Introduction to Toxicants

UNIT 1 INTRODUCTION TO TOXICANTS

Structure
1.0 Introduction
1.1 Objectives
1.2 Definition and Concepts
1.3 Sources of Toxicants
1.4 Mode of Action of Toxic Substances
1.5 Exposure Routes
1.6 Distribution and Storage of Toxins in Human Tissues
1.7 Let Us Sum Up
1.8 Key Words
1.9 References and Suggested Further Readings
1.10 Answers to Check Your Progress

1.0 INTRODUCTION
We are exposed to different substances in our everyday life and some of these
may be toxic to our health. The quality of our environment is also decreasing
and people are exposed to a variety of pollutants. These pollutants can have
acute, chronic, sub-acute and toxic effects on the living organisms as well as
human beings. Substances that we use in daily life starting from paints, detergents,
cleaning solutions, cosmetics etc. can have hazardous chemicals which can have
toxic effects on our health. Rachel Carson is considered the mother of
environmental toxicology. She published the book Silent Spring in 1962 which
discussed the toxic effects of the pesticide DDT. Living organisms can be exposed
to toxic substances at any stage of their life cycle. They can be accumulated in
the fatty tissues and lead to bioaccumulation. This can lead to biomagnifications
of specific toxicants. In this unit let us learn about toxins, toxicants, their types,
sources and the mechanisms of their action.

1.1 OBJECTIVE
After reading this unit, you should be able to:
 define toxins and toxicants;
 understand the different concepts and terminologies used in environmental
toxicology;
 explain the different sources of toxicants;
 describe the routes of exposure to toxicants;
 understand the mechanisms and site of toxic action by toxicants; and
 explain how toxins are stored in the various tissues of the human body.

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Introduction to Toxicology
1.2 DEFINITIONS AND CONCEPTS
1.2.1 Definitions
Let us now learn about some definitions and terms commonly used in
environmental toxicology.
a) Environmental toxicology: It is a branch of science that deals with the
harmful effects of different physical, chemical and biological agents on
living organisms. It is multidisciplinary in nature.
b) Ecotoxicology: This is a sub-discipline of environmental toxicology. This
deals with the harmful effects of toxicants at ecosystem and population
levels.
c) Toxicant: Any toxic material or substance is termed as a toxicant. They are
hazardous and poisonous. Toxicants are generally man-made and artificial
products introduced into the environment due to human activity. They
include bisphenol, insecticides and a number of industrial chemicals.
d) Toxins: These are produced naturally by living organisms. For example,
toxins from the mushroom plant and toxin from the venom of snake are
natural toxins.
e) Poisons: They are toxicants that cause death or illness in very small doses.
f) Toxicologists are scientists who deal with the study of toxicants and toxins.
g) Xenobiotic is referred to a foreign substance entering the body. It is derived
from the Greek word ‘xeno’ meaning ‘foreigner’.
h) Toxicosis/ Poisoning/ Intoxication: Any disease produced by a toxicant.
i) Tolerance: The ability of an organism to show less response to a specific
dose of a chemical than it demonstrated on a previous exposure; refers to
acquired and not innate resistance.
j) LD 50: The dose that is lethal to 50% of a test sample or population.
Expression of toxicant concentrations is in ppb or ppm in feedstuff, water,
air, tissue etc. Other expressions of dose are maximum nontoxic dose,
maximum tolerated dose, approximate lethal dose.

1.2.2 Basic Concepts of Toxicology

Both toxins and toxicants are referred to as toxic substances. Toxic substances
can be classified as systemic toxins and organ toxins. Systemic toxins have effects
on the entire body. An example of systemic toxin include: potassium cyanide. It
affects each cell and organ of the body causing complete damage. Some toxicants
affect specific tissues or organs. They are known as organ toxins. They do not
cause damage to the entire body. An example of organ toxins include: (1) benzene
which targets blood-forming tissues and (2) Lead which targets the central nervous
system, kidney, and the hematopoietic system.

