Principles of Toxicology : The Study of Poisons

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Principles of Toxicology The Study of Poisons

• Wongwiwat Tassaneeyakul
• Department of Toxicology
• Khon Kaen University
• wong_tas_at_kku.ac.th

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Objective of Learning

• To know scope and definition of toxicology,
• Describe how toxicologist work and manage
  toxicants,
• Understand dose-response relationship and
  interactions

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Lake Nyos
August 21st, 1986, 930 pm
gt1700 people and 3000 dead cow!!!
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Asia's arsenic crisis deepens Another Indian
state succumbs to well water poisoning. 15
February 2003 TOM CLARKE
Hand-pump wells tap into natural accumulations of
arsenic.
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Thalidomide tragedy
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Fixed drug eruption
Drug rash
SJS
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A villager uses a dip net to remove dead fish
from the Bang Pakong river. The fish, bred in
floating baskets, died from pollution in the
river. _ TAWATCHAI KEMGUMNERD Friday 15
November 2002 BangkokPost
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Intoxication
Toxicity
Hazard
Poisoning
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Definitions

• TOXICOLOGY The study of the adverse effects of
  a toxicant on living organisms.

Toxicology related closely to Pharmacology,
Biochemistry, Molecular biology, Chemistry,
Epidemiology, Pathology, Genetics, Public Health,
Medicine, etc.
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Definitions

• Hazard physical situation that can damage
• people
• plant
• Environment
• Risk likelihood of hazard occurring
• Risk hazard probability consequence

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Source Muckter, 2003
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3 Basic component in toxicology study

• Toxicant/ Toxin/ Poison/ Hazard
• any agent capable of producing a deleterious
  response in a biological system
• Adverse/Toxic effects
• any unwanted change from an organisms normal
  state
• dependent upon the concentration of active
  compound at the target site (receptor)for a
  sufficient time.
• Living organism
• cellular target sites/ storage depots and enzymes

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COMMON TOXICOLOGY QUESTIONS

1. What is a poison?
2. Where dose it come from? (exposure Q)
3. How does it get into living organism? (exposure
   Q)
4. What does it do to living organism? (mechanism Q)
5. How can we treat/prevent this toxicity? (clinical
   Q)

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Routes of Entry

• Oral Ingestion by mouth
• Dermal Skin exposure
• Inhalation Absorbed by lungs
• Ocular Eye exposure

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Bioaccumulation
Why human have to concern with other species
toxicology and/or environmental health?
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Classification of Toxic Agents

• Target organ/site (e.g., liver, kidney, blood,
  lung, nerves)
• Use (e.g., pesticide, solvent, food additive)
• Effects (e.g., cancer, mutation, liver injury)
• Labeling requirements (e.g., explosive,
  flammable, oxidizer)
• Poisoning potential (e.g., very or slightly toxic)

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Dose-Response Relationship
Allein die Dosis macht, daß ein Ding kein Gift
ist. (Dose determines toxicity)
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THE DOSE MAKES THE POISON

• All substances are poisons there is none that is
  not a poison. The right dose differentiates a
  poison and a remedy.
• Paracelsus
• (1493- 1541)

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DOSE
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What is a Response?

• Change from normal state
• could be on the molecular, cellular, organ, or
  organism level--the symptoms
• Graded vs. Quantal
• degrees of the same damage vs. all or none

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Dose-response
EFFECT
non-linear, threshold
linear, no threshold
Dose
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LD50 Comparison
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Toxicity rating


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THE DOSE-RESPONSE RELATIONSHIP
The dose-response relationship (from C.D.
Klaassen, Casarett and Doulls Toxicology, 5th
ed., New York McGraw-Hill, 1996).
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Type of Toxic Response

• Acute vs. Chronic
• Allergic (hypersensitivity)
• Idiosyncratic (e.g. G6PD def.)
• Local vs. Systemic
• Reversible vs. Irreversible

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Acute Toxicity

• (short-term exposure)

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Chronic Toxicity

• (repeated exposures)

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Examples Chronic Effects

• Carcinogens
• Cause cancer
• Mutagens
• Cause mutations in an organisms genetic material
• Teratogens
• cause birth defects in offspring following
  exposure of a pregnant female

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Drug rash
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Dose-response relationship LEAD
decreased erythrocyte delta-ALAD
activity increased zinc protoporphyrin
anemia
CNS effects
decreased peripheral nerve conductivity Nervous
paralysis, lead colics
Adapted from Elinder C-G et al., Biologisk
monitoring av metaller hos människa.
Arbetsmiljöfonden, Uppsala, 1991
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Toxicity Interactions

• Additive 22 4
• Synergism 23 10
• Potentiation 03 5
• Antagonism 2(-2) 0
• Chemical antagonism
• Dispositional antagonism
• Functional antagonism
• Pharmacological antagonism

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Synergist / Synergism
Synergism is increased activity (toxicity)
resulting from the effect of one chemical on
another.
LD50 DDT 250 mg/kg LD50 synergist 1,000
mg/kg LD50 DDT synergist 50 mg/kg
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Source van den Brandt et al. 2002
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Epidemiology study
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Epidemiology study
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Source A Primer on Toxics
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Conclusion

• What is toxicology ?
• Toxicity, poison, hazard, risk ?
• Why dose-response study is so important in
  toxicology?
• How can we classify type of toxicity ?
• Why people response differently to toxicant ?

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THE DOSE MAKES THE POISON

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