Essentials of Environmental Health Lecture 3, Principles of Toxicology - 2024

College of Public Health Department of Public Health Essentials of Environmental Health Lecture 3 Principles of Toxicology Dr. Mohamed Elfatih 2024  What is ? "the science of poisons." ...

College of Public Health Department of Public Health Essentials of Environmental Health Lecture 3 Principles of Toxicology Dr. Mohamed Elfatih 2024  What is ? "the science of poisons."  TOXICOLOGY (from the Greek toxinos , meaning “poison” )  Is the study of the adverse effects of chemicals on biological systems.  These adverse effects can range from mild skin irritation to liver damage, birth defects, and even death. Both natural and man- made chemicals are studied. history not impotrant So, Toxicology is the study of: ⚫ How toxicants enter the organism ⚫ How toxicants effect the organism ⚫ How toxicants are eliminated from the organism All substances are toxic if taken in the wrong quantities  What is a Poison? “defined as any agent capable of producing a harmful response in a biological system. practically every known chemical has the potential to produce injury or death if it is present in a sufficient amount.” All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy.  The breadth of topics in toxicology requires the field to take an interdisciplinary approach, borrowing techniques and methods from numerous scientific fields Physiology Chemistry Medicine Pharmacology Toxicology Biochemistry Epidemiology Pathology WHAT TOXICOLOGISTS DO: - involved in the recognition, identification, and quantitation of hazard - develops standards and regulations to protect health and the environment - involved in safety assessment and use of data as basis for regulatory control of hazards - determines risk associated with use of chemicals  Toxicology Today Mechanistic toxicology: The study of how a chemical causes toxic effects by investigating its absorption, distribution, and excretion. Descriptive toxicology: The toxic properties of chemical agents are systematically studied for various endpoints using a variety of different organisms. Clinical toxicology: The study of toxic effects of various drugs in the body. and are also concerned with the treatment and prevention of drug toxicity in the population.  important to know the diffrents Forensic toxicology: A branch of medicine that focuses on medical evidence of poisoning and tries to establish the extent to which poisons were involved in human deaths. Environmental toxicology: The study of the effects of pollutants on organisms, populations, ecosystems, and the biosphere. Regulatory toxicology: The use scientific data to decide how to protect humans and animals from excessive risk. In Public or Private Sector. Analytical toxicology : is concerned with the detection, identification, and measurement of drugs and other foreign compounds (xenobiotics) and their metabolites in biological and related specimens.  Toxic agent or substance What is Toxic agent? Is anything that can produce an adverse biological effect. It may be chemical, physical, , or biological in form ❖ Chemical: (inorganic substances, such as heavy metals (mercury) and carbon monoxide, and organic compounds, such as methyl alcohol.) ❖ Physical: (such as radiation) and ❖ Biological: are harmful chemical compounds produced by living organisms. They come from bacteria, dinoflagellates, algae, molds and fungi, plants, and animals. Some biological agents are highly toxic other example: (snake venom). Toxic substance is simply a material which has toxic properties. What is toxic? Toxic refers to a poisonous or deadly effect on a body caused by inhalation, ingestion, or absorption of, or direct contact with, a chemical. made by man Toxins vs toxicants ▪ Until the late 19th century, nearly all toxic substances were called toxins. ▪ But by the 1930s , a new term came to describe chemical-biological harm and its relations with living systems. ▪ The term “toxicant” replaced “toxin” in descriptions of pesticides in scientific literature (Ebling, 1940). Toxin is usually used when referring to a toxic substance produced naturally. Toxicant is usually used when referring to a toxic substance that is produced by, or a by-product of, man-made activities. Dose The amount of chemical entering the body This is usually given as mg of chemical/kg of body weight = mg/kg The dose is dependent upon : The concentration if you drink 5 liters of water The properties of the toxicant that contains 1 milligram per liter of fluoride concentration, The timing and frequency of exposure what is the Dose you have consumed? 5 The length of exposure The exposure pathway  Dose & Dosage dose: the amount of substance administered at one time the patient was given a dose of 500 mg of paracetamol. dosage: the amount and rate of administration of a substance The dosage was changed to 500 mg every 4 hours. Example: ❑ 400 mg of X (medication) ❑ taken by 10 kg infant every 8 hours. 1200 ❑ the appropriate dosage range (100-150) mg/kg per day. 1000 to 1500 shuld ❑ Calculate if this dosage within the desired range or not?  What is a Response? (Change from normal state ) The degree of responses depend upon the dose and the organism – could be on the molecular, cellular, organ, or organism level -the symptoms Local vs. Systemic Immediate vs. Delayed There are two types of Response according to the dose response: ❖ Monotonic – response increases with dose Ex. (cyanide and many traditional toxicants) ❖ Nonmonotonic – response does not increase with dose (hormones, micronutrients and vitamins) How toxicants enter organism ⚫ Inhalation (mouth or nose to lungs) then into blood ⚫ Ingestion (mouth to stomach) then into blood ⚫ Injection (cuts, punctures in skin) into blood ⚫ Dermal absorption (through skin) into blood Effects of Toxicants Irreversible Effects ⚫ Carcinogen - causes cancer ⚫ Mutagen - causes chromosome damage ⚫ Reproductive hazard - damage to reproductive system ⚫ Teratogen - causes birth defects Effects of Toxicants cont. May or may not be reversible ⚫ Dermatotoxic – affects skin ⚫ Hemotoxic – affects blood ⚫ Hepatotoxic – affects liver ⚫ Nephrotoxic – affects kidneys ⚫ Neurotoxic – affects nervous system ⚫ Pulmonotoxic – affects lungs Elimination of toxins ⚫ Excretion through kidneys, liver and lungs..etc. ⚫ Detoxification is the biotransformation of by liver chemicals into something less harmful ⚫ Storage in fatty tissue dose response curve A typical dose–response curve for an individual exposed to ethyl alcohol Source: Reprinted with permission from AE Marczewski, M Kamrin. Toxicology for the Citizen. 