Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya

*Joseph O. Lalah, Peter O. Otieno, Zedekiah Odira and Joanne A. Ogunah*

## **Abstract**

Pesticide use in Kenya plays a critical role in socio-economic development because its economy depends heavily on agriculture, which contributes to 30% of the GDP and accounts for 60% of export earnings. For agriculture and public health vector control, the country relies on pesticides, most of which (95%) are formulated products imported from China, India and Germany as the top exporters. In this chapter, we present the chemistry, manufacturing, importation and regulatory processes regarding pesticides in Kenya as well as their usage and impacts. All the various categories, organochlorine, organophosphate, carbamate, pyrethroid, neonicotinod insectides, as well as fungicides, herbicides and biopesticides, which are used in the country, are considered. A total of 1,447 and 157, which include formulations and active ingredients, respectively, for use in agriculture and public health sectors, with sufficient information on their usages and toxicities, are listed on the Pest Control Products Board (PCPB) database that is available to the public. A significant number of studies have been conducted in major agricultural regions, which have characterized pesticides, their toxicities, the types of crops and pests, the usage and human and environmental health risk indices, since the 2000, but the reports have not made any impacts on pesticide regulation, as some of the very toxic active ingredients, belonging to the WHO Class I and II, are still reported by farmers. However, a recent call from NGO's made an impact in government and parliament, and a bill was introduced in 2020 with the aim of banning some of the toxic ones that have already been withdrawn from the EU market.

**Keywords:** pesticides, regulations, usage, toxicity, human, environmental, impacts, Kenya

### **1. Introduction**

#### **1.1 Why are pesticides important?**

Human population development has been dependent on a steady increase in abundance of food supply over the years. The world population explosion began to be felt around 1600 AD; mainly as a result of two factors: (i) ability of man to control diseases and (ii) developments made in modern agriculture to increase food supplies [1]. Prior to 1800, there was little application of scientific information in agricultural production. Mass starvations occurred, whenever there were conflicts such as political conflicts, wars and climate change, which affected agricultural production and/or food flow. By about 1983, about 5 billion people existed, compared to the current global human population of approximately 8 billion. This population explosion to 8 billion over a period of just 38 years was possible because of developments in modern agriculture [1, 2] and ability of humankind to fight various diseases [3]. The fastest growth was realized in the 20th and 21st centuries when the population increased exponentially from about 2 billion in 1930 to about 7 billion in 2000 [2].

Kenya's *population*, which is equivalent to 0.69% of the total world population, was estimated at 53,771,296 people in 2020 [2], and this is expected to grow by around 1 million per year—3000 people every day—over the next 40 years, reaching approximately 85 million by 2050 [2]. The country will, therefore, rely on agriculture to provide food for the growing population. Agriculture contributes approximately 27% of Kenya's GDP and a large part of its rural population (approximately 80%) depends on subsistence farming as a source of food, employment and income [4]. The importation and use of pesticides are, therefore, foreseen to increase [3, 5].

Pesticides were originally introduced to control insects but have also nowadays been used to eradicate problems caused by nematodes, mites, rodents, birds, mollusks, parasitic fungi and weeds [1, 3]. Approximately 33% and 30% of food crops in the world are lost annually to pests and insects alone, respectively [1]. The losses occur in the field as well as during postharvest e.g. during storage or transportation. Tropical countries in Sub-Saharan Africa, which have a myriad of insects and disease pathogens, will have to continue relying on pesticides despite their negative impacts on the environment and human health.

Significant increases in different crop yields can be realized by using insecticides to control certain pests [1, 3]. In corn, 24.4%, 38.4% and 10.7% increases in yields have been achieved by controlling corn borers, leaf hoppers and corn root worms, respectively, using insecticides; whereas in wheat, 79%, 47%, and 29.5% increases have been realized by controlling brown wheat mites, cutworms and white grubs, respectively. In Irish potatoes, 45.6% and 42.8% increases in yields have been realized by controlling Colorado potato beetles and potato leafhoppers, respectively [3]. Bollworm and thrips can destroy cotton almost completely, reducing the yields to just 21.3% and 59.7%, respectively [3], if not controlled by insecticides. The FAO has estimated that 50% of cotton production in developing countries would be destroyed if there is no use of insecticides [3]. Pesticides not only reduce losses caused by pests and weeds but also increase profits for farmers by reducing the need for labor, specifically by using herbicides.

Many human diseases such as yellow fever and malaria, which are caused by mosquitoes, were eradicated or controlled in the past in industrialized countries by using pesticides [3]. The use of insecticides such as DDT contributed to the reduction of global annual malaria mortality rates from 6 million in 1939, to 2.5 million in 1965 and 1 million in 1991 [6]. Overcoming malaria is still a very big challenge for developing countries, especially in the Sub-Saharan African countries, partly because of failure to use pesticides effectively to control mosquito larvae, as recommended by the WHO [7]. Other diseases and their respective causes (as given here in parenthesis) have been controlled by use of insecticides including sleeping

*Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*

sickness (tsetse flies), anthrax (horseflies), bubonic plague (rat flea), dysentery (houseflies), filariasis, encephalitides, dengue fever, Chagas disease and West Nile virus (all these five caused by mosquitoes), hemorrhage and Q fevers (ticks and mites), bilharziasis (snails) and bronchial asthma (cockroaches) [3, 6, 8]. However, the agricultural sector consumes most of the conventional pesticides, e.g. approximately 77% in the USA [3, 5]. The situation is quite similar in Kenya, where most the conventional pesticides in form of insecticides, fungicides and herbicides are needed in the agricultural sector. Currently, some of the major classes of pesticides that have a significant stake in the global pesticide industry include organophosphate, carbamate, pyrethroid and neonicotinoid insecticides, fungicides and herbicides, respectively; and the organophosphates, carbamates, synthetic pyrethroids and neonicotinoids together account for 70% of the global insecticide sales [3, 5].

