Book: Pesticides Toxicity Specificity & Politics Chapter 3 - Chemistry & Specificity of Different Classes of Pesticides

CHAPTTER III

CHEMISTRY & SPECIFICITY OF DIFFERENT CLASSES OFPESTICIDES

It has been shown in the earlier chapter that the complex mix ofchemical pesticides with a variety of central atoms and a largevariety of substituents around them acts in different manner withthe targeted living species. The mechanism of this interactionforms the basis of their toxicity. This chapter is intended todescribe the chemistry of a few selected chemical classes ofpesticides with the purpose of illustration of the mechanism oftheir interaction with the targeted living species and the impactthat their usage has on the ecology including the livingenvironment. The organochlorines, organophosphates, carbamates,pyrethroids, phenoxys, thiocarbamates, and triazines are theimportant 14 classes of pesticides dicussed here. They form 70%of those that have been and are still in use. The pesticideclasses not discussed here include the amides, benzimidazole,benzonitrile, botanicals, dinitroanilines, phthalates, andtriazoles. The characteristics of the various pesticidesdescribed here are readily available on several websites,important among them being basic guides, carsoncouncil, EXTONETand PANNA.

ORGANOCHLORINES

Organochlorines, OCs are compounds that contain carbon, chlorine,and hydrogen.  They are a family of organic compounds in whichchlorine atoms have reduced the predominance of hydrogen atoms.They are produced by simple chlorination of organic compoundse.g. heptachlor and petcholine (a Pakistani product obtained bychlorination of the higher fraction of petroleum) or byinteraction of chlorinated hydrocarbons with other organiccompounds. DDT is for example prepared by the interaction ofchloral or chloral hydrate with chlorobenzene in the presence ofoleum as a dehydration agent. As is true of organic reactions,the interaction of various constituents does not yield just oneproduct but leads to by-products as well. In the case of OCs, theby-products include polychlorinated compounds such as the dioxinsand furans.

Production of OCs by replacement of hydrogen from a hydrocarbonis easy because of the gain in bond energy in forming the Carbon-Chlorine or C-Cl linkage. The C-Cl bond energy is very high andhence the replacement of hydrogen by chlorine atoms adds asignificant degree of stability to the final molecule. Thetremendous gain in bond energy suggests suggests that the breakdown of these bonds is not easy and explains why mostorganochlorine chemicals are so highly persistent in theenvironment. They are hydrophobic and highly insoluble in water,but are soluble in non-polar solvents such as petroleum. They arelipophilic and are easily absorbed by fats, fatty substances andadipose tissue of the body of an organism. They are resistant tomicrobial decay, are unaffected by elevated temperatures of up to800oC and are not readily oxidized under ambient environmentalconditions.

OCs like DDT, lindane, dieldrin, chlordane, 2,4,5-T, 2,4-D havebeen used as pesticides for the control of a large variety ofpests from the smallest in size like the fungi to the largestlike the locusts. Polychlorinated biphenyls, PCBs andpentachlorophenol, PCP are alsoOCs. While PCP was used as apesticide, PCBs were applied extensively in the electricityindustry as transformer coolants in the past.

The following are some of the OCs which were being produced andtraded extensively in the past but a majority of them have beenclassified as hazardous materials: Aldrin, chlordane chloroneb,chloropicrin, 4-CPA, D-D, DBCP, dieldrin, o,p-DDD, o,p-DDE, o,p-DDT, p,p-DDD, p,p-DDE. p,p-DDT, dicamba, dicofol, dieldrin, a-endosulphan, b-endosulphan, endrin, fenac, heptachlor,hexachlorophene, cis-hepta- chlorepoxide, hexachlorobenzene, a-hexachlorocyclohexane, b-hexachlorocyclohexane, g-hexachlorocyclohexane (lindane), methoxychlor, mirex, cis-permethrin, trans-permethrin, trifluralin, decachlorobiphenyl,trans-heptachlorepoxide, toxaphene, triclopyr.

They are all extremely hazardous compounds and most of them arehighly persistent in the environment. This property had giventhem the advantage of remaining effective against targeted pestsfor prolonged periods and that was one of the reasons for theirbecoming very popular products all over the world. The advantageseventually turned into disadvantages to the extent that most of

the OC pesticides that were pride of the time are banned. Theyhave gone from useful product to hazardous waste in a matter ofthirty years. Some of them are on the United Nations list ofPersistent Organic Pollutants, POPs and are the target ofcollection, segregation and disposal programme in many countriesunder UNEP auspices.

DDT was among the first organochlorines to have been used on alarge scale having been applied heavily on agricultural crops.This group of pesticides dominated the crop protection scenariofor almost 20 years before falling into disrepute and is nowamong the dreaded chemicals, called ‘dirty dozen’. Most OCpesticides are no longer sold for use in crop protection anywherein the world, except India. PCBs have properties in common withOCs but they are not considered as pesticides. They are by-products of OC production and were constituents of a variety ofindustrial products, such as electrical transformers but are nowplaced among the dirty dozen.

The OCs that had been in use since World War II were put to usein the public health sector. More than 5 million Italians weredusted with DDT in 1944 to suppress a typhus epidemic. DDTentered the market after the war while other OCs entered as beingsafe and effective pesticides. A sudden surge of pesticidepoisonings comprising cases of acute toxicity occurred with theintroduction of these compounds in the early 1950s. Fifteen totwenty years thereafter was about time for symptoms of chronictoxicity to emerge and by the mid-1960s cases of chronic toxicitysurfaced up. Credit goes to Raphael Carson for identifying theimpact of use of the persistent pesticides through herpublication: Silent Spring.

By this time i.e. the 1960s, it had become known that OCs areamong the most persistent groups of chemicals in the environment.This gave them the advantage of remaining effective againsttarget pests for prolonged periods which was the reason for theirbecoming very popular all over the world. They were however, alsofound to degrade slowly and to be fat-soluble. Soon enough, theirtoxicity was found to trail into and accumulate in food chains,and eventually in ending up stored in the adipose tissues ofhuman bodies. Living processes could under some circumstancesconvert these toxic chemicals into even more toxic by-products.Exposure to OCs was found to occur through the food chain but was

also found to occur through air pollution when the chemicalssomehow got adsorbed on the dust and soot particles and becameair-borne.

DDT: Dichlorodiphenyltrichoroethane, DDT or 1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene], or 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane was synthesized in 1873 in Germany andwas rediscovered in 1938 by Paul Muller  who was looking for achemical that had long-term activity against clothes moth.  Hefound subsequently that DDT was equally effective against fliesand mosquitoes. The finding immediately found extensiveapplication as a domestic and agricultural pesticide and was thepesticide of choice until it was banned by US EPA on January 1,1973 when its long residual effect and accumulation in food

chains was established(Basic Guide

to Pesticides: Their Characteristics and Hazards,

Rachel Carson Council and Toxic Release Inventory

Website, EXTONET, Extension Toxicology Network,

Pesticide Information Profiles Website) (S.J.

Gruber and M.D. Munn, USGS Fact Sheet 170-96,

September 1996).Fate in the Environment: DDT is very highly persistent inthe environment, with a reported half life of 2 to 15 years andis immobile in most soils. Routes of loss and degradation includethe slow processes of runoff, volatilization, and photolysis,besides biodegradation both aerobic and anaerobic. Breakdownproducts in the soil environment are DDE and DDD, which are alsohighly persistent and have similar chemical and physicalproperties. Due to its extremely low solubility in water, DDT isretained to a greater degree by soils and soil fractions withhigher proportions of soil organic matter. It may accumulate inthe top soil layer in situations where heavy applications are, orwere, made annually e.g. in apple orchards. DDT is invariablyfirmly adsorbed by soil organic matter, but it has been detectedalong with its metabolites in soil and groundwater where theorganisms present had consumed it. This is largely due to itshigh persistence and immobility or slight mobility. Over verylong periods of time it is able to leach into groundwater,especially from soils with low organic matter. Residues at thesurface of the soil are much more likely to be degraded ordissipated than those below several mm. Studies in desert soilshave shown that volatilization losses are significant: as high as

50% in 5 months and rapid due to low organic matter content, andhigh irradiation from sunlight. Volatilization loss varies withthe amount of DDT applied, proportion of soil organic matter,proximity to soil-air interface and the degree and extent ofexposure to sunlight.

Breakdown of DDT in Surface Water: DDT reaches surfacewaters primarily by runoff, atmospheric transport, drift, or bydirect application e.g. in the control of mosquito population.The reported half-life for DDT in the aquatic environment is 56days in lake water and approximately 28 days in river water. Themechanism for loss is volatilization, photodegradation,adsorption to water-borne particulates and sedimentation. Aquaticorganisms also take up and store DDT and its metabolites. Fieldand laboratory studies in the UK have demonstrated that verylittle breakdown of DDT had occurred in estuary sediments overthe course of 46 days. DDT has been widely detected in ambientsurface water sampling in USA at a median level of 1 part pertrillion.

Breakdown of DDT in Vegetation: DDT does not appear to betaken up or stored by plants to a great extent. It was nottranslocated into alfalfa or soybean plants, and only traceamounts of DDT or its metabolites were observed in carrots,radishes and turnips all grown in DDT-treated soils. Someaccumulation and slight translocation has been reported in grain,maize and rice plants, while residues were found primarily in theroots(Basic Guide to Pesticides: Their Characteristics and Hazards, Rachel Carson Council and ToxicRelease Inventory Website; EXTONET, Extension Toxicology Network, Pesticide Information Profiles Website).

Ecological Effects, Fate in Humans & Animals:Biological processes of the animal systems very slowly transformDDT. Initial degradation products in the mammalian systemsinclude DDE i.e. 1,1-dichloro-2,2-bis(p-dichlorodiphenyl)ethyleneand DDD i.e. 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, the twocongeners of DDT that are readily stored in fatty tissues. Thesecompounds in turn are ultimately transformed into DDA i.e.bis(dichlorodiphenyl) acetic acid by other metabolites(See Glossary for

definition) at a very slow rate. DDA and its conjugates(See Glossary for

definition) are readily excreted through the urine. Available datafrom analysis of human blood and fat tissue samples collected inthe early 1970s showed detectable levels in all samples, but a

downward trend in the levels over time. Later studies on bloodsamples collected in the latter half of the 1970s showed that DDTlevels were declining further, while DDT or metabolites werestill seen in a very high proportion of the samples. Accumulationof DDT or metabolites in high levels is noted in fatty tissuese.g. fat cells, the brain, etc. at levels of up to severalhundred times that seen in the blood. DDT or metabolites has alsobeen found to follow the pathway into milk by lactating women.

DDT has been linked to cancer and male infertility after it wasshown to block the action of male hormones. It has been banned inthe industrialized countries. The UNEP is trying to push througha worldwide ban on this hazardous chemical, but malariaspecialists have campaigned against this, since DDT is used inthe control of mosquitoes that carry the disease.

Effects on Birds: DDT was rated as slightly toxic to birds.Exposure to DDT among birds occurs mainly through the food chainby predation on aquatic and/or terrestrial species that carrysignificant quantities of DDT in their body, such as fish,earthworms and other birds. There has been much concern overchronic exposure of bird species to DDT and effects onreproduction, especially eggshell thinning and embryo deaths.

Eggshell thinning among fish eating birds proceeds through themajor metabolite, DDE which is effective in inhibiting thereaction of a specific enzyme that promotes the formation ofcalcium carbonate, the main constituent of eggshells, which areproduced in the body of the bird from calcium hydroxide andcarbon dioxide. The reaction having been inhibited, the eggshelldoes not contain as much calcium carbonate as to provide thedesired thickness to the cell. The egg is therefore thinner thannormal and vulnerable to breakage during incubation by accidentalcrushing of their own eggs by the adult birds. Laboratory studieson reproduction among these birds have demonstrated the potentialof DDT and DDE to cause subtle effects on courtship behavior,delays in pairing and egg laying and decreases in egg weight inring doves and Bengalese finches. There is evidence of thepossibility of synergism between DDT metabolites andorganophosphate (cholinesterase-inhibiting) pesticides to producegreater toxicity to the nervous system and higher mortality. PCBsmay likewise cause additive effects on eggshell thinning.

Effects on Aquatic Species: DDT is very highly toxic tomany aquatic invertebrate species. It is moderately toxic to someamphibian species and larval stages are more susceptible thanadults. In addition to acute toxic effects, DDT bioaccumulatessignificantly in fish and other aquatic species, leading to long-term exposure. This occurs mainly through uptake from sedimentand water into aquatic flora and fauna, and also fish. DDT uptakefrom the water is size-dependent with smaller fish taking uprelatively more than larger fish. A half-time for elimination ofDDT from rainbow trout was estimated to be 160 days. The reportedbioconcentration factor for DDT is 1,000 to 1,000,000 in variousaquatic species, and bioaccumulation may occur in some species atvery low environmental concentrations. Bioaccumulation may alsoresult in exposure to species which prey on fish or other aquaticorganisms e.g. birds of prey.

Earthworms are not vulnerable to acute effects of DDT and itsmetabolites at levels higher than those likely to be found in theenvironment, but they may serve as an exposure source to speciesthat feed on them. DDT is non-toxic to bees. Laboratory studieshad indicated that DDT released from stored body fat during longmigratory periods could affect bats.

DDT Relatives: DDT is not a single compound but is a familyof isomers viz. p,p’-DDT and o,p’-DDT and their breakdownproducts viz. p,p’-DDE, o,p’-DDE, p,p’-DDD, and p,p’-DDD. DDTdata are often expressed as the sum of these six components. DDEDichlordiphenyldichloroethylene is a product of the breakdown ofDDT in the body of most animals whose life processes tend todegradethe parent compound. DDE has been found in relativelylarger quantities in the body of female fish-eating birds.Biological degradation of DDT by these birds leads to theformation of DDE. DDD, or 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane is also produced by metabolism of DDT in someorganisms.

Dicofol or Benzenemethanol, 4-chloro-alpha-(4-chlorophenyl)-alpha-(trichloromethyl)-and also known as kelthane is an OCpesticide which is active against mites. This OC is used on awide variety of fruits, vegetables, ornamental plants and fieldcrops. It is manufactured from DDT. Recent developments in the

manufacturing processes produce technical grade dicofol whichcontains less than 0.1% DDT. Dicofol is moderately persistent insoil, with a half-life of 60 days.  It is vulnerable to chemicalbreakdown in moist soil and is subject to degradation by UVlight.  It is practically insoluble in water and is stronglyadsorbed by soil particles. It is therefore nearly immobile insoils and does not infiltrate groundwater.

Three other relatives of DDT are methoxychlor, ethylan, andchlorobenzilate. These pesticdes are strongly adsorbed by soilparticles.  They do not dissolve easily in water nor do theyevaporate easily into the air. They take several months to breakdown.

OTHER ORGANOCHLORINES: Chlordane, Aldrin, Dieldrin, Endrin,and Heptachlor belong to the chlorinated cyclodiene family. Ofall the pesticides, the chlorinated cyclodienes are the mostpersistent in the environment. Cyclodienes were developed afterWorld War II.  They are also persistent insecticides and arestable in soil.  Large volumes of these pesticides were used assoil insecticides for the control of termites and soil-borneinsects. During the 1950s, single treatments with Dieldrin,Aldrin, Chlordane, and Heptachlor could give months and years ofinsect control. A single Heptachlor treatment to alfalfa in earlyspring would keep killing insects through fall. Aldrin treatmentsto control grasshoppers on rangeland could provide control fortwo to three years. Chlordane treatments for termite control havelasted for more than 30 years. Tests for termiticidal activity ofchlordane that began before 1960 were still showing effectivecontrol from residual activity in the soil in 1992.

By the late 1960s and early 1970s, insect resistance to thechlorinated cyclodiene pesticides had reduced much of theirmarket share. Linkage of Aldrin to cancer had prompted itscancellation in 1972 i.e. much before FIFRA transferred pesticideauthority to EPA. Identification of this OC as a human carcinogenplaced many other chlorinated cyclodienes on the list ofcarcinogens and quickly reduced their markets. With increasingenforcement of regulation, the cyclodienes disappeared fromagriculture by the late 1970s and all their uses were banned by1987. They are however, still available on the asking for termitetreatment, suggesting either that they are still in production orthat the old over-produced stocks are not finished yet.

