Slide 1ClickersIntroductionHistoryImportant PeopleToxicologist’s ResponsibilitiesSlide 7Chloroform1906Chemical Warfare (1915)U.S. Prohibition (1919-1933)19251930193719381938WWIIArsenic poisoning in Bangladeshi villages – 1970sIraq - Mercury 1971-1972Mr. Yuk - 1971Love Canal (Niagara Falls, NY) 1978Love CanalAmerican Board of Toxicology (ABT) - 1979Tylenol Tamper - 1982Times Beach (Missouri) 1983Bhopal Disaster - 1984Lake Nyos Event - 1986Chernobyl Accident – 1986Fukushima Daiichi Nuclear DisasterSlide 30Tokyo Subway Sarin Gas Attack – 1995Vioxx – COX-2 Inhibitor (1999-2004)Fundamentals of ToxicologyDavid Shubert Ph.D125 Sherman [email protected]http://www.buffalo.edu/ubit/service-guides/teaching-technology.htmlService guideTeaching and technologyUbclicks for studentsUsing ResponseWare with smartphoneshttps://account.turningtechnologies.com/account/IntroductionToxicology Definition- study of the nature and mechanism of toxic effects of substances on living organisms and other biological systemsPurpose- protection of the health of individuals, contributes to the development of safer chemicals used as drugs, food additives, pesticides, and many other industrial chemicalsHistoryToxicology as a discipline is relatively new (mid 1900’s)However, the science of toxicology can be traced back thousands of years. ExamplesTetrodotoxin – puffer fishCurare – arrow poison Ricin – castor beanLead Hemlock (Socrates 399BCE)Conium maculatum (Hemlock or Poison HemlockImportant PeopleHomer (850 BCE)Writer (illiad and odyssey) Socrates (469 – 399 BCE)Philosopher –executed with poison hemlockHippocrates (460 – 377 BCE)Father of modern medicineMithridates IV (131 – 63 BCE)Studied how to counteract poisons Paracelsus (1493- 1541) “All things are poison and nothing is without poison, only the dose permits something not to be poisonous” father of ToxicologyToxicologist’s Responsibilities1. Develop new and better ways to determine the potential harmful effects of chemicals and the dose that will cause these effects (mechanistic data)2. Design and carry out carefully controlled studies of specific chemicals of social and economic importance to determine the conditions under which they can be used safely (that is, conditions that have little or no negative impact on human health, other organisms, or the environment (reliable data)3. Assess the probability, or likelihood, that particular chemicals, processes or situations present a significant risk to human health and/or the environment, and assist in the establishment of rules and regulations aimed at protecting and preserving human health and the environment (Risk assessment and establish guidelines)Research Founda-tions; 4.00%Consulting; 12.00%Government; 14.00%Academia; 21.00%Industry; 2.00%Other; 17.00%Pharmaceutical; 20.00%Other; 7.00%Chemical; 3.00%Toxicology CareersAdapted from the Society of ToxicologyChloroformChloroform1831 - First produced by French chemist 1847 – used as anesthetic during child birth - one of the earliest anestheticChloroform – discontinued as anesthetic early 1900’s because of liver toxicityUsed as a precursor for Teflon and refrigerants.1906Pure Food and Drugs Act (1906) Supported by the Department of Agriculture's chief Chemist Harvey W. Wiley, the Food and Drugs Act was created to protect consumers from potentially dangerous drugs and food. The act required sufficient that the consumer was given warning about the toxic or addictive nature of certain drugs or foods.Before this, patent medicines did not contain any ingredientsPaved the way for the FDAChemical Warfare (1915) By the middle of the 1910's, chemicals had been developed to be used by the military as weapons. Agents such as Chlorine, Chloropicrin, Phosgene and Mustard gas were all used in chemical warfare. Humans and dogs were fitted with gas masks.- Chlorine gas reacts with water (HCL) irritant, oxidizer- Phosgene –cocl2 acts on proteins in the lungs, compromises gas exchange- Mustard gas C4 H8cl2S- mutagen, carcinogenInstituted by the Eighteenth Amendment, prohibition in the United States created severe health hazards for those who consumed bootlegged alcohol. Bootleggers often used toxic chemicals and industrial grade alcohol to brew alcoholic drinks, which often led to cases of blindness and brain damage in its consumers. Methanol ch3oh (wood alcohol) metaolized to formic acid and formaladehyde U.S. Prohibition (1919-1933)1925Geneva Protocol (1925) Prohibiting the use of Biological and Chemical weapons, the Geneva protocol was a follow up of Germany's ban to use Chemical weapons under the Treaty of Versailles.1930FDA formed (1930) Formed to regulate the content and safety of consumer drugs and food, the FDA was established as a government agency in 1930. Some of the specific functions of the FDA are regulating data on food labels, overseeing clinical trials for new drugs and investigating consumer complaints about food and drugs.1937Elixir Sulfanilamide Disaster 1937 Over 100 people, many children died when Elixir Sulfanilamide was distributed without testing and contained diethylene glycol as a vehicle.Propylene glycol- excipient – bulk carrier1938Federal Food, Drug, and Cosmetic Act (FD&C) -1938Federal Food, Drug, and Cosmetic Act (FD&C) was passed by Congress in 1938 giving authority to the Food and Drug Administration (FDA) to oversee the safety of food, drugs, and cosmetics.1938Albert Hofmann 1938 Lysergic acid (LSD) synthesized in the Sandoz Laboratory (now Novartis). In 1943 Hoffman tested LSD on himself. Hofmann was a prominent Swiss scientist at Sandoz Laboratories, Basel (now Novartis),and best known as the "father" of LSD.WWIIGerhard Schrader (1903-1990) Born in Germany, Chemist Dr. Schrader accidentally developed the toxic nerve agents sarin, tabun, soman, and cyclosarin while attempting to develop new insecticides. As a result, these highly toxic gasses were utilized during World War II by the Nazi's. He is sometimes called the "father of the nerve agents".Arsenic poisoning in Bangladeshi villages – 1970sTubewells drilled to provide clean drinking water, are contaminated by arsenic resulting in millions of people harmed.Iraq - Mercury 1971-1972During the winter of 1971-1972, pink-colored seed grain coated with a