1. chapter introduction

1. BULE HORA UNIVERSITY
COLLEGE OF HEALTH AND MEDICAL
SCIENCES
DEPARTMENT OF PHARMACY
TOXICOLOGY
For 4th year Medical Laboratoy
Students
4/5/2022
Introduction to Toxicology 1
By:Aliyi G.(B.Pharm

2. CHAPTER ONE
INTRODUCTION TO
TOXICOLOGY
4/5/2022
Introduction to Toxicology
2

3. Outline
Introduction to toxicology
Historical Aspects of Toxicology
Toxicological terms and definitions
 Classification
Scope of toxicology
 Nature of toxic response
 Route of poisoning
Potential causes of toxicity
4/5/2022
Introduction to Toxicology
3

4. Objectives
At the end of this chapter, students will be able to:
Discuss introduction to toxicology
Discuss historical Aspects of Toxicology
Discuss toxicological terms and definitions
 Discuss classification
Discuss scope of toxicology
Discuss nature of toxic response
Discuss route of poisoning
Discuss Potential causes of toxicity
4/5/2022
Introduction to Toxicology
4

5. Definitions
Toxicology
 Is the science dealing with
property,
action,
toxicity,
fatal dose,
detection ,
estimation of poisons &
interpretation of the result of toxicological
analysis.
4/5/2022
Introduction to Toxicology
5

6. Definitions cont’d
Toxicology
 Derived from Greek word, toxikon and logos.
 a branch of science that deals with toxins, poisons, their effects
and treatment.
 is the qualitative and quantitative study of the adverse or toxic
effect of
 chemicals and
 other anthropogenic materials or xenobiotics on organisms.
 It also deals with foods and cosmetics for public consumption
both in alive or dead victims.
4/5/2022
Introduction to Toxicology
6

7. Historical Aspects of Toxicology
 It is only recently that the study of poisons becomes truly scientific
& in the past it was mainly a practical art utilized by murderers &
assassins.
 In Ancient time (1500 BC) earliest collection of medical records
contains
 many references and guidelines about poisons.
 Dioscorides (50 AD) a Greek physician,
 classify poisons as animal, plant or mineral & recognizing the value
of emetics.
 Maimmonides (1135-1204 AD), wrote poisons and their antidote
 which detailed some of the treatments consideration to be effective.
4/5/2022
Introduction to Toxicology
7

8. Historical aspects of toxicology cont’d
 Paracelsus (1493 AD), summarized his concept in the following
famous phrase ;
 “All substances are poisons; there is none that is not a poison. The
right dose differentiates a poison from a remedy
 Orifila (1787-1853 AD), Spanish physician
 who contributed to forensic toxicology by devising means of
detecting poisonous substances.
 From then on toxicology
 began in a more scientific manner &
 began to include the study of the mechanism of action of poisons.
4/5/2022
Introduction to Toxicology
8

9. Historical aspects of toxicology cont’d
 The 20th century- toxicology has now become much more than the
use of poisons.
 There are marked improvements in toxicological
 diagnosis & management (production of antidote for them).
4/5/2022
Introduction to Toxicology
9

10. Toxicological terms and definitions
 Toxin- a poison of natural (biological) origin.
 Toxicant (Poison)- a chemical that may harm or kill an organism.
 Toxic-having the characteristic of producing an undesirable or
adverse health effect.
 Toxicity-any toxic (adverse) effect that a chemical or physical agent
might produce within a living organism.
 Toxic Symptom - any feeling or sign indicating the presence of a
poison in the system.
 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.
4/5/2022
Introduction to Toxicology
10

11. Toxicological terms and definitions cont’d
 Hazard - is the likelihood that injury will occur in a given situation
or setting:
 the conditions of use and exposure are primary considerations.
 Risk - is defined as the expected frequency of the occurrence of an
undesirable effect arising from exposure to a chemical or physical
agent
 RISK= HAZARD + EXPOSURE
4/5/2022
Introduction to Toxicology
11

12. Toxicological terms and definitions cont’d
Acute poisoning
 is caused by an excessive single dose or several dose of
a poison
 taken over a short interval of time.
e.g. Strychnine, potassium cyanide
Chronic Poisoning
 is caused by smaller doses over a period of time,
 resulting in gradual worsening.
e.g. arsenic, phosphorus, antimony and opium
4/5/2022
Introduction to Toxicology
12

