## 2.3.1. Crop Protection Products

Author: Kees van Gestel

Reviewers: Steven Droge, Peter Dohmen

Learning objectives:

You should be able to:

- describe the role of crop protection products in agriculture
- mention different types of pesticides and their different target groups.
- distinguish and mention important chemical groups of pesticides
  - related to the chemistry
  - related to the mode of action
- describe major components included in a commercial formulation of a crop protection product beside the active substance(s).

Keywords: Insecticides, Herbicides, Fungicides, Active substances, Formulations

Introduction

Crop protection products are used in agriculture. The principle target of agriculture is the provision of food. For this purpose, agriculture aims to reduce the competition by other (non-crop) plants and the loss of crop due to herbivores or diseases. An important tool to achieve this is the use of chemicals, such as crop protection products (CPP). Accordingly, CPPs are intentionally introduced into the environment and represent one of the largest sources of xenobiotic chemicals in the environment. These chemicals are by definition effective against the target organism, often already at fairly low doses, but may also be toxic to non-target organisms including humans. The use of pesticides, also named Crop Protection Products (CPP) or often also Plant Protection Products (PPP, the latter term may be misleading for herbicides which are intended to reduce all but the crop plants), is therefore strictly regulated in most countries. The main pesticides used in the largest volumes world-wide are herbicide all s, insecticides, and fungicides. As shown in Table 1, pesticides are used against a large number of diseases and plagues.

Table 1. Classification of pesticides according to what they are supposed to control

Pesticide type | Target
acaricides | against mites and spiders (incl. miticides)
algicides | against algae
althelmintics (vermicides) | against parasites
antibiotics | against bacteria and viruses (incl. bactericides)
bactericides | against bacteria
fungicides | against fungi
herbicides | against weeds
insecticides | against insects
miticides | against mites
molluscicides | against slugs and snails
nematicides | against nematodes
plant growth regulators | retard or accelerate the growth of plants
repellents | drive pests (e.g. insects, birds) away
rodenticides | against rodents

Formulations

A pesticidal product usually consists of one or more active substances, that are brought onto the market in a commercial formulation (spray powder, granulate, liquid product etc.). The formulation is used to facilitate practical handling and application of the chemical, but also to enhance its effect or its safety of use. The active substance may, for instance, be a solid chemical, while application requires it to be sprayed. Or the active substance degrades fast under the influence of sunlight and therefore has to be encapsulated. One of the most used types of formulation is a concentrated emulsion, which may be sprayed directly after dilution with water. In this formulation, the active substance is dissolved in an oily matrix and a detergent is added as emulsifier to make the oil miscible with water. In this way, the active substance becomes quickly available after spraying. In so-called slow-release formulations, the active substance is encapsulated in permeable microcapsules, from which it is slowly released. Another component of a formulation can be a synergist, which increases the efficacy of the active substance, for instance by blocking enzymes that metabolize the active substance. Here an overview of main formulation constituents:

- Solvents: to ease handling and application of the active substances, they are usually dissolved. For a highly water soluble compound this solvent may just be water; however, most compounds have low water solubility and they are thus dissolved in organic solvents.
- Emulsifier, detergents, dispersants: used to provide a homogeneous mixture of the active substance in the aqueous spray solution.
- Carrier: solid formulations, such as wettable granules (WG). All wettable powder (WP) formulations often use inert materials such as clay (kaolinite) as carrier.
- Wetting agent: they help providing a homogeneous film on the plant surface.
- Adjuvant: may help to increase uptake of the active substance into the plant.
- Minor constituents:
  - Antifreeze agent: to keep the formulation stable also in cold storage conditions.
  - Antifoam agent: some of the formulants may result in foaming during application, which is not wanted.
  - Preservative, biocide: to prevent biological degradation of the active substance or the formulants during storage.
  - There are numerous additional specific additional constituents for specific purposes such as colours, detterents, stickers, etc

Four types of nomenclature are used in case of pesticides:

1. The trade name, e.g. Calypso®, which is given by the manufacturer. The same active substance is often sold under more than one different trade names (accordingly, the use of trade names only is not a sufficient description of the test substance in scientific literature).

2. The code name, which is the "common" name of the active substance. Calypso® 480 SC, for example, is a concentrated suspension containing 480 g/L of the active substance thiacloprid.

