Toxic Substances

Lecture 3

ENV 403
Dr. Md. Hafizur Rahman
 What is a Toxic Chemical?

• Any chemical which, when ingested,

inhaled, absorbed or injected into the
body, in relatively small amounts, by
its chemical action, may cause
damage to structure or disturbance
to function.
Types of Damage Caused by
a Toxic Chemical

❑ Damage to biological structure

❑ Disturbance of biological function
❑ Damaging both structure and
function
What makes a substance toxic?
These effects can strike a single cell, a group of
cells, an organ system, or the entire body.
A toxic effect may be visible damage, or a decrease
in performance or function measurable only by a
test.
All chemicals can cause harm. However, when only
a very large amount of the chemical can cause
damage, the chemical is considered to be
practically non-toxic. When a tiny amount is
harmful, the chemical is considered to be highly
toxic.
 Dependency Parameters of Toxic
Substances
✔ The toxicity of a substance depends on three
factors: its chemical structure, the extent to
which the substance is absorbed by the body,
and the body's ability to detoxify the substance.

✔ A central concept of toxicology is that effects

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.
 Are "toxic" and "hazardous" the same?

❑ No.

❑ Toxic is one type of hazard. A toxic substance

is hazardous, but a hazardous substance may
not be toxic.

For instance, compressed air is not toxic, but

it is hazardous.
Common Routes of Entry of
Toxic Substances
The most common routes of entry of
toxic substances are

Ingestion - via the mouth

Inhalation - through the lungs
Injection - via a puncture wound
Absorption - skin contact
A chemical is determined to be a hazard
depending on the following factors:
❑ Toxicity: how much of the substance is required to
cause harm
❑ Route of exposure: how the substance enters your
body
❑ Dose: how much enters your body
❑ Duration: the length of time you are exposed
❑ Reaction and interaction: other substances you are
exposed to at the same time.
❑ Sensitivity: how your body reacts to the substance
compared to other people.
 Types of Toxicants
✔ Carcinogens : cause cancer

