1 Pesticides

An enormous number of chemicals exist in trichogramma. The management of pests nature, which are used as pesticides, for actually disturbs the balance of nature, agricultural and non-agricultural purposes. thereby affecting biodiversity on Earth. Pesticides are introduced to manage popula- ­Pesticides can adversely affect non-target tions of living organisms, called pests, which organisms as well as affecting other ecologi- are deleterious to crops or the health of the cal components of the environment, which human race. A literal meaning of pesticide is they are not intended to do. ‘a substance used to kill undesired living organisms’. However the Food and Agricul- ture Organization (FAO, 2013) has defined 1.1 History pesticide as: any substance or mixture of substances Until the 1940s, during World War Two, intended for preventing, destroying, or ­pesticides were widely used for pest control controlling any pest, including vectors of to ensure food security by the introduction human or animal disease, unwanted species of inorganic chemicals such as calcium, lead of plants or animals, causing harm during arsenate and sulfur, and the use of common or otherwise interfering with the produc- salt and sodium chlorate as herbicides. The tion, processing, storage, transport, or organic molecules of this period were natu- marketing of food, agricultural commodi- ral products such as ­nicotine (extracted from ties, wood and wood products or animal tobacco) and rotenone (extracted from der- feedstuffs, or substances that may be administered to animals for the control of ris roots). These were named first-generation insects, arachnids, or other pests in or on pesticides. These pesticides, including heavy their bodies. The term includes substances metals, were toxic to humans and agricul- intended for use as a plant growth regula- tural plants. The growth in synthetic pesti- tor, defoliant, desiccant, or agent for cides accelerated in the 1940s with the thinning fruit or preventing the premature discovery of the effects of organochlorines, fall of fruit. Also used as substances applied known as second-­generation pesticides, such to crops either before or after harvest to as dichlorodiphenyltrichloroethane (DDT), protect the commodity from deterioration b-hexachlorocyclohexane (BHC), aldrin, during storage and transport. dieldrin, endrin, chlordane, parathion, cap- Pest management is also achieved by the use tan and 2,4-dichlor­ ophenoxyacetic acid (2,4- of other biological active agents, such as D). The discovery of DDT by Dr Paul Muller,

 CAB International 2019. Pesticide Risk Assessment (S. Arora) 3 4 Chapter 1 in 1939 was a turning point that revolution- During the 1970s and 1980s, a herbi- ized agricultural production. DDT was popu- cide, ‘glyphosate’, currently the world’s best- lar because of its broad-spectrum activity selling herbicide product, was introduced, (Unsworth, 2008) and was widely used. It followed by sulfonylurea and imidazolinone appeared to have low toxicity to mammals, products. The insecticide industry marked and reduced the incidence of insect-borne the era of the third generation of pesticides, diseases, such as malaria, yellow fever and with the introduction of avermectins, ben- typhus. Consequently, in 1949, Dr Paul zoylureas and Bt (Bacillus thuringiensis). The Muller won the Nobel Prize in Medicine for triazole, morpholine, imidazole, pyrimidine discovering its insecticidal properties. How- and dicarboxamide families of fungicides ever, in 1946, resistance to DDT in house were also introduced during this period. flies was reported and, because of its wide- The massive use of pesticides during the spread use, there were reports of harm to 1960s significantly increased agricultural non-target plants and animals and problems productivity leading to the ‘Green Revolu- with residues (Unsworth, 2008). These tion’ and a safe and secure food supply, along insecticides were observed to be toxic to with other secondary benefits. However, humans and agricultural plants, due to some of the first-generation pesticides had their bioaccumulation and biomagnification the drawback of persistence in soils and properties. aquatic sediments, bioconcentration in the Throughout the 1950s, consumers and tissues of invertebrates, moving up trophic most policy makers were not overly con- chains and affecting top predators. Many cerned about the potential health risks asso- chemicals that have been identified as endo- ciated with using these pesticides, as these crine disruptors are pesticides. Of these, were considered safer than the forms of 46% are insecticides, 21% herbicides and arsenic that were used and had killed people 31% fungicides; some of them were with- in the 1920s and 1930s (Wessel’s Living drawn from general use many years ago but ­History Farm, 1930). However, the indis- are still found in the environment (e.g. DDT criminate use of these highly persistent and atrazine) (Mnif et al., 2011). Endocrine organochlorines could generate a lot of disruptor compounds (EDCs) have been problems as highlighted by Rachel Carson in defined in 2002 by the World Health Organi- her 1962 book Silent Spring (Carson, 2002 zation (WHO): ‘An endocrine disruptor is an [1962]). The problems necessitated a search exogenous substance or mixture that alters for safer and more environmentally friendly the function(s) of the endocrine system and products, which ushered in the era of consequently causes adverse health effects smarter pesticides. Organophosphates and in an intact organism, or its progeny, or carbamates replaced the highly persistent (sub)populations’ (Combarnous, 2017). organochlorines (Table 1.1). In the 1930s, Pesticides with common modes of a German chemist Gerhard Schrader at IG action become more selective and generally Farben experimented with nerve poison lead to resistance problems. During the insecticides, organophosphates, which were 1990s research continued to find new mole- meant to be used as chemical warfare agents cules with greater selectivity and better during World War II (López-Muñoz et al., environmental and toxicological profiles. 2009). After World War II, the organophos- New families like strobilurins and azolone phate pesticides were synthesized in large were introduced as fungicides, as well as fip- quantities. Parathion was among the first roles and spinosyn as insecticides with lower marketed, followed by malathion and dosages in grams instead of kilograms per azinphosmethyl. These insecticides became hectare. The introduction of user-friendly more popular after many of the organochlo- and environmentally safer formulations has rine insecticides like DDT, dieldrin and hep- helped to combat the problem of resistance tachlor were banned in the 1970s. Although management. The integrated pest manage- less persistent in the environment, they are ment (IPM) approach has led to a reduction more lethal even at low dosages. in the load of synthetic pesticides because of Pesticides 5 ., al

et 1983 1983 1983 1983 1983 Mullaney, 2018 Metcalf, 1994 1983 2011 Reference Hummel, Hummel, Hummel, Hummel, Hummel, Gaalaas Metcalf and Hummel, Mnif plants and bioaccumulation biomagnification properties dosages at low more lethal even be combined with the synergist (PBO) butoxide piperonyl with compatible environment, pest management systems hazards environmental non-toxic and in dark (Fourouzan kept 2017) Farrokh-Eslamlu, endocrine system of both and humans wildlife Drawbacks to humans and agricultural Toxic Highly persistent due to their and Acutely potent nerve toxins can are axonic excitotoxins; They less harmful to the Selective, No human health or potent, and specific, Volatile, to sunlight, should be Sensitive Alter the normal functioning of the malaria control environment cycle of insects life ingestion patterns, behaviour mating or prevent delay and producing offspring synthesis of the insecticide cartap stage of insects Benefits management Pest for Highly effective Less persistent in activity Knock-down Disrupt and impede the produced following Toxins with normal Interfere Model compound tor the Target a critical life cycle a critical life Target botanical compounds carbamates synthesis inhibitors, moulting hormones, and precocenes, compounds that mimic their effects disruptors substance isolated from the marine annelid Lumbriconereis heteropoda ) Group of pesticides Inorganic and organic Organochlorines Organophosphates and Synthetic pyrethroids hormones, chitin Juvenile Bacillus thuringiensis (Bt) mating attractants, Sex (a neurotoxic Nereistoxin Man-made 1940 (widespread onwards 1940–1960) use, (widespread use, post-1970s) generation until date generation Period of marketing Period World War I; prior to I; War World 1940 I; War Post-World Early 1950s 1970s By 1975 Late 1970s Bt protein in 1990s Late 1990s Late 1990s Initiated from first as As, Cu and Pb as As, lindane malathion; carbaryl aldicarb, cypermethrin and deltamethrin regulator (Antifeedants, pheromones) products, (natural hormonebrain antagonist) disruptors Example Heavy metals such Heavy methoxychlor, DDT, Dimethoate, Permethrin, Insect growth Microbials modifiers Behaviour Promising leads Endocrine History of pesticides according to their generation.

Category First generation Second generation (synthetic) Third generation Fourth generation Fifth generation Table 1.1. Table dichlorodiphenyltrichloroethane. DDT, 6 Chapter 1 the other components for pest management pesticides tends to be more intense and that are involved. Resistant varieties, genet- unsafe. The regulatory, health and education ically engineered crops, cultural practices systems are weaker in developing countries, and biological control are a few of the com- leading to a lack of awareness of the latest ponents of the IPM strategy. techniques in agriculture and safe handling of pesticides.

1.2 Global Status of Use of Pesticides 1.3 Classification of Pesticides The first use of synthetic pesticides was in 1940. As per the EPA Pesticide Industry The pesticides could be broadly classified Sales and Usage Report of 2006 and 2007, into two groups: agricultural and non-agri- the world used approximately 5.2 billion lb cultural use, although some pesticides may (2.4 billion kg) of pesticides, with herbicides be placed in both categories. In some coun- constituting the largest part (40%) of world tries such as the UK, the competent author- pesticide use, followed by insecticides (17%) ity responsible for processing and approvals and fungicides (10%). In 2006 and 2007 the is different for each group. The approval pro- US used approximately 1.1 billion lb (0.5 bil- cesses for agricultural pesticides are man- lion kg) of pesticides, accounting for 22% of aged by the Pesticides Safety Directorate at the world total, including 857 million lb York, while non-agricultural pesticides are (388.7 million kg) of conventional pesti- governed by the Health and Safety Executive cides, which are used in the agricultural sec- (HSE) at Bootle. A similar kind of distinction tor (80% of conventional pesticide use) as is made between plant protection products well as the industrial, commercial, govern- and biocides by the European Union. Pesti- mental, and home and garden sectors. Pesti- cides are classified based on their target cides are also found in the majority of US pests (Table 1.2), chemical structure (Table households, with 78 million out of the 105.5 1.3), route of entry and mode of action million households indicating that they use (Table 1.4). some form of pesticide (Wikipedia, Decem- ber, 2014). In 1999 about 74% of house- holds in the US were reported to use at least 1.3.1 Classification according to their one pesticide in the home. The use of pesti- route of entry cides in the US doubled from 1960 to 1980, but total use has since remained stable or •• Stomach poisoning – the pesticide enters fallen. As of 2007, there were more than the body of pests via their mouthparts 1055 active ingredients registered as pesti- and digestive system and causes death cides (Goldman, 2007), which yield over by poisoning. For example, DDT, hexa- 20,000 pesticide products that are marketed chlorocyclohexane (HCH), etc. in the US (CDC and P, 2015). The consumption of pesticides has risen in developing countries, and the fastest Table 1.2. Classification of pesticides based on growing markets are observed to be in their target organisms. Africa, Asia, South and Central America and Group Pesticide type Target organism the eastern Mediterranean region. There is high pesticide use on crops grown for export 1 Insecticide Insects (Dr N. Besbelli, WHO, personal communica- 2 Fungicides Fungi tion, July, 2008) (Laborde, 2008). Although 3 Herbicide Weeds/plants consumption of pesticides in developing 4 Molluscicide Slugs, snails countries makes up only 25% of the pesti- 5 Rodenticide Rodents 6 Acaricide Mites cides produced worldwide, they account for 7 Nematicides Nematodes 99% of the deaths. This is because the use of Pesticides 7

Table 1.3. Classification of pesticides based on their chemical structure (with examples).

