The most ambitious definition of health is that proposed by WHO in 1948: “health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.” but, Practical definitions of health and disease are needed in epidemiology, which concentrates on aspects of health that are easily measurable and amenable to improvement. Definitions of health states used by epidemiologists tend to be simple, for example, “disease present” or “disease absent”

1. HARAR HEALTH SCIENSE COLLEGE
Course Title: Applied Toxicology
Chapter 1- Introduction to Toxicology
For 3rd Year Medical laboratory science Student
By:-MENBERE DEBELE
(BSc. C/Nurse, B.Pharm)
1

2. Outline
 Introduction to Toxicology
 Definition, areas of toxicology, scope, application,
and the medical laboratory scientist role in
toxicology
 Nature of toxic responses, routes of poisoning
 Potential causes of toxicity
2

3. Learning objectives
 At the end of this chapter you will be able to:
 Define toxicology & commonly associated
terms
 Differentiate the sub-disciplines of
toxicology
 Describe the classifications of toxic agents
 Explain Nature of toxic responses, routes of
poisoning
 Mention Potential causes of toxicity
3

4. I. Definitions in Toxicology

5. Definitions
 What is Toxicology?
 Derived from Greek word, toxikon and logos
 Toxicology is the study of the adverse effects of
xenobiotics
 Toxicology is the study of how natural or man-made
poisons cause undesirable effects in living
organisms
5

6. Definitions…
 What are harmful or adverse effects?
 Harmful or adverse effects are those that are
damaging to either the survival or normal function of
the individual
 What is Toxicity?
 The word “toxicity” describes the degree to which a
substance is poisonous or can cause injury
 The toxicity depends on a variety of factors:
• Dose, duration & route of exposure, nature of the
chemical, & individual human factors
6

7. Definitions…
 Poison- a chemical that may harm or kill an organism
 What is a Toxicant?
 A toxicant is any chemical that can injure or kill living
organisms
 The term “toxicant” is used when talking about toxic
substances that are produced by or are a by-product
of human-made activities
 What is a Toxin?
 The term “toxin” usually is used when talking about
toxic substances produced naturally
7

8. Definitions…
 What is a Toxic Symptom?
 This term includes any feeling or sign indicating the
presence of a poison in the system
e.g feeling and being sick, diarrhoea, stomach pain,
drowsiness, dizziness or weakness, high
temperature….etc
 What are Toxic Effects?
 This term refers to the health effects that occur due
to exposure to a toxic substance; also known as a
poisonous effect on the body
8

9. Definitions…
 What is Selective Toxicity?
 “Selective toxicity” means that a chemical will
produce injury to one kind of living matter
without harming another form of life,
eventhough the 2 may exist close together
9

10. Definitions…
 How does toxicity develop?
 Before toxicity can develop, a substance must
come into contact with a body surface such
as skin, eye or mucosa of the digestive or
respiratory tract
 The dose of the chemical, or the amount one
comes into contact with, is important when
discussing how “toxic” a substance can be
10

11. Definitions…
 What is a dose?
 The dose is the actual amount of a chemical that
enters the body
 The dose received may be due to either acute
(short) or chronic (long-term) exposure
• An acute exposure occurs over a very short period of
time, usually 24 hrs
• Chronic exposures occur over long periods of time
such as weeks, months, or years
 The amount of exposure & the type of toxin will
determine the toxic effect
11

12. Definitions…
 What is dose-response?
 Dose-response is a relationship b/n exposure &
health effect that can be established by measuring
the response relative to an increasing dose
 This relationship is important in determining the
toxicity of a particular substance
 Usually, the larger or more intense the dose, the
greater the response, or the effect
• “the dose makes the poison”
12

13. Definitions…
 What is the threshold dose?
 Given the idea of a dose-response, there should
be a dose or exposure level below which the
harmful or adverse effects of a substance are
not seen in a population
• That dose is referred to as the ‘threshold dose’
• This dose is also referred to as the no observed
adverse effect level (NOAEL), or the no effect
level (NEL)
13

