, the Mad Hatter in "Alice in Wonderland" got his name because
hatters in Lewis Carroll's day often displayed quite erratic behaviour.

Mercury is a liquid metal at ordinary temperatures and pressures. More

importantly, it is a reactive element. Since it was first isolated, mankind has
developed an increasingly vast array of uses for mercury. The advances in
mercury toxicology have turned full circle, the knowledge of mercury poisoning
comes from studies of cases of acute poisoning. The present danger presents itself
as a chronic, low-level chronic exposure, also known as mercurialism and
micromercurialism.

Most people are familiar with elemental mercury in liquid state found in a
thermometer or thermostat. The most common source of chronic exposure is from
Amalgam in dental fillings, amalgam has been used for mettallurgical purposes
releasing mercury vapor. Vaccinations contain thimerosal used as a preservative,
exposing undeveloped organs at a critical stage. Then bioaccumulation of methyl
mercury in seafood, industrial uses and coal fired power plants.

Today, the main problem effects of mercury exposure to humans are

understood to be neurological, renal (kidney), cardiovascular and immunological
impacts. Chronic exposure to mercury can cause damage to the brain, spinal cord,
kidneys, liver and developing fetus. Exposure to mercury while in the womb can
lead to neurodevelopmental lems in children. Mercury can impair the ability to
feel, see, move and taste, and can cause numbness and tunnel vision. Long-term
exposure can lead to progressively worse symptoms and ultimately personality
changes, stupor, and in extreme cases, coma or death. Recent findings have
described adverse cardiovascular and immune system effects at very low levels.

Most people are exposed to mercury as a result of normal activities such as

the inhalation of air, contact with water and soil and/or exposure to substances or
products containing mercury such as dental amalgam. The main pathways for
mercury intake in humans are through the consumption of food, especially fish,
and the application of dental amalgams as a tooth restorative. Recent research has
indicated that exposure to mercury vapour resulting from past spills of liquid
mercury in the home may also be an important pathway.

In what form is emitted Mercury?

Mercury is a global pollutant with complex and unusual chemical and

physical properties. The major natural source of mercury is the degassing of the
Earth’s crust, emissions from volcanoes and evaporation from natural bodies of
water.

World-wide mining of the metal leads to indirect discharges into the

atmosphere. The usage of mercury is widespread in industrial processes and in
various products (e.g. batteries, lamps and thermometers). It is also widely used in
dentistry as an amalgam for fillings and by the pharmaceutical industry. Concern
over mercury in the environment arises from the extremely toxic forms in which
mercury can occur.

Mercury is mostly present in the atmosphere in a relatively unreactive

form as a gaseous element. The long atmospheric lifetime (of the order of 1 year)
of its gaseous form means the emission, transport and deposition of mercury is a
global issue.

Natural biological processes can cause methylated forms of mercury to

form which bioaccumulate over a million-fold and concentrate in living
organisms, especially fish. These forms of mercury: monomethylmercury and
dimethylmercury are highly toxic, causing neurotoxicological disorders. The main
pathway for mercury to humans is through the food chain and not by inhalation.

The main sources of mercury emissions in the UK are from the

manufacture of chlorine in mercury cells, non-ferrous metal production, coal
combustion and crematoria. UK emissions of mercury are uncertain and it is
estimated that the range is from 13 to 36 tonnes per year (DERA). Emissions are
estimated to have declined by around ¾’s between 1970-1998 (NAEI), mainly
due to improved controls on mercury cells and their replacement, and the fall in
coal use.

Whilst there has been a decline in the level of European emissions of

mercury, emissions from outside of Europe have started to increase – increasing
the level of ambient concentrations in the continent.

Effects of Mercury on the environment

Mercury is a toxic substance which has no known function in human

biochemistry or physiology and does not occur naturally in living organisms.
Inorganic mercury poisoning is associated with tremors, gingivitis and/or minor
psychological changes, together with spontaneous abortion and congenital
malformation.

Monomethylmercury causes damage to the brain and the central nervous

system, while foetal and postnatal exposure have given rise to abortion, congenital
malformation and development changes in young children.

Monomethylmercury (MeHg) participates directly in biochemical

reactions. MeHg is crated both by humans and by the environment. Industry uses
MeHg, and in the past poisoning were due to industrial discharge. MeHg is also
created through biomethylation processes in the environment and bioaccumulates
primarily in fish and people who eat fish.

