Risks From Natural Versus Synthetic Insecticides

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RISKS FROM NATURAL VERSUS SYNTHETIC Annu. Rev. Entomol. 1994.39:489-515. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/07/15. For personal use only.

INSECTICIDES Joel

R. Coats

Department of Entomology, Iowa State University, Ames, Iowa

KEY WORDS:

50011

pesticides, hazards, chemicals, toxicity, toxicology

PERSPECTIVES AND OVERVIEW For centuries humans have used natural insecticides to combat insect pests that compete for our food and fiber or that affect public health. Some of these compounds were plant extracts or plant parts, others were mined from the earth. In the twentieth century synthetic insecticides have replaced natural ones as the standard means of controlling detrimental insects, ticks, and mites. Although early natural insecticides such as arsenicals and nicotine carried with them acknowledged risks, a populace that often faced hunger and vector-borne diseases was willing to tolerate a degree of risk to realize the benefits of the chemicals being used. Synthetic insecticides brought a new order of insect control, but also a new collage of risks. As people became more comfortable in the developed areas of the world, threats of starvation, arthropod-vectored diseases, or loss of clothing and shelter often became minor concerns. The quality of our food supply and the economics of production now govern the majority of pest and pesticide approaches, products, and methodologies. At the same time, new questions have arisen regarding environmental quality, especially contamination of water, air, and ' soil by a host of chemicals, some of which are pesticides or their degradation products. Our present society can afford to discuss long-term health implications of agents used to control insect pests. Many new and difficult questions have emerged about health and environmental nsks, giving rise to a distinct area of study called risk assessment. One of the most challenging questions 489

0066-4170/94/0101-0489$05.00

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asked is: Are natural products safer than synthetic ones? The answers are not easily defined, but the current dialogue includes hotly debated specific and general issues. The evaluation criteria are of great importance, and the processes of risk assessment are often new and subject to different inter pretations. This review poses and analyzes this difficult question, and the overall goal of this article is to clarify some of the confusion over risks and how they are assessed, especially with reference to natural and synthetic insec

Annu. Rev. Entomol. 1994.39:489-515. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/07/15. For personal use only.

ticides , and to describe the public perception of pesticides and their use. Human reactions to risks of various types are addressed as well. I discuss synthetic insecticides with regard to their safety versus their risks , drawing from examples of widely used products. Natural insecticides are then examined in the same light; this evaluation will also provide an opportunity to ascertain potential risks from insecticides of the future. Food safety is a major issue for some consumers. How important are insecticides in our food supply? Are the synthetic or natural insecticides of . greater consequence? The risk-assessment section of this article attempts to emphasize the need to use sound scientific information in order to reach valid conclusions. I offer some suggestions for minimizing controversy relative to the regulation of insecticides and their risks to humans or the environment, arguments in which entomologists are frequently involved.

PUBLIC PERCEPTION OF INSECTICIDES The general public has little experience with controlling insect pests, which is usually limited to insects in the house, yard, garden, or on pets. Recent estimates indicate that one fourth of all pesticides are used in urban situations, rather than in agriculture.

Public Distrust Although consumer buying practices reflect wide acceptance of pest-control chemicals, the g�neral populace displays considerable distrust when the products are in the hands of others . Most people seem to believe that the chemicals used for their own pest problems (e.g. fleas, flies, mosquitoes, roaches, ants, gypsy moths) have less effect on the overall environment than agricultural chemicals. Individuals may also trust their own choice of chemical and application methods more than those of strangers. , Other factors, such as experience and facts or intuition and folklore, can contribute to the public distrust of insect-control products. SYNTHETIC CHEMICALS

For the past 50 years most of the pesticides reg

istered have been synthesized from petroleum-based sources , as are many

NATURAL VS SYNTHETIC INSECTICIDES

491

industrial chemicals. First-generation synthetic insecticides were so persistent that even today the press features stories about residues of DDT, heptachlor, mirex, and other polychlorinated compounds contaminating fish, water, or soil. The second generation of synthetic insecticides comprised the organo phosphorus and carbamate esters. These were more biodegradable, but many

still manifested broad s pectrum toxicity, with a potential for poisoning nontarget insects, fish, wildlife, livestock, and humans. Some showed remarkable selectivity, but the majority were not safe enough to inspire a -


high level of public confidence in their value versus their risks. THE UNFAMILIAR