1.2.3 Historical Development of Toxicology

The historical development of toxicology started very early in human civilizations.
Our ancestors who were cave dwellers found plants and animals that had toxins
6 and these toxic extracts were used in hunting and warfare. The earliest medical
works of Hippocrates, Aristotle, and Theophrastus published during 400 to 250 Introduction to Toxicants
BC include the mention of poisons. Scriptures and records indicate that by 1500
BC hemlock, opium, arrow poisons, and certain metals were also used to poison
enemies or for state executions. Some of the notable poisoning victims include:
Socrates, Cleopatra, and Claudius. After Renaissance and Age of Enlightenment
some basic concepts fundamental to toxicology started to evolve. In toxicology
the study of Paracelsus (~1500AD) and Orfila (~1800 AD) are of importance.
Advances in toxicology took place during the time of Galen (AD 131–200) and
Paracelsus (1493–1541). Paracelsus in his study showed that specific chemicals
were responsible for the toxicity of a plant or animal poison. He also reported
that the dose of a chemical is an important factor for the human body’s response.
This is now studies as the dose-response relationship. It is an important concept
of toxicology. Hence, Paracelsus was one of the founders of modern toxicology.
His well known quote says that “All substances are poisons; it is the dose that
makes the poison”. Aspirin which is acetylsalicylic acid is a drug consumed by
people for medical ailments all over the world. It is relatively safe at recommended
doses but chronic use causes deleterious effects on the gastric mucosa, and it is
fatal at a dose of about 0.2 to 0.5 g/kg. In the 18th century ‘Ramazini’s Diseases
of Workers’ was published in 1700. He is known as the father of occupational
medicine. The incidence of scrotal cancer among those working in chimney
sweeps was observed by Percival Pott in 1775. Also Hill in 1761 said that nasal
cancer and snuff use is correlated. The founder of modern toxicology was Orfila,
a Spanish physician who worked at the University of Paris in the early 19th century.
He brought out the systematic correlation between the chemical and biological
properties of poisons of the time. He analyzed materials for poisons and showed
the effects of poisons on specific organs. He was responsible for identifying
toxicology as a separate science and he published the first book on toxicology in
1815. In the 20th Century descriptions on the DNA were given and this lead to an
advancement of knowledge on toxic effects of substances at the cellular and
DNA level. The Silent Spring published by Rachel Carson in 1962 was a landmark
publication influencing modern environmental toxicology. Her book served as a
catalyst for the establishment of the US Environmental Protection Agency and
she is regarded as the mother of the environmental movement. Recently with the
advent of molecular techniques in biology detailed studies have been done in
toxicology and xenobiotic metabolism.

1.3 SOURCES OF TOXICANTS

Toxic agents can be chemical, physical, or biological in nature and produce toxic
effects on the body. The different toxic agents include: chemical (cyanide),
physical (radiation) and biological (snake venom). There exist a number of
toxicants and they can be classified by various means. Classification may be by
exposure classes and by user classes. The different toxicants include the following:

1) Natural Pollutants: Toxic pollutants can also be released through natural

processes. For example, volcanoes emit particulate matter, sulfur dioxide,
hydrogen sulfide, and methane. Forest fires release smoke, unburned
hydrocarbons, carbon monoxide, nitrogen oxides, and ash. These can be
harmful to human health when inhaled. Dust storms release particulate
matter and oceans release aerosols in the form of salt particles. Plants
produce pollen and spores, which cause respiratory problems and allergic
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Introduction to Toxicology reactions.

2) Anthropogenic Pollutants. These are pollutants introduced due to human

activity/ man-made activities. These substances come primarily from three
sources: (1) combustion; (2) industrial; (3) mining and drilling processes.

Let us now learn about some important man-made sources of toxicants in detail.
They include the following.

1) Air pollutants: Humans have been polluting the air and there are also
significant natural pollutants such as terpenes from plants, smoke from
forest fires, and fumes and smoke from volcanoes. Among air pollutants
there are gaseous pollutants like carbon dioxide, carbon monoxide,
hydrocarbons, hydrogen sulfide, nitrogen oxides, ozone and other oxidants,
sulfur oxides. There are also fine particulates in the air. The particulates
include dust (coal, ash, sawdust, cement), fumes <1 ìm in diameter that
come from chemical processes, mist droplets, smoke (0.05–1.0 ìm) resulting
from incomplete combustion of fossil fuels and aerosols.

2) Indoor Pollutants: These are produced from heating, cooking, pesticides,

tobacco smoking, radon, gases, microbes from people and animals. Materials
used for construction of buildings can give out gaseous indoor chemicals
that have serious health concerns. Carbon monoxide and polycyclic aromatic
hydrocarbons released from wood, crop residues, animal dung used for
cooking cause acute respiratory infections in poorly ventilated areas.

