|A Note On…. “Classes on Toxicology”
It is planned to bring you a” Class on Toxicology”, every Friday. Today 28/09/2018, the Topic will be An Introduction to Toxicology. What is Toxicology and the general concept about Toxicology is explained. Dr. Fernandez, a professional Toxicologist is preparing the content of the Classes and available for your queries and suggestions through the Comments column. You are welcome to the classes.
These classes are meant for the general public, as a tool to get educated about our daily life in this Earth and understand how we are encircled by bad Air, contaminated Water and spoiled Soil. The Hon. Ministers, respected Citizens, Government servants, technical and administrative people in the Medical and Veterinary areas, persons working in any Industry, Agriculture and Fisheries, transports, Parents of normal as well as Special children, all will be benefitted by these classes. Toxicology will help in tackling the use of various commodities that we use daily or environments to which we are exposed.
Why this classes? And free?
I completed my studies and believe that public funds had been spent on me and my education. I earned a Doctorate from Kerala University. I was nominated to present before the Expert Committee assessing the University for Accreditation. “ I am a product of this University and I am happy to state that the way university curriculums are prepared and taught gave me needed exposure to master any strange topic and to be confident in executing any assigned jobs, to the satisfaction of the Superior.
Therefore, I feel that I am indebted to the Public to share my knowledge, with them. My decision to do so, is the result of bringing me up. My father Dr. Alfred Cyril Fernandez, a native of Quilon, was a product of Culcutta Veterinary College and he was the first Veterinary Surgeon of Corporation of Trivandrum. My Mother Mrs. Mariam, a native of Kottayam was my teacher, mender of my quality and made me always stay in the path of truth and truth only and be helpful to everybody to the extend possible, which made me a person acceptable to the majority and a patient listener. In case you miss a class from me on a Friday, just forgive me, it must be due to some personal reason.
My mobile no is 9447777985 and- mail ID is firstname.lastname@example.org.
Toxicology is commonly known as the study of poisons. The subject has been understood and explained in common terms from olden times. Toxicology was noted and in practice from the B.C era. It was connected with plant foods and agriculture products of different time eras. Some plants were found to be toxic or lethal to animals as well as to humans. Humans soon learned that these toxic materials could be used to the advantage to dissuade or eliminate predators or even fellow humans for various reasons. As time passed man learned that poisons are lethal but it depended on the strength and dose of the poison in question. He also understood that some poisons have medicinal properties at lower dose levels and useful for humans and animals. Some poisons were found useful to keep the pests away from the valuable agriculture plants as well as for safe storage of the plant products. As time passed it was found that poisons were also seen in animals. Modern times and industrial developments and the great world wars exposed the poisonous nature of metals, non metals, minerals, many manmade materials, radiation etc. Presently, Toxicology has become an interdisciplinary subject practiced in participation by Biologists, Biochemists, Chemists and Physicists. Further many other specialists like, Ecologist, Environmentalists, Drug designers, Cosmetic designers, Biomedical Device designers, Heavy Industrialists, Various transport designers including Space farers and Designers of Closed environments come into the realm of Toxicology as Man is the consumer of their products or the persons who has to endure the Toxic effects of their end products or bye products.