Group Pesticides

Organochlorines DDT, aldrin, dieldrin, heptachlor Organophosphates Phosphates, phosphonates, phosphinates, phosphorothioates, phosphorodithioates, phospharamides, phosphorothioamidates Carbamates n-methyl carbamates, dithiocarbamates, benzimidazoles Pyrethrum and Pyrethrins, cypermethrin, deltamethrin, fenvalerate synthetic pyrethroids Phenols Pentachlorophenols, dinoprop, DNOC Morpholines Fungicides such as amorolfine, fenpropimorph, dimethomorph, tridemorph Chloroalkylthiols Fungicides Organometallics Fungicides: mancozeb, maneb, zineb, metam sodium Azoles Fungicides: myclobutanil, tebuconazole, paclobutrazole, penconazole Ureas, thioureas Herbicides: sulfonylureas, linuron, benzthiazuron Anilines Pendimethalin, trifluralin, fluchloralin Chloronitrile Chlorothalonil, chloroxynil, dichlobenil

DDT, dichlorodiphenyltrichloroethane; DNOC, dinitro-ortho-cresol.

•• Contact poisoning – the pesticide enters 1.3.2 Classification according to the body of pests via their epidermis chemical structure (broad group-wise through contact and generally controls classification) a pest as a result of direct contact. Insects are killed when sprayed directly 1. Organochlorine pesticides: these pesti- or when they come across surfaces cides are synthetic organic compounds con- treated with a residual contact insecti- taining at least one covalently bonded atom cide. For example, pyrethrums, rote- of chlorine, which were the earliest discov- none, toxaphene and chlordane. ered and used. Their characteristics are •• Fumigation – the pesticide in gaseous broad spectrum, highly persistent with rela- form enters the body of pests via their tively low toxicity. Prolonged use in large respiratory system and causes death by quantities can easily lead to environmental poisoning. For example, HCN, chloro- pollution and accumulation in fat tissues of picrin, methyl bromide, dichlorvos mammals, resulting in cumulative poison- (DDVP), aluminium phosphide, etc. The ing or damage. Organochlorine pesticides soil may be fumigated to destroy grubs were therefore banned under general cir- attacking roots or to control cumstances and gradually replaced by other nematodes. pesticides. •• Systemic action – these are the toxicants 2. Organophosphate pesticides: the organo- that are rapidly absorbed and translo- phosphates or phosphate esters are the gen- cated to various parts of the plants in eral names for esters of phosphoric acid. amounts lethal to insects feeding on Organophosphate pesticides or acetylcho- them. For example, phorate, aldicarb, line esterase inhibitors are characterized by carobfuran. Systemic herbicides move their multiple functions and the capacity for within the plant to untreated areas of controlling a broad spectrum of pests. They the root, stem or leaves of plants. Trans- are nerve poisons that can be used not only location of these pesticides takes place as stomach poison but also as contact poison mostly through the xylem vessels. Pesti- and fumigants. These pesticides are also bio- cides consumed by a host organism will degradable, cause minimum environmental stay in its body fluids. Pests feeding on pollution and slow pest resistance. Teme- the body fluids of the host organism will phos and fenitrothion are examples of then be killed by poisoning. organophosphate pesticides. 8 Chapter 1

3. Carbamate pesticides: carbamate is an 1.3.3 Classification of pesticides organic compound derived from carbamic according to their mode or site of action acid (NH2COOH). Carbamate esters (e.g. ethyl carbamate) and carbamic acids are Pesticides can also be classified according to functional groups that are interrelated their mode of action or the way a pesticide structurally and often are interconverted destroys or controls the target pest. This is chemically. These pesticides work on a simi- also referred to as the primary site of action. lar principle to organophosphate pesticides For example, one insecticide may be an ace- by affecting the transmission of nerve sig- tylcholinesterase inhibitor and affect an nals resulting in the death of the pest by poi- insect’s nerves, while another may affect soning. They can be used as stomach and moulting. Similarly, a herbicide may mimic contact poisons as well as fumigant. More- the plant’s growth regulators and another over, as their molecular structures are largely may affect photosynthesis. A fungicide may similar to those of natural organic sub- affect cell division and another may slow the stances, they can be degraded easily in a formation of an important compound in the natural manner with minimum environ- fungus. The modes of action are limited in mental pollution. Carbaryl and carbofuran number but numbers of pesticides are many. are examples of carbamate pesticides. Some pesticides have the same mode of 4. Synthetic pyrethroid: synthetic pyre- action. The Insecticide Resistance Action throid pesticides are synthesized by imitat- Committee (IRAC) has classified pesticides ing the structure of natural pyrethrins. They according to their mode of action or the tar- are comparatively more stable with longer get site of action (Table 1.4). residual effects than natural pyrethrins. Synthetic pyrethroid pesticides are highly 1.4 Fungicides toxic to insects but of only slight toxicity to mammals. Pyrethroids now constitute the The chemicals used to kill or inhibit the majority of commercial household insecti- growth of fungi, the causal organisms of cides, being generally harmless to human plant disease, are called fungicides. Although beings in low doses, but they can harm sen- viruses, nematodes and bacteria also cause sitive individuals. They are usually broken diseases in plants, fungi are the number one apart by sunlight and the atmosphere in causes of crop loss worldwide. At times, the 1–2 days, and do not significantly affect symptoms caused by pathogens resemble groundwater quality. Allethrin and perme- the symptoms caused by abiotic factors such thrin are examples of synthetic pyrethroid as nutrient deficiency and air pollution. pesticides. Fungicides can be classified in a number 5. Microbial insecticides: microbial insecti- of different ways, including (i) mobility in cides control pests by means of pathogenic the plant, (ii) role in protection of plants, micro-organisms including bacteria, fungi (iii) breadth of activity, (iv) mode of action, and viruses. Bacillus thuringiensis israelensis (v) chemical group and (vi) Fungicide (B.t.i.) is an example of a microbial ­Resistance Action Committee (FRAC) group insecticide. ( https://www.ncipmc.org/action/­ 6. Insect growth regulators: insect growth Fungicide%20Manual4.pdf). regulators are compounds developed by copying insect juvenile hormone. The main 1. Mobility in the plant. Contact fungicide: functions are to interfere with the growth a fungicide that remains on the surface of and hatching of larvae into adults, and to the plant where it is applied but does not go prevent the formation of an exoskeleton so deeper; these fungicides have no post-­ as to prohibit the growth of the insect. As its infection activity. Repeated applications are ability to live as a living organism is cur- needed to protect new growth of the plant tailed, the insect as well as the whole insect and to replace fungicide that has been population may die eventually. Methoprene washed off by rain or irrigation, or degraded is an example of an insect growth regulator. by environmental factors such as sunlight. Pesticides 9 continued carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, formetanate, fenobucarb, ethiofencarb, carbaryl, carbosulfan, carbofuran, pirimicarb, oxamyl, metolcarb, methomyl, methiocarb, isoprocarb, furathiocarb, xylylcarb XMC, triazamate, trimethacarb, thiofanox, thiodicarb, propoxur, chlorpyrifos-methyl, chlormephos, chlorpyrifos, chlorfenvinphos, chlorethoxyfos, diazinon, dichlorvos/DDVP, demeton-s-methyl, cyanophos, coumaphos, EPN, ethion, ethoprophos, disulfoton, dimethylvinphos, dimethoate, dicrotophos, imicyafos, heptenophos, fosthiazate, fenthion, fenitrothion, fenamiphos, famphur, isoxathion, salicylate, O - (methoxyaminothiophosphoryl) isopropyl isofenphos, monocrotophos, methidathion, mevinphos, malathion, mecarbam, methamidophos, phenthoate, parathion-methyl, parathion, oxydemeton-methyl, naled, omethoate, pirimiphos-methyl, phosmet, phosphamidon, phoxim, phosalone, phorate, quinalphos, pyridaphenthion, pyraclofos, prothiofos, propetamphos, profenofos, tetrachlorvinphos, thiometon, terbufos, temephos, tebupirimfos, sulfotep, vamidothion trichlorfon, triazophos, bioresmethrin, cycloprothrin, cyfluthrin, bioallethrin isomer, s-cyclopentenyl beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin- isomers], deltamethrin, [(1 R )- trans empenthrinEZ )-(1 R )- isomers], [( flucythrinate, flumethrin, fenvalerate, fenpropathrin, etofenprox, esfenvalerate, imiprothrin, kadethrin, permethrin, halfenprox, phenothrin tau-fluvalinate, resmethrin, (pyrethrum), silafluofen, - isomer], prallethrin, pyrethrins [(1 R )- trans tefluthrin, tetramethrin, tetramethrin [(1 R )-isomers], tralomethrin, transfluthrin Active ingredients Active butoxycarboxim, butocarboxim, benfuracarb, bendiocarb, aldicarb, Alanycarb, cadusafos, azinphos-methyl, azinphos-ethyl, azamethiphos, Acephate, endosulfan Chlordane, fipronil Ethiprole, Acrinathrin, allethrin,allethrin, allethrin,bioallethrin, d- cis - trans d- trans bifenthrin, DDT methoxychlor Organophosphates organochlorines (fiproles) Pyrethrins methoxychlor Chemical subgroup Chemical subgroup ingredient or active 1A Carbamates 1B 2A Cyclodiene 2B Phenylpyrazoles 3A Pyrethroids 3B DDT Classification of pesticides according to their mode action.