CHLORDANE is a member of a sub-group of the chlorinatedcyclodiene. It was used extensively in the past in home andagricultural applications. It forms a large group of individualcompounds like cis-chlordane, trans-chlordane, cis-nonachlor,trans-nonachlor, and oxychlordane.  Chlordane data are notexpressed for an individual compound but for the technical mix ofits most abundant and persistent components and metabolites. Chlordane family of compounds is very persistent in theenvironment; it is not easily metabolized, has a strong affinityfor body fats, and biomagnifies in aquatic food chains. It wasbeing widely used as a termite killer until 1988, when it wasbanned for this use also.

TRANS-NONACHLOR, one of the major constituents of chlordanewas used extensively prior to 1983 and was discontinued after1988 when it was found to be among the most bioaccumulative ofthe chlordanes and when its carcinogenic properties becameapparent.

ALDRIN AND DIELDRIN:  Aldrin is 1,4:5,8-Dimethanonaphthalene,1,2,3,4,10,10-hexachloro-, 1,4,4a,5,8,8a-hexahydro-, endo,exo-while dieldrin is 1,2,3,4,10,10-hexachloro-6,7- expoxy-1,4,4a,5,6,7,8 8a-octahydro-endo-5,8-dimethanonaphthalene.Dieldrin is closely related to its metabolic precursor aldrin andmuch of the toxicological information on aldrin is applicable todieldrin. Aldrin is produced by the Diels-Alder condensation ofhexachlorocyclopentadiene with bicyclo[2.2.1]-2,5-heptadiene.

Aldrin Dieldrin

Aldrin and dieldrin are both insecticides with similar structureswith regard to different positions of the substituents in thecyclodiene ring but with the difference that dieldrin is theepoxide of aldrin. Sunlight and bacteria modify aldrin to yieldits epoxide dieldrin and hence the latter is predominant in theenvironment. The living environment near hazardous waste sitesmay potentially be exposed to dieldrin since aldrin decomposes todieldrin from contamination of water supplies. Acceptable dietaryintake limits were exceeded in one community built over acontaminated site(Van Wijnen & Stijkel, 1988, IPCS, INCHEM,

http://www.inchem.org/documents/pims/chemical/pim573.htm).

Both of these pesticides were in extensive use during the 1950 to1970 period in protection of crops e.g. corn and cotton. The twoinsecticides get strongly adsorbed on the soil and evaporate intothe air very slowly.  They are also stored in the fat of anorganism and leave it very slowly.  US EPA banned all uses ofaldrin and dieldrin in 1974 except for the control of termitesowing to concerns on the damages done to the environment and thepotential harm to human health. All uses of the two pesticideswere banned by the US EPAgency in 1987. They are now groupedamong the dirty dozen and the POPs.

ENDRIN or 1,4:5,8-Dimethanonaphthalene, 1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-

endo,endo- is another insecticide of the chlorinated cyclodienegroup. It is more acutely toxic than the others in the group butis less persistent in the environment. An epidemic of endrinpoisoning broke out in Talagang in Attock district in Pakistan in1984. It so happened that a truck loaded with sugar bags wassomehow also got loaded on its way with quite a few canistersfull of endrin. The canisters were improperly sealed and this ledto spillage on the sugar bags and contaminated it heavily. Thesugar was distributed in 18 villages and soon enough there werereports of acute convulsions among 194 persons, 19 of whom died.

HEPTACHLOR is 1-exo-hydroxychlordene or 1-4,5,6,7,8,8-hexachloro- 3a,4,7,7a-tetrahydro-4,7-methanionden-1-ol. It isphotodegraded forming a cyclic ketone 1,1a,2,2,3, exo-6-hexachloro-1a,2,3,3a,5a,5b-hexahydro-1,3-methano-1 H-cyclobuta( c,d) pentalen-4-one. It was isolated in 1946 from technicalchlordane in USA as well as Germany(IARC, 1974, 1979). Heptachlor, whichwas first introduced as a contact insecticide under the tradenames Velsicol 104 and E 3314, was registered in the USA in 1952as a commercial insecticide for foliar, soil, and structuralapplications, and for the control of malaria.

Heptachlor is produced commercially by chlorination of chlordenein the presence of a catalyst(IARC, 1974) such as Fuller's earth.This reaction is usually carried out at 0 - 5°C in carbontetrachloride. The solvent is then distilled off, and theresidue recrystallized from methanol before grinding. It is anon-systemic stomach and contact insecticide. The use ofheptachlor is confined almost exclusively to the control of soilinsects and termites. It had found extensive use in the cottonindustry. Heptachlor epoxide, its biotransformed product is moretoxic than heptachlor.

It is interesting to note here that the cyclodiene insecticidesare optically active which has a remarkable effect on theirtoxicity. The difference of toxicity is remarkable between theenantiomers chlordane and chlordane epoxide, while that of theracemates of heptachlor is stronger than either enantiomers. Ithas also been found that there are considerable differences incomparative metabolism between enantiomers; (-)-chlordene epoxide

is itself toxic but (+)-chlordene becomes toxic after itsmetabolic conversion to the corresponding (-)epoxide(A. Miyazaki, M.

Sakai and S. Marumo, IIa-23 Abstracts, Fifth International Congres of Pesticide Chemistry, 1982, Kyoto).

ENDOSULFAN is 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzadioxathiepin 3-oxide. Technicalendosulfan is a mix of its two isomers: the alpha- and betaforms(EXTONET, Extension Toxicology Network, Pesticide Information Profiles Website). It belongsto the chlorinated cyclodiene subgroup of the OCs. It acts as acontact insecticide and acaricide and is highly toxic to a widevariety of insects and mites. It is used primarily for protectionof a wide variety of crops including tea, coffee, cashew nuts,fruits, and vegetables, besides rice, cereals, maize, sorghum, orother grains in addition to preservation of wood.

Endosulfan is chemically very close to other pesticides that havealready been banned in 10 countries worldwide including Colombia,Germany, Sweden, Norway, Singapore, Indonesia and the Philippinesbut not so far in a number of developing countries, includingIndia which is its largets producer. Its use is severelyrestricted in another 22 countries. Its breakdown products arepersistent in the environment, with an estimated half-life ofnine months to six years. It is known to bio-accumulate in humansand other animals, collecting particularly in the liver, kidneysand fatty tissues. There is strong evidence that endosulfan is anendocrine disrupting chemical. The neurotoxic endosulfan is ratedas a Category I pesticide with Extremely High Acute Toxicity.Health effects of accidental exposure include central nervoussystem disorders such as dizziness, convulsions and loss ofconsciousness. Endosulfan exposure has been linked to a number ofdeaths in the USA and in other countries(EXTONET, Extension Toxicology Network,

Pesticide Information Profiles Website).

Acute toxicity: Endosulfan is highly toxic by the oral anddermal routes, but only slightly toxic by inhalation. Its alpha-isomer is more toxic than the beta-isomer. Stimulation of thecentral nervous system is the major characteristic of endosulfanpoisoning. Symptoms of acute toxicity are the same on humans asthose related to chlorinated cyclodienes viz. incoordination,imbalance, breathing difficuly, vomiting, diarrhea, agitation,convulsions, and loss of consciousness. Reversible blindness hasbeen documented for cows that grazed in a field sprayed with the

compound. The animals completely recovered after a monthfollowing the exposure. In an accidental exposure, sheep and pigsgrazing on a sprayed field suffered from lack of musclecoordination and blindness.

Chronic toxicity: High rates of mortality were noted within 15days among rats given oral high doses, while medium doses causedliver enlargement and related effects over the same period.Administration of medium doses over 2 years to rats also causedreduced growth and survival. Changes were noted in kidneystructure, and in blood chemistry of the rats.

Reproductive effects: Rats fed with small doses of endosulfanfor three generations did not show observable reproductiveeffects, but medium intensity doses caused increased mortalityand resorption. Female mice fed with the compound for 78 weeks invery small doses suffered damage to their reproductive organs.Oral high doses for 15 days in male rats caused damage to thesemeniferous tubules and lowered testes weights. Reproductiveeffects on humans were not reported but have been observed aswill be apparent from the episode in Kerala, India.

Teratogenic and Mutagenic effects: A small oral dose ofendosulfan resulted in normal reproduction in rats in a three-generation study, but administration of medium and high dosesshowed abnormalities in bone development in the offspring.Endosulfan is mutagenic to bacterial and yeast cells. Themetabolites of endosulfan have also shown the ability to causecellular changes. This compound has also caused mutagenic effectsin two different mammalians. These evidences suggest thatexposure to endosulfan may cause mutagenic effects in humans ifexposure is large and over a long enough period.

Carcinogenic effects: In a long-term study done with bothmice and rats, the males of the two groups experienced such ahigh mortality rate that no conclusions could be drawn. However,the females of both species failed to develop any carcinogenicconditions 78 weeks after being fed diets containing high doses.The highest tolerated dose of endosulfan did not cause increasedincidence of tumors in mice over 18 months, and a later studyalso showed no evidence of carcinogenic activity in mice or rats.

Organ toxicity: Data from animal studies reveal the organsmost likely to be affected include kidneys, liver, blood, and theparathyroid gland.

Breakdown in water: Both isomers disappeared in 4 weeks in rawriver water at ambient temperature and light exposure.Degradation products appear within a week. The degradation inwater is faster: 5 weeks under neutral conditions than at moreacidic conditions or basic conditions which may take 5 months.Under strongly alkaline conditions the half-life of the compoundis 1 day. Large amounts of endosulfan can be found in surfacewater near areas of application and at low concentration atplaces further away.

Breakdown in vegetation: Endosulfan is rapidly degraded inplants to corresponding sulfate. On most fruits and vegetables,50% of the parent residue is lost within 3 to 7 days. Endosulfanand its breakdown products have been detected in vegetables atlevels of 0.0005 to 0.013 ppm, in tobacco, in various seafoods0.2 ppt-1.7 ppb, and in milk.

Fate in humans and animals: Endosulfan is rapidly degradedinto mainly water-soluble metabolites and eliminated in mammalswith very little absorption in the gastrointestinal tract. Thebeta-isomer is cleared from blood plasma of the rabbits morequickly than the alpha-isomer, with reported blood half-lives ofapproximately 6 hours and 10 days, respectively, which mayaccount in part for the observed differences in toxicity. Themetabolites are dependent on the mixture of isomers and the routeof exposure. Most of the endosulfan seems to leave the bodywithin a few days to a few weeks.

Ecological Effects: Endosulfan is highly to moderately toxicto bird species like the mallards, and pheasants. Male mallardsfrom 3 to 4 months old exhibited wings crossed high over theirback, tremors, falling, and other symptoms only 10 minutes afteran acute, oral dose. The symptoms persisted for up to a month ina few animals.

Effects on aquatic and other organisms: Endosulfan is veryhighly toxic to four fish species: rainbow trout, fathead minnow,channel catfish, and bluegill sunfish besides two aquatic

invertebrates: scuds (G. lacustris) and stoneflies (Pteronarcys).Bioaccumulation for the pesticide may be significant; in themussel (Mytelus edulis) the compound accumulated to 600 times theambient water concentration. It is moderately toxic to bees andis relatively nontoxic to beneficial insects such as parasiticwasps, lady bird beetles, and some mites.

Environmental Fate: Endosulfan is moderately persistent in thesoil environment with a reported average field half-lifeof 50 days. The two isomers have different degradationperiods in soil. The half-life for the alpha-isomer is35 days, and is 150 days for the beta-isomer underneutral conditions. The two isomers are not persistentunder acidic conditions. The compound is degraded in thesoil by fungi and bacteria. Endosulfan does not easilydissolve in water. It has a moderate capacity to adhere

or adsorb to soils. Transport of this pesticide may occur if itis adsorbed to soil particles in surface runoff. It was reportednot to be very mobile or to pose a threat to groundwater. It has,however, been detected in California well waters.

Endosulfan has during, environmental assessments in Kasaragoddistrict in the Indian State of Kerala, been found in high levelsin the local water, soil and plant samples and has been heldresponsible for the unusually high cases of diseases includingcerebral palsy and other disorders of the central nervous system,congenital neurological disorders, deformations, cancer,reproductive disorders and miscarriages(Sanjay Kumar, Down to Earth, New Delhi, June

28, 2002). It is linked to the destruction of many natural predatorsof tea mosquitoes normally found on cashew trees, such asGurugunji tree ants and spiders.

POLYCHLORINATED BIPHENYLS, PCBs: PCBs first became thechemicals of commerce in 1929. They found extensive applicationsin electrical transformers, cosmetics, varnishes, inks,carbonless copy papers, pesticides, in coatings for generalweatherproofing and fire-resistant coatings on wood and plastics.Their production has been banned in many countries since theywere found to degrade very slowly in the environment and to buildup in the food chain. PCB has 209 different isomers,stereoisomers and conformers, each having between 1 and 10

chlorine atoms locatedat various positions onthe two rings of itsmolecule.

ortho-PCBs, are the class of PCBs which have one or morechlorines in the ortho-position i.e. positions 2 or 6 in thephenyl ring. The non-ortho PCBs assume a flat or planarconformation, which is close to that of the dioxins. Chlorines inthe para-positions have been found to be easily biodegraded. Thisis perhaps the reason that the ortho-PCBs are present in theenvironment at a higher concentration than the non-ortho PCBs.PCBs have now been found to contaminate river bottom mud in manyregions. Exposure to PCBs and other related chemicals has beenshown to impair the reproductive and immune function of Balticseals, resulting in marked population declines(ENS, August 13, 2002).

PCBs owe their toxic propensity to the structural orientation oftheir molecules, which is responsible for inducing enzymicactivity in the cytochromes P450 and P448 and associated systemsin rats. It has been observed that the preferred mean orientationof the molecule has a role to play in the biological effects ofthe planar structures. Induction of P448 activity requires planarstructures as a geometric requirement for effective non-covalentinteractions. Since biphenyls other than the ortho-substitutedbiphenyls are planar or have coplanar conformers in largeproportion, the former are biodegraded by the enzymic systemwhile the others are persistent in the environment(J.D. McKinney, P.A. albro

and E.E. McConnel, Abstract IId-19, Fifth international congress of Pesticide Chemistry, Kyoto, 1982).

DIOXINS & Furans: Dioxins are a class of organochlorinesknown as polychlorinated dibenzo-p-dioxins, PCDDs, and the furansa family of polychlorinated dibenzofurans, PCDF.  The PCDDs andPCDFs are two classes of tricyclic aromatic compounds that havesimilar physical, chemical and toxicological properties, withsome of them being extremely toxic. They were the root cause ofthe accidents and intoxications such as the Yusho accident inJapan in 1968, and in Taiwan in 1979, the Seveco accident inItaly in 1976 and the Love Canal Controversy in USA in 1968(C.Rappe

and S.Marklund, Abstract Vb-5, Fifth international congress of Pesticide Chemistry, Kyoto, 1982).

The entire dioxin family consists of 75 different dioxins and 135different furans. They are products of thermal degradation ofpolychlorinated pesticides that act as precursors to the PCDDsand PCDFs. They are byproducts of the manufacture of chemicalssuch as those used for the production of organochlorinepesticides and wood preservatives, of the chlorine bleachingprocess used in some pulp and paper mills, and of the incompletecombustion of materials that contain both chlorine atoms andorganic matter. Although they are most often associated withindustrial activities, some natural occurrences such as forestfires are believed to make a small contribution to the presenceof dioxins and furans in the environment. The dioxin 2,3,7,8-tetrachloro-p-dibenzo-dioxin, 2,3,7,8-TCDD isthe most toxic of the dioxins and furans. Both 2,3,7,8-TCDD and1,2,3,7,8-pentaCDD can be obtained by the thermal degradation ofpentachlorophenol. The toxicity of mixtures of dioxins and furansis usually expressed in terms of this substance i.e. in 2,3,7,8-TCDD toxic equivalents e.g. TCDD EQs or TEQs, which is theconcentration of 2,3,7,8-TCDD that would be expected to producethe same type and degree of response as the chemicals involved. 

