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• Introduction (terminologies used in toxicity evaluations, dose-

ENVIRONMENTAL response curves, bioaccumulation and biomagnification),

metabolism of xenobiotics (phase I and II) reactions,
biochemical and toxicology effects due to heavy metals,
TOXICOLOGY agrochemicals, oxides

• of carbon, nitrogen, sulphur, ozone, cyanides and organic

pollutants, environmental factors affecting toxicity, testing of
toxicity (bioassays, teratogenicity, carcinogenicity and
Prof. Priyani A. Paranagama mutagenicity), occupational health hazards, absorption,
distribution and excretion of toxic chemicals, toxicological
Chair & Senior Professor evaluation, air, water, soil and radioactive pollution (case study
Pullmudai sands) on health effects, risk management and
Department of Chemistry assessment, occupational safety, environmental impact on use
of energy.
University of Kelaniya

What is environmental toxicology ?

Toxicology
• ‘ecotoxicology’
The study of poisonous substances and their effects on
humans and other organisms
• Definition: ‘study of impacts of pollutants on the
Toxicologists assess and compare toxic agents, or toxicants, structure and function of ecosystems’
for their toxicity, the degree of harm a substance can
inflict.
• manmade poisonous chemicals and their effect on the
Environmental toxicology focuses on effects of chemical environment
poisons released into the environment.

www.toxipedia.org • Environmental toxicology is a new discipline that grew out

of studies on the environmental fate
A free toxicology encyclopedia and
resource center that anyone can edit. • The discipline ‘toxicology’ is as old as medicine – many
Toxipedia provides comprehensive, toxic plant chemicals are used as therapeutic agents in
accurate, and scientifically based
information on the hazards and risks of
medicine.
chemical and physical agents, with the goal
of advancing human and environmental • The term ‘ecotoxicology’ appeared in the literature in 1969
health. Toxipedia

• Field was pioneered by Rachel Carson

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Rise of synthetic chemicals

Widespread synthetic chemical production after WWII
Silent Spring and Rachel Carson
People are largely unaware of the health risks of many
Carson’s 1962 book alerted the public that DDT and other
toxicants.
pesticides could be toxic to animals and people.

Further research led the EPA to ban DDT in 1973.

The potent
insecticide DDT These developments were central to the modern
was sprayed environmental movement.
widely in public
areas, even on
people.

Environmental toxicology is highly interdisciplinary field

Rachel Carson

• 1907-1964
• Marine Biologist from Pennsylvania
• Author of ‘Silent Spring’
• Received much attention, because she wrote
and presented scientific facts well
• She was disturbed by the widespread and indiscriminate use of
pesticides
• Many of these pesticides were known to affect wildlife e.g. kill birds
• She lobbied very hard to control and ban certain highly toxic
chemicals
• Testified before congress in 1963 and called for new policies with
respect to human health and the environment

This lecture series will help you understand:

• Prevalence of toxic agents in
the environment
• Epidemiology, animal testing,
and dose-response analysis
• Factors affecting toxicity
• Environmental health
hazards
• Risk assessment and risk
management
• Policy on toxicants

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Synthetic chemicals are everywhere

in our environment Synthetic chemicals
Many thousands have been produced and released.
Some persist for long time periods or travel great distances. Of the 100,000 synthetic
chemicals on the market today,
2002 study: 80% of U.S. streams contain up to 82 wastewater very few have been thoroughly
contaminants, include antibiotics, perfumes, detergents, drugs, tested for harmful effects.
steroids, disinfectants, etc.

Figure 10.1

Environmental toxicology
Increase our understanding
Studies toxicants that come from or are discharged into the of how chemicals affect
environment, and: human health.
Health effects on humans
Effects on animals
Effects on ecosystems

Thalidomide Endocrine disruption

Some chemicals, once inside
 Introduced in 1956 as the bloodstream, can
sedative (sleeping pill) and to “mimic” hormones.
reduce nausea and vomiting
during pregnancy If molecules of the chemical
bind to the sites intended for
 Withdrawn in 1961 hormone binding, they cause
an inappropriate response.
 Discovered to be a human teratogen causing
absence of limbs or limb malformations in Thus these chemicals disrupt
newborns the endocrine (hormone)
 5000 to 7000 infants effected system.
 Resulted in new drug testing rules

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Units Used to Measure Chemicals Important Relationship

in the Environment

• PPM – Parts per million

For water at STP (standard temperature [23oC] and pressure [15 psi])
• PPB – Parts per billion
1 cc = 1ml = 1g

