《职业卫生与职业医学》课程授课教案（讲稿）农药讲稿 Chemical Hazards and Occupational Poisoning - Pesticides

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1首页格式及要求课程名称：《OccupationalHealthandOccupationalMedicine》第5周,第9讲次摘要Chapter 1 Chemical Hazards and Occupational PoisoningSectiongthPesticides授课题目（章、节）本讲目的要求及重点难点：【目的要求】1.Learnthehistoryofpesticides,thedevelopmentofenvironmentalprotectiontheclassification of pesticides,the mechanism of pesticides and thepreventiveprinciple of pesticidepoisoning. 2.Mastering the conceptions of pesticides and different types, the characteristic anddiagnostic principle of pesticides. 3. Be familiar with the diagnostic and therapeutic principle ofOrganophosphorus insecticides,andCarbamates.Inaddition,clinical featuresshouldbeknownbystudents.[重点1Mechanism of Organophosphorus insecticides and Carbamates【难点】The character,diagnostic principle and therapeutic methods of.Pesticides内容【本讲课程的引入】Pesticidesarewideusedintheworldandourcountryhasmanypesticidesnearly for 3,o00 types.With the production and use of pesticides, we need to know the concept,danger,benefits of thepesticides and the development history of“Environmentalism Movement"”We alsoneed toknowthe classification of pesticides and the clinical symptoms, treatment of someimportant pesticides. Writing on the blackboard "Pesticides and Pesticides poisoning"【本讲课程的内容】Part 1 Introduce the concept of pesticides插入各种昆虫Pesticides, whatarethey?图片。引导学生Pesticides:An Introduction对农药应用的We've all heard theterm pesticides before, but do we really know what they are?直观印象。Pesticides arechemicalsthatweusetokillundesireableorganisms.（不希望有的生物）When we say undesireable organisms, we are referring to organisms (plants, animals, insects, etc.)that are hamful to us Some of these organisms, or "pests," eat our crops, while others spreaddiseases. And it doesn't always have to be this serious. Weeds （杂草）can be considered a pest forjust growing in the wrong places (our yards). The point is, if we are using some type of chemical tocontrol these pests, that chemical would be considered a pesticide.The Need for PesticidesMany of the pesticides that we use make our lives easier.For instance,(using some of our earlierexamples) the pesticides in wool and our wood makes our clothes and furniture last longer.Youwouldn't want to have to buy a new wool sweater every year, would you?The fact that pesticides are in our food is probably what makes people themost uncomfortable.Dowe really need that? Why can't all the farmers just grow food organically?2

2 1 首页格式及要求课程名称：《Occupational Health and Occupational Medicine》第 5 周，第 9 讲次摘要授课题目（章、节） Chapter 1 Chemical Hazards and Occupational Poisoning Section 8 th Pesticides 本讲目的要求及重点难点：【目的要求】1. Learn the history of pesticides, the development of environmental protection, the classification of pesticides, the mechanism of pesticides and the preventive principle of pesticide poisoning. 2. Mastering the conceptions of pesticides and different types, the characteristic and diagnostic principle of pesticides. 3. Be familiar with the diagnostic and therapeutic principle of Organophosphorus insecticides, and Carbamates. In addition, clinical features should be known by students. 【重点】Mechanism of Organophosphorus insecticides and Carbamates. 【难点】The character, diagnostic principle and therapeutic methods of. Pesticides. 内容【本讲课程的引入】Pesticides are wide used in the world and our country has many pesticides nearly for 3,000 types. With the production and use of pesticides, we need to know the concept, danger, benefits of the pesticides and the development history of “Environmentalism Movement”. We also need to know the classification of pesticides and the clinical symptoms, treatment of some important pesticides. Writing on the blackboard “Pesticides and Pesticides poisoning” 【本讲课程的内容】 Part 1 Introduce the concept of pesticides Pesticides, what are they? Pesticides: An Introduction We've all heard the term pesticides before, but do we really know what they are? Pesticides are chemicals that we use to kill undesireable organisms.（不希望有的生物） When we say undesireable organisms, we are referring to organisms (plants, animals, insects, etc.) that are harmful to us. Some of these organisms, or "pests," eat our crops, while others spread diseases. And it doesn't always have to be this serious. Weeds（杂草） can be considered a pest for just growing in the wrong places (our yards). The point is, if we are using some type of chemical to control these pests, that chemical would be considered a pesticide. The Need for Pesticides Many of the pesticides that we use make our lives easier. For instance, (using some of our earlier examples) the pesticides in wool and our wood makes our clothes and furniture last longer. You wouldn't want to have to buy a new wool sweater every year, would you? The fact that pesticides are in our food is probably what makes people the most uncomfortable. Do we really need that? Why can't all the farmers just grow food organically? 插入各种昆虫图片。引导学生对农药应用的直观印象