Nerve action Nerve action Main group and primaryMain group site of action Acetylcholinesterase (AChE) inhibitors (AChE) Acetylcholinesterase GABA-gated chloride Sodium channel modulators Table 1.4. Table 10 Chapter 1 thiamethoxam Methyl bromide and other alkyl halides Methyl Chloropicrin Sulfuryl fluoride Borax emetic Tartar Pymetrozine Flonicamid diflovidazin hexythiazox, Clofentezine, Etoxazole Active ingredients Active thiacloprid, Acetamiprid, imidacloprid, clothianidin, dinotefuran, nitenpyram, Nicotine Flupyradifurone spinosad Spinetoram, lepimectin, milbemectin Abamectin, emamectin benzoate, methoprene kinoprene, Hydroprene, Fenoxycarb Pyriproxyfen milbemycins analogues 8A Alkyl halides 8B Chloropicrin 8C Sulfuryl fluoride 8D Borates emetic 8E Tartar 9B Pymetrozine 9C Flonicamid 10A Clofentezine Hexythiazox Diflovidazin 10B Etoxazole Chemical subgroup Chemical subgroup ingredient or active 4A Neonicotinoids 4B Nicotine 4C Sulfoxaflor 4D Butenolides Spinosyns Avermectins, hormone 7A Juvenile 7B Fenoxycarb 7C Pyriproxyfen Continued.

Miscellaneous non-specific (multi-site) inhibitors Miscellaneous non-specific (multi-site) Nerve action regulation Growth Nerve action activators Nerve action action Nerve and muscle regulation Growth a 9 Modulators of chordotonal organs inhibitors 10 Mite growth Main group and primaryMain group site of action 4 Nicotinic acetylcholine receptor (nAChR) agonists 4 Nicotinic acetylcholine receptor (nAChR) allosteric Nicotinic acetylcholine receptor (nAChR) Chloride channel activators hormone mimics 7 Juvenile 8 Table 1.4. Table Pesticides 11 continued . tenebrionis kurstaki , Bacillus thuringiensis sub sp . Bacillus thuringiensis sub sp . Cry34Ab1/Cry35Ab1 teflubenzuron, triflumuron noviflumuron, novaluron, lufenuron, , aizawai , Bacillus thuringiensis israelensis sub sp. Bacillus thuringiensis sub sp. Bt crop proteins (midgut) Vip3A, mCry3A, Cry3Bb, Cry1A.105,Cry3Ab, Cry1Ac,Cry1Ab, Cry1Fa, Cry2Ab, Bacillus sphaericus Diafenthiuron oxide fenbutatin cyhexatin, Azocyclotin, Propargite Tetradifon sulfluramid DNOC, Chlorfenapyr, cartap thiocyclam, thiosultap-sodium Bensultap, hydrochloride, hexaflumuron, flufenoxuron, Bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, Buprofezin Cyromazine tebufenozide methoxyfenozide, halofenozide, Chromafenozide, Amitraz Hydramethylnon Acequinocyl Fluacrypyrim thuringiensis and the insecticidal proteins they produce sphaericus miticides sulfluramid analogues 11A Bacillus 11B Bacillus 12A Diafenthiuron 12B Organotin 12C Propargite 12D Tetradifon DNOC Chlorfenapyr, Nereistoxin Benzoylureas Buprofezin Cyromazine Diacylhydrazines Amitraz 20A Hydramethylnon 20B Acequinocyl 20C Fluacrypyrim (includes transgenic crops expressing Bacillus crops expressing (includes transgenic for specific guidance however thuringiensis toxins, crops is not resistance management of transgenic based on rotation of modes action) Energy metabolism disruption of the proton gradient Energy metabolism blockers Nerve action regulation Growth regulation Growth regulation Growth regulation Growth Nerve action inhibitors Energy metabolism 11 Microbial disruptors of insect midgut membranes synthase 12 Inhibitors of mitochondrial ATP phosphorylation via 13 Uncouplers of oxidative channel 14 Nicotinic acetylcholine receptor (nAChR) type 0 15 Inhibitors of chitin biosynthesis, type 1 16 Inhibitors of chitin biosynthesis, Dipteran 17 Moulting disruptor, 18 Ecdysone receptor agonists 19 Octopamine receptor agonists III electron transport20 Mitochondrial complex 12 Chapter 1 Active ingredients Active tolfenpyrad tebufenpyrad, pyridaben, pyrimidifen, fenpyroximate, Fenazaquin, Rotenone (derris) Indoxacarb Metaflumizone spirotetramat spiromesifen, Spirodiclofen, zinc phosphide phosphine, calcium phosphide, Aluminium phosphide, Cyanide cyflumetofen Cyenopyrafen, flubendiamide cyantraniliprole, Chlorantraniliprole, Azadirachtin Benzoximate Bifenazate Bromopropylate Chinomethionat Cryolite Dicofol Pyridalyl Pyrifluquinazon insecticides acid derivatives derivatives Chemical subgroup Chemical subgroup ingredient or active 21A METI acaricides and 21B Rotenone 22A Indoxacarb 22B Metaflumizone and Tetramic Tetronic 24A Phosphine 24B Cyanide Beta-ketonitrile Diamides Azadirachtin Benzoximate Bifenazate Bromopropylate Chinomethionat Cryolite Dicofol Pyridalyl Pyrifluquinazon Continued.

inhibitors Energy metabolism Nerve action regulation growth Lipid synthesis, inhibitors inhibitors Energy metabolism action Nerve and muscle action) Main group and primaryMain group site of action 21 Mitochondrial complex I electron transport21 Mitochondrial complex sodium channel blockers Voltage-dependent 22 23 Inhibitors of acetyl CoA carboxylase IV electron transport24 Mitochondrial complex II electron transport25 Mitochondrial complex receptor modulators 28 Ryanodine or uncertainUN (compounds of unknown mode of Table 1.4. Table GABA, benzenethionophosphonate; p-nitrophenyl ethyl EPN: phosphate; dimethyl 2,2-dichlorovinyl DDVP, 3,5-xylyl methylcarbamate; XMC, dichlorodiphenyltrichloroethane; DDT, METI, mitochondrial dinitro-ortho-cresol; electron transport DNOC, inhibitors. adenosine triphosphate; ATP, acid; gamma-aminobutyric Pesticides 13

Chlorothalonil and captan are contact Multi-site fungicide: fungicide that fungicides. affects a number of different metabolic sites Systemic fungicide: a fungicide that is within the fungus. Examples are captan, absorbed into plant tissue and may offer chlorthalonil and Bordeaux. some post-infection activity. Very few fungi- 4. Mode of action. How a fungicide kills or cides are truly systemic (i.e. move freely suppresses a target fungus, which is the throughout the plant); however, some are ­specific biochemical process of the target upwardly systemic (i.e. move only upwards fungus that is affected by a fungicide (Table in the plant through xylem tissue), and some 1.5). Examples are damaging cell mem- are locally systemic (i.e. move into treated branes, inactivating critical enzymes or pro- leaves and redistribute to some degree teins, or interfering with key processes such within the treated portion of the plant). as energy production or respiration. Examples are tricyclazole and hexconazole. 5. Chemical group or class. The name given 2. Role in protection (some fungicides can to a group of chemicals that share a com- fall into more than one of these categories). mon biochemical mode of action and may or Preventative activity: in this activity, a may not have similar chemical structure. ­fungicide is present on the plant as a protec- Fungicides approved for use on field crops tive barrier before the pathogen arrives or fall into different chemical groups. The fun- begins to develop, that is, the fungicide gal growth inhibition by fungicides may be ­prevents infection from occurring (also due to damage in their cell membranes, referred to as a protective activity). For ­inactivation of critical enzymes or proteins, example, azoxystrobin, tebuconazole and or interference with key processes such as pyraclostrobin. energy production or respiration. Others Early-infection activity: occurs when impact specific metabolic pathways such the active ingredient of a fungicide can pen- as the production of sterols or chitin. For etrate the plant and stop the pathogen in example, phenylamide fungicides bind to the plant tissues, usually most effective 24 and inhibit the function of RNA polymerase to 72 h after infection occurs, depending on in oomycetes, while the benzimidazole fun- the fungicide. This type of activity is some- gicides inhibit the formation of beta tubulin times referred to as ‘curative’ or ‘kickback’ polymers used by cells during nuclear activity. Most fungicides that have early- division. infection activity also have preventative 6. FRAC group. The FRAC has classified activity and are most effective when applied fungicides as per their mode of action and before infection occurs. Triazoles like tebu- resistance risk (Table 1.6). The intrinsic risk conazole and penconazole are applied as for resistance evolution to a given fungicide early-infection treatments. group is estimated to be low, medium or Anti-sporulant activity: an ability to high according to the principles described in prevent spores from being produced. In this FRAC monographs. case, disease continues to develop (e.g. lesions continue to expand), but spores are not produced or released, so the amount of inoculum available to infect surrounding 1.5 Herbicide Classification http://( plants is reduced. For example, botanical en.wikipedia.org/wiki/Herbicide) fungicides. 3. Breadth of metabolic activity. Single-site A herbicide is a compound that is toxic to fungicide: fungicide active against only one plants, and capable of either killing or point or function in one of the metabolic severely injuring unwanted vegetation; and pathways of a fungus or against a single may thus be used for the elimination of ­critical enzyme or protein needed by the plant growth or the killing of plant parts. fungus. These fungicides tend to have sys- Herbicides can be grouped by: (i) activ- temic properties. Thiophanate-methyl and ity; (ii) use; (iii) mechanism of action; (iv) trifloxystrobin are examples. chemical nature; (v) type of vegetation 14 Chapter 1

Table 1.5. Classification of fungicides based on mode of action (Whitehead, 1995).

