EnS 115 Environmental Toxicity PDF

PALAWAN STATE UNIVERSITY College of Sciences EnS 115 Environmental Toxicity Introduction to Environmental Toxicity Module 1.1 History, Scope and Principle of Toxicity  Learning Objectives After going through in this module, you should be able to: ü LO1 Def...

PALAWAN STATE UNIVERSITY College of Sciences EnS 115 Environmental Toxicity Introduction to Environmental Toxicity Module 1.1 History, Scope and Principle of Toxicity  Learning Objectives After going through in this module, you should be able to: ü LO1 Define toxicology by familiarizing with its scope and principles 2 Page 1  Initial Activity Are all poisons toxic? In the age of enlightenment in the history of toxicology, a significant man as part of history of science and medicine was Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus. He was known for his statement, “All substances are poisons; there is none which is not a poison. The right dose differentiates poison from a remedy.” In your understanding of the words ‘poison’ and ‘toxin’, how would you differentiate them? Poison is _______________________________________________________. Toxin is ________________________________________________________. In your household and surroundings, list at least five that may be classified as poison, following your definition. 1. ______________________________ 2. ______________________________ 3. ______________________________ 4. ______________________________ 5. ______________________________ 6. ______________________________ Do you think these are also toxins? (Two to three sentences are enough) ____________________________________________________________________ 3 ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ Page 2  Discussion What is toxicology? The study of the adverse effects of xenobiotics and thus is a borrowing science that has evolved from ancient poisons (Gallo, 2008). Modern Toxicology --- goes beyond the study of adverse effects of exogenous agents to the study of molecular biology, using toxicants as tools. Currently --- Study of the mechanisms of endogenous compounds e.g. oxygen radicals and other reactive intermediates generated from xenobiotics and endobiotic Historically! Toxicology formed the basis of therapeutics and experimental medicine ü Develop and expand by assimilating knowledge & techniques from most branches of biology, chemistry, mathematics and physics ü Now additional is the safety evaluation & risk assessment ü Aside from the biomedical area, occupational hazards and public health in addition is Environmental toxicology (study of the effects of chemicals on flora and fauna). Toxicology is both science and an art. 4 Science - Deals with the observational and data-gathering phase Art - Utilization of data to predict outcomes of exposure in human and animal population Both are used in explaining the adverse effects of chemical agents in situ where there is litter or more information by extrapolation and hypothesis development. Page 3  Discussion Toxicologist Biomedical area – they are concerned with mechanisms of action and exposure to chemicals as a cause of acute and chronic illness ü Toxicologists contribute to physiological and pharmacology by using toxic chemicals to understand physiological phenomenon ü Involved in the recognition, identification and quantification of hazards resulting in occupational exposure to chemicals in the public health aspects of chemicals in air, water other parts of environment, food and drugs ü Develop standards and regulations designed to protect human health and the environment from the adverse effects of chemicals. 5 Page 4  Discussion History of Toxicology The evolution of toxicology is traced back to the earliest humans Modern Toxicology Age of 1900 Enlightenment Middle 1500 - 1800 Ages 1200 AD Antiquity 1500 BC 6 Page 5  Discussion Antiquity The era of the earliest humans known for hunting. They use animal venom and plant extracts for their activities such as hunting and warfare. In 1500 BC (circa) the Ebers papyrus contains information about poisons Hemlock – Greeks Aconite - Chinese arrow poison Opium - Poison & antidote Metals - Pb, Cu, Sn Plants considered poisonous due to alkaloids – digitalis & belladonna Literatures Hippocrates (circa 400BC) - bioavailability in therapy & overdosage Book of Job (circa 400BC) - poison arrows Ramon ‘emperor’ Nero - 1st classification poisons - plant, animal & mineral 7 Page 6  Discussion Middle Ages (Before the Renaissance) In AD 1185-1204, Writings of Maimonides (Mores ben Maimmon) --Treatise on the treatment of poisonings from insects, snakes and mad dogs -- Subject & bioavailability (milk, butter & cream which caused delayed absorption) In AD 1200 (circa), Alchemists of this period -- Search of universal antidote -- Learned to distil fermented products and made 60% EtOH beverages -- Club of eligible young wealthy widows (conspiracy of Rome) o incident on arsenic-containing cosmetics responsible for deaths Catherine de Medici (from Italy to France) -- Primary targets of women were their husbands -- She tested toxic concoctions as: o carefully notify the rapidity (onset of action) o effectiveness of compound (potency) o degree of response of the parts of body (specificity/site of action) o complaints of victims (symptoms) 8 Page 7  Discussion Age of Enlightenment In 1493-1541, Philippus Aureolus Theophrastus Bombastus von Hohenheim- Paracelsus quote “All substances are poisons; there is none which is not a poison. The right dose differentiates poison from a remedy.” From Aristotle to Parcelsus there was a substantial change in biomedical sciences. -- Between the philosophy & magic of classical antiquity and philosophy Paracelsus (physician alchemist) coined the “Toxicon” word means primary toxic agent. He formulated revolutionary view in structure of toxicology, pharmacology and therapeutics. 