CHAPTER IV

PESTICIDE TOXICITY & RELATED HEALTHPROBLEMS

It was noted in the last chapter that all pesticides including themost commonly used organochlorines, organophosphates, carbamates,pyrethroids, bipyridyls, chlorophenoxys, and triazines that togetherform a large group of about 1400 active ingredients pose the mostsignificant health hazards from acute as well as chronic toxicity.It has also been noted from their properties that use of pesticidesis associated with innumerable environmental problems whether theyare related to soil, water, air, birds, fish, animal or man. It isintended to discuss the toxicity trail in this chapter and continuethe discussion to the next chapter on the mechanism by which thepesticides are able to induce toxicity, reach the toxicity endpoints, and cause damage to the living system.

All groups of pesticides are toxic substances added deliberately tothe micro and macro environment for their toxicity and biocidaleffects to kill and harm living things. They do get added as theirfall out to the environment. This unintentional act has had all thedamaging effects not only on the microenvironment where they areused but also the macro and the global environment since their usehas become immensely widespread, and they and their degraded orbiotransformed products can be carried by air and water to far offdistances. They can now be found anywhere on earth, contaminatingsoil, air, groundwater, surface water, rain, snow, and fog. Even theArctic ice pack and the deep beds of the ocean are not spared fromtheir presence. They and their residues, which are often more toxicthan the parent compounds, have found their pathway into the foodchain and have poisoned the birds, fish, wildlife, domestic animals,livestock, and human beings, including newborn babies.

The impact of toxicity of pesticides is heavy as well as pervasiveowing mainly to a wide range of their application for cropprotection and home use as may be estimated from the share of theirdifferent classes in the market viz. herbicides 51%, insecticides25%, fungicides 20% and others 4%. Herbicides have a larger marketin the industrialized countries for home use for maintaining thelawns and for managing golf courses, parks and recreation areas. Theuse of insecticides and fungicides is extensive in crop protection

but their home use has grown substantially during the last twodecades. Homeowners and urban dwellers are thus at great risk ofexposure to the toxic trail of chemical pesticides.

The indiscriminate use of these chemicals on a massive scale such asthat mentioned above has had profound impact on the livingenvironment. According to a report by UNICEF, UNEP and WHO, theimpact of the use of highly toxic chemicals takes the toll of about5,500 children each day around the world from diseases caused bypolluted air, water, food and environmental contaminants, whichinclude the pesticides. Since the 1970s, the incidence of cancers,learning disabilities, autism, diabetes, early puberty, and abnormalpenile development has skyrocketed among the children who comprisethe most vulnerable group of citizens(ENS, May 10, 2002).

It has been pointed out earlier that synthetic chemical pesticideshad not been adequately tested for their chronic toxicity and notevaluated at all for their developmental toxicity. The study ofdevelopmental toxicology did not make such enviable progress asdevelopment of chemicals and that created a complete lack ofunderstanding on how life processes may be affected by potentiallytoxic chemicals such as the pesticides. Although hazards of chemicalpoisoning had taken toll of hundreds of lives in the past yet it wasnot until the mid-1960s that chronic toxicity of the pesticidesbecame a matter of concern. In the mean time evidences continued topile up on the linkage of many of the hitherto unknown disorderswith exposure to chemical pesticides that are carcinogenic,mutagenic, teratogenic and hormone disrupting.

Damages done to the health of individuals by chemical pesticideshave a wide range starting from acute toxicity with a single dose orexposure, to sub-chronic toxicity resulting from a few exposures andfinally to chronic toxicity due to long term persistent exposuresfor each possible toxic end point. The toxic end points includecancer, damage to organs like the liver, kidney or heart,developmental disorders, damage to the immune system, centralnervous system, reproductive system, and to the genes. Organisms,including test animals and man, react differently at differentstages of development, particularly while in the womb, where scoresof endpoints can be established, depending on the toxicity trail ofthe chemical pesticides and their end points. Such endpoints wereeither unknown for reasons of lack of understanding on developmentaltoxicology or were ignored when the pesticides and other toxicchemicals were introduced into the living systems.

Toxicity of Pesticides: Toxicity of pesticides reflectson their potential to kill the targeted pest. Toxicity is therelative ability of a substance to cause injury to a biologicaltissue while toxicology is the study of interaction, the cause andeffect of chemical or physical agents with an organism to produce animpact on its biological systems. Pesticides belong to the class ofhazardous substances whose impact on health becomes apparent whentheir exposure exceeds the safe limits of toxicity as well as thecumulative level of concentration at the exposed site of the body.

For purposes of determining the impact of pesticides on the healthof users it is important at the outset that toxicology of thepesticide and its acute as well as chronic toxicity is known. Hereit is relevant to quote Paracelsus (1493-1541) who said, "allsubstances are poisons; there is none which is not a poison. Theright dose differentiates between a poison and a remedy." Thisimplies that it is the dose or quantum of exposure that makes thechemical a poison to an organism and determines whether the effectsare toxic, non-toxic or beneficial.

Farm workers, mixers, appliers, and a host of household users whoapply them on lawns and inside homes are among those exposed to thehazards of pesticides. If the appliers follow the precautions setout on the labels of the packing and also adopt the minimumrequirements of the workers safety and protection standards, theexposure to this class of workers is found to be significantlyreduced, but not done away with completely. The increasing number ofcases being reported pertains to old cases of exposure and as saidrepeatedly in the earlier pages, it takes quite a while for thesymptoms of chronic toxicity to surface up and when they do thedamage has been done.

