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Essay on Toxicology
Essay # 1. Introduction to Toxicology:
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Of all the branches of life science, the study of toxicology has generated greater excitement and became a subject of general interest in the present century. Today toxicology is not merely a study of poisons — as many conceive falsely, based on the definitions given in dictionaries. It clearly indicates that toxicology has left the lexicographers way behind.
Toxicology, therefore, may be defined as the study of interaction of materials (drugs, chemicals, drinks, foods, polymers, pesticides, etc.) with a biological system and depiction of adverse responses. The word toxicology is derived from two Greek words – toxikon = poison + logos = discourse or study. However, in the present scenario, the word ‘poison’ has lost its original relevance. The ‘Poison Act’ was legislated in 1918 and since then much water has flown over it.
Centuries ago, Paracelsus (1493-1541) — the father of toxicology — categorically said that all substances are poisons. It is the right dose that differentiates a poison from a remedy. An old adage emphasises that even nectar (amrit or that which stops death) is also a poison, if consumed in excess. It has been proven more than correct in recent times.
Actually, response is related to the dose as the same chemical that acts effectively like a drug — in low doses — could be a poison in higher doses. This statement has evolved a dose-response relationship in toxicology. Arsenic and mercury were remarkable remedies for many illness in the early days of allopathy; at present no country will ever permit a new drug containing arsenic or mercury to be introduced without in-depth toxicological evaluation.
Apart from the normal responses, many xenobiotics could produce adverse reactions on widespread use. An interesting example relates to hexachlorophene, widely used since 1945 as mild bactericide in talcum powders and soaps. In 1970s, hundreds of children were severely affected and over 30 expired after applying a talcum powder containing 5% hexachlorophene in France.
In fact, the chemical had been cleared after essential sub-acute study by administration to rats for 30 days. Further, on a re-evaluation of the toxicology of the drug, it was found to react with white matter in the brain and spinal cord; and interfered with the mitochondrial metabolism leading to myelin (covering of nerves) degeneration producing spasms, convulsions, coma and consequent death. The chemical was subsequently banned for cosmetic use in various countries of the world.
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The role of the toxicologist may well be judged and we can thus relate toxicology as the science that defines the safety threshold of chemicals. However, in the broad sense, toxicology may be referred to as the basic science of poisons. A poison or toxicant may be any chemical substance which, on entering the body of an animal in insignificant amounts, cause malfunctioning of vital activities and may lead to impaired health.
Practically, there is no chemical which may be completely safe under all the exposure conditions. Contrarily, it is also true that there is no chemical which cannot be used safely by limiting the dose or the exposure.
Poison may be either a natural product of animal or plant origin or it may be a synthetic one. The poisons that are synthesized within the organism itself are referred to as endogenous poisons or toxins and those which enter an organism from the outside (environment) are referred to as exogenous poisons or toxins. Exogenous chemicals are also referred to as xenobiotics.
The basic science of toxicology encompasses biochemistry, pharmacology, pathology, and, to a great measure, chemistry. Statistical probability being an important ingredient of prediction, one cannot ignore the role of biostatistics in toxicology.
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Toxicology is essentially a predictive or speculative discipline of science, as humans cannot be used in experimenting with unknown chemicals. Almost all toxicological studies start with rodents, that is, rats and mice, which are referred to as target or test animals. This may also be carried on to larger animals like dogs, monkeys and rabbits, if experiment demands. The results of the animal studies have to be extrapolated to humans and actually this is the most difficult exercise, considering the wide difference in the organ systems of human and test animals.
In a nutshell, toxicology provides a sound basis for formulating measures to protect the health of workers against occupational toxicants in factories, mines and other occupational environments in particular and other population in general. It is also valuable in the protection of public health against hazards associated with toxic substances in food, air and water. Undoubtedly, toxicology has played — and will continue to play — a significant role for human health and welfare in the world.
The term “Environmental Toxicology” is relatively new and its exact usage is not established yet fully. The term ought to be reserved for all applications of toxicology to organisms other than man and his domestic animals. Defined in this way, Environmental Toxicology is the study of toxins in the restricted sense (poisons produced by living organisms including microbes).
Ecological Toxicology is the study of all toxicants produced by living organisms and their effects on overall ecological relationship. This discipline is much broader than toxicology.
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Wildlife Toxicology involves study of the effects of toxicants of any origin on wildlife, in exactly the same sense as the veterinary toxicology is related to domestic animals.