3) Water pollutants: Surface waters may be polluted from point and nonpoint
sources. Industrial effluents discharged into waters are an example of point
source. Fertilizer and pesticide application in agricultural fields that enter
surface waters through rainfall are an example on nonpoint source of
pollution. Industrial wastes discharged into waters contain organic and
inorganic wastes including hazardous chemicals. Toxic effects are seen in
humans when they consume this contaminated water.

4) Soil pollutants: When wastes are not properly disposed off then soil also
gets polluted. Soil contaminants include: domestic waste, solid wastes,
electronic wastes, municipal wastes, agricultural wastes that contain a
number of chemicals harmful to life. Further agricultural toxicants like
persistent pesticides that do not biodegrade remain in the soil of many years
and move into the food chain causing greater health impacts. The most
toxic hazardous pesticides are the organochlorine compounds such as DDT,
aldrin, dieldrin, and chlordane.

5) Heavy metals: Metals released from industrial activities cause toxicity. For
example, the heavy metals lead and arsenic are highly toxic and is found in
potable water in certain areas. Lead can enter water from lead pipes, lead
solder, lead toys, leaded gasoline, utensils and also paints containing lead.
Lead is used in cosmetics like lipsticks can regular usage can enter the
system and cause health effects. Lead induces neurological damage and
can penetrate the placental barrier and induce birth defects among children.
Arsenic toxicity is also a serious cause of concern especially in West Bengal
in India. It can leach into water from pesticide sprays, arsenic-containing
fossil fuels, and leaching of mine tailings and smelter runoff. Chronic high-
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 level exposures can cause abnormal skin pigmentation, hyperkeratosis, nasal Introduction to Toxicants
congestion, abdominal pain and cancers. Cadmium enters the food chain
through industrial activities. It can accumulate in the tissues of aquatic
organisms. Cadmium contaminated rice in Japan caused the disease Itai-
Itai. The disease was characterized by severe kidney damage, painful bone
and joint problems. Mercury from industries manufacturing plastics, vinyl
chloride is also highly toxic to living beings. The Minamata disease in
Japan occurred due to consumption of mercury contaminated fishes resulted
in neurological disorders, paralysis, and mental disorientation.

6) Nitrates and phosphate: These arise from contamination due to fertilizers,

discharge from sewage treatment plants, leachate from septic tanks, manure
and detergents which are hazardous. They leach into the soil and drinking
water. Nitrates in drinking water cause adverse health effects. It occurs due
to the formation of: (1) nitrosamine and (2) methemoglobinemia. The
nitrates are converted to nitrites by bacteria in the intestine. Thereafter nitrite
ions combine with hemoglobin to form methemoglobin. This reduces the
oxygen-carrying capacity of the blood and leads to the blue-baby syndrome.
This is seen in young or new born children who have ingested nitrate
containing water or milk foods.

7) Petroleum and oil pollutants: Shore animals, such as crabs, shrimp, mussels,
and barnacles, are also affected by the toxic hydrocarbons (oil and petroleum
compounds) ingested by them.

8) Volatile organic compounds (VOCs): They include halogenated solvents

and petroleum products. They are used in industries involving degreasing,
dry cleaning, paint, and in the military. The most important VOCs include:
trichloroethylene, toluene, benzene, chloroform, tetrachloroethylene, 1,1,1-
trichloroethane, ethylbenzene, trans-1,2-dichloroethane, xylene,
dichloromethane, and vinyl chloride. They can move quickly in
groundwaters. Exposure to high levels can result in headache, impaired
cognition, kidney toxicity, cancer and reproductive disorders.

9) PCB organic compounds: These include polychlorinated biphenyls (PCBs),

phenols, cyanides, plasticizers, solvents, and numerous industrial chemicals.
They are used as coolants in electrical transformers. PCB’s are stable,
lipophilic, and are broken down slowly only in tissues. Due to these
properties they accumulate to high concentrations in fish and waterfowl.

10) Solvents: Many types of solvents are used which have systemic toxic effects
on nervous system and the blood. Benzene is used in the rubber, canning,
printing, shoe manufacturing industries. Benzene affects the hematopoietic
tissue in the bone marrow and is an immunosuppressant. Benzene exposure
results in decrease of white blood cells, red blood cells and platelets.
Continued exposure causes severe bone marrow damage, aplastic anemia
and leukemia. Other toxic solvents include: aliphatic hydrocarbons,
halogenated aliphatic hydrocarbons, aliphatic alcohols, glycols, glycol ethers
and aromatic hydrocarbons.