1. Experimentation essential in examination of responses to chemicals 2. Distinction between the therapeutic and toxic properties of chemicals 3. Properties are sometimes but not always indistinguishable except by dose 4. Degree of specificity of chemicals and their therapeutic or toxic effects. For 300 years, Mercury was the drug choice for the treatment of syphilis. Then Paul Ehrlich formulated the Therapeutic index which was the first articulation of dose/response relation. It was also this time, pharmacology begun and dose- response relationship of therapeutic agents was established. Occupational hazards were associated with metalworking specifically the toxicity of mercury as well as Lead exposure from the goldsmith activity. 9 Experimental toxicology accompanied the growth of organic chemistry. Orfila (Spanish physician/toxicologist) first use autopsy material and chemical analysis systematically as legal proof of poisoning. In 1881, Liebreich at Phamacological Institute of Berlin studied the chronic toxicity of narcotics and other alkaloids. In 1920, Lewin studied the toxicity of methanol, glycerol, acrolein and chloroform Page 8  Discussion Modern Toxicology (1900s) Rapid growth in toxicology was traced during the World War II era which had a marked increased in the production of drugs, pestcides, munitions, synthetic fibers and industrial chemicals. A continued development of the biological and physical sciences during the 109th and 20th century. A beginning of modern era of genetics, medicine, synthetic chemistry, physics and biology. In 1850s – advent anesthetics and disinfectants and advancement of experimental pharmacology. The organic compounds such as ether, chloroform, carbonic acid led to several iatrogenic deaths. Other organic chemicals such as benzene, toluene & xylene were produced commercially. In 1890-1900 – Bacquel and The Curies (French scientists) discovered radioactivity Another discovery in this era was the large scale bioassay of vitamins or “vital amines” wheter they beneficial or harmful to laboratory animals. Another group of scientists, Hawk and Oser were responsible for the verification of toxicological assays which have significant contribution to food and drug regulatory In 1920s – Use of Arsenicals for the treatment of syphilis which was first used for agriculture which resulted in acute and chronic toxicity 10 Page 9  Discussion Modern Toxicology (World War II) In 1930s – main activity in Germany and America was the mass production of antibiotics and warfare agents. Herbert Hoover signed the establishment of National Institutes of Health in US. The chemicals and metals which were of interest in WWII: 1. Sulfanilamide – combating bacterial diseases; drug was sold in diethyelene glycol solution labeled as elixir; This led to a cytotoxic effect to the kidney tubules due to crystallization. Thus, Copeland bill in 1938 for the formation of the US Food and Drug Administration (FDA); 2. The focus of the Chicago team, Geiling et al., was on organophosphates, antimalarial drugs and radionuclides; 3. DDT and phenoxy herbicides – control of insect-borne diseases 4. Uranium – used in ‘bomb’ and studies on the relationship with DNA, RNA and growth factors; Manhattan project initiated the quantitative biology, drug metabolism and structure activity relationship (Antimalarial), radiotracer technology and inhalation technology The study on carcinogens was started in this period. Decade after WWII, 1947, the US Pesticide Act was signed into law. 11 Page 10  Discussion After World War II In 1950s – under Arnold Lehman. His famous quote, “ You too can be a toxicologist in two easy lessons, each of ten years.” It was Lehman, Fitzhugh et al. (1955) formalized the appraisal of food, drug and cosmetics through experimental program. This was updated in 1982 in the Gordon Research Conference. This led to the amendments to the Food, Drug and Cosmetics Act. It was Delaney reiterated carcinogenicity and his famous “one-hit” theory of carcinogens. Another event was the Thalidomide incident where several thousand of children were born with serious defects … Silent Spring published by Rachel Carson. IN 1960S – Analytical tools used in toxicology were developed which were more sophisticated which allowed the detection in tissues and other substrates at ppb concentrations. A famous AMES test for carcinogenic process. Cellular and molecular toxicology were developed. It was in this era, cradle to grave concept was created which covers the toxicology of chemicals from initial synthesis to disposal. 12 Page 11  References 1. Hodgson, Ernest. 2004. A textbook of modern toxicology. 3rd Ed. ISBN 0-471-26508X. John Wiley and sons, Inc. 2. Murray, R.K., A.A. Bender, K.M. Botham, P.J. Kennelly, V.W. Rodwell and P.A. Weil. 2012. Harper’s Illustrated Biochemistry. 29th ed. McGraw Hill.818 pp. 3. Stryer L., J.M. Berg and J.L. Tymoczko.2013. Biochemistry (Short course) 2nd ed. Freeman & Company. 862 pp. 13 Page 12