Toxicology Introduction Lect. One PDF

 Course Description Toxicology refers to the study of the adverse effects of xinobiotics=toxic agent on living organisms. Toxic agent is any substance that even in small quantities or low concentrations, after a single administration or repeated exposure, cause severe damage to, or the dea...

 Course Description Toxicology refers to the study of the adverse effects of xinobiotics=toxic agent on living organisms. Toxic agent is any substance that even in small quantities or low concentrations, after a single administration or repeated exposure, cause severe damage to, or the death of, the organism The purposes of toxicology as a science are protection of organisms and biological systems from deleterious effects of toxicants and prevention of development of selective toxicants. Topics in This Lecture include: 1. Historical Development of Toxicology 2. Branches of toxicology 3. Different types of toxic agents 4. Different type of toxicity 5. Mechanism of Cellular Injury 6. Factors Influencing Toxicity  Lecture ILOs Understand the basics and concept of toxicology Define different classification of toxic agents. Recognize factors affecting response to toxic agents. Understand principles of toxicokinetics & toxicodynamics of toxic agents What Do You Think About This Course! Are you feeling like a lot of information is about to come your way? The answer is YES. Now, lets begin  Historical Development of Toxicology It is one of the oldest practical sciences which began with early cave dwellers who recognized poisonous plants and animals and used their extracts for hunting or in warfare. By 1500 BC, hemlock, opium, and certain metals were used to poison enemies or for executions (Notable poisoning victims include Socrates and Cleopatra). The Death of Socrates, 1787 Jacques-Louis David By the time certain concepts fundamental to toxicology began to take shape especially by the studies of Paracelsus (~1500AD) and Orfila (~1800 AD). Paracelsus (1493 -1541): His famous words were : "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy." He was the first to determined that specific chemicals were actually responsible for the toxicity of a plant or animal poison. He also documented that the body's response to those chemicals depended on the dose received Orfila (founder of toxicology -19th century) Spanish physician who first correlated between the chemical and biological properties of poisons. The 20th century is marked by an advanced level of understanding of toxicology especially after the the widespread use of anaesthetics and disinfectants. DNA (the molecule of life) and various biochemicals that maintain body functions were discovered. The discovery of radioactivity and the vitamins, led to the use of the first large-scale bioassays (multiple animal studies) to determine whether those new chemicals were beneficial or harmful to laboratory animals. The 1960s started with the tragic of thalidomide incident, in which several thousand children were born with serious birth defects. Attempts to understand the effects of chemicals on the embryo and fetus and on the environment as a whole gained momentum.  Branches of toxicology Toxicology is multidisciplinary as it entails: 1-Descriptive toxicology It is concerned directly with toxicity testing in cell culture systems or experimental animals to give information and to evaluate the risks posed to humans and on the environment from exposure to specific chemicals. 2-Mechanistic toxicology It s concerned with identifying and understanding the mechanisms by which chemicals exert toxic effects on living organisms.. 2-Regulatory toxicology It has the responsibility for deciding, on the basis of data provided by descriptive and mechanistic toxicology whether a drug or a chemical poses a sufficiently low risk to be used in living system. Regulatory toxicologists assist in the establishment of standards for the amount of chemicals permitted in ambient air, industrial atmospheres and drinking water. For example: Food and drug administration (FDA) regulates drugs, food, cosmetics medical devices and supplies in USA 4-Occupational (Industrial) toxicology is concerned with the protection of workers from toxic substances and makes their work environment safe. 5-Environmental toxicology focuses on the impact of chemical pollutants in the environment on biological organisms, most commonly on nonhuman organisms such as fish, birds and terrestrial animals. 6-Ecotoxicology is a specialized area within environmental toxicology that focuses more specifically on the impact of toxic substances on population at the community and/or ecosystem level. 7-Forensic toxicology is concerned primarily with the medico-legal aspects of the harmful effects of chemicals on humans and animals, in establishing causes of death and in determining their circumstances in a postmortem investigation. 8-Analytical toxicology is a specialized area to identify the toxicant through analysis of body fluids, stomach content, excrement, skin, or suspected containers. 9-Clinical toxicology is concerned with disease caused by or uniquely associated with toxic substances. Efforts are directed at treating patients poisoned with drugs or other chemicals and at the development of new techniques to treat those intoxications. Clinical toxicology deals with emergency cases such as overdoses, poisonings, attempted suicides by: emergency care for patients, management of sign and symptom, identification and quantification of the drug ,poisons, chemicals…etc  Toxicity Toxicity is the degree to which a substance can harm humans or animal Different xenobiotics cause many types of toxicity by a variety of mechanisms. So, we have to take an idea about: -Different types of toxic agents -Different type of toxicity -Different mechanisms of toxic response  Toxic Agents Toxic agent: is the agent that can produce an adverse biological effect toliving organism. The most common terms used to describe a toxic agent are toxicant, toxin, poison.  