• PPT – Parts per trillion

Which means that Measures of Toxicity

• Toxicity is measured as clinical “endpoints” which include

1 liter of water = 1 kg • Mortality (death)
• Teratogenicity (ability to cause birth defects)
• Carcinogenicity (ability to cause cancer), and,
1 mg / kg = 1 ppm • Mutagenicity (ability to cause heritible change in the DNA)

1mm3 / liter = 1 ppm

1 mg / liter = 1 ppm

Primary Routes of Exposure Primary Routes of Exposure:

to toxic substances Oral Exposure
There are three primary routes by which organisms are exposed to
toxic substances Any exposure to toxic substances which occurs when the chemical is
Oral taken in through the mouth and passes through the gastrointestinal
Dermal tract
Inhalation
During oral exposure, although carried within the body, the toxic
substance is still outside of the body cavity

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Primary Routes of Exposure: Primary Routes of Exposure:

Dermal Exposure Inhalation Exposure
Occurs when a toxic substances is breathed into the lungs through the
Exposure of the skin to a toxic substances nose or mouth
Most common route of human exposure
Significant route of exposure for aquatic organisms
With proper hygiene this type of exposure is generally not serious
unless there is a specific, rapid toxicological effect (often eye effects) Not of toxicological concern until it crosses from the lung into the body
which is of concern (unless the chemical is corrosive)

Duration of Exposure Duration of Exposure:

Acute Exposure
Three terms are commonly used to describe the duration of dose(s)
Application of a single or short-term (generally less than a day) dosing
Acute by a chemical
Chronic
Subchronic If toxic symptoms are expressed, they are referred to as symptoms of
“acute toxicity”

Duration of Exposure: Duration of Exposure:

Chronic Exposure Subchronic Exposure

Expression of toxic symptoms only after repeated exposure to a
chemical in doses regularly applied to the organism for a time greater
than half of its life-expectancy
If toxic symptoms are expressed, they are referred to as symptoms of
“chronic toxicity”
Toxic symptoms are expressed after repeated applications for a
timeframe less than half the life expectancy of the organism – but
more often than a single dose or multiple doses applied for only a
short time
If toxic symptoms are expressed, they are referred to as symptoms of
“subchronic toxicity”

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Persistence
Airborne toxicants Some chemicals are more stable than others,
persisting for longer in the environment.

Volatile chemicals can travel long distances on atmospheric DDT and PCBs are persistent.
currents. Bt toxin in GM crops is not persistent.

PCBs (Polychlorinated biphenyl) 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.
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.)

Poisons move up the food chain

Poisons accumulate in tissues
The body may excrete, degrade, or store toxicants.
At each trophic level,
chemical concentration
Fat-soluble ones are stored.
increases:
biomagnification.
DDT is persistent and fat soluble,

… so builds up in tissues: bioaccumulation.

DDT concentrations
increase from plankton to
Bioaccumulated chemicals may be passed on to animals
fish to fish-eating birds.
that eat the organism—up the food chain…

All toxicants are not synthetic Studying effects of toxicants

Toxicologists study effects in several major ways:
Although toxicology tends to focus on man-made
chemicals, it’s important to keep in mind that
there are plenty of natural toxicants.
• Wildlife toxicology studies

• Human epidemiological studies

Many are toxins produced by animals or plants for
protection against predators and pathogens. • Dose-response studies in the lab

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Wildlife toxicology Human epidemiology

Determine causes of mortality in die-off events Long-term, large-scale comparisons of different groups of
people
or
Test animals in the lab for response to toxicants Contrast group exposed to substance or risk factor with
or group not exposed

Correlate chemical presence and animal presence in Follow them for health effects or mortality later in life
the field
Statistically analyze results to look for differences between
Problems in wildlife can act as a warning for people. groups

Measures of Toxicity: Measures of Toxicity:

The Median Lethal Dose The Median Lethal Concentration

LD50 LC50
The amount (dose) of a chemical which produces death in 50 % of a The concentration of a chemical in an environment (generally air or
population of test animals to which it is administered by any of a water) which produces death in 50% of an exposed population of test
variety of methods animals in a specified time frame

mg/kg mg/L
Normally expressed as milligrams of substance per kilogram of animal Normally expressed as milligrams of substance per liter of air or water
body weight (or as ppm)

Remember – Words again

• For toxic substances – less is more when dealing with toxicity
• The less you need to cause a toxic effect – the more toxic the
substance is
• Thus an LD50 of 25 mg/kg is more toxic than is one of 7,000 mg/kg Safe

