INTRODUCTION TO TOXICOLOGY
Household, environmental,
Pharmacology
 the study of the effect of drugs on the function
of living systems
 origin: Greek word “pharmakon” = drug
 Chemical agents that cause toxicity include:
 Drugs
 Insecticides/herbicides
 Plant toxins
 Animal toxins
 Chemical weapons
 Radioactive elements
Paracelsus (1493-1541)
‘Grandfather of Toxicology’
 "All things are poison and nothing is without
poison, only the dose permits something not to
be poisonous. “
 “ The dose makes the poison”
Mathieu Joseph Bonaventura Orfila
 Father of modern toxicology
 He focuses on the harmful effects of
chemicals and therapy of chemical
effects, and introduce quantitative
methodology into the study of the
actions of chemicals on animals
 Modern Toxicology
 A multi-disciplinary field, and as such it
borrows freely from several of the basic
sciences
 Knowledge of and an ability to study the
interaction between chemicals and
biologic mechanisms is predicated upon
a background in all of the basic physical,
chemical and biologic subjects
TOXICOLOGY
 Branch of pharmacology
 Deals with the undesirable effects of chemicals n
biologic system
 Study poisons (action, AE,&TX)
 Eg.
industrial or pharmacologic substance
 Science of poison w/c deals with origin,
properties, physiologic action and symptoms,
lethal dose, proper antidotes, specific
identification and quantitative determination,
evaluation and interpretation of these analytical
results.
DIVISIONS OF TOXICOLOGY
CLINICAL TOXICOLOGY
 concerned with disease caused by or uniquely
associated with toxic substances
 Effects of the intentional over dosage or
accidental poisoning to humans health
ENVIRONMENTAL TOXICOLOGY
 Concerned primarily with the harmful effects of
chemicals that are encountered by man either
incidentally
 Atmosphere
 Contact during occupation or
recreational activities
 Ingestion as food additives
ECONOMIC TOXICOLOGY
 Deals with the harmful effects of chemicals that are
intentionally administered to biologic tissue for the
purpose of achieving a specific effect.
 Qualities of a chemical that make it a drug are:
 Selectivity in regard to site of action
 Reversibility of action
 Ability to produce some useful effect which
is generally defined as a therapeutic effect
FORENSIC TOXICOLOGY
 hybrid of analytic chemistry and fundamental
toxicologic principles that focuses primarily on the
medicolegal aspects of the harmful effects of
chemicals on human and animals
DEVELOPMENT TOXICOLOGY
 Study of adverse effects on the developing
organism that may result from exposure to
chemical or physical agents before conception
 (either parent), during prenatal development, or
postnatally until the time of puberty.
 Teratology
- study of defects induced during development
between conception and birth
REPRODUCTIVE TOXICOLOGY
 study of the occurrence of adverse effects on the
male or female reproductive system that may
result from exposure to chemical or physical
agents
Toxicologist
 To diagnose, detect and estimate poisons in
order to evaluate their forensic and medical
importance
DIFFERENT AREAS
MECHANISTIC TOXICOLOGIST
 identifies e cellular, biochemical, and molecular
mechanisms by which chemicals exert toxic
effects in living organisms
 useful in designing and producing safer
chemicals and in rational therapy for chemical
poisoning and treatment of disease
DESCRIPTIVE TOXICOLOGIST
 concerned directly with toxicity testing, which
provides information for safety evaluation and
regulatory requirements.
REGULATORY TOXICOLOGIST
 responsible for deciding on the basis of data
provided by descriptive and mechanistic
toxicologist, whether a drug or another chemical
poses a sufficiently low risk to be marketed for a
stated purpose
 involved in the establishment standards for the
amount of chemicals permitted in foods, drugs,
ambient air, industrial atmospheres, and drinking
water.
