anticholinesterase pesticides (metabolism, neurotoxicity, and epidemiology) || epidemiological...

29EPIDEMIOLOGICAL STUDIES OFANTICHOLINESTERASE PESTICIDEPOISONING IN INDIA

P.K. GUPTA

Former Head of the Division of Pharmacology & Toxicology, and Advisor to WHO (Geneva), C-44, Rajendra Nagar, Bareilly243 122 (UP), India

29.1 Introduction 417

29.2 Regulation and Use 41829.2.1 Insecticide Act 41829.2.2 Prevention of Food Adulteration Act 418

29.3 Routes of Exposure 419

29.4 Incidence of Poisoning 420

29.5 Mass OP and CM Poisoning 422

29.6 Changing Trends of Intentional Poisonings 423

29.7 Carbide Pesticide Plant Disaster in Bhopal 423

29.7.1 Release of MIC and Reaction Products 42329.7.2 Toxic Effects 42429.7.3 Experimental Studies 42529.7.4 Epidemiological Studies 425

29.8 Occupational Exposure of Workers 425

29.9 Genotoxic Effects in Farmers 428

29.10 Assessment of Human Exposure 428

29.11 Conclusions 429

References 429

29.1 INTRODUCTION

Many cases of serious poisonings due to misuse of anticholi-nesterase agents (anti-ChE) such as organophosphorus (OP)and carbamate (CM) pesticides have been reported in Indiaover more than five decades. These generally occur becauseof (1) a lack of knowledge, (2) the absence of effective legis-lation and regulation, (3) largely inadequate protectionmeasures, and (4) unsafe handling practices (Gupta, 1986).OP and CM pesticides are some of the most widely usedinsecticides, and have a common mechanism of action.Although their chemical structures are diverse, the mechan-isms by which they elicit their toxicity are identical and areassociated with inhibition of the nervous tissue cholinester-ase. There is an ongoing need for careful assessment of therisks caused by pesticide exposure to occupational workers

and other exposed groups. Information on the assessmentof toxicity caused by these chemicals mainly comesfrom human (epidemiological studies) and animal studies.However, some supporting information may also be obtainedfrom clinical and in vitro studies. For example, the firstinformation about the carcinogenicity of benzene camefrom epidemiological studies of rubber workers (Infanteet al., 1977). It was not until several years later that benzenewas shown to cause cancer in animal studies (Maltoni et al.,1983). Studies of the London pollution event of 1952 demon-strated that high levels of pollution from coal com-bustion could cause mortality, particularly in the veryyoung, the elderly, and those individuals with existing cardio-vascular diseases (Lipfert, 1980). Evaluation of similareffects in animal studies would be difficult, given the com-plexity of the exposure in London and the lack of good

Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology. Edited by Tetsuo Satoh and Ramesh C. GuptaCopyright # 2010 John Wiley & Sons, Inc.

417

animal models for susceptible populations, such as asth-matics. In general, epidemiology has been particularly help-ful in the evaluation of working environments or otherenvironments where exposure concentrations are relativelyhigh. However, several factors limit the use of epidemiologi-cal studies by regulatory agencies. For example, it is difficultto define the causal elements in epidemiological investi-gations, particularly when complex exposures are involved.Another limitation is the frequent movement of workerpopulations and such studies may be difficult to apply to pre-dicting health effects in the general population. The advan-tages and disadvantages of epidemiological studies arebeyond the scope of this chapter. This chapter describesincidences of intentional and unintentional poisonings, theBhopal disaster, toxic manifestations in exposed workers,and epidemiological studies of OP and CM pesticides, asthey are relevant to India.

29.2 REGULATION AND USE

The rural population in India comprises 72.22% of the totalpopulation, most engaged in agriculture-related activities. InIndia, the use of pesticides to prevent agricultural lossesthrough pests, diseases, and weeds began around 1948–1949. In the field of public health, a National MalariaControl Program was initiated in 1953, the scope of whichwas extended in 1958 by launching National MalariaEradication Program, which had the objective of eradicat-ing malaria within 7–9 years (Gupta, 1986; Gupta andGupta, 1977).

There are two statutory laws controlling the use of pesti-cides and their residues in foods:

† the Insecticide Act 1968, operated by the Ministry ofAgriculture, and

† the Prevention of Food Adulteration Act, 1954, andRules made there-under, operated by the Ministry ofHealth and Family Planning.

29.2.1 Insecticide Act

The main objective of this act is to regulate the import,manufacture, sale, transport, distribution, and use of pesti-cides. This Act was enacted by the Government of India(Ministry of Agriculture) with the introduction ofInsecticide Rules, which came into force on August 1, 1971(Gupta, 1989).

The various regulatory provisions made in the Act includecompulsory registration of pesticides at the Central level,issue of licenses for the manufacture/formulation and saleat the State level, inter-departmental/ministerial organi-zational co-ordination in their various fields for the mattersarising out of the implementation of this act, establishment

of enforcement machinery such as insecticide analysts,insecticide inspectors, and so on. Under various sectionsof this Act, two statutory bodies, namely The CentralInsecticide Board and The Registration Committee, havebeen constituted.

Under the Insecticide Act, the registration committee mayregister a pesticide or its formulation for use in agriculturalcrops after becoming satisfied that use of the pesticide willnot leave behind hazardous residues. Data on the range ofresidues collected from supervised trials carried out in Indiaare to be maintained by the Registration Committee.

29.2.2 Prevention of Food Adulteration Act

The use of insecticides and pesticides on food is containedin Part XIV–Rule 65 (1) and (2) of the PFA Rules. Themaximum residue limits (MRL)/tolerance of pesticides areprescribed under the PFA Rules. Food is considered adul-terated if it contains a poisonous ingredient or any other ingre-dients injurious to health. Accordingly, any commoditybearing residues above the prescribed limits of toleranceis considered to be adulterated and prohibited from sale(Gupta, 1989). The other laws that are indirectly applicableto pesticides for the safety of human health and the environ-ment are reviewed elsewhere (Mahajan, 1988).

After World War II, thousands of OP and CM pesticideswere synthesized worldwide in a search for compoundswith species selectivity, easy biodegradability, and reducedtoxicity so that these could be used as pesticides more safely.This resulted in the introduction of OP and CM pesticides inthe 1950s. Of the 215 pesticides registered (including biopes-ticides) for use in India (CIBRC, 2008), more than 100 are OPand CM pesticides in use for a variety of purposes, includingpesticides used for the protection of crops and grains, gar-dens, indoors and around homes, as ectoparaciticide andendoparaciticides in veterinary practice. In human practice, anumber of anti-AChE agents are used for neuro-degenerativediseases such as Alzheimer’s disease, myoasthenia gravis,glaucoma, and so on. Tables 29.1 and 29.2 list OP and CMpesticides along with their common brand names.

Some of these agents may be extremely hazardous.However, they are still among the most popular and widelyused pesticides. The WHO recommended classification ofOP and CM pesticides by hazard, guidelines for assessmentof their risk end points, data on toxicity, and their usesother than as insecticides can be found elsewhere (Gupta,2006a; Gupta, 2007; Gupta and Agarwal, 2007). Eventoday, India ranks amongst the largest manufacturers of OPand CM pesticides in Asia. Currently, the consumptionof chemical pesticides is showing a slight declining trend,probably due to farmers’ shift towards the use of biopesti-cides, natural plant sources, and other alternative methods(Gupta, 2006b).

418 EPIDEMIOLOGICAL STUDIES OF ANTICHOLINESTERASE PESTICIDE POISONING IN INDIA

29.3 ROUTES OF EXPOSURE

Oral ingestion is the most common route of exposure incases of non-occupational/intentional poisonings causedby OP and CM pesticides. Several instances of acute

poisoning of farmworkers have resulted from dermalexposure to pesticides during spraying operations in fields.Dermal exposures have also resulted either in poisoning ordeaths of children who had been in contact with containers,presumably empty, used for storing highly toxic pesticides.