Many people are not comfortable with the widespread fully understand. For example, consumers have been reluctant to accept irradiation of food to sterilize it, or the use of bovine somatotropin to increase milk production, because these technologies are unfamiliar The health risks from inhaling benzene vapors while filling a car or lawn mower with gasoline are certainly higher than risks of the use of products they do not

.

above technologies, but we are familiar with gasoline, and its purpose is

quite clear. Many pesticides fall into the former category; people have a relatively poor understanding of how they work and what their purposes are. Many consumers complain that they have no voice in decisions that affect their exposure to pesticides, especially as the compounds may occur in trace quantities in food and water supplies. Also, spray drift and treated turfgrass often alienate consumers because of invol untary exposure. However, antimicrobial pesticides such as physician-pre

INVOLUNTARY EXPOSURE

scribed human antibiotics or fungicides are widely accepted, primarily

because we choose to expose ourselves to them. They also are familiar to us and their purpose is well understood. Because agriculturalists do not

explicitly ask the public's permission to use pesticides, involuntary exposure engenders a feeling of wrongful use.

LONG-TERM CONSEQUENCES UNKNOWN

Another cause of the public distrust of chronic exposure are currently known. Unfortunately, numerous insecticides, especially chlorinated hydrocarbons, were used for decades before their environmental or potential health effects were thoroughly understood. While these cases are disconcerting, the phenomenon is not peculiar to insecticides. Similar scenarios have developed with drugs such as thalidimide and diethyl stilbestrol, and with industrial chemicals such as asbestos, CFCs, and leaded gasoline. Consequently, one could argue strongly for the complete investi gation of a chemical prior to its registration and commercial utilization for of pesticides is the suspicion that not all of the subtle or delayed effects

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any possible deleterious effects that it may cause. The use of chemicals with unknown long-term effects is acceptable in certain circumstances, e.g. chemotherapy or other potent therapeutics, but in general the use of products should not be implemented unless the risks and benefits have been thoroughly evaluated.

Insecticide Use and Risk Assessment Annu. Rev. Entomol. 1994.39:489-515. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/07/15. For personal use only.

Recent surveys have shown that virtually every household in the US uses some form of pesticide, including insecticides , herbicides, fungicides, ro denticides, and bactericides . About 70% of consumers have applied a pesticide product within the past year. In addition, 20% of all households have their homes treated by pest-control operators for ants, roaches, fleas ,

15% of private lawns are treated by commercial lawn-care (106).

or wasps, while companies

The market for consumer use of pesticide products is estimated at $2.2 billion per year (53). Pesticide use by the private sector also includes Table 1

Causes of deaths from external causes in the US in 1988

Cause

Number

References

Tobacco

430,000 100,000 55,000 37,000 22,000 12,000 6,200 5,000 4,200 3,800 3,000 2,500 2,300 1,950 1,800 1,500 1,200 1,100 860 835 714

78 102 77 78 77 77 77 77 77 77 77 77 102" 102" 77 77 77 77 77

Tools and appliances

26

Football, scholastic

23 4

77 102" 77

Alcohol Motor vehicles Second hand smoke Homicide Falling Poisonings Fires Drowning Choking Nutritional deficiencies Motorcycles X-rays Railroads Natural and environmental factors Guns (accidents) Machinery Suffocation Bicycles Falling objects Electrical current

Fireworks

81980 data.

77 77


493

Table 2 Causes of deaths from poisonings and from natural and environmental factors in 1988 (77) Number


Cause Poisonings Drugs Analgesics eNS drugs (including anesthesias) Psychotropic drugs Antibiotics Others Gas and carbon monoxide Alcohol Petroleum products Cleaning agents Pesticides Food and poisonous plants Natural and environmental factors Cold Heat Hunger, thirst, neglect Animals Lightning Storms, floods Venomous animals and plants Earthquakes

4,900 1,200 1,800 370 60 2,090 720 334

58 14 14 3 1,785 850 450 200 89 82 59 48 7

treatment of restaurants, hotels, manufacturing plants, storage warehouses and grain elevators, retail stores, and offices. Numerous public areas such as parks, golf courses, and residential areas are treated for pest problems as well

(85).