Chemical group Compound Different modes of action Application Other uses

Inorganic Bordeaux mixture Protectant Spray Copper oxychloride Protectant Also bactericide Mercurous chloride Sulfur Protectant Also foliar feed Anilides Carboxim Seed dressing Benzimidazole (mbc) Thiabendazole Protectant, curative, systemic Spray Chlorophenyl Chlorothalonil Protectant Spray Quintozene Protectant Soil applied Conazole Flusilazole Protective, curative Spray Prochloraz Protectant, eradicant Spray Propiconazole Protectant, curative Spray Tebuconazole Curative Spray Triadimefon Protectant, curative, systemic Spray Dicarboximides Iprodione Protectant, eradicant Spray Dinitrophenyls Dinocap Protectant Spray Dithicarbamate Captan Protectant Spray Mancozeb Protectant Spray Maneb Protectant Spray Thiram Protectant Also animal repellant Morpholines Fenpropidin Protectant, curative, systemic Spray Fenpropimorph Curative, systemic Spray Tridemorph Protectant, eradicant, Spray systemic Phenylamide Metalaxyl Protectant Seed treatment Quinones Dithianon Protectant, eradicant Spray controlled; and (vi) Herbicide Resistance belowground plant parts, such as roots, Action Committee classification. bulbs, tubers or rhizomes. They are less effective on perennial plants, which are able to regrow from roots or tubers. 1.5.1 By activity Glufosinate ammonium is a broad-­ spectrum contact herbicide and •• Contact herbicides destroy only the plant ­paraquat is a non-selective contact tissue in contact with the chemical. herbicide. Generally, these are the fastest acting •• Systemic herbicides are translocated herbicides. For broadleaf weeds it will through the plant, either from foliar kill the above-ground leafy part of the application down to the roots, or plants. It will not directly kill the from soil application up to the leaves. Pesticides 15 FRAC FRAC code 4 8 32 31 1 10 continued various oomycetes but mechanism unknown. but oomycetes various management Resistance in powdery known mildews. management required mostly E198A/ target site mutations, Several gene G/K, F200Y in b -tubulin members cross-resistance to benzimidazoles Negative Comments Resistance and cross-resistance well known in known Resistance and cross-resistance well High-risk. resistance guidelines for phenylamide See FRAC Medium-risk resistance and cross-resistance Resistance not known Resistance known Bactericide. Risk in fungi unknown Resistance management required fungal species. Resistance common in many the group cross-resistance between Positive cross-resistance to NPhenylcarbamates Negative High-risk E198K. site mutation Target Resistance known. Resistance management required High-risk. kiralaxyl) mefenoxam)

(= (= thiophanate-methyl Common name Benalaxyl Benalaxyl-M Furalaxyl Metalaxyl Metalaxyl-M Oxadixyl Ofurace Bupirimate Dimethirimol Ethirimol Hymexazol Octhilinone Oxolinic acid Benomyl Carbendazim Fuberidazole Thiabendazole Thiophanate Diethofencarb pyrimidines Chemical group Acylalanines Oxazolidinones Butyrolactones Hydroxy-(2-amino-) Isoxazoles Isothiazolones acids Carboxylic Benzimidazoles Thiophanates carbamates N-phenyl (phenyl amides) (phenyl amino-) pyrimidines (methyl benzimidazole carbamates) carbamates Group name PA – fungicides PA Hydroxy-(2- Heteroaromatics acids Carboxylic MBC –fungicides N-phenyl Commercial fungicides according to their mode of action and resistance risk. (proposed) II (gyrase) mitosis mitosis

Target site and code Target A2: Adenosindeaminase A3: DNA/RNA synthesis A4: type DNA topoisomerase B2: in assembly b -tubulin A1: I RNA polymerase B1: in assembly b -tubuline

division

A: Nucleic acids synthesis acids Nucleic A: cell and Mitosis B: Mode of action Table 1.6. Table 16 Chapter 1 FRAC FRAC code 22 20 43 39 7 field populations and lab mutants field populations and lab H/L) at 257, 267, 272 or P225L, dependent on fungal species management Comments to medium risk Low Resistance management required Resistance not known Resistance not known Resistance not known fungal species in several for Resistance known H/Y (or e.g. in sdh gene, site mutations Target Resistance management required Medium to high risk resistance SDHI guidelines for See FRAC Common name Zoxamide Ethaboxam Pencycuron Fluopicolide Diflumetorim Olfenpyrad Benodanil Flutolanil Mepronil Isofetamid Fluopyram Fenfuram Carboxinoxycarboxin Thifluzamide thiazolecarboxamide benzamides carboxamides thiophene amide benzamides carboxamides carboxamides Chemical group Toluamides Ethylamino- Phenylureas Pyridinylmethyl Pyrimidinamines Pyrazole-5- Phenyl-benzamides Phenyl-oxo-ethyl Pyridinyl-ethyl- Furan-carboxamides Oxathiin- Thiazole- carboxamide dehydrogenase dehydrogenase inhibitors) Group name Benzamides Thiazole Phenylureas Benzamides Pyrimidinamines Pyrazole-MET1 SDHI (succinate Continued. mitosis proteins spectrin-like dehydrogenase oxido-reductase

Target site and code Target B3: in assembly b -tubulin B4: Cell division (proposed) B5: Delocalization of C2: succinate II: Complex C1: I NADH Complex C: Respiration C: Mode of action Table 1.6. Table Pesticides 17 11 continued Target site mutations in cyt b gene (G143A, site mutations Target F129L) and additional mechanisms the QoI group management Resistance known in various fungal species. fungal species. in various Resistance known all members of between Cross-resistance shown High risk resistance QoI guidelines for See FRAC Benzovindiflupyr Bixafen Fluxapyroxad Furametpyr Isopyrazam Penflufen Penthiopyrad Sedaxane Boscalid Azoxystrobin Coumoxystrobin Enoxastrobin Flufenoxystrobin Picoxystrobin Pyraoxystrobin Mandestrobin Pyraclostrobin Pyrametostrobin Triclopyricarb Kresoxim-methyl Trifloxystrobin Dimoxystrobin Fenaminstrobin Metominostrobin Orysastrobin Famoxadone Fluoxastrobin Fenamidone Pyribencarb carboxamides carboxamides Pyrazole-4- Pyridine- Methoxy-acrylates Methoxy-acetamide Methoxy-carbamates Oximino-acetates Oximino-acetamides Oxazolidine-diones Dihydro-dioxazines Imidazolinones Benzyl-carbamates (quinone outside inhibitors) QoI fungicides bc1 (ubiquinol oxidase) bc1 (ubiquinol oxidase) at Qo site ( cyt b gene) C3: cytochrome III: Complex 18 Chapter 1 FRAC FRAC code 21 29 30 38 45 9 23 medium to high (mutations at target site known at target site known medium to high (mutations Resistance management in model organisms). required in Japan risk risk assumed to be medium high (single-site Resistance management required inhibitor). sporadically in Oculimacula sporadically resistance management required Comments assumed to be Resistance riskbut unknown Also acaricidal activity Resistance not known. resistance claimed in Botrytis However, risk. Low Reclassified to U 14 in 2012 to medium Low Some resistance cases known. Low-risk Resistance reported. Resistance Not cross-resistant to QoI fungicides. , in BotrytisResistance known and Venturia Medium risk guidelines for anilinopyrimidine See FRAC Resistance management to medium risk. Low Common name Cyazofamid Amisulbrom Binapacryl Meptyldinocap Dinocap Fluazinam (Ferimzone) acetate Fentin chloride Fentin hydroxide Fentin Silthiofam Ametoctradin Cyprodinil Mepanipyrim Pyrimethanil Blasticidin-S crotonates compounds carboxamides pyrimidylamine antibiotic Chemical group Cyano-imidazole Sulfamoyl-triazole Dinitrophenyl 2,6-Dinitroanilines (Pyr.-hydrazones) tin Tri-phenyl Thiophene- Triazolo- Anilino-pyrimidines acid Enopyranuronic (quinone inside inhibitors) compounds carboxamides (quinone outside inhibitor, stigmatellin binding type) (anilino- pyrimidines) acid antibiotic Group name QiI fungicides Organo tin Thiophene- QoSI fungicides AP fungicides Enopyranuronic Continued. bc1(ubiquinone reductase) at Qi site phosphorylation phosphorylation, ATP synthase (proposed) bc1 (ubiquinone reductase) at Qo site, stigmatellin binding subsite (proposed)

Target site and code Target C4: cytochrome III: Complex C5: Uncouplers of oxidative C6: Inhibitors of oxidative C7: production ATP C8: cytochrome III: Complex D2: Protein synthesis D1: Methionine biosynthesis ( cgs gene)

synthesis

and protein protein and D: Amino acids acids Amino D: Mode of action Table 1.6. Table Pesticides 19 13 12 2 6 24 25 41 continued ) pathogens. Medium risk ) pathogens. glumae

P. ( Cross- Resistance management required. in Erysiphe necator resistance found (Uncinula) not in Blumeria graminis but to medium risk Low speculative. pathogens members management Resistance management required medium risk. risky pathogens if used for Resistance known in fungal and bacterial Resistance known Medium risk. known. Resistance to quinoxyfen mechanism sporadically, Resistance found Resistance management required Resistance common in Botrytis and some other in OS-1 , mostly I365S mutations Several the group Cross-resistance common between Medium to high risk resistance guidelines for dicarboximide See FRAC to Low in specific fungi. Resistance known Resistance management required Bactericide. Resistance known. High risk Resistance known. Bactericide. Resistance management required High risk Resistance known. Bactericide. Resistance management required Kasugamycin Quinoxyfen Proquinazid Fenpiclonil Fludioxonil Chlozolinate Iprodione Procymidone Vinclozolin Edifenphos (IBP) Iprobenfos Pyrazophos Isoprothiolane Streptomycin Oxytetracycline antibiotic antibiotic Hexopyranosyl Hexopyranosyl Aryloxyquinoline Quinazolinone Phenylpyrroles Dicarboximides Phosphorothiolates Dithiolanes Glucopyranosyl Glucopyranosyl antibiotic Tetracycline antibiotic (phenylpyrroles) dicarboximides thiolates antibiotic antibiotic Hexopyranosyl Hexopyranosyl Aza-naphthalenes PP fungicides Dicarboximides Formerly Phosphoro- Dithiolanes Glucopyranosyl Glucopyranosyl Tetracycline osmotic signal ( os-2 , transduction HOG1) osmotic signal ( os-1 , transduction Daf1 ) biosynthesis, methyltransferase (mechanism unknown)