13. Toxicological terms and definitions cont’d
Sub acute poisoning
 shows features of both acute and chronic poisoning.
Fulminant poisoning
 is produced by a massive dose
 in this death occur rapidly,
 sometimes without preceding symptoms.
4/5/2022
Introduction to Toxicology
13

14. Classification
Toxicology is broadly divided into different classes
Depending on:
 Research methodology
 Socio-medical
 Organ/specific effects.
4/5/2022
Introduction to Toxicology
14

15. Classification cont’d
I. Based on research methodology
Descriptive toxicology
 Descriptive toxicology deals with toxicity tests on chemicals
exposed to human beings and environment as a whole.
 Provide important clue to a chemical MOA
 Contribute to the development of mechanistic toxicology.
 Key component of risk assessment that are used by regulatory
toxicology.
4/5/2022
Introduction to Toxicology
15

16. Classification cont’d
Mechanistic toxicology
 Mechanistic toxicology this deals with the mechanism of toxic
effects of chemicals on living organisms.
 This is important for
 rational treatment of the manifestations of toxicity (e.g.
organophosphate poisoning reversed by oximes) ,
 prediction of risks (e.g. organophosphate poisoning →leads to
accumulation of acetylcholine → activete muscarinic and
nicotic receptors→respiratory failure) &
 facilitation of search for safer drugs (e.g. Instead of
organophosphates, drugs which reversibly bind to
cholinesterase would be preferable in therapeutics).
4/5/2022
Introduction to Toxicology
16

17. Classification cont’d
Regulatory toxicology :
 studies whether the chemical substances has low risk to be
used in living systems.
Establishment of standards for the amount of chemicals permitted
in ambient air, industrial atmospheres and drinking water.
Encompasses the collection, processing and evaluation of
epidemiological and experimental toxicology data
to permit toxicologically based decisions.
4/5/2022
Introduction to Toxicology
17

18. Classification cont’d
 Examples:
 Food and drug administration regulates drugs, food,
cosmetics medical devices & supplies in USA.
 Environmental protection agency regulates pesticides, toxic
chemicals, hazardous wastes and toxic pollutants in USA.
 Occupational safety and health administration regulates the safe
conditions for employees in USA authority.
 DACA - regulates drugs, food, cosmetics and medical devices &
supplies in Ethiopia.
4/5/2022
Introduction to Toxicology
18

19. Classification cont’d
Predictive toxicology
 Predictive toxicology studies about the potential and actual
risks of chemicals /drugs
 This is important for
 licensing a new drug/chemical for use.
4/5/2022
Introduction to Toxicology
19

20. Classification cont’d
II. Based on specific socio-medical issues
Occupational toxicology
 It deals with chemical found in the workplace.
 E.g – Industrial workers may be exposed to these agents during
the synthesis, manufacturing or packaging of substances.
– Agricultural workers may be exposed to harmful amounts of
pesticides during the application in the field.
4/5/2022
Introduction to Toxicology
20

21. Classification cont’d
Environmental toxicology
 This deals with the potentially deleterious impact of chemicals,
 present as pollutants of the environment to living organisms.
Ecotoxicology
 Ecotoxicology has evolved as an extension of environmental
toxicology.
 It is concerned with the toxic effects of chemical and physical
agents on living organisms,
 especially in populations and communities with defined ecosystems.
4/5/2022
Introduction to Toxicology
21

22. Classification cont’d
Clinical toxicology
 Clinical toxicology deals with diagnosis and treatment of the
normal diseases or effects caused by toxic substances of
exogenous origin.
 Clinical toxicologists are physicians who receive specialized
training in emergency medicine and poison management
 Efforts are directed at treating patients poisoned with drugs or
other chemicals and at the development of new techniques to treat
those intoxications.
4/5/2022
Introduction to Toxicology
22

23. Classification cont’d
Forensic toxicology
 Forensic toxicology closely related to clinical toxicology.
 It deals with the medical and legal aspects of the harmful
effects of chemicals on man.
 Aid in establishing the cause of death and
 determining its circumstances in a postmortem investigation.
Animal and plant toxicology
 deals with the diagnosis and treatment of harmful effects of
animals and plants.
4/5/2022
Introduction to Toxicology
23

24. Classification cont’d
III. Based on the organ/system effect
 Cardiovascular toxicology
 Renal toxicology
 Central nervous system toxicology
 Gastrointestinal toxicology
 Respiratory toxicology, etc
4/5/2022
Introduction to Toxicology
24

25. Scope of toxicology
 Toxicology is both a science and an art.
 The science of toxicology is defined as the observational
and data gathering phase.
 The art of toxicology consists of the utilization of the data to predict
outcomes of exposure in human and animal populations.
4/5/2022
25
Introduction to Toxicology