History Of Toxicology
Tracing back Toxicology, is really a retreat through olden literature in Chinese, Greek, Vedas, Persian, French, British etc. Chinese Medicine records that Shen Nung (2696 B C ) tasted 365 herbs and authored a Treaties “Herbal Medical Experiment on poisons.” Homer describes the use of Poisoned arrows in his epics “The Odyssey and Iliad” in 860 B C. Here he enlightens on Tokkicon or poisoned arrows used very commonly on wars conducted during his life period and the root of the word, Toxicology. Hippocrates (400 B C ) in his writings showed that toxins or poisons exerted their effects by getting absorbed into the living system and this could be treated by preventing absorption by various means. In the Treaties “ De Historia Plantarum, 370 B C”, Theophrastus describes numerous Poisonous plants. Nicander of Colophon 185 B. C., physician to King Attalus of Bythnia studied use of poisons, its effects, symptoms of poisoning and the effects of anti dots and nature of recovery or death on prisoners, with King’s permission. The use of linseed for inducing vomiting and sucking of poison from the wounds made by venomous animals are his suggestions as part of treatment. Lucius Cornelius Sulla of Roman empire enacted the first law against poisoning in 82 BC to protect against careless dispensing. The Greek physician Discorides ( 40 -90 AD ) travelled a lot, mostly along with the Greek Army and wrote about plants that have medicinal value as well as that were poisonous. He classified poisons as originating from Plants, animals and minerals. He is the one to suggest emetics as a means of treating poisonous cases especially if the route of poisoning is oral. Ibn Wahshya (860 -930 ), an Arab Botanist and thinker wrote a book on poisons. Moses Maimonides(1135- 1204 A. D. ) , a Jewish Philosopher and physician wrote about Poisons and their Treatments and criticized some of the methods of treatments of Poisoning, practiced earlier. His writings are considered as earlier notes on the Topic toxicology. Matheu Joseph Benavanthura Orfila (1787 – 1853) a Spanish Scientist, known as the founder of Modern toxicology, as well as that of forensic toxicology. His book “ Treaties on Poisons” was a breakthrough Moses Maimonides(1135- 1204 A. D. ) , a Jewish Philosopher and physician wrote about Poisons and their Treatments and criticized some of the methods of treatments of Poisoning, practiced earlier. His writings are considered as earlier notes on the Modern toxicology. Use of poisons in eliminating enemies saw a growth during this period. The beginning of 1900 saw the development of Chemistry in relation to Biology and the idea of mechanisms of action came to the fore. Rudolph Peters of Netherland, studied Arsenic gases used in the wars and came out with Anti Lewisite as an antidote for the exposure. From there on the Development of Science was very fast and embraced almost every aspect of life on earth. Man faced a situation where he has to find out ways to detoxify the Air, Water and the Soil he has to survive. His activities has contaminated even the Space and the two Arctic regions. So the modern world has the most modern techniques to assess the toxicity of any materials and to design a way to use them safely, with out which Human race could not survive for long, to write and read about Toxicity and Toxicology.
Classification of Toxicology
Analytical Toxicology, Applied Toxicology, Clinical Toxicology, Veterinary Toxicology, Forensic Toxicology, Industrial Toxicology, Environmental Toxicology are considered to be major divisions of Toxicology, in general. Toxicology as we know encompass the study of poisons, in the early years. At present, Toxicology touches any materials and it’s safety and it’s nature of hazard or risk in use or exposure. Thus Toxicology has become a broader Topic applied to various areas and subjects. When you want to study the hazards from food, it becomes food toxicology. You will observe that, to study food toxicology, the toxicologist has to have a team of experts to analyze the chemical composition, contamination if any, in the food before and after preparation, safety of packing material, bacterial contamination and sterility of the packed or served food. Likewise, drugs, cosmetics, dress materials, cleaning materials, insect repellants, construction materials of the Residence etc. needs to be safe for prescribed use and toxicology plays an important role in the day today life. Therefore, the general classification put up here is not a rigid one and could be added or changed. Academic toxicology, Regulatory toxicology, Occupational toxicology, Immune toxicology, Genetic toxicology, Contract toxicology, Political Toxicology etc. are some examples that we will come across. Toxicologist needs to understand the cause of toxicity and the extend of the damage brought about by the causative agent. For that he has to analyze the tissue samples, organ samples, blood, urine etc. and the causative material if any left. Spectroscopy, Chromatography and Immunological assays are used to detect, identify and measure the toxic material in question during a