14. Definitions…
 What is meant by ‘individual susceptibility?’
 This term describes the differences in types of
responses to hazardous substances, b/n
people
 Each person is unique, & b/c of that, there may be
great differences in the response to exposure
 Exposure in one person may have no effect, while
a second person may become seriously ill, & a
third may develop cancer
14

15. Definitions…
 What is a “sensitive sub-population?”
 A sensitive sub-population describes those persons who
are more at risk from illness due to exposure to
hazardous substances than the average, healthy
person
• Usually include the very young, the chronically ill,
& the very old
• It may also include pregnant women & women of
childbearing age
 Depending on the type of contaminant, other factors
(e.g., age, wt, lifestyle, sex) could be used to describe
the population
15

16. II. History of toxicology

17. History of toxicology
A. Antiquity
 The Ebers papyrus (circa 1500 B.C.)
describes many recognized poisons-
hemlock, aconite, opium, lead, copper,
antimony, digitalis, belladonna alkaloids
 Theophrastus (370–286 B.C.), a student of
Aristotle, wrote De Historia Plantarum
 Socrates (470-399 B.C.) received poison as
part of state execution
17

18. History of toxicology…
 Demosthenes (385– 322 B.C.) and Cleopatra’s (69–
30 B.C.)
 Voluntary took poison
 King Mithridates (134-63 B.C.) of Pontus
 Poisoned many criminals in his experiments to
identify antidotes
 Epidemic Poisonings in Rome lasted from 4th -1st
century B.C
 Dioscorides (Greek physician) 60 A.D.
 Described many poisons, devised categorization system (plant,
animal, mineral)
18

19. History of toxicology…
B. Middle Ages
 Moses Ben Maimon (Maimonides 1135–
1204 A.D.)
• Wrote poisoning and their Antidotes
 Renaissance Italians brought poisoning to a
zenith
 Catherine de Medici
 Catherine Deshayes ( “La Voisine” )
19

20. History of toxicology…
C. Age of Enlightenment
 Paracelsus led the change from the science of
Hippocrates and Galen to that of the 17th century
giants
 Championed the “toxicon,” as a chemical entity and
the following principles:
• Experimentation is essential in the examination of
responses to chemicals
• Therapeutic and toxic properties of chemicals
• Therapeutic and toxic properties are often
distinguishable by dose
• Specificity can be achieved for the therapeutic versus
toxic properties of chemicals
20

21. History of toxicology…
D. The Modern age
 Exponential growth parallels the World
War II with greatly increased
production of drugs, pesticides,
organic chemicals
 During this period, the use of “patent”
medicines was prevalent, and there
were several incidents of poisonings
from these medicaments
21

22. III. Branches of Toxicology

23. Branches of Toxicology
 The field of toxicology can be further divided into
the following sub-disciplines or subspecialties:
 Mechanistic Toxicology
 Descriptive Toxicology
 Regulatory Toxicology
 Environmental Toxicology
 Occupational (Industrial) Toxicology
 Food Toxicology
 Clinical Toxicology
 Forensic Toxicology
 Analytical toxicology
23

24. Branches of Toxicology…
 Mechanistic Toxicology
 It makes observations on how toxic substances
cause their effects
 Descriptive Toxicology
 It is concerned with gathering toxicological
information's from animal experimentation
 These types of experiments are used to establish
how much of a chemical would cause illness or
death
24

25. Branches of Toxicology…
 Regulatory Toxicology
 It gathers & evaluates existing toxicological
information's to establish conc-based standards of
“safe” exposure
• The std is the level of a chemical that a person can
be exposed to without any harmful health
effects
 Analytical toxicology
 It identifies the toxicant through analysis of body
fluids, stomach content, excrement, or skin
25

26. Branches of Toxicology…
 Environmental Toxicology
 It is concerned with the study of chemicals that
contaminate food, water, soil, or the atmosphere
 It also deals with toxic substances that enter
bodies of waters such as lakes, streams, rivers,
& oceans
26

