Toxicology

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Toxicology

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Toxicology

  1. 1. GOMATHI’S TOXICOLOGY
  2. 2.   TOXICOLOGY – STUDY OF POISONS (GREEK WORDS) TOXICAN – POISON ? LOGOS – STUDY
  3. 3. ………..  “All substances are poisons; there is none which is not a poison. The right dose differentiate a poison and a remedy” - Paracelsus (Grand Father of Toxicology)
  4. 4. INTRODUCTION  Toxic – the chemical/physical agent/substances having the characteristic of producing an undesirable or adverse health effects.  Toxicity – the ability of a toxic to cause adverse effects in living organisms.
  5. 5. DEFINITION - TOXICOLOGY  The science that deals with the study of the adverse effects chemicals/physical agents may produce in living organisms under specific conditions of exposure.  It is the science that attempts to qualitatively identify all the hazard as well as to quantitatively determine the exposure conditions.
  6. 6. “The science that experimentally investigates the occurrence, nature, incidence, mechanism and risk factors for the adverse effects of toxic substances.”
  7. 7. HISTORY The knowledge of poison substance (venom & plant extracts) –ancient periods – hunting.  Poisons such as Hemlock (blood of Socrates) 
  8. 8. 4,000 BC – Opium poppy – alkaloids such as morphine, codeine, Laudanum are all narcotics.  Morphine the very first medicinal compound ever isolated in pure form. 
  9. 9.  In 9th century Dioscorides, a Greek physician – classified poison 1. Plant poisons 2. Animal poisons 3. Mineral poisons
  10. 10. Paracelsus (1493) - contributed greatly to the fields of medicine and toxicology - the use of chemicals and minerals in medicine, (First Coined “Zinc”)  Certain illnesses of the body had chemical remedies that could cure them.  He was, therefore, a precursor to modernday medicine and to the use of vitamins and minerals to maintain health. 
  11. 11. Mathieu Orfila - Modern father of toxicology  First formal treatment – experimental toxicology laid down great success to pharmacology in 1813.  In 1815 Magendia - done atopsy & chemical toxicants and explain the mechanism of action of emitine & strychine – absorption, distribution of the compounds. 
  12. 12. 1850’s- advent of anesthetics & disinfectants began to understand.  During 1900, discovery of radioactivity & vitamins.  NIH- National Institute of Health assigned NIDA – National Institute of Drug Abuse.  FDA ASSIGNED U.S PESTICIDE ACT – 1947  1950’S additives of food, drugs, cosmetics Act passed.  Many toxicological journals, professional, governmental & other scientific organizations begins to broadcast 
  13. 13. TOXICOLOGIST Identify the toxic materials  Mechanism of toxins  Exposure assessment RESEARCH  Experimentally prove the toxicants  Risk characterization  Safety measures   IMPLEMENTATION / AWARENESS
  14. 14.  TOXICITY DEPENDS UPON,
  15. 15. MEASURES OF TOXICITY  Toxicity is measured as clinical “endpoints” which include  Mortality (death)  Teratogenicity (ability to cause birth defects)  Carcinogenicity (ability to cause cancer)  Mutagenicity (ability to cause heritable change in the DNA)
  16. 16. Toxic dose low (TDLO): The lowest dose of a substance introduced by any route, other than inhalation, over any given period of time, and reported to produce any toxic effect in humans or to produce tumorigenic or reproductive effects in animals. Toxic concentration low (TCLO): The lowest concentration of a substance in air to which humans or animals have been exposed for any given period of time that has produced any toxic effect in humans or produced tumorigenic or reproductive effects in animals. Lethal dose low (LDLO): The lowest dose, other than LD50 of a substance introduced by any route, other than inhalation, which has been reported to have caused death in humans or