In this article we will discuss about:- 1. Introduction to Toxicity of Pesticides 2. Insecticides 3. Classification of Pesticides 4. Toxicity of Pesticides and their Effects on Living Organisms.
Introduction to Toxicity of Pesticides:
The word pesticide literally means an agent used to kill an undesirable organism. In the amended US. Federal Insecticide, Fungicide and Rodenticide Act, the definition of an “economic poison” or pesticide was expanded to include.
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1. Any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest [insect, rodent, nematode, fungus, weed, other forms of terrestrial or aquatic plant or animal life or viruses, bacteria, or other microorganisms, except viruses, bacteria, or other microorganisms on or in living man or other animals, which the Administrator declares to be a pest and
2. Any substance or mixture of substances intended for use a plant regulator, defoliant or desiccant.
The major classes of pesticides in use today include herbicides, fungicides, rodenticides, insecticides, nematocides, and molluscides. Prior to about 1940, pesticides were primarily inorganic chemicals (e.g., arsenic) and a few natural agents from plant origin (e.g., nicotine and pyrethrum). With the discovery of the insecticidal activity of DDT, however, a burgeoning increase in the development and utilization of synthetic organic chemicals occurred.
From about 1940 to 1980, an exponential -increase in the production and use of these synthetic pesticides was evident worldwide. The major chemical classes of pesticides that are used today include inorganic and organic metals, chlorinated hydrocarbons, organophosphorus compounds, carbamates, pyrethroids, substituted phenols, substituted ureas, coumarins, organic acids, organic amides, and triazines.
Currently, over 1 billion pounds of about 600 different pesticides (active ingredients) are produced each year in the United States alone, with total worldwide production estimated at around 5 billion pounds.
Insects were the first major focus of pest control, whether to prevent the destruction of food or fiber crops or to limit the spread of insect vectors of disease. There is little doubt the use of insecticides had a profound effect on the further development of civilization. The control of anopheline mosquitoes and malarial infection, as well as vectors for typhus, plague, and yellow fever, by DDT undoubtedly saved millions of lives.
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Over the past several decades, however, the use of herbicides has dramatically increased and such efforts have markedly altered the methods of modern agriculture. As a result, herbicides now represent the most extensively used class of pesticides in the United States. Some food and fiber crops reportedly increased yields by 300 – 600% after the introduction and widespread use of synthetic herbicides.
While the public health and economic benefits of synthetic pesticide use over the past 50 years are indisputable, these benefits have not been without costs. Widespread environmental contamination by DDT and other organochlorine pesticides reaching global proportions, with concomitant deleterious effects on some members of the food web heralded the end of an era for their extensive use. DDT was banned from use in the United States in 1972 and most other organochlorines were subsequently banned, being replaced by the less environmentally persistent organophosphates and carbamates.
While these agents had considerably lower abilities to accumulate in environmental and biological media, they tended to be much more acutely toxic and thus more hazardous to utilize. The pyrethroids are generally regarded as safer than the anticholinesterase organophosphates and carbamates, but still constitute a smaller proportion of total insecticidal use. In general herbicides exhibit markedly lower acute mammalian toxicity than other classes of pesticides.
The relative toxicities of these agents are generally scaled, however, on the basis of acute reactions. Knowledge of the long term health consequences of prolonged, low-level exposure to various pesticide classes is still limited. A major challenge for toxicologists in the future is the continued acquisition of data pertaining to the long-term effects of low level pesticide exposures.
Insecticides:
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Many insecticides affect the nervous system of insects and since many have some activity against the mammalian nervous system, in man the neurotoxic effects of insecticides are often prominent.
There are a number of possible ways in which humans can be exposed to pesticides. The effects of pesticide residues in food and water probably cause the greatest public concern. However, reports of clinical poisoning by residues seem to be extremely rare. Food-borne pesticide intoxication, especially where clinical signs are non-specific or trivial, would probably pass unnoticed or may not be attributed to pesticides.
The problem of consumers who consume high levels of some foodstuffs is taken into account when residue levels are pronounced to be toxicologically acceptable by comparison with the acceptable daily intake (ADI) or the more recently developed concept of the acute reference dose (ARID). On the other hand, simultaneous exposure to more than one pesticide of the same type might occur.