26. Scope…..
 In most of the cases these phases are linked because facts
generated by the science of toxicology are
 used to develop extrapolations and hypotheses
 to explain the adverse effects of chemical agents in
situations where there is little or no information.
4/5/2022
Introduction to Toxicology
26

27. Scope…..
 Modern toxicology goes beyond A/E to
 study of molecular biology using toxicants as tools.
 Historically toxicology forms the basis for
 therapeutics and experimental medicine.
 Recent …..application of the discipline
 to safety evaluation and risk assessment.
4/5/2022
27
Introduction to Toxicology

28. Scope….
 The contributions and activities of toxicologists are diverse
and widespread|:
 In the biomedical area
 Toxicologists are concerned with mechanisms of action and
exposure to chemical agents as a cause of acute and chronic
illness.
4/5/2022
28
Introduction to Toxicology

29. Scope…..
 In physiology and pharmacology
 To understand physiological phenomena by using
toxicants
 They are involved in
 the recognition, identification and quantification of hazards
resulting from occupational exposure to chemicals and
 the public health aspects of chemicals in air, water, other
parts of the environment, foods, and drugs.
4/5/2022
29
Introduction to Toxicology

30. Scope …
 Toxicologists also participate in the development of standards
and regulations designed
 to protect human health and the environment from the
adverse effects of chemicals
 Molecular toxicologists
 are studying the mechanisms by
 which toxicants modulate cell growth and differentiation and cells
respond to toxicants at the level of the gene.
 Clinical toxicologists
 develop antidotes and treatment regimes
 to ameliorate poisonings and xenobiotic injury.
4/5/2022
30
Introduction to Toxicology

31. 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.
4/5/2022
Introduction to Toxicology
31

32. 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
E.g. when two organophosphate insecticides are given
together ⇒ the cholinesterase inhibition is usually additive.
4/5/2022
Introduction to Toxicology
32

33. 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
E.g Isopropanol is not hepatoxic, but enhance carbon tetrachloride
induced hepatoxicity .
4/5/2022
Introduction to Toxicology
33

34. Nature of toxic responses cont’d
Antagonism
- is the phenomenon of opposing actions of two chemicals on
the same system.
 Very desirable in toxicology and
 are the basis of many antidotes.
Example: 4 + 0 = 1
Dimercaprol (BAL) chalets with metal ions, As, Pb….
4/5/2022
Introduction to Toxicology
34

35. 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. 4/5/2022
Introduction to Toxicology
35

36. Nature of toxic responses cont’d
 A teaspoonful of a very toxic substance could have the same effect.
 When there is a substantial difference between LD50 values of two
different substances,
 the one with the lower value is said to be the more potent.
 Such a comparison must assume that the dose–response curves for
the two substances being compared have similar slopes.
4/5/2022
Introduction to Toxicology
36

37. Nature of toxic responses cont’d
 If this is not the case, the substance for which the dose–response
curve
 has the lesser slope may be toxic at a low dose, where the other
substance is not toxic at all.
 Death from exposure to a toxic substance is a relatively rare effect
that is irreversible.
 much more concern are sub lethal effects that are often
reversible,
 such as allergies, and birth defects.
 particular concern is the development of cancer from exposure to
toxic substances (carcinogenicity) that,
 although often fatal is not an acute effect.
4/5/2022
Introduction to Toxicology
37

38. Nature of toxic responses cont’d
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.
4/5/2022
Introduction to Toxicology
38

39.  Median toxic dose (TD50) – is the dose which is expected to
bring toxic effect in 50% of the population in the particular group.
4/5/2022
Introduction to Toxicology
Nature of toxic responses cont’d
39

40. 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.
 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.
4/5/2022
Introduction to Toxicology
40

41. 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.
4/5/2022
Introduction to Toxicology
41

42. Nature of toxic responses cont’d
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.
4/5/2022
Introduction to Toxicology
42

43. Routes of poisoning
 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.
4/5/2022
Introduction to Toxicology
43

44. Routes of poisoning cont’d
 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.
4/5/2022
Introduction to Toxicology
44

45. 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
4/5/2022
Introduction to Toxicology
45

46. Sources of Poison
 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. 4/5/2022
Introduction to Toxicology
46

47. 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
4/5/2022
Introduction to Toxicology
47

48. 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.
4/5/2022
Introduction to Toxicology
48

49. 4/5/2022
Introduction to Toxicology
49