Unit 3

2.CHEMICAL TOXICOLOGY

2.1 Toxicology is the study of poisons.

"All things are poison and nothing is without poison; only the dose makes a thing not a
poison." Only the right dose differentiates poison from a remedy .

Swiss-German physician Paracelsus

father of toxicology ( 1538)

Toxicology is the study of the adverse effects of poisonous substances on living organisms.
It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially
the poisoning of people.

Various Branches of Toxicology

• Forensic Toxicology – Forensic toxicologists are often involved in providing

toxicological information in support of legal activities.
• Environmental Toxicology – Environmental toxicologists are concerned with the
interaction of toxic substances with all components of the ecosystem.
• Regulatory Toxicology – Regulatory toxicologists are involved in compiling and
evaluating existing toxicological information to establish concentration-based standards
of “safe” exposure.
• Food Toxicology – Food toxicologists are involved in delivering a safe and palatable
supply of food to the consumer.
• Clinical Toxicology – Clinical toxicologists are concerned with diseases and illnesses
associated with acute or chronic exposure to toxic chemicals.
• Occupational Toxicology – Toxicology concerned with health effects from exposure to
chemicals in the workplace .The main aim is to protect workers from toxic environment
and to make work place safe .

1
2.2 TERMINOLOGY

• Toxic : Poisonous or deadly effects on the body by inhalation , ingestion ,adsorption or

dermal contact .
• Toxicant : An agent that can produce adverse biological effect .May be chemical ,
physical or biological in form .
• Toxin : Toxic substance produced naturally . It could be a poisonous substance of
microbial , plant or animal origin which reacts with a specific cellular component to kill
cells or organisms or can alter the growth or development of target organisms .eg
bacterial protein which cause tetanus or virus .

Such virus may cause Emerging and Re emerging diseases - not previously observed in
humans Usually jumps from animal host Ex: AIDS, lime disease, West Nile Virus
,SARS,MERS . Reemerging Disease- existed in the past and are recently increasing in
incidence Ex: tuberculosis, yellow fever, malaria

• Toxicity : Toxicity is the intrinsic capacity of a chemical agent to affect an organism

adversely .It basically defines the degree (sometimes related to quantity also ) to which
substance is toxic .

 Acute toxicity :Adverse effects occur within a short period after exposure to high
dose of toxicant leading to rapid development of symptoms . Can be reversed but
may result in death of individual also . In 1989, 5,000 people died and 30,000
were permanently disabled due to exposure to methyl isocyanate from an
industrial accident in India.
 Chronic toxicity :Adverse effects occur some time after exposure, or after
prolonged exposure to relative low dose of toxicant . It is often irreversible. Eg
Chronic bronchitis in long-term cigarette smokers.

A single compound may generate both acute and chronic toxic effects depending
on dose and duration of exposure .

 Selective toxicity : If two species are simultaneously exposed to any toxicant ,

The toxicity is selective to one species or one organ without harming another life
form . example: penicillin, DDT

2.3 TOXIC EFFECTS

• Lethal effect : Cause instant death

• Sub lethal effect : Serious but doesn’t lead to death . Workplace exposure to lead over a
period of several weeks can result in anemia.

2
 1. Local effect : are observed on the part of the body that first came in contact with
the chemical example: acid burns
2. Systemic effect : require that the chemical is uptaken and distributed to the target
organ. Adverse health effect is visible at the location distant to the point of
contact .
3. Cumulative effect : It is characterised by materials that tend to build up in the
body as a result of numerous chronic exposure .
4. Synergistic effect : When two or more hazardous materials are present at the
same time ,the resulting effect can be greater than the predicted effect based on
the individual substance.

2.3.1 Dose : The dose is the actual amount of a chemical that enters the body. “Dose”
refers to the concentration or amount of a substance inside an exposed person or organism

2.3.2 Response :Any biological effect by exposure is response . As the dose of toxic
substance increases , the mortality and morbidity of organism also increases .

2.3.3 Xenobiotics :It is a term for “foreign substances”, that is, foreign to the organism. Its
opposite is endogenous compounds. Xenobiotics include drugs, industrial chemicals,
naturally occurring poisons and environmental pollutants.

2.3.4 Target organs : An organ which is damaged by the xenobiotics . Target organ is the
primary or most sensitive organ affected after exposure.

