This document provides an introduction to toxicology for 4th year medical laboratory students. It defines key terms like toxicology, toxin, toxicant, toxicity and discusses the historical aspects and development of toxicology as a field. It outlines the chapter which covers the introduction, historical aspects, definitions, classification, scope, nature of toxic response, routes of poisoning and potential causes of toxicity. The document discusses in detail the definitions, classification based on research methodology and specific issues, scope, nature of toxic responses including terms like LD50, routes of exposure and reversibility.

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

2. CHAPTER ONE
INTRODUCTION TO
TOXICOLOGY
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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
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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
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5. Definitions
Toxicology
 Is the science dealing with
property,
action,
toxicity,
fatal dose,
detection ,
estimation of poisons &
interpretation of the result of toxicological
analysis.
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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.
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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.
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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.
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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).
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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.
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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
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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
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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.
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14. Classification
Toxicology is broadly divided into different classes
Depending on:
 Research methodology
 Socio-medical
 Organ/specific effects.
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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.
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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).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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24. Classification cont’d
III. Based on the organ/system effect
 Cardiovascular toxicology
 Renal toxicology
 Central nervous system toxicology
 Gastrointestinal toxicology
 Respiratory toxicology, etc
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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 .
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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….
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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
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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.
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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.
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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.
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39.  Median toxic dose (TD50) – is the dose which is expected to
bring toxic effect in 50% of the population in the particular group.
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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.
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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.
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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.
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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.
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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.
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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
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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
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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
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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.
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