Pharm 100 - Lesson F.1

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  1. Origins of Pesticides
    • With the exceptions of sulphur and copper salts (sulphate, arsenate) which saw particular use in the1800’s in vineyards, mercurials in seed treatment in the early 1900’s and carbamate (thiram, ziram)fungicides in the 1930’s, most chemical pesticides were introduced shortly after World War II. Many,e.g. organophosphorus esters and chlorophenoxyacid derivatives, were developed during the war aspotential chemical warfare agents. Hence, the media cry that all organophosphorus insecticides are“nerve gases”. Less toxic derivatives “from the chemists’ shelves” found instant, practical use aspesticides to control infestations, e.g. DDT, chlordane, parathion, 2,4-D, dinoseb. Agents such asthese heralded the era of the “quick fix” for agricultural, forestry and public health problems.
    • There is no dispute that pesticides increased both pre- and post-harvest yields of crops, protectedfibre (cotton, wood, etc.) and improved human health. Many examples can be cited where theintroduction of insecticides dramatically improved crop yields of potatoes, corn, cotton, grapes,apples, citrus fruits, etc. At one time, it was estimated that, in cereals, there was a 30 percent field lossdue to insects and fungi with an additional 50 percent post-harvest loss due to devastation of the storedcrop by insects, fungi and rodents. Treatment at the appropriate time with selective pesticidesincreased yields from some 35 percent to over 80 percent. Consider the dramatic events following theuse of DDT in 1944 in the city of Naples, Italy, to control a louse-borne, typhus epidemic where 1.5million inhabitants were “dusted”, with no loss of life due to the disease which usually has a highmortality rate. The success of the malarial control programs in the 1950’s and 1960’s using DDT wasphenomenal, but with the banning of DDT, the use of more expensive agents as well as continualwarfare in many malaria-ridden regions of Africa and southeastern Asia, most of these programscollapsed with reappearance of the disease. This comment can be extended to the control of otherinsect-borne diseases such as plague, yellow fever, dengue fever, onchocerciasis (river blindness) andtrypanosomiasis.
    • However, there were problems in this chemical-treated “paradise”, particularly with theorganochlorine-type insecticides. While effective, these agents were environmentally persistent, notreadily metabolized and degraded, lipid soluble, bioaccumulated upward in food chains, and posedserious problems to those species at the apex of the food chain; these agents accumulated sufficientconcentrations to elicit toxicological effects either directly on the nervous system or as estrogens orindirectly through their ability to interfere with normal steroid metabolism, thereby affecting normalreproduction. Replacement of this class of insecticides with the more acutely toxic organophosphorus and carbamate esters resulted in new and perhaps more severe problems of human intoxications. Theswing back to less toxic pyrethroid esters, derived from pyrethrum found in certain strains ofchrysanthemum flowers (and leaves), or newer heterocyclic, nicotinyl agents may reduce the humantoxicity somewhat, but these agents are not without adverse biological activity in non-target species,the human included.
  2. Definition of a Pesticide
    By the U.S.A. EPA definition, a pesticide is any substance or mixture of substances intended for thepreventing or mitigating (making less severe) any pest (a harmful, destructive or troublesome animal,plant or microorganism). The term also covers insect attractants (pheromones or sex hormones),repellants, defoliants, desiccants and plant growth regulators.
  3. Classification of Pesticides
    • Pesticides can be classified by target organism, e.g. acaricides, avicides, bactericides, fungicides,herbicides, insecticides, larvacides, miticides, molluscicides (snails), nematicides, piscicides (fish),rodenticides, etc. The word ending “icide” signifies death (lethality) or killing, all pesticidespossessing an inherent degree of toxicity to some life form. It should be remembered that allpesticides are toxic to some degree.
    • Pesticides can be classified by chemical structure, e.g. insecticides – organochlorine,organophosphorus esters, carbamate esters, pyrethroids, nicotinyl agents, and may be subclassified bytheir mechanism(s) of action, e.g. anticholinesterase-type (organophosphorus and carbamate esters) orneuronal conduction interference (organochlorines and pyrethroid esters).