Exposure is not limited to the above set of uses and users; it alsoresults from chemical spills that occur accidentally when thechemical containers get punctured, are broken or torn or crushed atthe manufacturing or formulation sites or warehouses or duringtransportation, or at the users end during mixing or application attheir site. Exposure also results from the leachates of toxic dumpssuch as those at the site of storage of outdated pesticides inPakistan and other developing countries, and at the superfund sitesin the USA as well as the landfill sites where the chemicalmanufacturers had dumped their waste products. It generally occursdue to failure on the part of the user to follow the instructionslaid down on the label for application, storage, or disposal.

Exposure is more significantly the result of failure to follow theworkers safety and protection standards owing to ignorance in thecase of users in developing countries and what comes as a matter ofright of the user i.e. Right-to-know, through regulations inindustrialized countries.

Health Problems Associated with Exposure toPesticides

The US Environmental Protection Agency had estimated the 1992 worldsupply of pesticides at about two million tons. This amounted to aper capita exposure of about 1,000 mg per day on a global scale. Afew mg of any pesticide, it may be reminded, is enough to producethe toxicity symptoms. The per capita exposure must have increasedsince the production of pesticides has not decreased during the lastdecade. The quantities just stated are frightening in view of thefact that the same have been available in the environment for thelast four decades.

The above quantities have been damaging the global environment whilethe status of the microenvironment where the pesticides are sprayedand the macroenvironment in which they are eventually distributedhas been generally degraded and greatly disturbed. This is evidencedby the per capita exposure of the population in the USA, where only25% of the global availability of pesticides is in use, out of which70% is applied in agriculture. The per capita exposure in USA is ofthe order of 5,500 mg/day. The population largely at risk toexposure of this huge quantity in the USA, one may be inclined tobelieve, comprises the spraymen, mixers, loaders, suppliers andmanufacturers. This is, however, not so, since it is a small groupthat makes up only a fraction of the 4.4 million agricultural labourforce there. Moreover, in 1992, most pesticide poisoning incidentsoccurred outside agriculture and they mostly involved children.

In the macro-environment, the agricultural workers while doing theirjob anywhere, in any country, represent the largest occupationalgroup at risk to pesticide exposure, compared with other groupsengaged in pesticide manufacturing and formulating plants, andworkers engaged in distribution, wholesale, and retail businesseswho routinely transport and store large volumes of pesticides aspart of their job. The latter group, in any case does not equal the2.1 million farm families or the estimated 4.4 million farmlabourers employed by agricultural businesses in USA. According toUS EPA and OSHA estimates, 2.3 million agricultural workers receive

pesticide exposure incident to their jobs annually. These workersare exposed directly or indirectly to pesticides and their residuesduring work in treated areas.

The pesticide manufacturers, however, put an innocent third groupcomprising the pesticide users in developing countries at risk byexporting unregistered, deregulated and banned pesticides. Between1997 and 2000 the USA exported about 1.5 million tons of pesticides,of which about 30,000 tons were banned or severely restricted forlocal consumption. Some of the banned pesticides included captafol,chlordane, isazofos, monocrotophos and mirex. 57% of these exportswere destined for the developing countries(PANUPS, January 11, 2002). Thisaction by the exporters of USA thus intentionally exposed the peopleand the environment of the developing countries and put them atrisk.

Unlike the situation in Pakistan and other developing countries,pesticide poisoning is not among the many occupational healthhazards faced by agricultural workers in USA. This is amply clearfrom the malathion accident in Faisalabad and Kohat in which 7 spraymen died and 2,800 out of 7,500 were poisoned. Also in point is thecase of tens of thousands of male workers engaged in spraying andother pesticide related activities in infested cotton fields thatare exposed to the pesticides during the sowing and subsequentoperations. Additionally an equal number of female cotton pickerswho have to remain in the field for collecting the crop and itsresidues, suffer from pesticide related illness during and after thecotton picking time of the year.

Several Federal and state regulations in the USA guarantee farmworkers a reasonable and safe environment. Accordingly agriculture,the largest user of pesticides, does not have the farm workers asthe largest group at risk. The Farmworkers Association of Florida,however, feels differently. It is of the view that pesticideexposures are responsible for the health problems of farm workers,but proving the same is fraught with pitfalls. Since there is no wayto measure the exposure of the pesticides and other contaminantsdirectly, it is difficult to link the same to chronic healthproblems. The toxicological proof providing the evidence for thelink to a particular health problem is required to be of such highstandards that it is very difficult to obtain from the meagerresources. The obvious link between pesticide and health problems isthus given low weightage, if not sidelined.

The group at large risk to the per capita exposure of about 5,500 mgpesticides per day in the USA and other industrialized countriesincludes by default the homeowners and their children living inareas where anti-microbials, disinfectants, and home gardenpesticides are used. Problems of pesticide poisoning and also oftoxicity end points have aggravated in living areas close to farmse.g. the villages near the cashew plantations in Kerala of SouthIndia or those near the citrus growing area in Florida or Californiawho are exposed to the spraying on the plantations. This nonethelessconstitutes a smaller group compared with the urban dwellers who inmaintaining their lawns, home gardens, golf courses and parks applyten to fifteen times more chemical pesticides per acre than farmers.The areas meant for exhibiting a high profile lifestyle, occupy moreland than any single crop, including wheat, corn or tobacco in USA,and such homeowners use massive quantities of pesticides, rangingfrom household ant and roach killers to home garden pesticides, andthat is one of the main reasons for the high per capita exposure topesticides.

The high per capita exposure accounts for most human poisoningincidents and for most of the calls to poison control centres fromhomeowners including the dwellers in rented homes, apartments,urban, suburban, and rural dwellers and their children in USA.According to several reports, children account for more than 80% ofthe poisoning incidents. Most exposures to poisons occur with commonhousehold drugs and chemicals including pesticides. Residents ofmany homes are unknowingly exposed to OCs e.g. chlordane, used astermiticide, DDT for malaria control, or the arsenicals for timberpreservation that may have been applied many years before theconcerned urban area nucleated. They may suffer from pesticideexposure in yards, gardens or their lawns. More than 60,000pesticide exposures occurred in the USA in 1989, which howeveramounted to only 3.8 percent of all poison exposures reported.

