TOXI LEC (1).pdf

as biological agents. An example of this is a virus that S1: INTRODUCTION TO TOXICOLOGY damages cell membranes resulting in cell death If the invading...

as biological agents. An example of this is a virus that S1: INTRODUCTION TO TOXICOLOGY damages cell membranes resulting in cell death If the invading organisms excrete chemicals which are BASIC TERMINOLOGY the basis for their toxicity, the excreted substances are TOXICOLOGY known as biological toxins. In that case, the organisms ○ an evolving medical science and are called toxic organisms. A specific example is toxicology terminology is evolving with it tetanus ○ study of the adverse e ects of chemicals or physical agents on living organisms Tetanus is caused by a bacterium, Clostridium tetani. TOXICOLOGIST The bacteria C. tetani itself does not cause disease by ○ scientist who determines the harmful invading and destroying cells. Rather, a toxin e ects of agents and the cellular, (neurotoxin) that the bacteria excrete travels to the biochemical, and molecular mechanisms nervous system and produces the disease responsible for the e ects TOXINOLOGY TOXIC SUBSTANCE ○ a specialized area of study, looks at ○ a material that has toxic properties. It microbial, plant and animal venoms, may be a discrete toxic chemical or a poisons, and toxins mixture of toxic chemicals. For example, TOXICANTS lead chromate, asbestos, and gasoline ○ substances producing adverse biological are all toxic substances. More specifically: e ects of any kind. May be chemical or ○ Lead chromate is a discrete toxic physical in nature. E ects may be acute chemical or chronic ○ Asbestos is a toxic material that does TOXINS not have an exact chemical composition ○ peptides or proteins produced by living but comprises a variety of fibers and organisms. Venoms are toxins injected by minerals a bite or sting ○ Gasoline is a toxic substance rather than POISONS a toxic chemical in that it contains a ○ toxins produced by organisms mixture of many chemicals. Toxic substances may not always have a constant composition. The composition of gasoline varies with octane level, manufacturer, time of season, and other factors Toxic substances may be systemic toxicants or organ toxicants SYSTEMIC TOXICANT TOXIC AGENT ○ a ects the entire body or many organs ○ anything that can produce an adverse rather than a specific site. For example, biological e ect. It may be chemical, potassium cyanide is a systemic toxicant physical, or biological in form in that it a ects virtually every cell and organ in the body by interfering with the cells’ ability to use oxygen. Toxicants may also a ect only specific tissues or organs while 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 toxicant in that it is primarily toxic to the blood-forming tissues Lead is also a specific organ toxicant; however, it has three target organs: central nervous The toxicity of the agent is dependent on the dose. system, kidneys, and A distinction is made for diseases people get from hematopoietic system living organisms. Organisms that invade and multiply A toxicant may a ect a specific type of tissue within another organism and produce their e ects by (such as connective tissue) that is present in biological activity are not classified as toxic agents but several organs. The toxic site is then considered the target tissue jt & pia | TOXI LAB | 1  ○ Often, people mistakenly assume that all TYPES OF CELLS man-made chemicals are harmful and The body is composed of many types of cells, natural chemicals are beneficial. In which can be classified in several ways. Table 1 reality, natural chemicals can be just as shows examples of one classification of one type harmful to human health as man-made of cells chemicals, and in many cases, more harmful. Figure 12 compares the toxicity of several natural and man-made CELL TYPES EXAMPLE chemicals Basic structure Cuboidal cells —-------------------------- SUMMARY ----------------------------- Tissue type Hepatocytes of the liver Toxicology is the study of adverse e ects of chemicals and physical agents on living Germ cells Ova and sperm organisms. A xenobiotic is a foreign substance taken into the Somatic cells Non-reproductive cells of body. the body A toxic agent is any chemical, physical, or biological agent that can produce an adverse GERM CELLS biological e ect. ○ are involved in reproduction and can give Toxic substances can be systemic toxicants, which rise to a new organism. They have only a a ect the entire body or multiple organs, or single set of chromosomes peculiar to a organ toxicants, which a ect a specific organ or specific sex. Male germ cells give rise to tissues. sperm and female germ cells develop into The dose of a substance is the most important ova. Toxicity to germ cells can cause determinant of toxicity. e ects in a developing fetus that lead to outcomes such as birth defects or S2: DOSE AND DOSE RESPONSE miscarriage SOMATIC CELLS ○ all body cells