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ALTERNATIVES TO ANIMAL MODELS

BY:

N.HARISH

RT/2014/604

GUIDED BY:

Dr.Chandraiah Godugu

15/04/2023

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CONTENT

Introduction

ICCVAM

Models

Role of models

Benefits

LimitationsConclusion

References

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Introduction

• “ The best test species for humans are humans. It is not possible to extrapolate animal data directly to humans due to interspecies variation in anatomy, physiology and biochemistry.”

To predict:

• Toxicity

• Corrosivity

• Effectiveness of a new product for humans

• Consumer products

• Medical devices involved the use of animals

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Cont..

• Industrial goal involves refinement of testing to reduce suffering of

animals.

• Experiments on animals are cruel, expensive, and generally

inapplicable to humans.

• Need of development of method to replace animals

• This include sophisticated tests using human cells and other

techniques.

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ICCVAM&iceatm

For need of Alternatives U.S Govt.in 1993

NIH re authorisation

Act

Hoc committee-ICCVAM

Perminant in 2000Comp.15 U.S federal

&Regulatory agencies

Intergency Center for evaluation of Alternative

Toxicological Methds ( ICEATM)

National toxicological

program

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ICCVAM and ICEATM Goals

• To promote the scientific validation and regulatory acceptance of new

alternative test methods

• More predictive of human health and ecological effects than current

methods refine, reduce, and replace animal use where scientifically

feasible.

• To contribute to improved public health

Þ Improved risk assessments

Þ Improved risk management

Þ Prevention of injury and disease

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ALTERNATIVE MODELS

• Cell cultures

• Human tissues

• In-chemico testing

• Organ on a chip

• Computer Models

• Micro dosing

• Volunteer studies

• Population research

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Cell cultures

• Almost every type of human and animal cell can be grown in culture Central to key research into

• Cancers

• Sepsis

• Kidney disease and AIDS

• Vaccine production and drug development.

Development of 3D structures –Providing more realistic cell models on which to test potential therapies.

• Already used to grow pea-sized structures that closely resemble the human brain and 3D models of human tumours.

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CONT..

 Embryonic Stem Cell Test (EST) 

• Technique used to find out if a chemical or drug may harm the developing

foetus.

• Replaces pregnant rats and rabbits animal test by mouse stem cell cultures.

• Involve use of microscope to classify toxic substance if they block the

development of stem cells.

Statistical significance:

• 78% accurate, with 100% accuracy at detecting very toxic chemicals.

• Animal test detect 60% of toxicants.

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LIMITATIONS

• In vitro techniques focus on the cellular level and therefore

cannot replace whole-body testing.

• It can’t determine the drug safety and efficacy.

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HUMAN TISSUES

• Healthy and diseased tissues provide more relevant way of studying human biology and disease than animal testing.

Sources of human tissue:

• Surgery (e.g. biopsies, cosmetic surgery and transplants)

• After a person has died (e.g. post-mortems).

• Can be used in many forms, including isolated perfused organs, frozen tissue or in cell cultures.

• In Multiple Sclerosis and Parkinson’s disease Post-mortem brain tissue has provided important leads to understanding brain regeneration.

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Reconstituted Human Epidermis (RHE) skin model

Reconstituted Human Epidermis (RHE) skin model

• Alternative made from human tissue

• Used to find out chemical or cosmetic irritating to the skin.

• Made up of small discs of skin cells grown from human skin donated

as a waste from cosmetic surgery.

• Instead of rubbing a substance onto the shaved skin of a rabbit in

the cruel animal test, it is applied to discs of human skin and

evaluated for signs of irritation

• More effective than the rabbit test it replaces.

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• The toxic potential of substances can sometimes be detected using relatively simple chemistry based methods and not requiring human cells.

• The techniques that now test whether shellfish have dangerous toxins in them are based on chromatography methods – high performance liquid chromatography (HPLC).

• They replace extremely cruel tests in which the shellfish mixture was injected to the animals.

IN-CHEMICO METHODS

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Direct Peptide Reactivity Assay (DPRA),

•  Used to assess whether a chemical or cosmetic will cause a skin allergy.

Mechanism of action:

• The binding of proteins found in the skin substance.

• If proteins bind to the substance then it causes an allergic reaction.

• The animal tests predict human reactions 72% of the time.

