Toxicology

• Toxicology is defined as the branch of science that deals with poisons
• Includes the study of harmful effects caused by physical phenomena like radiation, noise, etc.
• Study of detection, occurrence, properties, effects, and regulation of toxic substances
• Poison is any substance that causes a harmful effect when administered to a living organism
• Toxicant is specific chemicals that are poisonous
• Toxicity involves a cascade of events starting with exposure, progressing through distribution and metabolism, and ending with interaction with cellular macromolecules and the expression of a toxic endpoint
• Xenobiotics are man-made substances or those not normally found in the body
• Areas of Toxicology:

  • Mechanistic Toxicology identifies cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms
  • Toxicogenomics applies genetic data in the study of toxicology
  • Descriptive Toxicology concerns toxicity testing and provides information for the safety evaluation of specific chemicals
  • Regulatory Toxicology involves risk assessment and the establishment of standards
  • Forensic Toxicology deals with the medico-legal aspects of toxicology
  • Clinical Toxicology is concerned with diseases associated with toxic substances
• • Environmental Toxicology studies the impact of pollutants on biological organisms, focusing on pollutants like air and water
  • Ecotoxicology focuses on the impact of toxic substances on population dynamics
  • Teratology studies adverse defects induced during conception
  • Reproductive Toxicology studies the occurrence of adverse effects on the male or female reproductive system from exposure to chemicals or physical agents
• History of Toxicology:

  • Chinese Journals in 2700 B.C. discussed plants and animal poisons
  • Egyptian documents from 1900-1200 B.C. included directions for medicinal and poisonous recipes like Belladona, Henbane, and Strychnine
  • Hindu notes from India in 800 B.C. included information on poisons and antidotes
  • Greek physicians classified over 600 plant, animal, and mineral poisons
  • Romans used poisons for executions and assassinations
  • Avicenna in 980-1036 A.D. was an Islamic authority on poisons and antidotes
• • Paracelsus from 1493-1541 was the first father of Toxicology, explaining the relationship between dose and response of chemicals
  • Lex Cornelia de Sicariis et Veneficis in 82 B.C. was the first legislative enactment against poisoning
  • Mathieu Joseph Bonaventure Orfila in 1815 established toxicology as a distinct scientific discipline
• Paul Ehrlich developed safer chemical products, safer drugs, and treatments for chemical exposure
• Ethical dilemmas in Toxicology:

  • The need for well-articulated visions on human, animal, and environmental health
  • Health consequences of exposure
  • Social and ethical responsibility framework
• Median Lethal Dose (LD50):

  • Is the amount of a material that causes the death of 50% of a group of test animals when given all at once
  • Measures of acute lethality like LD50 may not fully reflect the toxicity or hazard associated with exposure to a chemical
• Toxin:

  • Refers to toxic substances produced by biological systems such as plants, animals, fungi, or bacteria
• Toxicant:

  • Refers to toxic substances produced or by-products of human activities
• Spectrum of Undesired Effects:

  • Chemicals can have a broad spectrum of undesired effects
  • Usually, only one effect is associated with the primary objective of therapy, while all other effects are considered undesirable or side effects
• Allergic Reactions:

  • Chemical allergy is an adverse reaction to a chemical resulting from previous sensitization
  • Allergic reactions can occur from exposure to very low doses of chemicals
  • Allergic reactions are dose-related for a given allergic individual
• Idiosyncratic Reactions:

  • Chemical idiosyncrasy refers to abnormal reactivity to a chemical that is genetically determined
  • Responses observed are usually qualitatively similar to those in all individuals but may vary in sensitivity to doses
• Immediate vs. Delayed Toxicity:

  • Immediate toxic effects occur rapidly after a single substance administration
  • Delayed toxic effects occur after some time has passed
• Reversible and Irreversible Toxic Effects:

  • The ability of tissue to regenerate largely determines if the effect of a chemical is reversible or irreversible
• Local vs. Systematic Toxicity:

  • Local effects occur at the site of contact with the toxicant
  • Systematic effects require absorption and distribution of the toxicant to a distant site where deleterious effects are produced
• Interaction of Chemicals:

  • Additive effect occurs when the combined effect of two chemicals equals the sum of their individual effects
  • Synergistic effect occurs when the combined effects of two chemicals are much greater than the sum of their individual effects
  • Potentiation occurs when one substance enhances the toxicity of another
  • Antagonism occurs when two chemicals interfere with each other's actions
• Tolerance:

  • Is a decreased responsiveness to a toxic effect due to prior exposure to the chemical
  • Mechanisms include a decreased amount of toxicant reaching the site of effect and reduced tissue responsiveness
• Dose-Response Relationship:

  • Describes the response of an individual organism to varying doses of a chemical
  • Most toxic substances have multiple sites for mechanisms of toxicity, each with its own dose-response relationship
• Effective Dose (ED50):

  • Widely used statistical approach in estimating the response of a population to a toxic exposure
• Dose-Response Curve:

  • Essential nutrients are substances required for normal physiological function and survival
  • Hormesis refers to non-nutritional toxic substances that may have beneficial effects at low doses
  • Threshold is the specific dose at which a response is exhibited
  • Therapeutic Index is the ratio of the dose required to produce a toxic effect to the dose needed for the desired therapeutic effect
• Margin of Safety and Exposure:

  • Indicates the difference between the estimated exposed dose to a human population and the number of observable adverse effects
• Toxicology is the branch of science that deals with poisons
• Includes the study of harmful effects caused by physical phenomena like radiation and noise
• Involves the study of detection, occurrence, properties, effects, and regulation of toxic substances
• Poison is any substance that causes a harmful effect when administered to a living organism
• Toxicant is a specific chemical that is poisonous
• Toxicity involves a cascade of events starting with exposure, progressing through distribution and metabolism, and ending with interaction with cellular macromolecules and the expression of a toxic endpoint
• Xenobiotics are man-made substances or those not normally found in the body
• Areas of Toxicology:

  • Mechanistic Toxicology identifies cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms
  • Toxicogenomics applies genetic data in the study of toxicology, focusing on the specific makeup of humans affected by poison
  • Descriptive Toxicology is concerned with toxicity testing, providing information for the safety evaluation of specific chemicals, including how they cause harm and how to prevent it
  • Regulatory Toxicology involves risk assessment and the establishment of standards
• • Forensic Toxicology deals with the medico-legal aspects of toxicology, determining how the body died
  • Clinical Toxicology focuses on diseases associated with toxic substances in living individuals
  • Environmental Toxicology studies the impact of pollutants on biological organisms, particularly in air and water, and how it affects people
  • Ecotoxicology focuses on the impact of toxic substances on population dynamics, including how they are passed on
  • Teratology studies adverse defects induced during conception and how they are passed from pregnant women to babies
• • Reproductive Toxicology studies adverse effects on the male or female reproductive system resulting from exposure to chemical or physical agents
• Toxicologists work to develop a mechanistic understanding of how chemicals affect living systems and determine the risks of chemical exposure
• Toxicologists develop safer chemical products, safer drugs, and treatments for chemical exposure