A brief introduction about Animal models used in toxicological studies

1. ANIMAL MODELS IN
TOXICOLOGICAL STUDIES
PRESENTED BY
Dr. SINDHU. K
MVSc SCHOLAR,
DEPT OF VPT,
POOKODE, WAYANAD.

2. ANIMAL
(According to ANIMAL WELFARE ACT, USA )
• Animal is defined as any live or dead dog , cat , non human
primate , guinea pig , hamsters , rabbit or any other warm
blooded animal , which is being used or is intended for use
for research , teaching , experimentation , exhibition or as a
pet.

3. ANIMAL MODEL
• An animal model is defined as a specific combination of an animal species,
challenge agent and route of exposure that produces a disease process or
pathological condition that in multiple important aspects corresponds to the
human disease or condition of interest.
• In the context of animal model qualification, the model-defining natural
history studies are the animal studies that establish the ranges of values of
key parameters of the disease or condition that will be specified in the context
of use for the qualified model and that will be used as measures of quality
control and quality assurance when the model is replicated.

4. .

5. CLASSIFICATION OF ANIMAL MODELS
1. EXPERIMENTAL : A model in which an experimenting induced
conditions mimic a human disease
2. NEGATIVE : A model in which particular condition cant be produced , &
is therefore studied to better understand the reason for the protective or
resistant affects
3. SPONTANEOUS : A model in which the animal naturally develops a
disease or some other conditions of interest
4. ALTERNATIVE MODEL is defined as technique that reduces or
eliminates the need for live animals & there by prevents potential pain &
distress in animals

6. ‘
• Computer models and cell cultures
are good for screening and are used
frequently.
• Such models cannot replicate
complicated interactions in the
whole system.
• Final testing depends on studies in
animals; sometimes it is required by
law.
• Animal and non-animal models used
in conjunction achieve the best
answer.

7. WHAT IS ANIMAL TESTING?
• The term "animal testing" refers to procedures performed on living
animals for purposes of research into basic biology and diseases,
assessing the effectiveness of new medicinal products, and testing the
human health and/or environmental safety of consumer and industry
products such as cosmetics, household cleaners, food additives,
pharmaceuticals and industrial/agro-chemicals.
• All procedures, even those classified as “mild,” have the potential to cause
the animals physical as well as psychological distress and suffering.
• Often the procedures can cause a great deal of suffering. Most animals
are killed at the end of an experiment, but some may be re-used in
subsequent experiments.

8. CAN ANIMAL MODELS OF DISEASE RELIABLY
INFORM HUMAN STUDIES?
"The value of animal experiments for predicting the effectiveness
of treatment strategies in clinical trials has remained
controversial, mainly because of a recurrent failure of
interventions apparently promising in animal models to translate
to the clinic”

9. EVIDENCES
Polio
• Landsteiner and Popper proved it infectious; able to transmit disease to
monkeys.
• Salk and Sabin developed their vaccine through work with chickens and
monkeys.
Diabetes
• Banting and Best showed importance of insulin in dogs.

10. Infant Mortality
• Studies in sheep and lambs led to use of steroids in treatment of
respiratory distress syndrome (formerly hyaline membrane disease), a
major cause of death in premature infants.
• Advances in understanding and treatment of sudden infant death
syndrome (SIDS) came from studies in rats, mice, dogs, and sheep
Cystic Fibrosis
• A major killer of young adults.
• Mouse models led to understanding role of chloride channels.
• Genetic therapies on the horizon are an outgrowth of work in mice.

11. `
High Blood Pressure (HBP)
• Goldblatt linked HBP to kidney in rats, cats, and dogs; led to diuretics and
angiotensin converting enzyme inhibitors to treat high blood pressure.
• Cushing linked HBP to brain in dogs; led to understanding sympathetic
nervous system influence on blood pressure and drugs to treat it.
Obesity
• Major risk factor for diabetes mellitus, high blood pressure, heart attack,
stroke and certain cancers.
• Epidemic in the United States: 64% of adults are overweight and 25% are
obese.
• Mouse models and Zucker obese rats shedding new light on causes of
overeating, importance of leptin receptors, and ways that obesity leads to
disease.