TABLE 29.1 Common Organophosphorus Pesticidesa

Generic Name Brand Name

Acephate Acemil, Acet, Acetaf, Agrophate, Asataf, Dhanraj, Hilfate, Hythane, Orthene, Ortran, Sicothene, Starthene, TorpedoAnilofos Aniloguard, Arozin, DhanudanChlorfenvinphos Birlane, ChlorfenvinphosChlorpyriphos Agrofas 20, Calban, Chlorofos 20, Classic, Coroban 20, Cyfos, Daspan, Dermite, Dermot, Dhanuchlor, Dhanvan,

Dursban, Force, Gilphos, Hildan, Hyban 20, Lasso, Lethal, Nuchlor, Phors 20, Primaban, Radar, Roban, Ruban 20,Sicobon, Strike, Suchlor, Tafaban, Tefaban, Tricel

Cyclopyriphos DurametDemeton methyl MetasostoxDiazinon Agroziron, Basudin, Bazanon, Ditaf, Suzinon, Tik 20, Zionosul 50Dichlorvos Agrovan 76, AGro 76 EC, Bangvas, Cockroach killer, Dash, DDVP, Divap, Divisol, Madhuvun, Nuvan, Nuvasul 76,

Paradeep, Savious, Vapona, Vapox, VegfruDimethoate Agrodimet 30, Agromet 30 EC, Bangor 30 EC, Corothate, Cropgor 30, Cycothate, Cygon, Devigor, Dimethoate,

Dimex, Entogor, Hexagor, Hygro 30, Klex Dimethoate, Krogar, Methovip, Milgor, NB, Dimethoate, Paragor,Parrydimate, Primogor, Ramgor, Rogor, Tagor, Tara 909, Tara Dimex, Sulgor, Tka 30, Unigor, Vijaygor, Vikagor

Ediphenphos Hinosan, NukilEthion Challenge, Demite, Dhanumit, Dhan-unit, Ethion, Ethione, Ethiosul 50, Fosmit, Mit 505, Mitex, Miticil, Mitvip

Phostech, RP-thion, Tafethion, VegFru Fosmite, VolathinFenitrothion Accothion, Agrothion, Danathion, Fenicol, Fenitrosul 50, Folithion, Sicothion, Sumithion, VikathionFenthion Agrocidin, Baytex, Fenthiosul, Labaycid, LebazateFormotnion AnthioIprobenfos TagkiteMalathion Agromal, Bharat, Celthion, Cythion, Dhuthione, Finit, Himalaya, Kathion, Licel, Madhuthione, Maladan, Maladol,

Malafil, Malathione, Malazene, Primothion, Sulmathion, VegFru MalatoxMethyl parathion Ant repellentb, Agropara, Agrotex, Ekatox, Folidol, Folidol-M, Harvest Kempar, Kilex-M, Metacid, Metapar, Metpar,

Milphor, Paracrop, Paradol, Parahit, Parataf, VegFru ParatoxMonocrotophos Atom, Azodrin, Balwan, Corophos, Entophos, Hilcrone, Luphos, Macrophos, Microphos, Monocil, Monochrovin,

Monocrome, Monocron, Monogrown, Monocyl, Monodhan, Monokem, Monostar, Monovip, Nuvacron, Sicocil,Sufos, Unicron

Oxydemeton methyl Dhanuciytax, Hexasystox, Hymox, Knock Out, Metaciyta, MetasystoxPhenthoate Agrofen, Deisan, Elsan, Guard, PhentoxPhorate Anuphorate, Croton, Dhan, Dhang, Dragnet, Fortan, Glorat, Luphate, Phorachem, Phoratox, Phrotax, Thimate 10G.

Thimet, VegFru Foratox, Vijayphor, VolphorPhosalone ZolonePhosmet PhosmitePhosphamidon Agromidon 85, Bangdon 85, Bilcran 85, Cildon, Delphamidon, Demacron, Demecron, Dimecron, Direction, Eagle,

Entecron 85, Hildon, JK Midon, Midon, Phamidon, Phosul, Rilon, Sudon, Sumidon, VimidonPhoxim PhoxinPrimiphos methyl AcetellicProfenfos Carine, Curacrone, Polytrine, ProfexQuinalphos Agroquin, Agroquinol, Bayrusil, Chemlox, Coroqueen, Dhanulux, Dyalux, Ekalux, Fact, Flash, Kilex, Quenguard,

Quick, Quinal, Quinaltof, Quinseed 25, Silofos, Solux, Vazara, VikaluxTemephos Abate 50 EC, Farmico’sThiometon

(morphothion)Agrothimeton, Ekatin

Triazophos Hostathion, Sutathion, Triphos, TrusoTrichlorphon Dipterex

aSource: From Pillay (2008).bCaution: The same brand name may refer to lindane.

29.3 ROUTES OF EXPOSURE 419

Another route of exposure is via the respiratory tract ofworkers exposed to pesticides during spraying operations orduring the manufacturing process (Gupta, 1985). Occasion-ally, the unusual way of intoxication by injection hasbeen resorted to by victims (Guven et al., 1997; Zoppellariet al., 1997).

Table 29.3 presents examples of this method of self-injection using intravenous or intramuscular routes.

For example, in 2006, a 32-year-old male injectedhimself intravenously with monochrotophos. The patientdeveloped intermediate syndrome and was managed withatropine, pralidoxime, and ventilatory support, leading tofull recovery (Badhe and Sudhakar, 2006). In another case,two patients injected themselves with the OP pesticidedichlorvos and showed the typical clinical picture of OPintoxication; one 24-year-old female healthcare worker wasadmitted with an alleged history of self-injection of Nuvan(dichlorvos-76% EC) (Fig. 29.1) and another 26-year-oldmale horticulturist was admitted with an alleged history of self-injection of Divax (dichlorvos-76% EC) into the left

deltoid (Fig. 29.2) (Raina et al., 2008).

29.4 INCIDENCE OF POISONING

Cases of intentional and unintentional poisoning due to OPand CM pesticides are very common throughout India.Details of poisoning cases, together with their differentregional locations, periods, and causative agents, are sum-marized in Table 29.4.

In the north (Chandigarh), an autopsy study of acute pes-ticide poisoning deaths in the period 1977–1997 revealed asteep increase in incidence from 1987. The majority (68%)of subjects were aged between 14 and 30 years, with amale preponderance (69%). The main victims were students

TABLE 29.3 Summary of Unusual Self Intoxication MethodUsing OP Pesticides

Age ofVictim(years) Gender

Name ofPesticide

Route ofAdministration

24 Female Nuvan(dichlorvos-76% EC)

Intramuscular

26 Male Divax(dichlorvos-76% EC)

Intramuscular

32 Male Monocrophos Intravenously80 Male Isofenphos Intramuscular

TABLE 29.2 Common Carbamate Pesticidesa

Aldicarb Aldrin, TemikCarbaryl Agrovin, Agroyl, Bangvin 50, Caravet,

Corovin, Hexavin, Kevin 50, KilexCarbaryl, Sevidal, Sevin 50, Sujacarb,Sulfarl 50

Carbaryl þ GammaBHC

Sevidol

Carbofuran Agrofuron 3G, Carbocil 3, Carburan,Crane, Furadan 3G, Hexafuran,VegFru Diafuran

Carbosulfan MarshalFenobucarb MerlinoMethomyl Astra, Dunet, Lannate, Lannet, MathoylMPMC (Xylylcarb) BipuinMTMC (Metolcarb) EmisanPropoxur Baygon, Isocarb, Protox BaitThiodicarb Larvin

aSource: Pillay (2008).

Figure 29.2 Photograph showing site of injection in left deltoid.From Raina et al., 2008. With permission.

Figure 29.1 Photograph showing hyperemia at the site of injec-tion in left forearm and elbow. From Raina et al., 2008. Withpermission.


and unemployed youths, followed by agricultural workersand domestic workers. The proportion of urban victimsincreased from 45% in the period 1972–1977 to 72% inthe period 1992–1997. The proportion of suicidal deathsincreased from 34% in the period 1972–1977 to 77% inthe period 1992–1997, and accidental deaths decreasedfrom 63% to 17% in the same period. OP pesticides (46%)became quite common between 1977 and 1982, and since1982, aluminum phosphide, OP and CM pesticides (65–70%) have become the most common poisons in India(Singh et al., 1999).