2.3.5 Immune system :

• The major function of the immune system is defense against bacteria, viruses, parasites,
fungi and neoplastic cells.
• When the body senses foreign substances (called antigens), the immune system works to
recognize the antigens and get rid of them. B lymphocytes are triggered to make
antibodies. Antibodies thus produced protect the person from future attack by the germ.
• Adaptive (or acquired) immunity creates immunological memory after an initial
response to a specific pathogen, leading to an enhanced response to subsequent
encounters with that same pathogen. This process of acquired immunity is the basis
of vaccination.
• Disorders of the immune system can result in autoimmune diseases , inflammatory
diseases and cancer

2.3. 6 Senstivity :

People may vary in their sensitivity . It depends on age ,sex ,diet , state of health .Generally infants with
undeveloped systems and old people (poor immune system) are more sensitive to toxic
chemicals

3
Tolerance to a chemical may occur when repeat exposures result in a lower response than what
would have been expected without pretreatment

2.4 DOSE –RESPONSE RELATIONSHIP :

• The dose-response relationship is the relationship between exposure and health effect.
With increasing dose a greater number of individuals in the exposed population will
usually be affected.
• A dose-effect curve may be obtained at the level of the whole organism, the cell or the
target molecule.
• Dose response relationship is based on observed data from experimental, human and
clinical trials . The logarithm of measured dose (mg , ugm or gm/ kg of body weight is
generally plotted on the X axis and the response is plotted on the Y axis .
• Below threshold dose there is no adverse effect from exposure to the substance as human
body possess the ability to remove small dose of toxic substance by breaking it down
through liver and kidney .

Response ↑
Dose mg/kg →
Threshold dose
LD 50%
Dose –response curve are basically used to statistically derive dose estimates of chemical
substance

LD90 –the statistically derived dose that will kill 90% of the sample population
LD50 –the statistically derived dose that will kill 50% of the sample population
LD10 –the statistically derived dose that will kill 10% of the sample population

For inhalation or aquatic toxicity ,air concentration are used for exposure value
LC90-Lethal Concentration 10%
LC50 Lethal Concentration 50%
LC90 Lethal Concentration 10%

4
Toxic dose are used to indicate doses that cause adverse toxic effects like reduced
enzymatic activity , loss of hearing ,nausea, fatty liver fever in given percentage of sample
population .
TD90 - the dose that will give a toxic effect in 90% of the sample population
TD50- the dose that will give a toxic effect in 50% of the sample population
TD10- the dose that will give a toxic effect in10% of the sample population
TD0-Non toxic

Examples . LD50 = 200 mg/kg (0f caffeine on rat)

economical and ethical issues involved (AS more than 100 animals are generally taken for for a
clinical test)

ED50 g Generally used for Pharmaceuticals

• 50% of the test organisms exhibited the therapeutic effect after consuming it
• ED50 of Paracetamol would be the dose that relieves high body temperature of the body
in 50% of the people .

Substance Non toxic/Effective Toxic Dose Lethal dose

dose
Alcohol in blood 0.05% 0.1% 0. 5%
level
CO %HB bound <10% 20-30% >60%
Aspirin 0.6 gm(2 tablet) 9.7gm(30 tablet) 34gm(105 tablet)

5
 Two terms often encountered are

No Observed Adverse Effect Level (NOAEL) : Highest dose at which no adverse effect
visible

Low Observed Adverse Effect Level (LOAEL): Lowest dose at which adverse effect
start appearing

They are the actual data points from human clinical or experimental animal studies.
NOELs and LOELs do not necessarily imply toxic or harmful effects and may be used to
describe beneficial effects of chemicals as well..

2.5 Route of Entry of Toxicant into the body

The route of exposure describes the way in which chemical substance enters in the body .

• Inhalation :absorption by respiratory tract through lungs

• Absorption : through skin
• Ingestion: through GI tract
• Intravenous : injected in bloodstream

2. 5.1 Chemical Interactions The effect that one chemical has on toxic effect of another
chemical is Chemical Interaction . Human beings are exposed to more than one chemical at a
point of time The presence of one chemical may drastically affect the response to other chemical
. It is difficult to estimate the total effect of a mixture of chemicals!

