. Introduction to Toxicology Copyright © Texas Education Agency, All rights reserved.

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. History of Poisons 2700 – 800 BC Chinese, Egyptians and Hindus documented vast amounts of information related to the collection, preparation and administration of many plants and animals used as medicines and poisons. Copyright © Texas Education Agency, All rights reserved.

. History of Poisons A.D. Greek physicians classified over 600 plant, animal, and mineral poisons. Romans used poisons for executions and assassinations. The philosopher Socrates was poisoned using hemlock for teaching radical ideas to youths. Copyright © Texas Education Agency, All rights reserved.

. History of Poisons AD In Islamic culture, Avicenna becomes the authority on poisons and antidotes. In Spain, Rabbi Maimonides wrote a first-aid book on poisonings. Copyright © Texas Education Agency, All rights reserved.

. History of Poisons AD Swiss physician Paracelsus is credited with being “the father of modern toxicology”. He introduced the notion that too much of anything, even if it is good for you, can be a bad thing. Copyright © Texas Education Agency, All rights reserved.

. History of Poisons 1700’s ’s Ramazzini, an Italian physician, first discussed environmental diseases such as those with asthma-like symptoms in laymen workers like bakers, farmers, glass-workers, tanners, millers, grain-sifters and stonecutters. In Spain, toxicology was established as a formal scientific discipline by Dr. Orfila. Copyright © Texas Education Agency, All rights reserved.

. History of Poisons 20 th Century While trying to create different tissue stains and procedures, Dr. Paul Ehrlich found how toxicants affected biological tissues. Rachel Carson alarmed people about dangers of pesticides in the environment. Dr. Alan Scot accidentally invented Botox, a neurotoxin caused by the one of nature’s deadliest bacteria. Copyright © Texas Education Agency, All rights reserved.

. Toxicology -- the study of poisons and their mechanism of action Toxicity -- the adverse effects that a chemical may produce Dose -- the actual amount of substance introduced into a body Exposure – contact providing the opportunity of obtaining a poisonous dose Hazard – the likelihood that the toxicity will be expressed Copyright © Texas Education Agency, All rights reserved.

. It’s All in the Dose You have heard that too much of a good thing can be bad for you. A normally benign and harmless substance can become toxic at high doses. On the opposite end of the spectrum, highly toxic chemicals can be life-saving when given in small controlled doses. Copyright © Texas Education Agency, All rights reserved.

. Exposure Concepts Toxic responses may arise from different: – Routes of exposure – Frequencies of exposure – Duration of exposure (acute vs. chronic) Copyright © Texas Education Agency, All rights reserved.

. Routes of Exposure Ingestion Injection Inhalation Absorption Copyright © Texas Education Agency, All rights reserved.

. Duration & Frequency of Exposure Acute exposure -- less than 24 hours; usually entails a single exposure Subacute – repeat exposure up to a month Subchronic -- repeated exposure up to three months Chronic – repeated exposure for more than three months Copyright © Texas Education Agency, All rights reserved.

. Exposure Concepts Environmental Occupational Therapeutic Dietary Accidental Deliberate Copyright © Texas Education Agency, All rights reserved.

. Xenobiotics Defined as foreign chemicals which are synthesized within a living body (Xeno- meaning “strange”) Many of these poisonous xenobiotics are defense mechanisms used for survival or are simply waste products in chemical form produced by plants, microorganisms, or animals, including humans. – Clostridium botulinum – waste product, not bacteria alone causes paralysis; use: Botox for relaxing muscles; still lethal – Clostridium tetani -- spores of bacteria found on rust cause paralysis; uses -- NONE Copyright © Texas Education Agency, All rights reserved.

. Xenobiotics Some chemicals are inactive until in the presence of another chemical to make their effects poisonous. Xenobiotics may also be produced by humans or bovine such as insulin converted into synthetic form for use Ancient plant Xenobiotics: digitalis for heart problems vs. hemlock for poisoning Copyright © Texas Education Agency, All rights reserved.

. Toxicokinetics -- Movement of Poisons Distribution -- the movement of poison through different routes Metabolism – the breakdown of chemicals from active to inactive forms starting with enzymes in the stomach and then in the liver Elimination -- removal of all by-products of poisons Copyright © Texas Education Agency, All rights reserved.

. Influencing factors affecting movement of poisons Different molecular weights Concentration of solutes versus solvent Victim’s status of health Copyright © Texas Education Agency, All rights reserved.

. Mechanisms of Action for Xenobiotics Sometimes xenobiotics will work better once metabolized and the by-products become the harmful substances Substances work by disrupting normal cell function – Denature proteins – Cause a defect in DNA – Target lipids Copyright © Texas Education Agency, All rights reserved.

. Types of Toxic Effects Death – absence of cell function; causes -- cyanide and arsenic Organ Damage – loss of cellular function causing chronic diseases that have no cure; causes -- lead and ozone exposure Mutagenesis –a process by which the genetic information of an organism is changed, resulting in a mutation. May occur in nature, or as a result of exposure to mutagens; causes -- UV light Carcinogenesis -- process by which normal cells are transformed into cancer cells; causes -- benzene, asbestos Teratogenesis – process by which congenital malformations are produced in an embryo or fetus; cause – thalidomide Copyright © Texas Education Agency, All rights reserved.

. Challenges / Potential Dangers in Herbal Medicines Not enough / too much chemical isolated Plant variations leading to poor chemical production Variations in extraction techniques Not endorsed by Food and Drug Administration – Growth requirements not standardized as in pharmaceuticals – Variations in standards of growth and isolation can affect final prices Copyright © Texas Education Agency, All rights reserved.

. Occupational Versus Environmental Toxicology Environmental – Environmental toxicants -- agents hazardous to air, sea or land and potentially all humans – Agents can be naturally occurring and synthetic in nature and BOTH can be just as deadly Copyright © Texas Education Agency, All rights reserved.

. Occupational Versus Environmental Toxicology Occupational: many examples of diseases are associated with specific occupations – Miner’s Disease came from inhaling metal vapors, and became foundation for chemotherapy – Linked chewing tobacco to cancer – Radium dial painters developed masses in mouth when they licked their brushes to make a fine point – Chimney sweepers were linked to scrotal cancer – Shoe salesmen who used fluoroscopes to take radiographs of client feet for fitting began to develop cancers Copyright © Texas Education Agency, All rights reserved.

. High cancer-risk occupations Health care workers Pharmaceutical Laboratory workers Refinery workers Rubber workers Furniture makers Pesticide workers Copyright © Texas Education Agency, All rights reserved.

. Methods of extracting poisons Gel-filtration chromatography -- separate particles by size Ion-Exchange chromatography -- separate particles by charge Electrophoresis -- separate particles by charge Affinity chromatography -- dependent on number of hydrogen bonds Copyright © Texas Education Agency, All rights reserved.