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1.

Introduction:

Toxicology is the study of adverse effects of chemical substances on biological system due to
their exposure. It includes study of mode of action, symptoms, detection and treatments of toxic
agent in biological system. The word “Toxicology” is came from the Greek word “toxicon”
which was used as a poisonous substance in arrowheads. Conventionally, the toxicology may be
defined as the science representing the character, source, knowledge, lethal dose, fatal effect,
analysis of poisons and their curative measures. More precisely, Toxicology can be said as the
study of antagonistic effects of chemical or physical agents on living organisms. A “toxicologist”
is competent to examine and lead into the nature of those effects on human, animal, and
environmental health. Toxicological study examines the cellular, biochemical, and molecular
mechanisms of action as well as functional effects such as neurobehavioral and immunological,
and assesses the likelihood of their event. The diversity of chemicals and that of their prospective
adverse effects in the environment make toxicology a comprehensive science, which often
demands specialization in a specific range of toxicology. Our society’s dependency on chemicals
and the requirement to assess impending hazards have made toxicologists an increasingly
important part of the decision making processes. The existing description would be somewhat
altered but not necessarily be incorrect as it regards with the study and analysis of Physical and
Chemical properties of Poisons. Where the Physical properties means the appearance e.g.,
colour, state, Melting Point, Boiling Point, etc. the Chemical properties has an important
characteristic in which the fatal dose, toxicity, action upon the body are studied including its
metabolism. The added labour in the field of Toxicology is the detection of any poison inside the
body, its Quantitative and Qualitative estimation and interpretation of results of the respective
toxicological analysis. Poison may be regarded as any substance which, when taken in sufficient
quantity, will cause ill health or death.

1.1. HISTORY OF TOXICOLOGY

Toxicology dates back to the earliest humans, who used plant extracts and animal venoms for
warfare, hunting, and assassination. Elucidating the mechanisms of the toxicity of venoms
continues today in the field of toxicology. The knowledge of these poisons must have pre-existed
detailed history. According to a presumption, prehistoric humans characterized some plants as
hazardous and others as safe. The same is possibly true for the classification of snakes and other
animals

2. Branches of toxicology

There are various branches of toxicology i.e. analytical toxicology, clinical toxicology, forensic
toxicology, veterinary toxicology, aquatic toxicology, environmental toxicology, etc. These
branches have been summarised below.

2.1. Analytical toxicology: Analytical toxicology is deals with evaluation of toxic substance
present in biological specimen as well as in raw form. Evaluation involves detection,
identification and quantification of poisons using various analytical techniques.

2.2. Clinical toxicology: Clinical toxicology is deals with diagnosis and treatment of human
poisoning.

2.3. Forensic toxicology: Forensic toxicology deals with the analysis of toxic substances which
involve various methods to study these poisonous substances to aid the legal investigation to
know the cause of poisoning. It is medico-legal aspect of clinical poisoning.

2.4. Veterinary toxicology: Veterinary toxicology is the specialised branch of toxicology which
deals with study, diagnosis and treatment of various toxic compounds in animal kingdom.

2.5. Aquatic toxicology: Aquatic toxicology deals with adverse effect caused by toxic substance
on aquatic system4.

2.6. Environmental toxicology: Environmental toxicology deals with the ill-effects of


environmental toxicants on human, animal, plants and the environment. Environmental toxicants
are the compounds which are released into environment from various sources such as disposal
from industries, domestic disposal etc which may be degradable or non-degradable.
3. Poison

Poison is a substance which when administered, inhaled or swallowed by living organism causes
ill effects on the body. Poison is any substance (solid, liquid, gas) which if assimilated in the
living body or brought into contact with any part thereof, will lead to deterioration of health or
may eventually lead to death by its constitutional or local effects. Every agent may be harmful if
acting on an organism at a high enough dose. Poison may also be defined, as a material which
when administered, inhaled or ingested is capable of acting deadly on the human body. Thus
almost anything is a poison. There is very minute difference between medicines or poison, a
medicine in a toxic dose is a poison and a poison in a small dose may be a medicine. According
to law the key distinction between a medicine and poison is the intent with which it is given to a
person. Therefore, if the substance is administered with the intention to save a life, it is a
medicine but it acts as a poison if it is given with the intent to cause harm to the body. A very
high percentage of all the poisonings happen at home. The most common domestic products
associated in poisonings cases are: cleaning solutions, fuels, medicines, and other materials such
as glue and cosmetics. Certain animals have the tendency to secrete xenobiotic poison commonly
referred to as venom; which is usually injected with a bite or a sting, while some others animals
harbor infectious bacteria. Some household plants can also prove to be noxious to humans and
animals

Causes of Poisoning

Poisoning may result from any of the reason, some of the reasons are stated below:

 Poisoning may be caused by the administration of poison for criminal purposes.