TOXICOLOGICAL TERMS
TOXICITY
 Ability of a chemical agent to cause injury.
 Injuries occur depends on the amount of chemical
absorbed
HAZARD
 Likelihood that injury will occur in a given situation
or setting; the conditions of use and exposure are
primary consideration.
RISK
 Expected frequency of the occurrence of an
undesirable effect arising from exposure to a
chemical or physical agent.
POISON
 Any substance applied to the body, ingested, inhaled
or developed within the body which causes or may
cause damage or disturbance of function.
TREATMENT
 Is the management and care of a patient or the
overcoming or combating of a disorder.
SYMPTOM
 Any evidence of disease or of a patient’s condition, a
change in a patient’s condition indicative of some
bodily or mental state
POISONING
 Is a morbid condition produced by a poison
POSOLOGY
 Treats of the form and quantity of medicines to be
administered at one time or within a certain period.
DOSE
 Is the quantity of medicine to be administered at one
time or within a certain period, usually one day.
MINIMUM DOSE
 Is the smallest amount which produces therapeutic
effects or beneficial action upon the sick.
AVERAGE DOSE/CUSTOMARY DOSE
 Is the dose which may be expected ordinarily to
produce the therapeutic effects for which the
preparation is employed.
MAXIMUM DOSE
 Is the largest amount which can be safely used in
ordinary cases
TOXIC DOSE/POISONOUS DOSE
 Is the dose that is harmful to both the healthy and the
sick, but is not-fatal
Routes of exposure
FATAL DOSE/LETHAL DOSE
 Ingestion
 Is the dose which kills or is the dose which is just
 Inhalation
sufficient to cause death
 Transdermal routes
 LD
 Parenteral
∞ Lethal dose
- greatest effect and most rapid response
 MLD
APPROXIMATED DESCENDING EFFECTIVENESS
∞ Minimum lethal dose
1. INHALATION
 LD50
2. INTRAPERITONEAL
∞ The amount (dose) which kills 50%
of a group of test animals (usually 3. SUBCUTANEOUS
10 or more) or tested on 50 animals 4. INTRAMUSCULAR
 LD100 5. INTRADERMAL
∞ The amount (dose) which kills 6. ORAL
100% of a group of test animals
(usually 10 or more) or tested on 7. DERMAL
100 animals Poison – related
MARGIN OF SAFETY
 Route of administration
∞ Is the magnitude of the range of doses involved in
 Solubility
progressing from a non-effective dose to a lethal
 concentration
∞ MOS= LD1
Patient – related
ED99
 Age
Brine shrimp Assay
 Social habits
 Simple assay to determine LD50 and LC50
 Generics
 Threshold limit value
 Idiosyncrasy
 Maximum amount of substance that is considered
safe. DURATION OF EXPOSURE
NUMBERS IN TOXICOLOGY  Acute exposure
Effect Concentration - exposed for less than 24hrs
Extremely toxic 1mg/kg or less - single administration / repeated
Highly toxic 1 – 50mg/kg administration within 24hr for some ST
or PNT chemicals
Moderately toxic 50 – 500mg/kg
 Subacute exposure
Slightly toxic 0.5 – 5gm/kg
- repeated exposure to a chemical for 1
Practically non-toxic 5 – 15gm/kg
month or less
Relatively harmless More than 15gm/kg
 Sub chronic exposure
 - 1 to 3 months

 Chronic exposure

- Multiple exposures continuing over a

long period of time

- more than 3 months

DOSE-RESPONSE RELATIONSHIP

 characteristics of exposure and the spectrum of

effects come together in a correlative
relationship customarily

- selected measurement

- relationship between the degree of

response of the biological system

- amount of toxicant administered

TYPES OF DOSE-RESPONSE RELATIONSHIP

1. INDIVIDUAL DOSE-RESPONSE RELATIONSHIP

 describes the response of an individual organism

to varying doses of a chemical

 “graded” response

- measured effect is continuous over a

range of doses
2. QUANTAL DOSE-RESPONSE RELATINSHIP

 characterizes the distribution of responses to

different doses in a population of individual
organisms

HORMESIS

 non-nutritional toxic substances impart

beneficial or stimulatory effects at low doses