Use of farm chemicals has undergone massive changes in theindustrialized countries but not in the developing countries whichare at least 25 years behind the former. Having no production,evaluation and monitoring facilities of their own, they have todepend on the MNCs and international agencies for use of chemicalpesticides for plant protection and for home use. Thus the concernon chronic toxicity of the pesticides and the toxicicity end pointsis of no consequence to them. Incidentally they blindly acceptwhatever is offered to them, much of it in some kind of aid package.

The amendments to FIFRA in 1988 in USA were instrumental in thechanges in the use of farm chemicals and in having many highly toxicpesticides sidelined, restricted, banned and in the re-registrationof more than 40,000 of the products that were canceled. Many ofthese pesticides are still being used in the developing countriesand also being manufactured in some of the producing countries suchas India and the USA.

The major shift in pesticide use during the past three decades wasdue to introduction of herbicides whose use dominated the spectrumof usage and relegation of insecticides and fungicides to second andthird place. The number of acres receiving treatments by the variouspesticides changed radically while raw tonnage of pesticidesremained unchanged during the last 20 years. Early in the 1980s,however, the use pattern of insecticides changed as a result ofcancellation of registration of some of the well known OCs and theintroduction of the third generation pesticides including thepyrethroids, which replaced large volumes of OPs and carbamates withtheir small volumes. Alachlor (Lasso®), Atrazine (Aatrex®),Glyphosate (Roundup®) and 2,4-D were among the top 5 herbicides usedin USA but by 1992, Treflan® (Trifluralin), Dual® (Metolachlor),Bicep® (Metolachlor + Atrazine), and Glean® + Ally® (Metsulfuron +Thiameturon) had replaced them. Now that the major OCs, OPs andatrazines have been banned or restricted and the cosmetic use ofpesticides is being phased out, the trend is changing again.Accordingly herbicides had a share of 46% in 2001 reduced from 51%in 1997 and pyrethroids are now being promoted with caution.

Market share of the cyclodiene pesticides was substantially reducedby the late 1960s and early 1970s due to the observed insectresistance. The link of aldrin to cancer initiated its ouster before1972 and simultaneously placed many of the chlorinated cyclodieneson the list of suspected carcinogens. That marked their de-registration from agriculture. Out of half a dozen cyclodienes, onlyEndosulfan (Thiodan®) remains in the market, but that is also bannedin more than 10 countries. The less persistent, but more toxic OPsand carbamates had replaced them temporarily and now their use isalso being restricted.

Chlorinated hydrocarbons that include the DDT family of pesticidesviz. DDT, DDD, DDE, Perthane, Kelthane, Methoxychlor (Marlate®),Chlorobenzilate, Chlorobenside, and several others are like thecyclodienes, highly persistent in the environment. Intensificationof DDT in the food chain and disappearance of certain bird speciesdue to thinning of their egg shells had by 1967 been established.

When EPA canceled the registrations for DDT in 1973 owing to itsbeing placed on the list of suspected human carcinogens, it hadsince lost most of its agricultural market owing to insecticideresistance. Only Kelthane and Methoxychlor in the DDT family stillhave broad use offered in small packages in home garden products.Pest tolerance has also eroded the market share of these products inagriculture. Some of these pesticides e.g. DDVP (Vapona®),Permethrin, Diazinon, and Chlorpyrifos, which replaced DDT and otherOCs for home use are already sidelined. Dursban® the commonhousehold formulation of Chlorpyrifos was implicated by poisoncontrol centres in many household pesticide exposures.

DDVP was offered in aerosol formulations with pyrethrins for controlof household pests. A very common formulation of DDVP was the resin"No Pest Strip®". DDVP and lindane both sublime directly from solidto the vapor state but the former recrystallizes and depositsresidues on walls, furniture, floors, in cracks and crevices. Long-term toxicology studies in 1988 showed that DDVP caused liver damageand tumors and that was sufficient reason for EPA to suspend all itsindoor uses in 1989. However, DDVP has not disappeared from theclosets and is still on shelves of many homes.

Diazinon, Dimethoate, Ethyl Parathion, and Phosdrin wereorganophosphate insecticides widely used in row crops. However,because of the damages done to crops, they were first subjected torestrictive regulation and sidelined subsequently. Due to itstoxicity to children and the risks it poses to workers, drinkingwater supplies, birds and other wildlife, the producers of diazinonproducts have agreed to completely eliminate this OP for residentialuse by December 31, 2004. Between 1994 and 1998, diazinon wasresponsible for more bird kill incidents in the United States thanany other pesticide. Its residential use accounted for over half ofthese incidents(ENS, July 15, 2002).

Permethrin also comes in some household pest control formulationsalthough it has a record of producing liver tumors in animals.

Cancellation of cyanide products, ethylene dibromide, and carbontetrachloride and carbon disulfide and their replacement by aluminumphosphide and the insecticide malathion has changed the use patternof grain and seed fumigants in the USA. Grain fumigants accountedfor many tons of this class of pesticides used annually while thesoil fumigants accounted for even more. Some of the most prominentfumigants such as Telone® and methyl bromide formulations are ontheir way out.

Fungicide use pattern has in like manner undergone changes, withmany of the EBDC fungicides, like Dithane®, Manzate®, Ferbam®,Polyram® and some others having been sidelined were replaced byChlorthalonil (Bravo®). The rise of Chlorthalonil to prominece isdue mainly to its broad use in ornamental lawns and gardens. Thebravo may, however, be running out of time because of its aromaticring having chlorine as a substituent.

