Full Description on Toxicology and its types

1. KARNATAKA COLLEGE OF PHARMACY
DEPARTMENT OF PHARMACOLOY
Pharmacological & toxicological
screening method
PRESENTATION ON
“TOXICOLOGY AND ITS TYPES”
BY : KASHIKANT YADAV
M.PHARM (Pharmacology)

2. CONTENTS
 INTRODUCTION
 TYPES
 THE MAJOR AREAS :
MECHANISTIC TOXICOLOGY
REGULATORY TOXICOLOGY
DESCRIPTIVE TOXICOLOGY

3. INTRODUCTION:
• History
• Phillip von Hohenheim (Paracelcius) is known
as the“ father of toxicology“
• “All things are poison and nothing is without
poison, only the dose permits something not to
be poisonous.”

4. BASIC DEFINITIONS
• Toxin
• Toxic substances that are produced naturally (nature
origin)
• Toxicants
• Any chemical that can injure or kill humans, animals,
or plants; (poison)
• Toxicity
• Describes the degree to which a substance is
poisonous or can cause injury.
• Factors: dose, duration and route of exposure, shape
and structure of the chemical itself, and individual
human factors.

5. Toxicology
• The study of how natural or man-made poisons cause adverse
effects in living organisms.
• It involves observing and reporting symptoms, mechanisms,
detection and treatments of toxic substances.
• It includes environmental agents and chemical compounds, as
well as pharmaceutical compounds that are synthesized for
medical use. These substances may produce toxic effects leading
to , discomfort, disease and even death in living organisms.

6. IMPORTANCE OF DOSE
• The dose 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.

7. PURPOSE OF TOXICOLOGY:
• It provides protection to humans and environment from
toxic effects of toxicants.
• This 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.

8. ROUTES OF EXPOSURE
• Skin & mucous membrane
• Lung (Inhalation)
• Ingestion
• Eye (Occular)

9. SKIN
• Chemicals that can penetrate
• healthy intact skin – aniline,
• hydrogen cyanide,
• organophosphate, etc.

10. LUNGS (inhalation)
• • Depends on :
• Size & Shape of particles
• Rate of physical work

11. INGESTION
• Mostly we can control
(unlike airborne)
• Depends on :
• • Concentration
• • Time
a) • Continuous
b) • Intermittent
• • Sometimes can
accumulate and cause harm
in later life e.g. Lead

12. GENERAL TYPES OF TOXICOLOGY:
• Analytical toxicology
• Applied toxicology
• Clinical toxicology
• Veterinary toxicology
• Forensic toxicology
• Environment toxicology
• Industrial toxicology

13. • Analytical toxicology:
• It is the branch of toxicology which deals with
the study of detection and assay of poisonous
chemicals including their metabolites that could
affect the biological system.
• Applied toxicology:
• It is the application of new and modern
methods or technologies for early detection of
toxicants in the field setting or practice area.

14. • Clinical toxicology:
• It is mainly involved in the study of
diagnosis and treatment of poisoning that
can occur in humans.
• Veterinary toxicology:
• Veterinary toxicology focus in the study of
diagnosis and treatment of animal
poisoning including the transmission of
toxin from animals to humans via milk,
meat, fish, food stuff and etc.

15. • Environmental toxicology:
• It is the branch of toxicology in which study
of presence of different toxicants including
their metabolites and degradation products
in the environment and their effects on
humans and animals.
• Industrial toxicology:
• It is the study of selective and specific area
of environmental toxicology.

16. THE MAJOR AREAS OF SPECIALIZATION
IN TOXICOLOGY :
• Mechanistic toxicology (basic biology and
chemistry)
• Regulatory toxicology (rule making and
compliance)
• Descriptive toxicology (testing)

17. MECHANISTIC TOXICOLOGY:
• It is a branch of toxicology that focuses on how the
cellular, biochemical, and molecular mechanisms of
chemicals exert toxic effects on living organisms and
how the biological system protects themselves against
these adverse effects.
• It aims at identifying the molecular events that lead
from initial exposure to the chemical to the ultimate
manifestation of toxic injury in an organism.