 The swallowing of poison in mistake for harmless substances can also lead to poisoning
 The inhalation of the vapors of a poison either accidently or by ignorance.
 The improper formulation of medicines containing a poison
 The accidental intake of large dose of medicine containing a poison
 Excessive self-medication
 Addiction of drugs
 Bite by a poisonous animal
 Food infected with bacteria or their toxins
3.1. Classification of poison

Poisons can be classified in various categories depending upon their;

(A) mode of action and

(B) physical state and

(C) medicolegal classification

(D) toxico-analytical

(A) On the basis of mode of action: On the basis of mode of action poison can be

categorized into:

(i) Corrosive Poisons


(ii) Irritant poisons,
(iii) Neurotic Poisons,
(iv) Cardiac Poisons and
(v) Asphyxiants.

(i) Corrosive Poisons: Corrosive poisons are the poisons which cause inflammation at the site of
contact. Both strong acids and alkalis are comes under this category.

(a) Strong acids: Concentrated sulphuric acid, nitric acid and hydrochloric acid

(b) Strong bases: Sodium hydroxide, potassium hydroxide and ammonium

hydroxide.

(ii) Irritant poisons: Irritants are those substances which cause irritation, pain, excessive
vomiting. These are further divided into

(a) inorganic poisons,

(b) organic poisons and


(c) mechanical poisons.

(a) Inorganic poisons: Inorganic poisons are consists of:

 Metallic – Lead, arsenic, mercury, antimony, copper and zinc etc.


 Non Metallic - Chlorine, bromine and iodine etc.

(b) Organic Poisons: Organic poisons consist of poisons of both vegetable origin and animal
origin.

 Animal poisons – Snakes venom, scorpion venom, spiders etc.


 Vegetable poisons – Croton oil, castor oil etc.

(c) Mechanical Poisons: Mechanical poisons are the poisons which cause irritation, perforation
obstruction in the gastrointestinal tract. For example, powder glass, diamond dust etc.

(iii) Neurotic Poisons: - Neurotic poisons are the poisons which affects the different part of
central nervous system such as cerebral poisons, spinal poison, peripheral poisons etc. and these
constitute of following poisons:

a. Cerebral Poisons –Alcohol, opium, barbiturates, benzodiazepines etc.

b. Spinal Poison – Strychnine.

c. Peripheral – Curare

(iv) Cardiac Poisons – Digitalis, tobacco.

(v) Asphyxiants – CO, CO2 etc.


(B) On the basis of their physical state: Based on physical state, poisons can be grouped into

(i) Solid poisons,

(ii) Liquid poisons and

(iii) Gaseous poisons.

(i) Solid poisons: Solid poisons don’t get absorbed easily into the blood. These should be
dissolved properly in liquid to get absorbed. For example lead, arsenic, mercury etc.

(ii) Liquid poisons: Liquid poisons contain both organic and inorganic liquid. Organic liquids are
more volatile than inorganic liquids. Liquid poison can be absorbed when administered orally or
by inhalation or through skin. As organic liquids are vaporises and organic vapours are absorbed
by lungs such as chloroform, acetone etc. and the organic vapours which are soluble in lipids get
easily absorbed through skin for e.g. furfural.
(iii) Gaseous poisons: Gaseous poisons are absorbed by inhalation such as carbon dioxide,
carbon monoxide etc. In atmosphere, there are aerosols particles in air and these are either
inhaled or deposited on the skin. They causes marked effect on lungs when inhaled during
breathing and causes obstruction into the lungs (asbestos) in comparison to those absorbed
through skin. Fibres and dust are also the examples of aerosols.

(C) Medicolegal classification of poison: Based on intention behind the crime, poisons are
classified into:

(i) Homicidal poisons,

(ii) Suicidal poisons,

(iii) Accidental poisons,

(iv) Abortifacient poisons,

(v) Stupefying agent/poisons,


(vi) Agents used to cause bodily injury

(vii)Cattle Poison

(viii) Used for malingering.