The cost of developing a pesticide active ingredient/compound is very expensive, ranging between US dollars 50 million and 100 million per active compound. These costs cover various aspects, including screening, synthesis, trials and regulation & registration; and the time period can take between 5 and 9 years before a product goes into commercial sale [3, 9, 10]. The developing countries such as Kenya, therefore, control a very small share of the pesticide industry, with Kenya importing most pesticides, which are already manufactured (95%) and only manufacturing a very small percentage (5%) of the products it needs [11].

#### **2. Pesticide chemistry and biochemistry**

Pesticides are classified in various ways, i.e. according to target pest, or according to their chemistry, chemical structures and particular functional groups on their molecules, respectively. The classification according to pests, including terminologies such as algaecides (developed to control algae), acaricides (mites), avicides (birds/ avian), bactericides (bacteria), fungicides (fungi), herbicides (weeds/plants), larvicides (larvae), molluscicides (mollusks e.g. snail, slugs), nematicides (nematodes), termicides (termites), ovicides (eggs), pediculicides (lice), predicides (predators e.g. coyotes and wolves), rodenticides (rodents), slimicides (slime) and silvicides (trees and brushes or entire forest), are used and usually indicated on the labels of the products [1]. However, in the industry as well as among scientists and researchers, pesticides are grouped broadly, according to their chemistry, chemical structures and mode of action, into four main categories, i.e. insecticides, herbicides, fungicides and biological control compounds/products such as microbial pesticides, as discussed in the following section.

#### **2.1 Insecticides**

Insecticides are used to destroy insects and can be classified according to their chemical structure as well as their mode of action as (i) Stomach poisons—which are lethal only to insects, which ingest them and were tested on target organisms through oral exposure; (ii) Contact insecticides—which kill insects following external bodily contact and do not have to be ingested to impart expected toxic effects and (iii) Fumigants—which act on the insect through its respiratory system, by emitting poisonous vapors, which can be inhaled and enter into the target organism through the respiratory system [12]. An insecticide can act by one or a combination of two or three of these modes. These classifications are taken as the tested modes of toxicity (based on trials) at the point of registration of the product and are normally given on the labels on the containers. During development, all insecticides are subjected to standard toxicity tests as described in the EU or USEPA standard methods [3, 13] and are expressed as LD50 or EC50 values. The LD50 is defined as the lethal dose of a compound that kills 50% of the target organism on exposure in a standard toxicity test procedure, in milligrams per kilogram weight of the test organism (mg/kg). The EC50 is defined as the effective concentration of the compound in water that kills 50% of the target organism in a standard toxicity test and is expressed in mg/L, and is normally conducted for aquatic organisms. The toxicity tests are done for: insects—to show effectiveness (as insecticides), rats—to show potential hazards to mammals especially humans, birds/fishes/bees etc.—to show potential hazards to the environment or non-target organisms. Pesticides are, therefore, ranked as hazards according to the WHO, where Class I, II, III and IV pesticides, respectively, where Class I are the most toxic with the least LD50 values [3].

Insecticides are subdivided into organochlorines, organophosphorus (or organophosphates), carbamates, pyrethroids, neonicotinoids, insect growth regulators (IGRs) and natural products (which include microbial insecticides), respectively. Brief descriptions of these seven categories, which are all popularly used in Kenya, are presented in the following sections.

#### *2.1.1 Organochlorine insecticides (OCs)*

The organochlorine insecticides are divided into three major classes, including the *DDT and its analogues*, the *benzene hexachloride (BHC) isomers* and the *cyclodiene compounds*, respectively. The DDT and its analogues include *DDT,* which is commonly known as *p,p*′*-DDT* (IUPAC nomenclature: 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane). It was the first synthesized chlorinated insecticide, manufactured in 1873 but was recognized as an insecticide at the beginning of the world war in 1939 [1, 5]. After DDT, more and more organochlorine pesticides were discovered and synthesized in Europe and USA. When DDT is synthesized, the technical mixture contains a lot of impurities, with only seventy per cent (70%) of the mixture being the active ingredient p,p′-DDT, and others—21% is the ortho-isomer (o,p′-DDT), 1% the o,o′-DDT; 4% the p,p′-DDD and 0.04% the o,p′-DDD. These isomer impurities are formed during synthesis and account for 30% of weight of the technical mixture (Note: the 'o' means 'ortho' and 'p' means 'para' position on the benzene ring). These impurities potentiate the toxicity of DDT and also add to the environmental burden of DDT because they are also persistent. Other metabolites of DDT also form in the organisms or the environment, e.g. DDE, which is more potent and persistent than DDT (**Figure 1a**). The isomeric impurities have little value as toxicants, since they are just <10% as toxic as the p,p′-DDT. DDT is toxic to non-targets and has an LD50 (oral, rats) of 250 mg/kg [3].

