Pesticide is a generic term that covers a wide range of natural and synthetic chemicals over 700 in total that are used to protect crops from attack from pests, both before and after har
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Pesticides
M Saltmarsh, Alton, UK
ª 1998 Elsevier Ltd All rights reserved.
This article is reproduced from the previous edition,
pp 869–874, ª 1998, Elsevier Ltd.
What are Pesticides?
Pesticide is a generic term that covers a wide range
of natural and synthetic chemicals (over 700 in
total) that are used to protect crops from attack
from pests, both before and after harvest There
are many different sorts of pests The term includes
insects, slugs and snails, nematode worms, mites,
rodents, weeds, molds, bacteria and viruses The
chemicals can be applied before and during growth
of the plant or on to the stored crop as, for example,
fumigants, which are used to kill pests that have
infested stored cocoa or grain Chemicals used to
treat pests on animals are not included; they are
considered as veterinary medicines
The pesticide formulation used by the farmer will
include the pesticide chemical itself and a number of
other chemicals that enable it to be applied and to
work as effectively as possible These will include
solvents, adhesives, and surface-active agents such as
emulsifiers In some cases other chemicals, known as
‘safeners,’ are applied to minimize the damage done
to the crop while maintaining the effectiveness of the
spray on the target
It is estimated that worldwide usage of pesticides
is around 2.5 million tons with a cost in 1997 of
US$21 billion
Why Do We Need Pesticides?
Food crops are subject to attack by a multitude of
pests and diseases and pesticides are applied to
mini-mize the damage to the crop It has been estimated
that without protection world cereal crop yields would fall by between 46 and 83% History is lit-tered with records of crop failures and famine caused primarily by rodent, insect or fungus Some
of these events have had a wide-ranging and long-lasting effect, like the 1845–1846 Irish potato fam-ine and the 1917–1918 German ‘turnip winter,’ the latter so called because the potatoes rotted and turn-ips were the only stored root crop that was available
to feed the population through the winter Both these events, in which 1.5 million and 700 000 peo-ple died, respectively, were caused by potato blight, infection by the fungus Phytophthora infestans Famine caused by massive swarms of locust is still all too common in Northern Africa and Arabia Less spectacular but as disastrous is the loss of an esti-mated 30% of harvested crops in India to rodents
In addition to the loss of the crop, pesticides are used to control agents which make the crop toxic rather than healthy Two examples are the toxins caused by fungi When an insect bores into a peanut
it allows spores of the fungus Aspergillus flavus to enter and grow, producing the aflatoxins, a series of carcinogens When rye (Secale cereale) grows in damp conditions a fungus, Claviceps purpurea, can grow on the seed If this seed is subsequently ground into flour and made into bread it can cause consu-mers to suffer hallucinations, gangrene, and death Outbreaks amounting to epidemics were common in the Middle Ages in Europe and one occurred as recently as 1951 in France
A second reason relates not so much to quantity
as to quality Supermarkets in the developed nations offer a wide range of fresh produce at competitive prices Consumers do not like holes made by slugs and snails in their fresh lettuce They do not expect scab marks on their apples, or holes made by small maggots in their carrots Flour millers do not expect
to have to clean the grain from weed seeds before milling Even small defects can dramatically reduce the value of the crop, or indeed make it unsaleable, and the need for a competitive price requires mini-mal labor input so that application of pesticide is essential
Types of Pesticides
There are currently around 600 pesticides, both natural and synthetic Natural pesticides include both chemicals derived from plant sources and biological agents such as parasitic wasps, mites, bacteria, and chemicals contained within or exuded by plants or bacteria While there is no inherent reason why natural products should be any safer than synthetic ones (after all, insect
Trang 2venoms and toxins and poisonous plants are
nat-ural), it appears that the risks do lie in their
potential impact on the environment rather than
on their effect in food There are also increasing
numbers of cases where plants have been given a
gene which expresses a natural pesticide (see
Bacil-lus thuringiensis, below)
At the time of writing, naturally derived pesticides
make up less than 5% of the world pesticide market,