Low Risk

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Signal Words
The relative acute toxicity of a toxic substance is
reflected on the label in the form of a “signal word”
The (toxicologically) appropriate signal word MUST
appear on every toxic substance label
The three possible signal words are
CAUTION
WARNING
DANGER
Signal Words:
WARNING
“Warning” reflects an intermediate degree of relative toxicity
All toxic substances with an LD50 of greater than 50 and less than 500
mg/kg must display this word on their label
toxic substances in this category are classed as “moderately toxic”
POISON!!!
• Legally defined term – not just anything you don’t like
• Any toxic substances with an LD50 of 50 mg/kg or less
• Labels must reflect this classification
• Label must have the signal word “DANGER” plus the word “POISON”
• Label also must display the skull and crossbones icon
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Signal Words:
CAUTION
“Caution” reflects the lowest degree of relative toxicity
All toxic substances with an LD50 of greater than 500 mg/kg must
display this word on their label
Actually includes two groups of toxic substances – those classed by the
EPA as “Relatively nontoxic (>5,000 mg/kg) and those classed as
“slightly toxic” (500 – 5,000 mg/kg)
Environmental Protection Agency (EPA)
Signal Words:
DANGER
“Danger” reflects the highest degree of relative toxicity
All toxic substances with an LD50 of less than 50
mg/kg must display this word on their label
toxic substances here are classed as “highly toxic”
Relative toxicity
• Organisms can’t differentiate between “natural” and “synthetic”
chemicals
• “Synthetic” does not mean toxic or poisonous
• “Natural” does not mean safe or even low risk
• Chemicals must be evaluated in their biological context of behavior in
organisms
• Mode of action is the concern of toxicologists and informed users of
toxic substances
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Relative toxicity Relative Toxicity:

• Some examples of pesticides and other chemicals are given to show Herbicides and Additives
relative risk of pesticides in the environment in which we live
• This is NOT to trivialize the pesticides mg/kg mg/kg
• Always treat them with caution and respect Paraquat 95 Limonene 5,000
• But, have a realistic recognition of their relative risk in a world of risks 2,4-D 375 Clopyralid >5,000
2,4-DP 532 Sulfometuron Met.. >5,000
Triclopyr 630 Imazapyr >5,000
• TCDD (Dioxin) 0.1 mg/kg
Tebuthiuron 644 Diesel oil 7,380
• Parathion 13.0 mg/kg
Dicamba 757 Picloram 8,200
• Nicotine 50.0 mg/kg Hexazinone 1,690 Fosamine am.. 24,400
• Carbaryl 270.0 mg.kg Glyphosate 4,320 Kerosene 28,000
• Malathion 370.0 mg/kg

Relative Toxicity: Relative Toxicity

Comparative information Comparative Information
Highly toxic chemicals Moderately toxic chemicals Slightly toxic chemicals mg/kg
0 – 50 mg/kg range 50- - 500 mg/kg range 500 – 5,000 mg/kg range • Formaldehyde 800
mg/kg mg/kg • Hexazinone 1,690
• Botulinus toxin 0.00001 mg/kg • 2,4-DP 532 • Asprin 1,700
• Dioxin 0.1 • Paraquat 95 • Triclpoyr 630 • Vitamin B3 1,700
• Parathion 13.0 • Caffeine 200 • Tebuthiuron 644 • Household bleach 2,000
• Strychnine 30.0 • Carbaryl 270 • Dicamba 757 • Table salt 3,750
• Nicotine 50.0 • Malathion 370
• 2,4-D 375

Relative Toxicity: Relative Toxicity:

Are all substances toxic?
Toxic substances are chemicals introduced into the environment to
All are toxic to some quantifiable degree perform a function
Sugar has an LD50 of 30,000 mg/kg The source of a chemical (synthetic vs. natural) is irrelevant when
The foresters favorite – ethanol has an LD50 of only 13,700 mg/kg considering its toxicity
Even water has a recognized LD50 of slightly greater than 80,000 Toxic substances should be treated with care and proper respect – but so
mg/kg should household cleaners, gasoline and kerosene, bleaches, paints and all
other chemicals

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Dose-response curve
Dose-response analysis
Method of determining toxicity of a substance by
measuring response to different doses

Lab animals are used.

Mice and rats breed quickly, and give data relevant to

humans because they share mammal physiology with us.

Responses to doses are plotted on a dose-response curve. LD50 = dose

Threshold = dose at lethal to 50%
which response begins of test animals
Figure 10.10

Dose-response curve Mixtures of toxicants

Dose-response curves allow us to predict effects of higher
doses.
By extrapolating the curve out to higher values, we can
predict how toxic a substance may be to humans at various
concentrations.
In most curves, response increases with dose.
But this is not always the case;
the increase may not be linear.
With endocrine disruption, it may decrease.
Substances may interact when combined together.
Mixes of toxicants may cause effects greater than the sum
of their individual effects.
These are called synergistic effects.
A challenging problem for toxicology:
There is no way to test all possible combinations!
(And the environment contains complex mixtures of many
toxicants.)