The other DDT analogues that were manufactured after DDT have various functional groups on the DDT molecule changed and include *methoxychlor*, *dicofol* and *chlorobenzilate*. As shown in **Figure 1a**, the various changes on the DDT molecule by researchers resulted in different pesticides, which were designed to be less toxic than DDT, with lower mammalian toxicities, e.g. methoxychlor has an LD50 (oral, rat) of 600 mg/kg, while dicofol has LD50 (oral, rats) of 595 mg/kg, chlorobenzilate

*Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*

#### **Figure 1.**

*(a) DDT and its analogues. (b) The general chemical structure of OPs, the starting phosphates, and two OP insecticides. (c) Chemical structures of two cyclodiene insecticides. (d) Chemical structures of two carbamate insecticides. (e) Chemical structure of permethrin, a pyrethroid insecticide.*

(3888 mg/kg) and p,p′-DDD (3400 mg/kg) [3]. The DDT analogues have similar chemical and physical properties but because of the slight differences in chemical structures have differences in toxicity and specificity. Dicofol and chlorobenzilate, for example, have lower insecticidal activity, but better acaricidal activities. The DDT group are considered as persistent organic pollutants (POPs) and are environmentally persistent since they are non-polar, highly lipophilic, stable to photolysis, and have very low water solubilities and low vapor pressures [14, 15]. They cause endocrine disruptive effects because of their ability to mimic sex hormones [14, 15]. Although DDT has been banned globally, it is allowed restrictively for use in Kenya, for malaria vector control, only. *Methoxychlor* has been banned in Kenya, but *dicofol* and *chlorobenzilate* though not banned are not used in Kenya.

The second subclass of organochlorines, the *Benzene hexachloride isomers,* was first discovered in 1942 [3]. They are chlorinated saturated six-carbon cyclic alkane molecules, which can adopt a chair conformation [6]. On each C atom, there is a chlorine atom, located in axial or equatorial position, respectively, on the molecule, which gives the various five isomers (α, β, γ, δ, ε). Only the γ (gamma) isomer exhibits pronounced insecticidal activity. It is the main isomer and is known as γ-hexachlorocyclohexane (γ-HCH) or *lindane*. Lindane is odorless and is widely used even in agriculture. Other BHC isomers have unpleasant odor, and this gives an off flavor in root and tuber crops, limiting their use in agriculture. Although banned in most countries, lindane is still allowed restrictively for non-food-related use in Kenya, like seed dressing [3, 6]. Lindane is more toxic than DDT group and has an LD50 (oral, rats) of 125 mg/kg. It has a higher vapor pressure (9 × 10−6 mmHg) than DDT and, therefore, is slightly more water-soluble (10 ppm in pure water) [16].

The third subclass, the *cyclodiene compounds* or *cyclodiene insecticides* were discovered in the USA after the War II (around 1948). They are cyclic hydrocarbons and include *aldrin*, *dieldrin*, *chlordane* (two isomers α and β-chlordane), *heptachlor*, *endrin*, *endosulfan*, *chlordecone*, *mirex* and *toxaphene* (**Figure 1b**). Although others are synthesized, toxaphene is strictly a chlorinated terpene, produced by passing chlorine into camphene, a natural product [3, 6]. Like other OCs, all these cyclodienes are heavily chlorinated compounds. Some of the cyclodienes have higher mammalian toxicity than the DDT group but the LD50s (oral, rat) vary widely, ranging from aldrin 38–67 mg/kg, dieldrin 37–87 mg/kg, chlordane 367–515 mg/kg, endrin 7–15 mg/kg, heptachlor 147–220 mg/kg, endosulfan 18–43 mg/kg, chlordecone 114–140 mg/kg, mirex 306 mg/kg and toxaphene 69 mg/kg [3, 6]. In this group, *aldrin, heptachl*or and other *cyclodienes* have long residual lives in soil, expressed in terms of 'half-life', and; therefore, cyclodienes were important agents for controlling termites and soil insects. They are very stable, lipophilic and have low vapor pressures (range of 10−5 to 10−7 mmHg). They have been banned or severely restricted because of environmental persistence and non-target toxicity in most countries, and even in Kenya some of them such as *aldrin, dieldrin, chlordane*, *heptachlor* and *endrin* have been banned [11]. The principal site of action of organochlorines is the nervous system, where they bind to the sodium channel and cause delayed Na-inactivation, resulting in a prolonged delay in Na-inactivation and subsequent interference with nerve impulse functions.

#### *2.1.2 Organophosphorus insecticides (OPs)*

After the OCs, the trend was to (i) avoid persistence (ii) build biodegradability and (iii) have a narrow spectrum of activity (more specificity). Therefore, the OCs have

*Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*


#### **Table 1.**

*Sub-classes of OPs and specific examples of active ingredients.*

now been replaced by OPs, carbamates, neonicotinoids and pyrethroids, which have these desirable properties. The OPs are very popular in Kenya and, as insecticides, dominate the Kenyan synthetic pesticide market. In general, they are more toxic to insects and mammals than OCs but are readily biodegradable. They were discovered as by-products of chemical warfare research involving the development of nerve gases such as *sarin, soman and tabun*, in Germany during War II [1, 3, 17], and esters of *phosphoric acid*, *thiophosphoric acid* (*phosphorothioate*), *phosphorothiolate*, *phosphorodithioate* or *phosphoramidate* are given in **Table1** and their structures in **Figure 1c**.

