Toxicology Lab: One 4th Year PDF

Toxicology Lab : one 4th year MSc. Mohammed Hussein Aljanaby Lecture topics: 01 04 HISTORY AND TOXICITY IN RELATION TO INTRODACTION Of FREQUENCY AND TOXICOLOGY DURATION OF EXPOSURE 02 Branches of Toxicology...

Toxicology Lab : one 4th year MSc. Mohammed Hussein Aljanaby Lecture topics: 01 04 HISTORY AND TOXICITY IN RELATION TO INTRODACTION Of FREQUENCY AND TOXICOLOGY DURATION OF EXPOSURE 02 Branches of Toxicology 03 TYPES OF TOXICANTS  01 History AND INTRODACTION Of TOXICOLOGY  History of Toxicology Toxicology is the study of poisons and their effects on living organisms. Its history dates back to ancient times when people recognized the toxic properties of certain plants and animals. - Early civilizations: Recognized and used poisons for various purposes, such as hunting and warfare. - Egyptian papyrus Ebers (1500 BC): One of the earliest surviving pharmacopeias. - Ancient Greeks and Romans: Hippocrates, Aristotle, Theophrastus, and Dioscorides studied and documented the effects of poisons. - Paracelsus (1493-1541): Laid the groundwork for modern toxicology by recognizing the importance of the dose-response relationship. - Ramazini (1700): Considered the father of occupational medicine. - Orfila (early 19th century): Established toxicology as a separate science and published the first book on toxicology. - 20th century: Significant advances in toxicology, including the study of mechanisms of toxic action, environmental toxicology, and the use of molecular biology techniques. - Rachel Carson (1962): Her book "Silent Spring" raised awareness about the harmful effects of pesticides and other chemicals, leading to the establishment of the US Environmental Protection Agency. - Modern toxicology: Focuses on understanding the mechanisms of toxic action, developing methods for detecting and analyzing toxins, and developing strategies for preventing and treating poisoning.  Toxicology The traditional definition of toxicology is “the science of poisons.” As our understanding of how various agents can cause harm to humans and other organisms. a more descriptive definition of toxicology is “the study of the adverse effects of chemicals or physical agents on living organisms.”. Explanations: Toxicology : the term The word “toxicology” is derived from the Greek word “Toxicon” which means “poison” and logy means to study. Adverse effects may occur in many forms, ranging from immediate death to subtle changes not realized until months or years later. They may occur at various levels within the body, such as an organ, a type of cell, or a specific biochemical. Also concerned with study of special effects of toxicants , developmental toxicity, teratogenicity, carcinogenicity, mutagenesis, immune-toxicity, neurotoxicity, endocrine disruption, etc.  Toxicologist:- is specially trained to examine the nature of the adverse effects of chemicals or drugs and to assess probability of their occurrence. Poison :- Any agent capable of producing a deleterious response in biological system, serious injury or producing death. Poison, any substance that produces disease conditions, tissue injury, or otherwise interrupts natural life processes when in contact with or absorbed into the body. Most poisons taken in sufficient quantity are lethal. A poisonous substance may be mineral, vegetable, or an animal. A poison, depending on the type, may attack the surface of the body or, more seriously, internal organs or the central nervous system. Explanations: Xenobiotic: the term Xenobiotics ( xeno is a Greek word which means “strange or alien”) are the substances which are foreign to the body and are biologically active. It is a very wide class and structurally diverse agents, both natural and synthetic chemicals such as drugs, industrial chemicals, pesticides, alkaloids, secondary plant metabolites and toxins of molds, plants and animals, and environmental pollutants How does the body deal with foreign substances? The body has multiple defense systems to deal with foreign substances, including: - Liver: The liver is the main organ that converts foreign substances into less toxic substances that can be excreted from the body. - Kidneys: The kidneys filter the blood and remove toxic substances and waste from the body. - Digestive system: The digestive system expels some foreign substances through the stool. - Skin: The skin can prevent some foreign substances from entering the body.  02 Branches Of Toxicology  Branches Of Toxicology Mechanistic toxicology makes observations on how toxic substances cause their effects. The effects of exposure can depend on a number of factors, including the size of the molecule, the specific tissue type, or cellular components affected.” Clinical toxicology deals with clinical concepts of intoxication such as treatments for poisonings and injuries caused by xenobiotics.  