except the reproductive DOSE germ cells. (Somatic cells include the "basic structure" and "tissue type" cells Dose by definition is the amount of a substance listed in Table 1). They have two sets (or administered at one time. However, other pairs) of chromosomes. In an exposed parameters are needed to characterize the individual, toxicity to somatic cells causes exposure to xenobiotics. The most important are a variety of toxic e ects, such as the number of doses, frequency, and total time dermatitis, death, and cancer. Figure 11 period of the treatment. illustrates the di erences between germ For example: cells and somatic cells ○ 650 mg acetaminophen (Tylenol® products) as a single dose. ○ 500 mg penicillin every 8 hours for 10 days. ○ 10 mg DDT per day for 90 days. Substances can enter the body from either: 1. Encountering them in the environment (exposure). 2. Intentionally consuming or administering a certain quantity of a substance. Environments in which xenobiotics are present include outdoor air, indoor air, and water. Xenobiotics can travel into the body through the skin, eyes, lungs, and digestive tract. Exposure to a xenobiotic (see below) can occur in any environment where a substance can enter the: ○ Skin through dermal absorption (air and water). ○ Respiratory tract through inhalation. ○ Digestive tract through ingestion. Exposure to a xenobiotic Measuring the amount of a substance a person encountered in the surrounding environment often is di cult, but a person's exposure to a xenobiotic can be NATURAL AND MAN-MADE CHEMICALS estimated by collecting samples from the jt & pia | TOXI LAB | 2  environment and analyzing which substances are FRACTIONING DOSES present in them and at what amounts. Fractionating a total dose usually decreases the probability that the total dose will cause toxicity. The reason is that the body often can repair the e ect of each subtoxic (a dose which elicits e ects that are below the level of detection with standard toxicological parameters) dose if su cient time elapses before the next dose is received. In that case, a total dose that would be harmful if received all at once is non-toxic when administered over a period of time. ○ For example, 30 mg of strychnine A dose can be considered either: swallowed at one time could be fatal to 1. A measurement of environmental an adult whereas 3 mg of strychnine exposures. swallowed each day for 10 days is not 2. The amount of a substance administered considered a fatal dose. over a period of time. The units used in toxicology are basically the Types of doses include: same as those used in medicine. ○ ABSORBED DOSE — the amount of a ○ The gram (g) is the standard unit. substance that entered the body through ○ Because most exposures are in smaller the skin, eyes, lungs, or digestive tract quantities, the milligram (mg) is and was taken up by organs or particular commonly used. tissues. Absorbed dose can also be called ○ For example, the common adult dose of internal dose. acetaminophen is 650 mg. ○ ADMINISTERED DOSE — the quantity administered usually orally or by injection (note that an administered dose taken IMPORTANCE OF AGE, BODY SIZE, AND TIME orally may not necessarily be absorbed). A person’s age and body size a ect the clinical ○ TOTAL DOSE — the sum of all individual and toxic e ects of a given dose. Age and body doses. size usually are connected, particularly in Not all substances that enter the body are children. This relationship is important because a necessarily absorbed by it. This concept applies person's body size can a ect the burden that a to water intake. When a person drinks a large substance has on it. For example, a 650-mg dose quantity of water at one time, some of it is of acetaminophen is typical for adults but it absorbed while the rest of the water is eliminated. would be toxic to young children. Therefore, a If an individual drinks 1 liter of water every hour tablet of an acetaminophen product designed for for 3 hours, each administered dose would be 1 children (Children's Tylenol®) contains only 80 mg liter. The total dose would be the amount the of the drug. person drank over the time period that the water One way to compare the e ectiveness of a dose was consumed. The absorbed dose, however, and its toxicity is to assess the amount of a would likely be less than the total dose because it substance administered with respect to body would depend on how much of the water the weight. A common dose measurement is mg/kg individual's body absorbed which can be a ected which stands for mg of substance per kg of body by various factors. The water intake example is weight. Another method used to compare doses represented in the table below: among di erent species is to use body surface area (see below), rather than simply body weight. DOSES ADMINISTERED TOTAL ABSORBED BODY SURFACE AREA DOSE DOSE DOSE ○ In toxicology studies, toxic e ects are tested in animals before any testing is Dose 1 (8 1L 1L