12. `
Bioterrorism
• Smallpox vaccine from calves
• “Two animal rule” – FADA mandates that all vaccines must be tested for
efficacy and safety in two animals (typically rodent and non-human primate)
before introduction in humans
• Botulinum antitoxin tested in mice and non-human primates
AIDS
• Numerous animal models in studies to understand the disease and how it
attacks the immune system.
• Current anti-AIDS treatment developed in animal models have greatly
extended life expectancy and quality of life for AIDS victims.
• AIDS vaccines being developed in monkeys.

13. HISTORY
• The earliest references to animal testing are found in the writings
of the Greeks in the 2nd and 4th centuries BCE.
• Aristotle and Erasistratus were among the first to perform
experiments on living animals.
• Galen, a physician in 2nd-century Rome, dissected pigs and goats,
and is known as the "father of vivisection".
• An Experiment on a Bird in an Air Pump,
from 1768, by Joseph Wright

14. • In the 1880s, Louis Pasteur convincingly demonstrated the germ theory of medicine
by inducing anthrax in sheep.
• In the 1890s, Ivan Pavlov famously used dogs to describe classical conditioning.
• Insulin was first isolated from dogs in 1922, and revolutionized the treatment
of diabetes.
• On November 3, 1957, a Soviet dog, Laika, became the first of many animals to orbit
the earth.
• In the 1970s, antibiotic treatments and vaccines for leprosy were developed using
armadillos, then given to humans.
• The ability of humans to change the genetics of animals took a large step forwards
in 1974 when Rudolf Jaenisch was able to produce the first transgenic mammal, by
integrating DNA from the SV40 virus into the genome of mice.
• This genetic research progressed rapidly and, in 1996, Dolly the sheep was born, the
first mammal to be cloned from an adult cell.

15. CLAUDE BERNARD
REGARDED AS THE "PRINCE
OF VIVISECTORS",
ARGUED THAT EXPERIMENTS
ON ANIMALS ARE "ENTIRELY
CONCLUSIVE FOR THE
TOXICOLOGY AND HYGIENE
OF MAN"

16. `
• Claude Bernard—who is sometimes known as the "prince of
vivisectors" and the father of physiology, and whose wife, Marie Françoise
Martin, founded the first anti-vivisection society in France in 1883
• In 1822, the first animal protection law was enacted in the British
parliament, followed by the Cruelty to Animals Act (1876), the first law
specifically aimed at regulating animal testing. The legislation was
promoted by Charles Darwin
• Opposition to the use of animals in medical research first arose in the
United States during the 1860s, when Henry Bergh founded theAmerican
Society for the Prevention of Cruelty to Animals (ASPCA), with America's
first specifically anti-vivisection organization being the American
AntiVivisection Society (AAVS), founded in 1883

17. • Toxicology testing became important in the 20th century.
• In the 19th century, laws regulating drugs were more relaxed. For example,
in the U.S., the government could only ban a drug after a company had been
prosecuted for selling products that harmed customers.
• However, in response to the Elixir Sulfanilamide disaster of 1937 in which
the eponymous drug killed more than 100 users, the U.S. congress passed
laws that required safety testing of drugs on animals before they could be
marketed. Other countries enacted similar legislation.
• In the 1960s, in reaction to the Thalidomide tragedy, further laws were
passed requiring safety testing on pregnant animals before a drug can be sold

18. REGULATIONS
• Licensing
• Registration
• Research facilities
• Attending veterinarian & adequate veterinary care
• Identification of animals
• Records
• Compliance with standards & holding period

19. STANDARDS
• Specification for human handling care
• Treatment & transportation of experimental animals

20. INDIAN MEDICAL
ORGANIZATIONS
To ensure uniform quality of
clinical research by Good
Clinical Practices throughout
the country and to generate
data for registration of new
drugs before use in the Indian
population.

