Quiz 3 Syllabus-A

Introduction to Toxicology – HSOH 2102
Instructor Name – Dr. Ravi Rangarajan

Room # 19.2.17
E-mail – [email protected]
Phone – 4495 2661
Industrial Toxicology
Organochlorines - DDT
➢ 1945-1960, used to control agricultural pests as well as disease-carrying insects.
➢ Growth in DDT production.
➢ 1953 - 38 million pounds;

➢ 1957 - 84 million pounds;
➢ 1959 - 125 million pounds.
Country Year Cases

Venezuela 1943 8,000,000
1958 800
India 1935 10,000,000
1969 286,000
Italy 1945 400,000
➢ Success of DDT in Controlling Malaria 1968 37
Taiwan 1945 1,000,000
➢ World Health Organization (WHO) 1969 9
credits DDT with saving 50,000,000
lives.
https://youtu.be/GCYEElzrK64
➢ It was too persistent in environment.
➢ Bioaccumulation and biomagnification in food chain.
➢ Long-term and uncontrolled use lead to development of DDT resistance in

insects.
➢ Controlling disease vectors such as mosquitoes, ticks etc and resurgence of

diseases.
➢ Broken down into DDD and DDE.
➢ Half-life of DDE is ~250 days while DDT
is ~30 days
➢ DDT and its products are insoluble in

water
➢ In insects it affects the synapses and cause

death.
Organophosphates
Parathion
➢ They block Acetylcholine

metabolism – Nerve impulse
conduction Neurotoxicity
Malathion
Organophosphates
➢ Phase I – Oxidation Reaction
➢ Phase II – Glutathione
conjugation
Paraquat
➢ Weed Killer - Non-selective Herbicide
➢ After almost 50 years of usage, discontinued due to enhanced toxicity

Paraquat
LD50 in mice – 30 mg/kg

Fluoroacetate
➢ Common Rodenticide
➢ Naturally occurs in 40 different sp. of plants
➢ FA was first synthesized in 1896 and found in plant genus like Gastrolobium,
Oxylobium and Acacia
Fluoroacetate
➢ Inhibition of the enzyme aconitase in the tricarboxylic acid cycle, caused by 'lethal
synthesis' of an isomer of fluorocitrate (FC).
➢ FA is found in a range of plant species and their ingestion can cause the death of
ruminant animals.
➢ PEL concentration is 15µg/L in urine

Drug Toxicity
➢ Adverse Effects or Side Effects – During proper therapeutic use
➢ Acute Toxicity – Over dosage
➢ Idiosyncratic reaction – Uncommon Side effects
Toxicokinetic Toxicodynamic
Paracetamol
➢ Antipyretic and analgesic effects.
➢ Acetaminophen increases the pain

threshold by inhibiting two isoforms of
cyclooxygenase enzymes (COX-1 and
COX-2)
➢ COX-1 and COX-2 are involved in

prostaglandin (PG) synthesis.
Prostaglandins are responsible for
eliciting pain sensations.
➢ When the prescribed doses are taken, the

desired therapeutic response is observe
with little or no toxicity.
➢ When excessive doses are taken,

hepatotoxicity can occur.
Paracetamol
➢ NAPQI is the
toxic metabolite
➢ If NAPQI is
formed, more
complex Amino acid
based conjugation
reactions are required
for elimination
➢ Toxicity – Acute
Toxicity - Over
dosage
For this reason, it is warned not to take

the prescribed dose more frequently
than every 4-6 hours and not to
consume more than four doses within a
24-hour period.
Aspirin
➢ One of the oldest man-made Analgesic and Antipyretic – Synthesized in 1899
➢ NSAIDs family (Non-Steroidal Anti-Inflammatory Drugs)
➢ Increases the pain threshold by inhibiting prostaglandin (PG) synthesis via

altering cyclooxygenase enzyme (COX-1 and COX-2)
Aspirin
➢ High lipophilicity of Salicylate helps in crossing membrane barriers and interstitial

fluids
Prolonged use in children
➢ Biotransformation and Elimination of Aspirin causes Reye’s syndrome
– Brain damage and
Liver problem
Halothane
➢ It is a Haloalkane, an Organofluorine
compound, an Organochlorine compound
and an Organobromine compound
➢ Low price anaesthetic agent
➢ Inhalation anaesthetics – General

anaesthetics
➢ Absorption is only through Inhalation
➢ Half Life – 4 to 7 hours at 1%

