Toxicology - Chaper 1 1

Introduction to
Toxicology
Toxicology - Chaper 1 2
The study of the adverse
effects of chemicals on living
organisms and the
underlying mechanisms
Toxicology
Toxicology - Chaper 1 3
Like medicine, toxicology is both a science
and an art. The science of toxicology is
defined as the observational and data-
gathering phase, whereas the art of
toxicology consists of the utilization of the
data to predict outcomes of exposure in
human and animal population.
Toxicology
Toxicology - Chaper 1 4
History of Toxicology
Antiquity: Ebers papyrus (1500 B.C.), Ben
Chao Gong Mu (Ming dynasty)
Middle ages: Renaissance - Poisons and Their
Antidotes (1198), arsenic-containing products
Age of enlightenment: Parcelsus (1493-1548)
All substances are poisons; there is none
which is not a poison. The right dose
differentiates a poison from a remedy.
Toxicology - Chaper 1 5
History of Toxicology
Age of enlightenment: Orfila (1787-1853)
the first toxicologist to use autopsy material
and chemical analysis systematically as legal
proof of poisoning.
Oswald Schmiedeberg (1838-1921) the first
toxicologist to train 120 students who later
populated the most important laboratories of
pharmacology and toxicology throughout the
world.
Toxicology - Chaper 1 6
History of Toxicology
Morden toxicology: 1900-
Development of early advances in analytic
methods: heavy metals
Early mechanistic studies: drugs, plants
Introduction of new toxicants and antidotes:
nitrite and thiosulfate for cyanide; DDT
(1944); organophophorus compounds(1952)
Development of new branches
Toxicology - Chaper 1 7
History of Toxicology
The Silent Spring (Rachel Carson, 1962)
The earths vegetation is a part of a web of life in
which there are intimate and essential relations
between plants and the earth, between plants and
other plants, between plants and animals.
Sometimes we have no other choice but to disturb
these relationships, but we should do so
thoughtfully, with full awareness that what we do
may have consequences remote in time and place.
Toxicology - Chaper 1 8

Three eras of development of
experimental toxicology
Toxicology - Chaper 1 9
Toxicology Branch
According to object of study:
Animal Toxicology
Human Toxicology
Plant Toxicology
Insect Toxicology
Livestock Toxicology
Toxicology - Chaper 1 10
Toxicology Branch
According to field of study:
Environmental Toxicology
Food Toxicology
Occupational Toxicology
Clinical Toxicology
Forensic Toxicology
Analytic Toxicology
Toxicology - Chaper 1 11
Toxicology Branch
According to target organ of study:
Liver Toxicology
Kidney Toxicology
Neurotoxicology
Immunotoxicology
Productive Toxicology
Hemotoxicolgy
Toxicology - Chaper 1 12
Toxicology Branch
According to mechanism of study:
Cellular Toxicology
Molecular Toxicology
Membrane Toxicology
Biochemical Toxicology
Genetic Toxicology
Toxicology - Chaper 1 13
Toxicology Branch
According to area of study:
Descriptive Toxicology
Mechanistic Toxicology
Regulatory Toxicology
Toxicology - Chaper 1 15
Main Areas of Toxicology Study
Descriptive Toxicology :
To test toxicity in experimental animals
to provide important clues to a
chemicals mechanism of action.
To yield information that can be used to
evaluate risks posed to humans and the
environment.
Toxicology - Chaper 1 16
Main Areas of Toxicology Study
Mechanistic Toxicology :
To identify and understand the cellular,
biochemical and molecular mechanisms
by which chemicals exert toxic effects
on living organisms.
To design and produce safer alternative
chemicals for therapy of poisoning and
treatment of diseases.
Toxicology - Chaper 1 17
Main Areas of Toxicology Study
Regulatory Toxicology :
To perform the risk assessment of a
potential hazard to the human health
and the ecosystem.
To establish standards for the amount
of chemicals permitted in ambient air,
industrial atmosphere, and drinking
water.
Toxicology - Chaper 1 18
Spectrum of Toxic Dose
Among chemicals there is a wide spectrum
of doses needed to produce deleterious
effects, serious injury, or death.
However, the measures of acute lethality
such as LD
50
may not accurately reflect
the full spectrum of toxicity associated
with exposure, e.g., carcinogenic or
teratogenic effects.
Toxicology - Chaper 1 19
Spectrum of Undesired Effects (1)
Allergic reactions
Chemical allergy is an immunologically
mediated adverse reaction to a chemical
and is dose-related for a given individual.
The incidence of allergic asthma has
increased substantially in recent years.
Toxicology - Chaper 1 20
Spectrum of Undesired Effects (2)
Idiosyncratic reactions
Referring to a genetically determined
abnormal reactivity to a chemical, i.g.,
extreme sensitive to low doses or
extreme insensitive to high doses.
Examples of chemical idiosyncrasy
include exposures to succinylcholine and
methemoglobin-inducing chemicals.
Toxicology - Chaper 1 21
Spectrum of Undesired Effects (3)
Immediate versus delayed toxicity
Most chemicals produce immediate toxic
effects but not delayed effects.
Delayed toxicity can be seen in
carcinogenic chemicals (years) and
organophosphorus pesticides (weeks)
such as TOCP to inhibit the neuropathy
target esterase (NTE).
Toxicology - Chaper 1 22
Spectrum of Undesired Effects (4)
Reversible versus irreversible toxic effects
The ability of exposed tissue to
regenerate largely determines where the
effects is reversible or irreversible.
Carcinogenic and teratogenic effects are
usually considered irreversible toxic
effects once they occur.
Toxicology - Chaper 1 23
Spectrum of Undesired Effects (5)
Local versus systemic toxicity
Local effects occur at the site of first contact of
chemicals, e.g., ingestion of caustic substances
or inhalation of irritant materials.
Systemic effects require absorption and
distribution of a toxicant from its entry point
to a distant site to produce damages, some of
the affected organs are referred to as the
target organs of a particular chemical.
Overview
of
Toxicology
Study
Xenobiotic
O
O
O
O
O
OMe
Target Organism
Community/
Population
Ecosystem
Absorption
Target Tissue
Target Cell
Exposure
Distribution
Metabolism
C
l
a
s
s
i
c
a
l