Toxicological study. Toxicologist has to evaluate the nature and mechanism of action of a poison or a material in biological systems, he applies various techniques available in Biochemistry, Pharmaco dynamics, Pharmacokinetics, Instrumental chemistry, Medicinal Chemistry etc. This area is denoted as Applied toxicology. When cases come up with over dose of medication, substance of abuse or poisoning, exposure to chemical burns or radiation in an Emergency Medicine Centre, the Clinician with special training in the management of such cases, evaluates each case, asses the extend of hazardous exposure and prescribe medical care for the patients. This area of Medical practice, where science of toxicology is employed in the treatment of patients is known as Clinical Toxicology. Like wise, the science of Toxicology used in conjunction with Veterinary Medicine is known as Veterinary toxicology. Other than the routine diagnosis and treatment animals, the study of contaminants entering human food through animals, ecological and environmental contamination of animal habitat and foods, accidental poisoning from plants and venomous animals etc. also are relevant under this topic. Use of science of Toxicology in investigating the cause of poisoning, death by poisoning, identifying the nature, quantity and time of poisoning, misuse of drugs and chemicals falls under Forensic toxicology. Industry is an important word in modern world. Whatever we use in our daily life is produced in an industry. Any material or any product comes out of chemicals, physical forces, temperature and through lot of mechanization. In the manufacturing process, in transportation of raw materials and finished products the environment of production, packing, transport are polluted by the raw materials, accessories used to aid production process, packing, labeling etc. The work force and the people staying near and around the industry are sure to get a share of contamination. It may be through Air, Water or the soil where the waste material from the industry is dumped. This result in the deterioration of health of the industry worker as well as the people, animals and plants in the locality where the industry is situated. Such situations has initiated the subject Industrial Toxicology. The occurrence of contaminated Air, Water and Soil is very common in any places on the Earth, even the Arctic regions and the Space. As we are aware, the environment is contaminated and the branch of toxicology concerned with the health of Human beings, animals, plants and all living beings is, Environmental toxicology. Science of toxicology, assures safety and lead us to capably use anything that is hazardous to our advantage by designing safe protocols for use.
Classes on toxicology:- Xenobiotics
Toxicology is all about materials or chemicals that are not normally found in an organism, a Xenobiotic. Living organisms will make reactions or responses towards the xenobiotics that enter the living organism. What is the xenobiotic in Question, the quantity that entered the body, the number of times the xenobiotic entered, the route of entry, the residue that is left in the organism etc. are questions which a Toxicologist ask and try his best to find out. Without these information he will not be able to access the true nature of the hazard and help to ameliorate the condition of the living organism. The xenobiotics that are usually hazardous are commonly known as poisons. In case the xenobiotic in question is a known material or poison, the toxicologist may get readily available information on the chemical nature, safe dose, possible responses of the living body towards the substance, degeneration within the body etc. and may be able to suggest methods to neutralize or detoxify the effects. The xenobiotics can enter the body from the environment or ingested knowingly or purposefully. The Air, Water and the Soil in the environment contain lot of xenobiotics, that will enter the living organism through inhalation, ingestion, absorption by skin. The same routes are used intentionally to consume poisons or administer poisons or substance of abuse.
Classes on Toxicology:- Dose
“Dose” simply means to the common man, the quantity of a medicine or drug prescribed by the Physician to be taken at a time. When we have fever, the doctor prescribes fever medicines. It is 500 mg of antipyretic for an adult, 3 times in a day, usually at 8 hr intervals, may be for 3 days or as advised by the Physician. Like this we know about the prescribed medicines for treating various illness have doses to follow. But in the case of Xenobiotics, when we are exposed, that can be a single dose as in the case of radiation or corrosive gases like chlorine or carbon monoxide, cosmetic cream applied to the skin. Here the dose is single exposure, but quantity of the xenobiotic is unknown and the effect of that exposure depends on the nature of the xenobiotic, period of exposure, the health of the exposed etc. How much xenobiotic was present?, the toxicologist has to estimate after studying the source, nature and period of exposure and clinical lab data from the exposed.