Concentration
➢ Modelled atmospheric Half Life - 1 Year Chloroform

Halothane
➢ Hepatotoxicity and Biotransformation
➢ HF (Hydrofluoric Acid) is released

Halothane
➢ Abnormal heart rhythm
➢ Decreased lung function
➢ Decreased oxygen in tissues/blood
➢ Hepatitis
➢ Kidney damage
➢ Malignant hyperthermia
➢ Problems with blood circulation
➢ Hepatotoxicity and Biotransformation

OSHA PEL - 2
➢ HF (Hydrofluoric Acid) is released ppm (16 mg/m³)
Thalidomide
Thalidomide
Thalidomide
Embryopathy
Environmental Toxicology
Food Additives
Common
Food
Additives
Food Additives - Tartrazine
➢ Sodium salt of Azo dye
➢ Azo food dye made from Petroleum

products
➢ These dyes can be used to create colors

not possible with natural products
➢ Common food products
➢ Certain breakfast cereals

➢ Refrigerated rolls and quick breads
➢ Cake mixes and pies
➢ Certain instant and regular puddings
➢ Certain ice creams and sherbets
➢ Certain candy coatings
➢ Hard candies
➢ Colored marshmallows
➢ Flavored carbonated beverages
➢ Flavored drink mixes
➢ Phase I – Reduction reactions
➢ Angioedema – Swelling of lips,

tongue etc., due to Histamine release
➢ Asthma
➢ Dermatitis
➢ Neurotoxin causing cytotoxicity
➢ Behavior problems in children –

ADHD
➢ Pregnancy intake - ADHD
➢ Carcinogen
Tartrazine Reduction
Food Additives - Saccharine
➢ Artificial Sweetener
➢ Single serving sugar
➢ It’s around 300–400 times sweeter than

regular sugar - Small amount is needed to
get a sweet taste.
➢ Saccharin is sometimes combined with aspartame, another low-calorie sweetener

commonly found in carbonated diet drinks.
➢ In addition to carbonated diet drinks, saccharin is used to sweeten low-calorie

candies, jams, jellies, and cookies. It’s also used in many medicines.
Food Additives - Saccharine
➢ Use of saccharin in human food has

been plagued by safety concerns.
➢ During the early 1970s, studies on

laboratory rats linked saccharin with the
development of bladder cancer in
rodents.
➢ Toxicokinetic studies - Linear

extrapolation of data from lower dose
studies.
➢ Saccharin has low acute toxicity, with an

LD50 of between 5 and 17.7 g/kg
Yet, further research discovered

that the cancer development in
rats was not relevant to humans.
Carbon monoxide - CO
➢ CO is eliminated through lungs
➢ Half Life of CO at room temperature –

3 to 4 hours
➢ 100% O2 reduces half life to 30-90

minutes.
➢ Hyperbaric 100% O2 at 2.5 atm

reduces half life to 15 minutes.
Ethylene Glycol
➢ Major component of Antifreeze liquid
➢ Used in hydraulic brake fluids
➢ Heat-transfer fluid
➢ Sweetener in Wine
➢ Manufacture of polyester fibers and

films
➢ Largest use in PET bottles
➢ Used in stamp pads, ballpoint pens,

inks and print shops
➢ Polymerized into PEG

Ethylene Glycol
➢ Polymerized into PEG
➢ Good Carrier agent

Ethylene Glycol
Ethyl Alcohol
➢ Hand Sanitizers – Ethanol or Isopropyl Alcohol
➢ We use methanol (or methyl alcohol) as a

component in fuel for cars and boats. It’s also
used to manufacture antifreeze, paint remover,
windshield wiper fluid, and many other
products.
➢ Isopropanol (or isopropyl alcohol) is the chemical

name for rubbing alcohol, which we use for
cleaning and disinfecting.
➢ Both methanol and isopropanol are poisonous

