Food Toxicology - Chapter 1 PDF

University of Agriculture Faisalabad CHAPTER 1 FOOD TOXICOLOGY Dr. Rana Muhammad Aadil Associate Professor, NIFSAT, UAF Introduct...

University of Agriculture Faisalabad CHAPTER 1 FOOD TOXICOLOGY Dr. Rana Muhammad Aadil Associate Professor, NIFSAT, UAF Introduction Traditionally toxicology defined as The science of poison It is understanding of how various agents can cause harm to humans and other organisms Word toxicology is derived from two Greek words: Toxikon- meaning poison Logos- meaning study  Toxicology is the study of adverse effects of chemicals or poisons on the biological system Toxic effects may be expressed in several ways , including lethal effects such as changes in growth, development, reproduction, pathology, pharmacokinetic responses, biochemistry, physiology and behavior These effects ranging from immediate death to subtle changes not realized until months or years later Poison Any solid, liquid or gas that can interfere with life processes and can exert physiological or psychological disorders The term poison was derived from Latin word “potionem” a drink; i.e., drink, eat, breathe, inject or touch Enough of a chemical to cause illness or death It is harmful to the body when eaten, breathed, injected or absorbed through the skin Any substance can be poisonous if enough is taken. Toxins The term toxic expresses the effect of poison Poisinous or deadly effects on the body by inhalation (breathing), ingestion (eating), or absorption, or by direct contact with a chemical. A toxin is any poisonous substance of microbial (bacteria or other tiny plants or animals), vegetable, or synthetic chemical origin that reacts with specific cellular components to kill cells, alter growth or development, or kill the organism. The term “toxin” usually is used when talking about toxic substances produced naturally. Difference between poison and toxin Poison Toxin Poisons are substances that A toxin is cause harm to organisms a poisonous substance when sufficient quantities produced within living are absorbed, inhaled cells or organisms or ingested A toxin is often considered Chemicals cause harmful a specific type of poison effects to living organisms E.g; hemotoxins – destroy E.g; dioxins red blood cells, from snake  Toxicosis describes the disease state that results from exposure to a poison (used as intoxication and poisoning) Toxicologist- who studies the nature of these adverse effects at the molecular, cellular, organ, organism, or even community level by understanding how these agents affect the system and how the system affects the agents Toxicants Any agent capable of producing a deleterious response in a biological system Toxic substances include any substance whose physiological action is harmful to health. The term “toxicant” is used when talking about toxic substances that are produced by or are a by-product of human-made activities Arsenic, a toxic metal, may occur as a natural contaminant of groundwater or may contaminate groundwater as a by-product of industrial activities. Toxins originating from biological processes are generally classified as biotoxins  Organic toxins: Substance which are originally derived from living organisms Contain carbon and often are large molecules can be synthesized as well as obtain from natural source These toxins are not harmful to the organisms themselves, but they may be toxic to other creatures, including humans, when eaten Inorganic toxins: Specific chemicals that are not derived from living organisms – Examples of metal compounds toxic to humans include manganese, lead, cadmium, nickel, and arsenic compounds beryllium oxide, and the elemental vapours, inorganic salts, and organic compounds of mercury. Toxic substances may be systemic toxins or organ toxins Systematic toxins: Affects the entire body or many organs rather than a specific site – Potassium cyanide is a systemic toxicant in that it affects virtually every cell and organ in the body by interfering with the cell's ability to utilize oxygen. Organo toxins:Toxicants that affect only specific tissues or organs – Not producing damage to the body as a whole – These specific sites are known as the target organs or target tissues. – Benzene is a specific organ toxin in that it is primarily toxic to the blood-forming tissues. Toxic substances are classified into the following  Heavy metal  Solvents and vapors  Radiations and radioactive material  Dioxins/furans  Pesticides  Plants toxins  Animal toxins Toxic substances fall into several classes in relation to the way man is exposed Drugs Food additives Pesticides Industrial chemicals Environmental pollutants Natural toxins Household poisons Effects of toxins Carcinogenic: cancer causing Mutagens: cause mutation in genes Teratogen: cause birth defects Allergens: initiate unnecessary immune response Neurotoxins: damage nervous system Endocrine disruptors: interfere hormonal function Toxicity It is the amount of a poison that under specific conditions cause toxic effects or results in detrimental biological changes It is the degree to which a substance is poisonous or can cause injury It depends on dosage, duration and route of exposure, shape and structure of chemical itself and also individual human factors Its is usually expressed as milligrams (mg) of toxicant per kilogram (kg) body weight that will produce a defined biological effect  Routes of Toxicity There are four different routes: a. Ingestion- toxin is taken up by oral root – Chemicals that inadvertently get into the mouth and are swallowed do not generally harm the gastrointestinal tract itself unless they are irritating or corrosive – Chemicals that are insoluble in the fluids of the gastrointestinal tract (stomach, small, and large intestines) are generally excreted – Soluble chemicals are absorbed through the lining of the gastrointestinal tract. They are then transported by the blood to internal organs where they can cause damage.  – toxin enters into blood through the walls of GI tract – Chemical properties of toxin determine whether it will be absorbed in the strongly acid stomach or nearly neutral intestine b. Inhalation- many toxins, as gases or aerosols, are inhaled and enter the blood through the lungs – Absorption and excretion depends on their aqueous solubility – For most chemicals in the form of vapors, gases, mists, or particulates, inhalation is the major route of entry. – Once inhaled, chemicals are either exhaled or deposited in the respiratory tract – If deposited, damage can occur through direct contact with tissue or the chemical may diffuse into the blood through the lung-blood interface. Upon contact with tissue in the upper respiratory tract or lungs – It may cause health effects ranging from simple irritation to severe tissue destruction – Substances absorbed into the blood are circulated and distributed to organs that have an affinity for that particular chemical – Health effects can then occur in the organs, which are sensitive to the toxicant. c. Dermal/Topical- toxin enters through the skin and move into bloodstream. – Epidermis largely limits the absorption – Skin (dermal) contact can cause effects that are relatively innocuous such as redness or mild dermatitis – Severe effects include destruction of skin tissue or other debilitating conditions – Many chemicals can also cross the skin barrier and be absorbed into the blood system. – Once absorbed, they may produce systemic damage to internal organs. – The eyes are particularly sensitive to chemicals  – Even a short exposure can cause severe effects to the eyes, or the substance can be absorbed through the eyes and be transported to other parts of the body causing harmful effects – Pesticides like malathion and parathion caused deaths in agricultural workers due to precutaneous absorption. – Chlorovinylarsine dichloride, a mustard gas, is readily absorbed through intact skin d. Parenteral administration- the entry of the toxin by injection: intravenous, intraperitoneal or intramuscular – Substances may enter the body if the skin is penetrated or punctured by contaminated objects – Effects can then occur as the substance is circulated in the blood and deposited in the target organs. – The most effective route of exposure is the intravenous while topical route is the least effective route – Food toxicology occurs primarily due to the oral route, i.e., consumption of contaminated food Dose “All substances are poisons, there is none which is not a poison. The right dose differentiates a poison from a remedy” ----Paracelsus (1493-1541) Dosage- amount of toxicant per unit of body weight Dose- total amount of toxicant received by a person – The dose is the actual amount of a chemical that enters/administered administered at one time Lethal dose (LD) is the lowest dose that causes death in any living organism during the period of observation LD 50 is commonly used measure of toxicology Types of dose Exposure dose – The amount of dose encountered in enviornment Absorbed dose – The actual amount of exposed dose that enters the body Administrated dose – The quantity administrated usually orally or by injection Total dose – Sum of all individual doses Dose Response A major concept- relationship of dose and response. The dose-response relationship is a fundamental and essential concept in toxicology According to Paracelsus (1493-1541) “all substances are poisons; there is none that is not a poison and the right dose differentiates a poison and remedy” A consistent mathematical and biologically plausible correlation between the number of individuals responding and a given dose over an exposure period. The dose-response relationship is a fundamental concept in toxicology and the basis for measurement of the relative harmfulness of a chemical  Usually, the larger or more intense the dose, the greater the response, or the effect. This is the meaning behind the statement “the dose makes the poison.” Dose- amount of substance entering into body Amount of dose, frequency and mode of action are all important parameters The shape, size and solubility of the toxicant will determine how easily it enters the body, distribute within the body and rate of its excretion from the body Dose-response curve Relationship between the dose of a chemical (dependent variable) and the response produced (independent variable) follows a predictable pattern In general, a given amount of a toxic agent will elicit a given type and intensity of response. Knowledge of the dose-response relationship – Establishes causality that the chemical has in fact induced the observed effects – Establishes the lowest dose where an induced effect occurs - the threshold effect – Determines the rate at which injury builds up - the slope for the dose response.  Adverse effect or response- is any change from any organism’s normal state that is irreversible at least for a period of time Toxicity to an individual will vary due to individual genetic variation, gender, age, nutritional status and health conditions NOAEL- no observed adverse effect level at very low amount In the middle ranges of doses-the linear 16-84% of the curve Larger amount of chemical will cause increasingly more severe biological responses until a maximum level of damage is reached Toxicokinetics Toxicokinetics is the study of kinetics of absorption, distribution, metabolism, and excretion of a xenobiotic under the conditions of toxicity evaluation Xenobiotics defined as chemicals to which an organism is exposed that are extrinsic to the normal metabolism of that organism.  