In the west (North Gujarat), of 377 cases of poisoningregistered in the period 1999–2000 at the Medical Centre,113 (30%) were OP poisonings. Cases of OP poisoningwere most common in the age group 21–30 years (46.9%),with 85% being males and 15% females. The most frequentreason for poisoning was suicide (73%), the other scenariosbeing occupational (15%), accidental (8%), and unknown(3.5%). Exposure via the oral route was the most common(78.8%), followed by inhalation (15.9%) and combined,that is, inhalation and dermal (5.3%). OP poisoning cases(44.2%) showed severe symptoms requiring 8–38 days ofhospitalization. The frequency of OP poisoning was higherin August and February. Farmers and farm labourers rep-resented the highest number of cases (42.5%). Of the cases69% were either uneducated or had only primary level edu-cation. The common pesticides used for suicide poisoningwere chlopyriphos, dimethoate, phorate, and monocrotohos(ICMR, 2000). Recent investigations indicate that of121 OP poisoning patients admitted in a hospital inAhmadabad, the major cause was found to be suicidal andintentional (80.2%) followed by occupational (9.1%), acci-dental (6.6%), homicidal (1.6%), and unknown (2.5%).The major signs and symptoms were muscarinic and nico-tinic manifestations. ECG abnormalities were recorded in46 cases (38%), with sinus tachycardia (24%), depressionof the ST segment and inversion of the T wave (7.4%), andsinus bradycardia (6.6%) found in other cases. Plasma andred blood cell (RBC) ChE activities in OP poisoning cases

were significantly decreased. The activities of serum LDHand CK activities were significantly elevated in poisoningcases, indicating muscular functional impairment due toOP toxicity. In a subset of samples, the serum levels ofIgA, IgG, and circulating immune complexes (C3 and C4)

TABLE 29.4 Pesticide Poisonings in Different Regional Locations of India

City Location Period Poisoning Cases Causative Pesticide Percentage

Chandigarh North–West 1977–1982 — OP 461982–1987 OP, CM and aluminum

phosphide65–70

1987–1992 OP 35.11992–1997 OP, aluminum phosphide 72

Jamnagar (North Gujarat) West 2004–2005 132 OP and others 53.79Maharashtra Central–West 2004–2005 237 OP and others 76.2Warangal (Andhra Pradesh) Central–East 1997–2002 182 Monochrotophos and endosulfan 67Mangalore (Karnataka) South–West 2003 325 OP and others 65Gulbarga South–West 1998–2003 1407 OP 65.6

OP, organophosphorus; CM, carbamates.

TABLE 29.5 Percent Distribution of Pesticide Poisoningin Jamnagar (North Gujarat)a

CompoundNo. ofCases Percentage

OP pesticides (71)Monocrotophos 20 20.41Malathion 15 15.31Methyl parathion 6 6.12Chlorpyriphos 2 2.04Phosphamidon 3 3.06Dimethioate 5 5.10Quinalphos 2 2.04Dichlorvos 2 2.04Phoselon 2 2.04Fention 1 1.02Phorate 1 1.02

CM pesticides Carbamates 4 4.08

Organochlorineinsecticide

Endosulfan 5 5/10

Benzenehexachloride

1 1.02

Pyrethroidinsecticide

Fenvalerate 2 2.04

Total 71Fumigants/

rodenticide (14)Aluminum

phosphide14 14.28

Hydrochloric acid 3 3.06

No poison detected 10 10.20

Total 98 100

aOf 132 cases, 17 were from snake bites and in 17 other cases, no report ofchemical analysis was received (Gupta and Vaghela, 2005).

29.4 INCIDENCE OF POISONING 421

were also found to be significantly increased (Agarwal, 1993;Agarwal et al., 2007).

In another survey (Gujarat), of 132 cases of poisoning, 71were as result of OP poisoning (53.79%; Table 29.5). Theorder of poisoning was monocrotophos . malathion .

aluminum phosphide . dimethoate . methyl parathion,followed by others (Gupta and Vaghela, 2005).

In the state of Maharashtra (central-west), of the 311cases of suicidal poisoning, 76.2% had consumed pesticides.Poisoning was more common in males (68%) than females.Most cases were from rural areas (83%) and almost 90%were laborers. Overall, 45% were due to OP pesticides and17% to other pesticides. Almost all cases were suicidal innature (93%) (Anon., 2006). Table 29.6 indicates that themain mode of intentional poisoning was through usingpesticides (76.2%).

In the central part of India (Warangal), 182 cases ofacute poisoning with an overall fatality ratio of 22.6% wereobserved, of which more than 60% were due to OP pesti-cides alone. Of the total, 96% of cases had intentionallyconsumed poisons. Two compounds, monocrotophos andendosulfan, accounted for the majority of deaths (Rao et al.,2005). In southwest Mangalore in the state of Karnataka, of325 patients of acute poisoning, 72% were intentional andonly 27% unintentional. OP pesticides were responsible formost of the deaths (65%), followed by aluminum phosphide(15%) (Singh and Unnikrishnan, 2006).

In the south (Gulbarga), the maximum number of OPpoisonings occurred in the age group 21–30 years, andwith lower socioeconomic status. The common causes of tox-icity were Tick 20, Rogor, and diazinon (Gannur et al., 2008).Overall, OP pesticides accounted for 65.60% of the totalpoisoning cases.

Recently, there has been a change in the use of chemicalsfor intentional/suicidal poisoning in India. A total of 2884patients with acute poisoning were admitted during thestudy period (1918 men). The mean age was 27.8 years(range 13–82 years). The commonest agents were anti-ChEagents (35.1%) and aluminum phosphide (26.1%). A seaso-nal variation in anti-ChE poisoning was observed (mostcases occurring July to September), but not for aluminum

phosphide. No difference in mortality was observed overdifferent months for different agents. The maximum casefatality ratio was due to aluminum phosphide exposures,followed by anti-ChE agents. The case fatality ratios foraluminum phosphide and OP poisonings declined from2000, despite an increase in aluminum phosphide exposures.The decline in aluminum phosphide mortality may be due tothe limited availability of 3 g tablets and improved intensivecare. Most of the victims now prefer aluminum phosphide,a better choice for suicide poisoning than OP pesticides(Murli et al., 2008).

29.5 MASS OP AND CM POISONING

The widespread use of pesticides has played havoc with thehealth of humans and other lifeforms. There have been alarge number of outbreaks of accidental poisonings fromOP pesticides that deserve special mention. Many of therecognized outbreaks have occurred in countries that main-tain no orderly collection of mortality data. The main causeof accidental poisoning by OP and CM pesticides has beenthrough the contamination of food by these pesticidesduring transportation or storage, and the use of pesticide-treated food grains. Outbreaks have been reported not onlyin India, but also in Pakistan, Columbia, Iraq, the UnitedStates, Guatemala, Turkey, Japan, and Singapore, amongothers (Gupta, 1986). The first report of poisoning from pes-ticides came from Kerala (southern part of India) in 1958,where over 100 people died after consuming wheat flourcontaminated with ethyl parathion (known as Folidol E605, introduced by Bayer). This was mainly caused by care-less handling and storage of wheat (Karunakaran, 1958).Subsequently, several cases of human and animal poisonings,as well as birds and fish, have been reported. In Indore(Madhya Pradesh), of the 35 cases of malathion (diazole)poisoning reported in the period 1967–1968, five died. In1978, six individuals died in Bhopal from exposure to phos-gene gas, the catastrophe of 1984 at Bhopal has no parallelin industrial history (Gupta, 1986). Similar cases of uninten-tional poisonings are also very common in other undeve-loped countries such as Afganistan, Nepal, and Pakistan.For example, in 1987, Choudhry and his associates reportedunintentional OP poisoning in 42 children between the agesof 26 days and 13 years. Twenty-seven children were affectedby OP poisoning following accidental oral ingestion, and themothers of two infants mistakenly administered malathioninstead of cough syrup. Thirteen children developed symp-toms following application of these chemicals either to hairfor treatment of lice or to clothes. Alterations in sensorium,excessive secretions, vomiting, irritability, and constrictedpupils were the most frequent manifestations. Headachewas observed in six of the eight children who had appliedthese compounds to their hair, and coughs and aspiration

TABLE 29.6 Mode of Suicide Reported in the Stateof Maharashtraa

Method Number of Cases Percentage

Consumption of pesticides 237 76.2Hanging 52 16.7Drowning 11 3.5Immolation 9 2.9Lying on train track 2 0.6

Total 311 100

aOf 320 cases, information on the mode of committing suicide was availablefor only 311 cases (Anon, 2006).


pneumonia were seen following oral ingestion. Nine of the 42(21.4%) children died, with mortality due to hair and skinapplications being higher (38.5%) than accidental oral inges-tion (13.8%) (Choudhry et al., 1987).

An episode of mass ethion, OP pesticide toxicity charac-terized by abdominal pain, vomiting, diarrhea, excessivesecretions, and respiratory distress was reported in NorthGujarat. Fifteen individuals developed signs and symptomsof OP poisoning, and ten died within 24 h. One person diedafter eight and a half months (ICMR, 2006). Table 29.7summarizes some of the reported incidences of OP and CMpesticide poisonings in India.