but a great deal of work is being devoted to the
screening of natural sources and this proportion
will certainly increase The most successful natural
product development so far has been that of the
pyrethrin insecticides, of which 33 are currently
available
The largest classes of pesticides are pyrethrins,
organochlorines, organophosphates, and
carba-mates, although there are many smaller classes
with only one or two members The chemical
struc-tures of the key members of the major groups are
given inTable 1
Important Pesticide Groups
This list covers the important pesticide groups and
some individual pesticides but does not attempt to
be comprehensive
Pyrethrins
Pyrethrins are chemically related to pyrethrin,
which is a secondary metabolite found in the
flow-ers of the pyrethrum plant (Chrysanthemum
ciner-ariaefolium) Dried pyrethrum flowers were used as
an insecticide in ancient China and in the middle
ages in Persia The dried flowers are still used
Current production is around 20 000 tons per
an-num centered in Kenya and Tanzania The
pyre-thrins are effective insecticides, having very low
dose rates and rapid knockdown of insects but
being harmless to mammals under all normal
con-ditions Natural pyrethrins break down rapidly
under the influence of oxygen and UV light This
limits their use in agriculture, but recently synthetic
analogs have been developed to overcome these
problems Starting from the structure of the natural
product a large number of synthetic compounds
have been made It is worth noting how they differ
in effectiveness: deltamethrin is a broad range
insec-ticide; allethrin is particularly toxic to house flies
(Musca domestica) but much less effective with
other insects; flumethrin is active against cattle
ticks; while others are acaricides or miticides with
little or no insecticidal activity
Bacillus thuringiensis
Bacillus thuringiensis is a widely distributed bacter-ium that during sporulation produces a crystal inclusion which is insecticidal when ingested by the larvae of a number of insect orders Susceptible orders include Lepidoptera, Diptera, and Colcop-tera The action of B thuringiensis was first observed in 1901 as the cause of a disease of silk-worms Several strains of the bacterium have been identified with activity against a range of insects including cabbage looper, tobacco budworm, mos-quito, black fly, and more recently nematodes, ants and fruit flies While the bacterium appears an ideal insecticide (having a toxicity 300 times greater than synthetic pyrethroids), it requires careful use It is most effective against neonates and early larval instars so that spraying must be timed for egg hatch It also has no contact activity and must be ingested so the plant must be well covered to ensure the insect receives a lethal dose Furthermore it has
a half-life in the field as short as 4 h, so careful timing is essential for it to be effective Despite these limitations, it has been shown to be an impor-tant component of crop management programes One way of overcoming the problems of applica-tion of B thuringiensis is to incorporate the gene responsible for expression of the protein into the crop plant This has been achieved with maize (Zea mays) to protect against the European corn borer, with cotton (Gossypium hirsutum) to protect against
a range of budworms and bollworms, and with potato (Solanum tuberosum) against Colorado bee-tle (Cotton may seem irrelevant in a text on food but cottonseed oil is used extensively in cooking oils, margarines, and industrial fats.) This genetic mod-ification has great benefits but care has to be taken that the food product has not changed in some unpredicted way All genetically modified foods have to be extensively tested and cleared by regula-tory agencies before release
Neem oil
This is an oil obtained from the neem tree, Azadirachta indica A Juss It has been used as an insecticide in India and Africa but is increasingly being developed as a significant commercial pro-duct It contains a number of compounds, one of the most active being azardirachtin, which is an insect antifeedant but also shows growth inhibitory and endocrine disrupting effects This product and its individual components is at the beginning of its commercial development, which is likely to result in
a series of products as significant as those from pyrethrum
Trang 3Microbial phytotoxins
These are herbicides and include the highly
com-mercially successful glufosinate, a synthetic form of
phosphinothricin, first isolated from Streptomyces
hygroscopicus, a soil-borne microbe This com-pound is a potent, irreversible inhibitor of gluta-mine synthetase which is used in plants for photorespiration Many attempts have been made
to make synthetic variants of phosphinothricin
