Introduction to Toxicology and Forensic Medicine PDF

Introduction to Toxicology and Forensic Medicine Toxicants classification L1&L2 AA (1446)  Different areas Introduction of toxicology Toxin and Toxicants...

Introduction to Toxicology and Forensic Medicine Toxicants classification L1&L2 AA (1446)  Different areas Introduction of toxicology Toxin and Toxicants or poisons Poison classification Toxicology Routes of Toxicity Toxicity Dose Forensic Response Medicine  Toxicology is derived from two greek words : ‘toxikon meaning poison and ‘logos’ meaning study It is the study of adverse effect of chemicals or poisons on the biological systems It includes ✓Identification of poisons ✓Their chemical properties ✓Their biological effects ✓Treatment of disease conditions that they may cause Introduction Toxic effects of poisons may be expressed in several ways: ✓Changes in growth, ✓development, reproduction ✓pharmacokinetic responses, pathology , biochemistry ✓physiology and behaviour.  Descriptive toxicologist is concerned directly with toxicity testing, which provides information for safety evaluation and regulatory requirements (drugs and food additives). Mechanistic toxicologist identifying and understanding the mechanisms by which chemicals exert toxic effects on living organisms. Forensic toxicology is concerned primarily with the medicolegal aspects of the harmful effects of chemicals on human and determining their circumstances in a post-mortem investigation. Different Clinical toxicology is concerned with disease caused by or uniquely associated with toxic substances. areas of Environmental toxicology focuses on the impact of chemical toxicology pollutants in the environment on biological organisms, most commonly on nonhuman organisms such as fish, birds and terrestrial animals.  Poison and Toxin: Poison is any solid, liquid or gas that can interfere with life processes of cells of the organism and can exert physiological or psychological disorders Another term used for poison is toxicant – any agent capable of producing deleterious response in a biological system Toxins originate from biological processes are Toxin and classified as biotoxins Toxicosis describes the disease state that results Poison from exposure to poison or poisoning and intoxication.  Toxicologist: Studies the nature of adverse effect of toxins at molecular, cellular, organ, organism or even community level by understanding how these agents affect the system and how the system affects the agents Toxicity is the amount of a poison that under a specific set of conditions causes toxic effects or results in detrimental biological conditions. Toxin and Expressed as milligrams (mg) of toxicant per kilogram (kg) body weight that will produce a Poison defined biological effect. Dosage: total amount of toxicant per unit of body weight Dose: total amount of toxicant received by a person Toxic agents Toxin: generally, refers to toxic substances that are produced by biological as plants, animals, fungi or bacteria Toxic agents are classified in terms of Their target Effects (cancer, Use (pesticide, Source (animal organs (liver, mutation, liver solvent) and plant toxins) kidney) injury) Poisoning potential Chemical stability or General chemical Physical state (extremely toxic, reactivity (explosive, structure (gas, dust, liquid) very toxic, slightly flammable) (aromatic amine) toxic). Biochemical mechanisms of action (e.g. alkylating agent) Poison Poison is a substance which, when introduced into the living body, is capable of producing deleterious effects, ill health or death. Types of Poisoning: Ø Acute Poisoning Ø Chronic Poisoning Ø Sub-acute Poisoning Ø Fulminant Poisoning Poisoning episodes may be classified into four types: ✓ Accidental poisoning: Accidental poisoning may occur in young or older children and adults particularly as a result of mishaps at school or work e.g. Paracetamol is a common cause of accidental poisoning in young children. ✓ Suicidal poisoning: the commonest form of poisoning in adults and accounts for at least 95% of all poisoning admission to hospital. Such patients intentionally take poisons or overdoses of drugs. ✓ Homicidal poisoning: killing of a human being by another human being by administering poisonous substance deliberately ✓ Non-accidental poisoning: May present as an unusual illness rather than poisoning (Child abuse).  There are four categories of action of poisons—(i) local action, (ii) remote action, (iii) local and remote actions, and (iv) general action. ✓Local action (Corrosives): Local action means direct action on the affected site of the body. Examples include irritation and inflammation in strong mineral acids and alkalis, congestion and inflammation by irritants, the effect on motor and sensory nerves, etc. Toxicant’s or ✓Remote action: Remote action affects the person due to poison absorption of that poison into the system of that person. For classification example, alcohol is absorbed in the system and then it affects the person. ✓Local and remote actions (irritant metallic ): Some poisons can affect both local and remote organs. Thus, they not only affect the area with contact to the poison but also cause toxic effect after absorption into the system, for example, oxalic acid. ✓General action: General action means the absorbed poison affects more than one system of the body, for example, mercury, arsenic, etc. Toxicant’s or