Although many insecticide products can harm humans if directions ate not followed, the number of accidental deaths resulting from these products annually is relatively low. The external factors resulting in the most deaths

in the US are tobacco, alcohol, and motor vehicles (Table number of poisonings by all types of substances was comparison, deaths attributed to AIDS numbered

6,043

O. The total in 1988. By

17,000 in that year.

Within

the accidental poisonings category, pesticides were responsible for only

0.2%.

Table

2

shows the mortality due to different classes of poisons, as

well as that from various types of natural and environmental factors. Naturally occurring bioactive chemicals, i.e. toxins from plants or animals, also contributed at a low level to the mortality data

(0.8%

combined). In

California, the state that uses the greatest quantity of insecticides, four deaths were directly attributable to pesticide exposure in

1990. Pesticide

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use in 1988 was confIrmed or implicated in 1,987 illnesses; disinfectants and antimicrobials accounted for 43%, while the other 57% was attributed to traditional pesticides (16).


Reactions to Risks People do not always respond to risks in a rational way, i.e. their responses do not conform to the statistics expressing the likelihood that a given hazard will affect an individual. Risks can be represented in several different ways in addition to the raw statistics shown in Tables 1 and 2. For example, the estimated average loss of life expectancy reveals that being a coal miner reduces life expectancy by 1100 days, being 20% overweight causes a. 900-day reduction, misuse of legal drugs causes on average a 90-day loss, and oral contraceptives account for a 5-day loss (1). Some regulatory agencies have adopted an approach that uses as an endpoint the risk of increasing an individual's chances of dying in any year by one in a million Examples of activities that yield that degree of risk include traveling 150 miles by car, 3500 miles by jet, 10 miles by bicycle, or 6 minutes by canoe; eating 40 tablespoons of peanut butter; having one chest X ray; living two days in Boston or New York City; or drinking Miami municipal water for a year (1). The differences between how experts and the general public rank risks often reveals how people react to those risks. Surgery, X rays, and alcohol use are more dangerous, in the opinion of experts, than pesticides, police work, or private aviation. The public however, considers these activities safer than pesticide use, police work, or private planes. Another comparison demonstrated that although statistics prove nuclear power to be safer than bicycles, the public does not perceive nuclear power as safe (94). Recent investigations into the processes through which people develop their perceptions of risk have established that two primary factors are involved: the degree to which a risk is unknown and the degree to which that risk is dreaded. Risks posed by electromagnetic fields or radon are poorly understood, i.e. unknown, while risks from automobile accidents or fireworks are e asily comprehended Nuclear war or nerve gas accidents are greatly feared, while the dangers posed by vaccines or 'power mowers are not. Insecticides, as well as pesticides of other types, are high on both the unknown and the dread scale. Other hazards registering high on both scales include nuclear reactors and genetic engineering (94). Table 3 presents some of the attributes of the unknownlknown and dreaded/not dreaded risks, and Table 4 lists aspects of risks that tend to make them more acceptable or unacceptable to the public. With regard to insecticide exposure through food, water, or air, it is usually involuntary; the chemicals used are usually unfamiliar and synthetic .

,

.


Table 3

495

Characteristics that influence the degree to which a ,hazard is

unknownlknown or dreaded/not dreaded (94) Unknown

Known

Not visible

Visible

Delayed effect


New

Immediate effect Old

Table 4

Dreaded

Not dreaded

Uncontrollable

Controllable

Fatal

Not fatal

Global Catastrophic

Local Individual

Characteristics affecting the

acceptability of risks (94) More Acceptable

Unacceptable

Voluntary

Involuntary

Familiar

Unfamiliar

Controllable

Uncontrollable

Fair

Unfair

Not memorable

Memorable

Not dreaded Natural

Dreaded Artificial

and are often perceived as unfair and uncontrollable; and the long-term effects are somewhat uncertain. Public concern is also exacerbated by case