    • In most situations, a combination classification is used, identifying a pesticide by target organism(insecticide), by mechanism and chemical structure, as outlined above. Chemical classification, saycarbamate esters, is non-specific since these agents can be insecticides, herbicides or fungicides, theproperties being quite different given the chemical structures and properties of the agents.
  4. Pesticides of Greatest Concern
    Being self-centred creatures, we tend to relate the seriousness of toxicity in terms of humanintoxications. Data from Costa Rica, a country using considerable amounts of pesticides, reveals thatof 1,274 pesticide poisonings reported in 1996, 490 (38.5%) were occupational in nature and 430(33.8%) were accidental. The majority of poisonings (438) involved organophosphorus andcarbamate esters. By contrast, only 8 involved organochlorine compounds. This typical pattern isseen in other regions, countries, states and provinces. Insecticides are the most acutely hazardousagents, organophosphorus and carbamate esters being major players in accidental- and occupationalrelated intoxications around the globe. Of necessity, more time should be devoted to their study inboth acute and chronic exposure although other classes of pesticides may be associated with adversebiological effects following chronic exposure.
  5. The Dose-Effect Relationship
    • The discipline of toxicology is founded upon the basic tenet that increased adverse effects areassociated with an increase in dose (or exposure). Any investigation of a pesticide’s toxicity shouldbegin at those experiencing high level exposure – the accidental and suicidal exposures and theoccupational exposures where a reasonable estimate of dose can be obtained. As is shown in Figure 1,such acute intoxications tend to be related to a relatively narrow dose range. As one moves to lowerdoses (exposures), the range tends to become broader and the adverse health effects are lesspronounced with only some (or a few) of the signs/symptoms being observed. On reaching thelevel(s) to which the general public are exposed (air, water, food, soil), the dose range can beextremely broad and the biological effects, real or perceived, difficult to assess.
    • A good rule of thumb is that if little or no acute or chronic effects are seen following exposure to highlevels, there is little likelihood of seeing anything significant at lower levels of exposure. There are,however, exceptions to this rule, and one must always be cautious in assessing toxicity, particularlythat of a chronic nature.
  6. Insecticides – Mechanisms
    • All of the classes of insecticides are neurotoxicants, acting on the peripheral and/or central nervoussystems, but different mechanisms are involved as is shown in Table 1, the agent(s) acting on theaxonal membrane, on enzymes in the axonal membrane or at neuronal endings and/or at specificneurotransmitter receptors.
    • The reader should review the physiological and biochemical events involved in nerve conduction. Basically, conduction is electrical in nature within a neuron, the electrical impulse being transmitted inrapid stages as a consequence of localized depolarization (from -80 mV to 0 mV) followed by rapidrepolarization. Conduction between neurons is chemical in nature using neurotransmitters such asacetylcholine (ACh), norepinephrine (NE), gamma-aminobutyric acid (GABA) to bridge the gapbetween a nerve ending and the dendrite of the next neuron. The neurotransmitter is usually releasedfrom storage vesicles localized near the nerve ending when depolarization occurs. This is followed bydiffusion across a narrow synaptic cleft to attach to specific receptors on the surface of thepostsynaptic membrane (of the next neuron) to initiate a depolarization of this neuron. Termination ofneurotransmitter activity is effected by enzymatic destruction of the neurotransmitter or reabsorptioninto the nerve ending.
  7. A. Organochlorine Insecticides
    • These chemicals see no use in North America or in western Europe due to their being banned (DDTin 1972, chlordane and others by 1983) because of properties described above. However, they areextensively used in tropical regions in developing or emerging nations since they are still effectiveagents and are cheap to manufacture. As will be discussed in a later section, application of theseagents in the tropics will be detected in the arctic and antarctic regions within a year or two of use.
    • While these agents have diverse structures, they can be classified into three structural groups – thedichloro-diphenylethanes, the cyclodienes and the chlorinated benzenes, and cyclohexanes (Figure2). As can be seen from Table 2, the lists of acute and chronic signs/symptoms show subtledifferences between the DDT-like compounds and the other two classes. More information can befound in the assigned references for those students wishing more information; it is not requiredreading.