(i) Homicidal poisons: The poisons which are used to kill the other person are known as
homicidal poisons such as aconite, abrus precatorius, strychnos nux vomica etc.

(ii) Suicidal poisons: Suicidal poisons are those poisons which are used for self killing such as
opium, barbiturate, organophosphorus, organochloro compounds.

(iii) Accidental poisons: Accidental poisons are those poisons which cause toxicity by accidents
or used in mistaken of others: Snakes bite, CO, and child takes dhatura’s seeds in mistaken of
capsicum seeds as it resemble to capsicum seed.

(iv) Abortifacient poisons: The poisons which are used to procure abortion are know as
abortifacient poisons for exemples Quinine (alkaloid), Calotropis etc.

(v) Stupefying agent/poisons: Stupefying agents are those poisons which are used to stupefy or
fool the person for example Dhatura and chloral hydrate are used to rob the stranger or for the
commitment of other crimes.

(vi) Agents used to cause bodily injury: Usually corrosive acids are used to cause injury on faces
and known as vitriol throwing.

(vii) Cattle Poison: Agents which are used to kill livestocks are known as cattle poisons. Abrus
precatorius, Calotropis are used to kill cattle.

(viii) Used for malingering: Some times semicarpus anacardium is used by malinger to escape
from duties as these produces to produce an artificial bruise.
(D) Toxico-analytical classification: Poisons can also be classified on the bases of method used
for extraction or analysis into:

(i) Gaseous and volatile substances,

(ii) Organic non-volatile substances,

(iii) Metallic poisons and

(iv) Anion.

(i) Gaseous and volatile substances: Poisons which are isolated by distillation or by headspace
are categorised into this group. Volatile substances (methanol, ethanol, benzene, toluene, acetone
etc.) can be separated from gaseous (ethane, butane etc.) poisons because they can be extracted
with alternate methods.
(ii) Organic non-volatile substances: Compounds which are isolated by solvent extraction
methods include in this group. For example drugs such as opiates and synthetic narcotics,
sedatives and hypnotics, stimulants, antidepressants etc and pesticides which include
insecticides, fungicides, herbicides, rodenticides, nematocides etc. In this group pesticides can be
separated from drugs, though both are organic non-volatile substances which are isolated by
solvent extraction method.

(iii) Metallic poisons: The substance which are isolated by dry ash method or by wet digestion
method constituting this group. The commonest poisons are arsenic, lead, mercury, etc.

(iv) Anion poisons: Anions are isolated by dialysis. Most commonly encountered anions in
poisoning cases are bromide, cyanide, fluoride, hypochlorite, nitrate, nitrite, phosphate, sulfide,
sulfate etc.
POISONING

Poisoning can be referred to as a development of unusual symptoms appearing in a living


organism after its contact with a potentially toxic substance. Such substances can enter the body
by several routes like through mouth (medicines, household products, etc.); through nasal
passage (carbon monoxide, pesticides, etc.), through the eyes (household products and industrial
chemicals, etc.), through the skin (caustics, pesticides, etc.) and many times also parenteral
(bites, stings, injected drugs, etc.). Summarily, it can be said that poisoning is a condition when a
toxic substance is administered to a living body and that body in response shows symptomatic
changes which must be apparently abnormal.

Classification of poisoning

1. Fulminating

Fulminant poisoning is produced by a enormous dose. In fulminating poisoning, death occurs


rapidly, sometimes without preceding symptoms and the patient appearing to collapse suddenly.

2. Chronic

Chronic exposure is any relative time period for which continuous or repeated exposure beyond
the acute phase is required for the same chemical to induce a toxic response. Chronic Poisoning
is caused by smaller doses over a period of time, resulting in gradual deteriorating. Small amount
of poison are repeatedly administered for a long period produces the toxic effects. The
substances commonly causing chronic poisoning are metallic poisons, opium, antimony, arsenic,
phosphorus, etc. Chronic toxicity is characterized by continued exposure and sublethal effects
stimulated through mechanisms that are distinctive from those that cause acute toxicity.