• Independent effect - two compounds are toxic independent of each other

2+2=2

• Additive effect - The sum of the the two independent effects caused by each drug .
example: toluene + xylene 2 + 2 = 4

• Synergistic effect - The united effect is stronger than the additive effect. Exposure to one
chemical dramatically increases effect of another chemical .
example: cigarette smoking and exposure to radon .2 + 2 = 8

• Potentiating effect - one of the compounds is not toxic in itself but enhance
The toxic effect of another compound 0 + 2 = 4
example: 2-propanol + carbon tetrachloride (hepatotoxic )

• Antagonistic effect - one compound opposes the effect of another 2 + 2 = 1

It is the basis of every antidote

2. 5.2 Damages caused by Toxic substances :

6
Harmful chemicals can get into the human body by breathing, eating, or drinking and they can
be absorbed through skin also. Toxicant may enter human body by two mechanism :

Systemic Toxicant: A systemic systemic toxin is one that affects affects the entire body or many
organs rather than a specific specific site . For example, potassium cyanide is a systemic toxicant
in that it affects virtually every cell and organ in the body by interfering with the cell's ability to
utilize oxygen.

Organ Toxicant : A organ toxin is one that affects affects only specific tissues or organs. Eg:
Benzene is a specific organ toxin in that it is primarily toxic to the blood-forming tissues. Toxic
effects may range from damage to an enzyme system ,disruption of protein synthesis , production
of reactive chemicals in cells and DNA damage .

1. Physiological damage

• Irritant : Cause inflammation of skin and mucous membrane

• Corrosive : A material that can destroy human tissue eg : acid , alkali

• Asphyxiant : A chemical substance which deprives tissue of Oxygen and causes

suffocation by displacing Oxygen .Eg: CO

• Anaesthetic :Depresses CNS .Eg: Alcohol, halogenated hydrocarbons

• Hepatotoxic : Toxic to liver bile duct and gall bladder . Can damage liver

• Nephrotoxic : Toxic to the kidneys. It can result in systemic toxicity. Decreased ability

to excrete body wastes

• Neurotoxic : Cause damage to cells of the central nervous system (brain and spinal cord)

and the peripheral nervous system (nerves outside the CNS). Eg: Hg, Pb

• Hematopoetic toxic : results from xenobiotics acting directly on cells in circulating

blood, bone marrow, and the heart.Eg Benzene , xylene , CO, cynide

• Pulmonary toxic Causes Pulmonary irritation, Asthma/bronchitis , lung disease

,Pneumoconiosis and Lung cancer eg Eg:Silica , Asbestos ,Mica

• Reproductive toxic Involves toxicant damage to either the male or female reproductive

system It will result in increased birth defects, and infertility. Eg :Pb

7
 2. Carcinogenic : Carcinogens are substances or factors that can cause cancer.

Examples can include chemicals, medical or environmental radiation, some viruses,

lifestyle factors, and even some medications eg :PAH.

3. Mutagenic : Anything that causes a mutation (a change in the DNA of a cell). DNA

changes caused by mutagens may harm cells and cause certain diseases, such as

cancer. Examples of mutagens include radioactive substances, x-rays, ultraviolet

radiation,

4. Teratogenic : Teratogens may cause a birth defect in the child. Or a teratogen may

halt the pregnancy outright. The classes of teratogens include radiation,

Pb,Thalidomide

2. 6 TOXIC CHEMICALS IN ENVIRONMENT

Toxic chemicals are substances which may be harmful to the environment or hazardous to health

conditions . Whenever chemicals are not properly managed they can put human health and

ecosystems at risk.

❖ Outdoor air pollutants World Health Organization estimates that more than 90% of the

world’s population breathes unsafe air.

1. Ozone (O3)
2. Nitrogen Oxides (NOx)
3. Carbon Monoxide (CO)
4. Sulfur Dioxide (SO2)
5. Particulate Matter (PM10 and PM2.5)

❖ Heavy metals: Heavy metals are important component of the earth crust and it comes

into atmosphere through mining ,metallurgical operations and manufacturing processes

8
 . Once introduced into the environment, it cannot be biodegraded. They persist

indefinitely and cause pollution of air, water, and soil. Some metals comes under the

category of essential minerals which are required for proper growth and metabolism for

eg Mg, Zn,Mn ,Fe,Cu .Some other metallic minerals are considered to be highly toxic

even in trace amount eg Cd,As,Hg Pb and Cr to name a few .