Here's something to think about:The world population is5billion and growing.Ofthose, 7o0 million are undernourished.Even with the use of pesticides, over one-third ofour food is lost topests.(Without pesticides, the losses will probably be even higher).Doyou think we can afford to feed the world organically?The answer, unfortunately, is that with current agricultural methods and technologies it isnot possibleto provide thequantities currentlyneededfor the number of people living inthe earth.Pesticides allowusto increase our harvests and feed morepeopleInadditiontoapplicationsinagriculture（农业），pesticideshavemanyotherimportant插入疮疾病人uses.Many pests transmit diseases which are verydangerous to us.红细胞图片Forexample,inthepast,malaria（宠疾）wasoncea seriousdiseasethatkilledmillions of people globally.(The photo to the left shows the red blood cells of someonewithmalaria.)Tofight this problem, weused thepesticideDDT, tokill themosquitoeswhichtransmittedthedisease.It was successful, and thenumber of peoplewhodiedfrommalariashrankdrastically.(Moreonthislater.)Here's another example that many of us can relateto:Millions of people in the US.haveallergic reactions to the cockroaches in our homes.The pesticides in insect sprays andbaitshelpreducethisproblem插入农药在大Dangers of Pesticides气、土壤、水及Presently, we are using more pesticides than ever. Here in the US, we use almost 4生物中的循环pounds of it annually per person! Although most modern pesticides are much safer than示意图theirpredecessors, afewofour commonlyusedpesticidesareconsideredtoxic.In lab tests where high doses of pesticides were given, researchers have observedsomesignificanthealtheffects.Geneticdamage，reproductive（生殖的）problems,and possible linkstocancerare just someof the risks associated withpesticides.As you can see, the pesticide issue is very complex.There is definitely a need for certainpesticides in such areas as agriculture and disease prevention, and yet there are also someobvious health risks from some of these chemicals.To illustrate the constant debate over pesticide usage and to helpyoudevelop your ownopinion about pesticides, we'll nowtalk aboutDDT, oneof themost powerful andcontroversial pesticides in the20th century.Part 2 The development history of environmental protection, especiallythe book“"The silent spring"written by Mrs. Carson"Silent Spring"is written by a courageous woman who pioneered the struggle forenvironmental protectionToday,environmental protection has becomea worldwidemovement. It is almost fashionabletotalk about this problem.But at the time this articlewasfirstpublished,theauthor whosenamewasCarson,wasverymuchunder attack.She was accused of being an alarmist. However Carson did not give in She went onfighting. Soon the idea caught on. More and more people began to join in So today thereis a general consensus that we are facing a very serious ecological problem, and we mustdoeverythingpossibletokeepourwaterandaircleanDuring the 1950s, farmers used powerful new pesticides to control pest populations.These synthetic pesticides killed many different insects and they worked rapidly2

3 Here's something to think about: The world population is 5 billion and growing. Of those, 700 million are undernourished. Even with the use of pesticides, over one-third of our food is lost to pests. (Without pesticides, the losses will probably be even higher). Do you think we can afford to feed the world organically? The answer, unfortunately, is that with current agricultural methods and technologies it is not possible to provide the quantities currently needed for the number of people living in the earth. Pesticides allow us to increase our harvests and feed more people. In addition to applications in agriculture（农业）, pesticides have many other important uses. Many pests transmit diseases which are very dangerous to us. For example, in the past, malaria（疟疾）was once a serious disease that killed millions of people globally. (The photo to the left shows the red blood cells of someone with malaria.) To fight this problem, we used the pesticide DDT, to kill the mosquitoes which transmitted the disease. It was successful, and the number of people who died from malaria shrank drastically. (More on this later.) Here's another example that many of us can relate to: Millions of people in the US. have allergic reactions to the cockroaches in our homes. The pesticides in insect sprays and baits help reduce this problem. Dangers of Pesticides Presently, we are using more pesticides than ever. Here in the US, we use almost 4 pounds of it annually per person! Although most modern pesticides are much safer than their predecessors, a few of our commonly used pesticides are considered toxic. In lab tests where high doses of pesticides were given, researchers have observed some significant health effects. Genetic damage, reproductive（生殖的） problems, and possible links to cancer are just some of the risks associated with pesticides. As you can see, the pesticide issue is very complex. There is definitely a need for certain pesticides in such areas as agriculture and disease prevention, and yet there are also some obvious health risks from some of these chemicals. To illustrate the constant debate over pesticide usage and to help you develop your own opinion about pesticides, we'll now talk about DDT, one of the most powerful and controversial pesticides in the 20th century. Part 2 The development history of environmental protection, especially the book “The silent spring” written by Mrs. Carson “Silent Spring”is written by a courageous woman who pioneered the struggle for environmental protection. Today, environmental protection has become a worldwide movement. It is almost fashionable to talk about this problem. But at the time this article was first published, the author whose name was Carson, was very much under attack. She was accused of being an alarmist. However Carson did not give in. She went on fighting. Soon the idea caught on. More and more people began to join in. So today there is a general consensus that we are facing a very serious ecological problem, and we must do everything possible to keep our water and air clean. During the 1950s, farmers used powerful new pesticides to control pest populations. These synthetic pesticides killed many different insects and they worked rapidly. 插入疟疾病人红细胞图片插入农药在大气、土壤、水及生物中的循环示意图