The change in use pattern mentioned above was largely the result oftracking the toxicity trail whose end points have been found toinclude cancer, damage to organs like the liver, kidney or heart,developmental disorders, damage to the immune system, centralnervous system, reproductive system, and to the genes sufferinginduced by pesticides which were put in the market without theirchronic toxicity and long term cumulative effects being adequatelyevaluated. Quite a few pesticides, such as the OCs have been de-registered and banned in the USA. Their use, however, has not beendiscontinued in many Latin American countries and other developingnations such as India where most of them are still being produced.

HEALTH HAZARDS POSED BY PESTICIDES

Hazards due to pesticides use are due to their toxicity which theycan induce by entering the body through the skin, mouth, eyes orlungs. They induce toxicity in two different ways:

1) Acute toxicity or toxic effects resulting from a short exposureto a substance and 2) Chronic toxicity or toxic effects resulting after a long exposureof up to several years.

Acute Toxicity can be due to a single dose but can causeimmediate concern to many persons around. It is therefore importantto take good cognizance of the signs and symptoms and to treat thevictims according to the type of poisoning. Symptoms of acutetoxicity are invariably similar. The victim develops nausea andvomiting followed by confusion, tremors, coma, seizures andrespiratory depression. If the pesticide is highly toxic, death canoccur within hours. Immediate effects appear in the form ofheadache; dizziness; nausea; vomiting; tremors; confusion; muscleweakness; involuntary eye movements; slurred speech; pain in chestand joints; skin rash; strenuous breathing; convulsions which mayoccur with a delay of several days after exposure; incoordination;hypersensitivity of skin, face and extremities; central nervoussystem stimulation followed by depression; diarrhea; brain wavedisturbances; hyperthermia; hypertension; salivation, and sweating.

Acute toxicity of a substance is measured in terms of its LD50, whichis the Lethal Dose needed to kill 50% of laboratory test animals andis measured as milligrams of poison per kilogram body weight of thetest animal. The smaller the LD50, the more toxic is the poison. LD50sare generated for many test animals and pests. Any substance can betoxic at a sufficiently high dose; the LD50 of ordinary table salt is3 grams per kilogram body weight; the lethal dose of salt for asmall child being about 2 tablespoons.

Chronic Toxicity: The main health risk associated withpesticides is not acute toxicity i.e. the immediate effect butchronic toxicity i.e. the long term effect. It may be sub-chronic ifthe toxicity is caused by a few exposures and chronic if caused bypersistent or a series of exposures. The symptoms may not be ofserious concern as to demand immediate action e.g. someone who mayeat vegetables and fruits sprayed with pesticides may get sick withvomiting and nausea and that sickness can be provided at least someshort term cure. What is overlooked is the upsurge of concentrationof the residues of the pesticides in the body due to continuousexposure over time. This may cause disease to develop slowly andfinally reach the toxic end points that include cancer, damage toorgans like the liver, kidney or heart, developmental disorders,damage to the immune system, central nervous system, the genes, andto the reproductive system, including placenta where they may causedeformities in the progeny by one of the mechanisms that have beendescribed later.

It may be reiterated that the users had readily accepted thepesticides for their demonstrated acute toxicity without waiting forthe impact of the chronic toxicity to be understood and recognized.Since it takes more than a decade for long-term effects to emerge,it was difficult for the users to understand the symptom, which werenonetheless confusing. It was equally difficult for those whointroduced and produced the pesticides to admit that whatever washappening to the users was due to chronic toxicity of pesticides.Even now, the damages already done to the environment by chronictoxicity of and the course adopted to reach the end points by thechemical pesticides is known only for a few while it is required forseveral hundreds of them.

Evidences are now available to indicate that all pesticides in agiven chemical group generally affect the life form by interactingwith the enzyme system in more or less similar manner. Pesticidesdamage the enzyme system by deactivating them. In case thedeactivation process is reversible or the concerned enzyme isimmediately regenerated, the toxic symptoms would soon disappear.The symptoms would persist in case the deactivation is notreversible and the deactivated enzymes are not replaced orregenerated during the course of time. The health problems vary withthe type of pesticide used, likewise the signs and symptomsassociated with poisoning by each type of these chemicals vary.Severity of the effects varies depending on the formulation,concentration, and toxicity of the pesticide besides the route ofexposure and toxicity trail involved. They can pose serious healthproblems like skin or eye disease, and the toxicity trail canterminate in birth defects, infertility or cancer.

Diagnosis of chronic toxicity resulting from pesticides exposure hasbeen problematic ever since the use of CWAs were introduced aschemical pesticides to control the incidence of disease due topests. A large number of toxicological distresses have been reportedbut not appraised for chronic exposure to pesticides and theirbreakdown products until the early 1970s. These toxicologicaldistresses were noted in the form of visual, dermal and reproductiveeffects and defects. The relation of chronic pesticide poisoningwith the distresses was difficult to establish mainly becausesymptoms of acute pesticide poisoning mask many symptoms of chronicand long-term toxicity, often confounded by pre-existing medicalconditions, related to diet, personal habits, genetics andenvironmental factors that include exposure to high intensity UVradiation, heavy metal contaminants, and airborne pollutants.

Regular blood cholinesterase testing provides baseline monitoringand diagnostic tests for chronic exposure of pesticides.Cholinesterase baselines also vary from one individual to anotherand depend on genetic structure. A reliable baseline thereforerequires a medical history of cholinesterase tests. A few states inUSA require regular cholinesterase monitoring of people engaged inpesticide handling and application. These tests are however, notconsidered sufficiently reliable to be included in the regulationsconcerning workers protection. As such standard universallyacceptable methods for monitoring health effects of exposure andreentry after pesticide treatment, to diagnose and treat healthproblems related to chronic pesticide exposure had to be evolved.Advanced technology was used (i) for development of instruments todetect pesticides and their residues to the level as small as onepart in a trillion and quadrillion, and (ii) for following theirpathways into different components of the environment and thusproviding evidence of toxicity trail. It was possible to detect onlytrace amounts of substances at one part per million the 1950s; by1965, it was possible to detect one part per billion, and by 1975the limit for detection had gone to the extent of one part pertrillion.