Table 1 Chemical structure and acceptable daily intake (ADI) of some pesticides
body weight) Deltamethrin Pyrethrin
O C
CN
H
CO2 C
Br
Br CH
CH3
CH3
0.01
CH
CCl3
0.02
Lindane (HCH) Organochlorine
Cl Cl
Cl Cl
Chlorfenvinphos Organophosphate
(mixture of two isomers)
Cl ,
C C H
Cl O
(CH3CH2O)2P (CH3CH2O)2P
O
Cl
C C Cl
H O
Malathion Organophosphate
CHCH2CO2CH2CH3
CO2CH2CH3 PS
S (CH3O)2
0.02
OCH(CH3)2
0.02
Simazine Triazine
N N
N
Cl NHCH 2 CH 3
NHCH 2 CH 3
0.005
CH3PCH2CH2CHCO2H
OH NH2
0.02
HO2CCH2NHCH2P(OH)2
0.3
Trang 4without success Other members of this group
include anisomycin and herboxidiene, derived
from other Streptomyces strains The veterinary
insecticide, avermectin is derived from Streptomyces
avermitilis
Organochlorines
The organochlorines were the first group of
syn-thetic insecticides and without them the dramatic
decrease in malaria observed in the 1950s would
have been impossible The best known of this
class is DDT (dichlorodiphenyltrichloroethane) but
others include 2,4 DD, hexachlorbenzene, and
lin-dane Of these only lindane
(-hexachlorocyclohex-ane, see Table 1) is still in use in the developed
world
These compounds are very slow to break down in
the environment and one result of this persistance
was the decline in bird numbers graphically
described by Rachel Carson in the book Silent
Spring The problem was that DDT was
concen-trated through the food chain and predator birds in
particular were failing to raise chicks Since the
organochlorine pesticides and other sources of
orga-nochlorines in the environment have been largely
phased out, numbers of many species of birds are
rising again It is recognized that pesticides are still
having an adverse influence on numbers of some
birds that inhabit farmland However, this is not a
straightforward effect In the case of the grey
par-tridge, for example, it is because herbicides have
reduced the number of weeds, which in turn has
reduced the number of insects that feed on the
weeds, resulting in fewer insects for the chicks
to eat
The mechanism of action of the organochlorines
is not known in detail although they appear to act
on the central nervous system In humans the
orga-nochlorine compounds tend to accumulate in the
body fat and in mothers’ milk While there is no
direct evidence that they cause mutations or cancers,
there is concern that lindane may be a carcinogen
and its role in breast cancer is still under review
However, in contrast, DDT and -HCH have both
been shown to inhibit tumors in mice initiated by
aflatoxin B1
Although organochlorine pesticides have largely
been phased out in Europe, analysis for them
con-tinues and low levels of lindane are still being
detected in milk in the UK (typically at
0.005 mg kg 1compared with the maximum residue
limit (see below) of 0.008 mg kg 1and an acceptable
daily intake (see below) of 0.05 mg per kg body
weight)
Organophosphorus compounds
Organophosphorus compounds generally contain both sulfur and phosphorus linked to carbon atoms Their discovery was a by-product of the development of nerve gases The group includes parathion, malathion, dimethoate, diazinon, and chlorfenvinphos They are used as herbicides, insec-ticides, and fungicides They break down quickly in the environment and do not concentrate in body fats, although they may be stored for some time However, their mode of action – inhibition of acet-ylcholine esterase – means that they affect both insects and mammals and their use depends on the effective dose in the target species being below the sensitivity of other species
Acute effects of sublethal doses of organopho-sphates in man include sweating, salivation, abdom-inal cramps, vomiting, muscular weakness, and breathing difficulties Concern has also been expressed about long-term effects following acute exposure Research suggests that some victims may show reductions in some neurobehavioral tests when tested some months after exposure There are also concerns that people who do not appear to have suffered acute poisoning have subsequently devel-oped debilitating illnesses Symptoms include extreme exhaustion, mood changes, memory loss, depression, and severe muscle weakness
Carbamates
Carbamates are derived from carbamic acid and are used against both insects and weeds They are also acetylcholine esterase inhibitors They are very reac-tive and are used up rapidly after application
Methyl bromide
Methyl bromide was for many years the fumigant of choice for destroying insects in stored crops, but it is now being withdrawn as part of the general restric-tion on volatile organohalogen compounds because
of their damaging effect on the ozone layer It is being replaced by a number of less environmentally damaging compounds, including phosphine, although none currently available is as effective or