However, they created serious direct and indirect problems in the environment longafter their initial usagePrior to the 1960's, DDT was the "wonder pesticide" that saved the lives of millions ofpeople, During wartime, it protected our soldiers from insect carried diseases, whichpreviously had taken more lives than battle itself.At that time,we did not complainabout the possibledangers ofDDT,as long as it was used to control human diseases.Then in 1962, Rachel Carson came out with her extremely influential work, SilentSpring. Eventually printed in 17 countries and in 10 languages, the work made thedangers of DDT well known. It aroused fear that we were being poisoned withpesticides.She called these pesticides"biocides"(杀生物剂)to implythat they werekilling everything living, not just pests. According to Carson, pesticides, andespeciallyDDT,were carcinogens（致癌物）whichwereupsettingthebalanceofnature.President Kennedy read Rachel Carson work. Shortly afterwards, the Life SciencePanel underthe President's ScienceAdvisory（顾问）was orderedto begin reviewingpesticide use. In 1963, the panel called for legislative measures to protect theenvironmentfromthesechemicals.1967,the EnvironmentalDefense Fund was created to furtherreview pesticideusage and safety.And by the late 1960's, there was already a tremendous growth inpublic concern over pesticidesIn 1972, the EPA put out a nationwide ban on DDT. It was subsequently replacedwith otherpesticides that degrademuchmore quickly than DDT.Today,over 20years later, do you think that DDT is still around us?DDT is still one of the most important and well known pesticide in the world. Whileit's no longer used in the U.S., its use continues in many other parts of the world. Infact, DDT usage in the world today is roughly the same as it was prior to the ban bymost of the Western countries. Some countries which still use DDT include India,China, South America, Africa, and Malaysia.Today, the environmental movement is very strong. In the United States, we spendroughly 600 million dollars every year in support of it Roughly 3/4 of the U.S.population agrees with it, and more than half of the us would be willing to pay moremoney just to get organic produce, What other economic factors result from not usingpesticides?Part3ClassificationofpesticidesTypes of PesticidesPesticides arechemicals used to control indoorand outdoorpests such as insects and4

4 However, they created serious direct and indirect problems in the environment long after their initial usage. Prior to the 1960's, DDT was the "wonder pesticide" that saved the lives of millions of people. During wartime, it protected our soldiers from insect carried diseases, which previously had taken more lives than battle itself. At that time, we did not complain about the possible dangers of DDT, as long as it was used to control human diseases. Then in 1962, Rachel Carson came out with her extremely influential work, Silent Spring. Eventually printed in 17 countries and in 10 languages, the work made the dangers of DDT well known. It aroused fear that we were being poisoned with pesticides. She called these pesticides "biocides"(杀生物剂) to imply that they were killing everything living, not just pests. According to Carson, pesticides, and especially DDT, were carcinogens （致癌物）which were upsetting the balance of nature. President Kennedy read Rachel Carson work. Shortly afterwards, the Life Science Panel under the President's Science Advisory （顾问）was ordered to begin reviewing pesticide use. In 1963, the panel called for legislative measures to protect the environment from these chemicals. 1967, the Environmental Defense Fund was created to further review pesticide usage and safety. And by the late 1960's, there was already a tremendous growth in public concern over pesticides. In 1972, the EPA put out a nationwide ban on DDT. It was subsequently replaced with other pesticides that degrade much more quickly than DDT. Today, over 20 years later, do you think that DDT is still around us? DDT is still one of the most important and well known pesticide in the world. While it's no longer used in the U.S., its use continues in many other parts of the world. In fact, DDT usage in the world today is roughly the same as it was prior to the ban by most of the Western countries. Some countries which still use DDT include India, China, South America, Africa, and Malaysia. Today, the environmental movement is very strong. In the United States, we spend roughly 600 million dollars every year in support of it. Roughly 3/4 of the U.S. population agrees with it, and more than half of the us would be willing to pay more money just to get organic produce. What other economic factors result from not using pesticides? Part 3 Classification of pesticides Types of Pesticides Pesticides are chemicals used to control indoor and outdoor pests such as insects and

5 rodents, as well as weeds and other harmful plants. Pesticides can also be biological in nature. There are various types of pesticides, including: • Herbicides（除草剂） - control weeds and other harmful plants • Insecticides （杀虫剂）- control insects such as termites and moths • Nematicides（杀线虫剂）- control roundworms • Fungicides （杀真菌剂）- control fungus • Rodenticides（灭鼠剂） - control mice, rats, and other rodents Pesticide Exposure People can be exposed to pesticides through food, air, and water: Food - since they are used on crops, trace amounts of pesticides can be found in many foods. Water - runoff from pesticide use can contaminate groundwater, rivers, lakes, and streams. Although drinking water provided through municipal systems is tested regularly for increased levels of pesticides, private wells are not. Air - air currents can carry pesticides that were sprayed in a nearby area. This phenomenon is known as pesticide drift. Exposure to pesticides can lead to serious side effects, including: • Redness, swelling, or blistering of the skin （皮肤红肿，起泡） • Stinging or swelling of the eyes, mouth, and nose • Shortness of breath • Nausea and vomiting （恶心和呕吐） • Diarrhea （腹泻） • Headache • Fatigue • Numbness （麻木） In addition to the above side effects, pesticide poisoning can also have severe effects on both the reproductive system and the endocrine system (system that controls the body's hormones). If you or a loved one has been harmed by pesticides, you may want to contact a personal injury attorney for more information. What types of injuries or health problems occur due to these chemicals? Pesticides are dangerous both at the moment of exposure and over the course of many years. Acute effects occur immediately following exposure to a pesticide. These reactions range from simple skin or eye irritation to serious damage to the internal organs. Chronic effects occur because of repeated exposure, and may take months or

