This presentation will give an idea about basic definition and different types of toxicology.

1. Basic definition
&
Types of toxicology

3. Introduction
 Toxicology is a branch of science that deals with toxins, poisons, their effects and treatment.
 Toxicological screening is very important for the developing new drugs and it gives idea
about therapeutic potential of existing drugs.
 Toxicology helps in predicting what, and how chemicals may cause harm and then shares
that information to so as to protect public health.
 Paracelsus is regarded as the Father of Toxicology. According to him “All things are poison
and nothing is without poison, only the dose permits something not to be poisonous”

4. Some basic terminologies.
 Toxins- Substances that are produced naturally (nature origin)
 Toxicity- Degree to which a substance is poisonous or can cause injury
 Toxic agent- Anything that can produce an adverse biological effect. It may be chemical,
physical, or biological in form. For example, toxic agents may be chemical (such as
cyanide), physical (such as radiation) and biological (such as snake venom).
 Toxicant- A chemical that can injure or kill humans, animals, or plants; (poison)
Systemic toxin:
Affects the entire body,
or many organs. Not
site specific
Organ toxin:
Affects only
specific tissues or
organ

5. Branches of Toxicology
Analytical
toxicology:
Study of detection
and assay of
poisonous chemicals
Applied toxicology:
Application of new
methods for early
detection of
toxicants.
Clinical toxicology:
Mainly involved in
study of diagnosis
and treatment of
poisoning.
Veterinary toxicology:
The study of diagnosis and
treatment of animal
poisoning.
Environmental toxicology:
The study of presence of different
toxicants in the environment and
their effects on humans and
animals.
Industrial toxicology:
Study of selective and
specific are of environmental
toxicology
IMMUNO TOXICOLOGY:
deals with the effect of
toxicant on immune
system
REPRODUCTIVE AND
DEVELOPMENTAL
TOXICOLOGY: Effect of
chemicals or toxins on the
reproductive system and the
developing embryo.

6. Routes of
exposure of toxins
Skin:
Chemicals that can
penetrate healthy
intact skin.
Examples: Aniline,
Hydrogen cyanide,
Organophosphate
Lungs:
Depends on : Size &
Shape of particles and
Rate of physical work
Ingestion:
Mostly we can control
Depends on
concentration & time
Sometimes can
accumulate with time
and cause harm.

7. Importance of dose
 It is an important factor in toxicology.
 All substances have the potential to be toxic if given to living
organisms in the right conditions and dose.
 LD50 : Refers to the dose of a substance that displays toxicity
in that it kills 50% of a test population

8. Importance of studying Toxicology
 Studying toxicology provides protection to humans and
environment from toxic effects of toxicants.
 study will ultimately lead toward the development of
newer, innovative and more selective drug therapies to
treat different diseases such as cancer having reduced
toxic potential to human body.

9. Types of Toxicology
 Mechanistic toxicology (basic biology and chemistry)
 Regulatory toxicology (rule making and compliance)
 Descriptive toxicology (testing)

10. Mechanistic toxicology
 The study of how chemical or physical agents interact with living organisms
to cause toxicity.
 The main aim of mechanistic toxicology is to identify that how xenobiotics
enter an organism and how these are distributed in the body.
 It addresses following questions:
• How do xenobiotics enter an organism and how are they distributed and
metabolized?
• How do xenobiotics interact with target molecules?
• How do xenobiotics exert their toxic effects at the molecular level?
• What are the downstream biological consequences?

11.  Mechanistic understanding helps the governmental regulator to establish legal
binding safe limits for human exposure.
 It is also useful in forming the basis for therapy and the design of new drugs for
treatment of human disease.
 Deeper understanding of mechanistic
toxicology will help in
• Easy data extrapolation
• Improve risk assessment of potentially
toxic chemicals for human safety .
• Improve risk assessment for
environmental pollutants in the workplace.
• Improve risk assessment for synthetic
and naturally occurring
hazards in food or in drinking water.

12.  Mechanisms of toxicity:
Site of Exposure/ the target
Reaction of the toxicant with the
target molecule

13.  Factors that cause cellular dysfunction:
• Chemicals that cause DNA adducts causes DNA mutations, which can activate cell
death pathway. If mutations activate oncogenes or inactivate tumor suppressors,
it can lead to uncontrolled cell proliferation and cancer (e.g. benzopyrene)
• Chemicals that cause protein adducts can lead to protein dysfunction which can
activate cell death pathways; protein adducts can also lead to autoimmunity; if
protein adducts activate oncogenes or inactivate tumor suppressors, it can lead to
uncontrolled cell proliferation and cancer (e.g. diclofenac glucuronidation
metabolite)
• Chemicals that cause oxidative stress can oxidize DNA or proteins leading to DNA
mutations or protein dysfunction (e.g. benzene, CCl4)
• Chemicals that specifically interact with protein targets - Chemicals that activate
or inactivate ion channels can cause widespread cellular dysfunction and cause
cell death and many physiological symptoms.