animals. Lethal dose fifty (LD50): A calculated dose of a substance which is expected to cause the death of 50 percent of an entire defined experimental animal population. It is determined from the exposure to the substance by any route other than inhalation. Lethal concentration low (LCLO): The lowest concentration of a substance in air, other than LC50, which has been reported to cause death in humans or animals. Lethal concentration fifty (LC50): A calculated concentration of a substance in air, exposure to which for a specified length of time is expected to cause the death of 50 percent of an entire defined experimental animal population.
  17. 17. ROUTES OF ENTRY ABSORPTI ON
  18. 18. MECHANISM OF TOXICANTS Allergic response or Hypersensitivity Biological pathways changes, Receptors, Ion channel, Enzyme mediated toxicity Example: The cyanide ion (CN−) blocks cellular respiration by inhibiting an enzyme in the mitochondria called cytochrome c oxidase. Organ directed toxicity Mutagenesis Carcinogenesis Teratogenesis
  19. 19. R
  20. 20. INGESTION ABSORPTIO N Gastrointestinal tract LUNGS DISTRIBUTIO N EXTRACELLULAR FLUIDS METABOLIS M LIVER BILE BLOOD & LYMPH KIDNEY DERMAL CONTACT INHALATION LUNGS ORGANS OF BODY SOFT TISSUES OR BONES SECRETI ON OF GLANDS BLADDER FAECES URINE EXPIRED AIR FATS SECRETION EXCRETI ON
  21. 21. ABSORPTION Passive diffusion - Diffusion occurs through the lipid membrane.  Filtration - Diffusion occurs through aqueous pores.  Special transport - Transport is aided by a carrier molecule.  Endocytosis - Transport takes the form of 
  22. 22. Large surface are for absorption of toxicants in small intestine.  Lipophilic toxicants highly absorbed than hydrophilic substances 
  23. 23. LUNGS – ALVEOLAR ABSORPTION
  24. 24. EXAMPLES OF RESPIRATORY TRACT TOXICANTS
  25. 25. SKIN  Absorbs lipophilic compounds of low molecular weight very quickly and also hydrophilic substances.
  26. 26. KINETICS OF ABSORPTION      Rate of absorption of toxic depends upon the nature of chemicals and their site of administration. Rate of absorption more for lipid – soluble molecules and slow for strong acids and bases. First order process: at low doses, rate of reaction is directly proportional to the amount of toxicant present. Zero order process: as the concentration of substances increase, a point may be reached at which there is no further increase in rate of absorption. Extent of absorption depends on the bioavailability of the substance.
  27. 27. INGESTION ABSORPTIO N Gastrointestinal tract LUNGS DISTRIBUTIO N EXTRACELLULAR FLUIDS METABOLIS M LIVER BILE BLOOD & LYMPH KIDNEY DERMAL CONTACT INHALATION LUNGS ORGANS OF BODY SOFT TISSUES OR BONES SECRETI ON OF GLANDS BLADDER FAECES URINE EXPIRED AIR FATS SECRETION EXCRETI ON
  28. 28. DISTRIBUTION Rate of distribution is rapid in plasma but slow in tissues.  Extent of distribution related to apparent volume of distribution (V). V = Ab C  Ab – total quantity of toxicants in the body  C – plasma concentration  Volume of distribution actual space in which toxicants distributed. Vd = D (dose administered) Cp 
  29. 29. INGESTION ABSORPTIO N Gastrointestinal tract LUNGS DISTRIBUTIO N EXTRACELLULAR FLUIDS METABOLIS M LIVER BILE BLOOD & LYMPH KIDNEY DERMAL CONTACT INHALATION LUNGS ORGANS OF BODY SOFT TISSUES OR BONES SECRETI ON OF GLANDS BLADDER FAECES URINE EXPIRED AIR FATS SECRETION EXCRETI ON
  30. 30. EXCRETION Rate of excretion is determined by apparent volume of distribution (V) and clearance (CL). Rate of elimination of chemicals  CL = Plasma concentration  Plasma clearance = sum of the clearance of metabolism (CLM), renal excretion (CLR), biliary excretion (CLB).  Metabolic clearance cannot measured easily so the total clearance(CL) = CLM + CLR CLM = CL - CLR 
  31. 31. WHY WE NEED TO STUDY TOXICOLOGY
  32. 32. NOT FOR………….

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