Toxicology Lecture PDF

Toxicology DR.MAMDOUH ORABY  Introduction Intended learning outcomes (ILOs) Identify the general principles of basic toxicology. Understand the principles of clinical management of toxicity. Studying the potential hazards of different toxic...

Toxicology DR.MAMDOUH ORABY  Introduction Intended learning outcomes (ILOs) Identify the general principles of basic toxicology. Understand the principles of clinical management of toxicity. Studying the potential hazards of different toxic agents, including heavy metals, pesticides, toxic gases, drug-induced toxicity, drug abuse. Identify the principles of forensic toxicology.  Introduction Introduction to toxicology ❑ Definition of Toxicology: Is the study of the adverse effects of chemical or physical agents on living organisms. It is a multidisciplinary field of science (involves many sciences such as chemical, biochemical, pathological and physiological, experimental observations) to understand why certain substances can cause toxic effects on biological systems.  Introduction Different areas of toxicology ❑ Different areas of Toxicology are specified as follows: 1- Descriptive toxicology: Concerned with toxicity testing (performed on cell culture & experimental animals). Provides information about safety & toxicity of chemicals on human beings and environment.  Introduction Different areas of toxicology May classified to study potential effects on: ✓ Humans (e.g., drugs & food additives). ✓Fish, birds, plants and other factors that can disrupt the balance of the ecosystem (e.g., company’s chemicals).  Introduction Different areas of toxicology 2- Mechanistic toxicology: Concerned with identifying and understanding biochemical and molecular mechanisms by which chemicals exert toxic effects on living organisms.  Introduction Different areas of toxicology 3- Regulatory toxicology: Deciding whether a drug or a chemical has low risk to be marketed as drug or food additive based on data provided by descriptive or mechanistic toxicology.  Introduction Different areas of toxicology ❑ The Food and Drug Administration (FDA): Is responsible for allowing drugs, cosmetics, and food additives to be sold in the market.  Introduction Different areas of toxicology 4- Forensic toxicology: Concerned with identification & study of toxic chemicals that can cause death (postmortem investigation). Apply analytical chemistry for identifying toxic chemicals in biological samples. 5- Clinical toxicology: Concerned with diagnosis & management of diseases caused by toxins (poisoned patients).  Introduction Different areas of toxicology 6- Environmental toxicology: Study the effect of chemical pollutants in the environment on biological organisms )deals with industrial hygiene(. 7- Toxicogenomics (genetic toxicology): Study the alteration in living cell genome in response to environmental toxins (e.g; genotoxic carcinogen). Deals also with genetic polymorphisms that affect the detoxification of certain chemotherapeutic agents.  Introduction Risk assessment Dependence of societies on chemicals necessitate the assessment of its potential hazards Toxicologists are important members of the decision- making process.  Introduction Risk assessment ❑ Risk assessment: is the quantitative estimate of the potential hazards of chemical exposures on human health and environments e.g., pesticide residues on food, contaminants in drinking water.  Introduction Risk assessment ❑ Four steps for risk assessment of a chemical: 1. Hazard identification Identify whether the exposure to the substance causes adverse health effects or not. Identify types of toxic effects of the hazard (e.g, hepato- ,reno-,neurotoxicity & birth defects & carcinogen). Identification of the hazard can be obtained from: ▪ Experimental studies (in vitro and in vivo analysis; toxicity testing) ▪ Epidemiologic Studies (Observations on human beings)  Introduction Risk assessment 3. Exposure assessment 2. Dose-response assessment ❑ Identify the quantitative ❑ Identify routes (oral, dermal, relationship between dose parenteral, inhalation) and duration (amount of exposure) and extent (frequency of dose) of exposures to of toxic response (adverse substance in question. effects). ❑ In dose assessment, NOAEL and LOAEL is calculated  Introduction Risk assessment 4. Risk characterization ❑ Estimate the nature of adverse effects of the hazard in a given population ❑ Estimate if there is a susceptible population ▪ Ex; Mexicans are more vulnerable to pesticides than others as many of them are agricultural workers.  Introduction Risk assessment  Introduction What is a Poison? ❑ A poison is any agent capable of producing a deleterious response in a biological system. But ▪ What is there that is not poison? ❑ Actually, all things and substances are poison (nothing without poison) if it is present is a in a toxic dose. ❑ Therefore, it has been stated that the “Dose makes the poison"  Introduction Different terms of poisons ❑ Toxin: ▪ Any toxic agent that is produced naturally ▪ Ex; Plants, Animals (snake venom), Fungi, Bacteria. ❑ Toxicant: ▪ Any toxic agent that is human-made (ex; industrial wastes). ▪ Substances that are human-made & occurring naturally are referred to as toxicants (ex; arsenic). ❑ Xenobiotic: ▪ A foreign substance to the normal physiology of the body (ex; drugs & toxic chemicals).  Introduction Sources (types) of toxic agents 1. Therapeutic agents: ▪ Toxicity from drug overdoses (Digoxin & Paracetamol) ▪ Frequent drug administration ▪ Drug interactions 2. Industrial chemicals: ▪ Chemicals that induce environmental pollution ▪ Cause direct hazards at the workplace (ex; heavy metals). 3. House-hold chemicals: ▪ Ex; Cleaning agents, Cosmetics, and personal products.  