as cheap as methyl bromide
Phosphine
Phosphine has been used as a fumigant for many years It is highly reactive and leaves no residues but great care has to be taken in its application because it is very toxic to humans
Trang 5Control of Pesticides
Control over pesticides is exercised in two ways:
stringent testing on new pesticides before they are
permitted and measurement of the residue in the
crop
Testing pesticides
There are a number of national and international
bodies that approve new pesticides within their
areas of responsibility These include Codex
Alimen-tarius, the European Union, and the US Food and
Drug Administration (USFDA) Currently, within
the European Union, registration of pesticides is
being harmonized under Directive 91/414 EEC
Annexe 1 of this directive will identify all active
ingredients permitted in pesticides As yet this
annexe is incomplete and member states are still
acting under their national laws
Within the UK pesticide registration is carried out
under the Control of Pesticide Regulations 1986 and
is the responsibility of the Ministry of Agriculture,
Fisheries, and Food who are advised by the Advisory
Committee on Pesticides
In the USA a new Food Quality Protection Act of
1996 replaced both the Food, Drug, and Cosmetic
Act and the Insecticide, Fungicide, and Rodenticide
Act to provide a comprehensive regulatory scheme
for pesticides
In order to gain approval for use, pesticides are
subjected to an extensive testing program including
toxicity tests on mammals, plants, insects, fungi,
birds, bees, fish, earthworms, and other soil
organ-isms The toxicity studies include effects of
pesti-cides on fetuses and infant animals There are also
environmental tests which include laboratory tests
on the breakdown and movement of the chemical in
plants, soil, water, air, mammals, birds, and fish
These latter tests determine the rate of decay in the
various species Laboratory tests are followed by
prolonged field trials to determine the fate of the
chemical and its breakdown products in the
envir-onment and to estimate how the pesticide is
concen-trated up the food chain On average it takes about
10 years to develop a new pesticide at a cost of
about £50 million The complete dossier of results
has to be submitted to the approval body who
deter-mine whether the tests have been sufficiently
rigor-ous to allow an acceptable daily intake (ADI) of the
pesticide to be set The ADI is defined as the amount
of a pesticide that can be taken in each day
through-out a person’s life with the practical certainty, on
the basis of all known facts, that no harm will result
This is determined on the basis of the highest level at
which the pesticide has no observable effect in
animal tests This is then reduced by a factor of 10
in case humans are more sensitive than the animals used in the tests, and by a further factor of 10 to allow for cases where some humans may be more sensitive than others In some cases, where the data show unusual effects, the safety factor can be increased from 100 to 500 or 1000 In practice the amount of pesticides to which the population is exposed is far below this level
Table 1 includes the ADI for a number of the more common pesticides There is no evidence that there are any cases where the combined effects of two pesticides are greater than the sum of their individual effects, in other words there is no evi-dence of synergy in toxicology between the different pesticides Once maximum residue limits (MRL see below) for foodstuffs have been set on the basis of good agricultural practice, a total dietary intake is determined by considering all commodities in which the pesticide is likely to be used, and assuming the upper range of consumption, all foodstuffs at the MRL and no losses during transport, storage or food preparation This figure is then compared with the ADI For all permitted pesticides in the
UK the figure is below the ADI
Maximum residue limits
Maximum residue limits (MRLs) are statutory limits set on individual active ingredient and foodstuff combinations They are based on residue levels which result when the pesticide is used according
to the instructions on the label and in accordance with good agricultural practice (GAP) MRLs may
be used to ensure that the pesticides are only being used in accordance with GAP Many countries have codes of good operating practice with training for farmers and operators to ensure that pesticides are used at optimal levels Some countries rely on the Codex Alimentarius Committee on Pesticide Resi-dues to establish MRLs, while others set their own (Codex Alimentarius is an international body which has over 120 countries as members and their stand-ards are increasingly being accepted as the basis of world trade in foodstuffs.)