years to surface.These effects may include cancer, birth defects, genetic defects, andhormonal changesPart4IntroductionofOrganophosphorus insecticides（有机磷杀虫药）FollowingtheSecondWorldWar，organochlorinepesticides（有机氯杀虫剂）madea major contribution to improvements in agricultural output and in thecontrolof disease vectors.Whilethepersistence ofthese compounds afterapplication wasofconsiderablebenefittotheuser,italso introducedproblems.Astheseproblemsbecame morewidelyappreciated, insect pest control began to rely more on theanticholinesterase（抗胆碱酯酶）organophosphorusandcarbamateesterpesticides.A largenumber of such esters havebeen introduced on themarket, and a muchgreaternumberhavebeen screenedforpesticidal activity.Unlikemany environmentalpollutants,pesticides aredeliberately added to the environment and are devised to belethal agentsEFFECTSONMAN1.Acute Cholinergic PoisoningTheclinical pictureof organophosphorus intoxication（中毒）resultsfromaccumulation of ACh at nerve endings.The syndrome is described in detail inseveral major references (Namba et al.,1971;Kagan,1977;Taylor,1980,HMSO,1983; Plestina, 1984)..The symptoms can be summarized in three groups as follows:(a)Muscarinicmanifestations（毒草碱样表现）increasedbronchial secretion, excessive sweating,salivation,andlachrymation,pinpoint pupils, bronchoconstriction, abdominal cramps (vomiting anddiarrhoea); andbradycardia（心动过缓）(b)Nicotinicmanifestations（烟碱样表现）fasciculation offine muscles and, in more severecases,ofdiaphragmandrespiratorymuscles,andtachycardia（心动过速）(c)Central nervous systemmanifestationsheadachedizziness（头晕，头昏，眩晕），restlessness,andanxietymentalconfusion,convulsions,andcoma,anddepression of the respiratory centre.All these symptoms can occur in different combinations and can vary in time ofonset, sequence, and duration, depending on the chemical, dose, and route ofexposure.Mild poisoning might include muscarinic and nicotinic signs only.Severe cases always show central nervous system involvement,the clinical picture isdominatedbyrespiratoryfailure,sometimesleadingtopulmonaryoedema（水肿），due to the combination ofthe above-mentioned symptoms.Clinical diagnosis is relatively easy and is based on(a)medical history and circumstances of exposure,and(b)presenceofseveral oftheabove-mentionedsymptoms,inparticulara

6 years to surface. These effects may include cancer, birth defects, genetic defects, and hormonal changes. Part 4 Introduction of Organophosphorus insecticides（有机磷杀虫药） Following the Second World War, organochlorine pesticides（有机氯杀虫剂） made a major contribution to improvements in agricultural output and in the control of disease vectors. While the persistence of these compounds after application was of considerable benefit to the user, it also introduced problems. As these problems became more widely appreciated, insect pest control began to rely more on the anticholinesterase（抗胆碱酯酶）organophosphorus and carbamate ester pesticides. A large number of such esters have been introduced on the market, and a much greater number have been screened for pesticidal activity. Unlike many environmental pollutants, pesticides are deliberately added to the environment and are devised to be lethal agents. EFFECTS ON MAN 1. Acute Cholinergic Poisoning The clinical picture of organophosphorus intoxication（中毒） results from accumulation of ACh at nerve endings. The syndrome is described in detail in several major references (Namba et al., 1971; Kagan, 1977; Taylor, 1980; HMSO, 1983; Plestina, 1984). The symptoms can be summarized in three groups as follows: (a) Muscarinic manifestations (毒蕈碱样表现) - increased bronchial secretion, excessive sweating, salivation, and lachrymation; - pinpoint pupils, bronchoconstriction, abdominal cramps (vomiting and diarrhoea); and - bradycardia（心动过缓）. (b) Nicotinic manifestations （烟碱样表现） - fasciculation of fine muscles and, in more severe cases, of diaphragm and respiratory muscles; and - tachycardia（心动过速）. (c) Central nervous system manifestations - headache, dizziness（头晕,头昏,眩晕）, restlessness, and anxiety; - mental confusion, convulsions, and coma; and - depression of the respiratory centre. All these symptoms can occur in different combinations and can vary in time of onset, sequence, and duration, depending on the chemical, dose, and route of exposure. Mild poisoning might include muscarinic and nicotinic signs only. Severe cases always show central nervous system involvement; the clinical picture is dominated by respiratory failure, sometimes leading to pulmonary oedema（水肿）, due to the combination of the above-mentioned symptoms. Clinical diagnosis is relatively easy and is based on: (a) medical history and circumstances of exposure; and (b) presence of several of the above-mentioned symptoms, in particular

