INTRODUCTION

TO TOXICOLOGY

MAIN REFERENCES

USMAR
FAKULTAS FARMASI UNIVERSITAS HASANUDDIN
 Toxicology

The Science of Poisons

The study of toxic effects of
chemicals on living systems
 Bag of
chemicals
(You)
HYSTORY OF TOXICOLOGY
GENERAL PRINCIPLES OF TOXICOLOGY

Casarett & Doull’s Toxicology

• Mekanistik
• Berkaitan dengan pengenalan mekanisme bahan kimia
menimbulkan efek toksik
• Deskriptif
• Berkaitan dengan uji toksisitas pada hewan uji untuk
mendaptkan informasi yg dpa digunakan untuk mengevaluasi
risiko pemaparan bahan kimia baik terhadap lingkungan
maupun terhadap manusia
• Regulasi
- Seorang toksikologi regulasi bertanggung jawab untuk
menentukan berdasarkan data yang diberikan oleh toksikolog
deskriptif apakah suatu bahan kimia cukup riskan untuk
dipasarkan.
• Forensic Toxicology
A forensic toxicologist is primarily invoked to aid in establishing the cause
of death and elucidating its circumstances in a postmortem investigations.
• Clinical Toxicology
It is a medical science concerned with the diseases caused by or associated
with toxic substances.
• Environmental Toxicology
It focuses on the impact of chemical pollutants found in the environment on
the biological organisms.
Ecotoxicology.
• Developmental and reproductive Toxicology
Mutagenic and teratogenic effects.
Jumlah zat kimia yg memasuki tubuh
Biasanya diberikan dalam satuan mg/kg
Bergantung pada
* Konsentrasi lingkungan
* Sifat toksikan
* Frekuensi pemaparan
* Lama pemaparan
* Jalur pemaparan
 Dose-Response Relationship:
As the dose of a toxicant increases,
so does the response.
4

RESPONSE
0-1 NOAEL
2-3 Linear Range 3
4 Maximum
Response
2

0 1 DOSE
DOSE DETERMINES THE BIOLOGICAL RESPONSE
• If Mortality is the response, the dose that is lethal to 50% of the
population LD50 can be generated from the curve
• Different toxicants can be compared-lowest dose is most potent.

• Therapeutic Index (TI) is the ratio of the dose required to produce a

toxic effect to that required to produce a desired therapeutic
response(LD50/ED50)
Casarett & Doull’s Toxicology
 What is a Response?
The response depends upon the dose and the organism

 Spectrum of Undesired effects

 Allergic Reactions
 Idiosyncratic reactions

 Immediate versus delayed toxicity

 Reversible versus irreversible toxics effects

 Local versus systemic toxicity

SYSTEMIC RESPONSES TO TOXIC AGENTS

 FACTORS CONTROLLING TARGET ORGAN

TOXICITY
 ROUTE OF EXPOSURE

 DISTRIBUTION IN THE BODY

 METABOLISM

 EXCRETION

 SENSITIZATION
Exposure: Pathways
 Routes and Sites of Exposure

 Ingestion (Gastrointestinal Tract)

 Inhalation (Lungs)

 Dermal/Topical (Skin)

 Injection

 intravenous, intramuscular,
intraperitoneal
 Typical Effectiveness of Route of Exposure
iv > inhale > ip > im > ingest > topical
MECHANISM OF TOXICITY
POTENTIAL STAGES IN THE DEVELOPMENT OF
TOXICITY AFTER CHEMICAL EXPOSURE

Casarett & Doull’s Toxicology

The process of toxicant delivery is the
first step in the development
of toxicity

Casarett & Doull’s Toxicology

 Reaction of the ultimate toxicant with
the target molecule: the
second step in the development of
toxicity.

Casarett & Doull’s Toxicology

 The third step in the development of toxicity: alteration of
the regulatory or maintenance function of the cell.

Casarett & Doull’s Toxicology

 RISK ASSESSMENT

• Risk assessment is the systematic scientific

evaluation of potential adverse health effects
resulting from human exposures to hazardous
agents or situations
Casarett & Doull’s Toxicology