Dioxin is produced in all chemical reations involving freechlorine, whether they are associated with combustion, bleachingor chlorination to produce the OCs including DDT, Agent Orange,and chlorophenol or other CWAs such as mustard gas. It was amongthe waste products that were discharged near their site by DowChemical Company. It is claimed that the elevated levels ofdioxin found in Midland soil most probably came from the burningof chlorinated compounds, while the dioxin in the Tittabawasseeflood plain came from waste ponds at the Dow complex thatoverflowed in the 1986 flood.

The process of chlorine bleaching produces dioxin in theproduction of all cotton garments that must be bleached whitebefore their dyeing. Dioxin was found in cotton t-shirts in 1994by scientists at Bayreuth University in Germany.Pentachlorophenol, used overseas as a defoliant of cotton leaves,as a preservative to prevent mildew and also in starch sizingbaths during cloth production, has been found to be the source ofdioxin.

It is a potent toxin that can cause cancer and disrupt the immuneand reproductive systems. The Love Canal disaster was the resultof the dumping of wastes containing dioxin. The several Superfunddumping sites that were identified subsequent to the incidence ofthe disaster at Love Canal were reported to contain dioxins.

HCB, HEXACHLOROBENZENE, Lindane or benzenehexachloride,Gamma BHC and also known as Cyclohexane, 1,2,3,4,5,6-hexachloro-,(1-alpha,2-alpha,3-beta,4-alpha,5-alpha,6-beta) has been usedextensively as a fungicide for the protection of stored grain inwarehouses and silos. Its beta-isomer has profound insecticidalactivity. It occurs as a contaminant in the production of otherchlorinated solvents e.g. carbon tetrachloride and in theproduction of nitroso-rubber for tyres and its surface run offfrom the roadways is the pathway for its entry into theenvironment. Its endocrine disrupting effects had been wellrecorded before most of its uses were canceled in USA. Itsproduction has, however, not ceased and like other OCs it is alsoavailable on the asking.

CHLOROPHENOLS: Pentachlorophenol, PCP and tetrachlorophenol,TCP are the two members of this family that were being used forwood and leather preservation but their use has ever since beendiscontinued. Chlorophenols are partially and fully chlorinatedphenols which have fungicidal and bactericidal properties. Theyhave been used primarily for long-term wood preservation and forshort-term wood protection to control sap stain and mold onfreshly cut lumber. Leather production systems were also usingthe chlorophenols for protection against fungi and mold.

OCs HAZARDS: All organochlorine insecticides are neurotoxicor are nerve poisons. They interfere with transmissions of nerveimpulses and disrupt primarily the central nervous system. DDTand other OCs are fast acting poisons that affect sodium channelsin axonic membranes i.e. they act on the sodium channels in thenervous system and disrupt the movement of action potential alongthe nerves. There are uncontrolled repetitive spontaneousdischarges along the nerve which is cause for their typicalsymptoms viz. uncoordinated muscle tremors and twitches.Chlorinated cyclodienes on the other hand act on the GABAreceptors which function as a channel for chloride ions throughthe nerve membranes. They reduce the flow of chloride ions by

binding to the GABA receptors. Their typical symptoms includeconvulsions(IPCS, INCHEM, http://www.inchem.org/documents/pims/chemical/pim573.htm). and acting as hormone-mimics.

OCs have the capacity to disrupt the normal hormonal balance andthus disbalance the chemical messenger system of the body. Aswill be evidenced by the several episodes described in asubsequent chapter, this results in a range of illnesses such astesticular and breast cancer, low sperm counts, early onset ofpuberty and reduction in male births.

OCs have been found to be quick poisons and deaths due to acuteexposures have occurred during their extensive use in the past.In case of significant exposure to OCs pesticides the victimsusually develop nausea and vomiting followed by confusion,tremors, coma, seizures and respiratory depression. Death canoccur within 4 to 8 hours. Immediate effects appear in the formof convulsions which may occur with a delay of several days afterexposure; un-coordination; induced rapid metabolism of drugs andnaturally occurring steroid hormones; hypersensitivity of skin orface and extremities; headache; dizziness; nausea; vomiting;tremors; confusion; muscle weakness; involuntary eye movements;slurred speech; pain in chest and joints; skin rash; laboredbreathing; central nervous system stimulation followed bydepression; diarrhea; brain wave disturbances; hyperthermia;hypertension; salivation, and sweating.

Slow poisoning or chronic effects of the OCs are more of concernsince people exposed to small amounts of these pesticides over along period of time have been found to develop a variety of non-specific complaints including headaches, nausea, fatigue, muscletwitching, and visual disturbances. OCs ran into disrepute asaffecting the immune and endocrine gland functions, affectinghormone levels. Long-term effects include cumulative depositionin fatty tissues; transfers through placenta to fetus;passageinto milk of lactating mothers; carcinogens; suspect teratogens;suspect mutagens; fetotoxins; aplastic anemia; reproductiveeffects; testicular damage; eye damage; central nervous systemdamage; bladder, kidney, liver, lung and thyroid damage; bloodand spleen damage; anemia; recurrent asthma; irregular hearbeat;atrophy of adrenal cortex; behavior changes in young of motherexposed at even low levels during pregnancy; embryotoxin;decreased fertility; immunotoxin; abnormal brain waves; increased

mortality in young; teratogens; porphyria cutanea tarda; sleepdisturbance; hallucinations.

OCs were so extensively produced and used since World War II thatthey and their residues as well as leachates of their wasteproducts are now widely dispersed into the environment. Wholeanimal populations and a number of living areas all over theworld are therefore at risk. The environmental effects of the OCsinclude persistence, volatility and capacity to travel longdistances in the atmosphere and settling in distant locations;groundwater contamination; bioaccumulation and biomagnification;decreased fertility and eggshell thinning in birds.

Their modification by fish-eating birds and the resultingthinning of their eggshells has been described above in thedescription of DDT and DDE. Their biomagnification is the resultof accumulation in fatty tissues of higher-trophic-level animalsingesting them followed by their transfer to the humans or anyother consumer of the product from the fatty tissues.  They havebeen found to affect humans who drink the milk of a dairy cowwhich has ingested them since they are excreted in its milk fat. 

The intentional production followed by intentional as well asunintentional release and that too on a massive scale during the30 years after World War II have elevated the levels of the OCsin the biosphere to levels far beyond that in the naturalbackground. The impact of these releases on the environment hasbeen heavy as may be apparent from the following:

OC pesticides and PCBs persist in aquatic ecosystems of thestudy unit, although most of these compounds are no longerin use.

p,p'-DDE, a common breakdown product of DDT, is the mostfrequently detected compound.

Land use practices, such as irrigated farming, drylandfarming and urbanization have greatly influenced thedistribution of organochlorines.

OCs are transported to the aquatic ecosystems by the forcesof erosion.

Concentration of several OCs exceeded the level provided in theguidelines for the protection of wildlife in streambed sedimentas well as fish in many areas of the user countries and hencewildlife in such areas has been at great risk. It has been known

since the early 1970s that DDT causes eggshell thinning e.g. ofthe bald eagle and other birds. Many OC pesticides and PCBs havebeen linked to hormone disruption and reproductive problems inaquatic invertebrates, fish, birds, and mammals since that time.These effects combined with a slow rate of breakdown make manyOCs a long-term environmental risk. Lindane has been linked tobreast and other cancers, and fertility problems; it has beenbanned in the UK and USA. A recent study suggests increasedpancreatic cancer mortality among long-time residents in areas ofhigh application rates of 1,3-d, which has been classified by USEPA as probable human carcinogen, captafol,pentacholoronitrobenzene, PCNB, and dieldrin (Am. J. Ind. Med. 43:306-313, 2003.

© 2003 Wiley-Liss, Inc.).

Despite the knowledge that many organochlorine pesticides areextremely persistent in the environment, and despite the cautioususe followed by a ban on the manfacture of many of them, with theprovision of Prior-Informed Consent, the OCs continue to bemanufactured in the USA and other pesticide manufacturingcountries, including India for use in developing countries whereenforcement of environmental legislation is faced withinnumerable difficulties. Although concentrations of thesecompounds are usually large where they are used the most, such asin agricultural areas, low levels of some compounds, such as DDT,are being found in surface and ground water all over the world.

It has been found that the agricultural soils of themanufacturing countries like the USA have been impacted the mostby the intentional as well as unintentional release of the OCs ortheir degradation products. The agricultural fields of thesecountries act as reservoirs of the contaminants as is revealed bya strong correlation between the percentage of irrigated landwith gravity irrigation, the amount of sediment in streams, andthe concentration of DDT in streambed sediment and fish. The sameis not the case with the developing countries since in the firstinstance they were late starters and secondly because they didnot use massive dosages for the simple reason that they were notavailable in large quantities.

OCs at Landfill Sites: It is common to find a range ofOCscompounds within the various old landfills. Some residues,according investigations at Love Canal, the Homebush Bay, and theTower Chemical, come from containers of household pesticide

products containing insecticides like dieldrin and chlordane,while others constitute the industrial wastes that were dumped atthe site.

Remediation of the contaminated sites involves excavation ofseveral hundred tons of OC wastes, which include thechlorophenols, chlorobenzenes, and other chlorinated compoundsbesides dioxins. These organochlorine wastes are subjected to atwo-stage remediation process. The first stage involves simplepurging with steam to desorb the soil and the second involvesdechlorination using an alkaline solution. The final products ofthis reaction are common salt, carbon dioxide and water.

ORGANOPHOSPHATES

Organophosphates, OPs are a group of organic compounds containingphosphorus. The generic term organophosphate includesinsecticides containing pentavalent phosphorus as the centralatom. They are generally phosphoric acid esters having beenderived from phosphoric or thiophosphoric acid and are generallythe most toxic of all pesticides to vertebrate animals.  Theyare, unlike the persistent OCs, chemically unstable.  They exerttheir toxic action by inhibiting the cholinesterase enzymes ofthe nervous system which results in the accumulation ofacetylcholine.  The continued accumulation interferes withneuromuscular junctions producing rapid twitching of thevoluntary muscles and eventually paralysis.

The following compounds are among the main OP group pesticides:Acephate, Acephate-met, Azinphos-ethyl, Azinphos-methyl,Bensulide, Chlorpyrifos, Cythioate, Dialifor, Diazinon,Dichlorvos, Dicrotophos, Dimethoate, Disulsulfoton, Ethoprop,Fenamiphos, Fosetyl-al, Glyphosate, Isazophos, Isofenphos,Malathion, Methamidophos, Methidathion, Methyl-parathion,Mevinphos, Monocrotofos, Naled, Omethoate, Parathion, Phosmet,Profenphos, Ronnel, Stirofos, Sulprofos, SulfoTEPP, Temephos,TEPP, Trichlorfon, and Vamidothion.

The OPs may be grouped into three sub-groups: (i) Aliphatic OPsthat are simple derivatives of phosphoric acid with short carbonchains.  Acephate, monocrotophos, dichlorvos, dicrotophos,

dimethoate, disulfoton, malathion, methamidophos, mevinphos,oxydemetonmethyl, and trichlorfon belong to this sub-group.

(ii) Phenyl OPs that are derivatives of phosphoric acidcontaining a benzene ring with one of the hydrogen atoms of thering displaced by a bond to phosphorus and other linkagesdisplaced by different substituents. The phenyl derivatives aregenerally more stable than the aliphatic OPs and hence theirresidues are longer lasting.  Isofenphos, Parathion, profenophos,stirofos, and sulprofos belong to this sub-group.

(iii) Heterocyclic OPs that are derivatives of phosphoric acidcontaining ring structures having different or unlike atoms. Theheterocyclic rings may have one or more of the carbon atomsdisplaced by oxygen, nitrogen, or sulfur atom and may be three,five, or six membered.  Some of these OPs are azinphosmethyl,chlorpyrifos, dialifor, diazinon, methidathion, and phosmet. These are complex compounds and generally have longer lastingresidues than many of the aliphatic or phenyl OPs.  They havenumerous breakdown products which make it difficult to appraisetheir residues in the laboratory.

Gerhard Schrader, as mentioned earlier developed the chemistry ofthe nerve gases and the organophosphate insecticides during the1930s. Esters of dialkylamidophosphorocyanidic acids were foundby him in 1937 to have extremely high mammalian toxicity inaddition to insecticidal activity. The highest military commandencouraged him to develop nerve gases for use as CWAs and heobliged with the finding of more potent groups viz. the esters ofthe alkylphosphonofluoridic acids. Tetraethylpyrophosphate, TEPP,was developed as the first OP insecticide. In the late 1930s, heproduced the two nerve agents Ethyl N-dimethylphosphoroamidocyanidate or Tabun, which is 20 times more toxic toman than phosgene, and isopropyl methylphosphonofluoridate orsarin. By the end of the war, Schrader had producedorganophosphate insecticides like ethyl and methyl parathion,schradan, TEPP, and dozens of other OPs.

TEPP proved to be an effective insect killer but it could not beutilized for this purpose for two reasons, one that it was highlytoxic to mammals and the second that it is highly unstable in thepresence of water and was found to break down rapidly in humidenvironment. Parathion, O,O-diethyl O-p-nitrophenyl

phosphorothioate and its oxygen analogue Paraoxon, O,O-diethyl O-p-nitrophenyl phosphate prepared in 1944 had wide spectruminsecticidal activity besides having desirable properties likelow volatility, stability in water and mild basicity in theenvironment. 

The disrepute of the OCs and the success of the OPs andcarbamates bestowed a feat on parathion and its analogue in themid-1960s. In these success stories, however, only the short termeffect was being noted and admired while their chronic toxicityremained a non-issue. Parathion was found to be highly effectiveagainst insects as well as humans and other mammals.  Over theyears many other OPs were synthesized with lower toxicity butwith their chronic toxicity yet to be determined. Parathionremained in the market as one of the most commonly usedpesticides for almost 10 years but it had to be banned when itstoxic effects were found similar to exessive stimulation ofcholinergic nerves resulting in the release of too much of thenerve transmitter: Acetylcholine.  Dubois and his colleguesshowed in 1948 that toxicity could be alleviated to a certainextent by administration of Atropine, an antagonist of theacetylcholine receptors. 

Chemistry of OPs: OPs, as stated earlier are esters ofphosphoric acids.  Their chemical structures may be groupedinto the following six groups:

Phosphate Phosphorothioate Phosphorodithioate

Phosphorothiolate Phophonate Phosphoramide

The following are some of the OPs belonging to the six groups:

Phosphate Phosphorothioate

Phosphorodithioate

Phosphorothiolate

Phosphonate

Phosphor

amide

TEPP Parathion Disulfoton Echothiophate DFP

Dichlorvos Diazinon Malathion Trichlorphon

Chlorfenvinphos

Methylparathion

Chlorothion

The basic chemical structure of the organophosphates is asfollows:

The leaving group X is an important constituent of the OPmolecules.  It is the ability and ease of this group to leavewhen the molecule binds to a site at the target that bestows theOPs their toxicity.

Effects/Symptoms of Attack: Investigations were under wayduring World War II in England, Germany and the USA on the nervetransmitter substance, acetylcholine and its esterase. Once thenature of the nerve acetylcholine was established, experimentswere undertaken on its interaction with phosphorylatedderivatives. Independently, German and British scientists workingfor agricultural chemical companies established theanticholinesterase potency of the organophosphate insecticides.The OPs damage the nerve functions by stopping the acetylcholinemediated signaling thus allowing the signal to persist at anexaggerated level.  The effects/symptoms of toxicity appear inthe form of exaggerated responses to the normal functions ofacetylcholine.

Immediate effects: Immediate effects of toxicity of OPs appearin the form of behavioral disturbances; lack of coordination;muscle twitching; headache; dizziness; nausea; anxiety;irritability; loss of memory; sleep pattern change; restlessness;weakness; tremor; abdominal cramps; diarrhea; sweating;salivation; tearing; excessive nasal discharges; blurred vision;constriction of pupil; slowed heartbeat; confusion; incontinence,and hypertension.

Long-term effects: Delayed neurotoxicity is manifested bytingling and burning sensations in the limb extremities followedby weakness in the lower limbs and ataxia. This culminates intoparalysis, which generally affects the upper limbs. Recovery isseldom complete in adults; with the passage of time the clinicalpicture changes from flaccid to a spastic type paralysis(WHO, 1986, p.