E2: MAP/histidine-kinase in E3: MAP/histidine-kinase in F2: Phospholipid D3: Protein synthesis E1: Signal transduction F1: D4: Protein synthesis D5: Protein synthesis

integrity

and membrane membrane and

E: Signal transduction Signal E: synthesis Lipid F: 20 Chapter 1 44 46 FRAC FRAC code 14 28 B. subtilis var.Bacillus subtilis and B. taxonomic (previous amyloliquefaciens classification) FZB24 strain additional mode of action for risk activity spectra different required are Bacillus amyloliquefaciens for Synonyms Resistance not known Resistance not known described as Induction of host plant defence Comments to medium Low in some fungi. Resistance known due to Cross-resistance patterns complex Resistance management to medium risk. Low a

a amyloliquefaciens amyloliquefaciens FZB24 strain amyloliquefaciens MBI600 strain amyloliquefaciens D747 strain Melaleuca (tea alternifolia tree) strain QST 713 strain B. amyloliquefaciens Bacillus Bacillus Bacillus from Extract Common name Biphenyl Chloroneb Dicloran (PCNB) Quintozene (TCNB) Tecnazene Tolclofos-methyl Etridiazole Iodocarb Propamocarb Prothiocarb Bacillus subtilis syn. and terpene alcohols hydrocarbons fungicidal lipopeptides produced Terpene hydrocarbons hydrocarbons Terpene Chemical group Aromatic 1,2,4-Thiadiazoles Carbamates and the Bacillus sp. (aromatic hydrocarbons) (chlorophenyls, nitroanilines) fungicides sp.) Plant extract Group name AH fungicides Heteroaromatics Carbamates Formerly CAA Microbial ( Bacillus Continued. (proposed) (proposed) acids fatty permeability, (proposed) pathogen cell membranes

F7: disruptionCell membrane Target site and code Target F3: Lipid peroxidation F4: Cell membrane F5: F6: Microbial disrupters of Mode of action Table 1.6. Table Pesticides 21 3 continued DMI fungicides incl. resistance mechanisms are known Several in cyp51 (erg 11) gene, target site mutations cyp51 A379G, I381V; Y137F, V136A, e.g. ABC transporterspromotor; and others against DMI fungicides active present between the same fungus no cross-resistance to other show (sbis), but SBI classes management There are big differences in the activity spectra of in the activity spectra There are big differences fungal species. in various Resistance is known wise to accept that cross-resistance is Generally DMI fungicides are sterol biosynthesis inhibitors Medium risk resistance SBI guidelines for See FRAC Triforine Pyrifenox Pyrisoxazole Fenarimol Nuarimol Imazalil Oxpoconazole Pefurazoate Prochloraz Triflumizole Azaconazole Bitertanol Bromuconazole Cyproconazole Difenoconazole Diniconazole Epoxiconazole Etaconazole Fenbuconazole Fluquinconazole Flusilazole Flutriafol Hexaconazole Imibenconazole Ipconazole Metconazole Myclobutanil Penconazole Propiconazole Prothioconazole Simeconazole Tebuconazole Tetraconazole Triadimefon Triadimenol Triticonazole Piperazines Pyridines Pyrimidines Imidazoles Triazoles triazolinthiones (demethylation (demethylation inhibitors) (SBI: Class I) DMI fungicides biosynthesis ( erg11 / cyp51 )

G1: in sterol C14-demethylase G: Sterol biosynthesis in membranes in biosynthesis Sterol G: 22 Chapter 1 FRAC FRAC code 5 17 18 26 19 40 but not to other SBI classes but management required activity Phytophthora infestans in Phytophthora CAA group resistance management for Comments powdery mildews Decreased sensitivity for found generally Cross-resistance within the group to medium risk Low resistance SBI guidelines for See FRAC Resistance management to medium risk. Low fungicidal and herbicidal Resistance not known, Medical fungicides only Resistance not known Medium risk. Resistance known. Resistance management required not viticola but in Plasmopara Resistance known all members of the Cross-resistance between CAA guidelines See FRAC to medium risk. Low Common name Aldimorph Dodemorph Fenpropimorph Tridemorph Fenpropidin Piperalin Spiroxamine Fenhexamid Fenpyrazamine Pyributicarb Naftifine Terbinafine Validamycin Polyoxin Dimethomorph Flumorph Pyrimorph Benthiavalicarb Iprovalicarb Valifenalate Mandipropamid antibiotic nucleoside carbamates Chemical group Morpholines Piperidines Spiroketal-amines Hydroxyanilides Amino-pyrazolinone Thiocarbamates Allylamines Glucopyranosyl Glucopyranosyl pyrimidine Peptidyl Cinnamic acid amides Valinamide Mandelic acid amides (‘morpholines’) antibiotic acid (carboxylic amides) Group name Amines Class II) (SBI: Class III) (SBI: Class IV) (SBI: Alucopyranosyl Alucopyranosyl Polyoxins CAA fungicides Continued. 87-isomerase in sterol 87-isomerase biosynthesis ( erg24 , erg2 ) C4-demethylation ( erg27 ) sterol biosynthesis ( erg1 ) biosynthesis

Target site and code Target G2: 14-reductase and G3: reductase, 3-Keto G4: in Squalene-epoxidase H3: and inositol Trehalase H4: Chitin synthase H5: Cellulose synthase

biosynthesis H: Cell wall wall Cell H: Mode of action Table 1.6. Table Pesticides 23 16.1 16.2 P 1 P 2 P 3 P 4 P 5 27 33 continued required Resistance not known Resistance known Medium risk Resistance management required Resistance not known Resistance not known Resistance not known Resistance not known Resistance not known Resistance claims described Resistance management to medium risk. Low pathogens resistance cases reported in few Few risk Low antibacterial and antifungal activity) Reynoutria sachalinensis (giant knotweed) and salts Fthalide Pyroquilon Tricyclazole Carpropamid Diclocymet Fenoxanil Acibenzolar-s-methyl (also Probenazole Tiadinil Isotianil Laminarin from Extract Cymoxanil Fosetyl-Al Phosphorous acid carboxamide (BTH) carboxamide ethanol extract oxime Isobenzo-furanone Pyrrolo-quinolinone Triazolobenzo-thiazole Cyclopropane- Carboxamide Propionamide Benzo-thiadiazole Benzisothiazole Thiadiazole- Polysaccharides mixture, Complex Cyanoacetamide- phosphonates Ethyl biosynthesis inhibitors – reductase) biosynthesis inhibitors – dehydratase) (BTH) carboxamide oxime MBI-R (melanin MBI-D (melanin Benzo-thiadiazole Benzisothiazole Thiadiazole- compound Natural Plant extract Cyanoacetamide- Phosphonates biosynthesis biosynthesis

I2: in melanin Dehydratase P2 P3 P4 P5 Unknown I1: Reductase in melanin P1: Salicylic acid pathway Unknown

wall induction

I: Melanin synthesis in cell cell in synthesis Melanin I: defence plant Host P: classified Not 24 Chapter 1 FRAC FRAC code 34 35 36 37 42 U 6 U 8 U 12 U 13 U 14 U 15 U 16 mildew. Medium risk. Resistance management Medium risk. mildew. required medium risk Resistance management (single-site inhibitor). required assumed to be medium. but unknown Resistance management required Comments Resistance not known Resistance not known Resistance not known Resistance not known Resistance not known Resistance in Sphaerotheca Resistance management required isolates detected in wheat powdery Less sensitive to Low inaequalis . in Venturia Resistance known Resistance management recommended Resistance not known Resistance not known Reclassified from C5 in 2012 Resistance risk assumed to be medium high Resistance risk Not cross-resistant to QoI. (bactericide) Common name Teclofthalam Triazoxide Flusulfamide Diclomezine Methasulfocarb Cyflufenamid Metrafenone Dodine Flutianil Ferimzone Oxathiapiprolin Tebufloquin sulfonamides thiazolidine hydrazones isoxazolines Chemical group Phthalamic acids Benzotriazines Benzene- Pyridazinones Thiocarbamate Phenyl-acetamide Benzophenone Guanidines Cyano-methylene- Pyrimidinone- Piperidinyl-thiazole- 4-Quinolyl-acetate sulfonamides hydrazones thiazole- isoxazolines Group name Phthalamic acids Benzotriazines Benzene- Pyridazinones Thiocarbamate Phenyl-acetamide Aryl-phenyl-ketone Guanidines Thiazolidine Pyrimidinone- Piperidinyl- 4-Quinolyl-acetate Continued. (proposed) (proposed) (OSBP) inhibition (proposed) binding site (proposed)

Target site and code Target Unknown Unknown Unknown Unknown Unknown Unknown Actin disruption disruptionCell membrane Unknown Unknown Oxysterol binding protein III: Complex cytochrome bc1, unknown Mode of action Table 1.6. Table Pesticides 25 NC M 1 M 2 M 3 M 4 M 5 M6 M 7 M 8 M 9 M 10 M 11 any signs of resistance developing to the signs of resistance developing any fungicides Resistance not known without considered as a low-risk group Generally oils, potassium oils, bicarbonate, material of biological origin salts) quinomethionate Mineral oils, organic oils, Mineral Copper (different Sulfur Ferbam Mancozeb Maneb Metiram Propineb Thiram Zineb Ziram Captan Captafol Folpet Chlorothalonil Dichlofluanid Tolylfluanid Guazatine Iminoctadine Anilazine Dithianon Chinomethionat/ Fluoroimide relatives (phthalonitriles) (anthraquinones) Diverse Inorganic Inorganic Dithiocarbamates and Phthalimides Chloronitriles Sulfamides Guanidines Triazines Quinones Quinoxalines Maleimide and relatives (phthalonitriles) (anthraquinones) Diverse Inorganic Inorganic Dithiocarbamates Phthalimides Phloronitriles Sulfamides Guanidines Triazines Quinones Quinoxalines Maleimide