bronch-oconstriction and pinpoint pupils not reactive to the light.Pulse rate is notof diagnosticvalue, because the AChEeffects on the heart reflect the complexinnervation of this organ.Ontheotherhand, sincechanges in the conduction andexcitabilityofthe heart might be life-threatening,monitoring should beperformed.Confirmation of diagnosis ismade by measurement of AChE in RBC or plasma-pseudoChE, and, also,of thedibucaine number (to rule out genetic deficiencies).Measurements of blood-ChE during therapy are also useful in assessing thetreatment with oximes,though there might not be a correlation between the severity ofsymptoms and the degree of ChE inhibition: comparison should be made withpre-exposure levels, wherever possibleChemical analysis of body fluids (urine, blood, gastric lavage) should be made inorder to identify the compounds that caused poisoning2. Treatment of Organophosphate Insecticide Poisoning in ManAll cases of organophosphorus poisoning should be dealt with as an emergencyand the patient sent to hospital as quickly as possible.Although symptoms maydevelop rapidly, delay in onset or a steady increase in severity may be seen up to 48 hafteringestionof someformulatedorganophosphorus insecticides.Extensivedescriptionsoftreatmentofpoisoningbyorganophosphorusinsecticides are given in several major references (Kagan 1977; Taylor 1980; HMSO,1983; Plestina 1984)and will also be included in the IPCS Health and Safety Guidestobepreparedfor selectedorganophosphorus insecticides.The treatment is based on:(a)minimizingtheabsorption,(b) general supportive treatment, and(c)specific pharmacological treatment.2.1MinimizingtheabsorptionWhendermal exposureoccurs,decontaminationproceduresincluderemoval ofcontaminated clothesand washing ofthe skin withalkaline soap orwitha sodiumbicarbonate solution.Particular care should be taken in cleaning the skin areawherevenupuncture is performed.Bloodmight be contaminated with direct-actingorganophosphorus esters, and, therefore, inaccurate measures of ChE inhibition mightresult.Extensive eye irrigation withwater orsaline should alsobeperformed.In thecase ofingestion,vomitingmightbe induced,ifthepatientis conscious, bytheadministration of ipecacuanha syrup (10-30ml)followed by 200 ml water.Thistreatmentis,however,contraindicated inthecaseof pesticidesdissolved inhydrocarbon solvents.Gastriclavage(withadditionofbicarbonate solution oractivated charcoal)can alsobeperformed,particularly in unconsciouspatients,takingcaretoprevent aspiration of fluids into the lungs (i.e., only after a tracheal tube has beenplaced).The volume of fluid introduced into the stomach should be recorded and samples7

7 bronch- oconstriction and pinpoint pupils not reactive to the light. Pulse rate is not of diagnostic value, because the AChE effects on the heart reflect the complex innervation of this organ. On the other hand, since changes in the conduction and excitability of the heart might be life- threatening, monitoring should be performed. Confirmation of diagnosis is made by measurement of AChE in RBC or plasmapseudoChE, and, also, of the dibucaine number (to rule out genetic deficiencies). Measurements of blood-ChE during therapy are also useful in assessing the treatment with oximes, though there might not be a correlation between the severity of symptoms and the degree of ChE inhibition: comparison should be made with pre-exposure levels, wherever possible. Chemical analysis of body fluids (urine, blood, gastric lavage) should be made in order to identify the compounds that caused poisoning. 2. Treatment of Organophosphate Insecticide Poisoning in Man All cases of organophosphorus poisoning should be dealt with as an emergency and the patient sent to hospital as quickly as possible. Although symptoms may develop rapidly, delay in onset or a steady increase in severity may be seen up to 48 h after ingestion of some formulated organophosphorus insecticides. Extensive descriptions of treatment of poisoning by organophosphorus insecticides are given in several major references (Kagan 1977; Taylor 1980; HMSO, 1983; Plestina 1984) and will also be included in the IPCS Health and Safety Guides to be prepared for selected organophosphorus insecticides. The treatment is based on: (a) minimizing the absorption; (b) general supportive treatment; and (c) specific pharmacological treatment. 2.1 Minimizing the absorption When dermal exposure occurs, decontamination procedures include removal of contaminated clothes and washing of the skin with alkaline soap or with a sodium bicarbonate solution. Particular care should be taken in cleaning the skin area where venupuncture is performed. Blood might be contaminated with direct-acting organophosphorus esters, and, therefore, inaccurate measures of ChE inhibition might result. Extensive eye irrigation with water or saline should also be performed. In the case of ingestion, vomiting might be induced, if the patient is conscious, by the administration of ipecacuanha syrup (10 - 30 ml) followed by 200 ml water. This treatment is, however, contraindicated in the case of pesticides dissolved in hydrocarbon solvents. Gastric lavage (with addition of bicarbonate solution or activated charcoal) can also be performed, particularly in unconscious patients, taking care to prevent aspiration of fluids into the lungs (i.e., only after a tracheal tube has been placed). The volume of fluid introduced into the stomach should be recorded and samples