14.  Acute, sub chronic and chronic toxicity mechanisms:
• Simple asphyxiants
• Chemical asphyxiants
• Central nervous system (CNS)depressants.
• Skin effects.
• Lung sensitization.
• Eye effects.
• Effect of toxicant on enzyme (anticholinestrase inhibition).
• Interaction with proteins.
• Metabolic activation.
• Effect of toxicant on receptor and ion channel
• Effect on lipids and nucleic acid.
• Cancer mechanism.
• Reproductive mechanisms
Acute toxicity
mechanism
Chronic and sub
chronic toxicity
mechanism

15. Regulatory toxicology
 It deals with the relationship between the discipline of toxicology and
regulatory institutions.
 Consists of collecting, processing and evaluating incidents, distribution,
and control of diseases towards the protection of health against
harmful toxicants.
 It supports the development of standard protocols and new testing
methods.
 The regulatory authorities have to protect the health of humans which
relies on toxicological principal and toxicity evaluation data to
formulate a decision.
 Its aim is to control production and use of dangerous materials to
prevent adverse effects on human health and the environment.

16.  National and international collaboration in regulatory toxicology:
• A number of international bodies and authorities promote the sound
management of chemicals at national and international level. They are:
ICH, WHO, FDA, OECD
 Regulatory Toxicologist
• Help governments to formulate regulations and put them into practice.
• They help to minimize the risk presented by chemicals which may be
hazardous to human health and the environment.
• They evaluate data from all branches of toxicology.
• With their help not only we understand the health hazards posed by a
chemical, but also how these translate into health risks.
• They help to enhance and safeguard the health of the public.

17.  Importance of guidelines in regulatory toxicity studies:
• Prevent duplication of clinical trials in humans .
• Ensure SAFETY, EFFICACY and QUALITY of medicines .
• Minimize the use of animal testing.
• Provides the definite parameters of evaluation.
• Provides a roadmap to prepare a study protocol.
• Increase international harmonization of technical requirements to
ensure that safe, effective, and high quality medicines are
developed.
• Supports economic growth, raise living standards, maintain
financial stability and contribute to growth in world trade

18. Descriptive Toxicology
 It is concerned directly with toxicity testing, which provides information for safety
evaluation and regulatory requirements.
 Focuses on toxicity testing of chemicals, usually on animals and then correlates to human
conditions.
 It provides dose-response information upon exposure to a harmful toxic agent.
 The toxicity assessment commonly involves following steps:
1. Hazard identification
2. Dose-response assessment
3.Exposure assessment
4. Risk characterization

19. 1. Hazard identification:
• It determines that the exposure to chemicals can increase the incidents of a
particular adverse effect.
• It is done by: Hazard identification Data, Human epidemiology data, Animal
bioassay, Supporting data, Prediction of hazard –Structure activity relationship
2. Dose- response relationship:
• Relationship between the exposure, appearance and duration of adverse effect.
• Two types of dose response relationship.
Graded dose response relationship- It describe the response of an individual
organism to varying dose of chemical
Quantal dose response relationship characterizes the distribution of intensity of
the effect to different doses in a population of individual organisms.

20. • No observed adverse effect level (NOAEL) It denotes the level of exposure of an
organism, at which there is no biologically significant increase in the severity of
any adverse effects.
• Lowest-observed-adverse-effect-level (LOAEL)- Lowest concentration causes an
adverse alteration of morphology ,growth ,or life span of a target organism
distinguishable from normal (control).
• Acceptable Daily Intake- Maximum amount of an agent, expressed on a body
mass basis, to which a subject may be exposed over his lifetime without
appreciable health risk.
3. Exposure Assessment:
• Process of estimating or measuring the magnitude, frequency and duration of
exposure to an agent, along with the number and characteristics of the
population exposed.
• It describes the sources, pathways, routes, and the uncertainties in the
assessment.
• In epidemiology used to distinguish between exposed and control groups, and to
protect workers from occupational hazards.

21. 4. Risk Characterization:
• Review toxicity and exposure assessment output
• Quantify risks
• Combine risks across all pathways
• Assess and present uncertainties
• Considers site specific human studies

22. Types of toxicity testing
 In vitro (test tube) :
• Useful in detecting potential biochemical and genetic effects.
• Uses model systems (bacteria, cultured animal cells, DNA interactions)
 In vivo (animal):
• Are essential for detecting health effects
• Experimental animals may be treated with high doses over a lifetime to
evaluate potential to cause cancer.
 In silico (computer-based):
• Biological experiments conducted by computer models.
• These depend on data previously collected in other experiments.

23. Importance of toxicity testing
 To have an idea of toxic doses of xenobiotic for certain organisms.
 Evaluation of safe doses of the toxicants for certain organisms.
 Recommendation of maximum permissible limits of those substances in the
ambient air and drinking water.
 The data on long term toxicity tests may be reliable for the evaluation of safe
level of toxicants.
 Evaluation and recommendation of maximum acceptable daily intake.
 Developing good air and water quality.