  8. (i) DDT Class
    The most striking observations in DDT-poisoned insects and mammals are: (1) the persistenttremoring and/or convulsions alternating with periods of little or no activity, and (2) the repetitiveseizures/convulsions (or tremors) caused by touch (tactile) or sound (auditory) stimuli. Theseobservations suggest that the sensory system is the target of DDT and similar compounds, providingclues to the mechanism of action.DDT causes a delay or a prolongation of the rate of repolarization (negative-after-potential) of adepolarized nerve, leaving the nerve membrane in a state of partial depolarization which is verysensitive to extremely small stimuli, resulting in complete depolarization again. DDT has severaltarget sites on the nerve membrane, all being affected simultaneously, e.g.: (1) causing reduced ionpermeability across the neuronal membrane (reduced potassium transport); (2) altering of themembrane sodium channels; (3) inhibiting neuronal adenosine triphosphatases (ATPases) involved insodium-potassium transport; and (4) inhibiting calmodulin binding of calcium ions, leaving freecalcium to cause additional release of transmitters.All of these mechanisms prevent the normal rate of neuronal repolarization, leaving the neuronsusceptible to depolarization again by the weakest of stimuli (which, under the normal repolarizedstate would not elicit any effect).
  9. (ii) Cyclodienes and Cyclohexanes
    The biological effects caused by these agents are different from DDT, their actions involving thecentral nervous system (CNS) rather than the peripheral nervous system (PNS). A variety ofmechanisms of action are involved, but the main effects appear to be associated with: (1) antagonismof the CNS gamma-aminobutyric (GABA) neurotransmitter, this neurotransmitter being responsiblefor chloride ion uptake; and (2) inhibition of calcium-magnesium ATPase, the enzyme essential for thetransport (both uptake and release) of calcium ions across neuronal membranes.
  10. B. Anticholinesterase-Type Insecticides
    • The anticholinesterase insecticides belong to two chemical classes – the organophosphorus esters(approximately 100 of diverse chemical structure being available,) and the carbamic acid esters (about15 commonly used). The basic structure(s) are shown in Figure 3. The uniqueness of these agents(target organism selectivity, rapid detoxification by non-target species, environmental breakdown,etc.) lies in the substituent groups which confer specific physical and chemical properties on themolecules.
    • The prime actions of both types of esters is by inhibiting the nervous tissue enzyme,acetylcholinesterase (AChE), which is responsible for the termination of the action of theneurotransmitter, acetylcholine (ACh), released at nerve endings in both the CNS and PNS. If ACh isnot destroyed, persistent stimulation of these nerve endings continues, giving rise to a number ofsigns/symptoms, the severity of which depends upon the level of exposure to the insecticide and thetarget site(s) in the CNS and PNS (Table 3).
    • The acute signs/symptoms of organophosphorus ester intoxication are persistent (possibly even forweeks) and very closely linked with the “dose”. In contrast, the signs/symptoms of carbamate esterintoxication may be intense, but usually are of short duration (less than 12 hr). This gives clues to therelative mechanism(s) of action as is shown in Figure 4.
    • The interaction of an organophosphorus ester and AChE (usually the active “oxon” metabolite)results in the binding of the ester to a serine hydroxyl group in the active site, with a second stage ofhydrolysis and loss of a “leaving group” (phenol, cresol, etc.) and the formation of an irreversiblyinhibited, phosphorylated enzyme which can be reactivated only with great difficulty. Thus, AChaccumulates at nerve endings to cause persistent stimulation. In contrast, carbamate esters attach tothe active site in much the same manner as ACh, with the loss of a “leaving group” and the formationof a carbamylated enzyme which can be hydrolyzed readily to reactivate the enzyme. Carbamateesters are just poor substrates of AChE.
    • Recently, there has been much interest in persistent long-term effects following acute poisoning, e.g.nausea, headaches, blurred vision, dizziness, night sweating, neuromuscular cramps, muscle weaknessand fatigue. These adverse effects appear to be related to ACh-induced destruction of ACh receptorsin neuromuscular junctions and in the CNS by a down-regulation of the number of receptors (amechanism found frequently with excessive neurotransmitter release) and a lack of re-synthesis, as yetnot understood. There is also evidence that organophosphorus esters can destroy neuronal AChreceptors directly.