21. CSIR
• Council of Scientific and Industrial Research
• is an autonomous body and India's largest Research and
Development (R&D) organization.
CDRI
• Central Drug Research Institute
• CDRI is the laboratory functioning under the aegis of the council of
scientific and Industrial Research of India.
SAFETY &
CLINICAL
DEVELOPME
NT--
TOXICOLOGY
• Toxicology group is involved in profiling of candidate drugs
according to schedule Y guidelines. Systemic toxicology,
reproductive toxicology, genetic toxicity, immunotoxicity, local
toxicity and carcinogenicity are being done for NCEs.

22. INDIAN REGULATIONS
• The Government of India has authorized the National Accreditation
Board of Testing and Calibration Laboratories (NABL), promoted by the
Department of Science andTechnology, to provide accredition services to
laboratories covering a wide range of subjects including biological and
clinical laboratories.
• The NABL is a full member of the International Laboratory
Accreditation Cooperation and the Asia Pacific Laboratory Cooperation.
• Such accreditation of animal facilities would demonstrate their
commitment to responsible animal care and use and good science since
such an accreditation is an indicator of an institution’s ability to comply
with its assurances.

23. INDIAN NATIONAL SCIENCE ACADEMY
• This report was submitted by the Expert Committee Constituted by the Indian
National Science Academy, New Delhi
• The need to maintain the animals under standard animal husbandry
conditions, to handle them gently and humanely, and limit unnecessary usage
by strictly enforcing ethical considerations demands utmost attention.
• A Committee was constituted to consider the various issues involved in the
ethical use of Animal Experimentation, and the Committee besides other
recommendations updated “Guidelines”.
• Published by S. K. Sahni, Executive Secretary, Indian National Science
Academy, Bahadur Shah Zafar Marg, New Delhi 110 002 and printed at Bengal
Offset Works, 335, Khajoor Road,Karol Bagh, New Delhi 110005
Tel : 3524200, 3610455, 7774614

24. INSA GUIDELINES
• In India, the need to develop guidelines for the use of animals in research has
been discussed at various forums. Unfortunately no standard document was
available for reference till 1992 when the Indian National Science Academy
developed the guidelines for use of animals in scientific research. Considering
the knowledge generated internationally over the years and the guidelines of
WHO,NIH associated NRC, USA and European Union, the INSA guidelines
have been updated.
• The INSA guidelines are the only ones available at the National level and
adopted by well established institutions in India for care and use of their
laboratory animals

25. LEGAL PROVISION
• The Prevention of Cruelty to Animal Act of 1960 has provided the
constitution of a committee under the Animal Welfare Board to control and
supervise experiments on animals.
• It has also provided inspection of all animal holdings through designated
inspectors and the institutions not abiding by the standard requirements
can be prosecuted. The relevant sections of the act can be obtained in
Chapter IV
• THE PREVENTION OF CRUELTY TO ANIMALS ACT, 1960 (59 OF 1960)
As amended upto 30th July, 1982
CHAPTER IV
EXPERIMENTATION OF ANIMALS

26. EUROPE
• Experiments on vertebrate animals in the European
Union are subject to Directive 86/609/EEC on the protection
of Animals used for Experimental and other scientific
purposes, adopted in 1986
• In November 2010, "Directive 2010/63/EU on the protection of
animals used for scientific purposes", which updates and
replaces the 1986 Directive 86/609/EEC, was finalized and
came into force. Full implementation of the new EU directive
starts January 1, 2013

27. FRANCE
• In France, legislation (principally the decree of October 19,
1980) requires an institutional and project license before
testing on vertebrates is carried out. An institution must
submit details of their facilities and the reason for the
experiments, after which a five-year license may be granted
following an inspection of the premises. The project licensee
must be trained and educated to an appropriate level.
Personal licenses are not required for individuals working
under the supervision of a project license holder. These
regulations do not apply to research using invertebrates

28. UNITED KINGDOM
• The types of institutions conducting animal research in the UK
in 2004 were:
• universities (42.1%);
• commercial organizations (33.3%);
• non-profit organizations (4.9%);
• government departments (2.4%);
• National Health Service hospitals (0.9%);
• public health laboratories (0.6%);
• other public bodies (15.8%).