27. Branches of Toxicology…
 Occupational (Industrial) Toxicology
 It is concerned with health effects from exposure
to chemicals in the workplace
 Food Toxicology
 It is involved in delivering a safe & edible supply of
food to the consumer
 All of the additives added during processing are
studied to determine if & at what amount, they
may produce adverse effects
27

28. Branches of Toxicology…
 Clinical Toxicology
 It is concerned with diseases & illnesses
associated with short term or long term exposure
to toxic chemicals
 Forensic Toxicology
 It is used to help establish cause & effect
relationships b/n exposure to a drug or chemical
& the toxic or lethal effects that result from that
exposure
28

29. Scope and Application of Toxicology
In forensic toxicology
 establishing the cause of death and elucidating
its circumstances in a postmortem investigations
Economic or industrial toxicology
 in drugs, pesticides, food additives,
containers(like cans and packing materials)
Environmental toxicology
 Pollutional studies, resedue analysis
 Industrial hygiene and occupational health
29

30. IV. Toxicokinetics &
Toxicodynamics

31. Toxicokinetics & Toxicodynamics
 Toxicokinetics
 It is the quantitation of the time course of
toxicants in the body during the processes of
ADME of toxicants
 It is a reflection of how the body handles
toxicants as indicated by the plasma conc of
that xenobiotic at various time points
 The end result of these toxicokinetic processes
is a biologically effective dose of the toxicant
31

32. 32
Fig. Routes of ADME of toxicants in the body

33. Toxicokinetics & Toxicodynamics…
 Toxicodynamics
 Refers to the molecular, biochemical, &
physiological effects of toxicants or their
metabolites in biological systems
 These effects are result of the interaction of the
biologically effective dose of the ultimate (active)
form of the toxicant with a molecular target
33

34. V. Spectrum of toxic dose

35. Spectrum of toxic dose
 “What is there that is not poison? All things are
poison and nothing [is] without poison. Solely the
dose determines that a thing is not a poison.”
Paracelsus (1493–1541)
35

36. 36
Table 1, which shows the dosage of chemicals needed to
produce death in 50 percent of treated animals (LD50)

37. 37
VI. The medical laboratory scientist
role in toxicology

38. The medical laboratory scientist
role in toxicology
 Clinical toxicology can be defined as the
analysis of drugs and toxins in body fluids
for the purpose of patient care.
 The mission of the clinical toxicology laboratory
is to effectively utilize available laboratory
resources and expertise to provide clinically
useful toxicology tests to support the needs of
the patients.
38

39. role in toxicology cont’d
 Most poisoned patients can be treated
successfully without any contribution from
the laboratory other than routine clinical
biochemistry and haematology.
 This is particularly true for those cases where
there is no doubt about the poison involved
and when the results of a quantitative analysis
would not affect therapy.
39

40. role in toxicology cont’d
 However, toxicological analyses can play a
useful role if the diagnosis is in doubt, the
administration of antidotes or protective
agents is contemplated, or the use of active
elimination therapy is being considered.
40

41. Basic information necessary for toxicology
laboratory
 Close communication b/n clinical & laboratory
personnel is essential.
 Suspected agent(s), suspected dose, time of
ingestion & sampling, clinical presentation &
location of the victim are very important basic
information necessary for toxicology laboratory.
41

42. VII. Nature of toxic responses
42

43. Nature of toxic responses
 The resulting biologic effect of combined exposure to
several agents can be characterized as:
Synergism
 when the effect of two chemicals is greater than the
effect of individual chemicals Example: 2 + 2 = 20
e .g carbontetrachloride + alcohol= more toxic to the liver
than the sum of the individual drugs.
43

44. Nature of toxic responses cont’d
Additive effect-
 when the total pharmacological action of two or
more chemicals taken together is equivalent
to the summation of their individual
pharmacological action
Example: 2 + 3 = 5
 Organophosphorus pesticides ⇒ Cholinesterase
inhibiters
44