In the USA the FDA used to set tolerances for pesticide/foodstuff combinations but under the
1996 Act it sets a level for each pesticide in all foods based on the principle of a reasonable cer-tainty of no harm This is defined as a lifetime cancer risk of less than 1 in a million There is also
a requirement that residue tolerances must be speci-fically determined as being safe for children Within the EU, individual member states have historically set their own MRLs which differ from
Trang 6state to state Directive 76/895 established a
com-mon MRL setting regime and a series of subsequent
directives has fixed the levels for a series of
pesti-cides in fruit, vegetables, cereal products, and
pro-ducts of animal origin There is an ongoing program
to harmonize the levels throughout the Union
Most industrialized countries have pesticide
sur-veillance programs which cover both
home-produced and imported commodities and these report
annually The EU has an annual specific coordinated
program to check compliance in nominated
combi-nations of pesticide and foodstuff MRLs require
sophisticated equipment for their determination
because the levels are so low and the minimum
detectable limit depends on the foodstuff For
exam-ple the tolerance for aldrin and dieldrin (two
orga-nochlorines) in the USA is between 0.05 and
0.1 mg kg 1 (parts per million), depending on the
foodstuff There are over 600 different active
ingre-dients available commercially Because there are so
many, laboratories around the world have
devel-oped sophisticated rapid analytical techniques to
allow them to screen pesticides by class so that
retailers, food manufacturers, and governments can
carry out analyses as a matter of routine
The MAFF 7th Report of the UK Working Party
on Pesticide Residues in 1996 showed 68% of
sam-ples had no detectable residue, 31% had residues
below the MRL, and <1% were over the MRL
Similar results were obtained by the FDA who
report results with relation to the tolerance to the
pesticide/commodity combination In 1995, of over
9000 samples analyzed, 64% had no detectable
resi-dues, 34% had residues below the tolerance, <1%
had residues over the tolerance and <1% had
residues for which there is no tolerance in that
par-ticular pesticide/commodity combination
In all cases where MRLs or tolerances are
exceeded follow-up action is taken For
home-produced materials, this involves investigation of the
grower and prosecution if necessary For imports,
exceeding the level causes the consignment to be
refused entry
Maximum levels of pesticides are also set for
drink-ing water Pesticides get into water from spraydrink-ing,
runoff, percolation or from treatment of fish in
aqua-culture Good practice is increasingly being developed
to minimize the levels in raw water and treatment
works are developing systems to reduce incoming
levels to levels acceptable for drinking water
Endocrine Disruption
The possibility that a number of chemicals
dis-charged into the environment as a result of human
activity may disrupt the endocrine system of a wide range of mammals has recently been given consider-able prominence Among the chemicals cited are the organochlorine pesticides, most of which have now been withdrawn for other reasons While there is no doubt that there are a significant number of cases of endocrine disruption, the evidence to point to any particular chemical as a cause is lacking It is also worth noting that deliberate endocrine disruption is
a mechanism of a number of natural insecticides which act so as to inhibit development of juvenile larvae to adults Fortunately these pesticides are reactive and usually have a short life in the field
It is also true that there are very many naturally occurring endocrine disruptors, including the phytoestrogens present in vegetables, notably soya beans, peas, beans, cabbage, and hops However, since this issue is very serious a considerable amount
of work has now been initiated and its results will have implications for future testing of pesticides
Future Prospects
In many parts of the world it is recognized that there has been too great a reliance on pesticide use and not enough on improving agricultural practices There is increasing pressure to move towards mini-mizing pesticide usage in order to both improve the environment and to reduce cost This is being done
by using newer, more specific pesticides and by adopting improved agricultural practices and inte-grated pest management (a combination of biologi-cal and chemibiologi-cal control)
Biological control is not new In the 1930s Macro-centrus homonae was introduced into Sri Lanka from Indonesia to control the tea small leaf roller (Adoxophyes) with such success that no chemical control measures are needed for this pest even today More recently there have been some impress-ive results from using predator insects, for example
in the control of cassava green mite (Mononchellus tanajoa) in West Africa and white fly in European greenhouses
In terms of agricultural practice, improved crop hygiene, crop rotation, better understanding of opti-mal timing of application, and varying sowing dates, together with the development of more powerful and more discriminating pesticides has brought about a decrease in pesticide inputs This is seen dramatically in the case of oil seed rape (canola) Less than 1% of the weight of herbicide applied to this crop in 1983 was applied in 1993
Unfortunately pests develop resistance to indivi-dual pesticides over time and research is continually
Trang 7needed to develop both new pesticides and resistant
varieties of crops to keep the pests in check There
has been some success with new pesticides having
new modes of action such as the antifeedants and
antimolting agents, but this will be a continuing
battle for the foreseeable future
See also: Phytochemicals: Classification and
Occurrence; Epidemiological Factors
Bacterial Contamination
N Noah, London School of Hygiene and Tropical
Medicine, London, UK
ª 2005 Elsevier Ltd All rights reserved.