to humans because our bodies metabolize them
as toxic substances which cause liver failure
(Illicit alcohol)
Isopropanol
➢ Drinking even a small amount of methanol or
rubbing alcohol can be fatal.
Ethyl Alcohol
➢ The only type of alcohol that humans can safely drink is ethanol.
➢ Ethanol (or ethyl alcohol) is the type of alcohol that over two billion people drink every
day. This type of alcohol is produced by the fermentation of yeast, sugars, and
starches.
➢ Alcohol produced by mere fermentation of raw material is undistilled alcohol, e.g.,

beer, port, champagne
➢ Alcohol formed by distilling the fermented product of raw material is distilled

alcohol, e.g., gin, whisky, brandy
➢ Alcohol toxicity
➢ Damages the liver

➢ Brain damage
➢ Inhibits the central nervous system
➢ Impaired coordination and judgment.
➢ Results in addiction.
Ethyl Alcohol
➢ The human liver can

metabolize ethanol, but
only in limited quantities.
➢ About 90 %is metabolized

to acetaldehyde, acetic acid
and then CO2 and H2O at a
rate of 10 - 20 ml/hr
SLS – Sodium Lauryl Sulphate
➢ Surfactant - A substance which tends to reduce the

surface tension of a liquid in which it is dissolved
SLS – Sodium Lauryl Sulphate
➢ Carcinogenic (Controversial) –
OSHA says No
➢ Accumulate in our organs
➢ Known irritant if left on the

skin for a prolonged period of
time
➢ Irritant if it comes in contact

with your eyes
➢ Harm aquatic life and lower

life forms
➢ Wastewater treatment
affected – Flocculation does
not happen
Cyanide
Hydrogen Cyanide
Methyl
Isocyanate
Na/K Cyanide
Iron Cyanide
Cyanide
➢ Leach from Landfills
➢ Mining
➢ Industrial Processes
➢ Pesticide Production
(MIC is an intermediate)
➢ Cyanogenic - Chemical
compounds that release
hydrogen cyanide when
chewed or digested
Cyanide
Cyanide
➢ Phase I Oxidation to Thiocyanate
➢ Vitamin B12 complex (Storage)
➢ These mechanisms can eliminate very small amounts of cyanide - 0.017 mg of CN

per kg of body weight per minute in the average person
Dioxins
➢ Dioxins are unwanted by-products of

a wide range of manufacturing
processes including
➢ Smelting
➢ Chlorine bleaching of paper pulp
➢ Manufacturing of herbicides and
pesticides.
➢ Burning of Plastics
➢ In terms of dioxin release into the

environment, uncontrolled waste
incinerators (solid waste and
hospital waste) are often the worst
culprits, due to incomplete burning.
Dioxins
➢ More than 90% of human exposure is

through food, mainly meat and dairy
products, fish and shellfish.
➢ Main POP
Dioxins
➢ Affects Cell Cyle and causes Cancer

VOCs
VOCs
➢ VOCs are a diverse group of organic chemicals that have a high vapor pressure
at room temperature.
➢ VOCs are mainly blood-borne and are exhaled via the blood-breath interface in
the lungs.
➢ VOCs diffuse across the pulmonary alveolar membrane from the compartment
with the higher vapour pressure to lower vapour pressure.
➢ Exogenous VOCs – Coming from outside of the body.
➢ Endogenous VOCs – Produced in the body and excreted out.
Common VOCs
VOCs
➢ Endogenous VOCs are generated by various biological pathways, including
cellular respiration, digestion, and microbial metabolism in the gut.
➢ Examples of endogenous VOCs include acetone, ethanol, and various

organic acids produced during metabolism.
Environmental Pollutants
➢ Point Sources - Specific, identifiable
locations or facilities from which pollutants
are discharged directly into the
environment.
➢ These sources typically have well-

defined discharge points, such as
pipes, smokestacks, or drainage outlets.
➢ Examples of point sources include

industrial facilities, wastewater
treatment plants, power plants, and
factories.
➢ Point source pollution is relatively

easier to monitor and control due to
its localized nature and identifiable
sources.
Environmental Pollutants
➢ Non-point Sources - Refer to diffuse,
dispersed sources of pollution that do
not originate from a single, identifiable
point. Instead, pollutants are carried by
runoff or leaching from multiple
sources.
➢ Common examples - agricultural

runoff (e.g., pesticides, fertilizers),
urban runoff (e.g., motor oil, litter),
atmospheric deposition (e.g.,
airborne pollutants settling onto land
or water), and soil erosion.
➢ Challenging to manage and control