11) Asbestos: This material is used in insulation, roofing for houses, asbestos
cements, brake linings, electrical appliances and coating materials. The
inhalation of asbestos causes ‘Asbestosis’, a respiratory disease characterized 9
Introduction to Toxicology by scarring of lungs, fibrosis, calcification, and also leads to lung cancer.

12) Therapeutic drugs: Generally all therapeutic drugs are toxic and produce
hazardous effects at some dose. This depends on many factors like: dose,
nature of the drug, individual (genetic) variation, diet, age, etc. The side
effect of chloroquinol, an antidiarrhea drug used in Japan in 1960 caused
stiffness of the joints accompanied by damage to the optic nerve. Birth
defects or teratogenesis can be caused by drugs particularly, thalidomide.
Dermatitis is a common side effect of topically applied corticosteroids.
Toxic effects on the blood are caused by chlorpromazine. Hemolytic anemia
is caused by methyldopa and megaloblastic anemia is induced by
methotrexate. Eye toxicity and glaucoma is caused by thioridazine and
systemic corticosteroids. There are many more drugs that cause toxicity to
organs.

13) Drugs of abuse: They include depressants of central nervous system

(ethanol, methaqualone, secobarbital), stimulants of central nervous system
(cocaine, methamphetamine, caffeine, nicotine; opioids - heroin, mependine,
hallucinogens - lysergic acid diethylamide (LSD), phencyclidine (PCP),
and tetrahydrocannabinol, the most active ingredient of marijuana. More
important is that these drugs are synthesized illegally and are contaminated
with compounds of unknown origin and highly toxic and hazardous to
health.

14) Biological toxicants: Some naturally occurring substances that cause toxicity
include plant, animal, algal, fungal and microbial toxins. They include many
phytotoxins and mycotoxins. It is pertinent to understand that a toxin is a
toxicant produced by a living organism and is not used as a synonym for
toxicant. All toxins are toxicants, but all toxicants are not considered as
toxins. Toxins are the metabolic products used for defense against pathogens.
These natural products are used in beneficial pharmaceutical purposes and
also in biological warfare. For example, Aflatoxins are products of
Aspergillus flavus. It is fungus that contaminates grain, maize, peanuts,
and so on. Aflatoxin B1 is the most toxic and is reported to have carcinogenic
effects.

15) Cosmetics: Cosmetics induce allergies and contact dermatitis. Lipsticks

contain lead at varying concentrations. Hair dyes contain resorcinol which
is toxic. In ladies, some of the fibroids are related to regular use of hair
dyes. Thioglycolates and thioglycerol used in cold-wave lotion and
depilatories have toxic effects. Sodium hydroxide and formaldehyde used
in hair straighteners also are reported to exert toxicity. Further paraffin wax
is used in some lotions which hinders skin breathing. Parabens and sodium
laureth sulfates used in shampoo and body cleansers show toxicity. All
these cosmetics are toxic in nature affecting human health.

These were some of the sources of toxicants that have harmful effects on human
health. Now let us see the mode of action of some toxicants.
Check Your Progress 1
Note: a) Write your answer in about 50 words.
b) Check your progress with possible answers given at the end of the
10 unit.
 Introduction to Toxicants
1) Describe the various sources of toxicants.
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2) Write short notes on (a) therapeutic drugs and (b) drugs of abuse as toxicants.
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3) Define environmental toxicology. Write a brief account of the historical

development in toxicology.
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1.4 MODE OF ACTION OF TOXIC SUBSTANCES

1.4.1 Levels of Toxic Action
The mode of action of toxicants can be at the cellular and molecular level and
also at the organ level. It depends on the following: (1) uptake, (2) distribution,
(3) metabolism, (4) mode of action, and (5) excretion of the substance involved.
The different levels and mode of action of toxicants are: (a) Molecular toxicology:
This includes effects at biochemical and molecular levels. It involves the enzymes
that metabolize xenobiotics and the generation of reactive intermediates. It also
involves the interaction of xenobiotics with macromolecules and gene expression
in metabolic activities inducing toxic pathways. (b) Behavioral toxicology: This
involves toxic effects on the peripheral and central nervous systems and the
endocrine glands. (c) Nutritional toxicology: This involves the toxic effects of
diet. (d) Carcinogenesis: It includes the effects that lead to proliferation of cells
in an uncontrolled manner. (e) Teratogenesis: It involves chemical, biochemical,
and molecular events that lead to toxic effects during development of the foetus.
(f) Mutagenesis: It involves toxic effects that occur on the genetic material and
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Introduction to Toxicology the inheritance of these effects causing mutagenecity. (g) Organ toxicity: This is
the toxic effects at the organ level. They are neurotoxicity - brain, hepatotoxicity
- liver, nephrotoxicity - kidney, reproductive toxicity depending on the organ
involved.