59). The following effects are generally observed, some of thembeing cumulative: persistent anorexia; weakness; malaise; nervedamage via destruction of myelin sheath around nerve fibres;carcinogens; mutagens; fetotoxins; hormonal inhibition; eyedamage; suspect mutagens; suspect carcinogens; sterility andimpotence; embryotoxins; suspect teratogens; immunotoxins;indication of bone marrow damage and aplastic anemia; death ofwhite blood cells; sperm and other reproductive abnormalities;suspect viral enhancers; ulcers; abnormal brain waves; reducedprotein synthesis in fetus; liver damage; kidney damage;suppressed antibody production; and decreased auditory attention,visual memory, problem solving, balance, and dexterity.

Environmental effects: OPs have been found to be surfacewater contaminants; to affect the feeding habits of birds; to beembryotoxic to them, and to affect their breeding. They have beenheld responsible for the death of large numbers of birds on turfand in agriculture.

Delayed Neurotoxic Effects: Exposure to OPs generally leads toOrganophosphorous-Induced Delayed Polyneuropathy, OPIDP i.e. aneurodegenerative disorder induced by OPs.  Abou-Donia andLapadula(M.B. Abou-Donia and D.M. Lapadoula, 1990, Mechanisms of organophosphorous ester-induced delayed neurotoxicity: Type I

and Type II.  Annual Rev Pharmacol Toxicol. 30: 405-440. Abou-Donia, MB. 1992. Triphenyl phosphite: A type II organophosphorous compound-induced delayed neourotoxic agent. I Organophosphates: Chemistry, fate, and effects, eds JE Chambers and PE LEvi, pp 327-351. NY: Academic

Press.) have characterized it as delayed onset of prolonged locomotorataxia resulting from a single or repeated exposure to an OPcompound. The clinical signs appear after two to three weeks ofexposure to a toxic dose.  Symptoms emerge in the form of longterm effects noted above. The biochemical signs includedegeneration of the axons and myelin of the long sensory andmotor pathways of the spinal cord and of the large fibres of theperipheral nervous system(Abou-Donia, 1992).

The cause of OPIDP is related to the phosphorylation and aging ofan enzyme called Neurotoxic Esterase found in nerve tissues. Thephysiological role of this enzyme, is unclear but it has beennoted that this enzyme is inhibited whenever an OP is found to bean inducer of OPIDP which is unrelated to acetylcholinesterasefunction. OPs that do not cause OPIDP do not inhibit this enzyme.OPIDP poisonings have been known to occur among the humans in thepast.  The OP: tri-ortho-cresyl-phosphate, TOCP is one of themost notorious of these poisons.  Several massive outbreaks haveoccurred in the past in Morroco and other countries as a resultof contamination of the drink or food with lubricating oil thatcontained some TOCP.

Chemical emergency of its own kind due to a toxic chemical waspossibly first recognized in the early 1930s and that was causedby TOCP. This chemical has widely been used as a plasticizer andfor making heat resistant greases. TOCP was responsible for theoutbreak of a disease which came to be known as Ginger Paralysissince it was contracted by the consumption of an alcoholicextract that had been adulterated with it to cut the strongginger taste. The 50,000 Americans in the mid-western and south-western states of USA, who drank the alcoholic extract of Jamaica

ginger during the Prohibition days in 1930, experienced numbnessof the arms and legs, followed by either temporary or permanentparalysis. The injury was related directly to the amount ofextract consumed but in each case the symptoms were typical ofOPIDP. There was an initial recovery from nausea and diarrhea,followed eight to fifteen days later by paralysis of limbs andarms. 15 of the 50,000 victims died while hundreds werepermanently paralysed(K.P. Shea, Nerve Damage, Environment, 16, 6, 1974).

TOCP claimed another 2000 victims in 1959 at Meknes, Morocco.Here its greasy form was used as an adulterant in the cookingoil. Greases and fats have been used in the developing countriesas adulterants by sheer ignorance of their toxic properties. Thecontaminated oil was sold in several markets in the poor sectionsof Meknes. One of the families got suspicious of the dark colourof the cooking oil and hence they fed some food cooked with it tothe family dog to see if it had any adverse reaction.Neurodegenerative disorders induced by OPs are delayed reactionstypical of OPIDP and hence symptoms did not appear immediately.Nothing happened to the dog and so the family ate the food. Theyand the dog both were paralysed within a few days(K.P. Shea, Nerve Damage,

Environment, 16, 6, 1974). Deaths due to cooking oil contaminated by greasysubstances have also occurred in Pakistan around the same timebut they were not adequately investigated.

Phosvel or leptophos is another OP that caused an epidemic ofparalysis and killed over 1200 water buffaloes in Egypt in 1971by the delayed nerve poisoning typical of OPIDP. The animals lostcoordination in the hind quarters due to damage to the motornerves that retarded their ability to stand or walk, and withlarge doses paralysis became more general and continued to thefront and upper extremeties. It resulted in death when chestparalysis caused asphyxiation and respiratory failure(Abou-Donia,

Neurotoxic effect of Leptophos, Experientia, 30(1), 63, 1974).

Carcinogenesis: Organophosphates were in the past considerednon-carcinogenic.  A number of OPs are now known to causemalignant tumor growth in experimental animals.  It has beensuggested that OPs act as alkylators to induce tumor formation. However, even the OPs that have been shown to be good alkylatorsin the laboratories were not shown to induce the function in theliving systems. 

Immunologic effects: Certain OPs have been shown to suppresssome aspects of the immune system in experimental animals. Methylparathion administration resulted in decreased resistanceto certain pathogens in rabbits and parathion decreased humoralimmunity, but only at near-lethal doses.  There are nowincreasing evidences that OPs do indeed depress the immuneresponse. 

Malathion: Malathion or diethyl (dimethoxy thiophosphorylthio)succinate is an alkyl OP. It is prepared by the esterification ofthe dimethoxyphosphinothioyl)thioic acid. The diethyl fumuratemoiety is the leaving group which along with the thioic acid isresponsible for the toxicity of this OP. Technical grademalathion is known to contain 11 impurities which together can beabout 10 times more potent than the laboratory grade in causingdeath to laboratory animals.  One of the main impurities is iso-malathion, the other is the ester diethyl fumarate while theothers are the transformation products like malaoxon which is aknown carcinogen, and 0,S,S-trimethyl phosphorothioate, which isbeing investigated for carcinogenic effects, if any. Diethylfumurate which has an ester linkage in malathion, has also beenfound synergistic with it.

Malathion was originally invented by American Cyanamid in theearly 1950s, and registered in the USA in 1956. Severalcompetitors, including Cheminova, began to manufacture malathionwhen the American Cyanamid patent expired in the late 1960s. In1984, US EPA issued a call for additional data to support themalathion registration. Cheminova and American Cyanamid jointlygenerated the necessary data. In 1988, US EPA initiated areregistration process for malathion products, which requiredregistrants to submit much more comprehensive data, the cost ofwhich was prohibitive for most of the existing producers. OnlyAmerican Cyanamid and Cheminova were then left in the market. In1991, Cheminova purchased the malathion interests of AmericanCyanamid and now there are only two suppliers of Malathion in theworld market viz. Cheminova and Ficon Organics Limited in India.In the domestic market of India, Hindustan Insecticides Limitedand Cyanamid India manufacture and supply Malathion.

Malathion witnessed renewed interest from health authorities,particularly WHO after the ban on DDT and BHC. However, its

application during the malaria eradication program in Pakistan in1976 had a disastrous effect; 2,800 out of 7,500 spray men,became poisoned and 7 died(Archives in Toxicology, 42:95-106, 1979). The majorcontaminant of the poisoning was identified as isomalathion whichwas produced during storage of the formulated malathion. It wassubsequently confirmed that there is actually an increase in theamount of malathion impurities during simple storage of overthree to six months. This makes malathion far more toxic thanwhen it is formulated by the manufacturers. The amount ofimpurities has also been shown to increase rapidly when exposedto temperatures over 50oC(Effect of Impurities on the Mammalian Toxicity of Technical Malathion

and Acephate. Journal of Agricultural Food Chemistry, 25, 946-953, 1977). Subsequentexperiments have also shown that the impurities in technicalmalathion that contributed to the epidemic of malathion poisoningcomprised various trimethyl phosphorothioate and -dithioateesters. These impurities acted by blocking the carboxyesterase-and the glutathione-dependent routes of malathion detoxificationactually potentiated the toxicity of malathion to mammals(K.H. Summer

and J.K. Malik, AbstractVIa-12, Fifth International Congress of Pesticide Chemistry, 1982, Kyoto). It hasbeen suggested that the esterase-inhibitory activity attributedto technical-grade malathion is due largely to the action ofmalaoxon (WHO, 1986, IPCS INCHEM, 1997).

Malathion poisoning cases have brought forward some additionalinformation on its toxicity trail on degradation in theenvironment. It was found that although malathion breaks down ina matter of hours of its application yet it was not known that itbreaks down into compounds which are more poisonous thanmalathion itself(N. E. Barlas, Department of Biology, Faculty of Science, Hacetepe University,

Turkey, www. Safe2Use.com). Furthermore the disappearance of pesticideresidues at a given location does not mean the end of theproblem; they can be translocated, biolocated or converted intomore dangerous chemicals e.g. the residues like the highly toxicmalaoxon. It was also found that exposure of mice to technicalgrade malathion and the breakdown products viz. the residues likethe highly toxic malaoxon together have extensive detrimentaleffects over a period of 15 weeks of treatment. Technical malathion has the ability to harm life by weakening theimmune system and the ability of the body to fight infections,gradual damage to the nervous system during pregnancy, theability to cause accelerated aging to organs such as the liverand kidneys, as well as the potential to accelerate damage to the

genes on the DNA molecule. Malathion does not appear to producepoint mutations in standard gene mutation assays in bacteria, butits metabolite malaoxon was positive in mammalian cell mutationtests. 

The agrochemicals used by the formulators of pesticides areinvariably technical grade or concentrated formulations, meaningthereby that the chemicals are moderately to highly toxic and canbe hazardous to human beings, if inappropriately handled orunnecessarily exposed. Technical grades also imply that theirpurity and impurities may differ from source to source andtherefore great care needs to be taken to account for thecomposition in making a formulation. Furthermore agrochemicalsusually have a relatively high vapour pressure and hence arehazardous through inhalation. They also have a high absorptionrate so that they can kill insects immediately on contact. Thisproperty renders the human skin vulnerable to their absorption.It is, accordingly very unsafe to formulate household pesticidesfrom technical grade agrochemicals.

Toxicological Effects: Acute toxicity: Malathion is slightlytoxic via the oral and dermal routes. Its effects are similar tothose observed with other OPs, except that larger doses arerequired to produce them. It has been reported that single dosesof malathion may affect immune system response. Symptoms of acuteexposure to OP or cholinesterase-inhibiting compounds include thefollowing: numbness, tingling sensations, incoordination,headache, dizziness, tremor, nausea, abdominal cramps, sweating,blurred vision, difficulty breathing or respiratory depression,and slow heartbeat. Very high doses result in unconsciousness,incontinence, and convulsions or fatality. The acute effects ofthis OP depend on product purity and the route of exposure. Otherfactors which influence its observed toxicity include the amountof protein in the diet and gender (EXTONET).

Chronic toxicity: Chronic health effects of this OP includeallergic reactions, behavioral effects, ulcers, eye damage,abnormal brain waves suspected mutagen and teratogen, delayedneurotoxin, and immuno-suppression. Malathion has been found toinduce neurodegenerative disorders, carcinogenesis andimmunologic effects. Studies published by Environmental Researchsuggest that malathion and its oxygen analogue malaoxon are both

quite carcinogenic and have been linked with increased incidenceof leukemia in mammals(Stephen L. Tvedten, safe2use).  Malathion produceddetectable mutations in three different types of cultured humancells, including white blood cells and lymph cells. Very lowdoses of malathion, of the same order as are within acceptablelimits for human intake, can produce direct mutagenic effects. 

This OP is a potent sensitizer of the skin and has been found tocause allergic dermatitis in human beings after a singleexposure. Subsequent exposures to even much smaller doses ofmalathion produced even more intense chromatid breaks, anindication that the toxic effects are cumulative. Certainpersons, when exposed to malathion and other OPs quickly getsensitized and develop skin eruptions on subsequent exposures,even to low quantities.  Contact with malathion can elicitallergic reactions ranging from a mild rash to severe asthma-likesymptoms.  Neurological abnormalities are reported to haveoccurred in rats exposed to low levels even though the chemicalwas undetectable in their blood samples.  This OP also producesrapid eye inflammation and edema.  The quantity of impurities aswell as inert materials that it contains increases with the agingof this OP and greatly enhances its toxicity by inhibiting thedetoxifying enzymes in the person or animal poisoned.

A study undertaken in the early 1990s after the aerial sprayingsof malathion over human populations in California found thatchildren who had been exposed to malathion during the secondtrimester of pregnancy were showing over two and a half timesmore gastrointestinal disorders (affecting the stomach and smallintestines) in comparison to children not exposed to malathion during pregnancy(No Spay Coaliton,

Journal of Pesticide Reform, New Living Magazine, Epidemiology, North American Butterfly Association,

Maryland Department of Health & Mental Hygiene, www. Safe2Use.com)

Two studies have shown that technical grade malathion containschemical impurities which can weaken immune system function,including weakening of a type of white blood cell calledcytotoxic lymphocytes, CTL, which attack cancer cells and virusinfected cells.  These lymphocytes can also attack viruses in thebody.  Malathion has been shown to significantly weaken theability of CTL to perform their function effectively since thelymphocytes are not able to remove viruses or cancer cells

efficiently and thus result in mild to serious healthdisorders(Journal of Immunology, 140 (2) : 564-570, University of Virginia, www. Safe2Use.com). 

Ecological Effects: Malathion is moderately toxic to birds.90% of the dose to birds is reported to have metabolized andexcreted in 24 hours via urine. It has a wide range of toxicitiesin fish, extending from very highly toxic in the walleye tohighly toxic in brown trout and the cutthroat trout, moderatelytoxic in fathead minnows and slightly toxic in goldfish. Variousaquatic invertebrates are extremely sensitive. It is highly toxicto aquatic invertebrates and to the aquatic stages of amphibians.Because of its very short half-life, malathion is not expected tobioconcentrate in aquatic organisms. However, brown shrimp didshow an average concentration several hundred times the ambientwater concentration in two separate samples. This OP is highlytoxic to honeybees(EXTONET).

Environmental Fate: Malathion has low persistence in soil withreported field half-lives of 1 to 25 days. Degradation in soil israpid and is related to the degree of soil binding. Breakdownoccurs by a combination of biological degradation and non-biological reaction with water. If released to the atmosphere,this OP breaks down rapidly in sunlight, with a reported half-life in air of about 1.5 days. It is moderately bound to soils,and is soluble in water, and hence poses a risk of groundwater orsurface water contamination in situations which may be lessconducive to breakdown. The compound was detected in 12 of 3252different groundwater sources in two different states of the USA,and in small concentrations in several wells in California(EXTONET).In raw river water, the half-life of this OP is less than 1 week,whereas it remained stable in distilled water for 3 weeks.Applied at 0.5 to 4 kg/acre in log ponds for mosquito control, itwas effective for 2.5 to 6 weeks. In sterile seawater, thedegradation was found to increase with increased salinity. Thebreakdown products in water are mono- and dicarboxylic acids.Residues of malathion were found mainly associated with areas ofhigh lipid content in the plant. Increased moisture content wasfound to increase the rate of degradation (EXTONET).

PARATHION: By chemical composition this organophosphatepesticide is O,O-diethyl O-4-nitrophenyl phosphorothioate andbecause of the two ethyl groups on the phosphorothioate moiety it

is also known as ethyl parathion. Likewise the homologous OP withtwo methyl groups on the phosphorothioate moiety is known asmethyl parathion. Presence of the p-nitrophenyl group places itamong the class of phenyl OPs. The p-nitrophenyl group whichacts as the leaving group in this case, is cause for enhancingthe toxicity of the OP in addition to its higher stability.Schrader and his colleagues synthesized this OP in 1944 but itsintroduction in the market had to wait for the displacement ofthe organochlorines. 