45. Nature of toxic responses cont’d
Potentiation effect
 when the net effect of two chemicals used together is
greater than the sum of individual effects (the capacity
of a chemical to increase the effect of another chemical
without having the effect alone) Example: 0 + 2 = 10
 Isopropanol is not hepatoxic, but enhance carbon
tetrachloride induced hepatoxicity
 Antagonism - is the phenomenon of opposing actions of
two chemicals on the same system Example: 4 + 0 = 1
 Dimercaprol (BAL) chalets with metal ions, As, Pb….
45

46. Nature of toxic responses cont’d
RELATIVE TOXICITIES
 Standard toxicity ratings that are used to describe
estimated toxicities of various substances to humans
 Their values range from one (practically nontoxic) to
six (supertoxic)
 In terms of fatal doses to an adult human of average
size, a “taste” of a supertoxic substances (just a few
drops or less) is fatal
46

47. 47

48. Nature of toxic responses cont’d
Parameters
 Median lethal dose (LD50) – is the dose which is
expected to kill 50% of the population in the particular
group.
 Median effective dose (ED50) –is the dose that
produces a desired response in 50% of the test
population when pharmacological effects are plotted
against dosage.
 Median toxic dose (TD50) – is the dose which is
expected to bring toxic effect in 50% of the population
in the particular group
48

49. Nature of toxic responses cont’d
REVERSIBILITY AND SENSITIVITY
a) Reversibility Vs. Irreversible
 Sub lethal doses of most toxic substances are eventually
eliminated from an organ system.
 If there is no lasting effect from the exposure, it is
said to be reversible
 However, if the effect is permanent, it is termed
irreversible
49

50. Nature of toxic responses cont’d
 Irreversible effects of exposure remain after the
toxic substance is eliminated from the
organism
 For various chemicals and different subjects,
toxic effects may range from the totally
reversible to the totally irreversible
50

51. Nature of toxic responses cont’d
b)Hypersensitivity vs. Hyposensitivity
 In some cases hypersensitivity is induced
 After one or more doses of a chemical, a subject may
develop an extreme reaction to it
 This occurs with penicillin, for example, in cases where
people develop such a severe allergic response to the
antibiotic that exposure results in death if
countermeasures are not taken
51

52. Nature of toxic responses cont’d
Hyposensitivity
 hyposensitivity is induced by repeated exposures to a
toxic substance leading to tolerance and reduced
toxicities from later exposures
 Tolerance can be due to a less toxic substance
reaching a receptor or to tissue building up a
resistance to the effects of the toxic substance
example, with repeated doses of toxic heavy metal
cadmium
52

53. VIII. Routes of poisoning
53

54. Routes of poisoning
• A route of administration in pharmacology and
toxicology is the path by which a drug, fluid,
poison, or other substance is taken into the
body.
• There are three major categories of route.
1)Enteral route
2)Parenteral route
3)Topical route
54

55. Routes of poisoning cont’d
 Oral route – the GIT is the most important route of
absorption, as most acute poisonings involve ingestions
 Dermal route – lipid solubility of a substance is an
important factor affecting the degree of absorption
through the skin
 Inhalational route – toxic fumes, particulate and
noxious gases may be absorbed through the lungs
 Intramuscular route – unreliable and varied from
patient to patient
 Intravenous route – is the most reliable and provides
the most rapid clinical response
 Rectal route – is generally considered to produce erratic
absorption
55

56. Routes of poisoning cont’d
 Oral (commonest)
 Inhalation: gas poison
 Parenteral (IM, IV, Sub-Cutaneous, Intra-Dermal)
 Natural Orifices other than mouth (Nasal, Rectal, Vaginal,
Urethral)
 Ulcers, wounds and intact skin
The decreasing order of effectiveness in different routes is:
 Intravenous, inhalation, intra-peritoneal, subcutaneous,
intramuscular, intra-dermal, oral, and dermal
56

57. Potential causes of toxicity
The potential causes of toxicities include:
 Therapeutic agents
 Industrial & house hold chemicals
 Environmental contaminants
 Animal & plant toxins
 Drugs of abuse
 Food preservatives
 Traditional drugs
 Fumes …..
57

