Modern toxicology is regarded as a multidisciplinary science. It is subdivided into four principal disciplines — Environmental, Economic, Clinical, and Forensic toxicology. However, Loomis (1968) refers only three basic subdivisions of toxicology, i.e., Environmental, Economic, and Forensic toxicology. He refers clinical and medicolegal aspects of toxicology under the head ‘Forensic Toxicology’.
Further, Klaasen (1986) incorporated three more categories of toxicology — Descriptive, Mechanistic and Regulatory toxicology. Few other branches of toxicology are Analytical toxicology, Behavioural toxicology, Aquatic toxicology, Industrial toxicology, Comparative toxicology, Speculative toxicology, Ethnic or Geographical toxicology, Immunotoxicology, Wildlife toxicology and Genetic toxicology.
The principal divisions and branches of toxicology are:
The environmental degradation due to the presence of various pollutants is referred as environmental toxicology. Thus environmental toxicology is the study of causes, conditions and effects of such chemicals on the living system and biosphere.
Environmental toxicology incorporates pollution studies, residue analysis, industrial hygiene and occupational health. In general, pollution can be defined as ‘matter in the wrong place’ or any substance released into the environment which degrades it.
According to Edward (1972) ‘Pollution is the release of substances or energy into the environment by mankind in quantities that damage either his health or resources’. The individual’s health status vis-a-vis his work in environment — termed ‘occupational health’ — and the efforts to keep the work place clean — called ‘industrial hygiene’ — go hand in hand.
Occupational health can be defined as the science and art devoted to the recognition, evaluation and control of those environmental factors or stresses arising in or from the work place which may cause sickness, impaired health and well- being or significant discomfort and inefficiency among workers. In simple words, the health status of individuals in relation to the environment of the working place is referred to as occupational health.
If the same definition is extended to include the environment outside the work place, and illness or death among the citizens of a community, then it is called environmental health.
Thus, occupational health relates to work place pollution while environmental health relates to environmental pollutions. However, the methodology for both studies is the same. The stresses at work place can be caused by noise, heat, chemical substances, gases etc., while, in the general environment, it can be the pollution of air, water and food.
Therefore, environmental toxicology may be regarded as a multi-disciplinary science involving chemistry, life sciences, agriculture, medical science, public health, sanitary engineering etc. In simpler terms, it is the science of chemical phenomenon in the environment. In this way, environmental toxicology may be treated as a branch of Environmental Chemistry which deals with the nature and action of toxicants on the living organisms.
In view of their nature and mode of action, the environmental components may be grouped into three terms:
A. Environmental Pollutant:
A substance present in nature, in greater than natural abundance due to human activity, which ultimately has a detrimental effect on the environment and, therefrom, on living organisms and human beings. Examples — Arsenic, Lead, Mercury, Cadmium, SO2, CO2, CO etc.
i. A pollutant is anything including a chemical, geochemical substance, or a biological product that deteriorates the natural environment.
ii. According to Holister and Porteus, a pollutant is a substance which adversely changes the natural environment by changing the growth rate of species, interferes with the food chain, is deleterious, or interferes with health, comfort, amenities, or property values of people.
iii. According to Odum – “Pollutants are the residues of the things we make use, and throw away”.
iv. According to Holdgate (1971), a pollutant may be defined as ‘something that is present in the wrong place, at the wrong time and in the wrong quantity’.
v. In the Environmental Protection Act, 1986, of India, ‘Environmental Pollutant’ means any solid, liquid or gaseous component present in such concentration as may be, or tend to be, injurious to environment, and ‘Environmental Pollution’ means the presence of any environmental pollutant in the environment.
B. Environmental Contaminant:
A component or material which does not occur in nature, but is introduced by human activity into the environment, affecting its composition.
A contaminant is classified as pollutant when it exerts a detrimental effect, e.g.:
i. MIC (Methyl Isocyanide) tragedy of Bhopal (M.P.) in 1984 Dec. 3rd;
ii. Chlorine gas escaped from a derailed railway tanker near Youngstown, Florida, in 1978 and killed eight persons driving on a nearby road.
Both the gases, i.e., MIC and Cl2, do not occur in the atmosphere, so both are, undoubtedly, contaminants. Because of their deleterious effects, both are also pollutants.
C. Environmental Toxicant:
Any substance in the environment which exerts toxic effect over the organisms is referred to as environmental toxicant and/or their metabolites adversely affecting certain structures of the organism. The structure may be non-specific such as any tissue in direct contact with corrosive chemicals. More often, it is specific, involving a particular subcellular structure. A variety of structures, including the ‘receptors’, may be affected.
The term “environmental toxicology” is relatively new and its appropriate use is not yet established. The term ought to be reserved for all applications of toxicology to organisms other than man and his domestic animals.