Pesticide poisoning might occur from:
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a. Spillage of pesticides on to food during storage or transport;
b. Eating gram or seed potatoes treated with pesticides, where the food article was not intended for human consumption;
c. Improper application of pesticides or failure to observe harvest intervals.
Weighed against the disadvantages of pesticides that accrue from their toxic effects is the fact that insects and fungi are important sources of agricultural loss and give rise to much damage to wooden buildings. Furthermore, many insects carry diseases such as malaria and sleeping sickness, which in the absence of control measures may render land uninhabitable or agriculturally unfit.
The key to a successful pesticide is selective toxicity. An ideal pesticide will interfere with a biological system in the pest, which has no counterpart in non-target species. This is the advantage of the juvenile hormone analogue insecticides. In the case of agricultural insecticides, the pesticide should be toxic to insects, but less toxic to plants, to humans and to other non-target organisms.
Classification of Pesticides:
This group includes DDT, hexachlorocyclohexane (HCH), the cyclodienes, dieldrin, endrin and heptachlor, and toxaphene. However, the use of organochlorines (OCs) has, in recent years, been severely restricted in most countries. This has mainly been done due to the persistence of OCs in the environment and wildlife and humans.
Despite the fact that OCs are less used than before their toxicology is still important because they continue to be present in the environment and in foodstuffs, specially in developed countries. OCs are excreted in breast milk and their persistence is shown by the continuing presence of OCs in human milk.
The most prominent effects of the OCs are on the nervous system, where OCs have an effect on Na+ channels. DDT produces tremor and incoordination in lower doses and convulsions in high doses. By contract HCH and the cyclodienes may produce convulsions as the first sign of intoxication, as well as fever, by a central effect possibly linked to disturbances in GABA-mediated inhibitory neurotransmission. OCs have been associated with a chronic toxicity syndrome, which includes apathy, headache, emotional liability, depression, confusion and irritability.
OC poisoning is treated symptomatically and diazepam is usually used to deal with the convulsions.
ii. Lindane (γ-HCH):
Lindane is used as a wood preservative, in arable agriculture and in human and veterinary medicine as an ectoparasiticide. It is the ã-isomer of 1,2,3,4,5,6- hexachlorocyclohexane (HCH), which is sometimes known as benzene hexachloride. HCH has eight stereo isomers, of which the á, â- and ã- isomers are the most important.
Of these isomers, only lindane (>99% a-isomer) is still approved in the West, but in some countries preparations of lesser purity continue to be available and these contain other isomers. The effect of lindane on the CNS is stimulatory, causing convulsions, whereas the a-and b-isomers have a depressant effect.
As with other OCs, lindane produces histopathological changes in the liver of experimental animals. The mutagenicity of lindane in vitro and in vivo has been reviewed and the preponderance of evidence is that the compound is not mutagenic.
Two groups of anticholinesterases, the organophosphates (OPs) and the carbamates are widely used as agricultural insecticides and veterinary medicines. Some anticholinesterase OPs are used as human drugs, for example Malathion in the treatment of head lice infestation and metrifonate (trichlorfon) in schistosomiasis.
Several carbamates are used in human medicine, for example pyridostigmine.in myasthenia gravis. The anticholinesterases are often more acutely toxic than the OCs. A variety of cholinergic symptoms and clinical signs occur at parasympathetic effector sites, including bronchorrhoea, salivation, constriction of the pupil of the eye and abdominal colic.
Sympathetic effects can also occur, together with signs of/central nervous system involvement, such as confusion and apprehension. Convulsions will occur in severe poisoning. Actions at the neuromuscular junction result in muscle fasciculation and later paralysis. The terminal event in fatal poisonings seems to be respiratory paralysis, which may be of central or peripheral origin.
It is often stated that the main difference between the OPs and the carbamates is that the former produce irreversible inhibition of acetylcholinesterase, whereas the latter produce reversible inhibition.
The numerous cholinesterases in the body show different intensities of sensitivity to inhibitors. Plasma cholinesterase is usually the cholinesterase most open to inhibition and it reactivates slowly thus it is a useful marker of exposure.
iv. Organophosphate:
OP anticholinesterases are esters of phosphoric, phosphonic or phosphorothioic or related acids. Their general formula is the R groups in pesticides are generally either both methyl groups or ethyl groups. The X or leaving group can be anyone of large variety of moieties.