Click icon to add picture Toxicokinetics Illustrtion of toxins exposure, behaviour and excretion Exposure An organism must be exposed to an agent before there is a risk Physical properties and the concentration of toxin in the environment will determine the extent of exposure The amount of the toxin entering into the body and its frequency will determine the extent of toxicity Acute toxicity will result in 24 hours if the dose is high enough Repeated dose of the toxin over a period of one month will result in subacute toxicity and when the exposure tends 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  Translocation Biotransformation is the process by which administered toxins or chemicals are modified by the organism The key organs for biotransformation are liver (high), lungs, kidneys, intestine (medium) and others (low) Biotransformation may take place in two phases 1. The enzymes make the toxicant more soluble 2. The enzymes link with a soluble agent (conjugation) The primary objective of metabolism is to make the chemical agents more water soluble and easier to excrete Absorption and Distribution 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 When the toxin is inhaled, it must penetrate alveolar sacs of lungs and then into capillary bed Food toxin, which is ingested, requires absorption through the GI tract The intraperitoneal toxin does not require absorption through GI tract Toxin through dermal or topical route need absorption through the skin Absorption and Distribution Distribution- a process in which a chemical agent translocates through the body The blood carries the agent to and from its cite of action, storage depots, organs of biotransformation and organs of elimination Storage- after absorption into the blood stream, the toxins penetrate into various fluid compartments such as plasma, interstitial fluid, transcellular fluid and cellular fluids The accumulation may serve as a storage depot for the chemical  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 urine b. Exhalation-volatile compounds are exhaled through breathing c. Biliary excretion via faeces- compounds can be excreted 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 Test for toxicity The design of any toxicity test incorporates: – a test organism, which can range from cellular material and selected strains of bacteria through higher order plants and animals – a response or biological endpoint, which can range from subtle changes in physiology and behavior to death an exposure or test period – a dose or series of doses The objective is to select a test species that is a good model of humans, a response that is not subjective and can be consistently determined for a given dose, and a test period that is relatively short. Food toxicology  The study of toxic effects of food and water on human being Food toxicology is the study of the nature, properties, effects, and detection of toxic substances in food, and their disease manifestation in humans. All hazards associated with ingestion of food and water are studied under food toxicology Health disorders occur from the consumption of optimal amount of food containing harmful substances These maybe natural constituents of food (intrinsic) or maybe picked up by the food on its way to dining table (extraneous)  Food-a basic necessity which cause toxicity due to the presence of toxins 1. Intrinsic (natural) 2. Extraneous (picked up by food) Intrinsic chemical provide nourishment but sometimes they may prove toxic especially when consumed for a long period of time E.g; Oxalates in potatoes, phytates in grains and goitrogens in radish and turnip Intrinsic chemicals may not cause serious illness, but the extraneous chemicals (arsenic, mercury and zinc) may prove fatal Health hazards related to food include gastrointestinal disturbance (diarrhea, bacillary dysentery) or may affect some other parts of body (e.g; food allergy, botulism, tuberculosis)  Can cause gastrointestinal disturbances or affect some other parts of body Food poisoning is restricted to gastrointestinal disorders only while food toxicology covers all irregularities in the human body due to ingestion of food containing toxic substances Intensity and symptoms of food toxicity depends on the nature of contaminant, the nature and quantity of the food and consumer’s immunity system Food poisoning It is known as food intoxication Can be by chemical or poisonous plant and animal or by microrganism Chemical which can cause poisoning may enter in food from pesticides, insecticdes or utensils Poisonus plants – fara beans, mushrooms etc Poisonous animal – snakes and some jelly fishes Food intoxication VS food infection Food intoxication Food infection Live cells delivered by Cause by preformed the contaminated toxin in the food; food organism may or may not be alive and growing Toxins Bacterial/viral/ (natural/preformed parasites bacterial/chemical) Salmonella; E. Coli Costridium botulinum; Staphlococcus aureus No invation or Invade or multiply in multiplication lining of intestine Food intoxication Food infection Minutes to hour incubation hours to days incubation period period Not communicable Communicable Inadequate handling, Factor-inadequate cooking, cooking, improper handling cross contamination, poor personal hygiene, bare hand-contact Symptoms Symptoms Vomiting, nausea, diarrhea, Diarrhea, nausea, weakness, respiration vomitting, abdominal faliure, numbness. cramps, fever Food toxication source It is caused by microorganisms is widespread, they are common feature of societies with low standards of hygiene (e.g., Asian and African countries) Some bacteria such as Vibrio cholerae, use food as a vehicle for transport into the human body and symptoms of such illness appear only when these have multiplied sufficiently in the gut On the other hand, such bacteria as Staphylococcus aureus and Clostridium botulinum essentially need to grow in the food and produce the toxin  Symptoms of such illness may appear within 2 to 6 hours of the consumption of contaminated food depending upon the amount of toxin produced in the food and ingested by the victim Serious toxicity results from extraneous substances of chemical nature (agricultural chemicals such as pesticides, fertilizers) During food preparation, food handlers may contaminate the food with microorganisms, while the equipment may add harmful chemicals or even microorganisms Water- important constituent of food Underground water contains chemicals dissolved in it and surface water is rich in contaminants of chemical and biological origin which may cause diseases such as cholera, typhoid, paratyphoid, bacillary dysentery, diarrhea and others  According to United Nation estimates, almost 60% people in developing countries do not have access to safe drinking water and each year between 10-25 million people die from diseases related to unclean or safe water supply The ultimate desire of food handler, processor and distributor is to make food safe from toxic substances Commercially processed foods, if properly handled during and after processing, are considered “low risk” as potential source of food toxicity