These starting organophosphoric acidic compounds for synthesis of OPs indicate the six subclasses of OP insecticides; e.g. when H atoms of phosphoric acid are replaced with organic radicals such as methyl, ethyl or phenyl, the compounds obtained are organophosphates. On the other hand, oxygen can be replaced with S, C, or N to yield different derivatives. *Phosphates* such as *dichlorvos* are few but many other subclasses also become *organophosphates* during metabolism by various organisms, for example by changing an S atom by an O atom through oxidation. In the subclass *phosphorothioates (*e.g. *chlorpyrifos* and *diazinon),* an S atom is double bonded to phosphorus, while in the subclass *phosphorodithioates (*e.g. *malathion* and *dimethoate)*, the molecule contains two sulfur atoms in the phosphoric acid part. In *phosphorothiolates,* there is a single bond between S and P atoms, and in p*hosphoramides (*e.g. *acephate),* there is a P atom bound to N atom (**Figure 1c**) [3, 6].

Organophosphates have different physical and chemical properties from the organochlorines. Overall, they have moderate-to-considerable water solubility, with some such as *oxydemeton-methyl*, *trichlorfon* and *phosphoramidates*, being very soluble. They also have moderate-to-considerable vapor pressures (generally ranging between 10−3 and 10−5 mmHg) and therefore are less volatile than most OCs, although some such as *naled, parathion* and *dichlorvos* are very volatile [6, 17]. The OPs are degradable in the environment, e.g. in water, soil and other compartments and are easily metabolized in the organisms, with the most common chemical reactions being hydrolysis, catalyzed by water and esterases*.* Insects, mammals and other organisms have esterases, which can metabolize OPs e.g. *malathion carboxylesterase,* which has been shown to *decarboxylate malathion* in rat liver [18, 19]. Another common reaction of OP compounds is oxidation of the P=S moiety on an OP molecule to P=O, which is mediated by the cytochrome P450 monoxygenases. This oxidation is referred to as oxidative desulfurization, e.g. conversion of *malathion* to *malaoxon,* which occurs in insects and mammals [3, 18]. The combination of physical (e.g. *water solubility*) and chemical (*hydrolysis and oxidation*) properties make the entire OP class of insecticides biodegradable and more easily excreted.

#### *2.1.3 Carbamate insecticides (CBs)*

Carbamates are esters of carbamic acid, HOOCONH2. The 3 H atoms in the molecule can be replaced by aliphatic or aromatic radicals to become carbamate insecticides. However, the second H on the nitrogen (N) is not replaced in making CB insecticides because the monoalkyl structure (NRH) is more toxic than the N-disubstituted compound (NRR″) [20]. Carbamic acid is similar in chemical structure to the pharmaceutical agent, physostigmine (eserine), whose synthesis started the curiosity on carbamates. Physostigmine is a poison, an acetylcholinesterase (AChE) inhibitor. A typical carbamate structure is represented by *carbaryl* (1-naphthylmethyl carbamate), which was the first carbamate insecticide to be synthesized. Substituted phenyl-N-methyl carbamate insecticides can be synthesized by addition of methyl isocyanate (CH3NCO) to various phenols, some of them with substituted alkyl or phenyl functional groups (R), as shown:

$$\text{RC}\_6\text{H}\_5\text{OH} + \text{CH}\_3\text{NCO} \oplus \text{RC}\_6\text{H}\_5\text{OOCNCH}\_3 \text{(R = alkyl or phenyl)}\tag{1}$$

During this synthetic process, all reagents and solvents are kept free from water because water reacts readily with methylisocyanate. The reaction is usually vigorous and thermic generating a lot of heat and can cause the release of methyl isocyanate, which is extremely toxic, from the reaction vessel. This is what caused the Bhopal accident in 1984, in which methyl isocyanate gas leaked from a Union Carbide factory in Bhopal, India, killing approximately 3800 people [1]. Making various changes to the carbamyl functional group (∙O∙(C∙O∙NH2) by varying R (alkyl or aryl) groups researchers resulted in many different CB insecticides (**Figure 1d**). The chemical structures of two CBs, *methomyl* and *carbaryl*, are shown in **Figure 1d**. Carbamates, like OPs, act by binding to and inhibiting *acetylcholinesterase* (AChE), resulting in a buildup of acetylcholine at the synapse, which causes excessive neuroexcitation, paralysis and death. The second mode of action is by binding and interference with neuropathy target esterases (NTE) located in the nervous system in insects.