Parathion hydrolyzes under mildly basic conditions. It is stableat normal temperatures but decomposes at temperatures above120oC, developing sufficient pressure to cause containers toexplode. Thermal decomposition releases toxic gases such asdiethylsulfide, sulfur dioxide, carbon monoxide, carbon dioxide,phosphorus pentoxide, and nitrogen oxides. Parathion poses a fireand explosion hazard in the presence of strong oxidizers. It canattack plastics, rubber and organic coatings. Consequentlypersons working with this OP for long periods of time in theindustrialized countries were, until all its uses were banned,advised to have frequent blood tests of their cholinesteraselevels. If the cholinesterase level fell below a critical point,no further exposure was allowed until it returned to normal. Nosuch consideration of safety issues was introduced among users indeveloping countries.

Parathion was used until 1992 as a broad spectrum pesticide forthe control of many insects and mites. It was used for its non-systemic, contact, stomach and fumigant actions and had a widerange of applications on many crops against numerous insectspecies. It enjoyed a notable position as a chemical of commercefor its short time effects, ignoring the long term effects whichsurfaced up after 15 to 20 years in the 1980s. Its high toxicityand risks of exposure to agricultural workers and to birdspresented compelling evidence to US EPA to cancel all its uses onfruit, nut and vegetable crops in 1992. An estimated 2,000 tonsof methyl parathion is, however, still being used annually in theUSA. Approximately 95% of this is used on cotton, soybeans, fieldcorn, peaches, wheat, barley and rice. Despite the damage done byparathion to the environment in the countries of its origin beingcolossal, its use in developing countries is continuing since theproduction has not been stopped in the producing countries.

Toxicological Effects: Acute Toxicity(EXTONET): Highenvironmental temperatures or exposure of parathion to visible orUV light increase its toxicity. It is highly toxic by all routesof exposure. In common with other OPs, it is a cholinesteraseinhibitor. When inhaled, the first effects are usuallyrespiratory and may include bloody or runny nose, coughing, chestdiscomfort, difficulty in breathing or short breath, and wheezingdue to constriction or excess fluid in the bronchial tubes. Skincontact causes localized sweating and involuntary musclecontractions. Eye contact causes pain, bleeding, tears, pupilconstriction, and blurred vision. It causes hyperkeratinizationor thickening and roughening of the skin(EXTONET).

Following exposure by any route, other systemic effects beginwithin a few minutes or are delayed for up to 12 hours. Theseinclude pallor, nausea, vomiting, diarrhea, abdominal cramps,headache, dizziness, eye pain, blurred vision, constriction ordilation of the eye pupils, tears, salivation, sweating, andconfusion. Severe poisoning affects the central nervous system,producing un-coordination, slurred speech, loss of reflexes,weakness, fatigue, involuntary muscle contractions, twitching,tremors of the tongue or eyelids, and eventually paralysis of thebody extremities and the respiratory muscles. In severe casesthere is also involuntary defecation or urination, psychosis,irregular heart beats, unconsciousness, convulsions and coma.Death has often been caused by respiratory failure or cardiacarrest(EXTONET).

Chronic Toxicity(EXTONET): Repeated or prolonged exposure toparathion results in the same effects as acute exposure includingthe delayed symptoms. Other effects reported in workersrepeatedly exposed include impaired memory and concentration,disorientation, severe depressions, irritability, confusion,headache, speech difficulties, delayed reaction times,nightmares, sleepwalking and drowsiness or insomnia. Aninfluenza-like condition with headache, nausea, weakness, loss ofappetite, and malaise has also been reported. One study foundthat small dietary doses produced toxic symptoms, growthretardation and death in rats. In another feeding study, the samesmall dietary doses for 2-years had no effect on rats, while

medium intensity doses produced only slight signs of toxicity andgrowth retardation, but no deaths(EXTONET).

Reproductive Effects: Once in the bloodstream, parathion cancross the placenta. Repeated feedings to female rats beforemating has been reported to result in adverse effects on thereproductive system. In laboratory animals, such as rats andmice, several such effects are seen. Fewer pups are born to damsfed parathion. These pups have reduced birth weight and do nottend to survive as well as normal pups(IARC Monographs, 16).

Teratogenic, Carcinogenic & Mutagenic Effects: Whileparathion is toxic to the fetus, it has not been reported tocause birth defects. However, Parathion is now known as apossible carcinogen. Dietary doses of parathion failed to producedominant mutagenic effects in mice. Mammary tumor incidence inthe parathion-treated rats was, in a study found to be 14.3%(EXTONET). Organ Toxicity: Parathion primarily affects the nervous systemthrough inhibition of cholinesterase. In humans poisoned withparathion, an increase in brain weight occurs, the reason ormechanism for this occurrence has not been reported. Delayedneurotoxicity is not been reported to be a problem withparathion(Toxicol. 23 (4):267-279. 1982).

Fate in Humans and Animals: Parathion is readily absorbedinto the bloodstream from the skin, lungs or gut. It is rapidlydistributed through the body. The liver metabolizes parathioninto the active metabolite: paraoxon, which actually inhibits thecholinesterase. Paraoxon is further metabolized to compounds suchas paranitrophenol which is readily excreted in the urine.Parathion may be stored in fat. Unlike the OCs e.g. DDT,parathion is rapidly degraded once it is mobilized from thestorage sites in the fats(EXTONET).

In two short-term studies, the proliferation of the milk ductstructures was examined in animals. It was found that the mammarytumor incidence in the parathion-treated rats was 14.3% and inmalathion-treated animals it was 24.3%. The studies confirmedthat the tumors were related to cholinesterase because treating

the animals with atropine allowed the milk ducts to developnormally and prevented the mammary cancers. They further indicatethat the cholinergic effects of OPs may, at sufficiently highexposure levels, promote the development of mammarytumors(Organophosphate Pesticides Linked To Mammary Tumors In Rats  A Review of: Cabello G,

Valenzuela M, Vilaxa A, Duran V, Rudolph I, Hrepic N, Calaf G., Environmental Health Perspectives:

2001, 109(5), 471-479).

Ecological Effects: Parathion is extremely toxic to birdssuch as mallards, pigeons, quail, sparrows and grouse. It is lesstoxic to pheasants. Among aquatic life forms, parathion ismoderately toxic to fish and aquatic invertebrates like crayfish,snails and worms. It has profound effects on the non-targetspecies like the honeybees and the mule deer in which some fatstorage of parathion is reported to occur. Upon release from fatstorage, however, this OP is rapidly broken down and eliminated.Bioconcentration of parathion is low to moderate. There is noevidence of its bioaccumulation in cattle, sheep or rabbits(EXTONET).

Breakdown in Soil, Water and Groundwater: Soilmicroorganisms, sunlight, plants and water degrade parathion. Itis bound firmly on soil particles and is degraded by biologicaland chemical processes within weeks. Degradation is faster inflooded soil. Residues of this OP can persist for many years, butusually remain in the upper 6 inches of the concerned soil.Adsorbed parathion is subject to degradation by microorganismsand chemical hydrolysis. It usually disappears in open waterwithin a week, mainly by adsorption to suspended particles andbottom sediments. Photodegradation occurs on soil surfaces. Thehalf-life for photo-degradation of parathion in water is 1 to 10days. Sunlight converts this OP into the more toxic metaboliteparaoxon. The breakdown of parathion in soil or water increaseswith increasing alkalinity(EXTONET).

Breakdown in Vegetation: Parathion residues on foliage decay,following spray applications, with a half-life of 1 day, reachinglow levels in a week or two. In orange groves, the half-life ofparathion is as long as one month but is usually closer to 10 to15 days. Most crops tolerate this OP very well. Only at highapplication rates do apples, cucumbers, and tomatoes suffer fromparathion misuse(EXTONET).

CHLORPYRIFOS: By chemical composition, Chlorpyrifos is O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate. Its otherwell known trade names are Dursban and Lorsban. Presence of thetrichloropyridyl group places it in the heterocyclic sub-group ofOPs. The trichloropyridyl moiety is the leaving group that leavesas trichloropyridinol, TCP and is responsible for enhancing thetoxicity as well as its stability. It was introduced in themarket in 1965 as a broad-spectrum insecticide, originally usedfor killing mosquitoes. It acts on pests primarily as a contactpoison, with some action as a stomach poison and was being usedinitially against common residential and crop pests. Its salespicked up in response to the needs of a good termiticide and tofill the vacuum created by the ban on OCs but is no longerregistered for this use. Almost all homeowner uses of this OPwere banned in USA as of December 31, 2001 but its manufacturefor other uses e.g. in agriculture continues.

Toxicological Effects, Acute Toxicity: Chlorpyrifos ismoderately toxic to humans; its poisoning affects the centralnervous, cardiovascular and respiratory systems, besides the skinand eye. In common with other OPs, symptoms of its acute toxicityinclude the following: numbness, tingling sensations,incoordination, headache, dizziness, tremor, nausea, abdominalcramps, sweating, blurred vision, difficulty in breathing orrespiratory depression, and slow heartbeat. Very high dosesresult in unconsciousness, incontinence, and convulsions leadingto death. Persons with respiratory ailments, recent exposure tocholinesterase inhibitors, cholinesterase impairment, or livermalfunction remain at increased risk from exposure to this OP.Its acute exposure does not produce immediate symptoms which maybe delayed by 1 to 4 weeks. In such cases, numbness, tingling,weakness, and cramping appear in the lower limbs and progress toincoordination and paralysis. Improvement may occur over monthsor years, and in some cases residual impairment may continue.Plasma cholinesterase levels activity has been found to beinhibited when chlorpyrifos particles are inhaled(EXTONET). Chronic Toxicity: Repeated or prolonged exposure to this OPmay result in the same effects as acute exposure including thedelayed symptoms. Some of the major long term effects noted amongbirds are leg weakness and delayed neurotoxicity; among the fish

and molluscs the effects are noted on their growth; those oncrustaceans are on their reproduction system and among someplants they are observed as toxicity. Effects reported in workersrepeatedly exposed to this case are the same as those observed inthe case of other OPs and include impaired memory andconcentration, disorientation, severe depressions, irritability,confusion, headache, speech difficulties, delayed reaction times,nightmares, sleepwalking, and drowsiness or insomnia. Aninfluenza-like condition with runny nose, headache, nausea,weakness, loss of appetite, and malaise has also been reported.Technical chlorpyrifos fed to dogs for 2 years producedenlargement of liver at moderate dose, with signs ofcholinesterase inhibition being reported at much lower levels. Ameasurable change in plasma and red blood cell cholinesteraselevels was seen in workers exposed to chlorpyrifos spray. Humanvolunteers who ingested small doses of chlorpyrifos for 4 weeksshowed significant plasma cholinesterase inhibition(EXTONET).

Reproductive effects: When rats were fed a small dose for twogenerations, the main effect observed was a slight increase inthe number of deaths of newborn offspring. No teratogenic effectsin offspring were found when pregnant rats were fed high doses.There is also no evidence that chlorpyrifos is mutagenic orcarcinogenic. It primarily affects the nervous system throughinhibition of cholinesterase, the enzyme that is required forproper nerve functioning. The long-term effects on mammalsinclude cumulative, fetotoxic and delayed neurotoxic effects,besides sterility and impotence in bulls(EXTONET).

Fate in Humans and Animals: Absorption of chlorpyrifosinto the bloodstream proceeds readily through thegastrointestinal tract on being ingested, through the lungs onbeing inhaled, and the skin on dermal exposure. This OP and itsprincipal metabolites are eliminated in humans primarily throughthe kidneys. It is detoxified quickly in rats, dogs, and otheranimals and the major metabolite found in rat urine after asingle oral dose is trichloropyridinol, TCP, which does notinhibit cholinesterase activity and is also not mutagenic.Chlorpyrifos does not have a significant bioaccumulationpotential. A portion is stored in fat tissues following anintake, but it is eliminated in humans, with a half-life of about62 hours. When it was fed to cows, unchanged pesticide was found

in the faeces, but not in the urine or milk. However, it wasdetected in the milk of cows for 4 days following spray dippingwith a low concentration emulsion(EXTONET).

Ecological Effects: Chlorpyrifos is moderately to veryhighly toxic to birds: pheasants, mallard ducks, house sparrows,and chickens. At high doses mallards laid significantly fewereggs. There was no evidence of changes in weight gain, or in thenumber, weight, and quality of eggs produced by hens fed averagedietary levels of this OP(EXTONET).

Effects on aquatic organisms: This OP is very highly toxicto freshwater fish, aquatic invertebrates and estuarine andmarine organisms. Cholinesterase inhibition was observed in acutetoxicity tests of fish exposed to very low concentrations of thisOP. Application of low concentrations of chlorpyrifos can causefish and aquatic invertebrate deaths. Its toxicity to fish isrelated to water temperature. When fathead minnows were exposedto Dursban for a 200-day period during which they reproduced, thefirst generation of offspring had decreased survival and growth,besides having a significant number of deformities. This occurredat low level exposure for a 30 day period. This OP accumulates inthe tissues of aquatic organisms. Studies involving continuousexposure of fish during the embryonic through fry stages haveshown significant bioconcentration values. Due to its high acutetoxicity and persistence in sediments, chlorpyrifos can present ahazard to sea bottom dwellers. Smaller organisms appear to bemore sensitive than larger ones. Wildlife and honeybees are posedwith serious hazards due to aquatic and general agricultural usesof this OP(EXTONET).

Environmental Fate: Chlorpyrifos has been detected ingroundwater, and in surface water. Its breakdown is slow in soiland groundwater. It is adsorbed strongly by soil particles andbeing almost insoluble in water, it is leached only slowly but itultimately contaminates the groundwater. The half-life ofchlorpyrifos in soil is usually between 60 and 120 days, but canrange from 2 weeks to over 1 year, depending on the soil type,climate, and other conditions. The soil half-life of chlorpyrifoswas from 11 to 141 days in seven soils ranging in texture fromloamy sand to clay and with soil pHs from 5.4 to 7.4. It was

found less persistent in soils with high pH. The adsorbed OP issubject to degradation by UV light, chemical hydrolysis and bysoil organisms. Trichloropyridinol, the principal metabolite isadsorbed weakly to soil particles and is moderately mobile andpersistent in soils(EXTONET).

Concentration and persistence of chlorpyrifos in water depends onthe type of formulation. Large increase in its concentrationoccurs when emulsifiable concentrates and wettable powders arereleased into water. With increase in adherence to sediments andsuspended organic matter, concentration of the pesticide rapidlydeclines. Increase in concentration of this OP is not as rapidfor granules and controlled release formulations in the water,but the resulting concentration persists longer. The primaryroute for the loss of chlorpyrifos from water is most likelyvolatilization. Volatility half-lives of 3.5 and 20 days havebeen estimated for pond water. The photolysis half-life ofchlorpyrifos is 3 to 4 weeks during summer. Its change into othernatural forms is slow. It is unstable in water, and the rate atwhich it is hydrolyzed increases with temperature. The rate ofhydrolysis is constant in acidic to neutral waters, but increasesin alkaline waters(EXTONET).

Chlorpyrifos is toxic to some plants, such as lettuce. Residuesremain on plant surfaces for approximately 10 to 14 days. Thereare evidences that this OP and its soil metabolites canaccumulate in certain crops(EXTONET).

CARBAMATES This class of pesticides comprises the esters of carbamic acidwith variations of substituents on the carbamate moiety producinga large number of products that have been used as insecticides,herbicides, fungicides, and fumigants and thus provides aversatile group that fits into almost all needs of protectionagainst pests. Most of the commercial carbamates are relativelynontoxic to warm blooded animals but quite a few that were beingused as pesticides have of late proved to be potentially toxic.Several such carbamates have come under close scrutiny byregulatory authorities the world over. Some of them have beenfound to contaminate ground water and their use has beenrestricted, while there are some that have lost their

registrations on several crops or for several formulationsbecause of toxicity to wildlife. A group of carbamate fungicides,the ethylene bis-dithiocarbamates, EBDCs have come under US EPAregulatory action because they have been found to pose humanexposure problems.