3. Sub- Acute

Sub-acute poisoning shows features of both, acute as well as chronic poisoning. Sub- acute
exposure generally refers to continuous or repeated exposure to a chemical for more than 72
hours but usually less than 1 month. A sub-acute exposure may include repeated exposure for a
period longer than 3 months. Thus, the terms are flexible adaptations to define the inception of
chemical intoxication.
4. Acute

Acute poisoning is caused by an excessive single dose, or several dose of a poison taken over a
short interval of time. In acute poisoning, whatever amount of poison is taken and the toxicity is
manifested immediately. Acute toxicity of a chemical can be viewed from two perspectives.
Acute toxicity may be the descriptor used as a qualitative indicator of incident of poisoning.

Types of poisoning

Homicidal Poisoning

Homicidal poisoning is the administration of poisonous substance by a person to kill another.


From the early ages Poisons are the favourite weapon for assassination. More often, known as
“Secret Killers”, they can be surreptitiously slipped into the edible items of the victim and rest
the poison ensures it. The essential quality of a homicidal poison is that it should be cheap, easily
available, odourless, highly toxic, no residual product left, signs and symptoms resembles natural
diseases, no antidote available, shows no post-mortem changes, capable of being administered
with food or drink, they must act rapidly even in small quantity, should not impart any colour or
taste when added in a covering agent (preferably food item) and most important that poison
should not be traced in the viscera. One of the most demanding poisons of such nature is
Arsenic. In 20th century a lady named Toffana who marketed specially prepared arsenic-
containing cosmetics. Accompanying the product were appropriate instructions for its use.
Toffana was succeeded by an imitator with organizational mastermind, Hieronyma Spara, who
provided a new impetus by directing her activities toward specific marital and monetary
objectives. A local club was formed of young wealthy married women, which soon became a
club of eligible young wealthy widows, evocative of the full-figured conspiracy of Rome
centuries earlier. Incidentally, arsenic-containing cosmetics were reported to be responsible for
deaths. Prominent Homicidal poisons are Arsenic, Aconite, Digitalis, Abrus precatorius,
Strychnos nux vomica.
Suicidal Poisoning

Suicidal poisoning is the intake of some poisonous substance by the individual himself for self-
killing. Ideal Suicidal poison should be easily available, should have no bad taste, most possibly
cause no pain or less pain, it must be cheap, highly toxic, tasteless or pleasant taste, capable of
being taken with food or drink. Prominent Suicidal poisons include Opium, Barbiturate,
Organophosphorus, carbolic acid, copper sulphate. Suicidal poisonings have been reported
involving the consumption of rat pastes containing zinc phosphide. Suicidal poisoning with
formic acid is relatively common in those areas where the chemical is easily available. Suicidal
deaths are reported from time to time since opiates are reputed to cause a painless death.

Accidental Poisoning

Accidental poisoning generally takes place due to the storage of poisonous and nonpoisonous
substances at the same place. The injudicious use of the magic remedies and love potions can
also result in accidental poisoning. Noticeable Accidental poisons includeAspirin,
organophosphorus, copper sulphate, snakes bite, Ergot, Carbon Monoxide, Carbon Dioxide,
Hydrogen Sulphide, etc.

Food Poisoning

Food poisoning can occur in many ways, and may be isolated instances, or may constitute an
epidemic (mass food poisoning). Food borne illnesses are among the commonest health
problems encountered world-wide, and are particularly rampant in third world countries such as
India, mainly due to a relative lack of sanitation and public hygiene. While, the biological causes
of food poisoning are Microbes, Parasites, Fungi, Plants, Animals, the chemical causecannot be
ignored which are the chemical agents introduced during food processing. Chemical
contaminants of food include heavy metals, pesticides, and food additives. Food additives may
be antioxidants, flavouring agents, colouring agents, sweetening agents, thickening agents, or
preservatives
Iatrogenic Poisoning

Iatrogenic Poisoning arises from the action of a doctor said of any adversative condition in a
patient resultant from treatment by a physician or surgeon, for instance, death after injection of a
wrong solution or of an appropriate solution in an inappropriate manner, e.g. hasty injections of
solutions of magnesium salts, unbuffered solutions of high alkalinity or acidity, or of a substance
to which the patient is hypersensitive. Iatrogenic poisoning caused by prescribing/ administration
errors or unrecognised adverse drug interactions has recently been identified as a significant
problem.