To sum up, environmental toxicology is the qualitative and quantitative study of injurious effects of chemical and physical agents.
Detection of causes of mortality due to any toxicant (poison) via medical examination is an allied aspect of toxicology and referred as Forensic Toxicology. Therefore, forensic toxicology deals with the poison, its type, symptoms and possible treatment. In precise form, forensic toxicology is concerned with the medicolegal aspects of deleterious effects of chemicals on human and other animals.
It is difficult to find a short but comprehensive definition of poison. A poison may be defined as a substance which, when absorbed into the living organisms, or when acting locally on its tissues, injures the health or destroys life.
Classification of Poisons:
For practical purposes, in toxicology, ‘Poisons’ may be divided into four classes:
III. Neurotics (Nerve Poisons)
IV. Cardiac (heart) poisons
Corrosive poisons destroy by chemical actions all tissues with which they come in contact. Strong minerals, inorganic acids such as H2SO4, HNO3, and HCl, organic acids such as acetic acid (CH3COOH), oxalic acid and also caustic alkalis— belong to the class of corrosive poisons.
The symptoms commence at once. Pain is immediately felt in the parts which have come in contact with the poison. When swallowed, there is a violent burning pain from the mouth to the alimentary tract, followed by immediate and uncontrolled vomiting. Symptoms of collapse quickly set in, the skin becomes cold and covered with sweat and the pulse becomes feeble. There is difficulty in breathing and intense thirst. Swallowing becomes difficult, rather, impossible. The mind remains clear till the last.
There are three ways of counteracting the action of the corrosives:
(a) Neutralization through an antidote. In case of acids, neutralization is done by giving mild alkalis and chalk, egg shells; while, in case of alkalis, by dilute acids viz., vinegar, lime juice etc.
(b) Dilution of the poison by giving plenty of water to drink.
(c) Administration of white of egg, butter, rice water, barley water etc. which provides soothing effect.
Irritant poisons produce inflammation of the part with which they come in contact, but do not, as a rule, destroy the tissues. Vegetable acids, juices of nuts, madder, lalchita etc. are local irritants.
Many other important poisons of this class, e.g., arsenic, mercury, antimony, besides causing local inflammation, produce certain specific symptoms when absorbed into the system.
When swallowed, the symptoms do not usually appear immediately, but there is usually an interval of about half an hour or so between the swallowing of the poison and the commencement of the symptoms. Pain is felt from the mouth to the stomach. Violent vomiting and purging set in. Thirst is always intense. Gradually, symptoms of collapse develop.
As in case of corrosives, acids should be neutralised by alkalis, and vice versa. Demulcent drinks should be freely given. Specific treatment only by a physician.
Neurotic poisons — after absorption into the system — act on the nerve centres, brain and spinal cord.
They may be divided into four groups, each exhibiting specific symptoms:
A. Narcotics (Opium — Morphine).
B. Deliriants (Datura – thorn-apple, its fruit or flower. Belladonna).
C. Excitants (Alcohol, Hemp, Cocaine).
D. Spasmodics (Strychin, Nux vomica).
A. Symptoms of Narcotics:
Narcotics produce drowsiness, passing on to deep sleep and coma.
B. Symptoms of Deliriants:
Deliriants produce active delirium, sudden fits of laughter, catching at imaginary objects, staggering and becoming insensate etc.
C. Symptoms of Excitants:
Excitants produce excitement, reduced control over movements, deep sleep passing on to coma.
D. Symptoms of Spasmodics:
Spasmodics produce muscular spasms and fixation of chest. Death results from suffocation or exhaustion.
Neurotically affected person should be kept under close examination and soon be treated by a competent physician. However, an attempt to induce vomiting should always be made as quickly as possible.
IV. Cardiac Poisons:
Cardiac poisons, prussic acid, aconite, tobacco etc., attack the heart and circulation.
Symptoms of Cardiac Poisoning:
The ordinary symptoms are giddiness, fainting, slow pulse and respiratory failure. Death results usually from cardiac failure.
Immediate intake of excess water followed by hospitalization.
Poisoning may be homicidal, suicidal or accidental. The poisons chiefly used in India are opium, arsenic, datura, aconite, mercury, copper salts, nux vomica, methylated spirit etc. For homicidal purposes, arsenic is most commonly used, and for suicidal purposes opium; opium is also used as infanticide.
Two frequently used poisons are arsenic and opium from which lives may be saved by timely treatment.
Description of their usual symptoms and treatment is given below:
Killers select this poison due to its easy availability from the market. It is tasteless, colourless and odourless and can be mixed with food, only a small quantity is required to destroy life, and the symptoms can be mistaken for that of cholera.