due to its diffuse nature and the
multitude of contributing sources
spread over large areas.
Air Pollution
➢ 5 major pollutants which
account to 98 % of all the air
pollution,
CO (52%)
SOx (18%)
HCs (12%),
Particulates (10%)
NOx (6%).
➢ The most visible form of air

pollution is of course smoke and
it contains various potentially
toxic gases.
➢ Industrial chemicals???
50
Air Pollution
➢ Smog – Smoke with fog
➢ Two types
1. Reducing smog - High level

of particulates and SOx
originating from coal burning in
particular.
2. Photochemical smog - High

concentration of ozone, NOx
and hydrocarbons.
➢ Photochemical smog is an oxidizing

pollutant mixture
➢ Arising particularly from the interaction of

the constituents of car exhausts in bright
sunlight.
Air Pollution – Indoor (IAP/IAQ)
➢ Harmful pollutants inside buildings
include carbon monoxide (CO), volatile
organic compounds (VOCs), particulate
matter (PM), aerosol, biological
pollutants, and others.
➢ Due to increased levels of urbanization,

focus has shifted from outdoor to indoor
environments, as it reflects lifestyle
changes.
➢ Indoor Air Pollution/Quality negatively

affect human health by causing
building-associated illness – Sick COPD – Chronic Obstructive
Building Syndrome (SBS) Pulmonary Disease
CHD – Coronary Heart
➢ Effects could be acute or chronic Disease
➢ Both short- and long-term IAP exposure

can cause a wide range of diseases
Air Pollution - PM
➢ Particulate Matter (PM) is defined as
carbonaceous particles in association with
adsorbed organic chemicals and reactive
metals.
➢ PM’s main components are sulfates,

nitrates, endotoxin, polycyclic aromatic
hydrocarbons (PAHs), and heavy metals.
➢ Depending on the particle size, PM

generally is classified into
(i) Coarse particles, PM10 of

diameter <10 µm
(ii) Fine particles, PM2.5 of diameter
<2.5 µm
(iii) Ultrafine particles, PM0.1 of
diameter <0.1 µm.
53
Air Pollution - PM
➢ Compared with PM10 and PM2.5, PM0.1 created by fossil fuel combustion represents a
greater threat to health due to its penetrability into the small airways as well as
alveoli.
➢ Depending on the particle size, PM
generally is classified into
(i) Coarse particles, PM10 of

diameter <10 µm
(ii) Fine particles, PM2.5 of
diameter <2.5 µm
(iii) Ultrafine particles, PM0.1 of
diameter <0.1 µm.
➢ Unspecified – Secondary particles are those that form in the atmosphere from other
gaseous pollutants by photochemical and other reactions (particularly SOx, NOx,
VOCs and Ammonia).
54
Air Pollution - PM
➢ It has been shown that indoor PM levels often exceed outdoor ones
➢ Indoor PM sources include
(i) particles that migrate from the outdoor environment

(ii) particles generated by indoor activities.
➢ Cooking, fossil fuel combustion activities, smoking, machine operation, and residential
hobbies are the main reasons why PM is distributed inside of buildings.
➢ Indoor PM exposure is linked to a variety of health impacts, including:
1. Eye, nose and throat irritation

2. Aggravation of coronary and respiratory disease
symptoms
3. Premature death in people with heart or lung
disease
55
Air Pollution – Acid Rain
➢ The two principal components are NOx and SOx.
➢ Sulfur dioxide (SO2) is the most common gas among the group of sulfur oxides
(SOx) present in the atmosphere.
➢ SO2 is primarily produced by the combustion process of fossil fuels, and

combines with aerosols and PMs to form a pollutant complexes
56
Air Pollution – Acid Rain
➢ Nitrogen oxides are nitric oxide (NO) and nitrogen dioxide (NO2)
➢ Under ambient conditions, NO is rapidly oxidized to form NO2; hence, NO2 is

usually considered as a primary pollutant.
Health Effects
Respiratory problems
Asthma, Dry coughs, throat irritation
Headaches
Leaching of toxins from soil and reabsorption by living systems
Systemic Toxicity
COPD – Chronic Obstructive