The OP pesticides have some similarities with the chemical warfare nerve agents, but these are often phosphonofluoridates.
Many pesticidal OPs are phosphorothioates and those containing P = S groups such as Malathion tend to be of lower acute mammalian toxicity than their corresponding phosphates and phosphonates. Thus paraxon is much more toxic than parathion as is malaxon compared to Malathion.
These features are called organophosphate-induced delayed polyneuropathy (OPIDP) and the so-called intermediate syndrome. Since the OP pesticides all have the same qualitative anticholinesterase action, and this property is responsible for their acute lethal toxicity.
Intermediate Syndrome:
As the syndrome developed before the late effects of OPs, the authors called this syndrome the intermediate syndrome. The syndrome comprises a proximal limb paralysis starting 1-4 days after poisoning. The progression is not altered by atropine or oximes and as the respiratory muscles are affected, respiratory support is necessary.
A myopathy has been described post mortem in cases of human poisoning and in experimental animals and this may be related to the intermediate syndrome. The myopathy appears to be initiated by calcium accumulation in the region of the motor endplate.
a. Organophosphate-Induced Delayed Polyneuropathy (OPIDP):
OPIDP is a symmetrical sensory-motor axonopathy, tending to be most severe in the long axons, occurring 7-14 days after exposure. It is a polyneuropathy in that there are central and peripheral components.
There is degeneration of axons and Schwann cell proliferation in the peripheral nervous system and also changes in the spinal cord and medulla oblongata. Clinically, the most disabling feature is the paralysis of the legs. Less severe cases exhibit a characteristic high-stepping gait, and some recovery may occur, but there is no specific treatment.
b. Other Delayed Effects of OPs on the Nervous System:
The behavioural toxicity of anticholinesterases, inter alia OPs, has been reviewed. Since acute intoxication with OPs can cause major effects such as convulsions, respiratory failure and cardiac arrhythmias, all of which can result in anoxia, it is hardly surprising that major intoxication is sometimes associated with long-term CNS changes.
More debatable is whether long-term low-dose exposure produces delayed or chronic effects. Such an outcome is biologically less, plausible than delayed effects of acute exposure, but the two problems have frequently been observed.
It should never be forgotten that OPs may have properties, some of which may be entirely independent of their anticholinesterase effects, including mutagenicity and carcinogenicity as well as organ-specific toxicity to the heart and kidney and other organs.
Carbamates are used as insecticides, herbicides and fungicides, but only the first groups have marked anticholinesterase activity. Methiocarb (see below), an anticholinesterase, is used as a molluscicide.
The anticholinesterase carbamate pesticides are closely related to human drugs such as physostigmine and pyridostigmine.
The general structure of most carbamate insecticides is as follows:
In most cases, the R group is substituted by a phenol or heterocycle, a notable exception being aldicarb, which is 2-methyl-2(methylthio)-propionaldehyde o- (methylcarbamoyl) oxime. Pirimicarb has two N-methyl groups.
In general the carbamates produce toxicity similar to that of organophosphates, but less severe. A major difference is that carbamate-inhibited cholinesterases reactivate more rapidly than enzymes inhibited by OPs, with the result that the effects do not last as long in carbamate poisoning. However, an insecticidal carbamate, aldicarb, is one of the few pesticides that has given rise to poisoning in consumers of treated food.
Residues have occurred in cucumbers, watermelons, squashes and similar products sufficient to cause illness, in some cases severe. Outbreaks have occurred in the USA and Canada and in the Irish Republic (Department of Agriculture and Food, 1992).
The reason for these problems is that aldicarb, in other respects a satisfactory pesticide, has a high mammalian toxicity, with an acute oral LD50 of about 1 mg (kg body weight)-1. An-opine is effective in carbamate poisoning but oximes less so and there is some evidence that, with certain carbamates, oximes are harmful.
vii. Pyrethroids (and Pyrethrins):
Pyrethrins are natural insecticides produced from, inter alia, pyrethrum, a plant of the Compositae group, and are esters of pyrethric or chrysanthemic acid. Pyrethrins are broken down and deactivated very readily in the environment, particularly by sunlight. The synthetic pyrethroids are structurally similar compounds rendered photostable by various substituent groups, such as chlorine, bromine or cyanide.