Toxicology is becoming an increasingly important subject of discussion of the modern society because of the adverse effects of the growing use of chemicals and high-tech radioactive appliances. It is a multidisciplinary subject with a vast and diffused literature.
Most of the living beings are exposed to a great variety of natural as well as man-made chemical substances. Under certain conditions, such exposures cause health hazards, ranging in severity from death to subtle biological alterations. Society’s ever- increasing desire to identify and prevent these effects has resulted in the dramatic evolution of toxicology from only a study of poisons to the present-day complex science.
Having realized the importance of toxicology, WHO (World Health Organization) in 1982 organized a Toxicology Training Course (TTC) in China as a part of the on-going China-WHO collaborative programme on medical sciences.
At the beginning of the 21st century ‘Toxicology’ has emerged as an important branch of pharmacology. It provides a sound basis for formulating measures to protect the health of factory workers, farmers, miners and others exposed to different toxicants. It is also valuable in the protection of public health against hazards associated with toxic substances in food, air and water. In fact, toxicology has played — and will continue to play — a significant role in the health and welfare of the world.
Essay # 2. Definition of Toxicology
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Toxicology is a Greek word—toxin or toxicum or toxicon = poison + logus = discourse or knowledge, i.e., “the science of poison”. In other words “the branch of pharmacology which deals with the various aspects of poisons and poisoning is known as toxicology”. Poison may be defined as a substance which, even in small dose, produces adverse effect in the metabolism of an organism and, consequently, may cause death.
Presently, toxicology is not restricted to the study of poisons only. Rather, it is the study of the nature and mechanism of toxic effects of substances on living organisms and other biological systems. Toxicology also deals with the quantitative assessment of the severity and frequency of these effects in relation to the exposure of the organisms. Along with other sciences, toxicology contributes to the development of safer chemicals used as drugs, food additives, pesticides etc.
Du Bois and Geiling (1959) defined toxicology as a branch of medical science that deals with the nature, properties, effects and the detection of poisons. It is, therefore, the science of poisons. In this definition, are included studies on the metabolism and excretion of poisons, on the action of poisons, and on the treatment of poisoning, as well as systematic chemical and physical analyses and diagnoses.
The first research institute of toxicology in India is ITRC (Industrial Toxicology Research Centre) established in 1969 in Lucknow (U.P.).
The term ecotoxicology was described by Truhaut in 1974. It is the study of the adverse effects of the environmental pollutants on an ecosystem — studied under natural conditions. At present, ecotoxicology is considered in a wider sense to include — in addition to toxic effects of chemicals (toxicants) on organisms — also their processes to environmental concern.
Essay # 3. History of Toxicology
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Toxicology predates human beings and in many ways is a part of their history, which began as an interest in poisons — from plants and animals.
1. The Early Era:
Hippocrates was the first to introduce primitive principles of toxicology around 400 BC. He gave quite a few tips to prevent the absorption of toxins.
The earliest man was well aware of toxic effects of a number of substances, such as snake venom, the poisonous plants, hemlock and aconite and the toxic mineral substances such as arsenic (As), lead (Pb), antimony (Sb) etc. Some of these were actually used intentionally for their toxic effects to commit homicide and suicide.
For centuries homicides (toxic substances) were not uncommon in Europe. To protect poisoning, there were continual efforts directed towards the discovery and development of preventive and antidotal measures. However, a more critical evaluation of these measures was only taken up by Maimonides (1135-1204) with his famous book entitled “Poisons and their Antidotes” published in 1198.
2. The Middle Ages (1300-1600):
More significant contributions to the evaluation of toxicology were made in the 16th century and Paracelsus (1493-1541) (father of toxicology) stated- ‘No substance is a poison by itself’, ‘It is the dose that makes a substance poison’ and, ‘The right dose differentiates a poison and a remedy’. These statements laid the foundation of the concept of ‘dose-response-relationship’ and ‘therapeutic index’ developed later.
Further, Bergsucht (1533-1534) described the clinical manifestations of chronic arsenic and mercury poisoning as well as miner’s disease. He may, therefore, be considered the forefather of occupational toxicology.
Later on Orfila, M.J.B. (1787-1853), a Spanish physician, also known as the father of modern toxicology, wrote an important treatise (1814-1815) describing a systematic correlation between the chemical and biological information on certain poisons. He also devised methods for chemical analysis and detecting poisons for legal proof of lethal intoxication.
