INTRODUCTION TO

TOXICOLOGY AND
TOXINS

Module I
 Toxicology
• Toxicology is the science which deals with poisons
with reference to their sources, properties, mode of
action, symptoms, which they produce, lethal dose,
fatal dose, treatment, methods of their detection
and estimation , and autopsy findings.

• Toxicology is the science which deals with toxins

produced by plants, animals, bacteria, and fungi,
which are harmful to man.
 Poison
 A poison is a substance which, when
administrated, inhaled or ingested, is a
capable of acting harmful on the human
body. Thus, almost anything is a poisons.

All substances are poisons;

there is none that is not a poison.
The right dose
differentiates a poison and a remedy.

[Paracelsus (1493-1541)]
 Drug
 Drug (WHO 1996): “Drug is any substance
or product that is used or proposed to be
used to modify or explore physiological
systems or pathological states for the
benefit of the recipient.” Eg: Paracetamol,
Ciprofloxacin, Salbutamol, etc.
Dose:-
The amount of chemical entering the
body
This is usually given as
mg of chemical/kg of body weight = mg/kg
The dose is dependent upon
* The environmental concentration
* The properties of the toxicant
* The frequency of exposure
* The length of exposure
* The exposure pathway
 Toxicant—any substance that causes a
harmful (or adverse) effect when in contact
with a living organism at a sufficiently high
concentration.

 Toxin—any toxicant produced by an

organism that is, naturally produced
toxicants. An example would be the
pyrethrins, which are natural pesticides
produced by pyrethrum flowers (i.e., certain
chrysanthemums) that serve as the model
for the man made insecticide class
pyrethroids.
 Route of Administration
 Oral/Ingestion (Gastrointestinal Tract)
 Inhalation (Lungs)
 Intramuscular
 Intravenous
 Dermal/Topical (Skin)
 Typical Effectiveness of Route of Exposure
iv > inhale > im > ingest > topical
 Toxicity
 Acute toxicity—an adverse or undesirable effect
that is manifested within a relatively short time
interval ranging from almost immediately to within
several days following exposure (or dosing). An
example would be chemical asphyxiation from
exposure to a high concentration of carbon
monoxide (CO).
 Chronic toxicity—a permanent or lasting
adverse effect that is manifested after exposure
to a toxicant. An example would be the
development of silicosis following a long-term
exposure to silica in workplaces such as foundries.
 Local toxicity—an adverse or undesirable effect
that is manifested at the toxicant’s site of contact
with the organism. Examples include an acid’s
 Systemic toxicity—an adverse or undesirable effect that
can be seen throughout the organism or in an organ
with selective exposure distant from the point of entry of
the toxicant (i.e., toxicant requires absorption and
distribution within the organism to produce the toxic
effect). Examples would be adverse effects on the kidney
or central nervous system resulting from the chronic
ingestion of mercury.
 Reversible toxicity—an adverse or undesirable effect
that can be reversed once exposure is stopped.
Reversibility of toxicity depends on a number of factors,
including the extent of exposure (time and amount of
toxicant) and the ability of the affected tissue to repair or
regenerate. An example includes hepatic toxicity from
acute acetaminophen exposure and liver regeneration.
 Delayed or latent toxicity—an adverse or undesirable
effect appearing long after the initiation and/or
cessation of exposure to the toxicant. An example is
cervical cancer during adulthood resulting from in utero
exposure to diethylstilbestrol (DES).
 ABSORPTION, DISTRIBUTION,
METABOLISM, AND EXCRETION OF
TOXICANTS (ADME)
Absorption:
 Absorption-the ability of a chemical agent to enter the
blood.
Intravenous - No limiting factors in absorption (100%
bioavailable)
Inhalation - Must penetrate alveolar sacs of lungs
but then into capillary bed
Ingestion - Requires absorption through GI tract
Intraperitoneal- Like ingestion but does not require
absorption through the GI tract
Dermal/Topical - Requires absorption through the skin
Distribution:
 Distribution—the process in which a
chemical agent translocates throughout
the body. The blood carries the agent to
and from its site of action, storage
depots, organs of biotransformation, and
organs of elimination.
 The rate of distribution is usually rapid, and
is determined primarily by blood flow and
the chemical characteristics of the toxicant
(its affinity for the tissue and the partition
coefficient). The distribution of a chemical
may change over time.
Metabolism:
 Metabolism (biotransformation)—the process
by which administered chemicals (parent
compounds) are modified by the
organism, usually via enzymes. The
primary objective of metabolism is to make
chemical agents more water soluble and
easier to excrete by
 Decreasing lipid solubility Decreased
amount that reaches target
 Increasing ionization Increased rate of
excretion Decrease toxicity
 In some situations, biotransformation results in
the formation of reactive metabolites—
Bioactivation.
Excretion:
 Toxicants are eliminated from the body by several
routes.
 Urinary excretion : Water soluble products are
filtered out of the blood and excreted into the urine.
 Exhalation : Volatile compounds are exhaled
through breathing
 Biliary Excretion via Fecal Excretion :
Compounds can be extracted by the liver,
biotransformed, and excreted into the bile. The bile
drains into the small intestine where the eliminated
compound can be excreted into the faeces.
 Faecal excretion also rids the body of non-absorbed
compounds which pass through the GI tract.
 Toxico-analytical
Classification of poisons
1. Gaseous poisons : (isolated by distillation)