❖ Radiation and Radioactive materials : Cosmic rays and the decay of radioactive

isotopes are the primary sources of natural ionizing radiation on earth . Ionizing

radiation can be generated artificially by X-ray tubes and various methods that

produce radioisotopes artificially. There are three types of nuclear radiation: alpha, beta

and gamma. Alpha is the least penetrating, while gamma is the most penetrating. Low

levels of radiation are not dangerous, but medium levels can lead to sickness,

headaches, vomiting and a fever. High levels can kill you by causing damage to your

internal organs. Exposure to radiation over a long time can cause cancer. Non-ionizing

radiation is relatively low-energy radiation that doesn't have enough energy

to ionize atoms or molecules. It's located at the low end of the electromagnetic

spectrum. Although considered less dangerous than ionizing radiation, overexposure

to non-ionizing radiation can cause health issues like altering the mechanism for DNA

❖ Polychlorinated Biphenyls : A polychlorinated biphenyl (PCB) is an organic chlorine

.compound with the formula C12H10−xClx 1-10 carbon atom attached to biphenyls . Polychlorinated

biphenyls are a group of 209 different chemicals which share a common structure but

vary in the number of attached chlorine atoms. They were once widely deployed

as dielectric fluids in capacitors , adhesives and plasticizers. It is classified as persistent

organic pollutants . In human being , they accumulate in fat tissues and undergo bio

9
 magnification and bioaccumulation . Microplastics are a major contributor of PCB's into

the biosphere and aquatic environment . Studies of PCBs in humans have found

increased rates of melanomas, liver cancer, gall bladder cancer, biliary tract cancer,

gastrointestinal tract cancer, and brain cancer . PCBs were banned in 2016 amid

suggestions that these chemicals could have unintended impacts on human and

environmental health.

❖ Pesticides : Pesticides are substances that are used to control pests .The term pesticide

includes herbicide, insecticidestermiticides, nematicide, molluscide, rodenticide,

bactericide, insect repellent, antimicrobial and fungicide .Pesticides include

Organophosphorous , Organochlorine and Carbamate pesticides . Over 98% of

sprayed insecticides and 95% of herbicides reach a destination other than their target

species, because they are sprayed or spread across entire agricultural fields. Runoff can

carry pesticides into aquatic environments while wind can carry them to other fields,

grazing areas, human settlements and undeveloped areas, potentially affecting other

species.

2. 6 .1 IMPACT OF TOXIC METALS ON ENZYMES

• An enzyme is a large protein molecule containing one or more active sites where

interaction with the substrate takes place . Toxic chemicals attach the active site of the

enzymes and thus inhibits enzymatic functioning .Metals commonly binds to biological

compound containg Sulphur,Nitrogen,Oxygen affecting the protein structure .

10
 • Heavy metals are electrophilic and reacts with nucleophilic group (viz SH,PO4,NH2

group )on enzymatic protein in the body .These heavy metals (Cd2+ ,Hg2+ etc )compete

with endogenous metals required by body like Ca2+,Zn2+ which also need to bind with

same active sites of the protein. One metal ion replaces another metal of same size.

• Example :Distruption of enzymatic function .

2. 6 .2 Arsenic: As(0) Non toxic due to insolubility in water and body fluid
As(iii) Most toxic Permissible limit (0.05mg/l)
As(V)
Organic Arsenoxides less toxic

Sources :

• The insecticides, fungicides and herbiacides contain arsenic.

• Pesticide in food : grapes ,tobacco plant , sea foods are sprayed with Arsenic
containing pesticide .
• As mineral inside the earth crust . Burning of fossil fuel.
• In industrial processes , it is a by product of smelting of many metal ores. In
electronic industry, Gallium Arsenide is used in semiconductors ,LEDs
,microwave devices ,chemical cells etc

Exposure pathways : Ingestion and inhalation . Almost 80percent of soluble Arsenic is

absorbed through GI tract in human body .Airborne Arsenic is As(iii).

Health Effects :

11
About 70% of the Arsenic absorbed into the body is converted by the liver to less toxic
methylated form that is efficiently excreted out .

Respiratory Effects : Effects of arsenic on the human respiratory system have been reported both
from occupational exposure as well as from underground water arsenic toxicity Chronic
asthmatic bronchitis and asthma is a common complications.