Some of the newer ones bear a more distant structural relationship to the pyrethrins. Because of their low mammalian toxicity, high insecticidal potency and lack of persistence in the environment, the synthetic pyrethroids have achieved widespread usage in agriculture, as household insecticides and in wood preservation. Synthetic pyrethroids are also used in mosquito control.
They have also been widely used on humans to treat such conditions as scabies. However, they are very toxic to aquatic organisms and their lack persistence can be a problem when used as wood preservatives. The advantageous properties of the synthetic pyrethroids result from the fact that they hydrolyse relatively easily, both in the mammalian body and in the environment. Consequently, bioaccumulation does not occur, nor do they persist in soils.
Pyrethroids can be separated into two classes on the basis of the central neurotoxic syndrome that they produce by parenteral routes in experimental animals. Type I synthetic pyrethroids, which include permethrin and resmethrin and also the components of natural pyrethrum, lack an á-cyano group and give rise to the T-syndrome.
The T-syndrome is characterized by fine tremor, hypersensitivity to stimuli and aggressive sparring, progressing to coarse whole body tremor; this syndrome is similar to that produced by some of the DCs. Type II compounds, which include detamethrin, flumethrin, cyfluthrin and a-cypermethrin, have an á-cyano group and give rise to the CS-syndrome.
The CS-syndrome consists of initial pawing and burrowing and later marked chore athetosis, salivation, coarse tremor and convulsions. In addition to these central effects in experimental animals, pyrethroids cause peripheral nerve damage with functional impairment when administered repeatedly. Axonal degeneration has been described, but generally at near lethal doses, and there is no evidence that pyrethroids can produce delayed neuropathy of the OP type.
Specific treatment of the effects of synthetic pyrethroids is rarely necessary as systemic effects are very unusual in humans.
Toxicity of Pesticides and their Effects on Living Organisms:
1. Toxicity to Fish:
The indiscriminate use of pesticide in agriculture and public health operations has increased the scope of disruption of ecological balance as many of the ‘non-target’ organisms which include important members of food chain that perish in the process thus adversely affecting the secondary and tertiary productivity of fresh water ecosystems.
The tragic incidence of ‘Handigod syndrome’ in Karnataka State was probably due to consumption of pesticide poisoned crabs and fish by the local population. It has been reported that the plankton samples from Arabian Sea between Bombay and Goa contain high levels of DDT. According to a rough estimate, 25% of pesticides used on land may ultimately find their sink in the sea and their cumulative effect to coastal water can be expected to be considerable.
In vitro studies by O’Brien (1967) have revealed that fish appear to be highly susceptible to organochlorine compounds in general and to endrin in particular. This is in accordance with the indication that fish lack mixed function oxidase enzymes responsible for drug oxidations. Presumably fish dispose of foreign lipid-soluble compounds directly by diffusion through gills or skin into the surrounding water without prior conversion to more polar derivatives.
However, Potter and O’Brien (1964) showed that trout liver slices converted parathion into paradoxes and since then several trout microsomal enzymes effecting drug oxidation have been described, all requiring NADPH and oxygen. The oxidizing system was different in one or more components of the electron transport chain as compared to mammalian liver and possibly the level of aldrin epoxidase was also low.
The lethal concentration of fenitrothion had an inhibitory effect on the cholinesterase activity in nervous and other tissues of fish with concomitant increase of acetyl choline content and decreased SDH and increased LDH activities indicated favouring of anaerobic metabolism in fenitrothion treated fish.
Toxicity studies in fish reported from India have revealed greater accumulation of organochlorines in tissues. Among the various chlorinated insecticides, viz., DDT, lindane, dieldrin, aldrin, endrin, endosulfan and chlordane, examined for their toxicity, endrin was extremely toxic to fish and endosulfan the least toxic. Thiodan and chlordane were also highly toxic to fish. In cat fish, endrin was reported to be 70,000 times more toxic than carbaryl.
Biochemical studies carried out with endrin in fish by some workers revealed that alpha-amylase activity was inhibited by more than 50% which could be regained in the presence of 1 ppm of sodium ion concentration.