29.6 CHANGING TRENDS OF INTENTIONALPOISONINGS

The history of poisoning in India shows that opium andarsenic were once commonly used poisons. Between 1972and 1977, barbiturates (37%) and copper sulfate (22%)became the most common causes of poisoning and wereresponsible for most deaths. During the 1960s, OP and CMpesticides emerged as the major contributor. Owing to theireasy availability, they are commonly used in suicide attempts,resulting in significant mortality and morbidity. They exerttheir toxic effects by inhibiting AChE and subsequentaccumulation of ACh at the nerve synapses and neuromuscu-lar junctions. Morbidity and mortality by OP and CM pesti-cides remains especially high in rural settings (ICMR,2005). During the period 1977–1982, 46% of poisoningswere due to OP pesticides alone. Pesticides account for a sig-nificant fraction of acute poisonings. In Indonesia, Malaysia,and Thailand, for example, the proportions of acute pesti-cide poisonings in suicide attempts were 62.6%, 67.9%,and 61.4%, respectively (Jeyaratnam, 1987, 1990).

Since 1982, OP, CM, and aluminum phosphide (fumigant,rodenticide) pesticides have become the most common agents

used in suicide poisoning (65–70%; Singh et al., 1999).Recently, isolated cases of human poisonings due to pesti-cides other than OP pesticides, such as aluminum phosphideor warfarin, are notably increasing. For instance, in 1992, sixdeaths due to aluminum phosphide were reported in UttarPradesh. Similarly, several cases of melacious poisoningsin cows, buffalo, and heifer calves, either from aluminumphosphide or other highly toxic OP pesticides, have beenreported (Gupta, 2004). Aluminum phosphide has becomethe pesticide of choice for intentional poisoning cases,particularly in urban areas (Murli et al., 2008).

The causative factors for the increased number ofintentional poisonings in India include overstress due tofinancial problems, lower socioeconomic status, dowry-menace, family or property disputes, marital conflicts,sterility, and so on (Batra et al., 2003).

29.7 CARBIDE PESTICIDE PLANT DISASTERIN BHOPAL

The Bhopal gas tragedy in the central part of India is a cata-strophe that has no parallel in industrial history. Bhopal is thecapital of the State of Madhya Pradesh, and lies south of NewDelhi. Union Carbide, an American company, establisheda chemical plant at Bhopal in the late 1960s, with the aimof supplying pesticides to protect Indian agricultural pro-duction. The main product was Sevin, a CM pesticide invol-ving methyl isocyanide (MIC) in its production. Initially,MIC shipped from the United States was used in Sevin pro-duction, but in the late 1970s a plant was constructed locallyfor manufacturing MIC at Bhopal. This plant was located onthe outskirts of the city. A densely populated shanty townhad grown up near the plant, with an estimated 100,000people living within a 1-km radius of the plant at the timeof the tragedy (Jackson, 1993).

29.7.1 Release of MIC and Reaction Products

In the early morning of 3 December 1984, at approximately00:30, an explosion at the Union Carbide India pesticideplant released 30–40 tonnes of toxic gases in the form ofMIC and its reaction products throughout the city. MIC isa colorless liquid with a low boiling point of 398C. MIC,when in contact with water, causes an exothermic reactionresulting in the formation of carbon dioxide, methylamine,and nitrogenous gases. Fire involving MIC results in hazar-dous decomposition products such as hydrogen cyanide,oxides of nitrogen, and carbon monoxide. According toguidelines issued by the National Institute for OccupationalSafety and Health in 1978, the permissible exposure limitof MIC was 0.02 ppm (averaged over an 8-h work shift).A gentle wind slowly moved the deadly cloud throughresidential areas surrounding the plant. Residents woke up

TABLE 29.7 Mass OP and CM Poisonings in India

Place YearNumbersAffected Deaths

CausativeAgent

Kerala 1958 360 100 Ethyl parathionMadhya

Pradesh1967 35 5 Malathion

MadhyaPradesh

1978 ? 6 Phosgene

MadhyaPradesh

1984 2,50,000 2500a MIC andreactionproducts

Gujarat 2005 15 11b Ethion

aUnofficial figure, 8000.bOne person had brain damage and died after eight and a half months.? indicates that the exact number of affected cases is not known.

29.7 CARBIDE PESTICIDE PLANT DISASTER IN BHOPAL 423

coughing and choking, with stinging eyes. By 02:00, most ofthe MIC had been dispersed over an area of 40 km. By theearly morning there were 1000 casualities, some as far as8 km from the plant. Approximately 90,000 patients wereadmitted to local hospitals and clinics within the first 24 h,and in total about 200,000 people suffered acute effectsfrom the MIC leakage (Gupta, 2004; Mehta et al., 1990).

Winds blew several tonnes of toxic gases over the city.The initial exposure to MIC and released products wasthrough inhalation. The extent to which subsequent exposuredue to contaminated water and food supplies occurredremains unknown. According to one study, thiocyanatelevels in Bhopal Lake and tap waters 15 weeks after the inci-dent were twice as high as those in Bombay, causing vastdestruction of life (Mehta et al., 1990).

29.7.2 Toxic Effects

The acute toxicity of inhaled MIC or its reaction products wasdevastating — most fatalities occurred during the first week.An estimated 8000 people (official figure 2500) and 4000 ani-mals died within minutes of exposure to the gas, and almost15,000 animals suffered toxic effects but survived. Detailsof the official figures are summarized in Table 29.8.

The most common acute symptoms were associated withrespiratory, ophthalmic, and psychological morbidities. Theimpact of MIC and its reaction products, together with thetoxic effects observed in humans and animals, are summar-ized in Table 29.9.

29.7.2.1 Acute Respiratory Impairments The acute res-piratory effects were consistent with inhalation of a highlyirritant and corrosive aerosol. Symptoms included breath-lessness, choking, coughing, chest pain, and hemoptysis. Alarge number of people died rapidly due to acute bronchialnecrosis and pulmonary edema. Acute toxicity studies inanimals later revealed the effects of MIC in causing inflam-matory reaction, destruction of alveolar architecture,damage to bronchial epithelial lining, and pulmonaryedema, suggesting that MIC predominantly damaged lung

tissue due to its corrosive action. Of 783 patients, 39%were found to have ventilatory impairment (by lung spirome-try tests; Mehta et al., 1990). Pulmonary edema was the causeof death in most cases, with many deaths resulting from sec-ondary respiratory infections such as bronchitis and bronchialpneumonia (Jain and Dave, 1986; Pandey, 1986).

Even days after the accident, treatment was limited tosymptom management only, as it was still uncertain whetherthe effects observed were due to MIC, phosgene, HCN,or other reaction products. Several months after the incidence,the pulmonary outcomes of survivors appeared to be oblitera-tive bronchiolitis and interstitial fibrosis. Lung function testsof 454 Bhopal residents exposed to the gas showed persistentsmall airways obstruction, 10 years after exposure. Long-termeffects have included chronic respiratory illness (Cullinanet al., 1997), but few long-term studies have been reportedsince the disaster occurred, and the extent of ongoing healthproblems is poorly documented.

29.7.2.2 Ophthalmic Adverse Effects Acute ophthalmiceffects, such as severe watering of the eyes, photophobia,

TABLE 29.8 Deaths due to MIC and Reaction ProductsDuring the Bhopal Gas Tragedya

Deaths Numbers

Human deaths 2500b

Buffalo 790Cows 270Goats 483Dogs 90Horses 23

aSource: Gupta (2004).bUnofficial figure — 8000.

TABLE 29.9 Toxic Effects Due to Exposure to MIC andReaction Products in Bhopal Gas Tragedy

Toxic effectsRespiratory

Breathlessness, choking, cough, chestpain and hemoptysis followed bydeath due to bronchial necrosis andpulmonary edema, obliterativebronchiolitis and interstitial fibrosis,persistent small airways obstruction

Ophthalmic Severe watering of the eyes,photophobia, profuse lid edema, andcorneal ulceration

Psychologicaleffects

Post-traumatic stress disorder

Children Breathlessness, cough, watery eyes,diarrhea and vomiting; some hadconvulsions, hemiparesis followedby coma and death

Epidemiologicalstudies

Maternal–fetal deaths, gynecologicaldisturbances and spontaneousabortion, higher incidence ofabnormal uterine bleeding, evidenceof chromosomal aberrations andgenetic defects, suppression ofcell-mediated immunity

Experimentalstudies

Skin and eye irritation, inflammatoryreaction, destruction of alveolararchitecture, damage to bronchialepithelial lining and pulmonaryedema.

Cause of death Pulmonary edema and secondaryrespiratory infections (bronchitisand bronchial pneumonia)


profuse lid edema, and corneal ulceration, were found.However, no blindness or irreversible eye damage wasobserved.