poison classification  Prevention of poisoning: Prevention of poisoning requires adequate knowledge of the hazardous properties of substances by users. When prescribing drugs, always be alert to their toxic potentialities so that the first signs will be recognized, and proper action taken  Factors modifying the action of poisons A- Factors related to the toxicant B- Factors related to the subject 1-Dose 1-Condition of the stomach 2-State of the poison i. Empty or full. 3-Methods of administration ii. Nature of the stomach content 4-Absorption iii. Gastric secretion 5-Distribution 2-Age of the patient 6-Metabolism 3-State of the patient’s health 7-Excretion 4-Tolerance or habituation 5-Personal hypersensitivity 6-Personal idiosyncrasy 7-Genetic factors  Poisons or toxins can enter the body through 4 different routes: Ingestion: The toxin is taken in the body by the oral route (eating or drinking). Toxins enters the blood through the walls of gastrointestinal tract Chemical properties of toxin will determine whether it will be absorbed in strongly acid stomach or the nearly neutral intestine Inhalation: Many toxins as gases or aerosols are inhaled and Routes of enter the blood through lungs. Absorption and excretion of the toxic gases and vapours depend primarily on their aqueous toxicity solubilities Dermal / topical: The toxins enters through the skin and moves into the bloodstream Epidermis largely limits absorption Parental Administration: The entry of the chemical is by injection: Intravenous, Intraperitoneal, Intramuscular. Food toxicity occurs primarily due to oral route e.g. consumption of contaminated food.  Selective toxicity means that a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact. An ideal antimicrobial agent exhibits Selective selective toxicity, which means that the drug toxicity is harmful to a pathogen without being harmful to the host. Often, selective toxicity is relative rather than absolute; this implies that a drug in a concentration tolerated by the host may damage an infecting microorganism.  Dose Response: ✓Major concept in toxicity is the relationship of dose and response ✓According to Paracelsus: All substances are poisons; there is none that is not a poison, and the right dose differentiates a poison and a remedy. ✓Any substance can provoke a dysfunction or injury at some degree of exposure--- the dose makes the poison, Dose Dose: The amount of substance entering into the body. This is usually given as milligrams of the chemical per Response kilogram of body weight (mg/kg) so that dose can be compared across specimens. The important parameters of toxicant to be considered are: ✓Duration and frequency, ✓Shape, size and solubility ✓How easily it will enters the body ✓How it will distribute within the body ✓The rate of its excretion from the body  Dose is the amount of drug to administered to produce a certain degree of response in a patient. Dose-response relationship has two components: ✓Dose-plasma concentration relationship ✓Plasma concentration-response relationship Response- the change in the activity of cell or tissue produced by the selected dose of the drug is called the Dose- response. response The dose and response is closely related to each other and this relationship is called dose response relationship. curve There is direct relationship between dose intensity of response of the curve, i.e. the intensity of response increases with the increase in dose. The typical curve showing the dose response relationship is called dose response curve (DRC). Dose-response curve As the dose of a toxicant increases, so does the response. For most toxicants, at very low amounts, there will be no detectable effect of the chemical i.e. no observed adverse effect level. Larger amounts of chemical will cause increasingly more severe biological responses until a maximum level of damage is reached. The amount of toxin entering into body and its frequency will determine the extent of toxicity. Acute toxicity will result within 24 hours if the dose is high enough. Repeated doses of the toxin over a period of 1 month will result in Subacute toxicity. When the exposure extends from 1 to 3 months then it will result in Subchronic toxicity. Chronic toxicity is caused by repeated doses of the toxin over a period of 3 months or more.  Threshold dose: is the minimal dose of any chemical that will produce effect. Dose Effective dose 50 (ED50):amount of drug that produces a therapeutic response or desired effect in 50% of the subjects taking it. ED50 is dependent upon the patient and can vary according to their age and health Therapeutic index (TI): A comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity: TI = LD₅₀/ED₅₀  Adverse effect or response of toxin: any change from an organism’s normal state that is irreversible at least for a period of time Producing an adverse effect depends on the concentration of the active compound at the target site. Adverse effect or Toxicity to an individual will vary due to individual genetic variation, gender, age, response nutritional status and health conditions. Individual variation of the organism will affect absorption, distribution, metabolism and excretion of the toxicant and therefore, its overall effect.  