Infectious disease
Environmental health
Assesses environmental factors that influence human
health and quality of life.
Seeks to prevent adverse effects on human health
and ecological systems.
Contains environmental toxicology within its scope.
In communicable or transmissable disease,
a pathogen attacks a host,
either directly or through a vector
(e.g., mosquito that transfers a malaria
parasite to hosts)
… and the pathogen can be transmitted from one host to
another.
Infectious disease causes 25 % of deaths in the world
and nearly half of deaths in developing nations.

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Infectious disease
Environmental health hazards
Synthetic and natural toxicants are only one type of
environmental health threat. Others are:
• Physical or climatic hazards (floods, landslides, radon, UV
exposure…)

• Biological hazards (viruses, bacterial pathogens…)

• Cultural or lifestyle hazards (drinking, smoking, bad diet,

crime in neighborhood…)
2nd-leading cause of 6 diseases account for 90%
death worldwide of infectious disease deaths

Environmental health hazards

Many health hazards exist indoors
Substances in plastics and
consumer products

Lead in paint and pipes

Radon

Asbestos

PBDE fire retardants

Risk Risk assessment

Analyzes risks quantitatively
Risk = the mathematical probability that some
Measures and compares risks involved in different
harmful outcome will result from a given action,
activities or substances
event, or substance
Helps identify and prioritize serious risks
Harmful outcome could be defined as injury, death,
environmental damage, economic loss, etc.
Helps determine threats posed to humans, wildlife,
ecosystems

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Risk management
Risk assessment Consider risk
Involves:
assessments in light of
• Dose-response analysis
social, economic, and
or other tests of toxicity political needs and
values.
• Assessing likely exposure
to the hazard Weigh costs and benefits,
(concentration, time, given both scientific and
frequency)
nonscientific concerns.

Decide whether or not to

reduce or eliminate risk.

Risk assessment and risk

management inform policy Federal agencies and risk management
Following risk management, policy decisions are made. most risk management is conducted by federal and
state agencies.

Particularly:

Environmental Protection Agency

and

Food and Drug Administration

Figure 10.14

Philosophical approaches Implications for product testing

“Innocent until proven guilty”:
“Innocent until proven guilty”: Industry can introduce any products it wants.
Assume harmless until shown to be harmful
Government bears the burden of proof to show if
Precautionary principle: products are dangerous.
Assume harmful until shown to be harmless
Precautionary principle:
Industry cannot introduce a product until it is very
thoroughly tested and shown convincingly to be
harmless.

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Implications for product testing

Industry has
Policy on toxicants
Key agencies and products they regulate:
pressured
government to take
an “innocent-till- Food and Drug Administration (FDA)
proven-guilty” food, additives, cosmetics, drugs, medical devices
approach.
Environmental Protection Agency (EPA)
Environmental pesticides, industrial chemicals, and any synthetic
advocates have chemicals not covered by other agencies
pressured
government to
follow the Occupational Health and Safety Administration (OSHA)
precautionary workplace hazards
principle.
Figure 10.15

EPA regulation: Industrial chemicals

EPA is charged with monitoring 75,000 industrial chemicals.
International policy on toxicants
Too many chemicals, too little time, people, resources Little or no effective regulation in most developing nations.

Only 10% of chemicals on the market are thoroughly tested.
Only 2% are screened for carcinogens, mutagens,
teratogens.
<1% are government regulated.
~0% are tested for endocrine, nervous, or immune effects.
Europe follows a policy closer to the precautionary
principle than does the U.S.
The EU is now considering a still-tougher policy.
Stockholm Convention, 2001: international treaty to phase
out 12 persistent organic pollutants (POPs), “the dirty
dozen”

“The dirty dozen” POPs Conclusions: Challenges

Synthetic chemicals are ubiquitous in our environment.

Very few chemicals on the market are thoroughly tested.

Our understanding of endocrine disruption and certain

other effects is still in its infancy.

Regulatory agencies are caught between pressure from

industry and environmental advocates.

People disagree over the roles of government and industry

in testing new chemical products.

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Conclusions: Solutions
Monitoring, public education, and regulation of industry
could together decrease our exposure to toxicants. Example for
Endocrine disruption and other novel threats are being
actively researched.
environmental disasters
EPA and other regulatory agencies do their best to continue due to toxic chemicals
assessing chemicals accurately and fairly.