Unknown Multi-site contact activity

classified

Not Not activity contact Multi-site 26 Chapter 1

They are capable of controlling peren- (valine, leucine and isoleucine). These herbi- nial plants. They can destroy a greater cides slowly starve affected plants of these amount of plant tissue than contact amino acids, which eventually leads to inhi- herbicides. Glyphosate is a systemic bition of DNA synthesis. They affect grasses non-selective, while fluroxypy­ r is a and dicots alike. The ALS inhibitor family ­systemic selective herbicide. includes sulfonylureas, imidazolinones (IMIs), triazolopyrimidines (TPs), pyrimidi- nyl oxybenzoates (POBs) and sulfonylamino 1.5.2 By use carbonyl triazolinones (SCTs). 3. EPSPS inhibitors. The enolpyruvylshiki- Soil-applied herbicides are applied to the soil mate 3-phosphate synthase enzyme EPSPS and are taken up by the roots of the target is used in the synthesis of the amino acids plant. tryptophan, phenylalanine and tyrosine. They affect grasses and dicots alike. Glypho- •• Pre-plant incorporated herbicides are sate (Roundup) is a systemic EPSPS inhibi- mechanically incorporated into the soil tor but is inactivated by soil contact. prior to planting. The objective for 4. Synthetic auxin is a synthetic analogue incorporation is to prevent dissipation and mimics the plant hormone. Synthetic through photodecomposition and/or auxins were discovered in the 1940s after a volatility. Trifluralin and imazethapyr long study of the plant growth regulator are pre-plant incorporated herbicides. auxin. They have several points of action on •• Pre-emergent herbicides are applied to the the cell membrane, and are effective in the soil before the crop emerges and prevent control of dicot plants. 2,4-D is a synthetic germination or early growth of weed auxin herbicide. seeds. Metolachlor and pendimethalin 5. Photosystem II inhibitors. These inhibit are pre-emergent herbicides, widely the electron transport system of photosyn- used for control of annual grasses. thesis. The transfer of electrons from Photo- •• Post-emergent herbicides are applied system II to Photosystem I is essential for after the crop has emerged. Imazamox, the production of photosynthetic energy. an imidazolinone, and carfentazone- They reduce electron flow from water to ethyl are examples of post-emergent NADPH2+ during the photochemical step. herbicides. They bind to the Qb site on the D2 protein, and prevent quinone from binding to this site. Therefore, this group of compounds 1.5.3 By mechanism of action causes electrons to accumulate on chloro- phyll molecules. As a consequence, oxida- 1. ACCase inhibitors are chemicals used to tion reactions in excess of those normally kill grasses, the monocots. Acetyl coenzyme tolerated by the cell occur, and the plant A carboxylase (ACCase) is part of the first dies. The triazine herbicides (including atra- step of lipid synthesis. Thus, ACCase inhibi- zine) are PSII inhibitors. tors affect cell membrane production in the 6. Photosystem I inhibitors are considered meristems of the grass plant. The ACCases to be contact herbicides and are often of grasses are sensitive to these herbicides, referred to as membrane disruptors. The whereas the ACCases of dicot plants are destroyed cell membranes result in leakage not. Fluazifop-p-butyl, quizalofop-p-tefuryl of cell contents into the intercellular spaces. and fenoxaprop-p-ethyl are some ACCase These are actually ‘electron thieves’ and inhibitors. divert electrons from the normal pathway 2. ALS inhibitors are DNA synthesis inhibi- through FeS to Fdx to NADP leading to tors. The acetolactate synthase (ALS) direct discharge of electrons on oxygen. As a enzyme (also known as acetohydroxyacid result, reactive oxygen species are produced synthase, or AHAS) is the first step in the and oxidation reactions in excess of those synthesis of the branched chain amino acids normally tolerated by the cell occur, leading Pesticides 27 to inhibitition of photosynthesis. Bipyridin- iv) Carbamates: Propham, chloropham, ium herbicides (such as diquat and paraquat) barban. inhibit the Fe-S–Fdx step of that chain, I. Thiocarbamates: Butylate, dilate, while diphenyl ether herbicides (such as triallate, s-ethyl dipropylthiocarba- nitrofen, nitrofluorfen and acifluorfen) mate (EPTC), molinate, pebulate, inhibit the Fdx–NADP step. vernolate, benthlocarb, aslum, 7. HPPD inhibitors inhibit 4- cycolate. hydroxyphenylpyruvate dioxygenase, which II. Dithiocarbamates: CDEC, is involved in tyrosine breakdown. The carot- metham. enoids, produced by tyrosine breakdown v) Nitralin (benzonitrates): Dichlobe- products, protect chlorophyll in plants from nil, bromoxynil, ioxynil. being destroyed by sunlight. Lack of carot- vi) Ditroanilines (Toluidines): Benefin, enoids results in plants turning white due to nitralin, trifluralin, butralin, dinitra- complete loss of chlorophyll, and plant death. mine, fluchlorine, oxyzalin, penoxalin. These inhibitors, discovered over 30 years vii) Phenoxy: 2,4-D; 2,4, 5-T; 4-(2- ago, are the newest class of chemicals in the methyl-4-chlorophenoxy) butyric acid herbicide world. This chemistry was first (MCPB); 2,4-DB; 2,4-DP; 2,4,5-TP introduced in Asia for weed control in rice, (silvex) but has primarily been used in maize in the viii) Ureas: Monuron, diuron, fenuron, USA. Mesotrione and sulcotrione are herbi- neburon, flumeturon, methabenzthia- cides in this class; a drug, nitisinone, was dis- zuron, buturon, chlorbromuron, chlo- covered in the course of developing this class roxuron, norea siduson, metoxuron. of herbicides. ix) Organic arsenicals: Cacodlic acid, monosodium methyl arsenate (MSMA), disodium methyl arsenate (DSMA). 1.5.4 By chemical nature and x) Aromatic carboxylic acids: composition I. Phenyl acetic acid: Fenac or 2,3,6-trichlorophenyl acetic acid. Compounds with chemical affinities are II. Benzoic acid: 2,3,6-trichlorobenzoic grouped together. This is useful in character- acid (2,3,6 TBA), amiben (2-amino- izing herbicides. 2,5-­dichlorobenzoic acid). III. Phthalic acid: Endothal, dimethyl 1. Inorganic herbicides: The first chemicals ester of tetrachloroterephthalic acid used for weed control before the introduc- (DCPA). tion of the organic compounds and contain I V. NPA or N-1 napthyl pthalamic no carbon. Examples: acid. i) Acids: Arsenic acid, arsenious acid, xi) Aromatics: arsenic trioxide, sulfuric acid. I. Substituted phenols: PCP or ii) Salts: Borax, copper sulfate, ammo- pentachlorophenol, PCP sodium nium sulfate, sodium chlorate, sodium salt, DNBP or dinitrophenols. arsenite, copper nitrate. II. Diphenyl ethers: Nitrogen, flu- 2. Organic herbicides: Oils and non-oils rodifen, oxyfluorfen. containing carbon and hydrogen atoms in xii) Heterocyclic nitrogen derivatives: their molecules. Examples: Simazine, atrazine, maleic hydrazide, i) Oils: Diesel oil, standard solvent, amitrol. xylene-type, aromatic oils, polycyclic, I. Triazines: Atrazine, simazine, aromatic oils etc. ametryne, terbuteryne, cyprazinc, ii) Aliphatics: Dalapon, TCA, Acrolein, metribuzin, prometryn, propazine. glyphosate methyl bromide. II. Sulfonylureas: Such as benz­ iii) Amides: Propanil, butachlor, ala- sulfuron, chlorimuron, chlorsulfu- chlor, CDAA, Diphenamide, Naptalam, ron, metsulfuron, sulfometuron, Propachlor. thiameturon. 28 Chapter 1

III. Imadazolinones: Imazapyr, ima- applied to the soil prior to weed seed germi- zaquin, imazethapyr, imazapic. nation. They provide good control of many I V. Uracils: Bromacil, terbacil. annual grassy weeds and are the best weapon V. Bipyridyliums: Paraquat, diquat. against crabgrass. As a general rule, most xiii) Others: Bentazon, piclaram, pyr- grassy weed herbicides will not control azon, pyrichlor, endothall, bensulphide, broadleaf weeds and vice versa. maleic hydrazide (MH), DCPA. 3. Sedge is another unique weed, which is neither a broadleaf nor grassy. Sedges are difficult to control. They form tubers con- 1.5.5 By type of vegetation controlled taining food reserves for plant survival. Her- bicide treatments will provide control of the It is important to know the life cycle of the shoots and leaves of the plant, but often vegetation or plant, that is, the length of multiple herbicide applications need to be time the plant lives, time of year it germi- made as sedges can regenerate from the nates and grows, and the type of reproduc- belowground nutlets. The new group of her- tive capabilities the plant possesses. Based bicides with low dosages, the sulfonylureas, on their life cycles, plants or weeds are are an important component of turfgrass grouped mainly into two categories: weed management. The halosulfuron and trifloxysulfuron herbicides are used for 1. Annuals are plants that complete their sedge control in turfgrass. life cycle in less than 1 year. Most annual weed seeds will remain viable in the soil for 1–7 years. The pre-emergent herbicides are used to manage these annual weeds. 1.5.6 By HRAC system 2. Perennials are plants that live for more than 2 years.Usually perennials do not pro- The Herbicide Resistance Action Committee duce seed in the year of establishment and (HRAC) system has been developed partly in survive for many growing seasons. Most cooperation with the Weed Science Society perennials reproduce by seed and many are of America (WSSA) and new herbicides have able to spread by vegetative means. The been categorized jointly by HRAC and most effective way to deal with perennial WSSA. For reference the numerical system weeds is through the use of post-emergent of the WSSA is listed, too. The WSSA and herbicides. HRAC systems differ only in minor ways. Herbicides in italics are listed in the HRAC The three categories that weeds fall into are classification system but are not listed in the broadleaf, grassy and sedges, as follows: WSSA classification (Table 1.7). (www.hrac- 1. Broadleaf weeds have different shapes global.com/Education/ClassificationofHer- and sizes with various patterns to their bicideSiteofAction.aspx). leaves. They are generally wider than their The aim of HRAC is to create a uniform length. The post-emergent herbicides such classification of herbicide sites of action in as 2,4-D, methylchlorophenoxypropionic as many countries as possible. Such a classi- acid (MCPP), 2-methyl-4-chlorophenoxy- fication system could be useful for many acetic acid (MCPA) and dicamba could be instances but there are cases where weeds used to effectively control these weeds. exhibit multiple resistance across many of 2. Grassy weeds tend to be narrower and the groups listed and in these cases the key longer, similar to grass. The leaf blades are may be of limited value. The system itself is longer than they are wide and have parallel not based on resistance risk assessment but veins. An example is crabgrass or dallisgrass. can be used by the farmer or researcher as a Proper pre-emergent herbicides like pendi- tool to choose herbicides in different sites of methalin, trifluralin and dithiopyr need to action groups, so that mixtures or rotations be selected for their control. These are of active ingredients can be planned. Pesticides 29

Table 1.7. Classification of herbicide according to HRAC.