1.4.2 Sites of Toxic Action

Toxicants can have different mechanisms and sites for initiating their toxic effects.
Some of the mechanisms are explained below.

a) Enzyme Inhibition/Activation: One important site of toxic action for metals

is the interaction with enzymes. It results in enzyme inhibition or activation.
Two mechanisms are significant. Enzyme inhibition can occur due to
interaction between metal and sulfhydryl groups on the enzyme, or the metal
can also displace an essential metal cofactor of the enzyme. For example, in
the zinc-dependent enzyme ä-aminolevulinic acid dehydratase, lead can
displace zinc thereby inhibiting the synthesis of heme.

b) Subcellular Organelles: Toxic metals have the ability to disrupt the structure
and function of a number of subcellular organelles. The enzymes associated
with the endoplasmic reticulum may be inhibited and metals can be
accumulated in the lysosomes. Also respiratory enzymes in the mitochondria
can be inhibited and metal inclusion bodies are produced in the nucleus.

c) Carcinogenic effects: Some chromium compounds, arsenic, nickel, cadmium

cause carcinogenic effects. It may be due to the interaction of the metallic
ions with DNA.

d) Kidney: It is the main excretory organ of the body and a common target
organ for metal toxicity. Cadmium and mercury are potent nephrotoxicants.

e) Nervous System: The nervous system is also a common target of toxic organic
metal compounds. For example, methylmercury is lipid soluble. It can readily
go across the blood-brain barrier and enter the nervous system. Also organic
lead compounds are mainly neurotoxicants.

f) Endocrine and Reproductive System: The reproductive organs are under

neuroendocrine and hormonal control. Hence any toxicant that alters any of
these processes can affect the reproductive system. Certain metals can act
directly on these organs. Acute exposure to cadmium can cause testicular
injury. Toxic exposures to lead can cause testicular degeneration, inhibition
of spermatogenesis, and the disease Leydig-cell atrophy.

g) Respiratory System: The system can be affected by inhalation of metal dust

that can cause irritations and inflammation of the respiratory tract. Chronic
exposure can give rise to fibrosis (aluminum dust exposure) or carcinogenesis
(arsenic, chromium, nickel metal exposures).

1.5 EXPOSURE ROUTES

The common absorption routes include the: skin, lung and the gastrointestinal
tracts. The skin is the largest organ in the human body and is a physical barrier to
the absorption of toxic substances. The other major routes are the respiratory
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and gastrointestinal tract. These give less resistance to toxicant absorption than Introduction to Toxicants
the skin. The respiratory tract is the most rapid route for entry and the skin is the
least rapid route for entry. This difference is due to thickness of the membranes.
Let us now see them in detail.

a) Skin: The skin is a complex multilayered tissue. It has a relatively large

surface area exposed to the environment. The factors like skin anatomy,
physiology, and biochemistry vary among species and within species. So
these factors can influence absorption. Our skin is permeable to many
toxicants. Dermal exposure to pesticides and industrial chemicals can result
in severe systemic toxicity. The human skin is 3 mm thick and the epidermis
provides the greatest resistance to toxicant penetration. Most of the systemic
absorption occurs at the capillary loops located at the epidermis-dermis
junction. Certain other factors like air flow, temperature and humidity etc.
can also influence dermal absorption.

