TOXICOLOGY

-study of poisons

FIELDS OF TOXICOLOGY
1. MECHANISTIC TOXICOLOGY
-concerned with the identification of the
mechanisms by which chemicals exert toxic
effects on living organisms

2. DESCRIPTIVE TOXICOLOGY
-concerned directly with toxicity testing;
concerned with gathering toxicological
information from animal experimentation to
predict what level of exposure will cause harm in
humans. This process is known as risk
assessment.

3. REGULATORY TOXICOLOGY
-responsible for interpreting the data from
mechanistic and descriptive studies to establish
standards that define the level of exposure that
will not pose a risk to public health or safety.
Ex. Established standards for the amount of
chemicals permitted in ambient air, in industrial
atmosphere or in drinking water.

4. FORENSIC TOXICOLOGY
-primarily concerned with the medicolegal
consequences of toxin exposure.
MAJOR FOCUS: establishing or validating the
analytical performance of the method used to
generate evidence in legal situations, including
the cause of death, aka post mortem
investigations.

5. CLINICAL TOXICOLOGY
-focuses on the effects of substances in
patients caused by accidental poisonings or
intentional overdoses of medications, drugs of
abuse, household products or various other
chemicals

a. EMERGENCY TOXICOLOGY
-involves identification of poisons
with suspected accidental or suicidal poisoning
to rapidly identify poisons which can be actively
treated.

b. THERAPEUTIC DRUG MONITORING

-measuring the serum or blood
concentration of a drug which is being
administered therapeutically to guide the
physician in adjusting dosage so that drug
concentration is within the effective dose

DEFINITION OF TERMS
1. TOXICITY degree to which the substance is
poisonous or can cause injury.
2. TOXICANT any substance that causes a
harmful effect when in contact with a living
organism at a sufficiently high concentration

3. INDIVIDUAL SUSCEPTIBILITY
-describes the differences in types of
response to hazardous substances between
people.
4. HAZARD ability of an agent to cause injury
in a given situation or setting.
5. RISK- expected frequency of the occurrence
of the undesirable effect, probability of injury.

6. DURATION OF EXPOSURE
-frequency of exposure and time between
exposures are important determination of a
dose and response.
7. DOSE- actual amount of exposure to an agent,
or the actual amount of chemical that enters the
body.
8. FATAL DOSE- quantity of medicine that can kill
an organism.

9. LD50 single dose of a chemical that can cause

death in 50% of the exposed population.
10. TERATOLOGY study of defects induced during
development between conception and birth
11. THRESHOLD DOSE/THRESHOLD LIMIT VALUE
-dose or exposure level below which the
harmful or adverse effects of a substance are not
seen.

12. SELECTIVE TOXICITY

-means that a chemical will produce injury
to one kind of living matter without harming
another form of life even though the two may
exist closely together.
13. POISON
-any agent that may cause serious body
harm,injury or death when being exposed.

TYPES OF POISON:
a. TRUE POISON
still poisonous no matter how
diluted it is.
ex. Snake Venom
b. IRRITANT
-causes irritation at the site of contact
-manifested by swelling or rashes
ex. Acid (corrosive) & Base (caustic)

c. NEUROTIC
-has a direct effect in the CNS
ex. Hallucinogens (LSD)
d. CARCINOGENS
-stimulates growth of cancer cells
ex. Benzene

e. TERATOGEN
-adversely affects developing fetus
ex. Thalidomide (phocomelia)
f. ASPHYXIANT
-causes dyspnea
ex. Carbon monoxide
g. LACRIMATOR
-stimulates flow of tears
ex. Organophosphates, tear gas,
pepper spray

h. STERNUTATOR
-causes sneezing
ex. Veratrine, capsaicin
i. ASTHENICS
-causes muscle weakness
ex. Neuromuscular blockers
(pancuronium)
j. NARCOTICS
-narcosis

k. TETANIC
-poison that acts directly on the
spinal cord, producing such
spasmodic and continuous
contractions of the muscles.
ex. Strychnine- inhibits glycine
(main inhibitory NT in the
spinal cord)

EXPOSURE TO TOXINS

ROUTES OF EXPOSURE
1. INGESTION
2. INHALATION
3. TRANSDERMAL

DOSE-RESPONSE RELATIONSHIP
POISON any substance that causes a harmful
effect on exposure.
The concept that any substance has the
potential to cause harm if given at the correct
dosage is a central theme in toxicology.

TYPES OF TOXICITY
1. ACUTE TOXICITY
-usually associated with a single, shortterm exposure to a substance, the dose of which
is sufficient to cause immediate toxic effects.

2. CHRONIC TOXICITY
-usually associated with repeated frequent
exposure for extended periods, at doses that are
insufficient to cause an immediate response.

DURATION OF EXPOSURE
1.
2.
3.
4.

ACUTE EXPOSURE
SUBACUTE EXPOSURE SUBCHRONICEXPOSURE CHRONIC EXPOSURE
-

<24hrs
<1 month
1-3 months
>3 months

CHEMICAL INTERACTIONS
1. ADDITIVE - 1+1 = 2
the sum effects when two drugs were
combined
ex. Warfarin + Related anticoagulants = Bleeding

Furosemide + Digoxin = hypokalemia

2. SYNERGISM 1+1=3
sum effects when combined is greater than
the individual
ex. Alcohol + Paracetamol = hepatoxicity
3. POTENTIATION 1+0=3
one compound is assumed to have no
intrinsic toxicity by itself
ex. Hexane + Acetone = Peripheral
neuropathy

4. ANTAGONISM 1+1=0
-cancellation of effects
ex. Epinephrine + Histamine
EPINEPHRINE = Blood vessels: Vasoconstriction
HISTAMINE = Blood vessels: Vasodilation

ANALYSIS OF TOXIC AGENTS

TWO STEPS:
1. SCREENING TEST
-rapid, simple, qualitative procedure
intended to detect specific substances or classes
of toxicants.
2. CONFIRMATORY TESTING
-to confirm the presumptive analysis

Examples of assays
THIN-LAYER CHROMATOGRAPHY
-relatively simple, inexpensive method of
detecting various drugs and other organic
compounds.
GAS CHROMATOGRAPHY (GC)
-widely used, well-established technique
for the qualitative and quantitative
determination of volatile substances.

TOXICOLOGY
OF
SPECIFIC AGENTS