Classification of Toxic Agents Toxic agents can be classified according to their nature as Chemicals:(as alcohols, phenols & heavy metals), Physical (radiation),and Biological (Snake & scorpion venoms). Toxic agents can be also classified in terms of their target organs toxicity they cause (hepatotoxic, nephrotoxic), use (pesticide, solvent), and effects (cancenogenic, mutagen). Toxic agents may also be classified in terms of their physical state (gas, dust, liquid), their chemical stability (explosive, flammable), general chemical structure (aromatic amine, halogenated hydrocarbon) or poisoning potential (extremely toxic, very toxic, slightly toxic). However, classification of toxic agents on the basis of their biochemical mechanisms of action (e.g. alkylating agent, methaemoglobin producer) is usually more informative than classification by general terms such as irritants and corrosives.  Types of Toxicity Systemic Toxicity Organ Specific Toxicity Toxicity may occur at Toxicity may occur at multiple sites. This is specific organ. This is referred as systemic referred as Target organ toxicity. toxicity. 1-Acute Toxicity (irreversable): It occurs almost immediately (hours/days) after an exposure to single dose or a series of doses received within a 24 hour period. Death is a major concern in cases of acute exposures. Examples are: -In 1989, 5,000 people died and 30,000 were permanently disabled due to exposure to methyl isocyanate from an industrial accident in Bhopal, India. -Many people die each year from inhaling carbon monoxide from faulty heaters. b-Subchronic Toxicity (reversible) It results from repeated exposure for several weeks or months. This is a common human exposure pattern for some pharmaceuticals and environmental agents. Examples are: -Ingestion of coumadin tablets (blood thinners) for several weeks as a treatment for venous thrombosis can cause internal bleeding. -Workplace exposure to lead over a period of severa weeks can result in anemia. c-Chronic Toxicity (irreversible) : It is a cumulative damage to specific organ or system and it takes many months or years to become a recognizable clinical disease. This damage is so severe that the organ can no longer function normally (irreversible) and a variety of chronic toxic effects may result. Examples are: -Cirrhosis in alcoholics who have ingested ethanol for several years -Minmata syndrom due to mircury poisining -Chronic bronchitis in long-term cigarette smokers -Pulmonary fibrosis in coal miners (black lung disease) d-Carcinogenicity: Carcinogenicity is a complex multistage process of abnormal cell growth and differentiation which can lead to cancer. e-Developmental Toxicity: Developmental Toxicity result from toxicant exposure to either parent before conception or to the mother and her developing embryo-fetus. f-Genetic Toxicity: Genetic Toxicity results from damage to DNA and altered genetic expression. This process is known as mutagenesis. The genetic change is referred to as a mutation and the agent causing the change as a mutagen. 2-Organ Specific Toxicity : Blood and Cardiovascular Toxicity Hypoxia due to carbon monoxide binding of hemoglobin preventing transport of oxygen Anaemia is produced by benzene and aniline. Haemolysis may be due to saponins.. Hepatotoxicity CCl4……..metabolized by HME…….CCl3 (causes lipid peroxidation in liver & lead to liver. necrosis.) Also chloroform is hepatotoxic. Nephrotoxicity kidney damage and nephritis are produced by poisons such as phenol and sulphonamides. Mercury & gentamycin are nepherotoxic. Neurotoxicity Antimony and arsenic cause neurotoxicity Organophosphorus compounds (insecticides)………damage to sensory fibers. CNS excitation and convulsions are produced by strychnine, ephedrine and picrotoxin. CNS depression may be caused by substances such as barbiturates, ether and chloralhydrate. Delirium may indicate alcohol, atropine and related drugs. Respiratory Toxicity Aluminum…..emphysema……inflated lung …….fibrosis(aluminosis). Cardiovascular system Toxicity Myocardial depression is produced by compounds such as quinine and quinidine. Digitalis toxicity may lead to arrhythmia and ventricular fibrillation. Arise in blood pressure is increased by sympathomimetic agents such as ephedrine. Hypotension is caused by reserpine and nitrites. Skeletal muscleToxicity: Muscle paralysis is produced by lead, curare and flaxedil.. Dermal Toxicity some poisons such as atropine and aconite produce dry skin. Skin rash is produced by poisons such as arsenic and antimony. Some poisons produce increase in sweating e.g. pilocarpine. Strong acids and alkalies cause tissue damage upon contact with the skin.Cyanosis is produced by poisons such as aniline. Eye Toxicity Acids and strong alkalis may cause severe corneal corrosion corticosteroids may cause cataracts ,methanol (wood alcohol) may damage the optic nerve leading to blindness. Poisons such as ergot and lead salts impair general vision. The contracted pupil may be from morphine, opium, nicotine and pilocarpine while the dilated pupil may be from atropine, acotine and cocaine. Sudden death; some poisons act quickly and produce sudden death e.g. aconitine, cyanide and barium compounds.