With the availability of advanced detection equipment, it ispossible to detect the presence of even trace amounts of chemicalpesticides and to identify and quantify their residues in food, airand water and to determine their presence practically everywherethough in minute quantities at the level of parts per trillion andeven quadrillion. Such measurements were necessary for determiningthe amount of environmental degradation in view of the high percapita exposure to decades of pesticide use which may havecontaminated every inch of soil under a crop or in home use anywhereon earth.

Measurements of quantities at low level have been extremely helpfulin correlating chronic toxicity or slow poisoning by pesticides withtoxicological distresses. They have helped in tracking the toxicitytrail due to exposure to even small amounts of chemical pesticidesover a long period of time, ultimately leading to different non-specific complaints that may include persistent headaches, nausea,fatigue, muscle twitching, visual disturbances, and different toxicend points. They have provided the much needed evidence of impact oftoxicity of pesticides on the health of those impacted.

Massive data on toxicity of chemical pesticides have now becomeavailable for regulating agencies to take note of the increasing

incidence of pesticide toxicity and the increasing number ofevidences on their toxic end points that surfaced up during the lastthree decades. The US EPA has accordingly classified potentiallycarcinogenic pesticides into five categories.

Group A - Human carcinogen Sufficient evidence from epidemiologic studies to support a causalassociation between exposure to agents and cancer.

Group B - Probable human carcinogen

B1 - Sufficient evidence of carcinogenicity from animal studies withlimited evidence of carcinogenicity from epidemiologic studies.

B2 - Sufficient evidence of carcinogenicity from animal studies,with inadequate or no epidemiologic data.

Group C - Possible human carcinogen Limited evidence of carcinogenicity in the absence of human data.

Group D - Inadequate or no human and animal data.

Group E - No evidence of carcinogenicity in at least two adequateanimal tests in different species in adequate epidemiologic andanimal studies. This classification is based on available evidenceand does not mean that the agent will not be a carcinogen under anycircumstances.

It is frightening to note here that the pesticides that were classedin the lower groups of carcinogenic pesticides like the No-evidence-of-carcinogenicity or Possible-human- carcinogen are passing on intohigher groups of Sufficient-evidence-of-carcinogenicity and Human-carcinogen. This is the result of mounting evidences that becameavailable and are now becoming increasingly available in addition toand as a result of the increased availability of equipment anddevelopment of methods of assay together with the intensive effortsmade by epidemiologists all over the world. These evidences haveconvincingly demonstrated that a majority of the pesticides thatwere considered safe in the past did not have their safety dataextended to identifying the toxic end points. With concerted effortsin this direction the toxicodynamic studies have been conducted onthe various pesticides in use. This has brought forward themechanism of reaction in addition to the understanding of the toxicend points that include the carcinogenic, mutagenic and teratogenicproperties of the pesticides.

With the availability of sufficient evidences it is possible tocategorize a majority of the hitherto considered safe chemicalpesticides in the class of hazardous substances. This is borne outby the observation in the following sections on signs and symptomsof poisoning by different classes of chemical pesticides and alsothe antidotes for initial treatment which indicate that toxicityinvariably trails in almost all of them to reach the same endpoints. Thus a majority of them can be considered hazardous tohealth of the humans and the environment.

OCs, including the cyclodienes, organophosphates, carbamates,pyrethroids, bipyridyls, and fumigants that together represent themain pesticide groups which pose the most significant healthhazards, proceed by first interacting with the enzymic system in theaerial, dermal or gastrointestinal tract and initiate the acutetoxicity symptoms. In case they get biotransformed by the bodyenzymes or by the antidotes provided by medication, the symptoms maysubside. In case the pesticides are not completely deactivated, theyand/or their biotransformed products proceed by exciting the nervecells causing physicochemical disturbances in the central nervoussystem that controls vision, hearing, speech, learning, memory, andmuscular movements. Different neurotoxic chemicals that include thechemical pesticides, affect different sites, the neurons, glialcells and myelin, the neurotransmitter system, and blood vesselssupplying the nervous system. Physicochemical disturbances caused bychemical pesticides may be local, non-propagated potentials calledsynaptic, generator or electronic potentials, and/or propagateddisturbances in the form of nerve impulses.

The pesticides and/or their biotransformed products may, in casethey are not completely deactivated, equally likely proceed toexcite the muscle cells producing an action potential that may betransmitted along the muscle cell membrane. The electrical events inboth cases disturb the ionic flux underlying them and cause changesin action potential that may lead to a series of disorders e.g. incell communication, which may lead to disruption of the neuralcommunication causing unpredictable changes in neurotransmitterrelease, and in endocrine communication which may constrain thehormones from reaching the cells through the circulating blood.

Nausea and vomiting are among the first few signs that becomeapparent soon after ingesting chemical pesticides. They comprise theinitial symptoms of attack on the nervous system. It may be notedthat swallowing, coughing, sneezing, gagging, nausea, vomiting,

blood pressure changes, sweating, and pallor are reflex responsesintegrated in the medulla oblongata. Chemoreceptor cells in themedulla initiate vomiting when the circulating chemical pesticidestimulates them.