2nd ed. East Lansing, Mich: Michigan State University, Center for Integrative Toxicology; 1991:5. FACTORS THAT AFFECT RESPONSES TO A TOXIC CHEMICAL Several factors determine whether an individual will respond to exposure to a toxic chemical and the type of response that occurs:  Route of entry into the body Inhalation (breathing) Skin (or eye) contact  Received dose of the chemical Swallowing (ingestion or eating)  Duration of exposure Injection  Interactions that transpire among multiple chemicals  Individual sensitivity Determining Health Effects of toxicants Major Types of Toxicity Chronic toxicity: It involves Sub-lethal concentration and long-term exposure Adverse effects occur some time after exposure, or after prolonged exposure to toxin Symptoms often mimic other diseases- hard to assess source Chronic toxicity test is used to derive Effective Dose (ED50): Is the dose by which half of the population has been affected Effect could be anything but not death ED50 is obtained by plotting, for a given dose the proportion of the population that responded to that dose and all lower doses  Major Types of Toxicity cont. Acute toxicity: It involves lethal concentrations and short-term exposures ( Adverse effects occur within a short period after exposure to toxin) The end point is usually death An LD50 (Lethal dose) is a dose of a toxic chemical that kills half of the population. LD50 is obtained by plotting, for a given dose the proportion of the population that responded to that dose and all lower doses  how toxic substances enter the body? TOXICANTS IN THE BODY skip After a person is exposed to a xenobiotic (a chemical foreign to the body), a sequence of steps determines the response to the chemical: Absorption into the body, Distribution throughout the body, Metabolism, and Excretion. Along the way, toxic effects may occur. Understanding the risks of a chemical exposure and how to reduce these risks requires understanding Toxicokinetic, that is, the processes in this toxicological sequence. Toxicokinetic describes how a toxicant (i.e., a poison) enters the body and reaches a target tissue. Toxicodynamic describes what happens to that tissue once the toxicant reaches an effective dose  Environmental Toxicology Is defined as the study of the fate and effects of chemicals in the environment. Although this definition would encompass toxic chemicals naturally found in the environment (i.e., animal venom, microbial and plant toxins). Environmental toxicology can be divided into two subcategories: Environmental health toxicology is the study of the adverse effects of environmental chemicals on human health. Ecotoxicology involves the study of the adverse effects of toxicants on myriad of organisms that compose ecosystems ranging from microorganisms to top predators The simplest definition found to date is that ecotoxicology is "the study of the harmful effects of chemicals upon ecosystems" (Walker et al, 1996).  It was after World War II that increasing concern about the impact of toxic chemicals on the environment led Toxicology to expand from the study of toxic impacts of chemicals on man to that of toxic impacts on the environment. This subject became known as Environmental Toxicology. Ecotoxicology is a relatively new discipline and was first defined by René Truhaut in 1969. It attempts to combine two very different subjects: ecology ("the scientific study of interactions that determine the distribution and abundance of organisms" Krebs 1985) and toxicology ("the study of injurious effects of substances on living organisms", usually man). In toxicology the organisms sets the limit of the investigation whereas Ecotoxicology aspires to assess the impact of chemicals not only on individuals but also on populations and whole ecosystems.  During the early years, the major tools of Environmental Toxicology were: detection of toxic residues in the environment or in individual organisms and testing for the toxicity of chemicals on animals.  It was however, a very big jump in understanding from an experimental animal to a complex, multivariate environment and the subject of ECOTOXICOLOGY developed from the need to measure and predict the impact of pollutants on populations, communities and whole ecosystems rather than on individuals. A more complete definition of Ecotoxicology comes from Forbes & Forbes 1994 “the field of study which integrates the ecological and toxicological effects of chemical pollutants on populations, communities and ecosystems with the fate (Transport, transformation and breakdown) of such pollutants in the environment”.  skip There are three main objectives in ecotoxicology (Forbes & Forbes 1994): 1) Obtaining data for risk assessment and environmental management. 2) Meeting the legal requirements for the development and release of new chemicals into the environment. 3) Developing empirical or theoretical principles to improve knowledge of the behaviour and effects of chemicals in living systems. Environmental Pollution and pollutants o Often difficult to link pollutants to their effects on people, Why? In environmental circles, many people confuse the terms of: ❖ Persistence ❖ Bioaccumulation ❖ Biomagnification These words are encountered when dealing with issues concerning the gradual build-up of toxic substances in the bodies of organisms; ultimately, in the human body  Persistence other file o A characteristic of certain chemicals that are extremely stable and may take many years to be broken down into simpler forms by natural processes ▪ Synthetic chemicals (those not found in nature) Ex: Persistent organic pollutants (POPs) such as DDT ▪ Natural decomposers (bacteria) have not evolved a way to break it down  Bioaccumulation o Bioaccumulation is defined as the increase in concentration of a substance(s) in an organism or a part of that organism. Toxic substances are lipophilic or fat-loving, the reason why these substances are deposited and concentrated in the fat tissues of the organisms. ▪ Synthetic chemical do not metabolize well ▪ They remain in the body for extended periods of time Examples: lead, mercury, dichlorodiethyltrichloroethane (DDT),  Biomagnification o Biomagnification is also called Bioamplification. It is simply the increase in concentration of a substance in a food chain, not an organism. o The increased concentration of toxic chemicals in the tissues of organisms that are at higher levels in food webs o Diagram is example of biomagnification of DDT thank you See you next lecture Insha Allah