The symptoms usually commence about half an hour after the poison is administered. An irritant poison, causes burning pain in the throat, stomach and abdominal pain, thirst, vomiting, purging and straining, also presence of blood in the vomitus and stools, scantiness or suppression of urine, cramps, feeble pulse, and, in some cases, headache, delirium etc. Death usually takes place within twenty-four hours.
Distinction between Cholera and Arsenical Poisoning:
Very often the symptoms of acute arsenical poisoning are mistaken for that of cholera. In arsenical poisoning the stool usually contains blood and there is burning in the throat before vomiting. In cholera, the stool from beginning is like ‘rice water’, and there is no pain or irritation of the throat before vomiting. In arsenical poisoning the vomiting usually starts first, followed by purging, while, in cholera, it is just the reverse.
Vomiting should be encouraged and the patient should be given mild warm water. Freshly prepared hydrated ferric oxide is used as an antidote of Arsenic. It should be given in tablespoonful dose every 5 or 10 minutes, until the symptoms are relieved. Doctor should be consulted at once.
Solid opium, often mixed with mustard oil, is often swallowed to commit suicide.
The symptoms commence in about half an hour. There is slight excitement lasting for a short time, followed by giddiness and drowsiness, followed by deep sleep, ending in coma and unconsciousness. The odour of the opium may be detected in the breath. The breathing becomes shallow and slow, the pulse is weak and irregular, the skin gets bathed in sweat and is cold, and the pupil gets contracted. Death usually occurs in about 12 hours.
Emetics should be induced as quickly as possible by using common salt and hot water. Tickling the throat excites vomiting. Patient should be kept awake by sprinkling of cold water on the face and head, and wet towel should be kept on the head. Patient should be given hot coffee to drink if he is conscious. Artificial respiration maybe given. Patient should be kept under observation of physician.
Subjects classified under this head — food, drinks, drugs, etc. — are directly and indirectly involved in the economics of the country, e.g., pure food contributes to good health and is of real value in the commercial export market.
In other words, economic toxicology is directly or indirectly related to the economics of the nation. It deals with the harmful effects of chemicals which are intentionally administered for the purpose of achieving a specific effect in the biological system.
Two aspects are closely related:
(i) Food toxicology, and
(ii) Drug toxicology.
(i) Food Toxicology:
The contamination of the food could be accidental, unintentional, or intentional adulteration for higher profits. In freshly cooked food, many of the contaminants would be eliminated at a high temperature. An interesting example is the poisoning due to cyanogenic glycosides from eating uncooked raw cassava (tapioca) in Africa.
In India, people eat cooked cassava and this problem does not exist. The possibilities of contamination are more in the processed foods. Food adulteration is an art in itself and not much can scientifically be said except about the common adulterants.
The Beer Epidemic of 1990:
Large scale poisonings used to occur in the early part of the 20th century and an interesting episode was the Beer Epidemic in U.K. In June 1990, a few people — alleged to be beer-drinkers – died in the north of U.K., around Liverpool. More deaths occurred in the following months at Manchester, Salsford, Lancashire and adjacent areas.
Initially, it was attributed to alcoholism, peripheral neuritis or multiple neuritis. But when the numbers affected reached a few thousands, the government appointed a commission of enquiry with Lord Kelvin as chairman. Analysis of the beer showed 1.45 – 2.6% Arsenic. Close investigation proved that the beer was from the brewery of Bostock at Garston near Liverpool.
Poisonings are not limited to the olden days. Cooking oil contaminated with Triorthocresol Phosphate (TOCP) killed 300 people in Spain in 1981 and left 20,000 with neurotoxic lesions. In 1960, a large number of people died in Kerala after using sugar contaminated with an insecticide, Folidol. In 1971,113 babies (out of 12,000 victims) died from dried milk powder contaminated with arsenic.
The use of Kesari dal (a banned item) for extended period of time produces lathyrism due to the presence of Oxalydiaminopropionic Acid (ODPA) and β-aminopropionitrile.
The Minamata disease due to consumption of fish contaminated with methyl mercury dumped as industrial waste into the Minamata Bay of Japan killed large number of people.
In 1972, in Iraq, about 6,000 people were affected seriously by consuming bread made from cereals contaminated with alkyl-mercury fungicides. Itai-Itai disease in Japan, which produced severe bone and joint pain like arthritis, was due to higher cadmium content in rice receiving effluent from a zinc cadmium mine upstream.
Major Contaminants in Food:
The major contaminants of food are microbial organisms, viz., small round virus (SRV) which causes gastroenteritis, environmental contaminants, viz., Pb, Hg, chromate, arsenic etc., natural toxicants, viz., mycotoxins, pesticide residues and food additives.
(ii) Drug Toxicology:
Actually the evolution of toxicology began with the work on poisons used as drugs. Paracelsus, father of toxicology, reported that it is the dose which determines the toxicity and not the drug by itself. The chemical would become a drug only if the side-actions are not significant in comparison to the major desired effect.