Cardiovascular Effects: Chronic inhalation of arsenic trioxide can increase the risk of death in
humans from cardiovascular disease. Long term inhalation of inorganic arsenic could injure the
blood vessels or the heart.

Gastro ntestinal Effect: Acute exposure of inorganic As (iii) may lead to gastrointestinal
irritation from acute arsenic poisoning include burning lips, painful swallowing, thirst, nausea,
irritation of stomach and intestine and several abdominal colic .

Hematological Effects: High concentration of arsine (10 ppm) cause death within hours due to
red blood cell haemolysis.

Renal Effects: May cause acute renal failure and chronic renal insufficiency .

Skin and Lung Cancer : dermal keratosis and lung cancer were detected on exposure of
humans to water-soluble inorganic arsenic through drinking water with high natural arsenic
content in some areas of West Bengal.

Neurological effect : Ingestion of inorganic Arsenic can result in neural injury,both the
peripheral and central components of the nervous system can be damaged by Arsenic causing
numbness loss of reflexes, and muscle weakness. In extreme cases it may result in gangarene of
lower limbs “black foot disease “

Reproductive effect : A very high exposure to inorganic arsenic can cause infertility and
miscarriage in women

Biochemical Effects of Arsenic : Arsenic is a protoplastic poison due to its effect on

sulphydryl group of cells interfering with cells enzymes, cell respiration and mitosis

• Complexation with enzymes : As (III) exerts its toxic action by attacking SH groups

of an enzyme thereby inhibiting enzyme action .

12
• Uncoupling of Phosphorylation : Being similar to P, arsenic interferes with the

generation of ATP (adenosine triphosphate. Normally ATP is obtained from

glecereldehyde -3 –phosphate by enzymatic synthesis of 1,3 diphosphoglycerate .

Arsenic interacts by producing 1-arseno-3-phosphoglycerate instead of 1, 3

diphosphoglycerate which prevents ATP formation.

• Coagulation of Protein : In biological systems, As (III) compounds at high

concentration coagulates proteins by attacking the sulphur bonds maintaining the
remaining part of the structure.

Blackfoot disease or Keratosis

13
2. 6 .3 Cadmium : Extremely toxic .Cadmium is a metal of the 20th century. It is a

byproduct of zinc and Pb production , found in association of zinc minerals. Almost 30,000 ton

of Cd is annually released due to weathering of rock .

It generally exists as a divalent cation, Occurs in nature as oxides , sulphides and carbonates
Soils and rocks, including coal and mineral fertilizers, contain some amount of cadmium.

Sources : Commercially, Cd is used in television screens, lasers, batteries, paint pigments,

cosmetics, and in galvanizing steel. Released from burning of fossil fuel
Cigarette smoking is considered to be the most significant source of human cadmium exposure

Route of Exposure : From inhalation and ingestion (20 -40 ug per day).

Health Effects : At high levels cadmium causes kidney problems, anemia and bone marrow disorder.
High level of cadmium ion causes renal dysfunction, hypertension and cancer.

Biochemical Effect of Cadmium

The major portion of cadmium ingested in our body is trapped in the kidneys and gets
eliminated by binding with the proteins namely metallothionein produced by the Liver.
Metallothionein boud Cd is released from liver into blood where it is filtered by kidney and 99%
gets eliminated .and rest is accumulated . With age the accumulation of cadmium in the body
increases.
When excessive amounts of Cd2+ are present in the body, it replaces Zn 2+ at key enzyme sites
causing metabolic disorders.
14
ITAI - ITAI Disease : Cadmium poisoning causing softening and fragility of the bones
Osteomalecia/Osteoporosis and kidney failure
2.6.4Mercury :
Metal Mercury : Hg(0).Ingested form is not absorbed ; Liquid butcan be vapoursised
Inorganic Mercury :Occurs in solid states as mercurous or mercuric salts
Organic Mercury CH3Hg : 90% of any methylmercury ingested is
absorbed into the bloodstream from the GI tract.

Source : Mercury is one of the most well known toxic metal.