However results presented by others suggested that phenobarbital and hexa-barbital in fish could develop some capacity to tolerate the toxicant, endrin, on the CNS level. During a study on the uptake and metabolism of DDT in Gambusia affinis, two metabolites of DDT, viz., p,p’DDE and p,p’DDT were detected. DDE was the major metabolite.
Unlike the chlorinated hydrocarbon insecticides, little accumulation of Organophosphorus insecticides in tissues had been reported. Effects of these insecticides on the metabolic fate and activities of different lysosomal enzymes in various tissues have also been noticed.
Several deformities were observed in fertilized eggs of Cyprinus carpio communis exposed to different concentrations of diazinon, Malathion, fenitrothion and phosphamidon. Parathion was reported to be highly toxic and dimethoate least toxic to fish.
Poultry birds are often exposed to a variety of pesticides either by ingestion of contaminated feed or through the use of pesticides in pent houses. Pesticides are lethal to poultry if ingested at a sufficiently high dose rate. However, the lethal dose of a pesticide is governed by the species of the bird and the nature of the compound.
Contamination of poultry with nonlethal levels may impair one or more of a number of production characteristics such as growth, egg production, egg size, shell thickness, fertility and hatchability, etc. Poultry feed contaminated with lindane, DDT, methoxychlor and chlordane when given ad libitum for about 24 weeks caused no death in chicken although other reports suggest that DDT and dieldrin contaminated feed, however, produced death in poultry birds.
The metabolism of ‘Organophosphorus insecticides’ in chicken and ducks was accomplished by hepatic microsomal enzyme system. It has been demonstrated that Malathion and parathion were converted to their respective and more potent oxygen analogs, malaoxon and paraoxon.
Toxicological studies carried out on poultry with a few organophosphate and chlorinated pesticides in India have shown interesting findings.
Thiometon when sprayed aerially for the protection of crops did not induce any toxic effect in poultry birds. Residues of rabon, an organophosphate insecticide, were found in the fat of all treated then. In the egg yolk, residues appeared two days after initiation of treatment and disappeared five days after the last treatment. Fenitrothion was found to be more toxic than Malathion to chick embryos.
The effect of fenitrothion on the growth rate was correlated with the growth promoting endocrine glands. The reduced utilization of several metabolites during embryonic development such as nicotinamide, nicotinic acid, and try prophan could also be responsible for the toxic manifestation. Inadvertent use of Malathion for the control of ectoparasites in poultry has resulted in their large scale killing.
Malathion inhibited the brain cholinesterase activity in house sparrow. A correlation has been found with ageing of house sparrow and inhibition of rat brain esterase by different organophosphates. Telodrin produced varying degrees of degenerative haemorrhagic changes in the liver and kidney of cockerels.
Metabolic effects of DDT in earthworms and snails, toxic effects of various insecticides to bees and the effect of Malathion on enzyme activities of acetyl cholinesterase, aspartate and alanine aminotransferases in snail have also been reported.
Ingestion of insecticide – contaminated forage crops by animals has shown residues in the body fat of such animals. The chlorinated hydrocarbons are by far the most common residues found in milk since they are concentrated and stored in the fat in animals and translocated to the milk fat. It was reported as early as 1947 that DDT residues appeared in milk of cows that ingested feeds treated with the insecticide.
Since that time DDT, dieldrin, BHC, lindane, chlordane, heptachlor, aldrin, endrin and toxaphene have all been detected in milk when the feed of the cow has been treated with these compounds at levels necessary to control the target insects. In contrast, the organophosphates have not shown such residual effects.
The work of Cook indicated that the absence of residues in the milk of cows fed with organophosphate compounds is due to the inactivation of the compound by the rumen fluid of the cow.
Insecticides could be detected in blood after exposure. DDT, dieldrin and lindane were identified in the blood of all animals. It was found that rats did not accumulate lindane and it was nearly completely excreted within 4 days of treatment. The metabolism and persistence of lindane have been explored in detail by various workers.
With regard to effects of chlorinated insecticides and the sequence of events which follow the administration of these insecticides in the animal, the mode of action has been studied by various workers. The stimulatory effect on protein biosynthesis altered the general metabolism and mixed function oxidases.