3. The chemical name of the active substance. Thiacloprid is [3-[(6-chloropyridin-3-yl)methyl]-1,3-thiazolidin-2-ylidene]cyanamide.

4. The name of the chemical group to which the active substance belongs, in case of thiacloprid: neonicotinoids.

Chemical classes

Pesticides represent quite a number of different groups of chemicals. Pesticides include inorganic chemicals (like copper used as a fungicide), organic synthetic chemicals, and biologicals (organic natural compounds). Pesticides from the same chemical group may be used against different pest organisms, like the organotin compounds (see below). Some chemicals have a broad mode of action: many soil disinfectants, such as metam-sodium, kill nematodes, fungi, soil insects and weeds. Other pesticides are more selective, like neonicotinoids acting only on insects, or very selective, like the insect-growth regulator fenoxycarb, which is used against leaf-rollers without affecting its natural enemies. Selectivity of a pesticide also indicates to what extent non-target species may be affected upon its application (side-effects). Integrated pest management (IPM) aims at an as sustainable as possible crop protection system by combining biological agents (predators of the pest organism) using chemicals having a selective mode of action. Such systems are nowadays receiving increasing interest in different agricultural crops.

Some groups of pesticides that were used or still are widely used are presented in more detail. Their modes of action are discussed in Chapter 4.

- Chlorinated hydrocarbons

Best known representative of this group is DDT (dichloro diphenyl trichloroethane; Figure 1), which was discovered in 1939 by the Swiss entomologist Paul Hermann Müller and seemed to be an ideal pesticide: it was effective, cheap and easy to produce and remained active for a long period of time. As a remedy against Malaria and other insect borne diseases, it has saved millions of human lives. However, the high persistency of DDT, its strong bioaccumulation and its effects on bird populations have triggered the search for alternatives and its ban in most Western countries. But in some developing countries, because of a lack of suitable alternatives for an effective control of malaria, DDT is still in use to kill malaria mosquitos.

Other representatives of chlorinated hydrocarbons are lindane, also called gamma-hexachlorocyclohexane (Figure 1), and the cyclodienes that include the "drins" (aldrin, dieldrin, endrin, See Section 2.1) and endosulfan (Figure 1). Because of their high persistence and bioaccumulative potential, most organochlorinated pesticides have been banned.

Volatile halogenated hydrocarbons were often used as soil disinfectant. These compounds were injected into the soil, and acted as a nematicide but also killed fungi, soil insects and weeds. An example is 1,3-dichloropropene (Figure 1).

Figure 1. Chemical structures of four different organochlorinated pesticides widely used in the past, from left to right: DDT: 1,1'-(2,2,2-trichloroethane-1,1-diyl)bis(4-chlorobenzene), lindane: gamma-1,2,3,4,5,6-hexachlorocyclohexane, endosulfan: 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro- 6,9-methano-2,4,3-benzodioxathiepine-3-oxide, and 1,3-dichloropropene. (Source: Steven Droge)

- Organophosphates

Organophosphates are esters of phosphoric acid and constitute important biological molecules such as nucleic acids (DNA) or ATP. Within the contents of pesticides this refers mainly to a group of organophosphate molecules which interfere with acetylcholinesterase. Nerve gases, produced for chemical warfare (e.g., Sarin), also belong to the organophosphates. They are much less persistent and were therefore introduced as alternatives for the chlorinated hydrocarbons. The common molecular structure of organophosphates is a tri-ester of phosphate, phosphonate, phosphorthionate, phosphorthiolate, phosphordithionate or phosphoramidate (Figure 2). With two of the three ester bonds, a methyl- or ethyl- group is bound to the P atom, while the third ester bond binds the rest group or "leaving group".

Figure 2: Chemical structure of organophosphates. R = methyl of ethyl group. (Source: Steven Droge)

Dependent on the identity of the latter group, three sub-groups may be distinguished:

1. Aliphatic organophosphates, including malathion (Figure 3) and a number of systemic chemicals.

2. Phenyl-organophosphates, which are more stable than the aliphatic ones but also less soluble in water, like parathion (no longer allowed in Europe; Figure 3).

3. Heterocyclic organophosphates, including chemicals with an aromatic ring containing a nitrogen atom like chlorpyrifos (Figure 3).

