Introduction of Toxicology, General Toxicology, Types of Toxicology, OECD Guidelines NO: 401,420,423,425

1. TOXICOLOGY
Presented By:-
Ms. Sayali S. Chavan
1ST Year M.Pharmacy
PDEA’S SGRS College of
Pharmacy.
Guided By:-
Mrs. Jagtap P.N
HOD of Pharmacology.
PDEA’S SGRS College of
Pharmacy.
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2. 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.
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3. 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.
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4. Types Of Toxicology:-
General
Toxicology
Mechanistic
Toxicology
Regulatory
Toxicology
Descriptive
Toxicology
Toxicology
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5. General Toxicology:-
 It includes:
Analytical toxicology
Applied toxicology
Clinical toxicology
Veterinary toxicology
Forensic toxicology
Environment toxicology
Industrial toxicology
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6.  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.
 Clinical toxicology:
It is mainly involved in the study of diagnosis and treatment
of poisoning that can occur in humans.
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7.  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.
 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.
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8. 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.
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9. 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.
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10. OECD Guidelines:-
 The mission of Organisation for Economic Co-operation and
Development is to promote policies that will improve the economic
and social well-being of people around the world.
 work with governments to understand what drives economic, social
and environmental change.
 Set international standards on a wide range of things, from
agriculture and tax to the safety of the chemicals.
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11.  Acute Oral Toxicity:
Test
Guidelines
No.
401
423
425
420
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12. Acute Toxicity Symptoms:-
 Tremor
 Salivation
 Muscle spasm
 Convulsion
 Lacrimation
 Weight loss
 Diarrhoea
 Altered Respiration
 Loss of righting reflex
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13. What Is LD50?
 LD50 represents the individual dose required to kill 50 percent of a
population of test animals. It is an index determination of medicine
and poison’s virulence. lower the LD50 dose, the more toxic the
pesticide.
What Is LC50?
 The concentrations of the chemical in air that kills 50% of the
test animals during the observation period is the LC50 value.
Other durations of exposure (versus the traditional 4 hours)
may apply depending on specific laws.
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14. Design of Oral Acute Toxicity
Test:-
 14 days study.
 Study on at least two species.
 One rodent –mice/rat.
 One non rodent –usually rabbit.
 Dose administered orally & parenterally.
 Various dose levels to groups of both sexes.
 Dose selection such that causing less than50% but not 0% and more
than 50% but not 100% mortality.
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15. OECD Guideline no. 401:-
 In a study of toxic characteristics of substance, acute oral toxicity
testing is initial step.
 Gives information on health hazards.
 Test substance administered orally, in graduated doses to several
groups of experimental animals.
 One dose used per group.
 At least 5 rodents at each dose level of same sex are used.
 Observations for effects & death are made.
 After completion of study in one sex, study in another sex is carried
out.
 Studies suggested in rodents but can be adopted for studies in non-
rodents
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16. OECD Guideline no. 420:-
 New approach in 1984 by British toxicology society.
 based on administration of series of fixed dose levels.
 Instead of death, clear signs of toxicity to animals as end point.
 Adopted as 1st alternative to conventional acute toxicity test.
 Testing in 1 sex usually females is considered sufficient.
 Reproducible procedure.
 Causes less suffering to the animals.
 Uses only moderately toxic doses, doses expected to be lethal
should be avoided.
 Uses fewer animal
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17. OECD Guideline no. 423:-
 No sighting study.
 3 animals of single sex per step.
 On avg. 2-4 steps may be necessary to allow judgment on the acute
toxicity of the test substance.
 Not intended to allow the calculation of precise LD50.
 Death of a proportion of animals as the major end point (response).
 LD50 cut off values are indicated.
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18. OECD Guideline no. 425:-
 Up and down testing approach was 1st described by Dixon and
Mood.
 Bruce in 1985 proposed to use it for acute toxicity determination of
chemicals.
 Estimates confidence intervals for LD50.
 In procedure (main test) 1-animal dosed at a time, at minimum of
48 hrs interval.
 Suggested starting dose is 175 mg/kg or can be selected from 1.75,
5.5, 17.5, 55, 175, 550, 2000, 3000, 5000mg/kg
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19.  Animal receives 1st dose a step below the level of the best estimate
of LD50.
 Depending upon the outcome for the previous.
 animal, the dose for the next animal is adjusted up or down.
 5 reversal in 6 consecutive animals when obtained test is
terminated.
 No. of animals limited to 15.
 Report.
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20. Some alternatives to use of
animals in testing:-
 In vitro (test tube) test methods and models based on human cell
and tissue cultures.
 Computerized patient-drug databases and virtual drug trials.
 computer models and simulations.
 stem cell and genetic testing methods.
 non-invasive imaging techniques such as MRIs and CT Scans.
 Microdosing (in which humans are given very low quantities of a
drug to test the effects on the body on the cellular level, without
affecting the whole body system).
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21. References:-
 www.slideshare.com, ppt on OECD guidelines for toxicity study, by
Jasdeep Singh.
 www.slideshare.com, ppt on Introduction to Toxicology, by Dr.
Badar Uddin Umar.
 www.slideshare.com, ppt on OECD guidelines, by Gandhi Sanket.
 www.slideshare.com, ppt on Toxicology and its types, by Kashikant
Yadav.
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