b) Lung: The respiratory system includes nose, mouth, pharynx, trachea, and
bronchus which can reduce the toxicity of airborne particulate substances.
There is little or no absorption in these structures. But the cells lining the
respiratory tract absorb agents that can cause toxicological effects. The
absorption site is the alveoli-capillary membrane that is very thin (0.4–1.5
ìm). It allows for rapid exchange of gases/vapors. The ‘residual volume’ is
the amount of air retained in the lung despite maximum expiratory effort.
Hence toxicants may not be cleared out immediately due to the slow release
from the residual volume. The rate of entry of some vapor-phase toxicants
is controlled by the alveolar ventilation rate. The site of deposition of particles
in the respiratory tract is dependent on several factors. They include:
aerodynamic behavior of the particles, particle size, density, shape,
hygroscopicity, breathing pattern, and lung airway structure. The particle
sizes less than 10 - 20 ìm which get through the nasopharyngeal regions and
reach the alveoli are medically significant.

c) Gastrointestinal tract: This is lined by a layer of columnar cells and protected

by mucous. It gives minimal resistance to toxicant penetration. Most of the
absorption occurs in the intestine and then in the stomach. Also buccal and
rectal absorption can further occur in some cases. Absorption is through
passive diffusion mostly, except for nutrients; glucose, amino acids, and
drugs. The smaller the particle size of the toxicant, the greater is the
absorption. For absorption in this tract the chemical should be in an aqueous
form. Bacterial endotoxins, large particles of azo dyes and carcinogens are
absorbed by endocytotic mechanisms. Gastrointestinal tract motility is
important in the absorption of any toxicant. Excessive rapid movements of
the gut can reduce absorption by reducing residence time. Increased blood
flow after a meal can result in absorption of several drugs.

1.6 DISTRIBUTION AND STORAGE OF TOXINS IN

HUMAN TISSUES
The quantity of toxicant that reaches the target tissue like bone, fat and so on is
dependent upon the amount of toxicant absorbed, the distribution in the body,
the metabolism and the rate of excretion of the toxic substance. The cell membrane
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Introduction to Toxicology is selectively permeable. Hence only some substances can pass through. This
depends on the molecular weight of the substance, lipid solubility and so on.
Most toxic substances pass through cell membranes by diffusion and 75% of the
cell membranes are composed of lipids. The electric charge on the toxicant is
also an important factor for diffusion. So, non-ionized toxic substances diffuse
easily than the ionized ones. Phagocytosis plays an important role in the
disposition of particulates that enter the respiratory tract. Asbestos dust and silica
dust are absorbed by the process phagocytosis and are engulfed by WBC’s in the
respiratory tract. Water soluble substances are absorbed in the small intestine by
pinocytosis.

a) Plasma: In humans the plasma protein binding can vary between and within
chemical classes. It is also species specific. The systems of human beings
bind acidic drugs more extensively than any other species. Further there
are also other variables that can alter plasma protein concentrations.
Pregnancy, malnutrition, carcinogenesis, liver abscess, kidney disease, and
age can reduce serum albumin. The á1-glycoprotein concentrations can
increase with age, inflammation, infections, obesity, kidney failure and
stress. These characteristics bring about changes in the body temperature,
in the acid-base balance and alter chemical protein-binding characteristics.

b) Liver and Kidney: Both these organs have a high affinity for toxic substances
and store more toxicants than any other tissue in the whole body. Lipophilic
substances like organochlorine pesticides and organic solvents like
trichloroethane, methyl chloroform, are readily absorbed in the liver. They
can remain in the liver for long periods if they are not biotransformed into
water-soluble substances. The liver is a major storage site for water-insoluble
toxic heavy metals. Some toxicants can be stored in the liver also. For
example, the antimalaria drug quinacrine accumulates in the liver as result
of reversible intracellular binding. The concentration in the liver can be
several thousand times than that of plasma. In the kidney certain large
molecules such as proteins do not easily pass through the walls of Bowman’s
capsule. Further, unbound metals like cadmium and mercury can be
reabsorbed in the cells of the proximal convoluted tubule. Inside the cell
they bind to metallothionein resulting in concentration of the toxicants in
the kidneys. The kidneys store ten times the amount of cadmium found in
the liver, and it can be stored for 10 years or more. Finally bioaccumulation
in the kidneys cause complete renal failure.

c) Lung: Some particulate material like asbestos, fiberglass toxicants <1µm

remain in the lungs. They give rise to respiratory diseases.

d) Fat tissue: Toxicants such as lipophilic pesticides, polychlorinated biphenyls

and lipid soluble gases accumulate in high concentration in the fat tissue.
The adipose tissue (fat) acts as a reservoir for lipophilic persistent organic
pesticides, a number of drugs and pollutants. They can sequester these
pollutants and then slowly release them into the bloodstream later.