The toxicity trails by some such mechanisms as discussed in the nextchapter, with symptoms such as persistent anorexia; weakness;malaise; eye damage; ulcers; worsening to nerve damage; abnormalbrain waves, and reaches the end points that lead to cancers;mutagenic, teratogenic, fetotoxic effects; hormonal inhibition;sterility and impotence; reduced protein synthesis in fetus; spermand other reproductive abnormalities; embryotoxic; immunotoxic; bonemarrow damage and aplastic anemia; alteration in white blood cellcount; suppressed antibody production; viral enhancement; liverdamage; kidney damage; and decrease in auditory attention, visualmemory, problem solving, in control of balance, and in dexterity.Many of these effects are cumulative. Long-term effects include suchtoxic end points as dysfunction of endocrine glands; cumulativedeposition in fatty tissues; transfers through placenta to fetus;into mother's milk; behavior changes in young of mother exposed toeven low levels during pregnancy; sleep disturbance, andhallucinations.

Symptoms and Antidotes for Organochlorines andCyclodienes: Nausea and vomiting, blood pressure changes,sweating, and pallor are the initial symptoms of attack soon afteringesting OCs. Symptoms that accompany or follow nausea and vomitinginclude other signs of disturbances in the nervous system andelectrolytic balance. These include apprehension, excitability,dizziness, headache, disorientation, weakness, a tingling orprickling sensation on the skin, and muscle twitching; followed byloss of coordination, convulsions similar to epileptic seizures andunconsciousness. When absorbed through the skin, apprehension,twitching, tremors, confusion and convulsions may be the first fewsymptoms. Acute poisoning from very large doses of OCs can producegastric irritation, vomiting, and later emesis or diarrhea. Moderatedoses can produce malaise, headache, sore throat, and fatigue, inaddition to coarse tremors, muscle twitching, or convulsions.

Cyclodienes produce a series of symptoms like malaise, headache,nausea, vomiting, dizziness, CNS stimulation and muscle tremors.Rhythmic convulsions occur without forewarning symptoms. Convulsiveepisodes alternate with periods of severe CNS depression. In the

acute phase leukocytosis, rise in blood pressure, and fever havealso been noted.

Symptoms of mild poisoning by DDT-related OCs and cyclodienes areextremely similar. In many ways, early mild symptoms of pesticidepoisoning mimic allergies, colds or infections. In fact, most of thecrop protection chemicals produce similar symptoms. Therapeutictreatment for poisoning by the two groups nevertheless has to bedifferent and has to vary from one poison to another.

Specific antidotes are not available for OC poisoning. However, thefirst thing to do in all cases of poisoning is to removecontaminated clothing immediately and then bathe and shampoo thevictim vigorously, with soap and water, to remove pesticide from theskin and hair. Those assisting the victim must wear rubber glovesand be careful to avoid exposure to the pesticide. In case thepesticide has been ingested, the stomach must be emptied as soon aspossible by medication or by inserting the finger into the throat.Time is extremely critical and hence emergency treatment is vitalfor survival.

The USEPA

cancelled or curtailed the availability of many OCs since they arenon-biodegradable and hence persistent in the environment;furthermore many of them have their toxic end point in cancer inlaboratory animals and are suspected human carcinogens. Toxaphene,

chlordane, dieldrin, endrin, and heptachlor were, when available,commonly involved in OCs poisonings. Others that are still in useare endosulfan (Thiodan®), methoxychlor (Marlate®), and dicofol(Kelthane®) have produced poisoning. These materials affect thenervous system as stimulants or convulsants. OCs and cyclodienes canbe distinguished through their different effects on cells. OCs arefast acting while the cyclodienes are slower; the former affectsodium channels in axonic membranes, while the latter most likelyaffect the chloride receptors.

Symptoms and Antidotes for Organophosphates, OPs andCarbamates: There are about 45 important OPs and carbamateinsecticides currently registered with US EPA. The National Academyof Sciences Report of 1993 concluded that these compounds pose risksto pregnant women, infants and children through a common mechanismof action of cholinesterase inhibition. In the case of the OPs, therecent International Life Sciences Institute review conducted forEPA reached the same conclusions, as have many other expert bodies.It is clear that OPs and carbamate insecticides pose human healthrisks through one common mode of action, but they pose widelydifferent levels of risk per unit of exposure, and also per acre-treated. For example, the LD50 of the most toxic OPs and carbamatesare under 5 mg/kg, while the least toxic OPs have LD50s over 1,000mg/kg. Similarly in terms of Reference Doses and chronic risks, themost toxic OPs are on the order of 1,000-fold more toxic than theleast toxic OP active ingredients.

Pesticide

poisoning by OPs or carbamates affects humans by inhibitingcholinesterase, the enzyme that is essential to proper functioningof the nervous system. The impact of exposure to OPs is particularlyrapid. Symptoms appear shortly after exposure but in many acutepoisoning cases they may even appear during exposure, while in somecases there may be a delayed reaction due to activation in the body.Symptoms even in such cases appear within 24 to 48 hours ofexposure. The onset of symptoms in mild exposures usually occurswithin 4 hours but it may take up to 12 hours after exposure.Accordingly the diagnosis of suspected poisoning must be rapid andit is imperative to be familiar with the signs and symptoms thatthese types of pesticides produce in victims. Poisoning in bothcases, however, proceeds by inhibition of cholinesterase and hencethe symptoms are usually those of nerve poisoning.

Symptoms of OP poisoning include headache, nausea, and dizziness.Hypersecretion, sweating, and rhinorrhea are also prominent. Anxietyand restlessness are common. Involuntary muscle twitching, weakness,tremors, incoordination, vomiting, abdominal cramps, and diarrhea

also may accompany organophosphate poisoning. Blurred or dark visionand myosis are often helpful signs.