of gastric lavage frozen and stored for subsequent chemical analysis.Iftheformulation of the pesticide involved is available, it should also be stored for furtheranalysis (i.e., detection oftoxicologically relevant impurities).A purge to removethe ingested compound can be administered2.2GeneralsupportivetreatmentArtificial respiration (viaa tracheal tube)should be started at thefirst sign ofrespiratoryfailureand maintained for as longasnecessary.Cautious administration of fluids is advised, as well as general supportive andsymptomatic pharmacological treatment and absolute rest.2.3Specificpharmacologicaltreatment2.3.1Atropine（阿托品）Atropine should be given, beginning with 2 mg iv and given at 15 to 30-minintervals.Thedose andthefrequencyofatropinetreatmentvariesfromcaseto case,but should maintain the patient fully atropinized (dilated pupils, dry mouth, skinflushing,etc.).Continuous infusionof atropinemaybenecessary in extremecasesand total dailydosesup to several hundred mg may benecessary duringthefirstfewdaysoftreatment2.3.2Oximereactivators（类还原剂)Cholinesterasereactivators（e.g.，pralidoxime解磷定，obidoxime双复磷）specifically restore AChE activity inhibited by organophosphates.This is not thecase withenzymes inhibited by carbamates.The treatment should begin as soon aspossible,because oximes are not effectiveon"aged"phosphorylated ChEs(section6.5.3).However, ifabsorption, distribution, and metabolism are thought to bedelayed for any reasons, oximes can be administered for several days afterintoxication,Effectivetreatment with oximesreducestherequired doseofatropine.Pralidoxime is the most widely available oxime.A dose of 1 gpralidoxime can begiven either im or iv and repeated 2-3 times per day or, in extreme cases, more often.Ifpossible,bloodsamplesshouldbetakenforAChEdeterminationsbeforeandduringtreatment.Skin should becarefully cleansedbeforesampling.Resultsofthe assays should influence thedecision whether to continue oxime therapy after thefirst2days.The possible beneficial effects of oxime therapy on CNS-derived symptoms isdiscussed in section 6.5.3.2.3.3Diazepam（安定）Diazepam should be included in the therapy of all but the mildest cases.Besides relieving anxiety,it appears to counteract someaspects of CNS-derivedsymptoms,which are notaffected by atropine.Doses of 10mg sc or ivareappropriate and may be repeated as required (Vale & Scott, 1974).Other centrallyacting drugs and drugs that may depress respiration are not recommended in theabsence ofartificialrespiration procedures8

8 of gastric lavage frozen and stored for subsequent chemical analysis. If the formulation of the pesticide involved is available, it should also be stored for further analysis (i.e., detection of toxicologically relevant impurities). A purge to remove the ingested compound can be administered. 2.2 General supportive treatment Artificial respiration (via a tracheal tube) should be started at the first sign of respiratory failure and maintained for as long as necessary. Cautious administration of fluids is advised, as well as general supportive and symptomatic pharmacological treatment and absolute rest. 2.3 Specific pharmacological treatment 2.3.1 Atropine (阿托品) Atropine should be given, beginning with 2 mg iv and given at 15 to 30-min intervals. The dose and the frequency of atropine treatment varies from case to case, but should maintain the patient fully atropinized (dilated pupils, dry mouth, skin flushing, etc.). Continuous infusion of atropine may be necessary in extreme cases and total daily doses up to several hundred mg may be necessary during the first few days of treatment. 2.3.2 Oxime reactivators (肟类还原剂) Cholinesterase reactivators (e.g., pralidoxime 解磷定, obidoxime 双复磷) specifically restore AChE activity inhibited by organophosphates. This is not the case with enzymes inhibited by carbamates. The treatment should begin as soon as possible, because oximes are not effective on "aged" phosphorylated ChEs (section 6.5.3). However, if absorption, distribution, and metabolism are thought to be delayed for any reasons, oximes can be administered for several days after intoxication. Effective treatment with oximes reduces the required dose of atropine. Pralidoxime is the most widely available oxime. A dose of 1 g pralidoxime can be given either im or iv and repeated 2 - 3 times per day or, in extreme cases, more often. If possible, blood samples should be taken for AChE determinations before and during treatment. Skin should be carefully cleansed before sampling. Results of the assays should influence the decision whether to continue oxime therapy after the first 2 days. The possible beneficial effects of oxime therapy on CNS-derived symptoms is discussed in section 6.5.3. 2.3.3 Diazepam （安定） Diazepam should be included in the therapy of all but the mildest cases. Besides relieving anxiety, it appears to counteract some aspects of CNS-derived symptoms, which are not affected by atropine. Doses of 10 mg sc or iv are appropriate and may be repeated as required (Vale & Scott, 1974). Other centrally acting drugs and drugs that may depress respiration are not recommended in the absence of artificial respiration procedures