  11. C. Pyrethroid Esters
    • Pyrethrum, a mixture of six esters extracted from certain strains of chrysanthemum flowers (andleaves), has been used since the early 1900’s, but the pressures of demand and short supply by the1950’s made it necessary to determine the complex molecular structure. Once this was achieved, anumber of synthetic pyrethroid esters appeared on the market in the 1960’s and 1970’s, showingspecies selectivity toward target and non-target insects, little toxicity to mammals and lowenvironmental persistence, all of this being associated with various substituents attached to two basicstructures.
    • In studying the mechanisms of action of these agents, it became very evident that they affectedneurons in exactly the same way as DDT (see DDT above), the sensory nervous system being the maintarget. These esters prolong the rate of repolarization of neurons, small stimuli causing repetitivedischarges of sensory and motor nerves.
    • There are distinct differences between the two basic ester types, giving rise to the terminology Type Iand II esters because of the different toxicity seen (Tables 4 and 5). Type II esters have a cyano group in the basic structure and cause dermal paresthesia (local anesthetic-like numbness, tingling) ifcontacting the skin. In poisoning situations (accidental ingestion or by suicidal intent), Type II esterscause CNS effects (disorientation, tremors, convulsions, coma, death) not elicited by Type I esters. Atthe neuronal tissue level, the differences between Type I and Type II esters is one of time in the rate ofclosure of sodium channels, being several minutes for Type II esters and only a few milliseconds withType I esters.
  12. Herbicides – Mechanisms
    • Herbicides constitute the greatest volume of any pesticide class used on crops, far more than the totalof insecticides and fungicides together. Use patterns can be differentiated into pre- and post-emergentchemicals, the former being applied to the seeded crop before germination in order to control weedproliferation while the latter agents are applied after germination of the seed crop.
    • By the broadest definition, an herbicide is any compound that is capable of either killing or severelyinjuring plants and is used for the elimination of plant growth or the killing off of plant parts. Thelatter part of the definition permits the inclusion of agents such as paraquat and diquat that are used as“top-kill” agents for the mechanical harvesting of potatoes.
    • For more than a century, chemicals have been used to control noxious vegetation (weeds) but manyof these (sulphuric acid, arsenic trioxide, sodium arsenite, iron and copper sulphate, petroleumdistillates) were either difficult to handle and/or were very toxic, non-specific and phytotoxic to thecrop as well as the weeds. By the 1930’s, many studies were conducted to find agents that wouldselectively destroy certain plant species (e.g. broad-leafed weeds). Many of these early chemicalswere more effective but still possessed mammalian toxicity. However, a few compounds served asprototype chemicals for further development. Today, there are some 10 to 15 different chemicalclasses of herbicides, all having different mechanisms of action on biochemical functions in plantswhich, for the most part, do not have counterparts in the mammalian system (Table 6). This does notmean, however, that these agents are without toxicity to mammals, some of which may be related tolow levels of impurities or by-products of synthesis or to vehicles (emulsifiers, co-solvents, petroleumdistillate solvents) needed to form either solutions or emulsions. Much of the current controversyaround these chemicals centres on demonstrated or suspected mutagenicity, teratogenicity and/orcarcinogenicity associated either with the agent(s) or with contaminants of manufacture found intechnical grade material. One example of this particular problem was the teratogenicity seen inexperimental animals with the chlorophenoxy herbicide, 2,4,5-T (technical grade) due to the presenceof up to 35 ppm of the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Teratogenicity wasnot observed with purified 2,4,5-T. Teratogenicity has been associated with Agent Orange (2,4-D and2,4,5-T) in both animals and in humans, again the potential toxicant being TCDD found in the productmanufactured for use during the Vietnam War.