Mercury compounds vapor can enter the body through various pathways,
including inhalation of vapor, ingestion, and skin contact. Most of the exposure to
elemental mercury comes from inhalation of mercury vapor, injections of
thimerosal and ingestion of MeHg.

Exposure Due to Food Consumption

Mercury emissions from natural and anthropogenic sources enter the

global mercury cycle and are distributed in the environment locally and globally
through various processes. Atmospheric emissions of mercury can enter the
environment through deposition onto soils and water. When mercury enters fresh
water bodies and the oceans, or settles into sediments and soils, it can become
involved in biogeochemical cycles, be transformed into the highly toxic form of
methylmercury, and bioaccumulate in the food chain. Predatory fish may attain
high levels of methylmercury that may be almost completely absorbed by human
or animal consumers.

While fish consumption is the main source of exposure to methylmercury,

Health Canada advises that the benefits and risks of eating fish should be
balanced, since fish are an excellent source of high-quality protein and omega-3
fatty acids, and are low in saturated fat. In order to protect Canadians from
mercury poisoning, a guideline of 0.5 parts per million, or 0.5 micrograms (1
microgram = one millionth of a gram) of total mercury per gram of fish tissue
(ug/g) has been established by Health Canada for most commercial fish.
Commonly consumed marine species such as salmon, cod, pollock, sole, shrimp,
mussels, scallops and canned tuna, have mercury levels that generally fall below
this limit and are therefore considered safe for consumption. The Canadian Food
Inspection Agency is responsible for testing mercury levels in canned tuna and
rejects any shipments bound for commercial sale in Canada if the 0.5 ppm limit is
exceeded.

Shark, swordfish and fresh or frozen tuna, which generally have

concentrations ranging from 0.5 to 1.5 ppm, are exempt from the 0.5 ppm limit
because they are considered "gourmet" fish not eaten in quantities sufficient to
pose a health hazard. Instead, Health Canada advises a consumption limit of one
meal per week of these fish for the average Canadian, and recommends that
women of child bearing age, pregnant women, and children should not consume
these fish more than once per month. Fish containing over 1.5 ppm are not
considered suitable for human consumption at any time.

Predatory, freshwater fish species such as pike, bass and walleye have also
been know to attain elevated methylmercury levels in various lakes and river
systems. If fish constitutes a staple part of the diet, such as for indigenous peoples
and recreational anglers, consumption of these species may pose an elevated risk
of mercury exposure. Federal, provincial and territorial agencies have issued fish
consumption advisories for the protection of the public, suggesting limited
consumption of specific fish species from certain lakes. In Canada, thousands of
advisories on fish species from individual water bodies are put in place in every
year due to excessive mercury contamination of fish tissues. Province-wide
advisories are in effect in New Brunswick and Nova Scotia while other provinces
have advisories for specific lakes and/or species.

Exposure Due to Inhalation

Based on available science, normal ambient air concentrations of mercury

vapour, averaging 1.6 nanograms per cubic meter of air, do not appear to be a
cause for concern (1 nanogram = one billionth of a gram). However, inhalation
can be a significant route of exposure when mercury-silver amalgam is used in
dental fillings, particularly for individuals that are hypersensitive to mercury.
Health Canada advises that mercury fillings should not be placed in the teeth of
pregnant women or people with impaired kidneys, and wherever possible, non-
mercury fillings should be used for children.

Exposure Due to Contact

Dermal contact is also a route of exposure to mercury with alkyl mercury

compounds being particularly notorious. While few Canadians come into direct
contact with mercury or its compounds, skin absorption can be lethal. In 1997, a
researcher named Karen Wetterhahn, from Dartmouth College in New
Hampshire, died when a single drop of dimethylmercury passed through her
protective latex glove and through her skin.

Heavy Metals adsorption process:

In the picture we can observe the way that follows the havy metals from the first
step of the pollution to the final step in the human body by menas the food.