✔ Mutagens: cause mutations in DNA

✔ Teratogens: cause birth defects

✔ Allergens: cause unnecessary immune response

✔ Neurotoxins: damage nervous system

✔ Endocrine disruptors: interfere with hormones

✔ Corrosives - corrode substances including flesh

✔ Flammables - burn
 Teratogens
The drug thalidomide, used to relieve nausea
during pregnancy, turned out to be a potent
teratogen, and caused thousands of birth
defects before being banned in the 1960s.
 Endocrine Disruption
❑ Some chemicals, once inside the bloodstream, can
“mimic” hormones.
❑ If molecules of the chemical bind to the sites intended
for hormone binding, they cause an inappropriate
response.
❑ Thus these chemicals disrupt the endocrine system.
The hormone system is geared to working with tiny
concentrations of hormones, so it can respond to tiny
concentrations of environmental contaminants.
❑ There is a hypothesize that endocrine disruptors are
behind the rise in testicular cancer in many nations.
 Toxicants Concentrate in Water
• Surface water and groundwater can
accumulate toxicants.
• Runoff from large areas of land drains into
water bodies, becoming concentrated.
• Toxicants in groundwater or surface water
reservoirs used for drinking water pose
potential risks to human health.
 Airborne Toxicants
• Volatile chemicals can travel long distances on
atmospheric currents.
• PCBs are carried thousands of miles from
developed nations of the temperate zone up
to the Arctic, where they are found in tissues
of polar bears and seals.
 Persistence Pollutants
• Some chemicals are more stable than others
persisting for longer in the environment. DDT
and PCBs are persistent.
• Temperature, moisture, sun exposure, etc.,
affect rate of degradation.
• Most toxicants degrade into simpler
breakdown products. Some of these are also
toxic. (DDT breaks down to DDE, also toxic.)
Contaminants of Current Concern Category:
Organic Types
❖ Chlorofluorocarbons (CFCs)- CFCs are used in
refrigerators and in the production of foams (e.g.,
Styrofoam). These gases cause ozone layer depletion
in the stratosphere. At high concentrations they can
be acutely toxic, causing several adverse effects,
including central nervous system depression, bronchial
constriction, chest tightness, cough etc.
❖ Organochlorine Alkenes- These compounds are
often used in large amounts as solvents and
degreaser (e.g., tetrachloroethene). These
compounds are frequently associated with ground
water contamination. Organochlorine toxicity
is mainly due to stimulation of the central nervous
system.
 Contaminants of Current Concern
Category: Organic Types
❖ Organophosphate Insecticides- These pesticides
persist less than organochlorine in the
environment but more toxic than
organochlorine. They accumulate in the fat or
oils. Organophosphates are used as medications,
insecticides, and nerve agents as a weapon.
Symptoms include increased saliva and tear
production, diarrhea, nausea, vomiting, small
pupils, sweating, muscle tremors, and confusion.
❖ Carbamate Insecticides- Like organophosphate
they also degrade faster but causes neural
dysfunction.
 Contaminants of Current Concern
Category: Organic Types
❖ Pyrethroid Insecticides- Acute exposure to these insecticides
causes neurotoxicity. Animal studies have shown that
pyrethroids can affect the immune system at very high doses
and can also cause neurobehavioral effects with chronic
exposure.
❖ Herbicides- They can enter water bodies from agricultural
fields. The mutagenic effects of the herbicides can result from
several reactions with the organism, as a direct action of the
compound on the nuclear DNA; incorporation in the DNA
during cell replication;, resulting in incorrect division of the
cell.
❖ Chlorinated Phenols- These contaminants are used as wood
preservatives and fungicides. These pesticides
cause neurological damage, endocrine disorders, and have
acute and chronic health effects.
 Contaminants of Current Concern
Category: Organic Types
❖ Chlorination Products -Produced when drinking water is
disinfected through chlorination and this is carcinogenic.
Long-term exposure to organochlorine pesticides
may damage the liver, kidney, central nervous system,
thyroid and bladder.
❖ Organochlorine Insecticides- These pesticides degrade
slowly. Bioaccumulation occurs through the food web.
Long-term exposure to organochlorine pesticides may
damage the liver, kidney, central nervous system, thyroid
and bladder. Example: DDT
❖ Dioxins- Dioxins are extremely toxic and enter in the
environment as contaminants in herbicides, wood
preservatives, combustion products and during the
bleaching process of Kraft pulp mills. These pesticides cause
neurological damage, endocrine disorders, and have acute
and chronic health effects.
 Viktor Andriyovych Yushchenko
Viktor Andriyovych Yushchenko (born February 23, 1954) is a Ukrainian
politician who was the third President of Ukraine from 2005 to 2010. Following
an assassination attempt in late 2004 during his election campaign,
Yushchenko was confirmed to have ingested hazardous amounts of
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxin. He
suffered disfigurement as a result of the poisoning but has been slowly
recovering.

2004 2006
 Contaminants of Current Concern
Category: Organic Types
❖ Polychlorinated Biphenyls (PCBs)- PCBs are used as
lubricants, heat conductors and in plasticizers. They are
slow degrading and have harmful effect to all biota.
Exposure to PCBs suppresses the immune system, thereby
increasing the risk of acquiring several human diseases
including cancers.
❖ Petroleum Related Compounds: Petroleum product
toxicosis may involve the respiratory, GI, or integumentary
systems or the CNS. In some cases of ingestion, no clinical
signs are evident; however, small animals are reported to
show oral irritation, salivation, and champing of jaws,
followed by coughing, choking, and vomiting.
 Contaminants of Current Concern
Category: Inorganic (Gaseous)

Inorganic Gases:
❖ Carbon dioxide, nitrogen oxides and sulfur dioxide
are increasing through time. Carbon dioxide causes
global warming whereas nitrogen oxides and sulfur
dioxide may produce acid rain and lung diseases.
For human health, its effects mainly include airway
inflammation, organ disorders, such as liver or
spleen, or systems, such as the circulatory or
immune system, which in turn cause pulmonary
infections and respiratory insufficiencies.
 Contaminants of Current Concern
Category: Metals and Metalloids
❖ Aluminum: A naturally abundant metal but dissolves in
high concentration in acid condition that can kill aquatic
species. Aluminum poisoning can affect blood content,
musculoskeletal system, kidney, liver, and respiratory
and nervous system, and the extent of poisoning can be
diagnosed by assaying aluminum compounds in blood,
urine, hair, nails, and sweat.
❖ Arsenic: Used in metal alloys, pesticides wood
preservatives etc. which is toxic and carcinogenic.
Arsenic is highly toxic in its inorganic form.
Contaminated water used for drinking, food preparation
and irrigation of food crops poses the greatest threat to
public health from arsenic. Long-term exposure to
arsenic from drinking-water and food can cause cancer
and skin lesions.
 Contaminants of Current Concern
Category: Metals and Metalloids