2.3.4Notesontherecommendedtreatmenta）Effectsofatropine（阿托品）andoxime（）The combined effectfar exceeds thebenefitofeitherdrug singly(b)ResponsetoatropineTheresponse of the eye pupil may beunreliable in cases of organophosphoruspoisoning.Aflushed skin and drying of secretions are the best guide to theeffectivenessofatropinisation（阿托品化），Althoughrepeateddosingmaywellbenecessary, excessive doses at any onetime may cause toxic side-effects.Pulse-rateshould notexceed 120/min.(c)PersistenceoftreatmentSome organophosphorus pesticides are very lipophilic and may be taken into,and then released from, fat depots over aperiod ofmany days.It is therefore quiteincorrectto abandon oximetreatment after1-2days on the supposition that allinhibitedenzymewillbeaged.Ecobichonetal.(1977)notedpromptimprovementinbothconditionandblood-ChEsinresponsetopralidoxime（解磷定）givenonthe11th- 15th days after major symptoms of poisoning appeared due to extendedexposuretofenitrothion（杀螺硫磷）（adimethylphosphate（二甲基磷酸盐）witha short half-life for aging of inhibited AChE)(d)Dosage ofatropineand oximeTherecommendeddosesabovepertaintoexposures,usual foranoccupationalsetting,but,in thecase ofvery severe exposure ormassiveingestion(accidental ordeliberate),thetherapeutic doses maybe extended considerably.Warriner etal.(1977)reported the case ofa patient who drank alarge quantity of dicrotophos, inerror, while drunk.Therapeutic dosages were progressively increased up to 6 mgatropineiv every15mintogether withcontinuous iv infusion of pralidoxime chlorideat 0.5 g/hfor72h, from days 3 to 6 after intoxication.After considerableimprovement, the patient relapsed and further aggressive therapy was given at adeclining rate from days 10 to 16 (atropine) and to day 23 (oxime), respectively.Intotal, 92 g of pralidoxime chloride and 3912 mg of atropine were given and the patientwasdischargedonthethirty-thirddaywithnoapparentsequelae（后遗症）Part5IntroductionofCarbamatespoisoning（氨基甲酸酯类农药中毒），especiallydiagnosticandtherapeuticprinciple（45min）Themetabolicfateofcarbamatesisbasicallythe sameinplants,insects,andmammals.Carbamatesareusually easily absorbed through the skin,mucousmembranes,and respiratoryand gastrointestinal tracts,butthereareexceptions.Generally,themetabolitesarelesstoxicthantheparentcompounds.However,incertain cases,themetabolitesare just as toxic or even moretoxic than theparentcarbamate.Inmost mammals, themetabolites aremainly excreted rather rapidlyinthe urine.Thedog seems to be different inthisrespect.Accumulation takes placeincertain cases,but isofminorimportancebecause of the rapid metabolismThe carbamylation of the enzyme is unstable,and the regeneration of AChE isrelativelyrapid compared with that from a phosphorylated enzyme.Thus,carbamatepesticidesare lessdangerous withregard tohumanexposurethan organophosphorusC

9 2.3.4 Notes on the recommended treatment (a) Effects of atropine（阿托品）and oxime（肟） The combined effect far exceeds the benefit of either drug singly. (b) Response to atropine The response of the eye pupil may be unreliable in cases of organophosphorus poisoning. A flushed skin and drying of secretions are the best guide to the effectiveness of atropinisation（阿托品化）. Although repeated dosing may well be necessary, excessive doses at any one time may cause toxic side-effects. Pulse-rate should not exceed 120/min. (c) Persistence of treatment Some organophosphorus pesticides are very lipophilic and may be taken into, and then released from, fat depots over a period of many days. It is therefore quite incorrect to abandon oxime treatment after 1 - 2 days on the supposition that all inhibited enzyme will be aged. Ecobichon et al. (1977) noted prompt improvement in both condition and blood-ChEs in response to pralidoxime（解磷定）given on the 11th - 15th days after major symptoms of poisoning appeared due to extended exposure to fenitrothion（杀螟硫磷） (a dimethyl phosphate（二甲基磷酸盐）with a short half-life for aging of inhibited AChE). (d) Dosage of atropine and oxime The recommended doses above pertain to exposures, usual for an occupational setting, but, in the case of very severe exposure or massive ingestion (accidental or deliberate), the therapeutic doses may be extended considerably. Warriner et al. (1977) reported the case of a patient who drank a large quantity of dicrotophos, in error, while drunk. Therapeutic dosages were progressively increased up to 6 mg atropine iv every 15 min together with continuous iv infusion of pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to 6 after intoxication. After considerable improvement, the patient relapsed and further aggressive therapy was given at a declining rate from days 10 to 16 (atropine) and to day 23 (oxime), respectively. In total, 92 g of pralidoxime chloride and 3912 mg of atropine were given and the patient was discharged on the thirty-third day with no apparent sequelae（后遗症）. Part 5 Introduction of Carbamates poisoning（氨基甲酸酯类农药中毒）, especially diagnostic and therapeutic principle（45min） The metabolic fate of carbamates is basically the same in plants, insects, and mammals. Carbamates are usually easily absorbed through the skin, mucous membranes, and respiratory and gastrointestinal tracts, but there are exceptions. Generally, the metabolites are less toxic than the parent compounds. However, in certain cases, the metabolites are just as toxic or even more toxic than the parent carbamate. In most mammals, the metabolites are mainly excreted rather rapidly in the urine. The dog seems to be different in this respect. Accumulation takes place in certain cases, but is of minor importance because of the rapid metabolism. The carbamylation of the enzyme is unstable, and the regeneration of AChE is relatively rapid compared with that from a phosphorylated enzyme. Thus, carbamate pesticides are less dangerous with regard to human exposure than organophosphorus