Toxic Effects

The severity of mercury's toxic effects depends on the form and

concentration of mercury and the route of exposure. Exposure to elemental
mercury can result in effects on the nervous system, including tremor, memory
loss and headaches. Other symptoms include bronchitis, weight loss, fatigue,
gastro-intestinal problems, gingivitis, excitability, thyroid enlargement, unstable
pulse, and toxicity to the kidneys.
 The key to understanding why MeHg is so toxic is to see that structural
similarities in biochemical reactions can lead to active transport of toxins. In the
case of organisms with a highly advanced CNS, this active transport can lead to
accumulation of MeHg in the brain. The pathway of MeHg from the bloodstream
to the brain is complicated, to understand the pathway a number of processes are
involved:

• MeHg in blood plasma can combine with cysteine, forming a compound

that is structurally similar to the amino acid methionine.
• This MeHg-cysteine compound is actively transported into the endothelial
cells in the BBB, on the methionine carrier.
• A high level of reduced glutathione is maintained in the endothelial cells,
and the MeHg switches from a cystein carrier to a glutathione carrier.
• MeHg-glutathione is actively transported out of the endothelial cells and
into the brain.
• In the brain, the hydrolysis of MeHg-glutathione generates MeHg-
cysteine.

This MeHg-cysteine can now enter nerve cells in the brain, where it
accumulates. The reason why it accumulates is unknown, but it is known that
reduced glutathione levels are low in some neurons. It is thought that this low
level of reduced glutathione might allow MeHg-cysteine to remain in the cells,
unlike in the endothelial cells.

Furthermore, since MeHg-cysteine is structurally similar to the amino acid

methionine, it may interfere with protein synthesis in nerve cells. This is
especially likely, since methionine is always the first amino acid involved with
protein synthesis. However, the exact process is not yet fully understood.

Exposure to inorganic mercury can affect the kidneys, causing immune-

mediated kidney toxicity. Effects may also include tremors, loss of co-ordination,
slower physical and mental responses, gastric pain, vomiting, bloody diarrhea and
gingivitis.
 The toxicity of MeHg in the developing brain is even more complicated.
MeHg has been shown to affect proteins that are involved in the assembly of
microtubules in the nerve cells cytoskeleton. By noting that microtubules are
essential for nerve cell division and migration, we see how MeHg can affect brain
growth and development. This is why the fetal brain is particularly sensitive to
MeHg. Also, the BBB of the fetal brain is about three times more active in amino
acid transport, which only makes the MeHg brain concentration rate higher.

MeHg also produces subtle changes in the production and secretion of

neurotransmitters in the developing brain, which alters brain development in
subtle ways. For example, MeHg has been shown to accumulate in astrocyte cells
in the developing brain. One role of astrocytes is to regulate levels of the amino
acid glutamate in the developing brain. It happens that glutamate is toxic to the
developing brain. Since an inhibition of astrocyte cell function will enhance
glutamate levels, we can see an indirect path for mercury poisoning in the brain.
This is a very complex subject, and very little is known about the exact
developmental changes that are expected from MeHg.

Symptoms of methylmercury toxicity, also known as Minamata disease,

range from tingling of the skin, numbness, lack of muscle coordination, tremor,
tunnel vision, loss of hearing, slurred speech, skin rashes, abnormal behaviour
(such as fits of laughter), intellectual impairment, to cerebral palsy, coma and
death, depending on the level of exposure. In addition, methylmercury has been
classified as a possible human carcinogen by the U.S. Environmental Protection
Agency. More recently, additional findings have described adverse cardiovascular
and immune system effects at very low exposure levels.

Prenatal exposure to organic mercury, even at levels that do not appear to

affect the mother, may depress the development of the central nervous system and
may cause psychomotor retardation for affected children. Mild neurological and
developmental delays may occur in infants ingesting methylmercury in breast
milk. Affected children may exhibit reduced coordination and growth, lower
intelligence, poor hearing and verbal development, cerebral palsy and behavioural
problems.

Much of our knowledge of mercury toxicity comes from studying cases of

occupational or acute community poisonings. In 1956, Minamata disease (later
found to be methylmercury poisoning) was officially "discovered" in a Japanese
community near a polyvinyl chloride plastic plant which was discharging
untreated effluent containing methyl mercury chloride into Minamata Bay and the
Shiranui Sea. Once in the bay's sediments, the mercury was readily absorbed by
marine species, which resulted in the contamination of the entire ecosystem.
Many of the local residents consumed fish and seafood from the mercury-
contaminated waters as a staple part of their diet. Thirty-nine years later, 2 252
patients had been officially diagnosed with Minamata disease, and over 1 000 had
died.