In the case of a drug or a xenobiotic the intake at a time could be “a dose”. The frequency at which the dose is repeated and the duration for which the dose is repeated is important and gives an idea of “total dose”. But when we take into consideration the response of the living system to eliminate the drug or xenobiotic, the quantity that is left in the body after elimination becomes the “internal dose”. The biological process involved in the elimination of Dose that is administered imposes problems in estimating the internal dose. “External dose” is another term denoting the dose equivalent received from radiation sources outside the body or living organism. Another common term used is “Threshhold dose” which means the lowest amount or exposure level of a toxic substance at which a specified and measurable effect manifests. I hope, the reading on “Dose” will give an idea about the different terms used in Toxicology. When we are dealing with response, mechanisms, biochemistry, testing etc. in Toxicology, we will come across more terms related to toxicology, pharmacology and medicine and will elaborate on them.
Classes in Toxicology:- Exposure
Exposure to a xenobiotic present in Air, Water or soil can happen through skin by dermal absorption, by inhalation through the respiratory system or by ingestion through the digestive tract. The same is true for drugs. Further xenobiotics can enter the body via food, drugs that are consumed as routine in daily life or administered intentionally by self or a third person. These are called route of exposure. Oral, inhalation and dermal are the common routes. Substances can enter the body through the Parenteral route too, ie. the entry of xenobiotics through intramuscular, intra dermal, subcutaneous, intravenous or artery. Food, medicines, water are the common materials we ingest and contamination through these vehicles is possible. Through inhalation we breath in air and any contaminants that is very common in the immediate environment surrounding us. Dermal absorption is common from the water we use, cosmetics, soaps and detergents, skin drugs or work related materials. Parenteral route commonly involved with prescribed medicines drugs of abuse or given by illegal means / options. Patterns of Exposure are important to be kept in mind. It can be one time, acute exposure or continuous, chronic exposure. This may be also a high dose acute exposure or a low dose chronic exposure.
When we talk about exposure we have to consider dose, age, body size and time also. Already we have noted basics about dose. An adult may need 650 mg (thrice a day) of antipyretic drug to control fever but for a child 650 mg is toxic. Child may need only may be less than 80 mg. Another parameter is that 100 mg of “X” substance will lead to death of an adult as a single dose, it need not lead to death if taken 10 mg per day over a period of 10 days. Commonly the dose is set by mg per kilogram body weight per day or, mg/liter for liquids and, mg/m3 for air and other units like parts per million, parts per billion and parts per trillion are well in use.
But when doses are compared with different species of animals it may be by body surface area. The unit of time during which a dose is administered is accepted is “a or one day”. When xenobiotics in question are strong poisons the dosage will be lesser that mg/kg, namely microgram, nanogram, picogram etc.
When we talk about exposure we have to know about the response also. What is the response of an organism to an acute or chronic exposure to a Xenobiotic, which will be another day’s topic.
Classes on Toxicology:-Response
We respond to friendly calls and conversations. Our response to fire is to douse it and call for help if required. In toxicology, response is the action or reaction of the organism towards exposure to a xenobiotic. We have seen that exposure can be through inhalation, ingestion, through skin etc. This response depends on the dose to which the organism was exposed. This reminds use of the basic principle in toxicology that the dose decides the response, whether a material is Toxic or nontoxic. The living organism could be exposed to various chemical, radiological, so called inert materials through the environment in which they exist. These exposures bring about responses according to the concentration of these xenobiotic, finding a way into the organism. Take the case of burning of waste in the open. There is heat and smoke. The nature of heat and smoke varies with the content of the waste. Our response is to avoid the smoke, as it gives a burning sensation to the eyes and suffocating to the lungs. These are immediate response. In reality the acidic nature of the smoke makes it dissolve in the tears and form acid which gives irritation to the eyes and make it appear red in color and swollen. The same effect is happening with in the lungs and the cells in the lung gets swollen and suffocation happens. Here the response is from the tissue and as time pass, the acidic portion is scavenged by the body and relief is obtained. So the initial response of the body gradually may fade if the nature of exposure is acute or temporary. If the exposure is going to be continuous or the concentration of the exposure is going up, then the response will become severe and the organism continues to be in the smoky environment, the response becomes more suffocation because of lung tissue, failure to supply oxygen to the whole body, resulting in a stand still of body functions and death. The response depends on the status of the environmental conditions and availability of emergency medical assistance. To understand and asses the response of living organism to toxic materials, various methods have been developed and in place. When we move ahead, we will look into these facts, where we will come across lot of scientific terms in relation to dose, exposure and response.