There are several classes of carbamates: the insecticidescomprise N-dimethylcarbamates, N-methylcarbamates, heterocycliccarbamates, and oxime carbamates; the herbicides that are mainlythiocarbamates, and the dithiocarbamates like EBDC that arefungicides. The thiocarbamates and dithiocarbamates workprimarily by disrupting cell membranes and cell division. Thecarbamate insecticides include such chemically diverse productsas Pirimor®, Sevin®, Carzol®, Furadan®, and Temik®.

Plant products containing the carbamate linkage have been usedsince ancient times as a poison. One such plant Physostigmavenenosumwas was being used in West Africa to detect crimes. Thesuspects in crime were forced to eat beans of this poisonousplant. If the suspect survived, the tribe assumed him to beinnocent otherwise he was declared guilty. It so happened thatthe innocent suspects, knowing that they were innocent, ate thebeans quickly. The beans, because of their potent emetic actioncaused vomiting and the beans came out without doing much harm tothe suspect. The guilty, because of the guilt feeling, ate thebeans slowly and got themselves subjected to slow poisoning oftheir systems. Killing of the suspects provided the final proofof the crime.

The nature of this poison was investigated by European chemistswho isolated the active principle, physostigmine or eserine in1864. Eserine was in 1925 found to be an ester of carbamic acid.The basis for its action on the body had to await the discoveryof acetylcholine as a neurotransmitter substance and the role ofacetylcholinesterase in degrading acetylcholine(Douglass E. Stevenson,

Physician’s Desk Reference to Pesticide Health Hazards, http://www-aes.tamu.edu/doug/MED/PGPHH.HTM).

The carbamates, as described arlier were produced as CWAs duringthe studies undertaken by British and Canadians since 1940. N-dimethylcarbamates were produced in 1947 as the firstinsecticidal carbamates by Geigy of Switzerland while Carbaryl orSevin®, the heterocyclic carbamate that came into prominence was

produced by Union Carbide in 1956. Most of the later carbamatesturned out to be aromatic, phenolic rather than naphtholic(DouglassE. Stevenson, Physician’s Desk Reference to Pesticide Health Hazards,

http://www-aes.tamu.edu/doug/MED/PGPHH.HTM).

Substitution of the proton on the carbamyl nitrogen atom by avariety of functional groups results in derivatives with reducedanticholinesterase activity. The necessary condition for asuitable insecticidal carbamate is lipid solubility and adequatestructural complimentarity to acetylcholine. Such carbamates havebeen highly favoured that have the N-substituted carbamateretained as part of the molecule that has a less basic and morelipid soluble component. Examples of carbamates pesticides are:Aldicarb, Asulam, Barban, Bendiocarb, Carbaryl, Carbofuran,Dioxacarb, Diram, Ethiofencarb, Fosamine ammonium, Methiocarb,Methomyl, Propham, Propoxur, Thiophanate ethyl, Thiophanatemethyl, Trimethacarb

Mode of Action: Carbamates behave as synthetic neurohormoneswhich produce the toxic effects by inhibitingacetylcholinesterase so that acetylcholine accumulates at thesynoptic junction and thus damages the nerve functions. Thesymptoms accompanying their action in intact animals aretypically cholinergic. They include lachrymation, salivation,myosis, convulsions, and fatality. The symptoms of poisoning bycarbamate insecticides follow the pattern described earlier forthe pesticides that act as neurotoxins. The carbamates typicallyshow erratic patterns of selective toxicity to insects. Thehousefly is rather insensitive; the honeybee is sensitive, whilethe German cockroach is almost immune(EXTONET).

Acute Toxicity: Carbamates cause sensory and behavioraldisturbances typical of neurotoxicity: incoordination; depressedmotor functions; malaise; muscle weakness; dizziness; sweating;headache; salivation; nausea; vomiting; abdominal pain; slurredspeech; difficult breathing; blurred vision; muscle twitching;spasms; convulsions; diarrhoea; depression of cholinesteraseseven more prominently in fetus, and skin sensitization(EXTONET).

Chronic Toxicity: Carbamates cause memory loss; behavioraldefects; cataracts; spleen, bone marrow, liver and testes damage;

reduced sperm levels; increased organ weights; decreased bodyweights; anemia; decreased hemoglobin; decreased fertility fromovary and testes damage. They are mutagens and suspect mutagens;carcinogens and suspect carcinogens; teratogens; fetotoxins;suspect viral enhancers; and may convert to N-nitroso compoundsin soil and in vivo with saliva(EXTONET).

Environmental effects: Carbamates can disrupt behavior offish; they are teratogens to fish; toxic to earthworms(thiophanate methyl); cause reduction in earthworm andinvertebrate populations (WHO 1986, pp. 56-57), and are groundwatercontaminants(EXTONET).

SEVIN OR CARBARYL is an archetypal carbamate pesticide andwill be described here as typifying this class. Chemically it is1-naphthol N-methylcarbamate and is produced by the interactionof methyl isocyanate and 1-naphthol. Its trade names includeCarbamine, Denapon, Dicarbam, Hexavin, Karbaspray, Nac, Ravyon,Septene, Sevin, Tercyl, Tricarnam, and Union Carbide 7744. It isa general use wide-spectrum pesticide which has been used in thecontrol of over 100 species of insects on citrus, fruit, cotton,forests, lawns, nuts, ornamentals, shade trees, and other crops,as well as on poultry, livestock and pets. It is also used as amolluscicide and an acaricide. Carbaryl is effective both asstomach as well as contact pesticide.

Carbaryl is produced as a solid which is stable to heat, lightand acids under storage conditions but it is not stable underalkaline conditions. It is non-corrosive to metals, packagingmaterials, and the application equipment. It is found in alltypes of formulations including baits, dusts, wettable powder,granules, oil, molasses, aqueous dispersions and suspensions.

Acute Toxicity: Carbaryl is a moderately to very toxicpesticide. It can produce adverse effects in humans by skincontact, inhalation and ingestion. The symptoms of acute toxicityare typical of the other carbamates: direct contact of the skinor eyes with its moderate levels cause burns; inhalation oringestion of very large amounts are toxic to the nervous andrespiratory systems and causes nausea, stomach cramps, diarrheaand excessive salivation. Other symptoms at high doses includesweating, blurring of vision, incoordination, and convulsions.

Occupational workers are potentially vulnerable to its exposurethrough inhalation or diffusion through the skin. The highestrisk of exposure to the general public is through ingestion ofcontaminated food. Occupational and accidental illnesses due toexposure to carbaryl have been reported and fatalities throughintentional ingestion have been documented(EXTONET).

Chronic Toxicity: Although it may cause minor skin and eyeirritation, carbaryl does not appear to be a significant chronichealth risk at or below occupational levels of exposure. Malevolunteers who consumed low doses of carbaryl for six weeks didnot show immediate effects, but tests indicated slight changes intheir body chemistry.

Reproductive and Teratogenic Effects: No reproductiveor fetal effects were observed during a long-term study on ratswhich were fed high doses of carbaryl. The evidence forteratogenic effects due to chronic exposure is minimal in testanimals. Birth defects in rabbit and guinea pig offspringoccurred only at dosage levels which were highly toxic to themother. A 1980 New Jersey epidemiological study found no evidenceof excess birth defects in a town sprayed with carbaryl for gypsymoth control. There is only limited evidence that carbaryl causesbirth defects in humans. The US EPA has concluded that carbaryldoes not pose a teratogenic risk to humans if used properly(EXTONET).

Mutagenic Effects: Numerous studies indicate that carbarylposes only a slight mutagenic risk. However, carbaryl can reactwith nitrite under certain conditions to give rise to N-nitrosocarbaryl. The latter has been shown to be highly mutagenicat low levels in laboratory test systems. This may be a concernto humans because there is a possibility that carbaryl, apesticide, and nitrite, a substance found in food additives andin human saliva, may react in the human stomach to formnitrosocarbaryl. Carbaryl has been shown to affect cell mitosisi.e. cell division, and chromosomes in rats(EXTONET).

Carcinogenic Effects: Carbaryl did not cause tumors in tenlong-term and lifetime studies of mice and rats. Rats wereadministered high daily doses of the pesticide for two years, andmice for eighteen months, with no signs of carcinogenicity.

However, N-nitrosocarbaryl, formed by the reaction of carbaryland nitrite, has been shown to be carcinogenic in rats at highdoses. Also, mice exposed to carbaryl in the product,tricaprylin, for four weeks each, developed lung tumors(EXTONET).

Organ Toxicity: Ingestion of carbaryl affects the lungs,kidneys and liver. Inhalation also affects the lungs. Nervedamage can occur after administration of high doses for 50 daysin rats and pigs. Several studies indicate that carbaryl canaffect the immune system in animals and insects. These effectshowever have not been documented for humans(EXTONET).

Fate in Humans and Animals: Most animal and humansystems, readily degrade carbaryl and rapidly excrete it in theurine and feces. Workers occupationally exposed by inhalation tocarbaryl dust excreted 74% of the inhaled dose in the urine inthe form of a breakdown product. This is consistent withinformation on other species which excreted nearly three quartersof a dose in their urine within 24 hours of administration. Themetabolism of up to 85% of carbaryl occurs within 24 hours afteradministration(EXTONET).

Ecological Effects: Carbaryl is lethal to many non-targetinsects. The pesticide is more active on insects than on mammals.The damages done to honeybee populations in sprayed areas havebeen shown earlier to have posed serious problems. Carbaryl ismoderately toxic to aquatic organisms, such as rainbow and laketrout, bluegill, and cutthroat. It is also moderately toxic towild bird species, with low toxicity to Canada geese(EXTONET).

Accumulation of carbaryl can occur in catfish, crawfish, andsnails, as well as in algae and duckweed. Residue levels in fishwere 140 fold greater than the concentration of carbaryl inwater. Carbaryl generally does not pose a significantbioaccumulation risk in alkaline waters due to its rapidmetabolism and biodegradation, but it does so under slightlyacidic conditions(EXTONET).

Fate in the Environment: Degradation of carbaryl occurs inthe soil mostly through sunlight and interaction with bacteria,while in crops it occurs by biochemical processes involving

hydrolysis in the plant system. In the soil it is bound byorganic matter and can be transported in soil runoff. It has ahalf-life of 7 days in aerobic soil and 28 days in anaerobicsoil. Its degradation is strongly dependant on acidity andtemperature of the environment(EXTONET).

Carbaryl has a short residual life on treated crops. It remainsat the application site, where it is slowly taken into the plantand metabolized. Its insecticidal properties are retained for 3to 10 days. Losses of carbaryl in the environment are due toevaporation and uptake into plants while those due to breakdownby sunlight are not significant. Metabolites of carbaryl havelower toxicity to humans than the pesticide itself(EXTONET).

Carbaryl degrades in pond water by bacteria through thebiological processes and not much by evaporation. Carbaryl has ahalf-life of from 1 to 32 days in pond water. Degradation ofcarbaryl was 50% within a 24 hour period in a stream thatreceived it in its drainage from a forest which had been sprayedwith this pesticide. It has been shown to degrade more slowly inthe presence of mud in aquatic habitats. It has been detected ingroundwater in three separate cases in California. It has a half-life in the air of one to four months. Crops, shade trees, shrubsand other vegetation in bloom are not recommended for spray withcarbaryl as bee kills have been reported(EXTONET).

PYRETHRINS AND PYRETHROIDS

Pyrethrins invariably refer to natural insecticides derived fromchrysanthemum flowers, while pyrethroids are the syntheticchemicals. Pyrethrum is a general name covering both sets ofcompounds.

For over 160 years, pyrethrum has been safely and effectivelyused as a pesticide the world over. The flowers of the daisyspecies, Chrysanthemum cinerariaefolium, Chrysanthemum coccineum etc.contain a mixture of pleasant-smelling non-nitrogenous esterscalled the pyrethrins. Over 5,000 tons of the flowers incompressed bales were imported in the USA in 1940 for extractionof the oleoresin in the form of a mix of several pyrethrins.Japan has, on the other hand been growing its own chrysanthemumfor the last 120 years having transplanted the same from Africa.

The flowers of the daisy species are harvested shortly afterblooming; they are then dried and powdered. The powdered materialis extracted with solvents which when removed give an oleoresincontaining the pyrethrins, all having highly unusual insecticidalproperties. The insecticidal properties are due to their uniqueability to repel insect pests and were considered as posinglittle threat to the environment. The pyrethrin containing dustsand extracts usually have an active ingredient content of about30%. The most prominent pyrethrins are pyrethrin-I and pyrethrin-II. They also have four other active ingredients: Cinerin I andII and Jasmolin I and II.

Pyrethrins constitute the natural mix of compounds usedprimarily for the control of mosquitoes, cockroaches, beetles,flies and lice. Pyrethrin dust containing only 0.3% to 0.5%active material is used at rates of up to 75 kg/ha for thecontrol of insects in horticultural crops. Other pyrethrincompounds are used in grain storage and poultry sheds and on dogsand cats for the control of lice and fleas.

The natural pyrethrins are effective contact poisons. Mostinsects are highly vulnerable to pyrethrins at lowconcentrations. Pyrethrins affect the central nervous system andquickly penetrate the nerve system of the insects causingimmediate knockdown. A few minutes after application, the insectcannot move or fly away. Flying insects drop almost immediatelyon exposure. Fast knockdown, however, does not necessarily meandeath, since many insects may recover after the initialknockdown. For this reason, pyrethrums are mixed with a synergistsuch as piperonyl butoxide, PBO or an OP, or carbamate to assurea lethal dose by delaying the enzyme action and thus increasingthe insect mortality. The pyrethrins are highly irritating toinsects and hence are used as a flushing agent or irritant tomake them come out of their hiding.

Pyrethroids: These comprise the class of synthetic chemicalsthat have been designed to imitate natural pyrethrum found in theflowers of chrysanthemums. The pyrethroids are less toxic tomammals and more effective as insecticides than naturalpyrethrins. They were introduced for the control of the attack byarmy worm, pseudaletia separate (Walker) which is a serious pest of

graminaceous crops and grass. The insect had developed resistanceagainst the pesticides available in 1970 and has on severaloccasions damaged the cotton crop in Pakistan. The pyrethroidswere introduced in the 1970s as very fast acting and very toxicto army worm.

Most insects that are highly vulnerable to pyrethrum are alsovulnerable to pyrethroids at low concentrations. The compoundsact rapidly on insects in like manner, causing immediateknockdown on flying insects upon exposure and their irritatingaction makes them useful in mosquito coils. Allethrin, producednearly 36 years ago in the USA constitutes the active ingredientof mosquito coils which have come into increasing use as mosquitorepellents. A mosquito mat contains only about 40 milligrams ofallethrin, which on slow evaporation gets dispersed in the air,with its long-term effects yet to emerge.

Pyrethroids comprise over 1,000 highly toxic broad-spectrumpesticides. They are widely used in agriculture under trade namessuch as allethrin, the one that is common; asana, astro,bioresmethrin, capture, cismethrin, cyfluthrin, cypermethrin,fenvalerate, flucythrinate, fluvalinate, mavrik, permethrin,pounce, resmethrin, and sumithrin, synthetic pyrethrum and/orpyrethrins.

The basic chemistry of pyrethroids is the same as that of thepyrethrins, but it has been modified to improve persistence,insecticidal activity, etc. The chemistry of the two groups i.e.pyrethrins and pyrethroids is nevertheless very complex and theirtoxicity depends on the stereochemistry of their isomers. Thereare a number of pyrethroids which have different configurationsin space and hence have as many isomers. Each isomer andstereoisomer exhibits its individual toxicity. 

The pyrethroids are produced by esterification of the analoguesof cyclopropanecarboxylic acid or the pyrethric acid or2,2dimethyl-3-(2,2-dichloroviny)cyclopropanecarboxylic acid withdifferent substituents in the pyrethric alcohol. Biologicalactivity of the pyrethroids is related to the substituents on theacid as well as alcohol moiety of the basic pyrethroid unit. Theproduct of estrification is usually a mix of several geometricaland optical isomers. The active component with the desired

activity and stability is separated into specified mixtures andreevaluated before application on crops. Pyrethroids inhibit sodium and potassium conduction in nervecells and block nerve impulse transmission. Pyrethrins as well aspyrethroids are nerve poisons; their toxicity proceeds by thedisruption of the permeability of nerve membranes to sodium. Theyare known to cause allergic reactions like asthma attacks,dermatitis and to interfere with functions of the nervoussystem.  Just their inhalation has been reported to causeasthmatic breathing, sneezing, stuffiness, headaches, tremors,convulsion, burning and itching among the persons sensitive tothem.  Other possible effects include: convulsions; diarrhea;headache; vomiting; labored breathing; excessive nasal mucousdischarge; irritability; sweating; sudden swelling of face,eyelids, lips, mouth, and throat tissues; hay-fever likesymptoms, and elevated pulse rate.