HRAC WSSA group Site of action Chemical family Active ingredient group

A Inhibition of acetyl CoA Aryloxyphenoxy- Clodinafop-propargyl, cyhalofop- 1 carboxylase (ACCase) propionate butyl, diclofop-methyl, fenoxaprop- (informally termed as p-ethyl, fluazifop-p-butyl, ‘FOPs’) haloxyfop-r-methyl, propaquizafop, quizalofop-p-ethyl Cyclohexanedione Alloxydim, butroxydim, clethodim, (informally termed as cycloxydim, profoxydim, ‘DIMs’) sethoxydim, tepraloxydin, tralkoxydim Phenylpyrazoline Pinoxaden (informally termed as ‘DEN’) B Inhibition of acetolactate Sulfonylurea Amidosulfuron, azimsulfuron, 2 synthase ALS bensulfuron-methyl, chlorimuron- (acetohydroxyacid ethyl, chlorsulfuron, cinosulfuron, synthase AHAS) cyclosulfamuron, ethametsulfuron- methyl, ethoxysulfuron, flazasulfuron, flupyrsulfuron- methyl-Na, foramsulfuron, halosulfuron-methyl, imazosulfuron, iodosulfuron, mesosulfuron, metsulfuron-methyl, nicosulfuron, oxasulfuron, primisulfuron-methyl, prosulfuron, pyrazosulfuron-ethyl, rimsulfuron, sulfometuron-methyl, sulfosulfuron, thifensulfuron-methyl, triasulfuron, tribenuron-methyl, trifloxysulfuron, triflusulfuron-methyl, tritosulfuron Imidazolinone Imazapic, imazamethabenz-methyl, imazamox, imazapyr, imazaquin, imazethapyr Triazolopyrimidine Cloransulam-methyl, diclosulam, florasulam, flumetsulam, metosulam, penoxsulam Pyrimidinyl(thio) Bispyribac-Na, pyribenzoxim, benzoate pyriftalid, pyrithiobac-Na, pyriminobac-methyl Sulfonylaminocarbonyl- Flucarbazone-Na, triazolinone propoxycarbazone-Na C1 Inhibition of Triazine Ametryne, atrazine, cyanazine, 5 photosynthesis at desmetryne, dimethametryne, photosystem II prometon, prometryne, propazine, simazine, simetryne, terbumeton, terbuthylazine, terbutryne, trietazine Triazinone Hexazinone, metamitron, metribuzin Triazolinone Amicarbazone Uracil Bromacil, lenacil, terbacil continued 30 Chapter 1

Table 1.7. Continued.

HRAC WSSA group Site of action Chemical family Active ingredient group

Pyridazinone pyrazon = chloridazon Phenyl-carbamate Desmedipham, phenmedipham C2 Inhibition of Urea Chlorobromuron, chlorotoluron, 7 photosynthesis at chloroxuron, dimefuron, diuron, photosystem II ethidimuron, fenuron, fluometuron (see F3), isoproturon, isouron, linuron, methabenzthiazuron, metobromuron, metoxuron, monolinuron, neburon, siduron, tebuthiuron Amide Propanil, pentanochlor C3 Inhibition of Nitrile Bromofenoxim, bromoxynil, ioxynil 6 photosynthesis at photosystem II Benzothiadiazinone Bentazon Phenyl-pyridazine Pyridate, pyridafol D Photosystem-I-electron Bipyridylium Diquat, paraquat 22 diversion E Inhibition of Diphenylether Acifluorfen-Na, bifenox, 14 protoporphyrinogen chlomethoxyfen, fluoroglycofen- oxidase (PPO) ethyl, fomesafen, halosafen, lactofen, oxyfluorfen Phenylpyrazole Fluazolate, pyraflufen-ethyl n-phenylphthalimide Cinidon-ethyl, flumioxazin, flumiclorac-pentyl Thiadiazole Fluthiacet-methyl, thidiazimin Oxadiazole Oxadiazon, oxadiargyl Triazolinone Azafenidin, carfentrazone-ethyl, sulfentrazone Oxazolidinedione Pentoxazone Pyrimidindione Benzfendizone, butafenacil Other Pyraclonil, profluazol, flufenpyr-ethyl F1 Bleaching: inhibition of Pyridazinone Norflurazon 12 carotenoid biosynthesis at the phytoene desaturase step (PDS) Pyridinecarboxamide Diflufenican, picolinafen Other Beflubutamid, fluridone, flurochloridone, flurtamone F2 Bleaching: inhibition of Triketone Mesotrione, sulcotrione 27 4-hydroxyphenyl- pyruvate-dioxygenase (4-HPPD) Isoxazole Isoxachlortole, isoxaflutole Pyrazole Benzofenap, pyrazolynate, pyrazoxyfen Other Benzobicyclon continued Pesticides 31

Table 1.7. Continued.

HRAC WSSA group Site of action Chemical family Active ingredient group

F3 Bleaching: inhibition of Triazole Amitrole (in vivo inhibition of 11 carotenoid biosynthesis lycopene cyclase) (unknown target) Isoxazolidinone Clomazone 13 Urea Fluometuron (see C2) Diphenylether Aclonifen G Inhibition of EPSP Glycine Glyphosate, sulfosate 9 (5-enolpyruvylshikimate- 3-phosphate) synthase H Inhibition of glutamine Phosphinic acid Glufosinate ammonium, 10 synthetase bialaphos = bilanaphos I Inhibition of DHP Carbamate Asulam 18 (dihydropteroate) synthase K1 Microtubule assembly Dinitroaniline Benefin = benfluralin, butralin, 3 inhibition dinitramine, ethalfluralin, oryzalin, pendimethalin, trifluralin Phosphoroamidate Amiprophos-methyl, butamiphos Pyridine Dithiopyr, thiazopyr Benzamide Propyzamide = pronamide, tebutam Benzoic acid DCPA = chlorthal-dimethyl 3 K2 Inhibition of mitosis/ Carbamate Chlorpropham, propham, 23 microtubule organization carbetamide K3 Inhibition of VLCFAs Chloroacetamide Acetochlor, alachlor, butachlor 15 (see table notes) (inhibition of cell division) Dimethachlor, dimethanamid, metazachlor, metolachlor, pethoxamid Pretilachlor, propachlor, propisochlor, thenylchlor Acetamide Diphenamid, napropamide, naproanilide Oxyacetamide Flufenacet, mefenacet Tetrazolinone Fentrazamide Other Anilofos, cafenstrole, piperophos L Inhibition of cell wall Nitrile Dichlobenil, chlorthiamid 20 (cellulose) synthesis Benzamide Isoxaben 21 Triazolocarboxamide Flupoxam Quinoline carboxylic quinclorac (for monocots) (also group 26 acid O) M Uncoupling (membrane Dinitrophenol *DNOC, dinoseb, dinoterb 24 disruption) continued 32 Chapter 1

Table 1.7. Continued.

HRAC WSSA group Site of action Chemical family Active ingredient group

N Inhibition of lipid synthesis Thiocarbamate Butylate, cycloate, dimepiperate, 8 – not ACCase inhibition *EPTC, esprocarb, molinate, orbencarb, pebulate, prosulfocarb, thiobencarb = benthiocarb, tiocarbazil, triallate, vernolate Phosphorodithioate bensulide Benzofuran Benfuresate, ethofumesate Chloro-carbonic acid *TCA, dalapon, flupropanate 26 O Action like indole acetic Phenoxy-carboxylic Clomeprop, 2,4-D, 2,4-DB, 4 acid (synthetic auxins) acid dichlorprop = 2,4-DP, MCPA, MCPB, mecoprop = MCPP = CMPP Benzoic acid Chloramben, dicamba, TBA Pyridine carboxylic Clopyralid, fluroxypyr, picloram, acid triclopyr Quinoline carboxylic Quinclorac, (also group L), acid quinmerac Other benazolin-ethyl P Inhibition of auxin Phthalamate Naptalam, diflufenzopyr-Na 19 transport Semicarbazone R ...... S ...... Z Unknown Arylaminopropionic Flamprop-m-methyl/-isopropyl 25 Note: While the site of acid action of herbicides in Group Z is unknown it is likely that they differ in site of action among themselves and from other groups. Pyrazolium Difenzoquat 26 Organoarsenical DSMA, MSMA 17 Other Bromobutide, (chloro)-flurenol Cinmethylin Cumyluron Dazomet Dymron = daimuron, methyl- dimuron = methyl-dymron, etobenzanid, fosamine, indanofan, metam, oxaziclomefone, oleic acid Pelargonic acid, pyributicarb