• DPRA detects skin sensitising potential of up to 91% of substance.

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ORGAN ON A CHIP

• Contain a series of tiny hollow chambers that are lined with real,

living human cells from different parts of the body.

• Chambers are linked by channels through which a blood substitute

flows, following same principle as in real processes in the body.

• Test drugs can be added to the blood substitute which then

circulates around the device while sensors within the chip feedback

information for computer analysis.

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CONT..

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applications

• For studying biological and disease processes as well as drug

metabolism

• This can accurately mimic the lung, heart, kidney and gut

• The ultimate goal is to use these chips to create a whole ‘human-on-a-

chip’

LIMITATIONS:

• Provides less information than whole-body testing

• For determining drug safety and efficacy requires testing in animals

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Cont..

• Use of human organ models for drug toxicity screening like heart-on-a-

chip, and human disease models for development of novel drugs.

• Models to investigate routes for optimal drug uptake in the body.

• Capturing the genetic variation present in the normal as well as the

diseased human population,

• To improve efficiency and reduce costs of drug development.

• Model systems for drug toxicity screening.

• Human disease models for drug target discovery and drug

development.

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Mathematical models and computer simulations

• These models produce computational disease and treatment models.

• By collecting human research data points, and carry out human clinical trials

virtually.

• Simulate sophisticated anatomical functions such as heart rate and, along with

other data, can be used to determine disease or predisposition to certain

illnesses.

• Eg: computer simulations of cancer cells are now used to test drug targets

within them, and “mathematical models have helped to further our

understanding of HCV [hepatitis C] dynamics and clinical trial results in

humans.”

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QSARs mODELS

• Computer programs which can predict the toxicity of new chemicals or drugs based on their similarity to more established compounds.

• Based on the principle that similar chemicals should have similar biological properties.

• Greater computer power and the ability to generate large databases are two potential advantages.

LIMITATION: Findings from computer models and simulations usually need to be confirmed in whole animals.

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MICRODOSING

• It is an innovative technique that measures how very small doses of potential new medicines are absorbed, distributed, metabolised and excreted by the human body.

• The microdose radio-labelled, injected into human volunteers and measured (usually in blood samples) using a very sensitive measuring device called an accelerator mass spectrometer.

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• 40% of drugs fail in human trials because the traditional ADME studies conducted

in animals do not accurately predict how the drug would behave in humans.

• In 2009, international drug regulators (ICH) endorsed the use of micro dosing in

early clinical trials to improve the speed and safety of drug development.

LIMITATION:

• Considered only Phase 0 of a clinical drug trial, the earliest phase; animal testing

with the full dose of a drug is needed to determine its safety and efficacy and for

drug approval.

Cont..

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• Micro dosing and imaging studies allow human volunteers to be

used safely because they utilise special equipment.

• However, less technical studies in research areas such

as nutrition, drug addiction and pain can still be performed by

exploiting the ability of humans to consent to unpleasant, but not

harmful, procedures.

VOLUNTEER STUDIES

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• Includes studying and comparing illnesses in human populations

• Identify the risk factors and causes of human diseases

• Understanding the roles of genes, lifestyle, diet and occupation

• For example, these types of studies have led to the discovery that

smoking causes cancer and that high cholesterol and poor lifestyle

choices increase the risk of developing heart disease

POPULATION RESEARCH

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benefits

• More reliable than animal tests.

• The use of human tissue in toxicity testing is more accurate than

the animal models.

• More cost-effective, practical, and expedient.

• Cruelty-free products are more environmentally friendly.

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CONCLUSION

• Alternative methods do help to reduce the number of animals required

for drug research.

• Less time is needed for completing the study compared with animal

models and cost effective.

• But there is no way they can completely eliminate the need for animals

in preclinical studies.

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REFERENCE

• Balls, M. 1997 The Thee Rs concept to alernatives of animal experimentation.In animal Altenatives,welfare Ethics, ed . By L.F.M by van Zutphene and M.Balls,app.27-41.Elsevier.Amsterdam.

• R E Hester R M Harrison et al. Alternatives To Animal Testing (Issues in Environmental Science and Technology) Royal Society of Chemistry; 1 edition (June 7, 2006)

• FRAME (2005). "Human microdosing reduces the number of animals required for pre-clinical pharmaceutical research". Alternatives to Laboratory Animals 33 (439).

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