pesticides.The ratio between the dose required to produce death and the doserequired to produce minimum symptoms of poisoning is substantially larger forcarbamate compounds than for organophosphorus compounds.Because oftheir chemical structure, carbamatesdonot causedelayedneuropathy.Healthhazardsformanoccurmainlyfromoccupationalover-exposuretocarbamate insecticides resulting in poisoning characterized bycholinergic symptomscaused by inhibition ofthe enzyme AChE.Various cases of intoxication have beendescribed.Mostof them were spraymen applyinginsecticidesinsidehouses inthetropics to control mosquito vectors of malaria, or plant protection workers.Themain routes of exposure areinhalationand skinCarbamates are effective insecticides byvirtue of theirability to inhibit AChE in thenervous system.AChEcatalyses thehydrolysis of the neurotransmitteracetylcholine (ACh)to choline and acetic acidACh is the synaptic mediator of nerve impulses in the nervous system ofmammalsand insects:(a)as a neurotransmitter in the brain ofmammals, and inthecentral nervous system of insects,（b）asapre-ganglionic（（神经）节前的）neurotransmitterintheautonomicnervous system ofmammals,(c)in post-ganglionic nerve endings of the autonomicnervous system,and(d)attheneuromuscular junctionofskeletal muscleCarbamates, like organophosphates,can inhibitesterases(酯酶）that have serinein their catalytic centre; these are called serine-esterases or beta-esterases.Althoughthe inhibition of serine-esterases other than AChE is not significant for the toxicity ofthe compounds,it mayhave significanceforthepotentiation oftoxicity of othercompounds after long-term low-level exposure (Sakai & Matsumura, 1968, 1971;Aldridge& Magos, 1978)To understand the mechanism of toxicity, it is necessary to examine the eventsthat takeplace at theneuromuscular junction.When amuscle isinnervated,asshown in Fig.2, a nerve impulse moving down a neuron reaches the nerve endingwhere ACh, which is stored in vesicles at the nerve endings, is released into thejunction.Within2-3ms,AChimpingesonthereceptorsideof themusclevesiolesACHChceptorAChsite1ACh"0nerve impulse0musclenerveendingAChE-AChcomplexWHO86120610

10 pesticides. The ratio between the dose required to produce death and the dose required to produce minimum symptoms of poisoning is substantially larger for carbamate compounds than for organophosphorus compounds. Because of their chemical structure, carbamates do not cause delayed neuropathy. Health hazards for man occur mainly from occupational over-exposure to carbamate insecticides resulting in poisoning characterized by cholinergic symptoms caused by inhibition of the enzyme AChE. Various cases of intoxication have been described. Most of them were spraymen applying insecticides inside houses in the tropics to control mosquito vectors of malaria, or plant protection workers. The main routes of exposure are inhalation and skin. Carbamates are effective insecticides by virtue of their ability to inhibit AChE in the nervous system. AChE catalyses the hydrolysis of the neurotransmitter acetylcholine (ACh) to choline and acetic acid. ACh is the synaptic mediator of nerve impulses in the nervous system of mammals and insects: (a) as a neurotransmitter in the brain of mammals, and in the central nervous system of insects; (b) as a pre-ganglionic（(神经)节前的） neurotransmitter in the autonomic nervous system of mammals; (c) in post-ganglionic nerve endings of the autonomic nervous system; and (d) at the neuromuscular junction of skeletal muscle. Carbamates, like organophosphates, can inhibit esterases（酯酶）that have serine in their catalytic centre; these are called serine-esterases or beta-esterases. Although the inhibition of serine-esterases other than AChE is not significant for the toxicity of the compounds, it may have significance for the potentiation of toxicity of other compounds after long-term low-level exposure (Sakai & Matsumura, 1968, 1971; Aldridge & Magos, 1978). To understand the mechanism of toxicity, it is necessary to examine the events that take place at the neuromuscular junction. When a muscle is innervated, as shown in Fig. 2, a nerve impulse moving down a neuron reaches the nerve ending where ACh, which is stored in vesicles at the nerve endings, is released into the junction. Within 2 - 3 ms, ACh impinges on the receptor side of the muscle

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