Synergistic Poisoning

A synergistic effect occurs when the collective effects of two chemicals are much greater than
the sum of the effects of each agent given alone. For example, both carbon tetrachloride and
ethanol are hepatotoxic compounds, but together they produce much more liver injury than the
mathematical sum of their individual effects on liver at a given dose would suggest. Barbiturates
have a synergistic effect with ethanol and antihistamines. Ethanol has a synergistic effect with
benzodiazepines.

Agro-chemical Poisoning

Poisoning due to other pesticides is relatively uncommon except among individuals who are
occupationally exposed. The causes of poisoning are many such as civilian, industrial, accidental
and deliberate. The problem is getting worse with time as newer drugs and chemicals are
developed in vast numbers.

Drug Poisoning

Drug in the broadest sense is any chemical entity or mixture of entities other than those required
for the maintenance of normal health, the administration of which alters the biological function
and bodily structure. Drug abuse refers to the use usually by selfadministration of any drug in a
manner that deviates from the approved medical or social pattern within a given culture. The
overdosage of the drug commonly occurs accidentally, intravenous injection carries the highest
risk of accidental overdosage, and when it occurs, the drug cannot be retrieved.
MISCELLANEOUS POISONING

Judicial Poisoning

It is known as judicial execution by administration of lethal injection to the condemned convict.


Lethal injection is the exercise of injecting a convict with a fatal dose of drugs which are
characteristically a barbiturate, paralytic, and potassium solution, for the direct purpose of
instigating instantaneous death. In another, though extinct process, the condemned or prisoner
persons were used to strapped to a chain in a closed room and several cyanide eggs are dropped
in to a pan of strong acid that leads to liberation of cyanide gas. Unconsciousness takes place
very rapidly though heart continues to beat for 10-15 minutes then death occurs. Sodium
pentathal, Pancuronium Bromide, Potassium Chloride, Barbiturates and Cyanide are the
favourite chemicals used for the purpose of Judicial Execution.

Aborifacient poisoning

Abortion is the termination of pregnancy by eliminating a foetus or embryo from the womb
before it can survive on its own and an abortifacient is a substance that induces abortion. There
are certain abortifacient drugs are which may terminate the pregnancy in various manners, for
example, Ecbolics act directly on the uterus and increase the uterine contraction that causes
abortion. Emmenogogues, such as Savin, Borax, Apiol produce an increase menstrual blood flow
and act as abortifacient when given in large doses. Irritants of genitourinary tract like Oil of
turpentine, Cantharides reflex uterine contraction to ensue abortion. Other common examples
include Ergot, Quinine, Calotropis, and Plumbago.

Stupefacient poisoning

The term “stupefaction” is loosely applied to the process of representing a victim suddenly
debilitated by exposing him to a deliriant poisons such as datura, etc., in order to facilitate
robbery or rape. An extract of the seeds is usually employed, which is mixed with food or drink
and administered to the unsuspecting victim. Sometimes, stupefaction is induced by exposing the
person to fumes of incense, by mixing datura with other constituents of an incense stick. Even
cigarettes may be adulterated in a similar fashion. Susceptible railway or bus passengers are the
usual victims who fall into the trap of accepting food, drink, or tobacco from the so called
“friendly” strangers. Examples include Dhatura, cannabis, chloral hydrate.

Cattle Poisoning

Young calves can catch lead poisoning if they lick lead paint or batteries. A number of plants are
lethal to cattle, including yew leaves, and acorns. Cattles may suffer nitrate poisoning when there
are high nitrate levels in meadow and crops, especially after dehydrated weather or where a lot of
nitrogen fertilizer has been applied in winter or spring. Poisoning follows because nitrate
accumulates at a faster than usual level in the rumen. Nitrate gets converted to nitrite in the
rumen, and is then absorbed into red blood cells, discolouring them and blocking the transport of
oxygen. In extreme cases the animal dies due to asphyxia.

ROUTE OF ADMINISTRATION/ABSORPTION

 Oral (commonest) eg: alphos, acids,


 Inhalation: gas poison
 Parenteral (IM, IV, Sub‐Cutaneous, Intra‐Dermal)
 Natural Orifices other than mouth (Nasal, Rectal, Vaginal, Urethral),
 Ulcers, wounds and intact skin.

Fate of poison in body:

Vomiting, purging and defecation.

Before absorption the poison may exert its effects in the G.I. Tract.

When absorbed, the poison reaches different parts of the body.

Cumulative poisons get accumulated in some organs or tissues.