• Granite rock accounts for more than 80% of the mercury found in the atmosphere and on
the earth’s surface
• Mercury is found in many industries, such as battery, thermometer, and barometer
manufacturing.
• Some consumer products that contain mercury include automotive equipment with halide
relay switches, fluorescent and high-intensity discharge lamps
• Inorganic salts of Hg is used in skin lightening cream. As dental amalgam
• Mercury in any form is toxic. The difference lies in how it is absorbed, how it is
biotransformed to other mercury forms

Exposure Pathways : Mercury poisoning can result from vapor inhalation, ingestion, injection,
or absorption through the skin.

Health effects : Mercury is very toxic and exceedingly bioaccumulative. Its presence adversely
affects the marine environment and hence many studies are directed towards the distribution of
mercury in water environment. Major sources of mercury pollution include anthropogenic
activities such as agriculture, municipal wastewater discharges, mining, incineration, and
discharge of industrial wastewater

Organic mercury primarily affects brain .CH3Hg is most toxic form and accumulates in
CNS causing neurotoxic effects in adults and even in foetus of expecting mother .

Inorganic Mercury Effects kidney and may lead to abdominal cramps and bloody
diarrohea . Sometimes get converted to organic mercury .

Metallic Mercury is slowly absorbed in GI tract and is not as toxic as CH3Hg but its
vapours can saturate the air .

Biochemical Effects of Mercury:

15
Inorganic Mercury : Mercury ions produce toxic effects by protein precipitation, enzyme
inhibition, and generalized corrosive action. Mercury binds to sulfhydryl groups of protein .
Enzymes ,once bound to mercury, are rendered inactive.

Organic Mercury : It is 100-1000 times more toxic .Highly lipophilic and get absorbed
through GI tract .Once absorbed ,it gets distributed through out the body accumuling in brain ,
kidney , liver ,hair and skin ,can even cross blood –brain barrier and placental barrier causing
birth defects . It also penetrates erythrocytes and cause neurological symptoms .

The toxicity or the toxic effects of mercury came to lime light in 1953-1960 in Japan by the
incidence of Minamata Disease. At Minamata Bay in Japan, more than 100 people died and
thousands were permanently paralysed by consuming fish contaminated with mercury. Even
genetic defects were observed in some new born babies whose mothers had consumed
contaminated fish from the Bay. The cause of the disease was contamination of water with
mercury rich effluents discharged into the Bay by Chisso Chemical Company.

CH3Hg in Food Chain :Bioaccumulation of Hg takes place inside the aquatic species .Once Hg
containing effluent is discharged in water , methylation of mercury in water bodies is brought
about by microorganisms called methanogenic bacteria. This process is called bio-methylation.
The bio-methylation takes place under anaerobic conditions. The process is facilitated by the
enrichment of water with organic impurities which permit growth of methanogenic bacteria, the
bio-methylation proceeds smoothly in the pH range 5.5-6.5.Inorganic Hg gets converted into
CH3Hg . It was absorbed by gills of fishes and aquatic organisms . Eventually fishes are eaten by
secondary and then tertiary consumers . The amount of CH3Hg keeps on increasing as it passes
through various level of food chain.

Metallic Mercury : Inhalation is a major exposure route of elemental mercury in the form of
mercury vapor. Inhaled mercury vapor is readily absorbed in the lungs, and quickly diffused into
the blood and distributed into all of the organs of the body . Absorbed elemental mercury is
oxidized to the mercuric form (Hg++) in the red blood cells and tissues.

2.6.5 Lead : Lead is an abundant toxic metal which is relatively easy to mine. Occurs as
compound eg PbCO3 .

Inorganic lead Toxic

Organic Lead Most toxic

16
Lead is spread so widely throughout the environment, it can be found in everyone's body today.

The major sources of lead released to water are lead water supply pipes ,plumbing and solder in
houses, schools, and public buildings.
• Food and beverages may contain lead if lead-containing dust deposits onto crops while
they are growing and during food processing. Imported food cans that are sealed with Pb
soldering .

• Smelting and refining industries, Steel welding and cutting operations, battery
manufacturing plants, gasoline stations, and radiator repair shops.

• The production of chemicals, including pain , pigments ,potteries .. Children who put toys
or other items in their mouths may also swallow lead if lead-containing dust and dirt are
on these items.