Carbamates produce malaise, muscle weakness, dizziness, sweating,and involuntary muscle twitching. They also produce headache,salivation nausea, vomiting, abdominal pain and diarrhea.Incoordination, slurred speech, dark or blurred vision, and myosisare also reported. Dyspnea, bronchospasm, and chest tightness havein some cases resulted in pulmonary edema.

Signs and symptoms associated with mild exposures to OP andcarbamate pesticides include the following: headache, fatigue,dizziness, loss of appetite with nausea, stomach cramps anddiarrhea; blurred vision associated with watery eyes and excessivetear production; contracted pupils of the eye, excessive sweating,runny nose and salivation, slowed heart beat, often fewer than 50per minute, and rippling of surface muscles just under the skin.

These symptoms are similar to allergies, colds or infections and canbe mistaken for those of influenza, upset stomach, heat stroke orheat exhaustion. Signs and symptoms associated with moderatelysevere OP and carbamate poisoning cases are similar to those found inmild poisoning but they also affect the victim in the followingways: inability to walk; chest discomfort and tightness; markedconstriction of the pupils; muscle twitching; involuntary urinationand bowel movement.

Signs and symptoms associated with severe poisoning by OPs andcarbamates are incontinence, unconsciousness and seizures. The orderin which these symptoms appear varies with the type of contact madewith the pesticide; if the product was swallowed then the stomachand other abdominal manifestations appear first, but if absorbedthrough the skin, then gastric and respiratory symptoms will appearat the same time.

Good antidotes have been developed and are usually available forvictims of OP or carbamate poisoning at emergency treatment centres,hospitals, and offices of many physicians. However, time isextremely critical and if pesticide poisoning is suspected, promptmedical treatment must be provided.

Symptoms and Antidotes for Pyrethroids: Systemic toxicityby inhalation and dermal absorption is low and only a few cases ofsystemic poisonings of humans by pyrethroids have been reported.Dermal contact results in skin irritations like stinging, burning,itching, tingling, leading to numbness. A few formulations ofpyrethroids have been reported to produce irreversible eye damagebut quite a few of them have demonstrated the symptoms of potentallergens. Deltamethrin was demonstrated to be an allergen at 0.13grams per 100 gallons when applied in dilute sprays by unprotectedapplicators in orchards.

Some pyrethroids are toxic by the oral route, but in general theiringestion presents relatively little risk. Incoordination, tremor,salivation, vomiting, diarrhea, and irritability to sound and touchmay be caused by large doses but rarely. Most of them are rapidlymetabolized and excreted. They are similar in action to OCs. Theyaffect the nervous system as stimulants through action on sodiumchannels in axonic membranes. Pyrethroids such as permethrin wasnoted in 1988 as a known oncogen.

Symptoms and Antidotes for Bipyridyls: Diquat and paraquatare the common bipyridyls of which the latter is more toxic. Thebipyridyls produce chronic abnormal cell growth in the lungs,cornea, and lens of the eye, nasal mucosa, skin and fingernails.Diquat affects the gastrointestinal mucosa, and the eye lens but itdoes not usually produce the deadly lung changes characteristic ofparaquat. Ingestion of diquat or paraquat causes severe irritationto the mucous membranes of the mouth, pharynx, esophagus and stomachand repeated vomiting usually follows. Diquat taken in large dosesalso produces restlessness and hyperexcitability and can affect the

lungs, kidneys, liver and adrenal glands. Fluid accumulation in thelungs can occur in one to three days and can be fatal. Lower amountsof paraquat can cause decreased urine volume in one to six daysbecause of kidney failure. Jaundice due to liver damage cansometimes occur. The initial phase is followed by a latent periodlasting up to two weeks. The victim may even appear to improveduring this period. However, since it concentrates selectively inthe pulmonary tissues, irreversible and progressive lung damageresults from rapid growth of connective tissue cells, which preventsproper lung function and eventually the victim dies from respiratoryfailure.

Dermal exposure to paraquat and diquat concentrates can cause severeskin irritations and burning, while contact with dilute liquids anddiquat dusts can cause slight to moderate irritation. Dermalabsorption of paraquat is apparently slight but diquat is absorbedand after repeated contact produces symptoms similar to thosefollowing ingestion.

Exposure to paraquat and diquat mists produces skin irritation,burning of the skin, nasal bleeding, irritation and inflammation ofthe mouth and upper respiratory tract, coughing and chest pain.Exposure to paraquat concentrates may cause blackening or loss ofthe nails and abnormal nail growth.

Specific antidotes are not available to counter the effects ofparaquat and other bipyridyl herbicides once significant exposuresand absorptions have occurred. In case of ingestion vomiting shouldbe induced immediately unless contraindicated by physical condition.The affected eyes should be flushed with water and the skin shouldbe washed with soap and water. As in other cases of pesticidepoisoning, medical treatment must be provided promptly.

Symptoms and Antidotes for Fumigants: The poisonous gasesor volatile liquids are toxic to insects, animals and humans. Theirtoxicity trails into the respiratory tract and is lethal to lifeforms by suffocation or by one of the mechanisms of toxification.Phosphine from aluminum phosphide; chloropicrin, ethylenedichloride, hydrogen cyanide, and methyl bromide are all commercialfumigants which are currently in use. Other brand name fumigants areBasamid®, Gas-Toxin®, Sprout-Nip®, Telone II®, Telone C-17®, Vapam®,and Vikane®. Fumigants like acrylonitrile, carbon tetrachloride,carbon disulfide, ethylene dibromide, hydrogen sulphide, Shell D-D®,and Vidden-D®, which have been de-registered but are lying in

authorized or unauthorized dumps or warehouses trickle out from thestorage for farm and even home use.