Figure 3: Malathion: diethyl 2-[(dimethoxyphosphorothioyl)sulfanyl]butanedioate (left), parathion: O,O-diethyl-O-4-nitrophenyl-phosphorthioate (middle), and chlorpyrifos: O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate (right). (Source: Steven Droge)

- Carbamates

Where organophosphates are derived from phosphoric acid, carbamates are derived from carbamate (Figure 4). Their mode of action is similar to that of the organophosphates. The use of older representatives of this group, like aldicarb, carbaryl, carbofuran and propoxur, is no longer allowed in Europe, but diethofencarb (Figure 4), oxamyl and methomyl are still in use.

Figure 4: Basic structure of carbamates (left) and diethofencarb: isopropyl 3,4-diethoxycarbanilate (right). (Source: Steven Droge)

- Pyrethroids

A number of modern pesticides are derived from natural products. Pyrethroids are based on pyrethrum, a natural insecticide from flowers of the Persian ox-eyed daisy, Chrysanthemum roseum. Typical for the molecular structure of pyrethroids is the cyclopropane-carboxyl group (the triangular structure), which is connected with an aromatic group through an ester bond (Figure 5). Pyrethrum is rapidly degraded under the influence of sunlight. Synthetic pyrethroids, which are much more stable and therefore used on a large scale against many different insects, include cypermethrin (Figure 5), deltamethrin, lambda-cyhalothrin, fluvalinate and esfenvalerate.

Figure 5: Cypermethrin: [cyano-(3-phenoxyphenyl)methyl]3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate. (Source: Steven Droge)

Neonicotinoids

Based on the natural compound nicotine, which acts as a natural insecticide against plant herbivores, but which was banned as an insecticide due to its high human toxicity, in the 1980s a new group of more specific insecticides has been developed, the neonicotinoids (Figure 6). Several neonicotinoids (e.g., imidacloprid, thiamethoxam) are systemic. This means that they are taken up by the plant and exert their effect from inside the plant, either on the pest organism (systemic fungicides or insecticides) or on the plant itself (systemic herbicides). The systemic neonicotinoids are widely applied as seed dressing in major crops like maize and sunflower. Other compounds are mainly used in spray applications, e.g. in fruit growing (thiacloprid, acetamiprid, etc.). Although neonicotinoids are more selective and therefore preferred over the older classes of insecticides like organophosphates, carbamates and pyrethroids, in recent years they have become under debate because of their side effects on honey bees and other pollinators.

Figure 6: Nicotine: (S)-3-[1-methylpyrrolidin-2-yl]pyridine (left) and the neonicotinoid insecticides imidacloprid: N-{1-[(6-chloro-3-pyridyl)methyl]-4,5-dihydroimidazol-2-yl}nitramide (middle) and thiacloprid: {(2Z)-3-[(6-chloropyridin-3-yl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide (right). (Source: Steven Droge)

- Isothiocyanates

Isothiocyanates were used on a large scale as soil disinfectant against nematodes, fungi and weeds. The large number of chemicals with different chemical origin belonging to the isothiocyanates have in common that they form isothiocyanate in soil. A representative of this group is metam-sodium (Figure 7).

Figure 7. Metam-sodium: sodium methylaminomethanedithioate forming methyl isothiocyanate. (Source: Steven Droge)

- Organotin compounds

Fentin hydroxide (Figure 8) was used as a fungicide against Phytophthora (causing potato -disease). Tributyltin compounds (TBT) were used as anti-fouling agent (algicide) on ships. TBTC (tributyltin chloride) is extremely toxic to shell-fish, such as oysters, and for this reason banned in many countries. Fenbutatin-oxide was used as an acaricide against spider mites on fruit trees (tributyltin chloride).

Figure 8: Fentin hydroxide: triphenyltin hydroxide. (Source: Steven Droge)

- Ryanoids

Also indicated as diamide insecticides, this group includes chemically distinct synthetic compounds such as chlorantraniliprole (Figure 9), flubendiamide, and cyantraniliprole, that act on the ryanodine receptor and are used against chewing and sucking insects.

Figure 9: Chlorantraniliprole: 5-bromo-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloropyridin-2-yl)pyrazole-3-carboxamide. (Source: Steven Droge)

- Phenoxy acetic acids

Phenoxy acetic acids are systemic herbicides, exerting their action after uptake by the leaf and translocation throughout the plant. Especially plants with broad, horizontally oriented leaves are sensitive for these herbicides. 2,4-D (Figure 10) is the best known representative of this group.