Carbamates are popular in Kenya, for example, *carbofuran*, *aldicarb*, *propoxur*, *carbaryl*, *methomyl*, *oxamyl*, *carbosulfan* and *pirimicarb* are often used in the agricultural sector [11]. Some of the carbamates are very toxic to non-target, with very low LD50 (oral, rats) values, e.g. *aldicarb* (LD50: 1 mg/kg), *methomyl* (17–26 mg/ kg), *oxamy*l (54 mg/kg) and *carbofura*n (5–13 mg/kg), while others such as *carbaryl* (500–700 mg/kg) and propoxur (95–104 mg/kg), are less toxic [3]. Carbamates are also very toxic to birds, i.e. *carbofuran* (LD50 25–39 mg/kg in birds), *carbosulfan* (10 mg/kg), *propoxur* (4–120 mg.kg), *aldicarb* (1.78–5.34 mg/kg) and *methomyl* (10–42 mg/kg), except *carbaryl* (LD50 > 2000 mg/kg). *Carbofuran* and *carbaryl* were popularly used in field crops including rice and maize farming, from 1980's to 2000 in Kenya. Due to their high toxicity, *aldicarb, carbofuran* and *carbosulfan* have recently been misused by pastoralists and farmers against wildlife, especially predators, which has led to carbofuran withdrawal pending banning in Kenya [21, 22]. Granular forms of carbofuran and aldicarb, which are fairly soluble in water, can be picked by small organisms such as worms and grasshoppers in farm fields and through food chain transfer, larger scavenger birds and other insect-eating species get poisoned [21, 22]. Liquid formulations of carbofuran are considered safer and are still allowed in other countries despite the ban on granular formulations [21].

*Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*

#### **2.2 Herbicides**

#### *2.2.1 Herbicide chemistry and biochemistry*

By definition, a herbicide is a compound that is capable of either killing or injuring plants (or weeds) and can control their growth. Herbicides are used to control weeds in farms as well as lawns, roads and other facilities, and their use has led to great reductions in agricultural production costs. Herbicides can be: (i) *selective,* killing only a particular group of plants such as the leafed plants or grasses or (ii) *non-selective*, making the ground barren of all plant life. They can be formulated either in (i) *granular form*, which is worked into the soil prior to planting the crop in a *preemergence* application or (ii) *liquid spray form,* which may be applied best at various stages after planting, *postemergence or preemergence*, the choice between (i) and (ii) depending on the particular chemical, weed, soil type and crop cultivated [3]. However, the use of herbicides is very intricate and several factors must be considered, e.g. it can destroy a lawn or the plant crops, which are meant to be protected against weeds. Therefore, there is a need to consider wind direction and proximity to wanted plants, when applying herbicides. Different species of plants in the same class may respond differently, some requiring one application and others up to 3 applications before being controlled. Herbicides can become effective either by (i) *direct contact* with plants or (ii) by movement through the entire plant following absorption (called *systemic action*) [23].

Generally, herbicides may, therefore, be classified into a number of groups, either (i) based on the *chemical structure* or (ii) based on when and how it is applied, e.g. *preplanting*—applied to soil before crop is seeded, *preemergenc*e—applied to soil before usual time of appearance of unwanted weeds/vegetation or *postemergence* applied to soil or foliage after the germination of the crop and/or weeds; or (iii) based on mode of exposure, e.g. as *contact herbicide*—which acts by impinging on plant foliage; or *translocated/systemic herbicide* – which are absorbed via the soil or through foliage into the plant xylem and Phloem; or (v) based on *mode of toxicity* in plants e.g. as *selective herbicide*—toxic to some species only or *non-selective,* which kills all plants (**Table 2**). There are two modes of toxicity of herbicides, the first one applies to *non-selective* herbicides, which interfere with photosynthesis and thereby starve the plant to death, with loss of its green color and withering due to lack of energy to carry out the life processes. The second one applies to *selective* herbicides, which act like hormones or biochemical catalysts that control a particular chemical change in a particular type of plant organism at a particular stage/state of its growth. Most selective herbicides today are *growth hormones*, which cause abnormal growth in a plant and swelling of cells, resulting in the leaf becoming so thick that nutrients and water cannot be absorbed [23].

For example, benzoic acids act as growth hormone herbicides, and move both from leaves to the terminal meristems of leaf, shoot and root, and also move in the transpiration stream, and this permits them to also be soil-applied [24]. The majority of herbicides act by inhibiting photosynthesis I and II (**Table 2**). Various chemicals such as calcium cyanamide (CaHCN), borates, arsenates, copper sulfates, sulfuric acid, and chlorates, were used as weed killers, and some formulations such as aqueous solutions of sodium chlorate NaClO3 (40%) and sodium metaborate NaBO2 (50%), respectively, are still used as *non-selective* herbicides [3]. The discovery of selective herbicides started in 1935, starting with nitrophenol [3], and later, more work was directed towards auxins or hormones, as selective herbicides.


#### **Table 2.**

*Herbicide classes and the corresponding modes of toxicity.*

In Kenya, *2,4-D* (2,4-dichlorophenoxyacetic acid), a selective phenoxyacetic herbicide, is still one of the most widely used, while *2,4,5-T* (2,4,5-trichlorophenoxy acetic acid), was highly effective but it is no longer used because it was banned in most countries due to non-target toxicity caused by dioxins, which are inherent in the technical mixture [3, 25]. The active ingredients of the various classes of herbicides presented in **Table 2** are very popular in Kenya, including *2,4-D, atrazine, glyphosate, diuron, metribuzine, hexazinone, paraquat, alachlor, metolachlor and fluconazole*, which are commonly used in cereal (maize and wheat), coffee, tea, sugarcane and horticulture. The enhanced efficacy and popularity of *atrazine* is because corn and

*Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*

certain types of crops are unaffected by it, rendering it harmless, yet killing weeds [3]. Herbicides are intensively used in certain crops in Kenya e.g. large-scale farming of maize and sugarcane, where large farm acreages are involved e.g. in Trans Nzoia maize farms and Nzoia Nucleus Estate sugarcane farms. In 2010, approximately 10,500 kg of various types of herbicides were used in a total acreage of 18,000 Ha of sugarcane farms in Nzoia [26]. Generally, in Kenya, even though herbicide use is increasing, insecticides are still being imported in higher amounts, which is different from the USA where 59% of all pesticides used are herbicides [3].