Different physiologic symptoms are produced by different fumigants,some of the initial symptoms caused by excessive exposure areheadache, dizziness, nausea and vomiting. Fumigant poisoningincidents occur quite frequently among workers in stored grain andmilling industry, among health care professionals engaged inlaboratory sterilization with methyl bromide, and among greenhouseand nursery workers, and pesticide applicators involved in soil orstructural fumigation.

Phosphine fumigants such as aluminum phosphide affect cell function,liver and lungs. Mild exposure symptoms appear in the form ofsensation of cold, chest pains, diarrhea and vomiting, while seriousexposures appear as cough, tightness in the chest, difficulty inbreathing, weakness, thirst and anxiety. Severe Exposures areindicated by stomach pain, loss of coordination, blue color of lips,pain in the limbs, enlarged pupils, choking and stupor. Severepoisoning leads to seizures, coma and death.

Cyanide fumigants such as acrylonitrile, Cyclon® (Zyglon-B®),calcium cyanide, M-44 coyote getter (sodium cyanide), and potassiumcyanide cause interference with normal cell metabolism. Presence ofcyano-haemoglobin produces a bright pink or red color in victims andmay induce sudden unconsciousness and respiratory arrest withoutwarning. Nausea, headache, and a sense of constriction in the throataccompany less severe exposures, followed by abnormally rapid ordeep breathing, dizziness and apprehension. Convulsions and suddencardiac arrest may occur as a result of massive respiratory exposureto cyanide.

Chloropicrin or methyl bromide, the halocarbon fumigants affect theCNS, lungs, heart, and liver in addition to the detoxifying enzymesystems. Those poisoned by such fumigants exhibit the signs andsymptoms common of fumigant poisoning, besides complaining ofabdominal pain, weakness, and showing slurred speech, mentalconfusion, tremors and convulsions similar to epileptic seizures. Afew liquid fumigants cause skin injuries indicated by areas ofredness or blisters that rupture leaving raw skin or deep ulcers.

Victims of fumigant inhalation must be moved to fresh airimmediately, keeping the individual quiet in a semi-recliningposition even if initial symptoms are mild. Mouth-to-mouth or mouth-to-nose resuscitation has to be given in case breathing has stopped

and cardiopulmonary resuscitation, CPR must be used if there is nopulse. Time is particularly critical in fumigant poisonings. Victimsmust therefore be given prompt medical attention.

Awareness on Pesticide Poisoning: Pesticide poisoning, bothacute and chronic have pathologies similar to many other medicalconditions. Consequently, clinicians have diagnosed pesticidepoisoning as the general conditions of poisoning.

The wide range of symptoms produced by pesticides neverthelessdemands that physicians and other health providers shouldfamiliarize themselves with pesticide poisoning. Physicians mustconsider pesticides in the differential diagnosis. Crop sheets canbe very useful to physicians in developing an awareness ofpesticides used locally. Physicians can get them from the Departmentof Agriculture or from Agricultural Extension Services and thetraining programs or from the Pesticide Manufacturers or theirAssociations.

Physicians and other health care professionals find crop sheetsuseful in dealing with suspected occupational diseases related topesticides. Crop sheets can provide information quickly and healthcare professionals can relate symptoms to possible causative agents.In addition to treatment they are of immense help in consideringother possible pesticide exposure cases that may involve pesticideapplicators, loaders, mixers, and handlers on the one hand andpesticide manufacturers, formulators, dealers, distributors,warehouse managers, and haulers, besides the users viz. homeowners,home garden pesticide users, and their children.

Diagnosis of Victims of Pesticide Poisoning: Victims ofpesticide poisoning frequently are under great stress and generallydo not have a clue to of their illness. This is quite often due tothe confusing symptoms which appear flu-like: headache, respiratoryproblems, nausea, and dizziness. Furthermore a large number ofchemical pesticides are neurotoxins, and hence symptoms such asmemory loss and confusion are fairly common. The confusion isconfounded by poisoning from chemical pesticides being due toexposure to more than one chemical. Despite the confusion, thevictim needs the most urgent attention, and needs to be protectedfrom the toxicity trailing to toxic end points. To add fuel to fire,it is quite common that the medical personnel providing treatmentmake a misdiagnosis and indications of toxicity end points thatinclude cancer, damage to organs like the liver, kidney or heart,

developmental disorders, damage to the immune system, centralnervous system, reproductive system, and to the genes are missed outcompletely. Even in the USA, according to a study of the issue forthe US EPA, only about 1% of the doctors are able to accuratelydiagnose cases of pesticide poisoning (Curt Guyette, Metro Times news editor e-mail:

cguyette@metrotimes.com).

The matter related to poisoning, even if it is unintentional,accidental and not fatal requires being reported to the appropriateauthorities including the law enforcement agencies, healthdepartments and Poison Control Centre, if any. It has been mandatedby law in almost every country to report laboratory examinationsthat reveal evidence of poisoning to the concerned authorities.Physicians, laboratory directors and others in charge of clinics orhospitals are accordingly responsible for reporting suspectedpoisoning to the concerned department or agency.

It may be seen from the above that constant investigation into theproperties particularly the toxicity of chemical pesticides has hadolder pesticides phased out and has subjected those remaining torestrictive registrations and with the decline in number of activeingredients and registered formulations, new and novel compounds areemerging but the scrutiny is severe. The new pesticides representthe fourth generation comprising less toxic, unusual modes of actionbut more environmentally compatible chemicals.

Some of the new products are the pheromone insecticides, thesulfonyl urea herbicides, and the sterol inhibiter fungicides,besides an increasing number of unique chemicals such as insectgrowth regulators and others that alter the growth of cells. Thedifficulty presented by the new products is that their clinicaltoxicology is still far from complete. These need much moreinvestigation since available publications on the new pesticidegroups are still scarce and the achievement of their predecessorshas brought almost each member of the class to disrepute.