histories of deleterious effects in humans as well as in fish and wildlife. A

poor grasp of risk assessment also contributes to public anxiety. One recent case, involving the plant growth regulator/ripening agent Alar (daminozide), exposed how widely divergent two different groups may view risk. One transformation product formed from daminozide, unsymmetrical dimethyl hydrazine (UDMH), was shown to be carcin08enic in rats. The National Resources Defense Council (NRDC) calculated a relatively high risk from apples and apple juice, using a higher potency factor, higher consumption data, and a longer exposure period than the US Environmental Protection Agency (EPA) used in their calculations. The NRDC calculations yielded a prediction of 240 cancers in a popUlation of one million, while the EPA estimated a nine in one million risk from the chemical. Both sets of calculations were constructed from worst-case scenarios, with a conservative safety margin factored in, and both groups agreed the risks were higher than desirable, but the major point of controversy was the accuracy of the data and the timing of removal of the product from the market (88, 98). The two factors ultimately responsible for stopping the use of Alar were extensive media coverage and public concern over the nature and severity of that unfamiliar risk.

496

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SYNTHETIC INSECTICIDES

Chlorinated Hydrocarbon Insecticides The discovery of DDT's insecticidal potency in 1939 heralded the dawn of the age of synthetic organic insecticides. Although a few synthetic chemicals had been utilized prior to that time, e.g. dinitro-ortho-cresol (DNOC), the majority of products were inorganics. Active ingredients usually included


arsenic, mercury, lead, selenium, or copper, among others. The amazing efficacy of DDT was equalled only by its remarkable safety to mammals, including humans, and it was often deployed on the body for louse control. In addition, it was used for mosquito control, in dairy barns, and on crops including fruits and vegetables. DDT's quantum leap in insecticidal activity over the inorganics and early organics made it very attractive, as did its long residual activity, which allowed a reduced frequency of application. The risks seemed to be minimal, until the bioaccumulation of residues in the food chain and in human adipose tissue and milk began to generate widespread concern. As fish and birds were affected, and residues appeared even in Antarctica, the environmental impacts became evident. Researchers found that the residues and effects of a metabolite, DDE, were widespread as well. DDT was banned after a checkered history that featured both acclaim and disgrace (69). Yet although it was shown to be a weak carcinogen in mice, the overall safety record to humans was very good. Acute toxicity was not a problem for mammals or birds, although fish and lower forms were affected; however, the chronic effects, as well as the environmental stability and mobility, presented greater risks than the public wanted to take. Other chlorinated hydrocarbons, such as aldrin, dieldrin, chlordane, hep tachlor, toxaphene, endrin, chlordecone, and mirex, also experienced com mercial success. However, some of these were more acutely toxic to humans and others had chronic effects, and they fell into disfavor once chronic and environmental effects were elucidated (58). Some chlorinated hydrocarbon insecticides have neurotoxic effects, while others are carcinogenic or ter atogenic (74). Certain compounds deleteriously affect fertility, growth, enzyme induction, and· the immune response

(74). Most chlorinated hydro

carbons were judged, like DDT, to exhibit too many health and environ mental risks to be widely used. On a global basis their economic and public health benefits often outweigh their risks, and they are still weapons in the first line of defense against locusts, some disease vectors, and other pests.

Organophosphorus and Carbamate Insecticides These two classes of synthetic chemicals represented a new generation of organic insecticides that continue to be widely used today. The members of these two categories exhibit widely disparate properties. The origins of



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Structures of some synthetic insecticides.

498

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the two groups are very different, but the design, synthesis, mechanism of action, use patterns, and environmental impacts are similar. The organophosphorus esters (OPs) were designed as nerve gases during World War II. Acute mammalian toxicity was the primary reason they were developed, and modem-day chemical warfare capabilities still are based on

toxic organophosphorus esters (e.g. soman, sarin, tabun). Mammalian LDsoS

for those acute neurotoxicants are extremely low; intravenous median lethal doses for mice range from 0.042 to 0.29 mg/kg (101). Eventually safer


analogues were developed that could be widely used in control of insects as long as workers were very careful to use protective gear. Highly successful products such as parathion posed very little threat from a chronic-exposure standpoint, and long-lasting residues were less of a problem in crops or in the environment compared with the chlorinated hydrocarbons. The major risk presented by the OP class of insecticides was acute toxicity to applicators

and reentry problems for workers picking fruit or vegetables. Acute LDso values for warm-blooded animals are extremely low for some OP insecticides