29. CONTD…,
• During 2002 House of Lords select committee inquiry into animal testing
in the UK, witnesses stated that the UK has the tightest regulatory system
in the world, and is the only country to require a cost-benefit assessment of
every licence application.There are 29 qualified inspectors covering 230
establishments, which are visited on average 11–12 times a year.
• A campaign document by Animal Aid alleges that the Animals (Scientific
Procedures) Act 1986 is a "vivisectors' charter," allowing researchers to do
as they please and making them practically immune from prosecution. The
document claims that licences to perform experiments are obtained on the
basis of a "nod of approval" from the Home Office Inspectorate, and that
the Home Office relies on the researchers' own opinions of the cost-benefit
assessment regarding the value of the experiment versus the amount of
suffering it will cause

30. GERMANY
• The German Animal Welfare Act is designed to enforce the
utilitarian principle that there must be good reason for one to
cause an animal harm and identifies that it is the
responsibility of human beings to protect the lives and well-
being of their fellow creatures. There are thirteen sections in
the Animal Welfare Act, each containing Articles that go into
detail of the specific sections.

31. JAPAN
• The system in Japan is one of self-regulation; there are no regulations
like Western countries, only the 3Rs principle are written into the Law
for Humane Treatment and Management of Animals.
• This law was amended in June 2005 and enforced in June 2006. The
Management of Animals is responsible for administering the newly
amended law.The amendment of this law was the conceptual idea of self-
regulation and not being restricted by legislative constraints, it was
approved by the members of the Japanese Diet who saw that care for
laboratory animals and the use of laboratory animals are two different
concepts that were concerned with science and animal welfare,
respectively.
• This law requires those using animals to follow the principles outlined
in the 3Rs

32. 3 R ` S

33. 3 R`S
• The 3Rs principle of animal experimentations was introduced to
the world by Russell and Burch in 1959.
• In terms of ethics in animal experimentation, it gave detailed
information on the guidelines that were formulated through the
concerns of the ministries and the Science Council of Japan.
• The 3Rs: Replacement, Reduction, and Refinement, which are
also known as "the standards relating to the care and
management of laboratory animals and relief of pain", are covered
in a detailed guideline based on the current law.

34. CHARACTERISTICS OF REGULATIONS ON
ANIMAL EXPERIMENTS IN JAPAN
• Laws specify the responsibility of the owner of the animal.
• Laws call for 3Rs emphasizing the alleviation of pain and
distress as well as humane death of animals used for scientific
purposes.
• Administrative guidance encourages the ethical use of animals.
• Self-regulation system similar to the US and Canada.
• Recommendation for designating Institutional Animal Care and
Use Committee (IACUC).
• Exemption from legal registration/inspection.

35. IACUC
• In 1985 the 3Rs were outlined into 11 principles by the Council of
International Organizations for Medical Sciences (CIOMS) which
have become the international standard to govern animal
experimentation.
• Japanese law is based on the idea of a self-regulation system for the
use of animals in laboratory experimentation.
• Due to this, notification only recommends designation of an
Institutional Animal Care and Use Committee (IACUC). Although
not required by law almost all pharmaceutical companies as well as
medical schools have established IACUCs; livestock and laboratory
animal facilities are exempt from registration with the IACUC and
legal inspection

36. UNITED STATES
• In the United States, animal testing on vertebrates is
primarily regulated by the Animal Welfare Act of
1966 (AWA), and the Animal Welfare Regulations which is
enforced by the Animal Care division of the Animal and Plant
Health Inspection Service (APHIS) of the United States
Department of Agriculture (USDA).
• The AWA contains provisions to ensure that individuals of
covered species used in research receive a certain standard of
care and treatment, provided that the standard of care and
treatment does not interfere with "the design, outlines, or
guidelines of actual research or experimentation