  13. A. Chlorophenoxy Compounds
    • Effective herbicides against broadleafed weeds, the acids, salts and amines of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and monochlorophenoxyacetic acid (MCPA) have been used since the mid-to-late 1940’s in agriculture, forestry and for thecontrol of brush and weeds on roadside, railway and utilities rights of way. These chemicals mimicthe actions of auxins, natural growth hormones related to indoleacetic acid in plants.
    • Concerns about the level of TCDD found in technical grade 2,4,5-T led to a banning of this chemicalin the early 1980’s. It has been suspected that the toxicology (chloracne, dermatitis, teratology,elevated hepatic enzymes, disturbances of lipid metabolism, porphyria, etc.) associated with 2,4,5-T isrelated to the TCDD contaminant rather than the phenoxy acid. A similar statement can be made forthe experimental animal carcinogenicity. Human epidemiological studies have been inconclusive todate. The agents 2,4-D and MCPA still see agricultural, forestry and rights of way usage.
    • Perhaps an interesting facet of chlorophenoxy toxicology should be presented. The U.S.A. EPArequested a toxicological update on the database for 2,4-D. The manufacturers (some sevencompanies) acceded to this request by treating 2,4-D as a new chemical and contracted out the entirerange of standard toxicity tests as would be required for a new chemical. When this was completed in1985, the industry-based task force found nothing of toxicological significance that was not alreadyknown about the chemical, with one exception. This exception, the appearance of astrocytomas (braincarcinoma) in the CNS of male rats of a specific strain (Fischer 344) exposed to the highest level of2,4-D, was reviewed and the findings suggested that this tumour incidence was not treatment-relatedbut was due to the genetics of the animal model.
  14. B. Bipyridol Derivatives
    • Two agents in this class have demonstrated significant mammalian toxicity. Both diquat andparaquat have seen extensive use globally for vegetation control in rubber plantations, orchards,coconut plantations, etc. and as “top-kill” on potatoes (Figure 5). These agents produce differenttoxicity, diquat producing hepatic and renal damage in poisoning cases while paraquat elicitspulmonary toxicity.
    • Paraquat, a non-selective contact herbicide, is an important non-insecticidal poisoning agent aroundthe world. For example, it was the leading cause of pesticide-related, fatal poisonings in Taiwan,(54.4%) of the total in the years 1985-1993), a favourite of those attempting suicide. It is one of themost exquisite pulmonary (lung) toxicants known, invariably fatal if ingested in concentratedformulation (20 percent active ingredient) since the victim develops hypoxia (lack of oxygen) over aperiod of three to four weeks and dies of asphyxiation. It is untreatable.
    • Paraquat seeks out tissues with a high oxygen content, e.g. the lungs. It is taken up selectively intopulmonary tissue by a specific polyamine-diamine transport mechanism where it acts as a true catalystby forming an oxygen-carrying, reactive intermediate which produces hydrogen peroxide with the aidof pulmonary oxygenases, the peroxide damaging the lipid membranes of alveolar cells responsible forO2/CO2 exchange. Damage to and death of these cells results in the proliferation of non-functionalfibrotic cells, a loss of elasticity, reduction in gas exchange, pulmonary hypoxia and eventual death byasphyxiation. During this time, the paraquat is still reactive.
  15. C. Glyphosate Toxicity
    • The other “favourite” herbicide popular in suicide attempts and successes is glyphosate(ROUNDUPTM, VISIONTM). This agent is rapidly replacing paraquat as the agent of choice insuicides. However, glyphosate is relatively non-toxic. It is the surface-active agent,polyoxyethyleneimine, in the formulation that is toxic, the literature being quite convincing in thisrespect. The manufacturer is re-formulating to eliminate this agent.
    • Since most herbicides are relatively strong acid amines, phenols, esters, etc., it is not surprising thatthey cause dermal irritation, rash and contact dermatitis even in diluted form. The presence of cosolvents, emulsifiers, surfactants may also contribute to the dermal problems, enhancing penetration ofthe agent. There are subpopulations of individuals susceptible to dermal rashes or respiratorydysfunction (asthma-like attacks) when exposed to herbicide aerosols applied to grass and from offtarget drift. Many “responders” can be shown to have other allergic problems. The reaction may notbe substance-specific but the individual’s responding to the irritant property.