Acute Toxicity: For a mixture of two isomers, the acutetoxicity depends on the ratio of the amounts of the differentisomers in the formulation.  For example acute oral LD50 ofpermethrin on the female rats increases several hundred-fold asthe proportion of trans isomer increases from 20 to 80%. Theroute of exposure is critical in assessing the acute toxicity ofsynthetic pyrethroids. The immediate effects include symptomssimilar to DDT and OC poisoning; T-syndrome: tremors; exaggeratedstartle response; hyperthermia; CS-syndrome: excessive writhingand salivation; decreased startle response; increase in adrenalinand blood sugar.   Some pyrethroids are toxic by the oral route, but in generaltheir ingestion presents relatively little risk. Incoordination,tremor, salivation, vomiting, diarrhea, and irritability to soundand touch may sometimes be caused by large doses. Most of themare rapidly metabolized and excreted.

Long-term or Chronic Toxicity of pyrethrins causes allergicreactions and liver damage specially when used with synergistsand propellants. A few formulations of pyrethroids have beenreported to produce irreversible eye damage and quite a few ofthem have been found to be potent allergens. Deltamethrin, for

example was found to be an allergen at low doses applied indilute sprays by unprotected applicators in orchards in 1981.

Pyrethroids are neurotoxins. Their chronic hazard comes fromoncogenic effects and permethrin was noted in 1988 as a knownoncogen. Some of them are already suspected of beingcarcinogens.  Their long-term toxic effects, some of which may becumulative, include those related to suspect mutagens; suspectteratogens; suspect carcinogens; immunotoxins, and decreasedhormone releases from brain. The half life of pyrethroids insoils ranges from 1 to 100 days.  However, permethrin, asynthetic pyrethroid is applied to soil for termite controlassuming that it remains active for 1 to 5 years.  Reports ofinsect resistance are now being increasingly reported. Pestsdevelop quick chemical resistance to pyrethroids and termiteshave been observed tunneling through pyrethroid-treated soil bylining their tunnels with clean soil particles(Nan-Yau Su, Professor of

Entomology for the University of Florida).

Persons with respiratory problems are more sensitive topyrethrins and pyrethroids. People with multiple sclerosis, MScan be on medication that affects sodium and potassium iondiffusion through neuron axons. Pyrethroids can modify behaviorin a number of ways(The Best Control, 2nd Edition).

The product FenDeet® which was a formulation containing an insectrepellent Deet and fenvalerate was marketed for use as aveterinary chemical. A large number of poisoning cases wereattributed among small, young cats to the synergistic effect ofthe two chemicals. Deet is readily absorbed through the skin,enhanced the absorption rate of fenvalerate in such proportion asto lead to development of toxic levels systematically(J. Am. Vet. Med.

Assn. 196, 100, 1990).

Persons sensitive to ragweed have been advised not to usepyrethrum or pyrethroids e.g. permethrin; not allow contact withmucous membranes e.g. the eyes, nose or mouth or use it near theeyes, and not to inhale or swallow the insecticide in anyform. The inerts in pyrethroid formulations used in USA areeither known or suspected carcinogens, examples being silica,trimethyl benzenes and ethyl benzene. Xylene and polyaromatichydrocarbons depress the functions of the central nervous system.Several pyrethroid formulations also contain hazardous

contaminants like ethylene oxide, benzene and arsenic(Journal of Pesticide

Reform, Fall of 1990). Demand® CS, for example contains the activeingredient Lamdacyhalothrin 9.7% (pyrethroid microencapsulatedfor gradual release) and also 90.3% inerts or petroleum solventwith 1,2,4 trimethylbenzene.

Environmental Effects include high toxicity to fish, bees,and aquatic arthropods. They are specially toxic to fish andother aquatic organisms. Unlike OPs and carbamates which are alsoneurotoxic, synthetic pyrethroids and DDT do not attack theperipheral, in addition to the central nervous system.

A case of chemical sensitivity is worth noting here. A 35-year-old limited licensed psychologist working with chronically illpatients at Detroit Receiving Hospital was exposed to pyrethrinin 1989, when an insecticide company sprayed her office becauseof a bug problem. She got some of the chemical mist on her handswhen she returned later. She felt sleepy and started to fallasleep at her desk. She was already a patient of asthma but shedeveloped symptoms such as headaches, frequent falling, kidneyproblems, memory lapses, fatigue. Her illness grew worse, and shehad to stop working in 1994. She was diagnosed with multiplechemical sensitivity, MCS, a chronic condition marked byheightened sensitivity to many different chemicals(Jewish News, Detroit

2/6/98).

Another case is that of the pyrethroid insecticides imitating thehormone estrogen and disrupting the endocrine function, or thenormal functions of the hormone systems. It has been found duringa study at the Mt. Sinai School of Medicine that four syntheticpyrethroids viz. sumithrin or phenothrin, fenvalerate, allethrinand permethrin cause cell proliferation. This has led to theconclusion that the pyrethroids that are being widely used andare prevalent in the environment, have the capacity to alter theestrogen homeostatis or its normal balance and equilibrium. Thereare evidences that pyrethroids can harm the thyroid. They havebeen shown to disrupt the endocrine system by mimicking theeffects of the female sex hormone estrogen. In men, endocrinedisrupters can lower the sperm count, and in women they can causethe growth of abnormal breast cells(The Best Control (2nd Edition).

Sumithrin is a type I pyrethroid insecticide widely used tokill the blood sucking pests. Inhaling it can cause coughing,wheezing, shortness of breath, runny or stuffy nose, chest pain,or difficulty in breathing. It can cause skin and eye irritation.Skin contact can cause a rash, itching, or blisters. It is aneurotoxin. Sumithrin has been shown to disrupt the endocrinesystem and to mimick the effects of estrogen. It has ben found tolower the sperm count and to cause the growth of abnormal breastcells(The Best Control (2nd Edition).

The half-life of sumithrin in soil is one day to sixteen weeks,depending on the type of soil.

Cypermethrin: This pyrethroid pesticide is (R,S)-alpha-cyano-3-phenoxybenzyl(1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylate. It is used in the control of anumber of pests, including moth pests of cotton, fruit, andvegetable crops. It is also used for crack, crevice, and spottreatment to control insect pests in stores, warehouses,industrial buildings, houses, apartment buildings, greenhouses,laboratories, and on ships, railcars, buses, trucks, andaircraft, besides mosquito coils. It has also been used in non-food areas in schools, nursing homes, hospitals, restaurants,hotels, in food processing plants, and as insect repellent inbarrier treatment for horses. Technical cypermethrin is a mixtureof eight different isomers, each of which may have itscharacteristic chemical and biological activity. It is stable tosolar radiation(EXTONET).

Acute Toxicity: Cypermethrin is a moderately toxic contact aswell as stomach pesticide. Symptoms of high dermal exposureinclude numbness, tingling, itching, burning sensation, loss ofbladder control, incoordination, seizures, and possible death. Itadversely affects the central nervous. Symptoms of high-doseingestion include nausea, prolonged vomiting, stomach pains, anddiarrhea which progresses to convulsions, unconsciousness, andcoma. It is a slight skin and eye irritant, and can causeallergic skin reactions. The oral lethal doses have a wide rangeof variation depending on the ratio of cis/trans-isomers anddifferent mixtures of isomers of the compound present in theformulation(EXTONET).

Teratogenic, Mutagenic & Carcinogenic effects:Cypermethrin is not teratogenic. No birth defects were observedin the offspring of rats and rabbits that were given high doses.It is also not mutagenic. However, tests with very high doses onmice caused a temporary increase in the number of bone marrowcells with micronuclei. Other tests for mutagenic effects inhuman, bacterial, and hamster cell cultures and in live mice havebeen found negative. Cypermethrin has, however, been classifiedby US EPA as a possible human carcinogen since availableinformation is not conclusive. It caused benign lung tumors infemale mice at high doses; however, no tumors occurred in ratsgiven high doses(EXTONET).

Organ Toxicity: Cypermethrin causes adverse effects on thecentral nervous system. Rats which were fed high doses of thecis-isomer of cypermethrin for five weeks exhibited severe motorincoordination, while 20 to 30% of them fed still higher dosesdied 4 to 17 days after the feed. Long-term feeding studies haveshown increased liver and kidney weights and adverse changes inliver tissues in test animals. Pathological changes in the cortexof the thymus, liver, adrenal glands, lungs, and skin wereobserved in rabbits repeatedly fed high doses ofcypermethrin(EXTONET).

Fate in Humans and Animals: In humans, urinary excretionof cypermethrin metabolites was found complete in 48 hours.Studies in rats have shown that this pyrethroid is rapidlymetabolized by hydroxylation and cleavage, with over 99% beingeliminated within hours. The remaining 1% is found stored in bodyfat and is eliminated slowly, with a half-life of 18 days for thecis-isomer and 3 to 4 days for the trans-isomer(EXTONET).

Ecological Effects: Cypermethrin is non-toxic to birds. Noadverse reproductive effects have been noted in mallards orbobwhite quail given 50 ppm, the highest dose tested. Thepesticide is however, highly toxic to bees(EXTONET).

Effects on Aquatic Organisms: This pesticide is veryhighly toxic to fish and aquatic invertebrates. It is metabolized

and eliminated significantly more slowly by fish than by mammalsor birds, which may explain the higher toxicity in fish comparedwith other organisms. The half-lives for elimination of severalpyrethroids by trout are all greater than 48 hours, whileelimination half-lives in birds and mammals range from 6 to 12hours. The bioconcentration factor for cypermethrin in rainbowtrout was 1200 times the ambient water concentration, indicatingthat there is a moderate potential to accumulate in aquaticorganisms. Elimination of half of the accumulated amount of thecompound took nearly eight days. After 14 days 70 to 80% of thematerial had been eliminated from the organisms(EXTONET).

Environmental Fate: Cypermethrin has a moderate persistencein soils. Under laboratory conditions, it degrades more rapidlyon sandy clay and sandy loam soils than on clay soils, and morerapidly in soils low in organic material. When applied to a sandysoil under laboratory conditions, its half-life was 2.5 weeks. Inaerobic conditions, its soil half-life is 4 days to 8 weeks. Itis more persistent under anaerobic conditions. Itsphotodegradation is rapid with a half-life of 8 to 16 days. Italso undergoes microbial degradation under aerobic conditions.Cypermethrin is not soluble in water and is strongly adsorbed tosoil particles. It does not, for this reason, cause groundwatercontamination(EXTONET).

Breakdown in Water: Cypermethrin hydrolyzes slowly inneutral and acid aqueous solutions, and rapidly in basic solutionwith pH 9 or more. Under normal environmental temperatures andpH, it is stable to hydrolysis with a half-life of greater than50 days and to photodegradation with a half-life of greater than100 days. It was observed in the laboratory and pond waters thatcypermethrin concentrations decreased rapidly due to scores offactors including sorption to sediment, suspended particles andplants in addition to microbial as well as photodegradation(EXTONET).

Breakdown in vegetation: When applied to strawberry plants,40% of the applied cypermethrin remained after one day, 12%remained after three days, and 0.5% remained after seven days,with a light rain occurring on day 3. The crop residues of wheatcontained 4 ppm of cypermethrin immediately after spraying anddeclined to 0.2 ppm 27 days later. It was not detected in the

grain. Similar residue loss patterns were observed on treatedlettuce and celery crops(EXTONET).

BIPYRIDYLIUM COMPOUNDS

The bypiridynium compounds contain diquaternary nitrogen groupsin the two pyridine rings, joined through a C-C bond. They arehighly soluble divalent cations. Paraquat and diquat are two wellknown members of this class. They are stable to light and heatbut are inactivated on contact with soil. They are non-selectivecontact-type herbicides widely used for broadleaf weed control.They generally show acute toxicity to mammals and are well knownfor their toxic effects in humans. Human toxicity results fromingestion or dermal contact with the compounds prior to theirapplication to weeds and soil(Douglass E. Stevenson, Physician’s Desk Reference toPesticide Health Hazards, http://www-aes.tamu.edu/doug/MED/PGPHH.HTM).

The toxicity profiles of paraquat and diquat are generallysimilar but differ in one important aspect. Paraquat activelyaccumulates in the lung by an energy-dependent, specific uptakeprocess within 10 hours of ingestion resulting in severe acute ordelayed pulmonary effects that are not seen after diquatingestion. The mechanism of interaction with the target isrelated to single electron reduction, oxidation withflavoproteins and molecular oxygen followed by peroxidation oflipid cellular membranes.

Paraquat is 1,1'-dimethyl-4,4'-bipyridinium dichloride. It isa quick-acting, nonselective compound that destroys green planttissues on contact and by translocation within the plant. It hasbeen employed for killing marijuana in the USA and Mexico. It isalso used as a crop desiccant and defoliant, and as an aquaticherbicide(EXTONET).

Occupational intoxications result mostly from localcontamination. Dermatitis that may sometimes be severe,epistaxis, conjunctivitis and ocular damage may be the result ofsplashes of concentrated paraquat. Nail damage following repeatedcontamination with diluted paraquat also occurs. In developingcountries like India, Malaysia, and Pakistan, paraquat is usedwithout adequate regulation and protection. Spraymen can easilybe seen stirring buckets or vats of these highly toxic materials

without protecting their arms, hands, face and feet. Paraquat isnevertheless poorly absorbed by inhalation owing to the largesize of the suspended droplets and significant toxicity has notbeen reported by this route.

Paraquat presents a very high hazard due to irreversible lungdamage. The most specific effect for paraquat is pulmonaryfibrosis. In acute intoxication, hepatic failure and renalinsufficiency are also common. Gastrointestinal and centralnervous system impairments also occur.

Toxicological Effects: Paraquat is highly toxic byingestion. Its toxic effects are due to the cation; the halogenanions have little toxicity to contribute. The dermal toxicity isonly moderate and this route has low contribution in the overalltoxicity scenario. It causes skin and eye irritation in rabbits(severe for some of the formulated products) and also causes skinsensitization in guinea pigs in some formulations. Effects due tohigh acute exposure to paraquat may include excitability and lungcongestion, which in some cases leads to convulsions,incoordination, and death by respiratory failure. If swallowed,burning of the mouth and throat often occurs, followed bygastrointestinal tract irritation, resulting in abdominal pain,loss of appetite, nausea, vomiting, and diarrhea. Other toxiceffects include thirst, shortness of breath, rapid heart rate,kidney failure, lung sores, and liver injury. Some symptoms maynot occur until days after exposure. Persons with lung problemsare at increased risk from exposure and many cases of illnessand/or death have been reported in humans owing to suchexposures(EXTONET).

Chronic Toxicity: Repeated exposures of paraquat cause skinirritation, sensitization, and ulcerations on contact. In animalstudies, rats showed no effects after being exposed for 2 yearsto paraquat at low doses. Dogs, however, developed lung problemsafter being exposed for 2 years at high doses. In a study of 30workers spraying paraquat over a 12 week period, approximatelyone-half had minor irritation of the eyes and nose. Of 296spraymen with gross and prolonged skin exposure, 55 had damagedfingernails as indicated by discoloration, nail deformities, orloss of nails(EXTONET).

Reproductive Effects: In a long-term study on rats at lowdoses of paraquat, no adverse reproductive effects were reported,but when injected intraperitoneally for 8 to 16 days, increasedfetal mortality was observed in these laboratory animals. Hensgiven high levels of paraquat in their drinking water for 14 daysproduced an increased percentage of abnormal eggs(EXTONET).