29.7.2.3 Psychological Effects The serious psychologi-cal effects included post-traumatic stress disorder (PTSD).According to McFarlane (1986), the incidence of PTSD fol-lowing a natural disaster can be 30–59%, and as high as 80%following a man-made disaster. It could be that the exposedpopulation of Bhopal has a high incidence of psychiatricsymptoms, but no such data are available in the literature.

29.7.3 Experimental Studies

MIC is a skin and eye irritant and when applied to rodents’eyes causes severe necrosis. LC50 tests in rats have shownMIC to have extreme acute toxicity from inhalationexposure and high acute toxicity from oral exposure(EPA, 1986). The office of the Air Quality Planning andStandards, which conducts hazard ranking under section112 (g) of the Clean Air Act Amendments, considers MICto be a “high concern” pollution based on severe toxicity(HSDB online database, 1993).

Animal studies have suggested that cyanide was notinvolved in the fate of Bhopal survivors and that MICis several times more toxic than HCN. Unlike MIC, cyanide isunlikely to produce long-term effects in animals (Andersson,1989). Subsequent animal studies have proved that MICcauses acute eye injury, but probably not permanent seriouseye damage (Mehta et al., 1990).

29.7.4 Epidemiological Studies

In an epidemiological survey nine months after the accident,it was seen that 43% of 865 pregnancies among exposedwomen resulted in fetal loss, compared to 6–10% amongthe general Bhopal population. The spontaneous abortionrate was highest among those exposed during their firsttrimester. There was a higher incidence of abnormal uterinebleeding and abnormal Pap smears among exposed women15 weeks post-exposure. Twelve months after exposure,71% of victims showed evidence of chromosomal aberra-tions, compared with 21% in a control population residing20 to 50 km away from the plant. Over 1000 children wereaffected with breathlessness, cough, watery eyes, diarrhea,and vomiting. Some even had convulsions, hemiparesis,and coma, and 119 deaths were reported in the first 12 days(Jackson, 1993). There is a possibility of long-term toxiceffects in the exposed pediatric population because so manychildren were affected by this tragedy. However, there is noproper follow-up program in most cases.

Few immunological toxicity studies have been reportedfor MIC. A study of humoral and cell-mediated immunity inexposed subjects two months after exposure found that

cell-mediated immunity was suppressed, and that MIC-specificantibodies persisted for several months. Several studies ofBhopal survivors suggest long-term immunological ill effectsincluding hypersensitivity reactions (Andersson, 1989).

Establishment of a dose–response relationship betweenenvironmental exposure to MIC and the health events wasnot possible, because large-scale measurements of MIC orits breakdown products could not be carried out in time(Koplan et al., 1990).

Note that the information available six years after theevent was not significantly different from that available inthe first weeks after gas leakage. This illustrates the needfor long-term studies to be instituted after such events todetermine their long-term health effects.

29.8 OCCUPATIONAL EXPOSUREOF WORKERS

In addition to intentional exposure (suicides and homicides),workers are exposed to occupational hazards in industrialsettings and during operations in the manufacturing units orduring distribution and use in the field. OP and CM pesticidesare toxic, and their handling itself is hazardous to humanbeings. Their effect on other forms of life is also wellknown. Direct and indirect effects of OP and CM pesticideson non-target species are beyond the scope of this chapterand have been reviewed elsewhere (Gupta, 1986).

In India, users are often illiterate, ill-trained, and ignorantof appropriate protective devices (Figs 29.3 and 29.4). Therisks are therefore magnified. Since 1970, several epidemio-logical surveys have been carried out. In a survey carriedout on 150 individuals employed in a fenitrothion-sprayingoperation, 48 showed signs of poisoning. Eleven of the 48cases (23%) showed paralytic signs, and ChE levels werelower than in controls (Wattal et al., 1975). The results of asurvey of 60 operators involved in spraying, sweeping,

Figure 29.3 Mixing pesticides by hand. From Chitra et al., 2006.With permission.

29.8 OCCUPATIONAL EXPOSURE OF WORKERS 425

brushing, cleaning, and fumigation of godowns and ware-houses revealed that 60% of workers were exposed tomalathion. However, no case of clinical poisoning attribu-table to occupational exposure to the pesticide was observed.Common symptoms observed in exposed workers were dizzi-ness, headache, lachrymation, burning sensation of eyes,nausea, and anorexia. In exposed workers a slight inhibitionof ChE activity was observed. Individuals employed inultra-low volume serial applications of malathion for mos-quito control at Ahmedabad developed symptoms of mildtoxicity (nausea and irritation of eyes). Workers showed sig-nificant inhibition of plasma ChE, but RBC ChE remainedunaffected (Gupta et al., 1979).

A peculiar joint disease termed as endemic familial arthri-tis of Maknad was reported in an endemic form in the villagesof Shimoga and Chikmagalur in Karnataka (south India).Pesticides used in this area included BHC, endrin, folidol,malathion, and methyl parathion. A survey showed that thevillagers who suffered from the disease consumed consider-able quantities of exposed fish and crab. Such organismsare known to accumulate pesticides. Members of the affectedcommunity suffered from congenital abnormalities of thelimbs, ichthyosis, scoliosis, dwarfism, achondroplasia, andmicrocephaly. In one affected community, of about 2000individuals, as many as 31 dwarfs were observed (Gupta,1986). Health surveillance in male formulators exposedto several pesticides (malathion, methyl parathion, DDT,and lindane) indicated several types of adverse effects,including reproductive problems (Gupta et al., 1984; Sayedet al., 1984). Of 160 workers exposed to a combinationof pesticides (malathion, parathion, DDT, and HCH), 73%showed toxic signs and symptoms of toxicity. Exposure of40 formulators to a highly toxic OP pesticide (phorate)showed that over 60% of the workers suffered from toxiceffects, in spite of using a complete set of protectiveclothing. A significant and progressive inhibition in wholeblood and plasma ChE activity was found during the two

weeks of exposure to phorate (Kashyap, 1986). Data on repro-ductive performance collected from 1106 couples engagedin spraying of organochlorine, OP, and CM pesticides incotton fields and from 1020 unexposed workers showedsome reproductive imbalances such as abortions, still births,neonatal deaths, and congenital defects (Rupa et al., 1991).The details of this study are summarized in Table 29.10.

In one survey, workers spraying methomyl, a CM pesti-cide, showed significant changes in ECG, indicating thecardiotoxic potential of OP pesticides (Sayed et al., 1992).Separate studies were conducted in malaria spray men usingseveral types of pesticides including HCH, DDT, malathion,and cyfluthrin. The workers showed increased levels ofserum IgG (malathion exposure) and serum IgA (cyfluthrinexposure) (Karnik et al., 1993).

According to the poison information center located in theNational Institute of Occupational Health in Ahmedabad,OP pesticides were responsible for most poisonings (73%)among all agricultural chemicals (Dewan and Sayed, 1998).In a study designed to study the thyroid functions offormulators exposed to a combination of pesticides, therewere indications of significant depression of T3 and amarginal decrease (7%) in T4 level. Thyroid secretion hor-mone (TSH) levels were increased by 28%, but the rise wasnot statistically significant (Zaidi et al., 2000). In anotherstudy, 59 workers exposed to different chemicals during themanufacture of quinalphos had altered plantar and anklereflexes, despite similar blood AChE levels in both theexposed and control subjects. Cognition nervous functionssuch as memory, learning, and vigilance were also affected.Such a change in the health status of workers could be dueto chronic low dose exposures to a group of pesticidesused/formed in the manufacture of quinalphos (Srivastavaet al., 2000).

In a study of 190 patients suffering from acute OP pesti-cide poisoning, muscarinic and cardiac manifestations suchas sinus tachycardia and depression of the ST segmentwere reported (Bhatnagar, 2001). Details of the survey aresummarized in Table 29.11.

In another survey conducted by the National Instituteof Occupational Health (NIOH) on chilli cultivators inGujarat, farmers commonly used phorate, monocrotophos,

Figure 29.4 Spraying pesticide with no personal protection. FromChitra et al., 2006. With permission.