37. CANADA
The federal government does not have jurisdiction to pass laws that involve
experiments on animals. The provinces have jurisdiction concerning that area.
The federal government, however, is involved in three areas: the criminal law
power, the health power, and the spending power.
• The Criminal Code of Canada Section 446 and 447 of the Criminal Code
protect animals from cruelty, abuse and neglect. This section of the Criminal
Code has been under review for several years.
• The Health of Animals Act The Health of Animals Act (1990) and its
regulations are aimed primarily at protecting Canadian livestock from a
variety of infectious diseases that would threaten both the health of the
animals and people, and Canadian trade in livestock with other countries.
This act is used both to deal with named disease outbreaks in Canada, and
to prevent the entry of unacceptable diseases that do not exist in Canada.

38. CONTD
• The Spending Power : the imposition of CCAC standards on facilities
receiving funding from the Canadian Institutes of Health Research and
the Natural Sciences and Engineering Research Council. Where the
government itself awards a contract on an academic or non-academic
institution, clause A9015C of Public Works Standard Acquisition Clauses
and Conditions Manual imposes conditions related to the care and use of
experimental animals in public works and government services

39. AUSTRALIA
• In Australia, Animal Ethics Committees (AECs) determine whether the
use of an animal is valid or not. AECs must follow the Code in order to
ensure the wellbeing of the animals used for research. The Code
emphasizes the responsibilities of investigators, teachers and institutions
using animals to:
• ensure that the use of animals is justified, taking into consideration the
scientific or educational benefits and the potential effects on the welfare of
the animals
• The researchers must submit a written proposal to an AEC stating what
is to be accomplished, a defense for the study, and the ethical and
wellbeing of the animals used reflecting the 3Rs.

40. NEW ZEALAND
• New Zealand’s Animal Welfare Act 1999 requires owners and people in
charge of animals to ensure the physical, health and behavioural needs of
animals are met, and that pain and distress are alleviated.
• In New Zealand, as in many countries, laboratory animals (mainly
rodents) and farm animals (mainly cattle and sheep) are used in research,
testing and teaching – commonly referred to as RTT. Animal use in RTT is
strictly controlled under the Animal Welfare Act 1999 and organisations
using animals must follow an approved code of ethical conduct.
• The Ministry for Primary Industries (MPI) administers the Act and leads
animal welfare policy and practice in New Zealand. The National Animal
Ethics Advisory Committee (NAEAC) was established under the Animal
Welfare Act to provide independent advice to the Minister for Primary
Industries

41. BRAZIL
• The federal law for the scientific use of animals was passed in 2008. The
law established the National Council for the Control of Animal
Experimentation (CONCEA) and demanded that institutions create an
ethics committee on the use of animals.
• In 2009, Decree 6899/2009 defined CONCEA as the governing and
advisory body, under the Ministry of Science and Technology, to authorize
accreditation to registered institutions and to license those institutions to
use animals in research. The same decree also states that an electronic
database be developed to allow breeding and research facilities to register
in order to apply for CONCEA accreditation.
• Brazil also reinforces the 3Rs.

42. GUIDE FOR THE CARE & USE OF
LABORATORY ANIMALS
1) INSTITUTIONAL POLICIES
• Monitoring the care & use of animals
• Personal qualifications
• Personal hygiene
• Occupational health
• Experiments involving hazardous agents
• Special consideration

43. 2) LABORATORY ANIMAL HUSBANDRY
• Housing
• Animal environment
• Food , water & bedding
• Sanitation
• Identification & record keeping
• Emergency , weekend & holiday care

44. 3) VETERINARY CARE
• Preventative medicine
• Surveillance , diagnosis , treatment & control of diseases
• Anesthesia & analgesia
• Surgery & post surgical care
• Euthanasia

45. 4) PHYSICAL PLANTS
• Physical relationship of animal facilities to
laboratories
• Functional areas
• Construction guidelines
• Aseptic surgery

46. ANIMAL PAIN
• In accordance with the AWA
• guide for the care & use of laboratory animals
• public health service policy for the human care
• Use of laboratory animals
Veterinarians & investigators must identify , eliminate
sources of pain & distress , with the exception of those
procedures that are essential to research in question &
approved by the IACUC

47. .