Pulmonary Disease
CHD – Coronary Heart
Disease
57
Water Pollution – Bioaccumulation and Biomagnification
➢ Bioaccumulation – The process of accumulation of chemicals in an organism that
takes place if the rate of intake exceeds the rate of excretion.
➢ Chemicals are introduced into the organism through exposure to the abiotic
environment (soil, water, air) or as dietary intake (trophic transfer)
➢ Biomagnification – Accumulation of a chemical

by an organism from water and food
exposure that results in a concentration that is
greater than environmental levels E.g. Mercury
58
Natural Toxins
➢ Natural toxins are chemicals that are naturally produced by living organisms.
➢ These toxins are not harmful to the organisms themselves but they may be
toxic to other creatures, including humans
➢ Generally metabolic products that appeared to have evolved as defense

mechanisms for the purpose of repelling or killing predators or pathogens
Natural Toxins
➢ Natural toxins can be classified according to chemical class, biological origin, target
organ toxicity, or mode of action, but are most commonly classified according to
source.
➢ Microbial toxins
➢ Mycotoxins
➢ Plant toxins
➢ Animal toxins
➢ Phycotoxins
Natural Toxins - Microbial
➢ Neurotoxin produced by Clostridium
botulinum
➢ There are 8 sub-types of this peptide
➢ Anaerobic Bacteria
➢ Botulinum toxin acts to block release of

acetylcholine from cholinergic nerve endings
➢ Anaerobic condition favors its growth
➢ Canned foods, packaged products and

anaerobic spots in vegetables and meats
➢ Home packaged and Small scale packaging
➢ LD50 of 0.4 ng/kg

➢ Tetanospasmin is the toxin
➢ Produced by Clostridium tetani –

Common in soil
➢ Tetanus Toxoid shots??

Natural Toxins - Microbial ➢ Tetanospasmin
➢ Produced by Clostridium tetani –

Common in soil
➢ Tetanospasmin prevents Ca2+-

dependent release of glycine, an
inhibitory neurotransmitter from
CNS neurons
➢ Resulting in unopposed
excitation of spinal neurons and
➢ The spores are extremely hardy muscle contraction.
and are resistant to heat, various
antiseptics, and boiling for ➢ The toxin does not pass the
several minutes blood–brain barrier.
➢ Spores are formed as a survival ➢ Lockjaw disease

mechanism to extreme
environmental conditions ➢ LD50 of 3 ng/kg
Natural Toxins - Fungal
➢ Toxic compounds that are naturally produced by certain types of moulds.
➢ The adverse health effects of mycotoxins range from acute poisoning to

long-term effects such as immune deficiency and cancer
➢ Mycotoxins appear in the food chain as a result of mould infection of crops both
before and after harvest.
➢ Aflatoxins are toxins produced by the mold Aspergillus flavus that can grow on food
ingredients.
➢ The most common types of aflatoxins are B1, B2, G1, G2, M1, and M2.
➢ Common food stuff include
➢ Groundnut & Corn

➢ Maize and Rice
➢ Figs and other dried foods
➢ Spices
➢ Crude vegetable oils
➢ Cocoa beans
➢ Milk Contamination
➢ ROE -
➢ Direct ingestion of contaminated food.
➢ Aflatoxin M1 is a metabolite of aflatoxin B1 and can be present in the milk of animals that
have consumed contaminated feed. This can lead to the ingestion of aflatoxins through
milk and dairy products.
➢ Carcinogenicity - Aflatoxin B1 is classified as a Group 1 human carcinogen by the

International Agency for Research on Cancer (IARC). It is associated with an increased
risk of liver cancer, especially in populations with high levels of aflatoxin exposure.
➢ Hepatotoxicity - They can cause acute toxicity, leading to symptoms such as abdominal
pain, vomiting, and liver damage.
➢ Immunotoxicity - Aflatoxins can impair the immune system, making individuals more
susceptible to infections and other health issues.
➢ Growth Impairment - In children, exposure to aflatoxins has been associated with growth
impairment and developmental issues.
➢ Biotransformation and Toxicity
Phase I
Bioactivation
Phase II
➢ Ergot alkaloids are a large group of

compounds produced by fungi
➢ Two common alkaloids are

Ergotamine and Ergovaline
➢ The major ergot fungus is Claviceps

pupurea
➢ Attacks a wide variety of grass

species, including small grains (rye),
during the growing season.
➢ They deposit ergots/sclerotia