TABLE 29.10 Reproductive Performances of CouplesEngaged in Spraying OC, OP, and CM Pesticidesa

ParameterExposed

PercentageUnexposedPercentage

Abortions 26 15Still births 8.7 2.6Neonatal deaths 9.2 2.2Congenital

defects3 0.1

aOC, organochlorine; OP, organophosphorus; CM, carbamate pesticides.


folidone, roger, sulfur powder, chlorpyriphos, fenvalerate,endosulfan, novacron, monocil, phosmite, fighter, and sumi-cidine. Most workers had typical symptoms of OP poisoningincluding nausea (3.9%), lacrimation (3.9%), abdominal pain

(18%), dizziness (5.9%), and skin itching (72.3%). Eight ofthe workers had a past history of acute pesticide poisoning.Plasma ChE and RBC ChE were significantly decreased.It was found that 73% of workers had sprayed pesticides11–20 times, and 15.3% had sprayed 21–30 times over theseason (ICMR, 2004). Details of the frequency of pesticidespraying by the agricultural workers during the season aresummarized in Table 29.12.

A season-long assessment of acute pesticide poisoningamong farmers was conducted in three villages in India.Fifty female cotton growers reported adverse effects experi-enced after exposure to pesticides by themselves and bytheir male relatives. Of 323 reported events, 83.6% wereassociated with signs and symptoms of mild to severe poison-ing, and 10% of the pesticide application sessions wereassociated with three or more neurotoxic/systemic signsand symptoms typical of poisoning by OPs. In 6% of spraysessions the neurotoxic effects were extremely serious. Lowincome marginal farmers were more often subject to severepoisoning than were their landlords (Mancini et al., 2005).

For farmers in South India, the relationship betweenthe extent of pesticide use and signs and symptoms of ill-nesses due to exposure has been reported (Chitra et al.,2006). During this survey, 631 farmers were interviewedusing pre-tested interview questionnaires (537 men and 94women). Of these, 433 (68.6%) farmers (of whom fourwere women) sprayed pesticides themselves and were there-fore directly exposed to pesticides. More than 75% of farmersused either “moderately” or “highly hazardous” pesticides.Many (88%) did not use any form of protection while hand-ling the pesticides. About 50% of sprayers mixed differentbrands of pesticides, many of which could be substitutedfor one another. It was found that 56% of farmers obtained

TABLE 29.11 Survey of Acute Poisoning Cases (%)due to OP Pesticides in Indiaa

Vomiting 96Nausea 82Miosis 64Excessive salivation 61Blurred vision 54CNS manifestations

Giddiness 93Headache 84Disturbances in conciousness 44

Cardiac manifestationsSinus tachycardia 25Sinus bradycardia 6Depression of ST segment 6

aSource: Gupta (2004).

TABLE 29.12 Frequency of Pesticide Spraying byAgricultural Workers During the Season in North Gujarata

No. of PesticideSpraying No. of Workers Percentage

1–10 24 10.211–20 173 73.521–30 36 15.331–40 1 0.541–50 1 0.5

aSource: ICMR, 2004.

TABLE 29.13 Signs and Symptoms of Illness Among the Study Population of Farmers (as Percentage)a

Sprayers (n ¼ 433) Non-sprayers (n ¼ 192) Total (n ¼ 625)

Excessive sweating 38.6 31.8 36.5Burning/stinging/itching eyes 37.6 31.3 35.7Dry/sore throat 27.3 21.7 25.5Fatigue 26.3 39.4 30.4Dizziness 25.6 34.3 28.4Skin redness/white patches on skin/skin scaling 21.9 17.7 20.6Numbness/muscle weakness/muscle cramps 21.7 28.8 23.9Runny/burning nose 18.0 13.1 16.5Blurred vision 16.2 29.3 20.3Chest pain/burning feeling 15.7 28.8 19.8Shortness of breath/cough 15.0 23.2 17.6Excessive salivation 14.8 12.6 14.1Tremors 13.4 17.1 14.6Nausea/vomiting 7.4 11.6 8.7Stomach pain/cramps/diarrhea 6.0 16.7 9.4Wheezing 5.3 10.1 6.8

aSource: Chitra et al., 2006.

29.8 OCCUPATIONAL EXPOSURE OF WORKERS 427

information on pesticides from retail shop owners. Farmersreported excessive sweating (36.5%), burning/stinging/itching of eyes (35.7%), dry/sore throat (25.5%), and exces-sive salivation (14.1%) (Table 29.13).

The most commonly used pesticides were Rogar/dimethoate (55%), Ekalux/quinalphos (49.4%), endosulfan(48.5%), and monocrotophos (45.9%). Of the sprayers,7.7% used pesticides that are extremely hazardous. Rogar,Ekalux, and endosulfan are classified as moderately hazar-dous by WHO, while monocrotophos is classified as highlyhazardous. Only a very few farmers (43, or 0.2%) used pesti-cides in class III (slightly hazardous) and class U (unlikely topresent acute hazard in normal use) (Table 29.14).

29.9 GENOTOXIC EFFECTS IN FARMERS

The toxic effects in patients who developed acute andreversible parkinsonism following OP pesticide exposuresuggests genetic susceptibility in individuals to OP pesti-cide-induced parkinsonism (Bhatt et al., 1999). Pesticides

may cause cytogenetic toxicity. Studies on 210 farmersexposed to pesticides and 160 non-exposed individualsshowed an increase in DNA damage and higher chromosomalaberrations in exposed farmers compared to control subjects(Naravaneni and Jamil, 2007). Another study reported arise in cancer cases, kidney ailments, and infertility as aresult of large-scale use of pesticides and fertilizer amongresidents of Punjab’s Malwa region, once referred to as“Makheon meetha Malwa” (sweeter than honey) for itsrich agricultural produce and cotton farming (Anon., 2007).

Recently, another survey was carried out in agricul-tural workers occupationally exposed to various pesticidesin Punjab (Kaur, 2008). The mean duration of pesticideexposure in workers ranged from 8.72 to 13.07 years, withat least 3–6 h/day. Only 8% farmers used some kind of pro-tection during spraying activity. An increase in geneticdamage was observed in the exposed group when comparedto control. The magnitude of genetic damage caused by thedifferent classes/types of pesticides, in decreasing order, isas follows:

herbicides . OPs . mixture of OPs and fungicide . mixtureof insecticides . pyrethroids . chlorinated hydrocarbons

No correlation was seen between genetic damage andan increase in the age of the workers or smoking. Non-vegetarians and alcoholics may be somewhat more sensitiveto genetic damage than vegetarians and non-alcoholics.The genetic damage caused by pesticides was repairable.

29.10 ASSESSMENT OF HUMAN EXPOSURE

As the use of OP and CM pesticides has increased andreached massive proportions, the darker side of contami-nation in our food and in our living environment has cometo light. As for any other product or service, there is someelement of risk involved in the use of pesticides. Pesticideresidue level is an indicator of accidental exposure and/oraverage measure of body burden to persistent pesticides.This could either be due to direct exposure or indirectexposure through the food chain. In India, the safety ofpublic is the joint responsibility of the All India Co-ordinatedResearch Project on Pesticide Residues (AICRP on PesticideResidues) of the Indian Council of Agricultural ResearchInstitute (ICAR), New Delhi, and NIOH, of the IndianCouncil of Medical Research (ICMR). In addition, someother independent bodies or individual institutions haveoccasionally brought the adverse effects of pesticides to thenotice of the Government.

Studies on contamination by pesticide residues on aworldwide basis have indicated that 79% of tested foodsamples do not show pesticide residues. Only 2% of theremaining 21% have pesticides above maximum tolerance

TABLE 29.14 Pesticides Commonly Used by Sprayers

Farmers(n ¼ 427)b

Class Chemical Family No. %

Ia. Extremely hazardousa

1 Phorate Organophosphate 33 7.7

Ib. Highly hazardousa

2 Monocrotophos Organophosphate 106 45.93 Profenofos and

cypermethrinCombination

pesticide63 14.8

4 Carbofuran Carbamate 11 2.6

II. Moderately hazardousa

5 Dimethoate Organophosphate 235 55.06 Qunalphos Organophosphate 211 49.47 Endosulfan Organochlorine 207 48.58 Carbaryl Carbamate 103 24.19 Chlorpyrifos Organophosphate 77 18.0

10 Cyhalothrin Pyrethroid 28 6.611 Fenthion Organophosphate 21 4.912 DDT Organochlorine 3 0.7

III. Slightly hazardousa

13 Malathion Organophosphate 6 1.4

IV. Unlikely to presentacute hazard innormal usea

14 Carbendazim Carbamate 32 7.515 Artizine Triazine 5 1.2

aWHO Classification of pesticides.bSome farmers sprayed more than one pesticide. Data for six farmers arenot available.


limits. In the early 1990s, ICMR indicated that 51% of Indianfood commodities were contaminated with pesticide residues,and 20% of these had pesticides above the maximum residuelimits (MRL). In the next multi-centric survey on pesticideresidues, 60% of samples were contaminated with pesticides,of which 14% showed contamination levels over the tolerancelimits, indicating a drastic decline in the percentage of foodcommodities with pesticides above the tolerance limits.From these studies it was interpreted that there is improve-ment in agricultural practices such as the use of integratedpest management, a shift of farmers’ to using OP and CMpesticides or organic farming, biopesticides, and biotechnol-ogy (Agnihotri, 1999; Gupta, 2004).