48. TERMINOLOGIES
COMFORT
A state of physiological , psychological & behavioural
equilibrium in which an animal is accoustomed to its
environment & engages in normal activities – feeding ,
drinking , grooming , social interaction , sleeping waking
cycles & reproduction

49. .
WELL BEING
A positive mental state that reflects the level of welfare
& comfort of an animal

50. .
DISCOMFORT
A minimal change in an animal`s adaptive level or
baseline state as a result of changes in its environmental
or biological , physical , social or psychotic alterations
Physiological or behavioural changes that indicates a
state of stress might be observed , but are not marked
enough to indicate distress

51. .
STRESS
The effect produced by external events or internal factors
referred to as STRESSORS , which include an alteration in
an animal`s biological equilibrium
DISTRESS
An adverse state in which an animal is unable to adapt
completely to stressors & the resulting stress & shows
maladaptive behaviours

52. .
ANXIETY & FEAR
Emotional states that are traditionally associated with
stress. They can be adaptive in that they inhibit an
organisms actions that could lead to harm or cause it to
act in ways allowing it to escape from potentially
harmful situations

53. .
PAIN
Results from potential or acute tissue damage
Pain can be considered a potent source of stress , that is ,
A STRESSOR.it can also be considered a state of stress
itself & can lead to distress & malabsorptive behaviours

54. CRITERIA`S TO BE CONSIDERED FOR
SELECTION OF LIVE ANIMAL
EXPERIMENT
• Procedure should yield results beneficial to well being
• The species & no of animals should be appropriate for
experimental purpose
• The proposed procedures shouldn’t unnecessarily duplicate
previous experiment
• Appropriate analgesics , anesthetics & tranquilizing drugs
to be used to minimize pain & discomfort

55. • Methods of euthanasia
• The individuals performing the experimental procedure
& caring for the animals need to be properly trained
In general procedures that causes minimal pain or
discomfort to humans & place the animals in minimum
distress are considered ACCEPTABLE

56. ANIMAL NUTRITION
• All animals require regular amount of clean pure water & food
• Complete balanced diet or certified diets are preferred for
research purposes
• Most toxicological studies employ ad libitum feeding conditions
In which animals are allowed to regulate their own dietary
intake to meet energy requirements
• Ad libitum feeding for long term rodent bio-assay impacts
longevity , carcinogenesis & over all animal health

57. FOOD & WATER REQUIREMENTS
SPECIES DAILY FOOD REQUIREMENT DAILY WATER REQUIREMENT
Mouse 3 – 6 g 3 – 7 ml
Rat 10 – 20 g 20 – 30 ml
Hamster 7 – 15 g 7 – 15 ml
Guinea pig 20 – 30 g 12 15 ml / 100 g
Rabbits 75 – 100 g 80 – 100 ml / kg
Cat 100 – 225 g 100 – 200 ml
Dog 250 – 1200 g 100 – 400 ml / day
Primate 40 g / kg 350 – 1000 ml

58. FASTING
• Like humans , animals are often fasted in preparation for
blood collection
Non human primates , G pig : 18 – 24 hrs
Mice : 4 – 6 hrs

59. ANESTHESIA & ANALGESIA
• Investigators using live animals must employ appropriate
anesthetic , analgesic , sedative agents necessary to control
pain & distress , unless use of such agents would interfere
with specific objectives of the research
• Most of the PAIN RELIEVING AGENTS are controlled
substances & must be ensured that drug supplies are
adequately protected & inventoried in accordance with the
requirement of the statute