Exposure Pathways :

• Body absorbs organic lead faster than inorganic lead.Organic lead is easily absorbed
through skin But most lead encountered today are inorganic due to gradual phasing out of
TEL as additive in gasoline fuel . For an average city dweller ,total intake is about 225
ug/day out of which 200ug/day is excreted out through urine and rest get stored in bone.s

• Exposure to lead can occur by contaminated air, water, dust, food, or consumer products.
Lead can enter into our body when we breathe air containing lead dust, drink water or eat
food containing trace of Pb .Almost all of the lead in the lungs enters the blood and
moves to other parts of the body. Children are most susceptible to lead poisoning .

Health Effects :

• Exposure to high levels of lead may cause kidneys of adults and children to be badly
damaged. Also, high levels of lead may affect the sperm or damage other parts of the
male reproductive system ,abdominal pain , vomiting , anorexia .

• Elevated Pb levels in blood causes anemia, brain damage, convulsions , mental

retardation in kids , learning difficulties and behavior problems also .

17
Biochemical Effects of Lead : Chronic poisoning usually presents with symptoms affecting
multiple systems, but is associated with three main types of systems , hematopoetic ,renal
and neurological system .

a) The major biochemical effect of lead is that its interference with heme-synthesis, which lead
to hematological damage. Pb inhibit the key enzyme involved in the overall process of heme-
synthesis. It inhibits conversion of delta amino livulinic acid to prophobiugen which is precursor
of hemoglobin . The overall effect is the disruption of the synthesis of hemoglobin.

c) Pb does not permit the utilization of O2 and glucose for life sustainaing energy production.
d) Regardless of how lead enters your body, most of it is stored in bone due to similarity with
Ca2+ , bones act as repositories of Pb in body . Lead stored in bone may be remobilized into the
blood during pregnancy, thus exposing the fetus.

e)Neurological Effect : The brain is the most sensitive organ to lead exposure. Lead is also
involved in interfering with the release of Neurotransmitters ( chemicals used by neurons to send
signals to other cells). For infants or young children, lead exposure has been shown to decrease
intelligence (IQ) scores, to slow growth, and to cause hearing problems.

f) Renal effect : increased risk of high blood pressure , irreversible nephropathy leading to
kidney damage. Functional impairment of tubular region leading to Aminoaciduria ,gycosuria
and phosphaturia

2. 6.6 Chromium

Chromium is the seventh most abundant element on earth Chromium occurs in several oxidation
states in the environment ranging fromCr2+ to Cr6+ and zerovalent Cr .The most common forms
of Cr are trivalent- Cr+3 and hexavalent-Cr+6 , with both states being toxic to animals, humans
and plants .

Sources :
• Chromium is naturally occurring element found in rocks ,animals, plants ,soil
,volcanic dust and gases .
• Hexavalent chromium can be found in some dyes and paints, as well as in some leather
tanning products .It is widely used in aerospace and automobile refinishing applications
• Zerovalent Cr is used in making steel and alloys.

18
 • Chromium(III), is an essential trace mineral in the human diet. It is also a nutritional

supplement . Chromium III is used in brick lining for metallurgical furnaces.

Exposure pathways : Since Cr(III) is poorly absorbed by any route, the toxicity of chromium is
mainly attributable to the Cr(VI) form. It can be absorbed by the lung and gastrointestinal tract,
and even to a certain extent by skin also .

Chromium III exposure can take place by ingesting food containing chromium III compound and
through dermal contact . Acidic food in contact with steel utensils contains high level of
chromium because of leeching through stainless steel .

Health effect :

• When inhaled in quantity more than 2ugm /m3, chromium VI is respiratory tract
irritants, resulting in airway irritation, airway obstruction, and lung, nasal, or sinus
cancer. Also adversely affect kidney and liver .
• Chromium (III) is an essential trace nutrient that helps the body use sugar ,protein and fat
. An intake of 70-200ug per day is recommended for adults as a dietary supplement
.Defeciency of CrIII leads to diabetic like condition and high dose causes skin irritation .

Biochemical effects :

• Chromium III enhances the action of Insulin , a hormone responsible for metabolism of
carbohydrate and protein in human body .

• Chromium VI gets easily absorbed than CrIII but once inside the body , it gets converted
to CrIII and get distributed to muscles , kidney and liver .

• Principal carrier protein for chromium is transferrin. Transferrin play a role in movement
of Cr from blood to LMW Cr-binding substance composed of glycine , cystine , glutamic
acid . Cr then passes through kidney and then eleminated through urine .

19
20