The burden of gastroenteritis (GE) in the world, in
terms of both morbidity and mortality, is enormous
In the developing world (e.g., Southeast Asia),
diar-rhea vies with acute respiratory tract infection as the
leading cause of death in childhood Even in the
more developed world, infectious GE is a significant
cause of illness and time lost from work, and death
does occur Infectious intestinal disease in England is
estimated to cost the country £743 million p.a (in
1994–95 prices) GE caused by bacteria was far
more costly than that caused by viruses The more
sophisticated surveillance systems become, the more
GE they uncover
Not all GE is caused by food Probably most GE
is caused by poor hygiene leading to direct or
indir-ect transmission of infindir-ection without the assistance
of food Nevertheless, a major cause of infectious
GE throughout the world is contaminated food The
definition of food poisoning (FP) is not
straightfor-ward In essence, FP is an acute gastroenteritis
caused by food Hepatitis A, typhoid, and
brucello-sis, however, are not usually considered as FP,
whereas botulism is, even though it causes paralysis
and not GE, as is listeria, which causes septicemia
and meningitis
Bacteria are the most common known cause of FP
and, with the possible exception of the Norwalk-like
viruses, of GE also As one would expect, bacterial
FP is more common in summer than winter
Bacteria produce their effects on the intestinal tract
either by direct invasion of the mucosa or by the
production of toxin Some of the toxins are produced
outside the intestinal tract—in the food; others are
formed in the intestine Some invasive bacteria also
produce a toxin in the intestine This article provides
an overview of the bacterial causes of FP
Bacterial Toxins
There are three main forms of bacterial enteric toxin:
Enterotoxin producing excess fluid secretion into the gut (cholera and some types of Escherichia coli) Cytotoxin causing inflammation and mucosal damage (shigella and enterohemorrhagic E coli) Neurotoxin affecting the nervous system (botulism and staphylococcal toxin)
Some E coli strains produce toxin; these are dealt with under Invasive Bacteria Red kidney bean, scombrotoxin and other fish toxins, and heavy metal poisoning are dealt with elsewhere in this book
Staphylococcal Food Poisoning
Background Staphylococcal food poisoning (SFP)
is one of the few causes of bacterial FP that can commonly be attributed to a food handler Humans frequently carry staphylococci either in an infected site or asymptomatically Infected sites include wounds and abscesses, which may be the source of large numbers of staphylococci Asymptomatic sites include throat, nostrils, fingernails, or hair In gen-eral, only coagulase-positive staphylococci (Staphy-lococcus aureus), and only certain types, produce enterotoxin Rarely, some coagulase-negative strains may occasionally produce toxin Because the organ-ism is also carried by many animals, outbreaks attributable to inadequate processing of a precon-taminated food can occur also
Growth and survival Staphylococci are killed by normal cooking temperatures Any staphylococci that survive because of inadequate heat penetration
or, more frequently, by postcooking contamination from a food handler will, if it is an enterotoxigenic strain and given the right conditions of warmth, moisture, pH, and time, produce toxin Growth of staphylococci and production of toxin are optimum
at approximately 20–37C, but growth can occur between 8 and 48C This toxin is fairly heat stable; boiling for approximately 30 min is required to destroy it Canning is usually, but not always, suffi-cient The toxin is also resistant to radiation Many foods can cause SFP Because the organism can grow in foods with high salt or sugar content (possibly because there is less competition from other organisms), ham is a common cause of SFP,