Based on the available information, it seems the humanhealth is faced with multifarious problems because theenvironment is enormously complex. In the course of trans-port and degradation, agents that were not originally toxicto man may become so, or chemicals that were initiallytoxic might also become less hazardous. There is no doubtthat humans are exposed to mixtures of pesticides and otherchemicals. In the literature describing the toxicity of mixturesof OP or CM pesticides, concern is expressed that mixturesof pesticides may be much more toxic than individualpesticides. This concern about potentiated toxicity is all themore worrisome because data are lacking about the toxicityof pesticide mixtures. In the absence of any such data, con-clusions on the toxicity of OP and CM pesticide mixturesare not possible. Conclusions drawn from various epide-miological surveys may be far from the truth, because it isdifficult to define the causal elements, particularly when com-plex exposures are involved. Second, the outcomes of limitedepidemiological investigations may not be applicable to thegeneral population.

29.11 CONCLUSIONS

OP and CM pesticides are toxic chemicals, and their ingestionis a common cause of self-poisoning in the developingworld because they are easily available and often stored inan improper manner due to lack of awareness of their hazards.Many such poisoning episodes are reported in India, andthousands of cases have not been documented. Acute toxicityas a cholinergic crisis and diagnosis are based on clinicalsigns and symptoms, as well as measurement of the inhibi-tion of erythrocyte (RBC) and/or plasma ChE activities.Exposure to pesticides in occupational settings may contrib-ute to modulation of the immune system.

Among agrochemicals and pesticides, OP and CM pesti-cides constitute 65–73% of all poisonings. The reasons forthe increased number of intentional poisonings in Indiainclude stress factors due to financial problems, lowersocio-economic status, dowry-menace, family or propertydisputes, marital conflicts, sterility, and so on.

There is a great deal yet to be learnt about the frequency ofreproductive disorders, genetic disorders, and other endocrinedisturbances caused by exposure to OP and CM pesticides,and the mechanisms by which these toxicants can causetheir effects. It is difficult to define the causal elementsin these epidemiological investigations, particularly whencomplex exposures are involved. Another limitation is the fre-quent movement of the worker population, and such studiesmay be difficult to apply to the prediction of health effectsin the general population.

The Bhopal event was the worst industrial disaster to haveoccurred to date, and provides a classic case to study from anenvironmental health point of view, as it raises importantissues, not only in terms of toxicology, but also in terms ofoccupational health and safety, air pollution, epidemiology,risk assessment, disaster management, and environmentalprotection. A lot has already been written about Bhopal,suggesting the lessons that should be learned in order to pre-vent tragedies of this kind from occurring in the future.

REFERENCES

Agarwal, S.B. (1993) Acute organophosphorus poisoning. Environ.Res. 62: 63–70.

Agarwal, S.B., Bhatnagar, V.K., Agarwal, A., Agarwal, U.,Venkaiah, K., Nigam, S.K., and Kashyap, S.K. (2007) Impair-ment in clinical indices in acute organophosphate insecticide poi-soning patients in India. The Internet Journal of Toxicology 4 (1).(www.ispub.com/ostia/index.php?xmlFilePath¼journals/ijto/vol4n1/poison.xml)

Agnihotri, N.P. (1999) Report on pesticide safety and monitoring.All India Coordinated Research Project on Pesticides. IndianCouncil of Agricultural Research, New Delhi.

Andersson, N. (1989) Long-term effects of methyl isocyanate.Lancet 333 (8649): 1259.

Anon. (2007) Pesticides Taking Huge Health Toll in Punjab’sMalwa Region. News Post India, 5 October 2007.

Anon. (2006) Poisoning cases in Yuvatmal medical college fromJuly 20042June 2005. Report on suicide of farmers inMaharashtra—background paper submitted by P.R. Bhatkule,Indira Gandhi Institute of Development Research, Mumbai, 26January 2006 to Govt of Maharashtra.

Badhe, A. and Sudhakar, S. (2006) An intravenous organophosphatepoisoning with intermediate syndrome: an unusual way of intoxi-cation. Indian J. Crit. Care Med. 10: 91–92.

Batra, A.K., Keoliya, A.N., and Jadhav, G.U. (2003) Poisoning:an unnatural cause of morbidity and mortality in rural. J.Assoc. Physicians India 51: 955–959. (http://www.japi.org/October2003/O-955.pdf.)

Bhatnagar, V.K. (2001) Pesticide pollution: Trends and perspec-tives. ICMR Bull. 31: 87–88.

Bhatt, Mohit H., Mikhail, A. Elias, Ami, K. Mankodi (1999) Acuteand reversible parkinsonism due to organophosphate pesticideintoxication. Neurology 52: 1467–1471.

REFERENCES 429

Chitra, G.A., Muraleedharan, V.R., Swaminathan, T., andVeeraraghavan, D. (2006) Use of pesticides and its impact onhuman health: A case of farmers in South India. Int. J. Occup.Environ. Hlth 12: 228–233. (http://www.econdse.org/hn/Pesticides.pdf.)

CIBRC (2008) Insecticides registered under/sections 9(3) of theinsecticide act, 1968. Central Insecticide Board of India,Ministry of Agriculture, New Delhi. (http://cirbc.nic.in/reg_products.htm.)

Choudhry, V.P., Jallali, A.J., Haider, G., Aram, G.N., and Ghani,A.R. (1987) Organophosphorus poisoning. Indian J. Pediatr.54: 427–430.

Cullinan, P., Acquila, S., and Dhara, V.R. (1997) Respiratorymorbidity 10 years after the Union Carbide gas leak at Bhopal:a cross sectional survey. Br. Med. J. 314: 338–342.

Dewan, A. and Sayed, H.N. (1998) Acute poisoning due toagricultural pesticides reported to the NIOH PoisonInformation Centre. In: Parikh, J.R., Gokani, V.N., Doctor,P.B., Gandhi, D.N., and Sayed, H.N. (eds) Proceedings of theWorkshop on Occupational Health Problems in AgricultureSector, National Institute of Occupational Health, Ahmedabad,p. 136.

EPA (1986) Health and environmental effects profile for methylisocyanate. Environmental Criteria and Assessment Office,Office of Health and Environment Assessment, Cincinnati,OH, USA.

Gannur, D.G., Maka, Prakash, and Narayan Reddy, K.S. (2008)Organophosphorus compound poisoning in Gulbargaregion—a five year study. Indian J. Forensic Med. Toxicol. 2:2–11.

Gupta, B.D. and Vaghela, P.C. (2005) Profile of fatal poisoningin and around Jamnagar. J. Ind. Assoc. Forensic Med. 27:145–148.

Gupta, P.K. (1985) Pesticides. In: Gupta, P.K. and Salunkhe, D.K.(eds), Modern Toxicology: Adverse Effects of Xenobioticsand Other Chemicals, vol. 2, Metropolitan Book Co. Pvt Ltd,Delhi, pp. 1–60.

Gupta, P.K. (1986) Pesticides in the Indian environment. Interprint,New Delhi.

Gupta, P.K. (1989) Pesticide production—an overview. In: Mishra,P.C. (Ed.) Soil Pollution and Soil Organisms, Ashish PublishingHouse, New Delhi, pp. 1–16.

Gupta, P.K. (2004) Pesticide exposure—Indian scene. Toxicology198: 83–90.

Gupta, P.K. (2006a) WHO/FAO guidelines for cholinesterase-inhibiting pesticide residues in food. In: Gupta, R.C. (Ed.)Toxicology of Organophosphorus and Carbamate Compounds,Elsevier, USA, pp. 643–654.

Gupta, P.K. (2006b) Status of biopesticides—Indian scene. Toxicol.Int. 13: 65–73.

Gupta, P.K. (2007) Toxicity of herbicides. In: Gupta, R.C. (Ed.)Veterinary Toxicology—Basic and Clinical Principals,Elsevier, USA, pp. 567–586.

Gupta, P.K. and Gupta, R.C. (1977) Debate on DDT (Review).Pesticides 11: 16–17.

Gupta, P.K. and Agarwal, M. (2007) Fungicides. In: Gupta, R.C.(Ed.) Veterinary Toxicology—Basic and Clinical Principals,Elsevier, USA, pp. 587–601.

