Good Laboratory practices - Toxicology Lab.pdf

GLP

1. GLP PRESENTATION
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Group Members:-
Kanwal Zeb
Bakhtawar Amjad
Aleena Khan
Zainab Kalsoom
Sania Shafique
Sundas Azad

2. Toxicology Lab

3. Introduction:-
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Generally toxicity testing referred to a series of toxicity testing
required by International regulation for compliance to Good
Laboratory Practices (GLP) for proof of safety in experimental
animal prior to their testing to human.
It comprises of:-
Acute
Sub-acute
Chronic toxicity.

4. Continued..
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These studies are conducted based on ‘OECD guidelines of
testing of chemicals’
International regulations relating to human health requires that
all pharmaceuticals drugs undergo preclinical investigation.
One of the phases of the preclinical investigation is the
toxicology studies.
It is conducted following an appropriate guideline and quality
system (OECD GLP).

5. Toxicology is the science
that dealing with action,
toxicity, fatal dose, detection
of, interpretation of the
result of the toxicology
analysis and treatment of
poison.

6. History of Toxicology
Studies:-
Paracelsus ( Father of Toxicology) determined
specific chemicals responsible for the toxicity of
plants and animals (dose-response relation).



“All substances are poisons; there is none which is
not a poison. The right dose differentiates a poison
and a remedy”
-Paracelsus

7. History:-
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Mathie Orfilia, determined the
relationship between poisons and
their biological factors.

He is referred to as the Father of
Modern Toxicology.

8. Basic Principle:-
The goal of toxicity assessment is to iden?fy adverse effects of a
substance. Adverse effects depend on two main factors:
i) routes of exposure (oral, inhala?on, or dermal)
and
ii) dose (dura?on and concentra?on of exposure). To explore dose,
substances are tested in both acute and chronic models. Generally,
different sets of experiments are conducted to determine whether a
substance causes cancer and to examine other forms of toxicity

9. Toxicology Screening:-
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Toxicology screening is very
important for the development
of new drugs and for the
extension of therapeu?c
poten?al of exis?ng molecules.
The US-FDA states that it is
essen?al to screen new
molecules for pharmacological
ac?vity and toxicity poten?al in
animals.
Toxicology tests are mostly used
to examine specific adverse
events or specific end points
such as cancer, cardiotoxicity. It
helps calculate the No Observed
Effect Level (NOAEL) dose and is
helpful for clinical traits.

10. Toxicologist as a profession:-
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A toxicologist is a scientist or medical personnel who specializes in the study
of symptoms, mechanisms, treatments and detection of venoms and toxins;
especially the poisoning of people.
Requirements:-
To work as a toxicologist one should obtain a degree in toxicology or a
related degree like biology,, chemistry, pharmacology or biochemistry.
Bachelor's degree programs in toxicology cover the chemical makeup of
toxins and their effects on biochemistry, physiology and ecology. After
introductory life science courses are complete, students typically enroll in
labs and apply toxicology principles to research and other studies. Advanced
students delve into specific sectors, like the pharmaceutical industry or law
enforcement, which apply methods of toxicology in their work.

11. Duties:-
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Toxicologists perform many different du?es including research in the academic, nonprofit and
industrial fields, product safety evalua?on, consul?ng, public service and legal regula?on.
In order to research and assess the effects of chemicals, toxicologists perform carefully
designed studies and experiments. These experiments help iden?fy the specific amount of a
chemical that may cause harm and poten?al risks of being near or using products that
contain certain chemicals.
Research projects may range from assessing the effects of toxic pollutants on the
environment to evalua?ng how the human immune system responds to chemical
compounds within pharmaceu?cal drugs. While the basic du?es of toxicologists are to
determine the effects of chemicals on organisms and their surroundings, specific job du?es
may vary based on industry and employment. For example, forensic toxicologists may look
for toxic substances in a crime scene, whereas aqua?c toxicologists may analyze the toxicity
level of water bodies.

12. Sources of Toxic Substances:-
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Classified based on their
chemical nature
mode of action.
exposure class ( food, air, water or soil) or Use class ( drugs as
drugs of abuse, therapeutic drugs, agriculture chemicals,
pesticides , plants toxins, food additives and cosmetics.

13. Biomedical Ethics:-
•Before conducting any
toxicology testing in animals
or collecting tissues/cell lines
from animals, the study should
be approved by IAEC or the
protocol should satisfy the
guidelines of the local
governing body.

14. Toxicity Testing Methods:-
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Acute toxicity testing.
Sub-chronic toxicity testing.
(repeated dose=/> 90 day)
Chronic toxicity testing
(repeated dose <90day)

15. Acute toxicity studies:-
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Acute toxicity testing study the effect of a single dose on a particular
animal species.
Acute toxicity testing be carried out with two different animal
species( one rodent and one non-rodent)
In acute toxicology testing, the investigation product is administered
at different dose levels, and the effect is observed for 14 days.
All mortalities caused by the investigational product during the
experimental period are recorded and morphological, biochemical,
pathological, and histological changes in the dead animals are
investigated.

16. Sub-acute toxicity studies:-
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Rodents and non-rodents are used to study the sub-acute
toxicity of substance.

This lab testing is used to determine maximum tolerable dose
and nature of toxicity.