(reproductive fungal bodies)
➢ Ergotism occurs from ingestion of Ergot alkaloids
➢ It is one of the oldest known mycotoxicoses with ancient records of its occurrence.
➢ One of the most publicized events was the human epidemics produced by ergot in the
Middle Ages known as St. Anthony’s fire with symptoms of gangrene, central
nervous and gastrointestinal effects.
Natural Toxins - Plants
➢ Plant toxins are generally the secondary metabolites produced by plants

against predation.
➢ Natural toxins are present in numerous types of plants and these are consumed in
large quantity or not cook properly leads to food poisoning.
➢ Some of the drugs of abuse such as cocaine, caffeine, nicotine, morphine, and the
cannabinoids are plant toxins.
Classification and examples of Plant Toxins
➢ Alkaloids – Heterocyclic nitrogenous compounds - Strychnine

➢ Cyanogenic Glycosides
➢ Proteins – Ricin, Abrin, Lectins (Kidney Beans)
➢ Furocoumarins - Stress toxins and Phototoxic
➢ Solanines – Glycoalkaloids – Potato sprouts
➢ Muscimol and Muscarine – Poisonous mushrooms
➢ Fluoroacetate
➢ Strychnine is highly toxic alkaloid
➢ Found in Strychnous genus (South Asia and

Austraia)
➢ Rapidly absorbed through the mucous membranes

of the mouth, stomach, and small intestines,
➢ Theoretically it may be used as a military toxic or

terroristic agent.
➢ Strychnine is found mixed with “street” drugs

such as LSD, heroin, and cocaine
➢ The oral LD value in rats is ∼15 mg kg−1.
➢ Intravenous routes of exposure are more toxic;

LD50 values in laboratory rodents range from 1 to
4 mg kg−1
➢ Ricin is carbohydrate binding protein
➢ It’s a hemagglutinin (RBC clumping)
➢ Found in Ricinus communis (Castor plant)
➢ At lower doses, it has antitumor activity.
➢ Undergoes Phase I hydrolysis

➢ Mimicking Endogenous Molecules (Factors controlling toxin entry)
➢ Endocytosis of Galactose
➢ LD50 is approximately 1 mg/kg body wt.

Cyanogenic Glycosides –
➢ Amygdalin from the seeds of Stone fruits

➢ Linamarin from Cassava
➢ Taxiphyllin from Bamboo
Cyanogenic Glycosides –
➢ Amygdalin from the seeds of Stone fruits

➢ Linamarin from Cassava
➢ Taxiphyllin from Bamboo
Natural Toxins - Animals
➢ Tetrodotoxin (TTX)
➢ Found in liver and sex organs (gonads) of puffer

fish, globefish, and toadfish, and in some
amphibian, octopus, and shellfish species.
➢ Its synthesized by marine bacteria in symbiosis

with organisms
➢ Tetrodotoxin – Blocks Voltage Gated Sodium Channels (VGSCs)
➢ Exposure occurs due to ingestion of fish or other food containing tetrodotoxin.
➢ Analogs are present in bivalves and gastropods.

➢ Batrachotoxin - BTX
➢ Native Indians have used this venom for

hundreds of years to poison blow darts
➢ Batrachotoxin is extremely toxic with a LD50 of

less than 100 ng/kg for mice.
➢ The site of action for batrachotoxins is the
voltage-dependent sodium channel of nerve
and muscle
➢ Batrachotoxin appears to bind to an open

form of the sodium channel, preventing the
closing of the channel.
➢ A dietary origin for the toxin - Ants

➢ Snake venoms contain complex mixtures of hundreds of different pharmacologically

active molecules
Low-molecular mass compounds (e.g., histamine and alkaloids),

Small peptides,
Proteins.
➢ Snake venoms are usually classified as hemotoxic or neurotoxic.
➢ Snakes of the Viperidae (vipers and rattlesnakes) family have venoms containing
proteins and peptides
➢ Disrupt the coagulation cascade, the hemostatic system, and tissue integrity
(hemotoxic).
➢ In contrast, neurotoxic venoms are typical of the Elapidae snakes (mambas, cobras,
and corals).
➢ They contain a number of toxins that primarily affect the peripheral nervous system,
in particular the neuromuscular junction.
➢ Most of the potent snake venoms target specific targets mostly affecting the
neuromuscular junction and/or hematologic systems.
➢ In the wild, this would result in immobilization of their prey. For Humans,
Antidotes given in time can save them.
Toxins and Antidotes
➢ Antidote - Drugs designed to counteract toxins.
➢ They act by altering the chemical nature of the toxin, or by interfering with toxin
binding to biologic sites - reduce morbidity or mortality.
➢ Common antidote actions
1. Chelating agents - These act by reacting with the compound to form a

water soluble complex which can be eliminated.
Eg. Penicillamine used for treating lead poisoning,