60. GENERAL PRINCIPLES REGARDING ANESTHESIA ,
ANALGESIA & TRANQUILIZATION
• The effect of technique on experimental objectives , including drug
interactions & interferences with test substances say competing
metabolic pathways
• The health of animal should be carefully evaluated before
instituting any tranquilizing procedure
• The specific drug selected selected should provide minimal level of
CNS depression necessary

61. STAGES OF ANESTHESIA
STAGE 1 ANESTHESIA
• Involuntary excitation
• Dilation of pupils
• Possible increased salivation
• Loss of consciousness
• Spontaneous voiding of urine & feces

62. 2) STAGE 2 ANESTHESIA
• BREATHING pattern becomes more rapid & shallow
• Orbital movement of eyes becomes apparent ( NYSTAGMUS )
3) STAGE 3 ANESTHESIA
• Referred to as surgical stage anesthesia & is sub divided into 4
different PLANES of progressively deeper unconsciousness
• Plane 2 is routinely used for minor surgery & for some major
surgical procedures

63. PLANE 1
• Muscle tone is decreased
• Pedal reflex disappears but Palpebral & corneal reflexes
remains unchanged
• Pulse rate & blood pressure are usually normal
PLANE 2
• Pupil constricts & palpebral reflex absent
• Laryngeal reflex diminishes
• Salivation stops
• Corneal reflex remains intact

64. PLANE 3
• Corneal reflex disappears completely
• Breathing becomes abdominal & slow
• Heart rate may decrease
PLANE 4
• Pupils dilate
• Thoracic breathing stops
• Death follows

65. COMMONLY USED ANESTHETIC & TRANQUILIZING
AGENTS IN ANIMAL MODEL STUDIES
• Atropine as pre anesthetic
• Acepromazine + ketamine
• Diazepam – schedule IV drug { Anticonvulsant properties }
• Narcotic agents : hypnotic & analgesic effects with resulting depression of
cardiovascular & thermoregulatory systems
Morphine , meperidine , etorphine , fentanyl
• Innovar – vet : narcotic analgesicfentanyl @ 0.4 mg / ml + tranquilizer
droperidol @ 20 mg / ml
• Ketamine : state of chemical restraint & anesthesia but reflex remains
constant. Wide margin of safety, short duration with recovery, minimal
adverse effects

66. ,
• Pentobarbital , thiamylal & cholarlhudrate others with small
margin of safety
INHALANT ANESTHETICS
• DIETHYL ETHER : Although it provides good analgesia & muscle
relaxation , vapors irritate the respiratory mucosa
extremely flammable & explosive
• HALOTHANE : highly volatile requires a vapourizer to produce
precise concentrations

67. `• METHOXY FLURANE : non explosive inhalant , low volatility
produces good analgesia & muscle relaxation
• ISOFLURANE : non flammable , non explosive general inhalant
anesthetic agent
• NITROUS OXIDE : potent inhalant anesthetic , nonirritating , non
explosive , often used in conjunction with other agents
CONTRAINDICATIONS
Mouse : chloroform
Cats : morphine
G pigs : innovar – vet i/m inj
Rats : methoxyflurane

68. EUTHANASIA
• Methods of euthanizing laboratory animals are chosen to induce rapid
unconsciousness and humane death without pain or distress.
• The methods that are preferred are those published by councils of
veterinarians.
• The animal can be made to inhale a gas, such as carbon
monoxide and carbon dioxide, by being placed in a chamber, or by use of a
face mask, with or without prior sedation or anesthesia

69. • PHYSICAL EUTHANASIA : cervical dislocation & decapitation
recommended only when scientifically justified
Cervical dislocation is considered humane for poultry , mice , rats
weighing less than 200 g & rabbit weighing less than 1 kg
• VERIFICATION OF DEATH : irregardless of specific
euthanasia methods used , it is imperative that death be
verified by examining the animal for cessation of vital signs

70. .

71. REFERENCES
• CRC handbook on toxicology
• Wikipedia : animal models
• Google images

72. THANK
YOU