(from I to

25 mg/kg), including tetraethylpyrophosphate (TEPP), parathion,

terbufos, fonofos, and numerous others. On the other hand, malathion and many other OPs have acute LDsoS in the hundreds or thousands of milligrams

per kilogram, and consequently represent a very slight risk of acute poisoning under proper usage (38). These OPs are used on humans, pets and livestock with little threat of acute or chronic toxicity effects. A

few

OPs

cause

organophosphorus-induced

delayed

neuropathy

(OPIDN), a serious degenerative neurotoxic syndrome. The most widely studied case history inv6lved leptophos and an even more potent transfor

mation product, desbromoleptophos (47). In addition to inhibiting acetyl cholinesterase,

leptophos

inhibits

neuropathy

target

esterase

(NTE).

Structure-activity relationships (l08) and mechanistic studies may shed light on this debilitating and irreversible effect. Recently more environmental questions were raised regarding avian tox

icity of granular formulations of some OPs and carbamates. Also, some of

the more acutely toxic OPs are responsible for occasional fish kills following

runoff events. Overall, the principal environmental concerns with OPs

parallel those for humans-acute poisonings represent the greatest potential

problems. As a class, then, OPs include high-risk compounds, low-risk

compounds, and many that fall in between these two extremes. Acute toxicity from occupational exposures accounts for most cases of accidental poisoning. Pets and livestock are also at some risk of acute intoxication. The synthetic carbamates were patterned after physostigmine, which was a therapeutic agent isolated from the calabar bean (Physostigma venenosum).

Like the OPs, the carbamate insecticides are readily degradable esters that are susceptible to oxidative and hydrolytic detoxification. Also like the OPs,



499

the potency of the carbamate-class compounds ranges between highly toxic and nontoxic. Aldicarb, one of the most acutely toxic insecticides registered, has an oral LD50 of 0.5 mglkg for test mammals. In a poisoning episode involving aldicarb-treated melons in California, the toxicant affected 692 people, 6 of whom died. The efficiency of the systemic uptake of the aldicarb in the plants made it a desirable, but illegal, choice to combat sucking insect pests such as whiteflies. The chemical was readily transported into the fruits of the plant and was stored there or metabolized to its equally toxic sulfoxide and sulfone metabolites. The extreme toxicity of the carba mate and its transfonnation products then contributed to the circumstances that spawned tragedy. Residues in groundwater have also been of concern for this insecticide/nematicide and its metabolites (71). Carbofuran has oral LD50 values around 5 mglkg in experimental animals, and so requires great care in its use. Its granular fonnulation is being phased out of use for com rootwonn control because of avian toxicity (99). Birds apparently in search of grit ingest the carbofuranlclay particles. Many carbamates are safer than OPs because their inhibition of acetylcholinesterase is reversible and recovery from intoxication is quick if the lethal threshold is not exceeded. Carbaryl has been widely used for over two decades with few reported cases of adverse effects. Its LDso in most mammalian species is 500--1000 mglkg. No long-tenn or chronic effects have been demonstrated, and it seems to be a safe selective insecticide. In addition to acutely toxic compounds of concern to vertebrate species, the carbamates and OP classes include some chemicals with low toxicity to higher animals. From an environmental perspective, most are biodegrad able, but they are not without some environmental risks, especially acute toxicity to fish and wildlife. Residue problems in air, food, and water have been limited primarily to aldicarb in shallow water tables, although other relatively water-soluble carbamates and OP insecticides could enter aquifers used for drinking water. Oxidative transfonnations of many OPs and some carbamates can be of toxicological significance in the environment, as well as in organisms. Sulfoxides, sulfones, and oxons are among the toxic degradation products (2 1, 22, 3 1, 7 1).

Pyrethroid Insecticides The inhabitants of Persia and Dalmatia discovered the utility of this class of compounds over 150 years ago, when they used crushed dried chrysan themum flowers to kill insects on their bodies and in their houses. By 1860, this natural insecticide was used in Europe and the United States (67). The organic solvent extract of the flowers was tenned pyrethrum, and it possessed many favorable properties. Its safety for mammals and rapid photodegrada-

500

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tion led to many uses in situations that required low mammalian toxicity (on humans, pets, livestock) and no residue problems (dairies, vegetables). This combination of desirable characteristics fueled numerous attempts to develop synthetic analogues that would be more widely available and perhaps more potent. The earliest synthetic pyrethroids retained most of the beneficial proper� ties. Allethrin varied from pyrethrin I only in the three�carbon length of the side chain on the cyclopentenone ring.