#### **2.3 Pyrethroids**

Synthetic pyrethroids entered the market in 1980s and by 1982, 30% of worldwide insecticides (in terms of sales) in the market were pyrethroids [3, 25, 27, 28]. They arose from a much older class of botanical insecticides, the pyrethrum. Pyrethrum is a mixture of five (5) insecticidal esters, *pyrethrin I, pyrethrin II, cinerin I, cinerin II and jasmins*, which are all extracted from dried pyrethrum flowers [3]. The *chrysanthemum* variety of pyrethrum grown in Kenya yields the highest proportions of active ingredients. In 1965, the world production of pyrethrum was 20,000 tons, with Kenya accounting for 10,000 tons. However, pyrethrum production dwindled around the 1990s due mainly to competition with synthetic pyrethroids. It is however currently being revived again [3, 25, 27, 28]. The increase in usage of pyrethrum extracts amidst plenty of other various types of insecticides (e.g. OPs and CBs) lies in the fact that it has rapid knockdown effect or paralytic action on flying insects. In addition, pyrethrum extracts have lower mammalian toxicity due to their more efficient enzymatic biodegradability, and good selectivity due to low toxicity in some insects. Due to high demand, chemists synthesized analogues of pyrethrum extracts, called *synthetic pyrethroids*, with better stability in air, more persistent residual effect, better selectivity to target insects, lower mammalian toxicity and cheaper costs. The term '*pyrethroids*', therefore, includes both the *pyrethrum flower extracts* and the *synthetic* analogues. The active ingredients in the *synthetic* analogues are called *Pyrethrins*. Pyrethrin consists of esters, namely *Pyrethrin I and II and Cinerins I and II*, each of which are comprised of a combination of two different alcohols, *pyrethrolone* and *cinerolone*, respectively, and two different carboxylic acids - *chrysanthemic* and *pyrethric acids*, as follows: (a) Pyrethrin I (an ester of chrysanthemic acid + pyrethrolone); (b) Pyrethrin II (an ester of pyrethric acid + pyrethrolone); (c) Cinerin I (and ester of chrysanthemic acid + cinerolone and (d) Cinerin II (an ester of pyrethric acid + cinerolone).

Pyrethrin I is the most active ingredient of the pyrethrins for lethality. Pyrethrin II possesses remarkable knockdown properties for a wide range of household, veterinary and postharvest storage pests. The esters formed from the alcohols and respective carboxylic acids are the different active ingredients used in pyrethroid insecticide formulations, whose composition includes synergists and other adjuvants [3, 25, 27, 28]. The various changes in functional groups of pyrethrins and alcohols have resulted in different chemical structures of synthetic pyrethroids (**Figure 1e**). Based on their chemical structures, there are two types of pyrethroids, Type I pyrethroids (*e.g. permethrin, resmethrin, tetramethrin, allemethrin, bifenthrin and metofluthrin*) and Type II pyrethroids (*e.g. cypermethrin, fenvalerate, esfenvalerate, deltamethrin, fenprothrin, lambda-cyhalothrin, tefluthrin, cyfluthrin, acrinathrin and imiprothrin*). The main structural difference between Type I and Type II pyrethroids lies in the fact that Type II synthetic pyrethroids contain a cyano (C∙N) group, whereas Type I do not. Type I general structure can be abbreviated as R1(C3)C∙O(OR2) and that of Type II

as R1(C3)C∙O(C(CN)R2), where R1, R2 are alkyl or phenyl groups, C3 is a rigid cyclic propane and CN is the cyano group. Therefore, distinct chemical structures of synthetic pyrethroids convey selectivity towards certain insect species and mammals [3].

Synthetic pyrethroids have unique properties because of structural differences, which are seen in form of *stereoisomerism, i.e. geometric (cis-trans) and enantiomerism (or optical isomerism), e.g.* a technical mixture of *permethrin* contains 40% cis and 60% *trans* isomers, with the *cis* isomer being five times more toxic against tobacco budworms [3, 27, 28]; and the active isomer in the *deltamethrin* is the *dextro (+)-cis-*deltamethrin [3]. They have low water solubility, low vapor pressures (10−6 to 10−7 mmHg) and high efficacy, being very effective against most agricultural pests at low rates, especially the Type II compounds, which are more effective than organophosphorus or carbamate insecticide [3]. Apart from their application in agriculture, synthetic pyrethroids are frequent components of household sprays, flea preparations for pets, and plant sprays for green houses, among others. Currently pyrethroids are used widely in Kenya in the domestic, public health vector control, as well as agricultural sectors, where both Type II and I are widely used. Most Type I pyrethroids belong to Category WHO Class III pesticides (oral LD50 (rats) of 500–5000 mg/kg range), Type II pyrethroids mostly are more toxic and belong to Category WHO Class II pesticides (oral LD50 (rats) of 50–500 mg/kg range) and just a few belong to WHO Class I, according to the WHO rating which is based on LD50's oral rats [3]. Pyrethrum (the extract) is a safe insecticide (oral LD50 1500 mg/kg in rat) and very fast-acting on insects, causing immediate paralysis. Both the natural pyrethrins and synthetic pyrethroids were more active as *contact* than *stomach* poisons, although more recently some of the synthetic pyrethroids tend to show particular potency when ingested and less susceptibility to biotransformation by insects and mammals [3, 27, 28].