Classes on Toxicology:- Dose and Response
From the previous readings we understood the basics of Dose and Response separately. Today we will try to understand how they relate to each other in a toxicological study setting. Dose, response relationship is described based on studies conducted on experimental animals, clinical trials in human beings and cell culture studies. When a population is exposed to a toxicant or poison the response may vary from person to person or to say there may be a group that is affected severely and another group affected in general. That indicates there could be variation in response at a particular dose. But in general you can observe an increase in response as the dose increase and reaches a stage where all exposed are severely affected or dead. The final dose which brings in death is known as the lethal dose. The lowest dose at which an observed response is evident is known as threshold dose. If you are plotting the response to a xenobiotic or a poison in a standard graph, the X axis for dose and Y axis for response, the point at which the response is noted becomes the threshold dose level and as the dose increases the curve also increases and the point at which the response is 100% severely affected or mortality. The threshold level will vary for each substance and the potency increases as the slope becomes greater. The quantity of xenobiotic or to a poison to which an individual or organism is exposed or administered over a period of time or in several and individual doses may be considered as administered dose, the dose at which the individual or organism responds initially is called the threshold dose, the division of the total dose and its administration at different period of time decreases the toxic effect. All these factors are necessary for determining dose response relationship. As we have noted earlier, the common dosage unit is mg per Kilogram body weight per day. As we read on we will come back to the basics of dose and response and their relationship to acute and chronic exposures and responses.
Classes on toxicology:- Acute Exposure
We now know what is meant by Exposure in the toxicology field. Daily we are exposed to hundred and one items through the air we breath, water we drink, food we eat, the drugs we consume, the cosmetics we use almost every day, the secondary smoke from smokers around and so on. These are all exposures in general, may be in small doses which may not bring about any noticeable responses. But when we get exposed to some chemical or a poison and experience some untoward response from the body, the exposure become acute exposure to the particular chemical or poison. Acute exposure of a poison at a small dose may not result in any harm to the body but exposure to even a very small dose of hydrogen cyanide will bring death. Acute toxicity response can be a result of a single dose or multiple doses during a day or 24 hrs and may be without knowledge of what the Toxin to which the exposure is made. On exposure to small doses/ an acute exposure to a hazardous material may initiate symptoms like nausea, vomiting, stomach pain, head ache, irritation of skin and eye, cough, edema, seizures, respiratory failure etc. Toxicity data on almost every existing chemicals and xenobiotics are available. These data is arrived at after carrying out experiments in Laboratory animals.
Classes on Toxicology: Chronic Exposure
In our day today life we may be exposed to some material each day repeatedly for over a period of time for more than 90 days, it may be called a chronic exposure. This may be due to work conditions, environmental conditions, or may be due to modern life style or use of certain drugs eg. for Asthma. These materials may be hazardous or debilitating in the long run. Exposure to lead or mercury through food or water, pesticides during agriculture work or the vehicle solvents in many inhalation drugs. These kinds of chronic exposures to low concentrations have deleterious effects of living systems, symptoms slowly developing and expressing. The symptoms expressed owing to a chronic exposure may not subside as soon as the exposure is with held or stopped. These symptoms may be the outcome of the toxic or hazardous nature of the material to which the exposure is made. Hazardous substance need not always be a toxic material or a poison. Fibrosis of liver due to consumption of alcohol, kidney problems due to slow lead poisoning, neurological problems due to mercury poisoning, chronic bronchitis of chain smokers, fibrotic lung disease of coal workers, cancer of asbestos miners are some examples of chronic toxicity outcomes. Drugs for asthma, blood thinners, pain killers, thyroid problems are some examples which people take without medical supervision and end up in chronic exposure resulting in untoward results.
