ree oe st Tu | TOXICOLOGY Introduction to Toxicology Theoretical toxicology Dr. Sarah Jaafar Lecture: 1 College of Pharmacy Stage: 4t Al-Ayen Iraqi University What is there that is not poison? All things are poison and nothing (is) ithout poison. Solely the at a thDefinition of Toxicology * Toxicology is the study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment, including the prevention and amelioration of such adverse effects. * These toxic substances include naturally occurring harmful chemicals, or toxins, as well as foreign substances called xenobiotics. * Toxicology is a highly interdisciplinary science that borrows from and intersects with other sciences such as, pharmacology, physiology, medicine, biochemistry, molecular biology, pathology, and environmental science. Theoretical tonicology lecture by Sarah Jaafar * Toxinology, a sub discipline of toxicology, studies biological exposures, such as insect stings, poisonous mushrooms and plants, venomous snakes and aquatic life. * The words poisonous and venomous are distinct. A venom requires a delivery mechanism. Thus, because a snake, for example, injects its venom into its victim, it is considered a venomous animal. Instead, a toxic mushroom must be ingested to make its effect felt. Thus, it should instead be considered as poisonous. * The toxicology is also concerned with physical hazards, such as radiation and noise.* Toxins are poisons that originate from plants and organisms and also include venoms released by animals, while, toxic chemicals are referred to as toxicants, rather than toxins, because, although they may be naturally produced, they are not produced by biological systems, where as xenobiotics are synthetics substances such as pharmaceuticals and pesticides. * Toxicology is largely concerned with the interaction of toxicants and biological organisms. While toxicodynamics investigates the effect of the toxicant on the organism, toxicokinetics looks at how the organism affects the toxicant (e.g., absorption, biotransformation, distribution, and elimination). * Toxicology is traditionally associated with chemical exposures, such as the effects of drugs, industrial chemicals, pesticides, food additives, household products, and personal care items. * Toxic substances can generally classify based on their target organs, their use, their sources and their consequences. In addition, can be classified on basis of their mechanism of action such as endocrine disruptors and cholinesterase inhibitor. Known or Suspected alHost and Environmental Factors * There are many factors affecting the toxic effects of substances. Not all humans respond to toxicants in the same manner and to the same degree as each other. * Multiple factors modify one’s susceptibility to adverse outcomes these factors refer to host factors. The important modifiers include genetic variation among a population, age, sex and hormonal status. * Other influences that can impact the extent of toxicity include the concomitant use of tobacco, alcohol, nutraceutical, pharmaceutical and illicit drugs, exercise, and nutritional state. * However, environmental factors may contribute to the response for a given chemical, such factors as air pollution, workplace and living conditions, personal habits (such as diet and personal activity), and previous chemical exposure. + Age: is an important factor that can alter susceptibility to toxicity. Metabolic processes that aid in xenobiotic clearance are often altered at juvenile and advancing ages. * For example, newborns have relatively low gastric emptying, gastrointestinal motility, and expression of the metabolic enzymes. Reduced metabolic capacity can decrease the clearance of some chemicals and increase the risk of toxicity.* Genetics: Hereditary differences in a single gene that occur in more than 1% of the population are referred to as genetic polymorphisms. Genetic variants are being identified that impact a variety of target organ toxicities. * For example, it is recognized that approximately 50% of the Caucasian population has a gene deletion for the enzyme (GSTM1). This enzyme has no significant physiological function, and thus those who lack the normal gene are functionally and physiologically normal. However, studies showed that smokers have a gene deletion is slightly at increased risk of respiratory disease compared with smokers without gene deletion. Subdisciplines of Toxicology *The professional activities of toxicologists fall into three main categories: mechanistic, hazard assessment, and regulatory. *A mechanistic toxicologist identifies the cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms. In risk assessment, mechanistic data may be useful in determining whether an adverse outcome observed in laboratory animals may occur in humans. *A hazard assessment toxicologist conducts toxicity testing that provides information for the evaluation of a chemical’s safety and to meet important regulatory requirements.* The appropriate toxicity tests in cell culture systems or experimental are designed to give information to identify potential hazards and associated risks posed to humans and the environment. * A regulatory toxicologist has the responsibility for deciding, on the basis of data provided by descriptive and mechanistic toxicologists, whether a drug or other chemical poses a sufficiently low risk to be marketed for a stated purpose. * In addition to the above categories, there are other specialized areas of toxicology such as clinical, forensic, and environmental toxicology. * Clinical toxicology is the field of medical science concerned with disease caused by or associated with toxic substances and provide treating of poisoned patients with intoxications. Forensic toxicology covers the medicolegal aspects of the harmful effects of chemicals on human and animals. Environmental toxicology focuses on the impact of chemical pollutants in the environment on organisms. * Developmental toxicology is the study of adverse effects on the developing organism occurring anytime during the life span of the organism that may result from exposure to chemical or physical agents before conception (either parent), during prenatal development, or postnatally until the time of puberty.Toxic Effects * Some toxic effects of chemicals are reversible, whereas others are irreversible. The possibility of a toxic response to be reversed largely depends on the ability of an injured tissue to adapt, repair, and regenerate, for tissues such as the liver and GIT that have a high ability to regenerate, many injuries are reversible. * By comparison, the CNS has a much more limited ability to divide and replace damaged neurons making damage largely irreversible. Homework: about toxicological interactions what does mean of: additive effect, synergistic effect, potentiation and antagonism? Thank you References: 1-Curtis D. Klaassen (2019). Casarett and Doull’s toxicology:the basic science of poisons. 9" edition. McGraw-Hill Education.