RRR

1. Limitations of Animal test
&
Alternatives Approach Animal
use
Part- I
Dr. Kuppala Manohar Babu
Professor
VJ’s College of Pharmacy

2. Contents
Limitations of Animal studies
Interspecies differences
Stressful environments and protocols
Methodological quality
Chronic high dose rodent studies
Alternate approach to Animal studies
Reduction
Replacement
Refinement

3. Animals do not reliably predict human outcomes, because:
1. Interspecies differences
2. Stressful environments and protocols
3. Methodological quality
4. Chronic high dose rodent studies

4. Alternatives of Animal use is needed because
Causes: 1. Interspecies differences
• Altered susceptibility to and progression of diseases
• Differing absorption, tissue distribution, metabolism, and excretion of
pharmaceutical agents and toxins
• Differences in the toxicity and efficacy of pharmaceuticals

5. Causes: 2. Stressful environments and protocols
Most laboratory animals spend most of their lives in small, relatively barren
cages.
Deleterious neuroanatomical, psychological and physiological effects
Laboratory procedures
Common laboratory species suffer marked stress, fear and possibly distress
when subjected to:
 Handling
 Blood sampling
 Gavaging
This stressful alteration of normal physiological parameters also predisposes
to pathologies and distorts scientific results

6. Causes: 3. False positive results of chronic high dose rodent studies
• Overwhelming of natural physiological defences such as
epithelial shedding, inducible enzymes, DNA and tissue repair
mechanisms, which effectively protect against many naturally
occurring toxins at environmentally relevant levels
• Differences in rodent physiology when compared to humans,
e.g.: increased metabolic and decreased DNA repair rates
• Variable, yet substantial, stresses caused by handling and
restraint, and frequently stressful routes of administration, and
subsequent effects on hormonal regulation, immune status and
disease predisposition

7. Causes: 4. Poor methodological quality of animal experiments
Common deficiencies are
Lack of:
• sample size calculations
• sufficient sample sizes
• randomised treatment allocation
• blinded outcome assessment
• conflict of interest statements

8. The common causes of reduced external validity of animal studies:
 Animals used for experiment are young and healthy, whereas in patients the disease
mainly occurs in elderly people with co-morbidities.
 Assessment of treatment efficacy in a homogeneous group of animals vs. a
heterogeneous group of patients.
 Insufficient similarity for inducing a disease/injury in animal models .
 Differences in outcome measures and assessment timing between preclinical and
clinical study.
POOR VALIDITY OF ANIMAL STUDIES

9. Alternateapproaches to Animal testing

13. Thank
you