Transcript Chapter 20
Chemistry for Changing Times 11th Edition Hill and Kolb Chapter 20 Poisons John Singer Jackson Community College, Jackson, MI © 2007 Prentice Hall Chemical Toxicology Poison A poison is a substance that causes injury, illness, or death of a living organism. “The dose makes the poison.” All substances are poisonous, depending on the amount. Toxicology is the study of poisons, their effects, detection, identification, and antidotes. Natural Poisons Many natural substances are acutely toxic. Socrates was put to death by drinking a cup of hemlock. Hemlock contains coniine, which is an alkaloid. Natural Poisons Poisons in the Garden and on the Farm Many of the berries, flowers, and leaves found in a common garden are toxic. Farmers and ranchers have to deal with plants which poison their livestock. Locoweed is one such plant. Corrosive Poisons: A Closer Look Acids and bases can catalyze the hydrolysis of amides. The peptide bond of proteins is an amide linkage. Exposure to acids and bases can denature proteins by hydrolyzing the peptide bonds. If the protein is an enzyme, it can be deactivated by hydrolysis. Acids are particularly damaging to the lungs, where they can lead to the breakdown of lung tissue. Corrosive Poisons: A Closer Look Oxidizing Agents Many airborne pollutants are damaging to living tissue. Ozone, peroxyacetyl nitrate (PAN), and other oxidizing agents found in photochemical smog can cause the deactivation of enzymes. Poisons Affecting Oxygen Transport and Oxidative Processes Blood Agents Carbon Monoxide (CO) binds tightly to the iron in hemoglobin, preventing the transport of oxygen. Nitrate ions (NO3-), found in some foods and in drinking water in some areas, is converted to nitrite ions (NO2-). Nitrite ions oxidize Fe2+ in hemoglobin to Fe3+, forming methemoglobin, which is incapable of carrying oxygen. The result is a condition known as methemoglobinemia or “blue-baby syndrome.” Poisons Affecting Oxygen Transport and Oxidative Processes Blood Agents Cyanide ions (CN-) bind to the iron(III) ions in oxidative enzymes known as cytochrome oxidases. This puts an end to cellular respiration and brings near immediate death. Make Your Own Poison: Fluororacetic Acid When fluoroacetic acid is ingested, it is converted to citric acid. Citric acid is normally broken down in the citric acid cycle, releasing energy. Fluoroacetic acid effectively shuts down the citric acid cycle, making it an effective poison. Natives in South Africa used a plant containing fluoroacetic acid from the giftblaar plant to poison the tips of their arrows. Heavy Metals Poisons Many metals are toxic. Heavy metals with densities at least 5x greater than water are especially so. Most heavy metals display their toxicity by reacting with sulfhydryl groups (-SH), deactivating enzymes. Heavy Metals Poisons Mercury Mercury is used in many places. Many people have dental amalgams containing mercury. It is used in thermometers and thermostatic switches in homes. It is used as fungicide on seeds used in farming. Mercury vapor is toxic when inhaled. The body converts the mercury to Hg2+. Heavy Metals Poisons Lead Lead, too, has many uses and is found in the environment. It was once widely used in household paints and in gasoline. Lead can cause brain, liver, and kidney damage. Treatment for lead and mercury poisoning can involve the use of chelating agents. Heavy Metals Poisons Cadmium Cadmium is used in alloys, electronics, and rechargeable batteries. Cd2+ ions lead to loss of Ca2+ ions in bones. They also cause severe abdominal pain, vomiting, and diarrhea. More Chemistry of the Nervous System Acetylcholine (ACh) is a neurotransmitter. ACh carries a nerve impulse across a synapse. It is then hydrolyzed to acetic acid and choline by the enzyme acetylcholinesterase. The receptor releases these products, which are then converted back to ACh by other enzymes. More Chemistry of the Nervous System Nerve Poisons and the ACh Cycle The following nerve poisons affect the ACh cycle: Botulin is a powerful ACh antagonist. It blocks the synthesis of ACh. Curare, atropine, and some local anesthetics act by blocking receptor sites. Anticholinesterase poisons inhibit the enzyme cholinesterase. More Chemistry of