2. Volatile poisons : (isolated by distillation)

3. Drugs or Non-volatile poisons : (isolated by solvent extraction)

4. Pesticides : (isolated by solvent extraction)

5. Metallic poisons : (isolated by ashing or by wet oxidation of

organic matter)

6. Toxic anions : (isolated by dialysis or extraction)

7. Miscellaneous poisons : (requires special extraction techniques such

as ion-exchange columns, formation of derivatives or ion-pairs,
freeze-drying and continuous extraction with a polar solvent. The
 1. Gaseous Poison
 The presence of this group of poisons is
usually indicated by circumstances of the
incident.
 For example- some compounds which are
gases at normal temperature and pressure
can be detected by gas chromatography.
 Gas chromatography can detect butane,
ethane, methane, nitrous oxide,
propane, and low boiling fluorocarbons.
 Only two poisons require routine exclusion,
these are cyanide and carbon monoxide.
 2. Volatile poison
 This group includes alcohols (methanol,
ethanol, etc.), aldehydes, ketones,
benzene, toluene, acetone, halogenated
hydrocarbons and the “glue-sniffing”
compounds.
 Rapid onset of symptoms, followed by
serious illness or death is the most valuable
clue to the presence of this group.
 3. Non-volatile poisons/
drugs
 This group includes: analgesics, opiates
or synthetic narcotics, sedatives and
hypnotics, stimulants,
antidepressants, etc.
 In general, postmortem stomach contents,
blood and urine samples may be analyzed.
Analysis can also be performed for drug
overdose, for suspicious deaths or criminal
cases.
 Extraction can be carried out by using
Stas-Otto methods, or general solvent
extraction, modified by a few additional
 4. Pesticides
 Pesticides include insecticides, fungicides,
herbicides, rodenticides, nematocides,
molluscides and acaricides.
 Pesticides cover a wide variety of substances
which is used to destroy undesirable life
forms.
 The common names approved by the British
Standards (BSI) and the International
Organization for Standardization (ISO) have
been used for convenience and brevity. IUPAC
names can be obtained from the Pesticide
Manual.
 5. Metallic poison
 Metallic poison should be checked as a
matter of routine if vomiting and diarrhoea
are noted as symptoms.
 The commonest poisons are – arsenic,
antimony, lead, cadmium, lithium,
mercury, thallium, chromium,
selenium, etc.
 The Reinsch test detects only seven of
twenty potentially toxic metals.
 6. Anions
 Most commonly encountered anions may
be found in biological fluids, albeit at low
concentration.
 Possible sources for excessive
concentrations of some anions of
toxicological significance are- borate,
bromide, chlorate, cyanide, fluoride,
hypochlorite, iodide/iodine, nitrate,
nitrite, oxalate, phosphate, sulfate,
sulfide and thiocyanate.
 Qualitative test for anions may be
performed on stomach washing, gastric
contents or vomit.
 Classification: On the
basis of mode of action
 1. Corrosives
 Strong Acids:
Mineral or inorganic acids: Sulphuric acid,
nitric acid and hydrochloric acid
Organic acids: Carbolic acid, Oxalic acid,
acetic acid and salicylic acid.
 Strong alkalis: Hydrates and