Branches Of Toxicology Forensic toxicology deal with cause of death, legal aspects. Such as homocides , suicides Environmental toxicology deals with environmental pollutants  Branches Of Toxicology Food toxicology deals with adverse effects of processed or natural food components Regulatory toxicology assigns risk to substances of commercial importance. General methods for assessing the risks of poisons regardless of their type: Quantitative assessment: This includes determining the lethal dose and permissible exposure limits. Chemical classification: To assess the chemical and physical properties of the poison. Animal tests: To assess the toxicity of the substance to animals. Clinical tests: On human samples to assess the effects of human exposure. Epidemiological studies: To track the relationship between the level of exposure and the occurrence of effects. Sensitivity assessment: To identify the most sensitive groups to exposure to the poison. Dose-response modeling: To predict effects at different levels of exposure. Risk-reciprocal assessment: To compare the risks of the poison with the benefits of its use.  03 TYPES OF TOXICANTS Natural toxins: found in nature, such as snake venom, the venom of some plants (such as oleander), and poisonous fungi. Synthetic toxins: made by humans, such as pesticides, radioactive materials, and chemicals used in industry. TYPES OF TOXICANTS Poison : derived from Latin “ potus ” a drink that could harm or kill. It is any substance which when taken inwardly in a very small dose or applied in any kind of manner to a living body depraves the health or destroys life. the word toxicant has essentially the same medical meaning. Toxicant : is synonym of poison, produced by living organism in small quantities and is generally classified as biotoxin. These may be phytotoxins (produced by plants), mycotoxins (produced by fungi), zootoxins (produced by lower animals), and bacteriotoxins (produced by bacteria). TYPES OF TOXICANTS Venom : is a toxicant synthesized in a specialized gland and ejected by the process of biting or stinging. Venom is also a zootoxin but is transmitted by the process of biting or stinging. Pollutant : It is any undesirable substance to solid, liquid, or gaseous matter resulting from the discharge or admixture of noxious materials that contaminate the environment and contributes to pollution. TYPES OF TOXICANTS Systemic Toxicant : It is a toxicant that affects the entire body or many organs rather than a specific site. For example, potassium cyanide is a systemic toxicant that affects virtually every cell and organ in the body by interfering with the cell’s ability to utilize oxygen. Mechanisms of action of systemic toxins: The mechanisms of action of systemic toxins vary depending on the type of toxins, their concentration, and the duration of exposure. Some common mechanisms include: - Interaction with biomolecules: such as proteins and DNA, leading to disruption of cell function. - - Damage to cell membranes: leading to leakage of materials and cell damage. - - Generation of free radicals: unstable molecules that interact with cell components and cause oxidative damage. - - Interference with enzymes: leading to disruption of normal metabolic processes in the body. Examples of systemic toxins: Heavy metals: such as lead, mercury, and cadmium. Pesticides: Many pesticides are systemic toxins. Organic solvents: such as benzene and toluene. Some medications: when used in excessive doses or incorrectly. Radioactive materials: can cause widespread radiation damage. Organ Toxicant : It is toxicant that affects only specific organs or tissues (may be called tissue toxicant) while not producing damage to the body as a whole. For example, benzene is a specific organ toxicant in that it is primarily toxic to the blood-forming tissues. How do Organ Toxicant work? The mechanism of action of organic toxins varies depending on the type of toxin and the target organ, but in general, these toxins work by: - Interacting with biomolecules: such as proteins and DNA, which disrupts cell functions. - Destroying cell membranes: which leads to leakage of materials and cell damage. - Accumulation in tissues: Some toxins accumulate in certain organs, leading to gradual damage. Examples of target organs and the most common toxins that affect them: - Liver: Many chemicals, such as paracetamol in overdose, alcohol, and many medications, can cause liver damage. - Kidneys: Heavy metals such as lead