e) Bone: Toxicants can be stored in the bone and it can become a reservoir
which allows the slow release of chemicals such as lead. Calcium is an
important component of bone. Lead can easily replace calcium and is stored
in the bones. The effects can be acute or chronic depending on how the
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 toxicant is suddenly released or mobilized from these depots. Also perfusion Introduction to Toxicants
of tissues is an important factor for toxicant storage and distribution. The
organs like heart, kidney, liver and brain are well perfused than fat and
bone. In the fat and bone slow elimination of toxicants occurs. Bone can
store toxicants for 10 to 20 years. The toxicants stored in the bone may not
be toxic to the bone. It becomes toxic when it is released slowly resulting
in nerve damage and so on.

f) Blood: The circulatory system and components in the blood stream are
primarily responsible for the transport of toxicants to the target tissues or
reservoirs. Erythrocytes and lymph also transport the toxicants. Absorption
also depends on physiological factors and physicochemical properties of
the drug. Hence a reversible movement of toxicants occurs between blood
and tissues. Most toxicants pass by simple diffusion down a concentration
gradient from the blood to tissues. Tissue mass, blood flow, molecular
weight, lipid solubility are also important factors for toxicant distribution.
Water soluble toxins are stored here. Also heavy metals like arsenic, thallium,
cadmium and chlorinated pesticides, bisphenyl A targets the blood. The
toxic substances upon entering the bloodstream bind with plasma proteins
such as albumin, transferrin, globulin, and lipoproteins. Most toxic
substances are known to bind with the plasma protein albumin.

g) Passage of toxicants across placenta: Toxicants can cross the placental

barrier and affect the growing foetus by simple diffusion. It occurs readily
and easily when the toxicants are lipid-soluble. So the foetus is exposed to
almost all drugs even if low lipid solubility drugs are consumed by the
mother.

h) Blood-brain barrier (BBB): This limits the distribution of toxicants into

the central nervous system and cerebrospinal fluid. There are several
membranes the toxicant has to cross in order to get into the cerebrospinal
fluid. Certain diseases like meningitis disrupt this barrier and allow
antibiotics and toxicants to penetrate.

Toxic substances are absorbed and distributed in our body. They are also
eliminated, biotransformed and detoxified by the liver and kidneys. Further details
will be discussed in the following units.
Check Your Progress 2
Note: a) Write your answer in about 50 words.
b) Check your progress with possible answers given at the end of the
unit.
1) Describe the various routes of exposure to toxicants.
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Introduction to Toxicology 2) Where are toxic substances stored in the human body?
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1.7 LET US SUM UP

In this unit we have studied about the various toxicants, their mode of action and
sites of action. We have also learnt about the routes of exposure through which
toxic substances can enter our healthy body. The toxicants can be absorbed,
distributed and also stored in the various tissues and organs of the human body.
If the toxic substances are not detoxified or biotransformed, they can remain in
the organs causing organ failure and disease. Hence environmental toxicology is
a very important aspect that deals with effects of toxicants on human health.

1.8 KEY WORDS

Environmental Toxicology : It is a branch of science that deals with the
harmful effects of different physical, chemical
and biological agents on living organisms. It is
multidisciplinary in nature.
Toxicant : Any toxic material or substance is termed as a
toxicant. They are hazardous and poisonous.
Toxicants are generally man-made and artificial
products introduced into the environment due
to human activity. They include bisphenol,
insecticides and a number of industrial
chemicals.
Toxins : These are produced naturally by living
organisms. For example, toxins from the
mushroom plant and toxin from the venom of
snake are natural toxins.
Xenobiotic : is referred to a foreign substance entering the
body. It is derived from the Greek word ‘xeno’
meaning ‘foreigner’.

Toxicosis/ Poisoning/ : Any disease produced by a toxicant.

Intoxication
Organ toxicity : Toxic effects at the organ level. They are
neurotoxicity - brain, hepatotoxicity - liver,
nephrotoxicity - kidney, reproductive toxicity
depending on the organ involved.