Translocation: Biotransformation is the process by which administered toxins or chemicals are modified by the organism. ✓This can occur at any point during the compound’s passage from absorption to excretion. ✓The key organs of biotransformation are Liver, Lungs, Metabolism, Kidneys, Intestine ✓Biotransformation may take place in two phases: Phase 1- absorption, enzymes make the toxicant more soluble, Phase 2- distribution, enzymes link with a soluble agent (Conjugation). and excretion The primary objective of metabolism is to make the of the chemical agents more water soluble and easier to excrete. toxicant ✓In some cases, biotransformation results in the formation of reactive metabolites – bioactivation. ✓There are two types of metabolism, detoxification and bioactivation. Detoxification is the process by which a xenobiotic is converted to a less toxic form. Bioactivation the metabolic activation of xenobiotic compounds into reactive, toxic compounds.  Absorption: The toxicant may have to pass many barriers to get to its site of action. Absorption is the ability of a chemical agent to enter the blood which is in equilibrium with the other tissues and target sites. In intravenous route there is no limiting factor in absorption and the toxin is 100 % bioavailable. Absorption When toxin is inhaled, it must penetrate alveolar sacs of lungs and then into capillary bed. & The intra-peritoneal toxin does not require absorption Distribution through the GI tract Toxins through dermal and topical route need absorption through the skin. Distribution: The process in which chemical agent translocates throughout the body is termed as distribution. The blood carries the agent to and from its site of action, storage, depots, organs of biotransformation and organs of elimination. The rate of distribution is usually rapid and is determined primarily by blood flow and the chemical characteristics of the toxicant.  Storage: After absorption into the blood stream, the toxins penetrate into various fluid compartments such as plasma, interstitial fluid, transcellular fluid and cellular fluids. Generally, equilibrium in most tissues takes place rapidly, In bone and adipose tissues with rather poor blood supply, relatively longer time is required to achieve equilibrium in the toxins. Some drug is stored in fatty tissues, while lead and Storage and fluoride are stored in the bones. Some chemicals may accumulate in various areas as a result of binding or due to Excretion their affinity for fat. Excretion: Toxicants are eliminated from the body through several routes: a) Urinary excretion – water soluble products are filtered out of the blood and excreted into the urine. Impaired renal function cause slower elimination of toxicants and increases their toxic potential. b) Exhalation – volatile compounds are exhaled through breathing. c) Biliary excretion – via faeces – compounds can be extracted by the liver, biotransformed, and excreted into the bile. The bile drains into the small intestine where the eliminated compounds can be excreted into the faeces. Faecal excretion also rids the body of non absorbed compounds which pass through the GI tract. Routes of absorption, distribution, and excretion of toxicants in the human body.  Conditions of the body: ✓Age factor: Poisons have greater effects at two extremes of age ✓Idiosyncrasy: Which is inherent personal hypersensitivity ✓Habit: Effect of certain poisons decreases with Conditions habituation. It results from a decreased reaction between the chemical and the biological effectors. of the body ✓State of Health: A healthy person tolerates better than a diseased one ✓Sleep : Action of some poisons get delayed if a person goes to sleep ✓Cumulative Action: Those poisons which are slowly eliminated from the body, may gradually accumulate and then may produce poisonous symptoms  Forensic medicine Definition: Forensic medicine is a branch of medicine where the principles and knowledge of medicine is used for purposes of the law, (both civil and criminal) and justice. Branches of Forensic Medicine Forensic ✓Forensic Pathology: The knowledge of medicine is used to medicine find out the cause of death. ✓Clinical Forensic Medicine: Medicolegal examination. ✓Forensic Toxicology: Deals with the sources, characters, properties of poisons, the symptoms they produce, their fatal effects & fatal doses & the remedial measures that should be taken to combat their actions or effects. ✓Forensic Thanatology: Investigates the mechanisms and forensic aspects of death.  Forensic Science is the parent course which has various sub-fields. While Forensic Science consists of Toxicology, Serology, Ballistics to Psychology, Forensic Medicine is a branch which deals in civil or criminal legal cases (investigation). Forensic Medicine is also known as Forensic Pathology. forensic Forensic medicine uses several different types of science and techniques forensic ✓Autopsy – earliest technique ✓DNA Typing – most recent technique medicine ✓Forensic Anthropology ✓Odontology (teeth examination) ✓Testing blood or Serology Key points By the end of this topic, you able to Identify and describe Identify the Toxin describe the Routes of toxicology, different and poison, their Toxicity , selective areas of toxicology classifications toxicity and interaction List the Factors Identify and describe modifying the action Dose response and Identify dose of poisons or toxin Dose-response curve Explain the Metabolism, Explain Adverse effect or response of absorption, Identify Forensic distribution, and Medicine toxin excretion of the toxicant