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Toxicology

Toxicology. Lecture 1. Introduction. Science that deals with poison Poison: Any substance that are harmful to living organisms In Broader Sense: S tudy of the detection, occurrence, properties, effects, and regulation of toxic substances

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Toxicology

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  1. Toxicology Lecture 1

  2. Introduction • Science that deals with poison • Poison: Any substance that are harmful to living organisms • In Broader Sense: Studyof the detection, occurrence, properties, effects, and regulation of toxic substances • Toxicity: Cascade of events (Exposure, Distribution, Metabolism, Interaction with DNA or Protein and expression of toxic end product) or Degree of toxic effect of a toxin • Almost any substance being toxic at some doses but at the same time harmless at some lower dose e.g. Aspirin (acetylsalicylic acid) 0.2- 0.5 g/kg dose 15 % death in Children

  3. Toxicity • Toxicity can be acute, subchronic, or chronic. • Acute involves harmful effects in an organism through a single or short-term exposure (Death of Socrates 1787 AD) • Subchronic: The ability of a toxic substance to cause effects for more than one year but less than the lifetime of the exposed organism • Chronic: The ability of a substance or mixture of substances to cause harmful effects over an extended period, usually upon repeated or continuous exposure, sometimes lasting for the entire life of the exposed organism. • LD50 (Dose at which half of the population die at stated condition)

  4. Exposure • Exposure of humans and other organisms to toxicants may result from many activities: Intentional ingestion Occupational exposure Environmental exposure Accidental and Intentional (suicidal or homicidal) • Experimental Route of Administration: Intravenous (IV) Intraperitoneal (IP) Intramuscular (IM) Subcutaneous (SC) injection (Different routs give quite variable results)

  5. Fate and effect of toxicants in the body

  6. Modes of Toxic Action • Mechanism of toxin: Important molecular event in the cascade of events leading from exposure to toxicity eg inhibition of acetylcholinesterase by organophosphorus and carbamate insecticides • Biochemical and molecular toxicology: Considers consider events at the biochemical and molecular levels (Xenobiotics metabolizing enzymes, interaction with macromolecules, gene expression, and signaling pathways) • Behavioral toxicology: deals with effects of toxicant on the animal and human behaviors (CNS, PNS and endocrine system) • Nutritional toxicology: Relationship b/w nutrition and toxicology (influence of nutrition on toxicities; influence of toxicants on nutrition; and toxicities of nutrients)

  7. Carcinogenesis: Includes the chemical, biochemical, and molecular events that lead to cancer. • Teratogenesis: Includes the chemical, biochemical, and molecular events that lead to deleterious effects on development. • Mutagenesis: Deals with the toxic effects on genetic materials and their inheritance.

  8. Measurement of Toxicants and Toxicity Deals with analytical chemistry, bioassays and applied mathematics to answer some questions. Following are some related fields • Analytical toxicology (Identification & assay of toxin) • Toxicity testing (Estimation of toxic effect on living organism) • Toxicologic pathology (Toxic effects expressed as changes in morphology) • Structure-activity (Relation of physical and chemical properties of toxicants with toxicity) • Biomathematics and statistics (Data analysis and determination of significance) • Epidemiology (Population study for exposure and disease relationship)

  9. Applied Toxicology Application of toxicology in fields sittings • Clinical toxicology • Veterinary toxicology • Forensic toxicology (Medicolegal aspects such as identification of chemicals in clinical and other samples) • Environmental toxicology • Industrial toxicology

  10. Chemical Use Classes Toxicity of chemicals for commercial uses. • Agricultural chemicals (insecticides, herbicides, fungicides, and rodenticides) • Clinical drugs (Testing of clinical drugs for toxicity) • Drugs of abuse (Toxicity of drugs used for psychological effects) • Industrial chemicals • Naturally occurring substances (phytotoxins, mycotoxins, and minerals) • Combustion products (Toxicity of chemicals released from burning of fuels)

  11. Dose Response Relationship Paracelsus first time recognize dose response relationship. According to him “the right dose differentiates a poison from a remedy,” a concept that is the basis for pharmaceutical therapy. threshold dose Dose-response curve

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