Chapter 1 2 Introduction to Toxicity and Toxicology

Chapter 1. 2: Introduction to Toxicity and Toxicology • It is not intended in this module to produce a detailed and comprehensive course in toxicology • However, in order to discuss food chemical risk assessment we need as a starting point to introduce the concept of chemical toxicity, and the discipline of toxicology which is used to examine chemical toxicity in a structured way. 1

Historical aspects of Toxciology Estimated 40, 000 deaths due to ergotism Ebers scrolls ”Traité des Poisons” Bonaventura Orfila Socrates’ conviction ? ~1550 B. C. 399 B. C. 0 ”Everything is a poison…it is only the dose that makes it not a poison” (Paracelsus, 1493 -1541) ~1000 ~1500 ~1800 2

Example: Socrates was ultimately sentenced to death by drinking a hemlockbased extract Hemlock contains the pyridine alkaloids coniine, Nmethylconiine, conhydrine, pseudoconhydrine and γ-coniceine. The most toxic of these is coniine, which has a chemical structure similar to nicotine. . Coniine containing plants have actions similar to nicotine. Clinical effects will depend on the dose of coniine or coniine-like alkaloid ingested. The nicotinic effects are biphasic, with stimulation followed by CNS depression and paralysis of respiratory muscles. Initial symptoms may be vomiting, confusion, respiratory depression, and muscle paralysis. Death, when it occurs, is usually rapid and due to respiratory paralysis. http: //toxnet. nlm. nih. gov/cgibin/sis/search/a? dbs+hsdb: @term+ @DOCNO+3474 3

Mathieu Joseph Bonaventure Orfila (24 April 1787 – 12 March 1853) was a Spanish born French toxicologist and chemist, often seen as the founder of the science of toxicology. Role in Forensic Toxicology If there is reason to believe that a murder or attempted murder may have been committed using poison, a forensic toxicologist is asked to examine pieces of evidence such as corpses and food items for poison content. At Orfila's time the primary poison in use was arsenic, but there were no reliable ways of testing for its presence. Orfila developped new techniques and refined existing techniques in his first treatise, Traité des poisons, greatly enhancing their accuracy. In 1840, Marie La. Farge was accused for the murder of her husband using arsenic. Mysteriously, although arsenic was available to the killer and was found in the food, none could be found in the body. Orfila was asked by the court to make further investigations. He discovered that the test used, the Marsh Test, had been performed incorrectly, and that there was in fact arsenic in the body, allowing La. F arge to be found guilty. And arsenic is still poisonous (Bangladesh) from arsenic naturally occurring in water 4

Paracelsus (1493 -1541) • “Alle Ding' sind Gift und nichts ohn' Gift; allein die Dosis macht, dass ein Ding kein Gift ist. – "All things are poison and nothing is without poison, only the dose permits something not to be poisonous. " 5

One of the most important concepts in toxicology “The dose makes the poison” LOW EXPOSURE = LOW RISK 6

What does it mean that something is Toxic? Let us get some suggestions! 7

Other words (expressions) for toxic? • Poisonous • Health impairing • or to some extent • Hazardious • Lets get an explanation on the last ! • http: //map. ais. ucla. edu/go/1002739 8

What can be toxic? • An element (lets get examples)! • A chemical compound (examples)! • A ”product” (examples)! • Naturally occurring/”man made” • Any difference? 9

Introduction to Toxicity What can be Toxic? A solid, liquid or gas ”element” (examples)! • Lead (Pb) (metal found in some crops and seafoods). • Arsenic (As) (metalloid in grains such as rice) • Mercury (Hg) (converted to methylmercury in seafood, marine plants etc) • Calcium, copper, iron, sodium, magnesium, manganese, porassium (essential dietary minerals but can be toxic at high cncentratons) 10

Introduction to Toxicity What can be Toxic (cont’d). . A chemical compound (examples)! • Sodium Chloride (Na. Cl also known as salt!) • Carbon dioxide (CO 2) • Ethanol (CH 3 CH 2 OH) • Cyanide (HCN) 11

Introduction to Toxicity What can be Toxic (cont’d). . . A ”product” (examples)! • Agricultural and veterinary chemicals – pesticides, insecticides, fungicides • Pollutants – lubricants, cleaning agents, dioxins and PCBs • Food additives – preservatives, artificial colours, acidifiers etc 12

Introduction to Toxicity What can be toxic (Cont’d). . Naturally Inherent Plant Toxicants Examples • Macromolecular polyphenolic substances (hydrolysable and condensed tannins) • Toxic fatty acids/lipids • Non-protein amino acids • Alkaloids • Furanocoumarins • Polyacetylenes • Mono-, sesqui- and diterpenes; and • Toxic glycosides of various types (glucosinolates, cyanogenic glycosides, saponins) 13

Introduction to Toxicity What can be toxic (Cont’d). . Naturally Inherent Plant Toxicants Examples • • • Cyanogenic glycosides in casava and apricot kernels produce HCN. Tannins in processed products such as tea, coffee and wine. Proteinase inhibitors in legumes (e. g. Soybeans) Alkaloids in foods and beverages (e. g. Caffeine) Pyrrolizidine Alkaloids in grains, teas and herbal supplements Gossypol in cotton seed oil 14

A chemical compound (or a mixture) that is toxic may e. g. be called: • A Poison • A Toxin • A Biotoxin • A toxicant • What are the differences? • http: //en. wikipedia. org/wiki/Toxin • http: //en. wikipedia. org/wiki/Toxicant 15

What is toxicology? • The study of toxins/toxicants (=toxic substances) • ”Toxic substances disturb the physiological balance to the extent that the organism becomes ill” • Multidisciplinary field of science building on basic disciplines 16

What is Toxicology Some References to consider for further reading: 1. Analytical toxicology (A. Wallace Hayes, Principles and Methods of Toxicolog, 3 rd Edition; Casarett and Doull’s Toxicology, 5 th Editiin) ; http: //www. who. int/ipcs/publications/training_poisons/analytical_toxicology/en/ind ex. html • 2. Clinical toxicology (Ellenhorn’s Medical Toxicology, 5 th Edition). • 3. Occupational toxicology (A. Wallace Hayes, Principles and Methods of Toxicolog, 3 rd Edition; Casarett and Doull’s Toxicology, 5 th Edition) • 4. Environmental toxicology (A. Wallace Hayes, Principles and Methods of Toxicolog, 3 rd Edition; Casarett and Doull’s Toxicology, 5 th Edition) • 5. Regulatory toxicology (A. Wallace Hayes, Principles and Methods of Toxicolog, 3 rd Edition; Casarett and Doull’s Toxicology, 5 th Editiin); http: //www. ncbi. nlm. nih/gov/pubmed/11814699 17

Quantitative aspects: Dose-response relationship • Dose • Acute/chronic toxicity • Quantal (all or nothing) • Graded response (degree of symptoms in a single animal) • Species specific 18