  16. Fungicides – Mechanisms
    • Fungicides have been developed from a wide range of chemical classes (acids, amides, anilines,arsenicals, bipyridyls, carbamates, phenols, phenoxyacids, triazines), most of them acting throughmechanisms and metabolizing reactions that convert the agents into one or more active mutagens,resulting in lethal mutations in the target organisms – fungi. A non-mutagenic fungicide would be oflittle use.
    • There is toxicity associated with exposure to these agents, particularly at high levels found inoccupational and accidental exposure. A good example is the contact dermatitis seen in tree planterswho routinely handle seedlings, the roots of which have been dipped in a protective fungicide. Fungicides are irritants to mucous membranes (eyes, nose, throat) and will produce agent-specificcontact dermatitis with repeated exposure (are dermal sensitizers – positive patch testing).
    • Since fungicides are mutagenic in the microbial assays (Ames Test, etc.) used as toxicologicalendpoints, positive results raise the spectre of teratogenicity (birth defects) and cancer asconsequences of exposure, these adverse health effects being considered to arise from non-lethal cellmutations.
    • The thiocarbamate fungicides (maneb, mancozeb, etc.) are teratogenic, but this may wellbe related to their known antithyroid activity.The thiocarbamate fungicides are also neurotoxic, producing signs/symptoms that look very muchlike carbon disulphide neurotoxicity. It has been demonstrated that carbon disulphide is onebreakdown product. I find it hard to believe that even the most careless individual could absorbenough agent to produce enough carbon disulphide.
  17. Organomercurials
    • Mercurials, both inorganic salts and organic compounds, have been used as seed dressings (antifungalagents) since the early 1900’s on cereal grains, vegetables, cotton, soybeans and sugar beets. Despitetheir recognized neurotoxicity and a number of tragic poisoning epidemics, these agents were used upuntil banned in the mid-1970’s. There are still reports of continued use in developing nations intropical climates because of their effectiveness and low cost. Thus, they still present a toxicologicalproblem. The basic structures of these agents are shown in Figure 6.
    • Acute intoxication generally involves the liver and kidneys as target organs, the actions being due tothe mercuric cation and inhibition of enzyme activities by binding to sulphydryl groups on proteins,resulting in distortion of the secondary and tertiary structures. In contrast, chronic exposure willinvolve most organ systems but will manifest itself in the CNS and PNS, particularly a debilitation ofperipheral sensory and motor neurons. The developing fetus and newborn are particularly at risk,transplacental exposure affecting the development of the nervous system – essentially an arrestation ofdevelopment at a “fetal stage” with no further myelination, astrocyte and glial cell development. Remember Minamata disease in Japan (methylmercury intoxication from contaminated seafood). Their continued use means that they remain a potential threat to environmental and human health.
  18. Global Pesticide Problems
    • The best database relating to pesticide poisonings is being generated in what are known as developingor emerging nations that are entering the global marketplace by producing fruits and vegetables forexport to countries in temperate climates such as ours. Many of these tropical countries (Central andSouth America, Southeastern Asia, Africa) can grow two or three crops in a year and are rapidlybecoming “breadbaskets” for Europe and North America. Increased food production means increaseduse of insecticides, herbicides and fungicides but, because of the high costs of importing the newerchemicals registered for use in North America and Europe, older and more toxic (and cheaper) agentsare being applied.
    • In addition to the inherent greater toxicity of these older agents, governments have rudimentarypesticide legislation and regulations at best, permit the importation of any pesticide (including thosebanned in the countries of origin and/or manufacture), and take little or no role in pesticide education or the protection of workers (applicators, farmers, etc.). Some of the banned pesticides are evenmanufactured “at home”, an aspect of industrialization steps being taken. Data coming out of suchcountries “finger” the organophosphorus and carbamate esters as being the major culprits inoccupational and accidental intoxications, but there are a surprising number of paraquat poisonings aswell as those from pyrethroid esters.
