Basic of toxicology and regulatory guidelines for toxicity. MPHRAM, 2ND SEM, UNIT 1

1. Basic of toxicology and regulatory
guidelines for toxicity
studies(OECD, ICH)
INSTITUTE OF PHARMACEUTICAL SCIENCES
KURUKSHETRA UNIVERSITY, HARYANA
Submitted to-
Prabjeet ma’am
Submitted by –
Arshi khanam
M.Pharm
pharmacology(2nd sem)

2. What is toxicology
 the study of the of the adverse effects of chemical or
physical agents on living organisms.
 Toxicology is a field of science that helps us
understand the harmful effects that chemicals,
substances, or situations, can have on people,
animals, and the environment. Some refer to
toxicology as the “Science of Safety” because as a
field it has evolved from a science focused on
studying poisons and adverse effects of chemical
exposures, to a science devoted to studying safety.

3. Why toxicology is important?
 It provides protection to human and environment
from toxic effects of toxicants.
 Toxicity study will ultimately lead towards the
development of newer, innovative and more safe
selective drug therapies to treat different disease
such as cancer drugs with reduced side effects.
 Safest drug in trails
 Animals are also protected somehow.

4. Basic terms in toxicology
 Toxin: A harmful substance produced within living
cells or organisms.
 Toxicants: any chemical that can injure or kill
human, animals or plants.
 Poison: substance that can cause immediate death
or illness when introduced in small quantity.

5. History of toxicology
 Humans have long history of using poisons. Some of
the well known toxicants were hemlock used for
punishment, aconite used for the arrow poisons.
 Paracelsus(1500AD) stated that “all substances are
poisons”, it is the dose that make them poison.
 Orfila(1800AD) referred as the founder of the
toxicology, Because it was the one who created a
systemic correlation between the chemical and
biological properties of poison.

6. Types of toxicants
1. Systemic toxin: it is the one that affect the entire
body or many organs rather than a specific site.
2. Organ toxin: it is the one that affects only specific
tissues or organ.
 Toxicants could be –
• Chemical( e.g. Cyanide)
• Biological(e.g. Snake venom)
• Physical (e.g. Radiation)

7. Routes of exposure to toxicity
 Ocular
 Ingestion
 Lung
 Skin
 Parenteral
 Mucous membrane
 Environmental circumstances

8. Types of toxicology
1. General type toxicology
2. Mechanistic type toxicology
3. Descriptive type toxicology
4. Regulatory type toxicology

9. Other types of toxicities
 Acute toxicity : It refers to those adverse effects
occurring following oral or dermal administration of a
single dose of a substance, or multiple doses given within
24 hours, or an inhalation exposure of 4 hours.
 Sub acute Toxicity: It resembles acute toxicity except
that the exposure duration is greater, from several days
to one month.
 Sub chronic toxicity: It is the toxic exposures repeated
or spread over an intermediate time range (1 – 3 months)
 Chronic Toxicity: It is the exposures (either repeated
or continuous) over a long (greater than 3 months)
period of time.

10. 1. General types of toxicity
I. Analytical toxicology
II. Applied toxicology
III. Clinical toxicology
IV. Forensic toxicology
V. Environment toxicology
VI. Industrial toxicology
VII. Reproductive and developmental toxicology
VIII.Immune toxicology

11. 1. Analytical toxicology: 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.
2. 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.

12. 3. Clinical toxicology: It is mainly involved in the
study of diagnosis and treatment of poisoning that
can occur in humans
4. Veterinary toxicology: 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.

13. 5. Environmental toxicology: The study of
presence of different toxicants including their
metabolites and degradation products in the
environment and their effects on humans and
animals
6. Industrial toxicology: It is the study of selective
and specific are of environmental toxicology.

14. 7. Immuno toxicology: It deals with the effect of
toxicant on immune system.
8. Reproductive and developmental
toxicology: It focus on the effect of chemicals or
toxins on the reproductive system and the
developing embryo.

15. 2.Mechanistic toxicology
 The study of how chemical or physical agents
interact with living organisms to cause toxicity.
 Aim of mechanistic toxicology is to identify that how
xenobiotic enter an organism and how these are
distributed metabolize in the body.
 Knowledge of the mechanism of toxicity of a
substance enhances the ability to prevent toxicity
and design more desirable chemical .

16.  Mechanistic understanding helps the governmental
regulator to establish legally 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.

17.  Two important concept of mechanistic toxicology-
1. Toxicodynamics refers to the molecular,
biochemical, and physiological effects of toxicants
or their metabolites in biological systems.
2. Toxicokinetics is the quantitation of the time
course of toxicants in the body during the processes
of absorption, distribution, biotransformation, and
excretion or clearance of toxicants.

18. Mechanism of toxicity

19. Understanding of this mechanism will help
investigator in-
 Extrapolate data better
 Improve risk assessment of potentially toxic
chemicals for human safety, and also for pollutants,
chemicals in the workplace.
 Improve risk assessment for synthetic and naturally
occurring hazardous compounds in food and water.

20. 3. 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.

21.  The toxicity assessment commonly involves
following steps-
1. Hazard identification
2. Dose response assessment
3. Exposure assessment
4. Risk characterization

22. 4. Regulatory toxicity
 It deals with the relationship between the discipline of
toxicology and regulatory institutions.
 The regulatory authorities have to protect the health of
humans which relies on toxicological principal and
toxicity evaluation data to formulate a decision.
 The authority has to take a decision on Acceptable Daily
Intake (ADI) of a chemical so that quantity of that
chemical exposure is adjusted safe in terms of health.
 The authority also have the power to formulate some law
or regulatory roles and to implement them rigidly.

23.  Principle of toxicology says no chemical is safe all
chemicals are potentially toxic depending upon their
exposure, concentration , time, frequency and
nature.
 Regulators formulate the threshold doses to reduce
exposure concentration so that risks can be
minimized to highest level.

24. Regulatory authorities
 WHO- World heath organization
 ICH- international conference on harmonization
 EPA- Environmental Protection Agency
 OECD- Organization for Economic Co-operation
and Development
 FDA- The Food and Drug Administration

25. Importance of toxicology study
 The data on acute toxicity test for various chemicals
against various organisms may be valuable in following
ways:
 To have an idea of toxic doses of xenobiotic for certain
organisms.
 Fixation of sub lethal doses for long term toxicity test.
 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.