A part of poison is eliminated as such through different route of elimination.

But major part is detoxified or metabolized in the body than excreted.

Liver is the main organ to detoxify or metabolize most of the poisons.

Certain poisons like Chloroform, Phosphorus, Nitrates and Acetic acid disappear by evaporation
or oxidized or destroyed in the body and no trace of them can be detected in the body of post‐
mortem is delayed.
Excretion of poisons

Unabsorbed poisons are excreted through faeces and vomitus. Absorbed poisons are excreted
mostly by urine. A part of volatile poison is exhaled out. Some portion of poison is excreted
through bile, saliva, milk, sweat, tear, hair and nails.

Factors influencing the actions of a poison in the body

1. Quantity:
 Large = more effect ?
 Idiosyncracy (individual susceptibility to a substance)
 Addiction (tolerance)
 Different actions of different doses

A high dose of poison acts quickly and often resulting in fatal consequences. A moderate dose
causes acute poisoning. A low dose may have sub‐clinical effects and causes chronic poisoning
on repeated exposure. Very large dose of Arsenic may produce death by shock without dose
irritant symptoms, while smaller dose than lethal dose produces its therapeutic effects.

2. Physical form:
 Physical State: ‐ Gas > liquids > powders > solids Some poisonous vegetable
seeds may pass through the intestinal canal ineffective when taken intact due to
their impermeable pericarp. But when taken crushed, they may be rapidly fatal.
 Chemical Combination: Ag nitrate and HCL.
 Mechanical Combination: ‐ relative density of the poison and the vehicle
3. Chemical form: Chemically pure arsenic and mercury are not poisonous because they are
insoluble and are not absorbed, but white arsenic (arsenic oxide) and mercuric chloride
are deadly poisonous. Barium sulphide is deadly toxic but barium sulphate is non ‐toxic.
4. Concentration (or dilution): concentrated form of poison are absorbed more rapidly and
are also more fatal but there are some exceptions too.
5. Condition of the stomach: food content presence of food ‐ stuff acts as diluent of the
poison and hence protects the stomach wall. Dilution also delays absorption of poison.
Empty stomach absorbs poison most rapidly. In cases of achlorohydria/hypochlorhydria
(a state where the production of HCl in gastric secretions of the stomach and other
digestive organs is absent or low), KCN and NaCN is ineffective due to lack of
hydrochloric acid, which is required for the conversion of KCN and NaCN to HCN
before absorption
6. Route of administration: The degree and rate of absorption of a poison is dependent on
the mode of exposure. The absorption is quicker through the inhalational route or by
injection compared with the oral route. A poison acts most rapidly when inhaled in
gaseous or vapours form or when injected Intra Venous followed by Intra Muscular or
Sub Cutaneous and least rapidly when swallowed.
7. Age: some poisons are better tolerated in some age groups. Opium and its alkaloids are
tolerated better by elderly subjects but badly by children and infants. Belladonna group of
drugs are better tolerated by children than by adults.
8. State of body health: A well-built person with good health can tolerate the action of
poison better than a weak person.
9. Presence of disease: In certain diseased conditions some drugs are tolerated exceptionally
well e.g.: sedatives and tranquilizers are tolerated in very high dose by manic and
deliriant patients.
10. Intoxication arid poisoning states ‐ In certain poisoning cases some drugs are well
tolerated, like, in case of strychnine poisoning, barbiturates and sedatives are better
tolerated. Whereas in case of barbiturate poisoning any sedative or tranquilizer will
accentuate the process of death.
11. Sleep ‐ Due to slow metabolic process and depression of other body functions during
sleep, usually the absorption and action of the poison is also slow. But depressant drugs
may cause, more harm during the state of sleep.
12. Exercise ‐ Action of alcohol on C.N.S. is slowed during exercise because more blood is
drawn to the muscles during exercise.
13. Cumulative action of poisons: Preparations of cumulative poisons (poisons which are not
readily excreted from the body and are retained in different organs of the body for a long
time) like lead may not cause any toxic effect when enters the body in low dose. But
when such poisons enter over a long period of time, may cause harm when their
concentration in different tissue reaches high level due to their cumulative property.
14. Tolerance may develop by individuals on long term exposure to a particular poison.
15. Idiosyncracy: some persons may react adversely to a particular drug though the general
population tolerates the drug well.

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