The introduction of this approach developed a new discipline of modern toxicology, namely, forensic toxicology. Orfila became the Professor of Jurisprudence at the University of Paris and pioneered Forensic Toxicology.
Another renowned toxicologist of this era was Francois Mogendie (1783-1855), a physiologist, who studied the mechanism of action of emetine and strychnine. Claude Bernard (1813-1878) used poisons as tools in analyzing physiological aspects of organic systems.
Initially there was a tendency to treat toxicology as a part of pharmacology; but, with all the developments and catastrophes, toxicology could not catch public attention until Alexandre Dumas devoted a separate chapter to Toxicology in his world-famous novel ‘Count of Monte Cristo’.
Essay # 4. Recent Developments in Toxicology
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With increasing population, the modern society demands improvement of the health and living conditions, including nutrition, clothing, dwelling and transportation. In order to fulfill these growing needs, a large variety of chemicals, many of them in large quantities, must be manufactured and used. It may be emphasized that tens of thousands of various chemicals are in commercial production in industrialized countries.
In one way or the other, these chemical compounds come in contact with various segments of the population, e.g., people engaged in their manufacture, handling, use, consumption, or even misuse. Furthermore, people may also be exposed to the more persistent chemicals via various environmental media as well.
It is, therefore, essential to assess the toxicity of a vast number of chemicals to make them more manageable. As an attempt to fulfill this need, criteria have been proposed and adopted for the selection of chemicals to be tested according to their priority.
In modern disciplines a variety of toxicological testings have been used viz., carcinogenicity, mutagenicity, immunotoxicity etc.
Advances made in biochemical and chemobiokinetic studies — as well as those in the genetic toxicology, immunotoxicology and morphological studies at subcellular level — have contributed to a better understanding of the nature, site and mechanism of action of toxicants. Recent studies have shown that the responses to toxicants are better correlated with the effective dose, i.e., the concentration of the toxicant at the site of action, rather than the administered dose.
Furthermore, where the effect results mainly or entirely from an active metabolite, the concentration of the metabolite is more important rather than that of the parent chemical.
To translate scientific knowledge into basic tools for health profession, the toxicologists are more involved in the determination of safe exposure limits or assessment of the risks. The former includes the acceptable daily intake (WHO, 1962) and the threshold limit values (Federal Register, 1971), whereas, the latter is applied to such substances which are believed to have no threshold or their threshold cannot be determined.
These determinations include comprehensive studies of the toxic properties, demonstration of dosages that produce no remarkable adverse effects, establishment of dose-effect and dose-response relationship, chemobiokinetic and bio-transformational studies.
Essay # 5. Toxicity
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Actually, toxicity is a relative term generally applied in comparing one chemical with another. Toxicity of a chemical may be defined as the capability to cause injury in a living organism. A highly toxic substance is that which causes damage to an organism if administered in a very small amount. But a substance of low toxicity will not produce an effect unless the amount is very large.
In fact, toxicity may not be defined without reference to the quantity of a substance administered or absorbed (dose), the way in which this quantity is administered (e.g., inhalation, ingestion, injection), and distributed in time (e.g., single dose, repeated doses), the type and severity of injury and the time required to produce that injury.
Thus, toxicity is a relative property of a chemical which refers to its potential to have a deleterious effect on a living organism. Also, toxicity is a function of the concentration of the chemical and the duration of exposure. Toxicity data are generally used in comparing toxic potentialities of chemicals.
The nature and extent of toxicity varies depending upon the origin of toxicants. They may be natural or synthetic in origin.
Naturally occurring toxicants may originate from animal, plant or mineral sources. Animal toxins as venom belong to this category. Many plants contain toxic agents and many of these are developed for pharmacological applications. Some among these are atropine, opium, reserpine, quinine, picrotoxin etc. A number of antibiotics come from microbes, including mycotoxins. The majority of toxicants stem from industrial or commercial pool of synthetic chemicals.
The toxic effects of the chemical may be physiological, biochemical and pathological in nature. The changes produced by the toxicants may be complex, damaging one or different organs/ tissues/cells. These, in action, may be corrosives, irritants, narcotics etc.
Toxic effects may be grouped into:
i. Local and systemic effect
ii. Reversible and irreversible effect
iii. Immediate and delayed effect
iv. Morphological effect
v. Functional effect
vi. Biochemical effect
Essay # 6. Principal Aspects of Toxicology
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The following are the principal aspects of toxicology:
1. Toxicometrics:
It is the study of measurement of poisons.