Dicobalt edetate used for the treatment of cyanide poisoning
2. Detoxifiers - Specifically increase the detoxication of a reactive

metabolite.
Eg. Thiosulphate administration as antidote for cyanide poisoning.

N-acetylcysteine is used for the treatment of paracetamol overdoses
Toxins and Antidotes
➢ Common antidote actions
3. Inhibition of Metabolism
Eg. PEG, Alcohol
4. Receptor antidotes
Eg. Atropine for Organophosphates
5. Reversal of Receptor Blockade
Eg. Treatment of Carbonmonoxide poisoning with oxygen
6. Use of antibodies or antibody fragments.
Eg. For toxins such as snake venoms, antivenoms may be available which
specifically bind the protein(s) in the venom

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Introduction to Toxicology – HSOH 2102

Instructor Name – Dr. Ravi Rangarajan

➢ Growth in DDT production.

➢ 1953 - 38 million pounds;

Country Year Cases

➢ Bioaccumulation and biomagnification in food chain.

➢ Long-term and uncontrolled use lead to development of DDT resistance in

➢ Controlling disease vectors such as mosquitoes, ticks etc and resurgence of

➢ DDT and its products are insoluble in

➢ In insects it affects the synapses and cause

➢ They block Acetylcholine

➢ Phase I – Oxidation Reaction

➢ After almost 50 years of usage, discontinued due to enhanced toxicity

LD50 in mice – 30 mg/kg

➢ Naturally occurs in 40 different sp. of plants

➢ PEL concentration is 15µg/L in urine

➢ Acute Toxicity – Over dosage

➢ Idiosyncratic reaction – Uncommon Side effects

➢ Acetaminophen increases the pain

➢ COX-1 and COX-2 are involved in

➢ When the prescribed doses are taken, the

➢ When excessive doses are taken,

For this reason, it is warned not to take

➢ One of the oldest man-made Analgesic and Antipyretic – Synthesized in 1899

➢ NSAIDs family (Non-Steroidal Anti-Inflammatory Drugs)

➢ Increases the pain threshold by inhibiting prostaglandin (PG) synthesis via

➢ High lipophilicity of Salicylate helps in crossing membrane barriers and interstitial

➢ Low price anaesthetic agent

➢ Inhalation anaesthetics – General

➢ Absorption is only through Inhalation

➢ Half Life – 4 to 7 hours at 1%

➢ Modelled atmospheric Half Life - 1 Year Chloroform

➢ Hepatotoxicity and Biotransformation

➢ HF (Hydrofluoric Acid) is released

➢ Abnormal heart rhythm

➢ Decreased lung function

➢ Decreased oxygen in tissues/blood

➢ Problems with blood circulation

➢ Hepatotoxicity and Biotransformation

➢ Azo food dye made from Petroleum

➢ These dyes can be used to create colors

➢ Common food products

➢ Certain breakfast cereals

➢ Angioedema – Swelling of lips,

➢ Neurotoxin causing cytotoxicity

➢ Behavior problems in children –

➢ Pregnancy intake - ADHD

➢ Single serving sugar

➢ It’s around 300–400 times sweeter than

➢ Saccharin is sometimes combined with aspartame, another low-calorie sweetener

➢ In addition to carbonated diet drinks, saccharin is used to sweeten low-calorie

➢ Use of saccharin in human food has

➢ During the early 1970s, studies on

➢ Toxicokinetic studies - Linear

➢ Saccharin has low acute toxicity, with an

Yet, further research discovered

➢ CO is eliminated through lungs

➢ Half Life of CO at room temperature –

➢ 100% O2 reduces half life to 30-90

➢ Hyperbaric 100% O2 at 2.5 atm