18. IT ADDRESSES A NUMBER OF FUNDAMENTAL
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?

19. MECHANISMS OF TOXICITY CAN BE
STUDIED AT DIFFERENT LEVELS:1.
2.
3.

21. DEEPER UNDERSTANDING OF SUCH
MECHANISMS WILL HELP US TO:
• Extrapolate data better.
• Improve risk assessment of potentially toxic
chemicals for human safety .
• Improve risk assessment for environmental
pollutants, chemicals in the workplace.
• Improve risk assessment for synthetic and
naturally occurring hazardous compounds in
food or in drinking water.

22. • It’s a complex mixture of organic chemicals.
• Causes tumors in kidney of male rats.
• Active subtance “tert-butyl alcohol”.
• binding with specific protein α2u-globulin (
protease inhibitor )

23. REGULATORY TOXICOLOGY:
• It 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.
• Its aim is to control production and use of dangerous
materials to prevent adverse effects on human health
and the environment.

24. NATIONAL AND INTERNATIONAL COLLABORATION IN
REGULATORY TOXICOLOGY
• These standards are implemented worldwide for
sustainable development with the goal of improving the
quality of life for all people.
• A number of international bodies and authorities
promote the sound management of chemicals at
national and international level. They are:
• ICH
• WHO
• FDA
• OECD

25. QUALITY ASSURANCE IN REGULATORY
TOXICOLOGY
• Reliable data are essential for the assessment and evaluation of
the toxicological characteristics of chemical substances
• Data reliability is closely linked with the minimization of errors
and mistakes in the generation of data.
• These objectives can be reached by the implementation of
appropriate Quality Assurance (QA) systems.
• An important part of such systems is Quality Management (QM).

26. REGULATORY TOXICOLOGISTS
• 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.

27. 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

28. 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 correlated to human conditions.
• It provides dose-response information upon
exposure to a harmful toxic agent.
• The results from the toxicity testing are typically
applied to approval of product use and regulating
allowable concentrations in the environment.

29. THE TOXICITY ASSESSMENT
COMMONLY INVOLVES FOLLOWING
STEPS
• 1. Hazard identification
• 2. Dose-response assessment
• 3. Exposure assessment
• 4. Risk characterization

30. 1. HAZARD IDENTIFICATION
• It determines the exposure to chemical 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

31. 2. DOSE-RESPONSE ASSESSMENT
• Relationship between the exposure, appearance
and duration of adverse effect.
• 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.

32. 3. EXPOSURE ASSESSMENT
• • Exposed population (General public or selected
groups)
• • Types of substances (pharmaceuticals, chemicals or
environmental pollutants)
• • Single substance or mixture of substances
• • Duration of exposure
• • Pathways and media

33. 4. RISK CHARACTERIZATION
• • Review toxicity and exposure assessment output
• • Quantify risks
• • Combine risks across all pathways
• • Assess and present uncertainties
• • Consider site specific human studies

34. TOXICITY IS REFLECTED BY BROAD SPECTRUM
OF RESPONSES LIKE:
▫ Functional effects, such as immunological
responses
▫ Growth inhibition
▫ Reproductive impairment
▫ Increase in cancer incidence
▫ Mortality

35. 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.

36. IMPORTANCE OF TOXICITY TESTING
• • To have an idea of toxic doses of xenobiotic for certain
organisms
• • Evolution of safe doses of those 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.
• • Evolution and recommendation of maximum acceptable
daily intake.
• • Developing the air water quality.

37. PRIVATE AND PUBLIC SECTORS INVEST IN TOXICITY
TESTING THAT AIMS TO PROTECT HUMAN HEALTH
• They are:
• • Chemical Manufacturers
• • Pharmaceutical Industry
• • US Federal Agencies and Programs
• National Toxicology Program (NTP)
• Environmental Protection Agency (EPA)
• National Institute of Environmental Health Sciences
(NIEHS)
• Food and Drug Administration (FDA)
• •State and Local Governmental Bodies

38. •THANK YOU!!