Introduction Sources (types) of toxic agents 4. Natural toxins: ▪ Ex, Snake venom & botulinum toxins ▪ Toxicity can arise from biting and stinging or contamination of food. 5. Drugs of abuse: ▪ Recreational drugs (not for medical purposes) that alter consciousness & cause feelings of well-being.  Introduction Sources (types) of toxic agents ❑These drugs have high potential for dependence and addiction (e.g. alcohol, opioids, nicotine,………..(. 6. Environmental contaminants: ❑ Such as pesticides, smokes of factories and vehicles. ❑ Environmental contaminants may be released into air, water, or dumped onto land.  Introduction Routes and sites of exposure 2- Inhalation 1- Ingestion ▪ Through lungs. ▪ Through GIT. ▪ Ex; toxic gases, ▪ Ex; Cleaning agents, (fumes, carbon drugs, plants, foods. monoxide, ammonia, chlorine). 3- Percutaneous 4- Parenteral ▪ Through skin ▪ Through injection ▪ Ex; Cleaning agents, ▪ Ex; animal bites & drugs, or corrosives. intentional injection of drugs of abuse.  Introduction Types of toxicity 1- According to circumstances of toxicity a) Accidental toxicity b) Deliberate Toxicity (non-intentional) (suicidal or criminal) ▪ Occurs by mistake ▪ Occurs when person ▪ Common between attempts to kill himself children. or another person ▪ Ex; Aspirin & ▪ Ex: cyanide & kerosene & pesticides salicylates  Introduction Types of toxicity 2- According to incidence of toxicity I. Occupational toxicity ❑ Ex; industrial & agriculture poisoning (inhalation of pesticides). II. Home toxicity ❑ Ex; potassium hydroxide disinfectants  Introduction Types of toxicity 3-According to the onset of toxicity - Acute toxicity - Sub-acute - Sub-Chronic - Chronic-toxicity ▪ Occurs after toxicity - Results from -Results from single exposure to -Results from repeated repeated poison for less repeated exposure to a exposure to a than 24 hr. exposure to chemical for chemical for more ▪ Ex: Asphyxiation a chemical than 3 months 1 to 3 months from exposure to a for 1 month - Ex: Cirrhosis in high concentration alcohols. of CO.  Introduction Types of toxicity  Introduction Toxicological effects 1- Allergic reactions (hypersensitivity reactions) Immunologically mediated toxicity to a chemical / a structurally similar one. Resulting from previous sensitization to that chemical. Allergic reactions may not be dose related (can occur from exposure to low doses of chemicals) It can be dose related (ex; allergy to pollens in sensitized patients; occurs in response to pollen concentration in the air). Allergic reactions is a toxic response which are sometimes fatal.  Introduction Toxicological effects 2- Immediate versus Delayed toxicity: Immediate toxicity: Occurs rapidly after a single administration of a substance. ❖ Ex: Toxicity from CO Delayed toxicity: Develop after a long latency period. ❖ Ex: Carcinogenic effects of chemicals take from 20 to 30y after the initial exposure, to occur in humans (e.g; diethylstilbestrol-induced vaginal cancer).  Introduction Toxicological effects 3- Reversible versus irreversible toxic effects: Some toxic effects of chemicals are reversible & others are irreversible. The ability of a tissue to regenerate after pathological injury by a chemical largely determines whether the effect is reversible or irreversible.  Introduction Toxicological effects Ex: liver has a high ability to regenerate, so most liver injuries are reversible. Ex: CNS injuries are largely irreversible. ❑ Carcinogenic and teratogenic effects of chemicals are considered irreversible toxic effects.  Introduction Toxicological effects 4- Local versus Systemic Toxicity a. Local effects - Occur at the site of first contact between the biological system and the toxicant. - Ex 1; ingestion of caustic substances. - Ex 2: inhalation of irritant material (e.g.; chlorine gas causes inflammation & swelling of lung tissue)  Introduction Toxicological effects N.B: Local toxicity may cause indirect systemic effects (severe acid burns-induced kidney damage) b. Systemic effects - Requires absorption & distribution of a toxicant. - Ex: Tetraethyl lead produces effects on skin at the site of absorption and is then transported systemically to produce its toxic effects on the CNS and other organs.  Introduction Interaction between toxicants Several terms have been used to describe pharmacologic and toxicologic interactions. 1- Additive effect: Occurs when the combined effect of two chemicals is equal to the sum of the effects of each agent given alone. Ex; if compound A produces a toxic effect equal= 2; while compound B produces toxic effects equal = 3 ▪ The combined additive toxic effect equal = 5 Ex: Exposure to two organophosphate insecticides → additive cholinesterase inhibition.  Introduction Interaction between toxicants 2- Synergistic effect: ✓Occurs when the combined effects of 2 chemicals are much greater than the sum of the effects of each agent given alone (e.g.; 2 + 3 > 5). ✓ EX: CCl4 (carbon tetrachloride) + ethanol = more liver injury than the mathematical sum of their individual effects on liver at a given dose.  Introduction Interaction between toxicants 3- Potentiation: ✓ When one substance does not have a toxic effect on a certain organ or system but when combined with another chemical makes that chemical much more toxic (e.g.; 0 + 2 > 2). ✓ EX: Isopropanol (non-hepatotoxic) + CCI4 (hepatotoxic) = higher hepatoxicity of CCI4 than when it is given alone.  Introduction Interaction between toxicants 4- Antagonism: ✓Occurs when two chemicals administered together interfere with each other’s actions or one interferes with the action of the other (Ex: 4 + (-4)= 0 ; 4 + 0 = 1 or < 4). Antagonism may be functional, chemical, dispositional (effect on absorption, distribution or metabolism), or receptor (blockers). Thank You