2. Toxicodynamics:
It deals with the biochemical and physiological effects of xenobiotics and mechanisms of their action.
3. Toxicokinetics:
It deals with the absorption, distribution, biotransformation and excretion of xenobiotics.
Essay # 7. Scope and Importance of Toxicology
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Toxicology incorporates a very broad scope. It is primarily concerned with the identification of deleterious agents and, secondly, with the treatment of these agents for detoxification, i.e., removal of the toxin. Apart from this a toxicologist is also concerned with the character, properties, signs and symptoms and the chemical detection of the toxin, where offensive intent is suspected.
Actually, toxicology has its impact on human life from the day of conception in the womb till the last moments of life. Nevertheless, certain toxicants are even deleterious for the sperms and the ova.
Toxicology deals with the toxicity studies of chemicals used:
1. In medicine for diagnostic, preventive and therapeutic purposes.
2. Iren food industry as direct and indirect additives.
3. In agriculture as pesticides, growth regulators, artificial pollinators, and animal food additives.
4. In chemical industry as solvent, components and intermediates of plastics and many other types of chemicals.
5. Toxicology is also concerned with the health, effects of metals (as in mines and smelters), petroleum products, paper and pulp, toxic plants and animals toxins.
The study of toxicology may be system-wise – and also agent-wise. In this way, we may have systemic toxicology involving toxicology of central nervous system, hepatic system, respiratory system, ophthalmic system etc. The study would include defences of each of these systems against assault from foreign chemicals, responses and reactions as also injuries caused through excesses.
An agent-wise study would take up drugs, pesticides, food additives, chemicals, heavy metals, trace elements, polymers, radiation, chemical carcinogens, and teratogens. There is hardly much of generalization which can be made and many of the agents have to be studied individually in different species before being precisely conclusive.
Application of toxicology for practical purposes can be broadly divided into three areas which are, however, flexible and overlapping:
1. Forensic toxicology where medical science has a role.
2. Economic or industrial toxicology which includes drugs, pesticides, food additives, containers (like cans and packing materials) etc.
3. Environmental toxicology which includes pollution studies, residue analysis, industrial hygiene and occupational health.
Besides, many other divisions and names are also given by different scientists.
When standard procedures may not be able to predict the toxicity in human, then the predictions have to be based on chemical and physical properties, molecular structure, biological activity relations, pharmacokinetics etc. This is termed as Speculative Toxicology and is based upon certain speculative studies.
Usefulness of the study of toxicology to human beings may be described in the following points:
1. Toxicology may be helpful in the development of:
(i) Suitable and safer food additives,
(ii) Suitable and safer pesticides,
(iii) Suitable drugs against any specific disease.
2. The data on acute toxicity tests for various xenobiotics against different fauna may be valuable in following ways:
(i) Provides an idea of toxic dose of a specific toxicant for specific animal.
(ii) Makes certainty of sublethal doses of the toxicants for specific animal.
(iii) Provides precise idea about maximum permissible limits for the pollutants in the ambient air or the drinking water.
(iv) Assists in evaluation of maximum acceptable daily intake of specific chemical.
(v) Aids in determination of sensitive species.
(vi) Aids in ascertaining sublethal dose of any chemical for long-term toxicity tests.
3. The data on long-term toxicity tests provides reliability for:
(i) In evaluation of safer levels of xenobiotics.
(ii) In determining the most sensitive stage of a particular target animal against any toxicant.
(iii) In elucidation of mode of toxicity of chemicals.
(iv) In rational therapy of intoxication.
(v) In establishment of sensitive predictive tests useful in achieving information for risk assessment.
4. Toxicology may be helpful in the antidotal therapy.
5. It may be helpful in the monitoring of environmental pollution.
6. Toxicology may be helpful in monitoring of risk assessment.
7. An understanding of the mechanism of toxic action also contributes to the basic knowledge of pharmacology, physiology, biochemistry and cytology.
8. Analytical toxicology provides suitable procedures to evaluate the presence or absence of different types of substances and their levels in the environment.
9. It also contributes an idea about the permissible limit of any toxicant in any segment of the environment.
10. Comparative toxicology is concerned with the study of different species of animals exposed to chemical stresses to evaluate how close these are to human systems.
11. It gives an idea about the factors affecting the toxicity of any toxicant.