the Nervous System Organophosphorus insecticides inhibit the enzyme acetylcholinesterase. ACh builds up, causing overstimulation of muscles, glands, and organs. More Chemistry of the Nervous System Research on organophosphorus insecticides has allowed for the development of powerful chemical warfare nerve poisons such as Tabun, Sarin, and Soman. The Lethal Dose The toxicity of substances is often quantified by the LD50. LD50 stands for lethal dose for 50% of a population exposed. The Lethal Dose The larger the LD50, the less toxic the substance. The Liver as a Detox Facility Through the use of enzymes, the liver is able to detoxify many compounds through oxidation, reduction, or coupling. Sometimes the products of these reactions are actually more toxic than the reactants. Chemical Carcinogens: Slow Poisons A carcinogen is a substance that causes the growth of tumors. Tumors can be either benign or malignant. Benign tumors grow slowly and do not invade surrounding tissue. Malignant tumors (cancers) grow rapidly and invade and destroy neighboring tissue. Chemical Carcinogens: Slow Poisons What Causes Cancer? The U.S. Occupational Safety and Health Administration (OSHA) has a National Toxicology Program (NTP). NTP lists carcinogens into two categories: Known Human Carcinogens, and Reasonably Anticipated to be Human Carcinogens. The latter compounds are structurally similar to known carcinogens. The vast majority of carcinogens are naturally occurring substances. Chemical Carcinogens: Slow Poisons What Causes Cancer? Chemical Carcinogens: Slow Poisons How Do Cancers Develop? Genetics play a role. Some carcinogens modify DNA, scrambling the code for replication and protein synthesis. Oncogenes seem to cause certain normal cells to become cancerous cells. Suppressor genes prevent the development of cancers. Chemical Carcinogens: Slow Poisons Chemical Carcinogens A variety of natural and synthetic chemical substances are carcinogenic, including polycyclic aromatic compounds, aromatic amines, nitrosoamines, vinyl chlorides, heterocyclic compounds, and epoxides. Chemical Carcinogens: Slow Poisons Anticarcinogens Some substances in our food appear to act as anticarcinogens, including the food additive butylated hydroxytoluene (BHT), and antioxidant vitamins A, C, E. Diets rich in cruciferous vegetables (cabbage, broccoli, Brussels sprouts, kale, and cauliflower) have been shown to reduce the risk of cancer. Three Ways to Test for Carcinogens The Ames test assumes that most carcinogens are also mutagens. It uses a special strain of bacteria that require histidine. The bacteria are incubated in a medium with the suspected carcinogen and without histidine. If they mutate and grow, the substance is likely a carcinogen. Three Ways to Test for Carcinogens Animal Testing Suspected carcinogens can be tested on animal populations such as rats or mice. Such tests are expensive and there may not be a strong correlation to humans. Three Ways to Test for Carcinogens Epidemiological Studies Epidemiological studies involve studying a population of humans that show more than a normal rate of cancer. The population is studied to see if there are common factors that could lead to cancers. Epidemiological studies have concluded that cigarette smoking, asbestos exposure, and exposure to vinyl chloride cause cancer. Birth Defects: Teratogens Teratogens are substances that cause birth defects. Epidemiological studies have shown that a number of substances are teratogens, including thalidomide, isotretinoin (Accutane, an anti-acne medication), and ethyl alcohol. Ethyl alcohol is by far the most hazardous teratogen in terms of the number of children affected. Hazardous Wastes Hazardous wastes are substances that cause or contribute to death or illness or environmental damage when improperly managed. Hazardous Wastes Hazardous wastes can be divided into 4 categories: Reactive wastes Flammable wastes Toxic wastes Corrosive wastes Hazardous Wastes Hazardous wastes can be dealt with by recycling, treatment to render less hazardous, incineration, or storage in a landfill. What Price Poisons? The use of any substance includes potential risks and benefits. Generally it is the misuse of chemical substances that leads to tragedy.