Carbonates of sodium and

potassium.
 2. Irritants
 Inorganic:
Non-metallic: Phosphorus, chlorine, bromine, iodine.
Metallic: Arsenic, lead, mercury, copper, zinc,
thallium etc.
 Organic
Vegetable poisons: Castor oil seeds, croton oil,
madar, emicarpus anacardium, calotropis,
capsicum, aloes, Abrus precatorius
Animal poisons: Cantharides, snake venom, insects,
scorpion, spiders etc.
Mechanical: Powdered glass, diamond dust, chopped
hair etc.
 3. Neurotoxic
 Cerebral
 Somniferous: Opium, barbiturates
 Inebriants: Alcohol, Ether and chloroform
 Deliriant: Dhatura, Belladonna, Cannabis,
Hyocyamus, Cocaine.
 Spinal: Nux vomica and gelsemium.
 Peripheral: Curare, Conium.
 4. Cardio toxic poisons:
 Aconite, Quinine, Digitalis, oleander,
nicotine and hydrocyanic acid.

5. Asphyxiants:
• Irrespirable gases: carbon dioxide, carbon
monoxide, hydrogen sulphide and coal gas.
This category also includes the cyanides.
 6. Miscellaneous
 Agro-chemicals
 Pesticides and insecticides:
organophosphates, carbamates,
organochlorines etc.
 Herbicides (weed- killers): paraquat,
bromoxynil etc.
 Rodenticides : zink posphide, thallium
sulphate etc.
 Domestic and Commercial poisons
 Petroleum distillates
 disinfectants
Medico- Legal Classification
of Poison

1. Homicidal: Arsenic, Aconite, Digitalis, Abrus

Precatorius, Strychnos nux vomica.

2. Suicidal: Opium, Barbiturate, copper sulphate,

carbolic acid, Organophosphorus.

3. Accidental: Aspirin, organophosphorus, copper

sulphate, snakes bite, Ergot, CO, CO2, H2S.

4. Abortifacient: Ergot, Quinine, Calotropis, Plumbago

5. Stupefying agent:Dhatura, cannabis,
chloral hybrate.

6. Agents used to cause bodily injury:

Corrosive acids
and alkalies.

7. Cattle Poison: Abrus precatorius,

Calotropis, plumbago.

8. Used for malingering: semicarpus

anacardium
 Action of Poison
 Local:
 Direct tissue injury at the point of
application. e.g. skin, or opharynx.
 Poisons act directly on the tissues and cause
corrosion, irritation and inflammation.
 General/Remote:
 Secondary absorption into the bloodstream to
cause systemic effects/organ damage.
 As the poison gets absorbed systemically, it
produces both specific CNS, spinal cord, cardiac
and nonspecific shock
 Factors modifying action of
poison
1) Dose: Some poisons are dose dependent and will not
cause deleterious effects until a certain critical dose is
exceeded.
2) Concentration: Mainly a feature of corrosives, which if
diluted, may have relatively little effect.
3) Rate of administration: If this is slow, the body's
detoxification systems may be able to effect some
protection from noxious consequences.
4) Tolerance: A person accustomed to taking a drug, or who has been
exposed to low doses of a poison over a period of time may be able to
tolerate far more than the usual lethal dose e.g. drug addicts or
people on continuous drug therapy such as epileptics. Amphetamines,
barbiturates, benzodiazepines and morphine and its derivatives all
exhibit this phenomenon.
5) Age: In general, children and the elderly are more susceptible to
poisons. Hepatic detoxification systems are relatively underdeveloped
in young children.
6) Route of absorption/administration: Food in the stomach may delay
the action of ingested poisons. The lethal dose of a poison by injection
is much lower than by oral administration.
7) State: A poison in liquid form will be absorbed more quickly from the
stomach than the same substance in powder or tablet form. The
chemical state of the poison may also be important e.g. two different
salts of the same metal may vary in their toxicity.
8) Health: In general, ill-health is likely to accelerate the effects of a
poison. This is especially true if there is dysfunction of the organ
primarily responsible for the detoxification of the poison
concerned.
9) Idiosyncrasy: (an abnormal physical reaction by an individual to
a food or drug.) Because of hypersensitivity a person may give
in to a much smaller dose of a drug/poison than normal.
Penicillin, aspirin, cocaine and heroine fall into this category.
10) Synergism: (Interaction b/w 2 poisons) Two compounds may
combine to cause a much more lethal effect than the dose of
either one by itself would have been expected to do e.g.
barbiturates taken with alcohol.
11) Cumulative effect: Some poisons may accumulate in the body
over long periods until a toxic dose is eventually reached e.g.
chronic lead poisoning.