Figure 10. 2,4-D: the anionic form of 2,4-dichloro phenoxy acetic acid (pKa 2.73). (Source: Steven Droge)

- Triazines

Triazines are heterocyclic nitrogen compounds, whose structure is characterized by an aromatic ring in which three carbon atoms have been replaced by nitrogen atoms. Triazines are usually applied to the soil before seed germination. The use of several compounds (atrazine, simazine) has been banned in Europe, while others like metribuzin and terbuthylazine (Figure 11) are still in use.

Figure 11. Terbuthylazine: N-tert-butyl-6-chloro-N'-ethyl-1,3,5-triazine-2,4-diamine (left), common replacement of the EU-banned herbicide atrazine (right). (Source: Steven Droge)

- Bipiridyls

This group contains the herbicides diquat and paraquat (Figure 12) which mainly act as contact herbicides. This means they damage the plant without being taken up. In soil, they are rapidly inactivated by strong binding to soil particles. The use of paraquat is no longer allowed in Europe, but diquat is still in use.

Figure 12. Paraquat: 1,1′-Dimethyl-4,4′-bipyridinium dichloride (left), and diquat: 1,1'-Ethylene-2,2'-bipyridylium dibromide (right). (Source: Steven Droge)

- Glyphosate and Glufosinate

As an alternative to the above mentioned herbicides, glyphosate and later glufosinate were developed. These are systemic broad-spectrum herbicides with a relatively simple chemical structure (Figure 13). Their low toxicity to other organisms triggered pesticide producers to introduce genetically modified crops (e.g. soybean, maize, oilseed rape, and cotton) that contain incorporated genes for resistance against these broad-spectrum herbicides. This type of resistance allows the farmer to use the herbicide without damaging the crop. For this reason, environmentalist fear an unrestricted use of these herbicides, which indeed is the case especially for glyphosate (better known under the formulation name Roundup®).

Figure 13. Glyphosate: N-(phosphonomethyl)glycine in the two species most relevant for natural pH range (left), and glufosinate: (RS)-2-Amino-4-(hydroxy(methyl)phosphonoyl)butanoic acid in the most relevant species for natural pH range (right). (Source: Steven Droge)

- Triazoles

Several modern fungicides are sharing a triazole group (Figure 14). These fungicides have gained importance because of problems with the resistance of fungi against other classes of fungicides. Members of this group for instance are epoxiconazole, propiconazole and tebuconazole.

Figure 14: Triazole: 1H-1,2,3-Triazole (left), and epoxiconazole: (2RS,3SR)-1-[3-(2-chlorophenyl)-2,3-epoxy-2-(4-fluorophenyl)propyl]-1H-1,2,4-triazole (right). (Source: Steven Droge)

- Biological pesticides

Biological pesticides are produced in living organisms as secondary metabolites to protect themselves against predators, herbivores, parasites or competition. They can be highly effective and act at low concentrations (high toxicity), but in contrast to some synthetic pesticides they are usually sufficiently biodegradable. Compounds like pyrethrum or strobilurin are produced within the plant or within the fungus and are thus protected against photolysis or other environmental degradation. Furthermore, the living organism can produce additional quantities of the secondary metabolite on demand. When used as a pesticide applied as a spray, however, the molecule needs to be modified to enhance its stability (for example against photolysis) to remain sufficiently active over a sufficient period of time. Accordingly, synthetic derivatives of these biological molecules are often more stable, less biodegradable. Examples are the Bt insecticide, which contains an endotoxin highly toxic to insects produced by the bacterium Bacillus thuringiensis, and avermectins, complex molecules synthesized by the bacterium Streptomyces avermitilis. Avermectins act as insecticides, acaricides and have anthelminthic properties. In nature, eight different forms of avermectin have been found. Ivermectin is a slightly modified structure that is synthesized and marketed commercially. Other compounds belonging to this group are milbemectin and emamectin.

Genetically modified plants containing a gene coding for the toxin produced by the bacterium Bacillus thuringiensis (or Bt) are another example of genetic modification being applied in agriculture produce insect-resistant crops.

References:

EU Pesticides Database