#### **2.4 Other botanical insecticides**

There are six botanical insecticides currently available in the market. These are *pyrethrum, nicotine, rotenone (rotenoids), azadirachtin, sabadilla and ryania;* which are naturally occurring agents of plant origin that have been used to control insect pests. Despite many formulations of synthetic insecticides being present in the market, the botanical insecticides are still found in the market and are now becoming popular in Kenya, especially in the horticulture sector, because they are perceived to have eco-toxicological advantages compared to traditional synthetic insecticides. The advantages include less negative impacts on ecology, low human toxicity and less environmental persistence [3, 29–31]. Botanical insecticides are composed of secondary metabolites such as alkaloids, amides, chalcones, flavones, phenols, lignans, neolignans or kawapirones. They act as repellents with unpleasant odors or irritants, growth regulators and some have deterrence on oviposition and feeding, as well as biocidal activity [29, 30].

*Nicotine* was first used as botanical insecticide in 1763. It is highly toxic to both target and non-target species, with moderate to high toxicity in vertebrates (oral LD50 in rats: 55 mg/kg) and is toxic to insects such as bugs, beetles and cockroaches (LD50 ranging from 190 to 650 mg/kg) [31, 32]. It is an alkaloid extracted from leaves of tobacco plant by Soxhlet (with solvents such as toluene) or with alkali using steam distillation and is used in home gardens and greenhouses for controlling sucking insects such as leafhoppers, aphids, scales, thrips and white flies, and therefore is also used in horticulture e.g. in Naivasha, Kenya [11]. Its demerits include high mammalian toxicity, ready absorption by skin and, therefore, increased exposure.

#### *Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*

Nicotine sulfate and other salts in the form of crystals such as nicotine benzoate, oxalate, salicylate and tartrate, as well as fixed nicotines (water-insoluble salts such as nicotine tannate and nicotine bentonite) are stable and have been used as insecticides, baits and for control of ectoparasites in livestock, respectively [32]. Nicotine is also used most commonly as a fumigant and as a contact spray in greenhouses [32]. Preparations of tobacco teas from tobacco products sold for smoking and chewing as homemade preparations for use against pests can also be used. Nicotine poisons insects and mammals by a similar mode of action, i.e. inhibition of acetylcholine esterase by mimicking acetylcholine which binds to postsynaptic receptors [3, 33], and since its breakdown is not catalyzed by acetylcholinesterase, it causes repeated stimulation of the receptor.

*Rotenone i*s present in the roots of *Derris spp* plant and similar Leguminosae family of plants found in Malaysia, the East Indies and other East Asian countries [31]. It is an alkaloid extracted by solvent extraction (e.g. Soxhlet), purified and crystallized; often added in combination with other insecticides. It is a selective insecticide with acaricidal properties used against garden insects, lice and ticks on animals; such as headlice (by topical application). It is very toxic to fish and can control unwanted fish species in lakes, streams and reservoirs, which are used for power generation [31]. The LD50 is 132 mg/kg oral in rats, obtained by administering crystalline rotenone. Rotenone is toxic not only to insects and fish but also to humans and animals, with oral LD50 in rats being approximately 60–135 mg per kg of body weight. Liquid preparations of derris or Derris dust can also be used. It acts by blocking electron transport in mitochondria, inhibiting oxidation linked to NADH, by binding to NADH dehydrogenase thereby interfering with electron transfer, and is referred to as mitochondrial complex I inhibitor [31].

*Azadirachtin* is a secondary metabolite belonging to the limonoid group present in neem seeds. This compound is found in the seeds (0.2–0.8 percent by weight) of the neem tree, *Azadirachta indica*. *Azadirachtin* is the main compound of the neem oil with insecticidal activity and can be found in its fruits and leaves. *Azadirachtin* is the active ingredient in many pesticidal products or formulations in the market, including TreeAzin and Terramera Cirkil [31, 34, 35], and it has been used as a biopesticide in Kenya. Azadirachtin has various modes of activity, including being a broad-spectrum insecticide, and acting as a feeding deterrent, insect growth disruptor (IGD) and sterilant, respectively, and is used to control various agricultural pest species, including Coleoptera, Hymenoptera, Diptera, Orthoptera and Isoptera [29, 30].