T
o
x
i
c
o
l
o
g
y

Xenobiotic
O
O
O
O
O
OMe
Membrane
Transport
Organism
Toxicity
Tissue
Toxicity
R
e
g
u
l
a
t
o
r
y

T
o
x
i
c
o
l
o
g
y

Excretion
Epidemiology/
Environmental Toxicology
Target
Molecule
Cellular and
Molecular Events
Cellular
Toxicity
M
o
l
e
c
u
l
a
r

a
n
d

C
e
l
l
u
l
a
r

T
o
x
i
c
o
l
o
g
y

Genetic Susceptibility
Biomarkers
Risk assessment
Mechanisms
and treatment
of toxicity
Risk characterization
Biology
Response
Metabolism
Information Resource of
Toxicology, Hazardous Chemicals, and the Environment

1. Chemical Information
Identify chemical, its synonyms, and CAS number

www.chemfinder.com
find chemical structure, chemical surrogate based on structure
similarity. Can be searched by using a chemical name, CAS
Number, molecular formula, or molecular weight

toxnet.nlm.nih.gov/ (ChemID)
find which National Library of Medicine (NLM) databases
contain information on the chemical.

2. Toxicology Information

http://toxnet.nlm.nih.gov/ Summarize toxicological study results, etc.
http://toxnet.nlm.nih.gov/ search for original studies.
http://ntp-server.niehs.nih.gov/ National Toxicology Program
http://ehis.niehs.nih.gov/ Environmental Health Information Service
www.epa.gov Environmental Protection Agency
www.fda.gov Food and Drug Administration
www.osha.gov Occupational Safety and Health Administration
www.atsdr.cdc.gov Agency for Toxic Substances and Disease Registry
www.acgih.org American Conference of Governmental industrial Hygienist
www.iarc.fr The International Agency for Research on Cancer
www.fao.org Food and Agriculture Organization of the United Nations
http://www.toxicology.org/Information/siteofinterest/sites.html#Government
Toxicology - Chaper 1 27
Toxicology is a science for the
wellbeing of mankind