and mercury, and some medications, can accumulate in the kidneys and lead to kidney failure. - Nervous system: Lead, mercury, and neurotoxicants affect the central and peripheral nervous systems. - Heart: Some drugs used to treat cancer, and industrial chemicals, can cause damage to the heart muscle. - Lungs: Toxic gases such as carbon monoxide, and chemical fumes, can cause irritation and inflammation in the lungs. TYPES OF TOXICANTS  TOXICITY AND TOXIC EFFECTS Toxicity: It is a state of being poisonous or capacity to cause injury to living organisms. Toxicosis: : It is the condition or disease state that results from exposure to a toxicant. The term toxicosis is often used interchangeably with the term poisoning or intoxication. Toxic effects: : These are undesirable effects produced by a toxicant/drug which are detrimental to either survival or normal functioning of the individual.  04 TOXICITY IN RELATION TO FREQUENCY AND DURATION OF EXPOSURE  TOXICITY IN RELATION TO FREQUENCYAND DURATION OF EXPOSURE : The exposure of experimental animals to chemicals can be divided into four categories: acute exposure and repeated exposure (subacute, sub chronic, and chronic). Acute exposure: : is defined as an exposure to a chemical for less than 24 hours. The exposure usually refers to a single administration; repeated exposures may be given within a 24-hour period for some slightly toxic or practically nontoxic chemicals. Acute exposure by inhalation refers to continuous exposure for less than 24 hours, most frequently for 4 hours.  TOXICITY IN RELATION TO FREQUENCYAND DURATION OF EXPOSURE Repeated exposure: : Repeated exposure is divided into three categories: (1) subacute, (2) sub chronic (3) chronic. subacute exposure to a chemical is for 1 month or less, sub chronic for 1-3 months, and chronic for more than 3 months (usually this refers to studies with at least 1 year of repeated dosing).  05 DURATION OF EXPOSURE Microbiology is a vital science that's advanced rapidly. It's used in many industries, like food and medicine, to improve our lives. But, microbes can also cause problems, like food poisoning and diseases. Microbiology studies these microbes, both the good and the bad, to help us keep food safe. Bacteria: Among the most significant bacterial genera causing food and feed spoilage or poisoning are: Salmonella, Shigella, Micrococcus, Staphylococcus, Streptococcus, Bacillus, and Clostridium. Mold or fungus: Aspergillus is considered one of the most important molds causing food and feed spoilage and poisoning, and it is the most dangerous. Algae: Algae growing in freshwater or saltwater release toxins into these waters and transfer to marine life.  Molds Bacteria Aspergillus Micrococcus Algae -Bacterial toxins: in Starchy foods, cooked meet, rice. - Fungal toxins :in Nuts, dried fruits, spices, grains, seeds. - Algae toxins : in seafood. These toxins also different in the conditions that must be met to produce the toxin as follows: Therapeutic index (TI) The therapeutic index (TI); also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. Clear example: We have two drugs, drug A and drug B. Drug A: has a TD50 value of 100 mg/kg and an ED50 value of 10 mg/kg. Drug B: has a TD50 value of 50 mg/kg and an ED50 value of 5 mg/kg. Calculation of therapeutic effect: A: TI = 100 / 10 = 10 B: TI = 50 / 5 = 10 In this case, both drugs have the same therapeutic effect, which means that they are both relatively safe. TOXICITY RATING The higher the toxicity rating for a particular substance the greater is the potency. The toxicity rating based on toxic potential of substances (super toxic, extremely toxic, very toxic, moderately toxic, lightly toxic, and practically nontoxic) FACTORS AFFECTING TOXICITY : 1.Host factors (factors related to subject) 2.Factors related to toxicant 3. other factors FACTORS AFFECTING TOXICITY : 1.Host factors (factors related to subject) A. species Toxic responses can vary depending on the species Example1: rats cant vomits and expel toxicants before they are absorbed whereas human are capable of vomiting Example 2: antibiotics are toxic to micro-organisms while virtually nontoxic to human FACTORS AFFECTING TOXICITY : 1.Host factors (factors related to subject) C. Gender : Physiologic differences between men and women, including differences in pharmacokinetics and pharmacodynamics, can affect drug activity. In comparison with men, pharmacokinetics (ADME(Absorption, Distribution, Metabolism, and Excretion)in women generally can be impacted by their lower body weight, slower gastrointestinal motility, reduced intestinal enzymatic activity, and slower kidney function (GFR/glomerular filtration rate).