20. PRINCIPLES OF ANIMAL TOXICOLOGY

Animal toxicology is the study of harmful effects of chemicals, drugs, and environmental substances on animals. It helps scientists understand how safe a drug is before it reaches humans. Toxicology forms the backbone of preclinical drug testing, ensuring that only safe and effective medicines enter clinical trials.


Objectives of Animal Toxicology

  • Identify harmful effects of chemicals
  • Determine safe dose ranges
  • Understand how toxins enter, move through, and leave the body
  • Predict possible human risks using animal data
  • Study long-term and short-term toxicity

Key Concepts in Toxicology

1. Dose–Response Relationship

The toxic effect of any substance depends on the dose. Even harmless substances can be toxic in high amounts. Toxicity increases as dose increases.

Important Terms

  • LD50: Dose that kills 50% of test animals. Used to compare toxicity levels.
  • ED50: Dose that produces the desired effect in 50% of animals.
  • Therapeutic Index (TI): Ratio of LD50 to ED50, showing drug safety margin.

2. Types of Toxicity

a. Acute Toxicity

Occurs after a single high dose. Symptoms appear quickly.

b. Subacute Toxicity

Develops after repeated doses for up to one month.

c. Chronic Toxicity

Occurs after long-term exposure (months or years). Helps detect cancer-causing or organ-damaging effects.

d. Reproductive and Developmental Toxicity

Assesses effects on fertility, embryo development, and birth defects.

e. Mutagenicity and Carcinogenicity

Tests whether a chemical causes genetic mutations or cancer.


Factors Affecting Toxicity

  • Route of exposure: oral, inhalation, skin, injection
  • Duration of exposure: single or repeated dose
  • Species and genetic differences
  • Age: young and elderly animals are more sensitive
  • Nutritional status
  • Drug interactions

Toxicokinetics

Toxicokinetics describes how toxins move inside the body. It includes:

  • Absorption: entry of toxin into the bloodstream
  • Distribution: spread around organs and tissues
  • Metabolism: breakdown of toxins, usually in the liver
  • Excretion: removal through kidneys, lungs, or bile

Common Tests in Animal Toxicology

1. Acute Toxicity Test

Determines LD50 and identifies immediate toxic symptoms.

2. Subacute and Subchronic Tests

Performed for 14 to 90 days to study repeated exposure effects.

3. Chronic Toxicity Test

Evaluates long-term effects such as cancer risk or organ failure.

4. Reproductive Toxicity Test

Assesses fertility, embryo survival, and birth defects.

5. Mutagenicity Tests

Examples include the Ames test to detect gene mutations.

6. Carcinogenicity Studies

Long-term tests to check if a chemical causes tumors.


Safety Evaluation

Before any drug can be tested in humans, it must pass multiple safety tests in animals. Key indicators include:

  • No severe organ damage
  • Acceptable safety margin (therapeutic index)
  • Predictable toxicity profile

Ethical Considerations

Animal testing must follow strict ethical guidelines:

  • Use the smallest number of animals necessary
  • Ensure humane handling and proper housing
  • Apply the “3 Rs” principle – Reduce, Replace, Refine

Applications of Animal Toxicology

  • Drug development and approval
  • Industrial chemical risk assessment
  • Safety testing of cosmetics and food additives
  • Environmental pollution studies

Detailed Notes:

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