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 Introduction to Toxicants
1.9 REFERENCES AND SUGGESTED FURTHER
READINGS
Abel, P. D., ed. Water Pollution Biology. London: Taylor and Francis, 1996.
Costa, D. L. Air pollution. In Casarett and Doull’s Toxicology: The Basic Science
of Poisons, 6th ed., C. D. Klaassen, ed. New York: McGraw-Hill, 2001,
pp. 979–1012.
Doull, J. Recommended limits for occupational exposure to chemicals. In Casarett
and Doull’s Toxicology: The Basic Science of Poisons, 6th ed., C. D.
Klaassen, ed. New York: McGraw-Hill, 2001, pp. 1155–1176.
Hodgson, E., and R. C. Smart, eds. Introduction to Biochemical Toxicology, 3rd
ed. New York: Wiley, 2001. Hodgson, E., R. B. Mailman, and J. E.
Chambers, eds. Dictionary of Toxicology, 2nd ed. London: Macmillan,
1998. Klaassen, C. D. ed. Casarett and Doull’s Toxicology: The Basic
Science of Poisons, 6th ed. New York: McGraw-Hill, 2001. Timbrell, J.
A. Principles of Biochemical Toxicology, 3rd ed. London: Taylor and
Francis, 2000. Wexler, P. Information Resources in Toxicology, 3rd ed.
San Diego: Academic Press, 2000.
Hoffman, D. J., B. A. Rattner, G. A. Burton, and J. Cairns, eds. Handbook of
Ecotoxicology, 2nd ed. Boca Raton: Lewis, 2002.
Holgate, S. T., J. M. Samet, H. Koren, and R. Maynard, eds. Air Pollution and
Health. San Diego: Academic Press, 1999.
Larson, S. J., P. D. Capel, and M. S. Majewski, eds. Pesticides in Surface Waters.
Chelsea, MI: Ann Arbor Press, 1998.
Thorne, P. S. Occupational toxicology. In Casarett and Doull’s Toxicology: The
Basic Science of Poisons, 6th ed., C. D. Klaassen, ed. New York:
McGraw-Hill, 2001, pp. 1123–1140.

1.10 ANSWERS TO CHECK YOUR PROGRESS

Answers to Check Your Progress 1
1) Your answer should include the following points:
 Air pollutants
 Indoor Pollutants
 Water pollutants
 Soil pollutants
 Heavy metals
 Nitrates and phosphate
 Petroleum and oil pollutants
 Volatile organic compounds (VOCs)
 PCB organic compounds
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Introduction to Toxicology  Solvents
 Asbestos
 Drugs of abuse
 Biological toxicants
 Cosmetics
2) Your answer should include the following points:
 therapeutic drugs
 drugs of abuse as toxicants.
3) Your answer should include the following points:
 Environmental toxicology: It is a branch of science that deals with the
harmful effects of different physical, chemical and biological agents on
living organisms. It is multidisciplinary in nature.
 The historical development of toxicology started very early in human
civilizations. Our ancestors who were cave dwellers found plants and
animals that had toxins and these toxic extracts were used in hunting
and warfare.
 Paracelsus in his study showed that specific chemicals were responsible
for the toxicity of a plant or animal poison. He also reported that the
dose of a chemical is an important factor for the human body’s response.
Hence, Paracelsus was one of the founders of modern toxicology. His
well known quote says that “All substances are poisons; it is the dose
that makes the poison”.
 In the 18th century ‘Ramazini’s Diseases of Workers’ was published in
1700. He is known as the father of occupational medicine.
 The founder of modern toxicology was Orfila, a Spanish physician who
worked at the University of Paris in the early 19th century.
 Rachel Carson, 1962, Silent Spring.

Answers to Check Your Progress 2

1) Your answer should include the following points:
 The common absorption routes include the: skin, lung and the
gastrointestinal tracts. The skin is the largest organ in the human body
and is a physical barrier to the absorption of toxic substances. The other
major routes are the respiratory and gastrointestinal tract. These give
less resistance to toxicant absorption than the skin. The respiratory tract
is the most rapid route for entry and the skin is the least rapid route for
entry. This difference is due to thickness of the membranes.
 Skin
 Lung
 Gastrointestinal tract

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2) Your answer should include the following points: Introduction to Toxicants

 The quantity of toxicant that reaches the target tissue like bone, fat and
so on is dependent upon the amount of toxicant absorbed, the distribution
in the body, the metabolism and the rate of excretion of the toxic
substance. The cell membrane is selectively permeable allowing the
passage of some substances depending on the molecular weight of the
substance, lipid solubility and so on.
 Plasma
 Liver and Kidney
 Lung
 Fat tissue
 Bone
 Blood
 Passage of toxicants across placenta
 Blood-brain barrier (BBB)

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