58. IX. Sources of toxic compounds
58

59. Sources of toxic compounds
 Given the enormous number of toxicants, it is difficult to
classify them chemically, either by function or by
mode of action, since many of them would fall into
several classes
 Some are natural products, many are synthetic
organic chemicals of use to society, while others are
by-products of industrial processes & waste
disposal
 It is useful, however, to categorize them according to:
 The expected routes of exposure or their uses
59

60. Sources of Poison cont’d
 Exposure classes
 Include: toxicants in food, air, water, & soil as well as
toxicants characteristic of domestic & occupational
settings
 Use Classes
 Include: drugs of abuse, therapeutic drugs,
agricultural chemicals, food additives & contaminants,
metals, solvents, combustion products, cosmetics, &
toxins
• Some of these, such as combustion products, are the
products of use processes rather than being use
classes
60

61. Sources of Poison cont’d
Other classification
 Domestic or household sources
 Agricultural and horticultural sources
 Industrial sources
 Commercial sources
 From uses as drugs and medicines
 Food and drink
 Miscellaneous sources - snakes bite poisoning,
city smoke, sewer gas poisoning etc.
61

62. Sources of Poison cont’d
 Domestic or household sources - detergents,
disinfectants, cleaning agents, antiseptics, insecticides,
rodenticides etc.
 Agricultural and horticultural sources- different
insecticides, pesticides, fungicides and weedicide
 Industrial sources- In factories, where poisons are
manufactured or poisons are produced as by products
 Commercial sources- From store-houses, distribution
centres and selling shops
62

63. Sources of Poison cont’d
 From uses as drugs and medicines – Due to wrong
medication, overmedication and abuse of drugs
 Food and drink – contamination in way of use of
preservatives of food grains or other food material,
additives like colouring and odouring agents or other
ways of accidental contamination of food and drink
 Miscellaneous sources- snakes bite poisoning, city
smoke, sewer gas poisoning etc
63

64. Common poisons and drugs
 Corrosive poisons
 Irritant poisons
 Analgesic, Hypnotic, Tranquilizer, and Narcotic poisons
 Stimulants, Excitants, and Convulsants poisons
 Paralytic, Anticholinesterase and Antihistamine poisons
 Gaseous and Volatile poisons
 Industrial gaseous and Volatile poisons
 Poisons by Plants, flora, and fungi
64

65. Factors that influence toxicity
 There are numerous factors which may modify the pt's
responses to the toxic agent
 For examples;
 Dose of toxicant
 Route of exposure
 Duration of exposure to toxicant: acute vs chronic
 Toxicant’s properties: shape, structure, solubility,
stability, etc.
 Individual factors, e.g. genetics, age, overall health,
etc
65

66. Major Factors that influence toxicity cont’d
Quantity:
 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
66

67. Factors that influence toxicity cont’d
Physical form:
 Gaseous or volatile poisons are very quickly
absorbed and are thus most rapidly effective
 Liquid poisons are more rapid than solid poisons
 Some poisonous vegetable seeds may pass through the
intestinal canal ineffective when taken intact due to
their impermeable pericarp
67

68. Factors that influence toxicity cont’d
Chemical form:
 Chemically pure arsenic and mercury are not
poisonous because these 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
68

69. Factors that influence toxicity cont’d
 Concentration (or dilution):
 Concentrated form of poison are absorbed more
rapidly and are also more fatal but there are
some exceptions too
69

70. Factors that influence toxicity cont’d
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, 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
70

71. Factors that influence toxicity cont’d
Route of administration:
 Absorption rate is different for different routes. Eg. Based
on the Decreasing order
IV, inhalation, intra-peritoneal, subcutaneous, intramuscular,
intra-dermal, oral, and dermal
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
71

72. Factors that influence toxicity cont’d
State of body health:
 A well built person with good health can tolerate the
action of poison better than a weak person.
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
72

73. Factors that influence toxicity cont’d
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
73

74. Factors that influence toxicity cont’d
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.
Exercise
 Action of alcohol on C.N.S. is slowed during exercise
because more blood is drawn to the muscles during
exercise
74

75. Factors that influence toxicity cont’d
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
75