Greater public participation in the risk management

process would promote regulatory decisions that favor
citizens.

Bhopal Disaster
• Rachel Carson --- Silent Spring
•
•
1907-1964
Marine Biologist from Pennsylvania
Amongst one of the worst
• was published in 1962, it generated a storm of
Industrial Disasters
controversy over the use of chemical pesticides
• Silent Spring facilitated the ban of the pesticide,
DDT for agricultural use in 1972 in the United States
• Describing the death of numerous birds around her
property resulting from the aerial spraying of DDT to kill mosquitoes
• She lobbied very hard to control and ban certain highly toxic
chemicals
• She was disturbed by the widespread and indiscriminate use of
pesticides
• Many of these pesticides were known to affect wildlife e.g. kill birds

Union Carbide Corporation

• The Union Carbide plant at Bhopal produced the product The gas leak accident
‘Sevin’ an insecticide for spraying on crops.
• A pesticide plant in India produced the compound Methyl • 41 T of MIC and its reaction products released
Iso Cyanate (MIC) as an intermediate product in the
process. • Cold winter midnight of 2nd – 3rd December 1984
•MIC is an extremely toxic and unstable substance and even • Between 00:40 and 02:30 AM
in very small quantities is fatal. • approx. 30m (100ft) height
•Large quantities of the MIC were stored in steel tank. The
tank had many safety features to maintain the product in a
safe and stable form.

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Animal Slaughter
Eg. – Minamata Disease in Japan
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Among the 500,000 people exposed to the
gas, 20,000 have died till date and 120,000
continue to suffer devastating health effects
as a result of their exposure.
Post-mortem Reports
• Cerebral oedema
• Massive pulmonary oedema
• Massive destruction of lung tissues
• Massive Coagulation of blood
• Damaged liver and kidneys
What is Minamata Disease?
• The most massive pollution problem to strike Japan in the post
WWII period.
• A neurological syndrome caused by methyl mercury in the
industrial wastewater.
• Continued from 1932 to 1968 (36 years)
• 2 cities (Minamata and Niigata were affected in Japan)
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Where are Minamata and Niigata? Source of Methyl Mercury

• Minamata City: The Nippon Chisso Corporation's Minamata Chemical
Factory

• Niigata City: The Showa-Denko’s Niigata Chemical Factory

Niigata

Minamata

The difficulty of determining

The discovery of Minamata Disease
its cause
• In 1956: official discovery • It was taboo to speak of the Chisso’s wastewater in the
• Eight patients suffering from a yet
unheard-of disease were brought to Chisso castle town
the Chisso Corporation’s factory
hospital
• The engineering dept. of Kumamoto University was
• 40 patients had been discovered in predisposed not to co-operate with the medical
a year research group of the same university in this regard

Consequences Methyl Mercury

• 2,955 victims have been officially recognized (2,009 of whom have
died) as of March 2006
• Over 10,000 have received financial compensation from the
Chisso co.
• Over 2 million people may have eaten fish contaminated with
methyl mercury from the Chisso factory
CH３Hg
• Volatile and very lipidsoluble
• Readily and completely absorbed by gastrointestinal tract
• Found complexed with free cysteine and with proteins and peptides
containing that amino acid
• Recognized by amino acid transporting proteins as methionine

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Methyl Mercury Methyl Mercury

H OH
I / H OH H OH
H3N-C-C I
H3N-C-C
/ I
H3N-C-C
/ • Mimicry of Methionine
I \\ → I \\ I \\
CH2 O
|
CH2 O CH2 O ↓
| |
SH S
|
CH２
| • Across the blood-brain barrier and placenta
Hg S
|
CH3
|
CH3
• Strong binding to proteins
Cysteine
↓
+
• Easy to become a part of body
CH3Hg
Methionine • Not readily eliminated (less than 1% of load)
Methyl Mercury

Toxic Effects of Methyl Mercury Conclusion

• Inhibits acetylcholine synthesis • Mercury intoxication ≒ Minamata disease
• Fatigue, memory loss, mood change, tremors, pallor, weakness and loss of vision • The difficulty of in determining its cause
or taste • Spreading out of the disease
• Impairs • Lipid soluble, strong binding to protein, high affinity for -SH
• glycolysis • Readily and completely absorbed
• nucleic acid biosynthesis • Not readily eliminated
• aerobic respiration
• Highly Toxic with small amount
• protein synthesis
• neurotransmitter release • We can find anything when we know what there is, but it is very
• Oxidative injury, altered calcium homeostasis difficult to determine the cause of yet unheard disease.
• The injured neurons eventually die

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