This document provides an overview of toxicology and its various branches. It defines key terms like toxicants, toxicity, acute toxicity, chronic toxicity, dose, etc. It describes the different types of toxicology like general toxicology, mechanistic toxicology, descriptive toxicology, and regulatory toxicology. For each type, it provides examples and explains their purpose and importance. It also discusses the importance of guidelines in regulatory toxicity studies for ensuring safety, efficacy and quality of medicines.

1. Pharmacological And Toxicological Screening
Methods - II
Name :- Chetana Pandurang Dakhare
Roll No:- 01 Semester II (1st year)
M.Pharm (Pharmacology)

2. Introduction :
The study of how natural or man-made poisons cause adverse effects
in living organisms is called as Toxicology.
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”.
In short “The dose makes the poison”
Mathieu Orfila is considered the modern “Father of Toxicology”.

3. Q. Write the Basic
definitions and Types
of toxicology ?

4. Basic Definitions :
 Toxin: Toxic substance that are produced naturally (Nature origin)
Toxicants : Any chemical that can injure or kill humans, animals or plants
(Poison)
A toxicant is any substance that has the potential to cause harm to living
organisms. This can include chemicals, physical agents (such as radiation), or
biological agents (such as viruses or bacteria).
Toxicity : Describes the degree to which a substance is poisonous or can cause
injury.
Toxicity is the degree to which a toxicant can cause harm to living organisms. The
toxicity of a substance depends on factors such as its chemical structure, the
route of exposure, and the susceptibility of the organism.

5.  Acute toxicity: Acute toxicity refers to the toxic effects of a substance that occur
shortly after a single exposure. The severity of acute toxicity can range from mild
to severe and can be life-threatening in some cases.
Chronic toxicity: Chronic toxicity refers to the toxic effects of a substance that
occur after repeated or prolonged exposure over a period of time. Chronic
toxicity can lead to long-term health effects, such as cancer, organ damage, or
developmental abnormalities.
Ecotoxicology: Ecotoxicology is the study of the effects of toxicants on the
environment and non-human organisms. It involves the assessment of the impact
of toxicants on ecosystems, including the effects on biodiversity and the food
chain.
Dose: The dose is the amount of a toxicant to which an organism is exposed. The
severity of the toxic effects of a substance depends on the dose and duration of
exposure.

6. Toxicology
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.

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
disease such as cancer having reduced toxic potential to human body.

8. 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.

9. Types of Toxicology
General toxicology
Mechanistic toxicology
Descriptive toxicology
Regulatory toxicology

10. General toxicology
General toxicology focuses on understanding the adverse effects
of chemicals and other substances on living organisms. This
includes evaluating the dose-response relationship, identifying
the target organs or systems affected, and determining the
potential health risks associated with exposure to these
substances.

11. Types of General Toxicology :
Analytical toxicology
Applied toxicology
Clinical toxicology
Veterinary toxicology
Forensic toxicology
Environment toxicology
Industrial toxicology

12. Analytical toxicology: Analytical toxicology is the study of the
detection and quantification of toxic substances in biological and
environmental samples.
It involves the use of analytical techniques such as chromatography and
spectrometry to identify and measure toxicants.
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.
Clinical toxicology : It is mainly involved in the study of diagnosis and
treatment of poisoning that can occurs in humans.

13. 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, etc.
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: Industrial toxicology is the study of the effects
of toxic substances in the workplace. It involves the identification and
evaluation of potential hazards, and the development of strategies to
prevent occupational exposures to toxic chemicals.

14. 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.

15. IT ADDRESSES A NUMBER OF FUNDAMENTAL
QUESTIONS.
How do xenobiotics enter an organism and how are theydistributed 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?

16.  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.

17. 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.

18. 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 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.

20. 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.

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

22. 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

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
INREGULATORY 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 authoritiespromote the sound
management of chemicals at national and international level.
They are :
 ICH
WHO
FDA
OECD

25. 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.

26. IMPORTANCE OF GUIDELINES INREGULATORY 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

27.  PRIVATE AND PUBLIC SECTORS INVEST IN TOXICITYTESTING
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

28. Q. What is schedule Y ?

29. Schedule Y :
Schedule Y is a part of the Drugs and Cosmetics Act, 1940, and its purpose
is to provide guidelines for conducting clinical trials for drugs and
pharmaceuticals in India.
It contains the requirements and procedures for conducting clinical trials,
including the approval process, ethical considerations, and responsibilities
of various stakeholders.
Here is a detailed overview of Schedule Y:
General Requirements:
Schedule Y lays down general requirements for conducting clinical trials,
which includes the following:
The clinical trial should be conducted as per Good Clinical Practice (GCP)
guidelines. The protocol for the clinical trial should be approved by the
Ethics Committee (EC) and the Drugs Controller General of India (DCGI).

30. The sponsor should obtain written informed consent from the study
participants before enrolling them in the trial.
The clinical trial should be conducted in accordance with the relevant
guidelines issued by the regulatory authority.
Responsibilities of Sponsors : Schedule Y outlines the responsibilities of
sponsors who initiate and fund the clinical trial.
 Some of the key responsibilities include:
Providing adequate funds for conducting the clinical trial.
Appointing a qualified investigator to conduct the clinical trial.
Providing the necessary information and documentation to the regulatory
authority.
Ensuring that the clinical trial is conducted as per GCP guidelines and the
approved protocol.
Monitoring the clinical trial to ensure that it is conducted in accordance
with the approved protocol.

31. Responsibilities of Investigators:
Investigators play a crucial role in conducting clinical trials. Schedule Y
outlines their responsibilities, which include:
Ensuring that the clinical trial is conducted in accordance with the
approved protocol.
Obtaining informed consent from study participants.
Ensuring the safety of study participants.
Reporting adverse events to the sponsor and regulatory authority.
Maintaining accurate and complete records of the clinical trial.
Ethics Committee (EC):Schedule Y mandates the formation of an EC to
review and approve the clinical trial protocol. The EC plays a critical role in
ensuring that the trial is conducted in an ethical and safe manner.
The responsibilities of the EC include : Reviewing the clinical trial protocol
to ensure that it is scientifically valid and ethically sound.

32. Reviewing the informed consent form to ensure that it is clear and
understandable.
Monitoring the clinical trial to ensure that it is conducted in accordance with
the approved protocol.
Reviewing and approving any changes to the clinical trial protocol.Approval
Process:
Schedule Y lays down the approval process for conducting clinical trials in
India.
The approval process involves the following steps:
Submission of the clinical trial protocol to the regulatory authority and the EC.
Review of the protocol by the EC and regulatory authority.
Approval of the protocol by the EC and regulatory authority.
Submission of the approval letter to the regulatory authority for obtaining
permission to conduct the clinical trial.

33. Clinical Trial Phases:
Schedule Y also outlines the various phases of clinical trials, which include:
Phase I: This phase involves the initial testing of the drug in a small group
of healthy volunteers to determine the safety profile and dosage range.
Phase II: This phase involves testing the drug in a larger group of
participants to determine its effectiveness and side effects.
Phase III: This phase involves testing the drug in a large group of
participants to confirm its effectiveness, monitor side effects, and compare
it with existing treatments.
Phase IV: This phase involves post-marketing surveillance to monitor the
long-term safety and effectiveness of the drug.
In conclusion, Schedule Y provides comprehensive guidelines for
conducting clinical trials in India. It ensures that the clinical trials are
conducted in an ethical and safe manner, and that the data generated from
these trials is reliable and scientifically valid.

34. THANK YOU
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