    • With uneducated workforces producing much of the export food supply, there is concern in importingcountries about residues of pesticide in and on fruits and vegetables entering the country. Not only isthere concern about above-tolerance levels of residues of agents registered (in the importing country)for use on the crop, but also about illegally used (non-registered) chemicals. There is a simplicity ofthought among such farmers that they will not be discovered/detected. This, of course, is false sinceimported produce is tested by government agencies of the importing countries to ascertain pesticidelevels (both registered and non-registered agents). Discovery of many samples not meeting thestandards of the importing country results in more frequent testing of produce coming from thatparticular exporter, giving rise to the accusation that the importer is “picking on” that exportingcountry. Unfortunately, countries wanting to get into the global export market have to learn the hardway. They must meet the stringent requirements of the importing country – the subject of manytraining and education programs.
    • Are residues a problem in our fresh produce? Extensive market basket studies in the U.S.A. andCanada have revealed that approximately 1.0 to 3.0 percent (1 to 3 per 100 samples) may exceed thetolerance established for a particular pesticide. Usually, when the investigators research the problem,they find that too much agent was applied (non-compliance with application rates) or that the crop washarvested too early following a pesticide application (non-compliance with good agricultural practicesfound on the label of the pesticide formulation). There are provincial legal and punitive proceduresfor such situations.
    • What about food residues in produce in the food supply in developing nations? Unfortunately, it is“open season”, no domestic testing being done, illegal chemicals being used, agents well abovetolerances (World Health Organization levels) appearing in regular food sources. Most people in thesecountries live largely on vegetable diets, creating genuine concerns about the “safety” of their foodwhether home-grown or purchased daily from street vendors (who purchase from market gardeners). There are few programs of consumer education to teach people about peeling fruits/vegetables, othertechniques of handling the fresh produce they buy or precautions that should be taken.
  19. Environmental Impact of Pesticides
    • Since no pesticide is exclusively specific for a given target (insect, weed, fungus, etc.), the firstconcerns have to be the impact on non-target organisms. Given the fact that the applicator isattempting to suppress or eradicate an epidemic-sized outbreak of some pest (the benefit of using apesticide), the risk involves the destruction of populations of “friendly” or useful organisms.
    • Considering insecticide use, the non-target organisms will include mites, spiders, natural predators ofthe target organism, pollinators, moths, butterflies, damsel flies and dragonflies, etc. The suppressionof one species may result in the suppression of all, with little chance for the natural predators of the target organism to exert an effect. What is created is a sterile environment except for the population ofthe pest organism. The non-target organisms are food sources for other living things – birds,salamanders, snakes, etc. – and lack of food results in a reduction in reproduction and perhaps eventhe loss of another species. Such scenarios are common, but one frequently finds that the pest is stillthere.
    • Recently, an article in the Saturday Globe and Mail reported the “discovery” of pesticides in the snowin the Canadian Rocky Mountains, the trend being that the higher the samples were taken, the greaterwere the levels detected. This is hardly surprising since the same phenomenon has been recognizedand studied in Arctic and Antarctic regions for many years. Frequently, the pesticides found (e.g.toxaphene) are not agents used in Canada or northern Europe but are used elsewhere. Essentially, thisphenomenon is similar to the “cold finger condensation” technique used in chemistry, volatile agentsin the air reaching upper levels where winds drive them to polar regions where, because of the coldtemperatures, the agents condense to liquids or particles and precipitate. Once on the earth’s surfaceor on water (ice), these lipid soluble agents begin to accumulate at different trophic levels in foodchains and bioconcentrate in species living in polar regions. Most resident species, including humans,have large body fat stores, the perfect place for these agents. There are potential human healthproblems among aboriginal people in the Arctic who have higher than average body fat burdens oforganochlorine compounds who pass these on to their newborn children via breast milk and who donot have alternative food sources to avoid these chemicals.
    • In teaching people in developing countries about pesticides, I tell them that what they spray this yearmay wind up in my country within one or two years, and the short-term gains they envisage whenusing these chemicals produce some long-term problems that are not easily solved.
  20. many tables.....
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Pharm 100 - Lesson F.1
2011-07-26 06:04:43

Lesson F.1
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