According to information and comments the following herbicides are classified in the January 2005 version in HRAC (WSSA) groups: B (2): cancelled: #9; #9; procarbazone (approved ISO name: propoxycarbazone); E (14): cancelled: pyrazogyl (approved name: pyraclonil). DCPA, dimethyl tetrachloroterephthalate; VLCFA, very long chain fatty acid; DNOC, dinitro-ortho-cresol; EPTC, s-ethyl-n,n-dipropylthiocarbamate; TCA, 2,4,5-trichloroacetic acid; 2,4-D, 2,4-dinitrophenylhydrazine; 2,4-DB, 4-(2,4-dichlorophenoxy)butyric acid; 2,4-DP, 2-(2,4-dichlorophenoxy)propionic acid; MCPA, 2-methyl-4- chlorophenoxyacetic acid; MCPB, 4-(2-methyl-4-chlorophenoxy) butyric acid; MCPP/CMPP, methylchlorophenoxypropionic acid or mecoprop; DSMA, disodium methyl arsenate; MSMA, monosodium methyl arsenate. Pesticides 33

Criteria for descriptors of the quality of Additional information regarding sub- mechanism of action information groups is provided in Table 1.8. Strong evidence that Potent effects on the The cross-resistance potential between action at this protein function of the target subgroups is higher than that between dif- (or protein complex) protein and either ferent groups, so rotation between sub- is responsible for resistance due to groups should be avoided. In exceptional insecticidal effects mutation/overexpression/ circumstances (i.e. when effective registered removal of this protein or insecticides from other mode of action correlation of potency groups are unavailable), rotation may be between effects on the protein and biological considered following consultation with local activity for a set of expert advice and where cross-resistance analogues does not exist. These exceptions should not Good evidence that Highly potent effects on the be considered sustainable resistance man- action at this protein function of the protein agement strategies, and alternative options (or protein complex) combined with clearly should be sought to maintain pest is responsible for consistent physiological susceptibility. insecticidal effects effects Compounds affect the Compounds (or their function of this metabolites) have protein, but it is not moderate or low potency 1.6 Classification of Pesticides clear that this is on the function of the According to Risk Involved what leads to protein, and there is little biological activity or no evidence associating this effect There is always a risk to human health when with biological activity. handling pesticides and their formulated Compounds may be products. Pesticide exposure can occur via grouped because of ingestion, inhalation, dermal absorption or similarity of structure and ocular contact. There is a stringent need to distinctive physiological identify whether signs and symptoms of effect pesticide poisoning are due to the active Target protein Compounds may be ingredient (the pesticide itself), inactive responsible for grouped because of biological activity is similarity of structure and ingredients, solvents or additives, which unknown, or distinctive physiological may vary by region, country, manufacturer uncharacterized effect or individual preference. In 1973, WHO sug- gested a tentative classification of pesticides to distinguish between the more and less hazardous forms of each pesticide (extract Notes regarding subgroups from WHO Chronicle, 1975), taking into account the views of members of the WHO Subgroups represent distinct chemical Expert Advisory Panel on Insecticides and classes that are believed to have the same other expert advisory panels with special mechanism of action but are different competence and interest in pesticide tech- enough in chemical structure or mode of nology, as well as the comments of WHO interaction with the target protein that the Member States and of two international chance of selection for either metabolic or agencies. The WHO recommendations for target site cross-resistance is reduced com- classification of pesticides were based on pared to close analogues. Subgroups may their hazard levels. The proposal for recom- also distinguish compounds that are chemi- mendations was approved by the 28th World cally similar but known to bind differently Health Assembly in 1975 and was published within the target or to have differential in the WHO Chronicle (1975) as an annex, selectivity among multiple targets. but was not considered as part of the 34 Chapter 1

Table 1.8. Additional information about particular subgroups.

Subgroups Notes

3A and 3B Because DDT is no longer used in agriculture, this is only applicable for the control of human disease vectors such as mosquitoes 4A, 4B,4C Although these compounds are believed to have the same target site, current evidence and 4D indicates that the risk of metabolic cross-resistance between subgroups is low 10A Hexythiazox is grouped with clofentezine because they exhibit cross-resistance, even though they are structurally distinct, and the target site for these compounds is unknown. Diflovidazin has been added to this group because it is a close analogue of clofentezine and is expected to have the same mode of action 11A Different Bacillus thuringiensis products that target different insect orders may be used together without compromising their resistance management. Rotation between certain specific Bacillus thuringiensis microbial products may provide resistance management benefits for some pests. Consult product-specific recommendations Bt crop proteins: Where there are differences among the specific receptors within the midguts of target insects, transgenic crops containing certain combinations of the listed proteins provide resistance management benefits 22A and Although these compounds are believed to have the same target site, current evidence 22B indicates that the risk of metabolic cross-resistance between subgroups is low

DDT, dichlorodiphenyltrichloroethane. classification initially. However, the Member determinations are standard procedures in States and pesticide registration authorities toxicology. Where the dermal LD value of a suggested further guidance for classification compound is such that it would place it in a of individual pesticides. Guidelines were more restrictive class than the oral LD value first issued in 1978, and have since been would indicate, the compound will always be revised and reissued every few years. classified in the more restrictive class. The pesticides are assigned to a Toxicity WHO has categorized pesticides into Class, based on their acute risk to human five classes, according to the risk involved health (i.e. the risk of single or multiple in their use (Table 1.9). The US EPA has a exposures over a relatively short period of ‘toxicity ranking’ with four categories. The time). It takes into consideration the toxic- EPA warnings are often used on pesticide ity of the technical active substance and also labels. describes methods for the classification of A colour code has also been introduced formulations (in particular, allowance is for pesticide containers. A red stripe on the made for the lesser hazards from solids as label indicates that the chemical is extremely compared with liquids). There is a list of poisonous, yellow indicates highly poison- common technical grade pesticides and rec- ous, and blue and green indicate that they ommended classifications together with a are moderately and slightly poisonous, listing of active ingredients, believed to respectively. These colours are used at the be obsolete or discontinued for use as bottom of the pesticide label, along with ­pesticides, pesticides subject to the prior ­pictures to show the type of protective informed consent procedure (Rotterdam ­clothing that should be used while handling Convention), limitations to trade because of them. the Stockholm convention of persistant The WHO classification system has been organic pollutants (POPs), and gaseous or modified and replaced with the latest classi- volatile fumigants not classified under these fication, that is, the Globally Harmonized recommendations. The classification is ­System of Classification and Labelling of based primarily on the acute oral and Chemicals (GHS), which has been widely ­dermal toxicity to the rat since these used for the classification and labelling of Pesticides 35

Table 1.9. WHO classification of pesticides as per their hazard.

LD50 for the rat (mg/kg body weight)

Medium LD by the oral Medium LD by the dermal Colour of route (acute toxicity) route (dermal toxicity) identification

S. LD50 mg/kg body LD50 mg/kg body weight band on the no. WHO class weight of test animals of test animals label

1 Ia Extremely hazardous <5000 <5000 Bright red 2 Ib Highly hazardous 05–50 050–200 Bright yellow 3 II Moderately hazardous 0050–2000 0200–2000 Bright blue 4 III Slightly hazardous >2000 >2000 Bright green 5 U Unlikely to present acute hazard 5000 or higher

chemicals worldwide. For this revision of the considered less hazardous, should only be classification, the WHO Hazard Classes have applied by trained and supervised operators. been aligned in an appropriate way with the GHS Acute Toxicity Hazard Categories for acute oral or dermal toxicity as the starting point for allocating pesticides to a WHO 1.7 Conclusion Hazard Class (IPCS, 2009). As has always been the case, the classification of some pes- After the pesticide era of inorganic mole- ticides has been adjusted to take account of cules, during World War I, the organic mole- severe hazards to health other than acute cules, based on natural products, such as toxicity. The GHS Acute Toxicity Hazard Cat- nicotine (extracted from tobacco) and rote- egory for each pesticide is now presented none (extracted from derris roots), were alongside the existing information. The introduced. These were known as first-­ WHO system could be further developed generation pesticides. Second-generation over time in consultation with countries, pesticides included organochlorines. How- international agencies and regional bodies. ever, the indiscriminate use of these highly The GHS meets this requirement as a persistent organochlorines could generate ­classification system with global accep- a lot of problems as highlighted by Rachel tance following extensive international Carson in 1962 in her book Silent Spring. The consultation. problems paved the way for safer and more There are reports of acute pesticide environmentally friendly organophosphates ­poisoning (APP) cases, which account for including parathion, followed by malathion ­significant morbidity and mortality world- and azinphosmethyl. The herbicides glypho- wide, especially in developing countries sate, sulfonylurea and imidazolinone came (­Jeyaratnam, 1990; Kishi and Ladou, 2001). onto the market during 1970–1980. The The severity and likelihood of effects from introduction of pesticides, such as avermec- APP can vary according to specific agent, tins, benzoylureas and Bt, led to the era of dose, underlying physiologic reserve, comor- third-generation pesticides. New families of bidities, route of exposure, organ system, pesticides with user-friendly and environ- age, poverty, education and other factors mentally safer formulations, and lower dos- (­Thundiyil et al., 2008). It is advisable to ages in grams instead of kilograms per avoid pesticide products, classified by the hectare, were introduced; for example, stro- WHO as either extremely dangerous (WHO bilurins and azolone as fungicides; fiproles Class Ia) or highly hazardous (WHO Class and spinosyn as insecticides, leading to the Ib). However, it must be kept in mind that combatting of the problem of resistance even WHO Class II products, which are management. The IPM approach has led to a 36 Chapter 1 reduction in the load of synthetic pesticides Gaalaas Mullaney, E. (2018) Bacillus thuringenesis because of the other components for pest bacterium. Encyclopedia Britannica. Available management involved. Resistance variety, at: https://www.britannica.com/science/Bacillus- genetically engineered crops, cultural prac- thuringiensis (accessed 27 September 2018). Goldman, L.R. (2007) Managing pesticide chronic tices and biological control are a few of the health risks: US policies. Journal of Agromedi- components of the IPM strategy. cine 12(1), 67–75. The insecticides can be classified on the Hummel, H.E. (1983) Insecticides and their design. basis of their target organisms, chemical Journal of Nematology 15(4), 616–638. structure, route of entry and mode of site of IPCS (2009) International Programme on Chemical action, while fungicides are classified accord- Society. 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