Gupta, R.C., Dave, S.K., Shah, M.P., and Kashyap, S.K. (1979) Amonitoring study of workers handling pesticides in warehousesand godowns. J. Environ. Sci. Hlth 14B: 405–416.

Gupta, S.K., Jain, J.P., Sayed, H.N., and Kashyap, S.K. (1984)Health hazards in pesticide formulators exposed to a combinationof pesticides. Indian J. Med. Res. 79: 666–672.

Guven, M., Unluhizarci, K., Goktas, Z. et al. (1997) Intravenousorganophosphate injection: An unusual way of intoxication.Hum. Exp. Toxicol. 16: 279–280.

HSDB online database (1993) National Toxicology InformationProgram. National Library of Medicine, Bethesda, USA

ICMR (2000) NIOH Poison Centre: Organophosphorus (OP) pesti-cide poisoning. Annual Report 1999–2000. (http://www.Icmr.nic,in/annual/eoh.htm.)

ICMR (2004) NIOH Poison Centre: Pesticide exposures among farmworkers: Phase 1 chilli cultivators of Gujarat. Annual Report2003–2004, pp. 28–29. (http://www.Icmr.nic,in/annual/eoh.htm.)

ICMR (2005) NIOH Poison Centre: NIOH report on cholinesteraseand paraxonase patterns on organophosphorus pesticide poison-ing. Report 2004–2005, pp. 18–19. (http://www.Icmr.nic,in/annual/eoh.htm.)

ICMR (2006) Mass organophosphate (Ethion) poisoning with highmortality. Annual Report (executive summary) 2005–2006,pp. 15–18. (http://www.Icmr.nic,in/annual/eoh.htm.)

Infante, P.F., Rinsky, R.A., Wagoner, J.K., and Young, R.J. (1977)Leukemia in benzene workers. Lancet 2 (8028): 76–78.

Jackson, B. (1993) Disaster at Bhopal. Report by retired VicePresident, Health, Safety and Environmental Programs, UnionCarbide Corporation, USA.

Jain, S.K. and Dave, S.K. (1986) Working manual-1 on “The healthproblems of Bhopal gas victims: Assessment and management.”India Council of Medical Research, New Delhi.

Jeyaratnam, J. (1987) Survey of acute pesticide poisoning amongagricultural workers in four Asian countries. Bull. World HlthOrg. 65: 521–527.

Jeyaratnam, J. (1990) Acute pesticide poisoning: A major globalhealth problem. Wld Hlth Statist. Quart. 43: 139–144.

Karnik, A.B., Suthar, A.M., Patel, M.M., Sadhu, H.G., Venkaiah,K., and Nigam, S.K. (1993) Immunological profile in workersexposed to pesticides. Indian J. Ind. Med. 39: 110–112.

Karunakaran, C.O. (1958) The Kerala food poisoning. J. IndianMed. Assoc. 31: 204–205.

Kashyap, S.K. (1986) Health surveillance and biological moni-toring of pesticide formulators in India. Toxicol. Lett. 33:107–114.

Kaur, R. (2008) Assessment of genetic damage in workers occupa-tionally exposed to various pesticides in selected districts ofPunjab. PhD Thesis, Dept. of Human Biology, PunjabiUniversity, Patiala (India).

Koplan, J.M., Falk, H., and Green, G. (1990) Public health lessonsfrom the Bhopal chemical disaster. JAMA 264: 2795–2796.


Lipfert, F.W. (1980) Sulfur oxides, particulates, and human mor-tality: Synopsis of statistical correlations. J. Air Pollut. ControlAssoc. 30: 366–371.

Mahajan, K.K. (1988) Environmental legislation in India—Anoverview and its implications in controlling environmentalpollution. In: Gupta, P.K. and Prakash, R. (Eds) Advances inToxicology and Environmental Health, Jagmander BookAgency, New Delhi, pp. 7–64.

Maltoni, C., Conti, B., and Cotti, G. (1983) Benzene: A multipoten-tial carcinogen. Results of long-term bioassays performed at theBologna Institute of Oncology. Am. J. Ind. Med. 4: 589–630.

Mancini, F., Ariena, H., Bruggen, V.C., Janice, L.S.J., Ambatipudia,A.C., and Murphy, H. (2005) Acute pesticide poisoning amongfemale and male cotton growers in India. Int. J. Occup. Environ.Hlth 11: 221–232. (http://library.wur.nl/wasp/bestanden/LUWPUBRD_00341230_A502_001.pdf.)

McFarlane, A. (1986) Implications for disaster planners and emer-gency services. MJA 145: 561–563.

Mehta, P.S., Mehta, A.C., Mehta, S.J., and Makhijani, A.B. (1990)Bhopal tragedy’s health effects, a review of methyl isocyanatetoxicity. JAMA 264: 2781–2787.

Moeller, D. (1992) Environmental health. Harvard University Press,Boston.

Murli, R., Bhalla, A., Singh, B., and Singh, J. (2008) Acute pesticidepoisoning: 15 years experience of a large north-west Indianhospital. Clin. Toxicol. (Phila) 1: 4. (http:www.ncbi.nih.govt.pubmed/18608278.)

Naravaneni, R. and Jamil, K. (2007) Determination of AChE levelsand genotoxic effects in farmers occupationally exposed topesticides. Human Exper. Toxicol. 26: 723–731.

Pandey, N.N. (1986) Report on “Immediate and residual effects onMIC gas exposure on animals of Bhopal gas tragedy.” IndianVeterinary Research Institute, Izatnagar.

Pillay, V.V. (2008) Comprehensive Medical Toxicology, 2nd edn.Paras Medical Publisher, Hyderabad, India.

Raina, S., Mahesh, D.M., Sood, V., Kaushal, S.S., and Gupta, D.(2008) Self injection of dichlorvos, an organophosphorus

compound. Online J. Health Allied Sci. 7(2): 9. (http://www.ojhas.org/issue26/2008-2-9.htm.)

Rao, C.H., Srinivas Venkateswarlu, V., Surender, T., Eddleston, M.,and Buckley, N.A. (2005) Pesticide poisoning in south India:opportunities for prevention and improved medical management.Trop. Med. Int. Hlth 10: 581–588.

Rupa, D.S., Reddy, P.P., and Reddy, O.S. (1991) Reproductive per-formance in population exposed to pesticides in cotton fields inIndia. Environ. Res. 55: 123–128.

Sayed, H.N., Gupta, S.K., Jain, J.P., and Kashyap, S.K. (1984)Cardiac toxicity in pesticide formulators exposed to organopho-sphorus insecticides. Ind. J. Med. Res. 80: 494–497.

Sayed, H.N., Sadhu, H.G., Bhatnagar, V.K., Dewan, A., Venkaiah,K., and Kashyap, S.K. (1992) Cardiac toxicity following shortterm exposure to methomyl in spray-men and rabbits. HumanExp. Toxicol. 11: 93–95.

Singh, B. and Unnikrishnan, B. (2006) A profile of acute poisoningat Mangalore (South India). J. Clin. Forensic Med. 13: 112–116.

Singh, D., Jit, I., and Tyagi, S. (1999) Changing trends in acute poi-soning in Chandigarh zone: A 25-year autopsy experience from atertiary care hospital in northern India. Am. J. Forensic Med.Pathol. 20: 203–210.

Srivastava, A.K., Gupta, B.N., Bihari, V., Mathur, N., Srivastava,L.P., Pangtey, B.S., Bharti, R.S., and Kumar, P. (2000) Clinical,biochemical, and neurobehavioral studies of workers engagedin the manufacture of quinalphos. Fd Chem. Toxicol. 38: 65–69.

Wattal, B.L., Bhatnagar, V.N., and Sharma, R.P. (1975) Monitoringof cholinesterase enzyme activity under fenitrothion application.J. Comm. Dis. 7: 65–71.

Zaidi, S.S.A., Bhatnagar, V.K., Gandhi, S.J., Shah, M.P.,Kulkarni, P.K., and Sayed, H.N. (2000) Assessment of thyroidfunctions in pesticide formulators. Human Exp. Toxicol. 19:497–500.

Zoppellari, R., Borron, S.W., Chieregato, A., Targa, L., Scaroni, I.,and Zatelli, R. (1997) Isofenphos poisoning: Prolonged intoxi-cation after intramuscular injection. J. Toxicol. Clin. Toxicol.35: 401–404.

REFERENCES 431

anticholinesterase pesticides (metabolism, neurotoxicity, and epidemiology) || epidemiological...

Documents