17. Chronic toxicity studies:-
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Chronic toxicity studies are conducted with minimum of one
rodent and one non rodent species.
A chronic toxicology studies provide inferences about the long
term effect of test substance in animals, and it may be
extrapolated to the human safety of test substance.
The test compound is administered over more than 90 days,
and the animals are observed periodically.

18. Laboratory of Toxicology:-
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It mainly involve the following activities:
scientific research
public services(primarily forensic toxicology)
education

19. Objectives of Toxicology Lab

20. Key Goal:-
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Conducted for public health to identify the virtually safe dose,
provides the foundation for the field of risk assessment for
chemical hazards.

21. Objective 1:-
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To point out the difference between dose and effect.
For every substance there is a dose below which no effect occurs and
another above which poisoning occurs. Thus all the substances and
poten?ally safe or poisonous.
This depends only on dose.

22. Objective 2:-
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To point out that natural substances may be highly poisonous
and man made substances may be of low toxicity.

For example Clostridium botulinum toxin is poisonous at very
low dose but synthesized Sorbitol has a very low toxicity.

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To explain fundamentals ideas in toxicology clearly so that
students can understand the hazards and risks associated with
chemicals.
To have an idea of toxic doses of xenobiotics for certain
organisms.
Fixation of sub lethal dose for long term toxicity test.
Evaluation of safe doses of those toxicants for certain organisms.
Recommendation of maximum permissible limits of those
substances on the ambient air and drinking water.

24. Main focus:-
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Toxicologists mainly focus to get the following important
information about toxins:
Detection of toxin
Occurrence of toxin
Properties of toxin
Effects of toxin
Treatment
Toxin regulation.

25. Working of toxicology lab

26. Working Mechanism:-
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Delivery: site of exposure to the target.
Reaction of ultimate toxicant with the target molecule.
Cellular dysfunction and resultant toxicity.
Repair or disrepair.

29. How and where the Analysis is performed?
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Forensic toxicologist employ a large number of analytical
techniques to determine the drugs or poisons relevant to a case
investigation, the capacity of a lab to conduct routine analysis
will vary dependent upon equipment, technical capability and
analyst experience.

30. How the evidence is collected?
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Specimens sent for toxicology testing are usually collected by
the forensic pathologist.
Specimens must be clearly identified, labelled and sealed as
soon as practicable after collection.
Blood, urine, liver are the specimens often used for detecting,
quantifying and interpreting drugs and other toxicants.

31. Testing:-
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Testing of biological fluids and tissues for durgs and other
substances is a complex process requiring sophisticated
instrumentation and specially trained analysis.

In the typical autopsy fluids and tissue samples are collected
specifically for toxicology testing and a series of tests will be
conducted.

32. Types of toxicology:
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There are various types of toxicology as outlined below:
Analy?cal toxicology
Applied toxicology
Clinical toxicology
Veterinary toxicology
Forensic toxicology
Environment toxicology
Industrial toxicology

33. Analytical toxicology:
•It is the branch of toxicology which deals with the study
of detec?on and assay of poisonous chemicals including
their metabolites that could affect the biological system.

34. Applied toxicology:
•It is the applica?on of new and modern methods or
technologies for early detec?on of toxicants in the field
se?ng or prac?ce area.

35. Clinical toxicology:
•It is mainly involved in the study of diagnosis and treatment of
poisoning that can occurrin humans.

36. 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.

37. Environmental toxicology:
•It is the branch of toxicology in which study of presence
of different toxicants including their metabolites and
degrada?on products in the environment and their
effects on humans and animals.

38. Industrial toxicology:
•It is the study of selec?ve and specific are of environmental
toxicology.

39. QUALITY ASSURANCE
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Toxicity tes?ng laboratories can employ quality management
systems to help meet test acceptability requirements and
ensure quality results. Cri?cal components of quality
management systems for tes?ng programs include:
emphasis on analyst training, par?cularly with regard to culture
and maintenance of test organisms
maintenance of standardized opera?ng procedures

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maintenance of method-required environmental condi?ons
use of standard reference toxicants
tes?ng mul?ple control or reference samples with each batch
of toxicity tests
keeping detailed records
performing appropriate sta?s?cal analyses
rou?ne laboratory audits

41. •Environmental Standards provides a corporate liability
overview by documen?ng the defensibility of the
quality assurance and quality control in your in-house or
contracted toxicity tes?ng laboratories. We shield our
clients from undue exposure to liability from the use of
poor quality data

42. Technical Testing Specifications
•Quality Assurance professionals can prepare comprehensive
technical specifica?ons covering QA/QC measures to be
followed by contracted toxicity tes?ng laboratories. We employ
our exper?se in specifying metrics that must be achieved when
tes?ng client samples using EPA, ASTM or other published
toxicity test methods.

43. Risks of toxicology labs
•Working as a toxicologist entails some risk. Although modern
toxicology labs are typically equipped with all the latest safety
equipment, and toxicologists are extremely careful to follow
good laboratory prac?ce, accidents do happen and people get
hurt. Although workplace accident sta?s?cs are not broken
down for toxicologists, they certainly have greater risks than the
average lab worker given they work almost exclusively with toxic
substances.

44. Long Hours in a Lab
•Most toxicologists spend long hours working in a lab,
some?mes five days or more a week. The daily rou?ne of lab
research and analyzing the results can become stul?fying
over ?me, so it is important for toxicologists and other lab
researchers to take regular breaks and stay ac?ve in their
lives outside of the lab. Back and eye strain can also become
issues with long hours using lab equipment and staring at a
computer monitor.