Various concentrations of dieldrin solution when coated on the skin of monkeys and dogs produced loss in body weight and histopathological changes in the skin. Buffalo calves developed signs of poisoning within 16 hours of dieldrin administration. The blood glucose and blood lactic acid levels were increased by 2.5 and 4 fold respectively. BHC (0.27%) increased the weight of liver and altered the microsomal protein content and the level of cytochrome P450.
Acute exposure to chlordane produced a significant increase in the serum alkaline phosphatase activity and chronic exposure produced hyper proteinemia, hyperglycemia and significant increase in serum acid and alkaline phosphatase activities in Indian Desert gerbils. Carcinogenic action of DDT in Swiss mice, effect of dietary DDT, effect of DDT on rat adipose tissue lipolytic activity, metabolism of DDT, and acute and chronic toxicity studies of DDT in albino rats have been reported.
Significant increases in levels of liver and kidney enzymes by beta isomer of ERC has been observed while gamma ERC produced significant alterations in hepatic aspartate aminotransferase and the hepatic alkaline and acid phosphatases.
Among the organophophorus insecticides, toxicity of Malathion in rat has been studied in detail. It was shown that inhibition of acetylcholineesterse activity due to Malathion administration in brain and heart was dose-related, while such a relationship was not observed in other tissues.
In another study conducted to investigate the effects of Malathion on hepatic drug metabolism and lipid peroxidation in young rats, the protein content was found to increase significantly in males and significantly decreased in females and there was an increase in aminopryrine N- demethylase activity and also acetanilide hydroxylase activity in both male and female rats. Other insecticides studied included metasystox, phorate, pyrethrum, dichlorvos and baygon. Recently, the effects of pesticides on reproduction in mammals have been highlighted.
While assessing the health hazards of pesticide residues, two types of injury have to be considered. First the possibility of an acute illness resulting from ingesting residues on a single day or in a few days and secondly the long-term effects that may occur after ingesting small quantities of residues daily for many years. Residue poisoning appears to cause, only a mild disease manifestation. Gastrointestinal symptoms usually predominate.
Residue poisoning also differs epidemiological from poisoning by direct exposures. In connection with residue poisoning, it has been observed that majority of individuals frequently become sick. Whereas, in poisoning after direct exposure to formulations it is unusual to have more than one or two cases among any group of workers.
Of a total of 252 cases reported in California during 1957 of systemic human poisoning attributed to agricultural chemicals, 189 involved the Organophosphorus compounds. The accidental poisoning in the state of Karnataka and the involvement of members of food chain like fishes and crabs in the “Handigod Syndrome” have focused attention together caution and control in the spread of pesticides to villages.
Periodical surveys have indicated that humans in India show significantly higher storage levels than their counterparts in U.S.A. Dieldrin has been reported to be present, in the body fat of the U.S. population as a result of extensive application of this chemical. Acute poisoning has often been reported in people exposed to dieldrin.
Signs of intoxication due to aldrin and dieldrin involve the central nervous system and may include electroencephalographic changes, muscle tremors and. convulsions. Levels of liver enzymes, namely, SGOT, SGPT and LDH are greatly enhanced in the group occupational exposed to pentachlorophenol. Very high levels of alkaline phosphatase are found on exposure to common organochlorines.
Levels of albumin and beta and gamma globulins were found also to vary significantly with different types of occupational exposures. Exposure to the chlorinated hydrocarbon pesticides can be estimated from the storage level of the compounds or of their metabolites in adipose tissues or in certain instances from excretion of biotransformation products in urine.
With regard to Organophosphorus pesticides, cases of acute poisoning were reported in individuals exposed to these in their occupations. Over 100 deaths in India during the spring of 1985 resulted from eating food accidentally contaminated with parathion during shipment. Most of the Organophosphorus insecticides have relatively high acute toxicities and have caused fatal and non-fatal poisonings in man.
Men who were occupationally exposed to parathion frequently showed some depression of blood cholinesterase activity, even though, they remained outwardly well. Generally, exposure to the Organophosphorus compounds can be determined by measurement of blood cholinesterase activity.
Exposure to parathion and other Organophosphorus compounds which on hydrolysis, from paranitrophenol or allied metabolites can be estimated by determination of these phenolic compounds in urine. There are two types of biochemical reactions which might play an important role in determining the toxicity of these Organophosphorus insecticides, which become significant inhibitors of cholinesterase only after an oxidative biotransformation.