Replacement of that photolabile ring with the furan ring and the photo� stable benzene ring generated pyrethroids (e.g. resmethrin) with slightly more residual time following their application (26). In the 1970s great strides were made in the United Kingdom and Japan toward enhancing insecticidal potency, increasing photostability, and improving the chemistry to achieve a host of commercially viable synthetic pyrethroid insecticides. The evolution of this class of compounds has since yielded a vast array of molecules, some with greater lipophilicity, extremely low water solubility, and consid� erable persistence because of the use of single or multiple halogen atoms

(20). Mammalian and avian studies on the toxicity of the synthetic pyrethroids have demonstrated, in general, retention of safety for warm�blooded species.

The LDsoS of many of the photostable analogues were more than 100 or even 1000 mg/kg in mammals, and were even greater in birds. However, some of the most powerful compounds, e.g. lambda�cyhalothrin (89),

deltamethrin, tefluthrin. and flucythrinate (14). have LDsoS of 20-70 mg/kg in rats and mice. Stereoselective syntheses and purifications now can generate the most potent individual stereoisomers for production. The mammalian and avian acute toxicity values cause some concern, but these worries are offset by the extremely low concentrations of active ingredients in the formulations and the low application rates required for insect suppression. Although the majority of studies have demonstrated favorable selectivity

y

ratios for synthe c pyrethroids, a few effects have been reported in mam mals. A transitory tingling of the skin can occur during occupational exposures (15). Permethrin caused increases in tumors in mice

••

but they

were benign tumors. The EPA does not consider this chemical to present a significant health hazard to humans (79). A metabolite formed from cholesterol and the chlorophenyl isovaleric acid portion of the R,S-isomer of fenvalerate reportedly caused a liver granuloma condition in rats (80). From an environmental perspective, the pyrethroids represent improve� ments in many ways over the previously used classes. The widely used pyrethoids seem to present no problem to birds or other wildlife. Bees, important nontarget arthropods, are only affected if sprayed directly; other wise, the pyrethroids effectively repel them from foraging in fields that


501

have been sprayed (79). Fish and aquatic arthropods are generally very susceptible to these compounds, but the bioavailability of these compounds depends on suspended solids in the water (24).


luvenoids As the structure and function of insect juvenile hormones (JH) were elucidated, the potential utility of these compounds became apparent. In gestion or topical application results in supernumerary instars of nymphs or larvae, retardation of development to normal pupal and/or adult stadia, and loss of fertility (50). The subsequent development of synthetic juvenoids has produced several useful commercial products that induce eSi>entially the same effects as the natural juvenile hormones. Methoprene and hydroprene are two juvenoids that are effective, slightly more stable than the natural JHs, and extremely safe for mammals, birds, fish, and other vertebrates. Fenoxycarb also exhibits juvenoid activity, although its structural similarity to JH is not as close as is that of methoprene. These extremely selective insecticides affect very few nontarget organisms, have virtually no residue problems, and model the level of sophistication that pest control agents will need to attain in the future.

A Fluorinated Sulfonamide Another example of a novel synthetic insecticide is sulfluramid, a new toxicant used in baits for ants and roaches. This is a highly fluorinated sulfonamide that acts as an uncoupler of oxidative phosphorylation. Because the parent molecule is degraded readily to des-ethyl sulfluramid, residues of the former may not bioaccumulate significantly in tissues or persist in the environment. However, the perfluorooctane sulfonamide is more persis tent in tissues (45), and environmental residues could persist as well.

Overview of Synthetic Insecticides As a group, the synthetic compounds include both very hazardous and very safe chemicals. The hazardous examples exhibit acute or chronic toxicity and/or have residue problems. On the other hand, the safe compounds often have little or no toxicity to mammals. Some are extremely selective, and some pose no residue problems at all. NATURAL INSECTICIDES Numerous chemicals occur naturally and function to some degree as insec ticides. Most are present in living organisms; from the blue-green algae to fungi to the angiosperms, plants of many different families contain secondary chemicals. Those substances are typically not important to basal metabolism

502

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