Morphine, which was being used as an analgesic, earlier produces respiratory depression and also addiction. So the use of morphine as an analgesic today is highly restricted. Cortisone and penicillin can produce immunological reactions, but their good effects outweigh the adverse ones and so are yet in use.
In Japan (1960) a number of people were affected by Sub-acute Myelo-Optico-Neuropathy (SMON). It caused abdominal pain and persistent diarrhea followed by a kind of paralysis of the extremities of the legs. In severe cases, blue-red visions, blindness and sensory disturbances preceded death. Investigations traced that SMON was due to intake of clioquinol, which is actually iodochloro-8 hydroxy quinoline, marketed as Mexaform and Entero Vioform in India.
It was previously thought to be a neurotoxic response of clioquinol, but toxicological investigations proved this to be due to the amine- rich diet of the Japanese, mainly fish, interacting with the clioquinol, which was found to be a mono- amino oxidase inhibitor — causing disturbances of amine metabolism and accumulation. This is an excellent example of geographical toxicology where drugs and food habits are contradictory to each other. SMON may not be produced in India where dietary intake of amines (fish products) are far less.
Drugs like antipyrine and theophylline are metabolised at a faster rate by high protein-low carbohydrate intake. Quite a lot of information has been collected on drug toxicity on newborn and immature rats, and higher toxicity has been observed.
Antihistamines, chlorophenilamine maleate and diphenyl hydramine show high toxicity in very young rats due to rapid absorption from the site of ‘ingestion. These drugs are very poorly tolerated by young children too.
Causes of Higher Toxicity of Drugs in Infants:
The following are the possible causes of higher toxicity of drugs in infants:
i. The larger volume of extracellular fluid in infants (almost thrice that of adults) which increases drug retention and slows down its excretion.
ii. The immaturity of drug metabolising enzymes. Chloromycetin (chloramphenicol) can cause cardiovascular collapse due to this particular reason.
iii. Slower excretory mechanism can also be a reason, for example, Niliclixic acid is retained in blood for 15 days in newborn calves, while its half-life is one and a half hour in seven month old calves.
The margin of safety (therapeutic index) is the guiding factor in developing a chemical as a drug. Actually margin of safety is the difference between LD50 and ED50; the wider the gap between the two values, better the chemical as a drug.
It deals with diagnosis and treatment of the effects of harmful diseases caused by toxic substances of exogenous origin i.e., xenobiotics. These include accidental and intentional abuse of chemical substances, including therapeutic agents; undesirable excessive and non-therapeutic drug effects; injurious interaction of xenobiotics; accidental exposure to toxic substances in house and industry, intentional and inadvertent food additives; environmental contaminants, and naturally- occurring toxic hazards.
Clinical toxicology is closely related to forensic toxicology. The application of antidotal substances to prevent the toxic actions of poisons are also important aspects of clinical toxicology.
It is a branch of toxicology which is associated with the elucidation of mechanisms by which xenobiotics exert their deleterious effects on living beings.
The study of changes at the cellular and subcellular levels as a result of toxic action of chemicals is designated as biochemical toxicology.
It is a branch of toxicology which deals with the imposition of certain restrictions on the entry of chemicals in the environment with the help of law. For this purpose, legislations are framed and passed by the government (State and Central) and regulatory agencies enforce these legislations.
It deals with the study of the nature and types of chemical substances emitted by the industries in ambient air and water, and possible effects of such contaminants on the living biota including human beings. It is much close to environmental toxicology. It also considers the suggestions regarding proper measures to treat hazardous substances released from the industries and, thus, to minimize their release into the environment.
It deals with the study of deleterious effects of xenobiotics, if any, on chromosomes and, more specifically, upon the genetic constitution of individuals. It is closely related to the mechanistic as well as biochemical toxicology.
This branch deals with the evaluation and recommendation of suitable measures for the protection of environment and its living resources.
It is chiefly concerned with the study of alterations in the behaviour of organisms following exposure to specific toxicant.
This branch deals with the adverse effects of chemicals on a particular system of organisms, viz., respiratory system, immune system, nervous system, cardiovascular system etc.
This branch deals with the study of relative- toxicities of xenobiotics to various organisms.
Toxinology is the study of toxins in the restricted sense (poisons produced by microorganisms, viz., bacteria and viruses etc.).
It involves the study of the effects of toxicants of any origin on wildlife, in exactly the same way as the veterinary toxicology is related to domestic animals.
It is a recent area concerned with the puzzling phenomenon that certain toxic drug reaction seems to be more frequent in particular countries or in one continent. It analyses various factors (climate, nutritional practices, genetic factors and other environmental influences) which might account for these differences in responses of the human body to a xenobiotic.