❖ Cadmium: This metal is used in alloy production,

electroplating, batteries, pigments and
galvanizing. Smokers are exposed to high levels of
cadmium in cigarettes. It is toxic and carcinogenic.
Long-term exposure to cadmium through air,
water, soil, and food leads to cancer and organ
system toxicity such as skeletal, urinary,
reproductive, cardiovascular, central and
peripheral nervous, and respiratory systems.
Cadmium levels can be measured in the blood,
urine, hair, nail and saliva samples.
 Contaminants of Current Concern
Category: Inorganic

❖ Chromium, Copper, Lead, Mercury, Nickel,

Selenium and zinc are the other heavy metals
of current concern.
❖ Radioclides can be very toxic and have long
term effect.
❖ Nitrogen, Phosphorus, nitrate, nitrite and
ammonia have much effect on ecology.
 Dose Threshold, Lethal Dose and
Lethal Concentration
• Dose threshold: is the minimum dose required to
produce a measurable effect.
• Lethal dose: is the dose that is highly likely to
cause death.
• Lethal concentration: of an inhaled substance is
the concentration that is highly likely to result in
death. With inhaled substances the duration of
exposure is critical because the amount inhaled
increases with every unprotected breath.
Acute and Chronic Effects and Exposures
• Acute effects and exposures involve a sudden
dose of a highly concentrated substance. They
are usually the result of an accident that
results in an immediate health problem
ranging from irritation to death.
• Chronic effects and exposures involve limited
continual exposure over time. Consequently,
the associated health problem develops
slowly.
 Carcinogen & Sick Building Syndrome
❑ A carcinogen is any substance that can cause a
malignant tumor or a tissue that may become
cancerous.
❑ Sick building syndrome
A sick building is one that makes people sick
because it has become infested with mold,
mildew, spores or other airborne micro
organisms.
 Threshold limit value (TLV)
• Threshold limit values: refer to airborne
concentrations of substances and represent
conditions under which it is believed that nearly
all workers may be repeatedly exposed day after
day without adverse effect.
• Threshold limits are based on the best available
information from industrial experience, from
experimental human and animal studies, and
when possible a combination of the three.
Time weighted average and ceiling
• The time weighted average for a conventional
8-hour workday and 40-hour work week for a
given substance to which it is believed that
nearly all workers may be repeatedly exposed
daily without suffering ill effects.
• Ceiling: the concentration of a given substance
that should not be exceeded at any point
during an exposure period.
 Pharmacokinetics
• Pharmacokinetics may be simply defined as
what the body does to the drug, as opposed
to pharmacodynamics which may be defined
as what the drug does to the body.
 Pharmacokinetics
• Pharmacokinetics, sometimes abbreviated as PK, is a
branch of pharmacology dedicated to the determination
of the fate of substances administered externally to a
living organism. The substances of interest include
pharmaceutical agents, hormones, nutrients, and toxins.
• It attempts to discover the fate of a drug from the
moment that it is administered up to the point at which
it is completely eliminated from the body.
• Pharmacokinetics describes how the body affects a
specific drug after administration through the
mechanisms of absorption and distribution, as well as
the chemical changes of the substance in the body and
the effects and routes of excretion of the metabolites of
the drug.
 Toxicokinetics
• Toxicokinetics (often abbreviated as 'TK') is the
description of what rate a chemical will enter the body
and what happens to it once it is in the body. It is an
application of pharmacokinetics to determine the
relationship between the systemic exposure of a
compound in experimental animals and its toxicity.
• It is used primarily for establishing relationships
between exposures in toxicology experiments in
animals and the corresponding exposures in humans.
However, it can also be used in environmental risk
assessments in order to determine the potential
effects of releasing chemicals into the environment.
 Pharmacodynamics
• Pharmacodynamics is the study of the
biochemical and physiological effects of drugs on
the body or on microorganisms or parasites within
or on the body and the mechanisms of drug action
and the relationship between drug concentration
and effect. One dominant example is
drug-receptor interactions as modeled by
• L + R ↔ L.R
• where L=ligand (drug), R=receptor (attachment
site), reaction dynamics that can be studied
mathematically. Pharmacodynamics is often
summarized as the study of what a drug does to
the body.
 Toxicodynamics
• Toxicodynamics, termed pharmacodynamics in
pharmacology, describes the dynamic interactions of a
toxicant with a biological target and its biological
effects.
• A biological target, also known as the site of action,
can be binding proteins, ion channels, DNA, or a
variety of other receptors. When a toxicant enters an
organism, it can interact with these receptors and
produce structural or functional alterations.
• The mechanism of action of the toxicant, as
determined by a toxicant’s chemical properties, will
determine what receptors are targeted and the overall
toxic effect at the cellular level and organismal level.