Classes on Toxicology: Testing
Today we will try to understand “Testing” in the toxicology field.
Testing for poisonous materials in humans or animals, which are consumed orally, inhaled or absorbed through the skin or injected parent erally is the common practice. This is for ascertaining the quantity if the suspected material is known, if not known for identifying the material too. This type of toxicology testing is also known as toxicology screening. Toxicology screening is very common in suspected poisoning in individual case, industrial settings, sports and games, drug abuse, clinical settings etc. Toxicology testing carried out on a dead body is Forensic Toxicology. Routine Toxicology testing is carried out by drawing samples of Urine and Saliva. Forensic Toxicologists use also use body/ organ fluids, cells, tissue etc. for testing. “Toxicity Tests” have another explanation. If a chemical or consumer product has to get a license to sell or commercial use, it has to undergo a battery of tests to prove it is not hazardous and safe to use. These tests are set up by FDA or EPA and used by the manufacturers of the product. They submit their test samples to accredited testing Laboratories for carrying out toxicology Tests or for Toxicology screening of their products. In the next class we will go through some of the glossary in Toxicology, which will make us understand the topics we have read through so far.
Classes on Toxicology : Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007)
J. H. DUFFUS et al
absolute lethal dose (LD100) Lowest amount of a substance that kills 100 % of test animals under defined conditions.
absolute lethal concentration (LC100) Lowest concentration of a substance in an environmental medium which kills 100 % of test organisms or species under defined conditions.
absorbed dose (of a substance) internal dose Amount (of a substance) taken up by an organism or into organs or tissues of interest.
absorption (in biology) uptake Penetration of a substance into an organism and its cells by various processes, some specialized, some involving expenditure of energy (active transport), some involving a carrier system, and others involving passive movement down an electrochemical gradient. Note: In mammals, absorption is usually through the respiratory tract, gastrointestinal tract, or skin into the circulatory system and from the circulation into organs, tissues, and cells.
absorption (of radiation) Phenomenon in which radiation transfers some or all of its energy to matter which it traverses.
absorption, systemic Uptake to the blood and transport via the blood of a substance to an organ or compartment in the body distant from the site of absorption.
abuse (of drugs, substances, solvents, etc.) Improper use of drugs or other substances.
accidental exposure Unintended contact with a substance or change in the physical environment (including, e.g., radiation) resulting from an accident.
activation (abiotic) Conversion of a xenobiotic to a more toxic derivative by modification not involving biological catalysis
active ingredient. Component of a mixture responsible for the biological effects of the mixture.
active metabolite. Metabolite causing biological and (or) toxicological effects.
active transport Movement of a substance across a cell membrane against an electrochemical gradient, in the direction opposite to normal diffusion and requiring the expenditure of energy.
- Of short duration, in relation to exposure or effect; the effect usually shows a rapid onset.
2. In clinical medicine, sudden and severe, having a rapid onset.
acute effect. Effect of finite duration occurring rapidly (usually in the first 24 h or up to 14 d) following a single dose or short exposure to a substance or radiation.
acute exposure. Exposure of short duration.
acute toxicity. 1. Adverse effects of finite duration occurring within a short time (up to 14 d) after administration of a single dose (or exposure to a given concentration) of a test substance or after multiple doses (exposures), usually within 24 h of a starting point (which may be exposure to the toxicant, or loss of reserve capacity, or developmental change, etc.). 2. Ability of a substance to cause adverse effects within a short time of dosing or exposure
acute toxicity test short-term toxicity test Antonym: chronic toxicity test Study in which organisms are observed during only a short part of the life span and in which there is often only a single exposure to the test agent at the beginning of the study.