Teratogenic, Mutagenic & Carcinogenic Effects:Offsprings of mice given high doses of paraquat during the organ-forming period of pregnancy had less complete bone developmentthan the mice given lower doses. Offsprings of rats given similartreatment showed no developmental defects at any dose, but fetaland maternal body weights were lower than normal. Other studiesof paraquat using rabbits and mice have shown no teratogeniceffects. The evidences available suggest that paraquat does notcause birth defects at usually administered doses. It has beenshown to be mutagenic in microorganism tests and mouse cellassays. The evidence regarding carcinogenic effects of paraquatis, on the other hand inconclusive since mice fed paraquatdichloride for 99 weeks at high levels did not show cancerousgrowths but rats, fed on high doses for 113 weeks to males andfor 124 weeks to females, developed lung, thyroid, skin, andadrenal tumors(EXTONET).

Organ Toxicity: This pesticide has been found to affect thelungs, heart, liver, kidneys, cornea, adrenal glands, skin, anddigestive system.

Fate in Humans and Animals: Paraquat is not readilyabsorbed from the stomach, and is even more slowly absorbedacross the skin. Oral doses of this pesticide in rats areexcreted mainly in the feces, while paraquat injected into theabdomen leaves through urine. In the stomach and gastrointestinaltract, paraquat metabolites have been found to be more readilyabsorbed than the parent compound, but their identities andtoxicities are not known. Paraquat has been found to concentratein lung tissues, where it can be transformed to highly reactiveand potentially toxic forms. In one study, farm animals excretedover 90% of the administered paraquat within a few days. It wasslightly absorbed and metabolized in the gastrointestinal tract.Milk and eggs contained small amounts of two paraquatmetabolites(EXTONET).

Ecological Effects: The compound is moderately toxic tobirds. It is slightly to moderately toxic to many species ofaquatic life, including rainbow trout, bluegill, and channelcatfish. Paraquat was detected in the gut and liver, but not inthe meat of rainbow trout when the fish was exposed to it for 7days. Aquatic weeds were found to bioaccumulate the compound. Inone study, 4 days after paraquat was applied as an aquaticherbicide, weeds samples showed significant residue levels. Athigh levels, it was found to inhibit the photosynthesis of somealgae in stream waters. Paraquat was found nontoxic to honeybees(EXTONET).

Environmental Fate: Paraquat is highly persistent in thesoil environment, with reported field half-lives of greater than3 years. In one study its reported half-life ranged from 16months in aerobic laboratory conditions, to 13 years in thefield. Ultraviolet light, sunlight, and soil microorganisms werefound to degrade this pesticide to products which are less toxicthan the parent compound. The strong affinity for adsorption bysoil particles and organic matter possibly limits itsbioavailability to microorganisms, earthworms, and plants. Thebound residues have been found to persist indefinitely and to betransported in runoff with the sediment. It is not significantlymobile in most soils. Matter non-associated with soil particleswas decomposed to a nontoxic end product by soil bacteria. Thusparaquat has not been found to present a high risk of groundwatercontamination. Of the 721 groundwater samples analyzed, only onecontained paraquat, at a medium concentration(EXTONET).

Paraquat being strongly adsorbed to suspended or precipitatedsediment has been reported to be highly persistent in the aquaticenvironment than on land due to limited availability of oxygen.It had a half-life of 13.1 hours in a laboratory stream watercolumn. In other studies, it was found stable up to 30 days, andlow levels in water, with half-life of 23 weeks(EXTONET).

Breakdown in Vegetation: Paraquat dichloride dropletsdecompose when exposed to light after being applied to maize,tomato, and broad-bean plants. Small amounts of residues werefound in potatoes treated with this pesticide as a desiccant, andboiling the potatoes did not reduce the residue(EXTONET).

Health Effects on Humans: Paraquat produces chronic abnormalcell growth in the lungs, cornea, and lens of the eye, nasalmucosa, skin and fingernails. It affects the eye lens andgastrointestinal mucosa, and causes frequently fatal lung changesthat are characteristic of this pesticide. Its ingestion causessevere irritation to the mucous membranes of the mouth, pharynx,esophagus and stomach and repeated vomiting usually follows.Lower amounts of paraquat can cause decreased urine volume in oneto six days because of kidney failure. Jaundice due to liverdamage can sometimes occur. The initial phase is followed by alatent period lasting up to two weeks. The victim may even appearto improve during this period. However, since it concentratesselectively in the pulmonary tissues, irreversible andprogressive lung damage results from rapid growth of connectivetissue cells, which prevents proper lung function and eventuallythe victim dies from respiratory failure(Douglass E. Stevenson, Physician’s DeskReference to Pesticide Health Hazards, http://www-aes.tamu.edu/doug/MED/PGPHH.HTM).

Dermal exposure to paraquat concentrates can cause severe skinirritations and burning, while contact with dilute liquids anddusts can cause slight to moderate irritation. Dermal absorptionof this pesticide is apparently slight but after repeated contactit produces symptoms similar to those following ingestion.

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

CHLOROPHENOXY COMPOUNDS

These plant hormone-type compounds are chlorophenoxy derivativesof acetic acid. They are selective herbicides which kill or stuntthe targeted weed without harming the main crop/plants. They aretranslocated within the plant to destroy roots and other partsnot exposed to the pesticide. Systemic toxicity in humans hasbeen reported following ingestion, inhalation of vapors and skincontact with these compounds. They enter the body duringoccupational exposure through aerial and dermal routes. They

produce toxic effects through uncoupling of oxidativephosphorylation and decreased oxygen consumption in tissues,besides causing disturbances in carbohydrate and other metabolicprocesses. Irritative and allergic effects and development ofporphyria cutanea tarda are typical of this group of compounds.

Chlorophenoxy group of herbicides have been found to affect thegastrointestinal system and the central and peripheral nervoussystems. Peripheral neuropathy with paresthesia and reversibleparalysis has been reported. The myotic effects observed in theircase result from muscle damage and atrophy. Other systems andorgans that are affected include the liver, cardiovascularsystem, thyroid gland and hemopoietic system.

The chlorophenoxy compounds are widely used herbicides and wereused extensively during the Vietnam conflict as exfoliants. Thisgroup includes 2,4-dichlorophenoxyacetic acid or 2,4-D, 2,4,5-trichlorophenoxyacetic acid or 2,4,5-T, 4-chloro-2-methylphenoxypropionic acid, dichlorprop, MCPA, MCPP, mecoprop,and silvex.

2,4-Dichlorophenoxyacetic Acid or 2,4-D was initiallydeveloped during the World War II programmes in the British andAmerican military and agricultural laboratories. Other herbicidessuch as 2,4,5-T that are now well known, were also developedthen. The toxic effects of the two herbicides are highly lethaland are most probably augmented by dioxin, which is a majorcontaminant in the 2,4,5-T production(EXTONET). Its degradationproducts include: 2,7-dichlorodibenzo-p-dioxin; 1,3,7-trichlorodibenzo-p-dioxin; TCDD; 1,3,6,8-tetrachlorodibenzo-p-dioxin; 1,3,7,9-tetrachlorodibenzo-dioxin, and 2,4-dichlorophenol.

Toxicological Effects: Acute toxicity: 2,4-D has slight tomoderate toxicity by the oral as well as dermal route. Itsprolonged breathing by humans causes coughing, burning,dizziness, temporary loss of muscle coordination and othersymptoms of nerve poisoning like fatigue, weakness with possiblenausea. With high levels of exposure, there can be inflammationof the nerve endings with muscular effects(EXTONET). Acute toxicityeffects include skin and mucous membrane irritation; dizzinesswith prolonged inhalation; vomiting; chest pain; diarrhea;

headache; confusion; muscular stiffness; unconsciousness;increased acidity of blood; hyperventilation; nerve damage; brainwave changes; eye irritation; swelling of extremities;incontinence; sweating; stupor; respiratory depression.

Chronic Toxicity: High doses of 2,4-D in the diet for 2 yearswere found to show no adverse effects among rats, but dogs givenlower amounts in their food for 2 years died, probably becausethese animals do not excrete organic acids efficiently. A humanexperiment with 500 mg/day for 32 days resulted in lapse into astupor showing signs of incoordination, weak reflexes, and lossof bladder control(EXTONET).

Reproductive Effects: High levels of 2,4-D administeredorally to pregnant rats did not cause any adverse effects onbirth weights or litter size. Higher doses resulted in fetuseswith abdominal cavity bleeding and increased mortality. DNAsynthesis in the testes was significantly inhibited when micewere fed large amounts of 2,4-D(EXTONET). The observed reproductiveeffects in animals being at very high doses, do not necessarilymean that the problems associated with 2,4-D may not be observedon humans. Adverse effects have, on the contrary been observed aswill be seen subsequently.

Teratogenic Effects: 2,4-D may cause birth defects at highdoses. Rats fed high doses on days 6 to 15 of pregnancy hadoffspring with increased skeletal abnormalities, such as delayedbone development and wavy ribs. This suggests that 2,4-D exposureis unlikely to be teratogenic in humans at expected exposurelevels(EXTONET). Subsequent studies have, however, shown that 2,4-Dhas teratogenic characteristics(Basic Guide to Pesticides:Their Characteristics and

Hazards, Rachel Carson Council).

Mutagenic Effects: 2,4-D has been very extensively tested andwas found to be nonmutagenic in most systems. 2,4-D did notdamage DNA in human lung cells. However, in one study,significant effects occurred in chromosomes in cultured humancells at low exposure levels. These data may suggest that 2,4-Dis not mutagenic or has low mutagenic potential(EXTONET), but laterstudies have confirmed of their being mutagenic(Basic Guide to

Pesticides:Their Characteristics and Hazards, Rachel Carson Council).

Carcinogenic Effects: Feeding of 2,4-D to rats for 2 yearscaused an increase in malignant tumors. Female mice given asingle injection of 2,4-D developed cancer (reticulum-cellsarcomas). Another study in rodents showed low incidence of braintumors at moderate exposure levels over a lifetime. However, anumber of questions have been raised about the validity of thisevidence and thus about the carcinogenic potential of 2,4-D. Inhumans, a variety of studies give conflicting results. Severalstudies suggest an association of 2,4-D exposure with cancer. Anincreased occurrence of non-Hodgkin's lymphoma was found among aKansas and Nebraska farm population associated with the sprayingof 2,4-D. Other studies carried out in New Zealand, Washington,New York, Australia and on Vietnam veterans from the USA were allnegative. There was considerable controversy about the methodsused in the various studies and their results (EXTONET). It hasfinally been resolved in subsequent studies that 2,4-D producescarcinogenic effects.

Recent studies indicate that the long-term effects of 2,4-D onmammals are related to their being carcinogen; suspect mutagen;teratogen; suspect fetotoxin; immunotoxin; and causing toxicinjury to liver, kidney, and central nervous system. It hasendocrine disrupting effects and has been listed on the ToxicsRelease Inventory of US EPA(Basic Guide to Pesticides:Their Characteristics and Hazards,

Rachel Carson Council).

Organ Toxicity: Most symptoms of 2,4-D exposure disappearwithin a few days, but there is a report of liver dysfunctionfrom long-term exposure(EXTONET).

Fate in Humans and Animals: The absorption of 2,4-D isalmost complete in mammals after ingestion and just about theentire dose is excreted through the urine. The compound isreadily absorbed through the skin and lungs. Men given smalldoses excreted about 82% of the dose as unchanged 2,4-D. Thehalf-life is between 10 and 20 hours in living organisms. Thereis no evidence that 2,4-D accumulates to significant level inmammals or in other organisms. Peak concentrations of 2,4-D werefound in the blood, liver, kidney, lungs, and spleen of ratsbetween 6 and 8 hours after small doses. There were lower levelsin muscle and brain. After 24 hours, there were no detectabletissue residues. Only traces of the compound were found in the

milk of lactating animals for 6 days following exposure. 2,4-Dpasses through the placenta in pigs and rats. In rats, about 20%was detected in the uterus, placenta, fetus, and amniotic fluid.Chickens given moderate amounts of 2,4-D in drinking water frombirth to maturity had very low levels of the compound ineggs(EXTONET).

Ecological Effects: This herbicide is slightly toxic towildfowl and slightly to moderately toxic to birds; it can affecttheir egg production. Some of its formulations are highly toxicto fish while others are less so. Limited studies indicate ahalf-life of less than 2 days in fish and oysters. Moderate dosesof 2,4-D severely impaired honeybees brood production; at lowerlevels of exposure, however, exposed bees were found to livesignificantly longer than the controls(EXTONET).

Fate in the Environment: 2,4-D has low soil persistence.The half-life in soil is less than 7 days. Soil microbes areprimarily responsible for its degradation. Despite its shorthalf-life in soil and in aquatic environments, the compound hasbeen detected in groundwater supplies. Very low concentrationshave also been detected in surface waters throughout NorthAmerica(EXTONET).

Microorganisms readily degrade 2,4-D in aquatic environments, therate of breakdown increasing with increased nutrients, sedimentload, and dissolved organic carbon. Under oxygenated conditionsthe half-life is 1 week to several weeks(EXTONET).

2,4-D interferes with normal plant growth processes. Uptake ofthe compound is through leaves, stems, and roots. Breakdown inplants is by a variety of biological and chemical pathways. Leafmalformation due to its toxic effect is noted among most broadleaf crops, especially cotton, tomatoes, beets, and fruittrees(EXTONET).

TRIAZINES: This group of pesticides is used as herbicides ormicrobiocides which contain a triazine ring. Triazines were firstintroduced in France in 1962 and used primarily on maize andsorghum crops but also in orchards and vineyards. In 1999, Frenchgrowers applied atrazine to 100% of sorghum crops and 80% ofmaize, according to the national farm ministry.

The main pesticides of this class are ametryn, anilazine,atrazine, chlorinated isocyanurates, cyanazine, promaton,promatryn, propazine, simazine, and terbutryn. The triazine ringcompounds are biologically highly reactive. Accordingly allmembers of this class are highly toxic. They act by disturbingthe metabolism of vitamins. Their immediate effects appear in theform of skin and eye irritation; nausea; vomiting; diarrhea;muscular weakness; salivation. In terms of their long-termeffects they are carcinogens; suspect mutagens; immunotoxin;adrenal damage; kidney and urinary tract stone formation;teratogens; lung damage; suspect fetotoxins; and are known tocause liver and kidney damage, besides disturbances in spermproduction. They are groundwater contaminants, frequently foundin groundwater, along with their transformationproducts(http://members.aol.com/rccouncil/ourpage/samples.html).

Atrazine and simazine are the two well known members of thisclass of herbicides. Both have high to very high toxicity foraquatic insects; high for molluscs; medium for bees; low to highfor fish; low to medium for crustaceans. In terms of theirchronic toxicity on mammals, they are both carcinogens; mutagens;immunotoxins and they are known to cause adrenal damage. Bothhave been found in groundwater and surface water. Atrazine hasbeen found to reduce populations of soil invertebrates and hasbeen suggested to have impaired the reproduction ofamphibians(http://members.aol.com/rccouncil/ourpage/samples.html). The breakdownproducts of Atrazine can persist in lakes and groundwater fordecades. It also has a half-life in soil surfaces of over 100days and can potentially persist for years below the soilsurface.

Atrazine was till recently one of the two most commonly usedagricultural pesticides in USA. A study by US Geological Surveyhad in 2001 found atrazine in rivers, streams and groundwater inall 36 of the river basins studied. In air or rain, atrazine wasfound to travel long distances from application sites. It wasfound in nearly 100% of the sites where rainfall was collected,in some cases in concentrations that exceeded drinking waterstandards(PANUPS November 16, 2001).

The herbicide atrazine most often found in rain and river water,was acknowledged by US EPA to have exceeded its level of concern

for chronic toxicity to fish reproduction. Several studies areavailable that show atrazine to be an endocrine disruptor, whichby disturbing the immune system enhances the risk of infectiousdisease and cancer. It inhibits testesterone, progesterone andestrogen functions. It has been shown in laboratory studies tocause genetic damage and delay puberty. There are also evidencesthat link atrazine exposure to reproductive deformities in frogs.

Studies carried out in France had found degraded atrazineproducts in 50% of samples taken from surface water and 52% ofgroundwater supplies. Based on these findings, the Frenchauthorities had ordered people not to drink tap water in areaswhere triazine content exceeded recommended levels. In September2001 the French Government decided to put a nationwide ban onatrazine and related triazine herbicides, due to threats theypose to human health and their generalized presence in watersupplies, as part of its policy to reduce significantly the useof pesticides and promote food safety in that country.