The reactions, both of which are catalyzed by microsomal enzymes are- (i) an oxidative biotransformation which converts the original compound into a more potent anticholinesterase (e.g. conversion of parathion to paraoxon) and (ii) the hydrolysis of the original compound or the oxidation product into non-toxic agents.
A number of workers from India have reported the poisoning of humans due to ingestion or exposure to organophosphate and chlorinated hydrocarbon insecticides. All the Organophosphorus pesticides have been reported to cause depression in the cholinesterase activity of blood. The work done in India with special reference to toxic effects of these in human beings is briefly summarized as follows-
Thirty four cases of diazinon poisoning were admitted to the Ruby Hall Hospital, Pune between January 1967 and May 1969. Diazinon was shown to cause rapid and severe depression of serum cholinesterase activity in 17 patients. Similar studies were taken in 158 males of Delhi and Punjab including 84 occupationally exposed to Organophosphorus pesticides.
The exposed group of individuals showed a significant depression in cholinesterase levels. A significant relationship of blood cholinesterase activity with the total duration of exposure was observed. Electrocardiographic (ECG) changes were observed in 12% of the 86 cases of diazinon poisoning. Neurological manifestations of Organophosphorus insecticide poisoning in 200 consecutive cases of suicidal ingestion have also been described.
The authors found impairment of consciousness in 10%, fasciculation in 27%, convulsion in 1%, toxic delirium in 50% and paralysis in 26%. A field study on the toxicological hazards to humans of ULV aerial spray of phosphamidon was presented.
Maximum percentage of plasma cholinesterase inhibition, which occurred 1-3 days post spray were 0-25% in 11 subjects, 26-50% in 19 subjects and over 50% in 2 subjects. The distribution of insecticides viz. ethyl parathion, malathion, dimethoate, smnithion and phosphamidon in human body tissues such as stomach, intestine, lung, spleen and heart in five different cases of suspected poisoning have been reported.
With regard to the effects of chlorinated hydrocarbon insecticides in humans, the following information is available in the literature.
Data for DDT residues and its metabolites in blood samples from 182 people in Delhi have been reported. The average total DDT concentration in the whole blood ranged from 0.177 to 0.683 mg/1 in males and from 0.166 to 0.32 mg/l in females. The DDT metabolites detected were p,p’ DDE, p,p’ DDD and p,p’ DDT. DDE accounted for most of the total DDT.
Eleven members of a small village community and five domestic animals developed neurotoxicity in the form of colonic jerks and major motor seizures on being exposed to chlorinated group (aldrin and gammaxene) of insecticides for a period of 6 to 12 months. A report of eight cases with grand mal epilepsy in a village of Uttar Pradesh, secondary to accidental contamination of food grain by BHC was presented.
The distribution of endrin in different autopsy tissue from five different victims was assayed by ILC and the workers observed that the largest amounts of the poison remained in the stomach and intestine. The deaths occurred within 1-2 hr of the ingestion of this insecticide. Small amounts of Organophosphorus, organochlorine and carbamate insecticides in human biological material by TLC were detected.
Toxicological experiments on occupational exposure to pesticides in pest control operators and warehouse workers have been conducted by National Institute of Occupational Health, Ahmedabad in collaboration with Industrial Toxicology Research Centre, Lucknow. A total of 120 exposed workers, sixty each of warehouse and godown workers and pest control agencies workers were examined with the major objective of determining if measurable or observable effects could be detected which were attributable to this occupational exposure.
Workers from warehouses and godowns were mostly found to be exposed to celphos, DDVP and Malathion, while the PCA workers were mostly exposed to chlordane, aldrin, Malathion and heptachlor. A significant reduction in plasma and RBC cholinesterase level was found. Liver function tests, viz., SGPT and alkaline phosphatase showed no significant difference between control and both the exposed groups.
Besides the field studies from exposure to pesticides, laboratory experiments have been carried out to test the carcinogenicity of BHC and DDT, DDT and BHC in long and short term studies were found to be weak carcinogens in Swiss mice. BHC was found to produce more number of liver tumors of compared to DDT.