The largest ever outbreak of mercury poisoning occurred in Iraq in 1971

and 1972 when the population accidentally ate bread made from seed-grain
treated with a mercury-based seed treatment pesticide. About 6 000 cases of
mercury poisoning were diagnosed. Over 500 cases were fatal. Instances such as
these highlight the critical need for governments to implement mercury
management strategies and to educate the public on the risks of mercury exposure.

Metabolism

When an individual is exposed to mercury, a certain percentage is

absorbed, depending on the route of exposure and the form of the mercury. About
80% of elemental mercury is absorbed when inhaled, however less than 1% of
ingested liquid mercury is absorbed. Methylmercury, on the other hand, is readily
absorbed irrespective of the exposure pathway. Approximately 95% of ingested
methylmercury is absorbed, and absorption through the lungs and skin is also
believed to be quite high. Both elemental and methylmercury can cross the blood-
brain and placental barriers. The critical target organ for elemental mercury is the
adult and fetal brain, and the critical target organs for methylmercury are the brain
and the kidneys.

Mercury vapor is nonpolar, monatomic gas, and lipid-soluble. For

example, let's follow the path of inhaled mercury vapor. From the lungs it
dissolves in blood plasma, and from there it has access to diffuse into the cell in
the body. Once inside a cell, mercury dissolves in blood plasma, and from there it
has access to diffuse into any cell in the body. Once inside a cell, mercury vapor,
itself unreactive is oxidized to the highly toxic mercury (+2) ion. This is also
known a divalent mercury. This oxidation process is mediated by the enzyme
catalase. Catalase normally functions in a two-step process to remove hydrogen
peroxide from cells. However, in the second step of this process, mercury vapor
can be oxidized to divalent mercury. There is also oxidized to divalent mercury,
this divalent mercury in the brain leads to strange symptoms, including erethism.
Mercury is also found to be the process linking behavioral symptoms and
Alzheimer's.

Inorganic mercury compounds do not readily migrate through the blood-

brain or placental barriers, but do accumulate in the kidneys. Absorption of
inorganic mercury varies with the type of inorganic salt. Within the body, the
kidneys accumulate the highest concentrations of all forms of mercury, yet
mercury can also concentrate in the brain, the central nervous system, the liver,
and indeed in most organs in the body.

Mercury is predominantly excreted from the body in urine and feces, but
usually at a slower rate than that of uptake, leading to the accumulation of
mercury in living tissue. Mercury is deposited in hair as it grows, and it may also
be found in breast milk. This may result in high concentrations in infants whose
mothers are heavily exposed. The unborn child also receives some of the maternal
mercury body burden because mercury compounds cross the placental barrier,
yielding equal or higher blood concentrations in the fetus than in the mother.

The standard methods for determining the concentration of mercury

compounds in the body involve urine, blood, fecal and hair samples with a
challenge test using a small portion of chelator to push out mercury. The problem
with these methods is that they only show a recent history of mercury exposure,
whereas mercury is a cumulative toxin. Since these tests cannot account for past
exposures, they are only valid indicators of recent, acute exposure. This is part of
the reason that there is so little known about chronic, low-level mercury exposure.

Unfortunately, by the time symptoms appear, usually the damage is

already done. This is complicated by the fact that mercury toxicity is difficult to
diagnose. However, when mercury contamination is diagosed and there is still a
concentration of mercury in the body. Removal of all sources is first necessary,
followed by chelation therapy that may help. Chelation therapy involves the
formation of a complex of mercury with a chelate ligand. DMSA, EDTA and
DMPS are such chelating ligands used in the treatment of heavy metals. Do not
use a chelator without fully understanding which metals they chelate and the
possibility of permanent damage due to the organs lack of ability to remove
toxins. Doses of chelating agents increase the blood and urine concentrations of
mercury, and thus help eliminate it from the body.

Mercury molecule and mercury molecule bound as in chelation.

Most of the effects involve complex biochemical reactions that are

affected by the presence of mercury compounds. These include the immune
system, particular organs, brain growth and development and behavioral patterns.
Chronic mercury exposure is an important area of study.
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hc.cfm+pathway+toxic+body&cd=30&hl=id&ct=clnk&gl=id

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