*Sabadilla* use as a pesticide dates back to 1819 when a basic substance from sabadilla seed was isolated [33]. *Sabadilla* is a plant that grows in countries such as Central America and Mexico. It is toxic and is used in farming as an insecticide since it contains alkaloid compounds including *veratran, cevadine, veratridine, sabadine and sabadiline,* which have insecticidal activity. The veratrine alkaloids comprise approximately 0.3% of the weight of aged sabadilla seeds; of these alkaloids, cevadine and veratridine are the most active insecticidally and have been tested successfully in citrus thrips [31]. Sabadilla alkaloids from the dried ripe sabadilla seeds of a member of the lily family, S*choenocaulon officinal*e, are often used and considered as generally safe and non-persistent insecticides. Veratrine, which is the term now used to describe the alkaloid mixture from sabadilla, has long been known for its toxicity to certain species of insects. The powdered seed itself or kerosene extract of it has been tested and used as an insect repellant. Sabadilla alkaloids have also been formulated as a wettable powder and then mixed with water and applied by either aerial or ground equipment on citrus, avocados and mangos. In making a commercial formulation,

the active ingredients of sabadilla are synergized by piperonyl butoxide (PBO) and N-octyl bicycloheptene dicarboximide (MGK 264) [3, 33]. The mode of action of sabadilla is similar to that of the pyrethrins, as it affects the voltage-dependent sodium channels of nerve axon [33], i.e. affect nerve cell membrane function by binding to the sodium channel causing loss of nerve function, paralysis and death.

*Ryania* insecticide preparations are derived from the *woody stem tissue* of the shrub *Ryania speciosa* (family *Flacourtiaceae*), a plant that is native to South America and has been used in the USA since 1940s. A mixture of components is present in extracts or powders of this plant material, and eleven compounds with insecticidal activity have been identified [31], the most abundant active constituents of these alkaloids (*ryanoids)* being *ryanodine* and *dehydroryanodine.* Most commercial formulations are crude dust (50% ryania powder), though the constituent alkaloids can be extracted in water, alcohol, acetone, ether or chloroform to produce liquid or wettable powder formulations. Ryania extracts or powders have very low mammalian toxicity (LD50 rats ranging from 750 to 4000 mg/kg), but the active ingredients are much more toxic to mammals [33]. Ryania's toxicity to insects can result from contact or ingestion; it is synergized by PPO and used most often for control of caterpillar pests of fruits and foliage, the codling moth and thrips in fruit trees (apples, pears, citrus), as well as European corn borer in corn, by organic farmers [33]. Like *rotenone,* ryania persists longer in the field after application than most other plant-derived insecticides, with residues giving some degree of residual control for up to 3–5 days after application on plant surfaces. The mode of action *of ryania is by Ryanodine effects on* the calcium cation (Ca2+) release channel in muscle, resulting in poisoning of insects and mammals by a sustained contraction of skeletal muscle without depolarization of the muscle membrane, causing cardiac arrest and then eventual paralysis [33]. The binding of raynodine changes the structure of the Ca2+ channel and prevents its complete closure. This binding affects the cardiac and skeletal muscles.

#### **2.5 Neonicotinoids**

Neonicotinoids (meaning "new nicotine-like insecticides"), also known as chloronicotinyls, are synthetic analogues of nicotine, but unlike nicotine, they are relatively non-toxic to mammals. Neonicotinoids are a new class of insecticides with widespread use in veterinary and crop production, and include *imidacloprid, acetamiprid, dinotefuran, thiamethoxam, clothianidin, amitraz and chlormideform*. *Imidacloprid* (LD50 450 mg/kg (oral rats)), *acetamiprid* (417 mg/kg), *thiamethoxan* (LD50 > 5000 mg/kg) and *thiacloprid* (LD50 836 mg/kg), are all systemic insecticides, which have been used widely in agriculture against sucking insects such as aphids, leafhoppers, planthoppers, thrips, white flies [3], as well as soil insects, termites and biting insects, in Kenya.

Neonicotinoids first entered the market in the early 1990s and appeared to address the concerns associated with some earlier pesticide compounds, because they are effective, possess a high degree of selectivity to insects and have low mammalian toxicity, making them safer for human use than the organochlorines, organophosphates and carbamates [3]. Therefore, they soon became some of the most widely used insecticides in the world by 2014. Neonicotinoids are used to manage many honeydewexcreting pests, which are primary pests in most agricultural systems, including field crops, vegetables, fruit and nut production, tree plantations and urban forests, and therefore they have a strong potential to reach non-target pest species, which are essential in agriculture, such as bees [3]. They are most often applied as a seed coating and are absorbed into plant tissues, localizing the protectant and reducing contamination

*Pesticides: Chemistry, Manufacturing, Regulation, Usage and Impacts on Population in Kenya DOI: http://dx.doi.org/10.5772/intechopen.105826*

to the environment. The insecticide's ability to translocate into plant tissues could keep environmental concentrations low and minimize exposure to sensitive non targets such as quail and other wildlife, but experimental data suggest that environmental concentrations are usually higher than anticipated [36, 37]. It was estimated that approximately 5% of the pesticide a.i. applied as a seed coating would be absorbed by the plant while the rest (95%) would be blown away during sowing, which has led to their deposition in the surrounding soil and water, leading to soil residue concentrations up to 1000 ppb, in some cases [36, 37]. Compared to OPs and carbamates, neonicotinoids differ in that they are more strongly attracted to acetylcholine esterase receptors in the invertebrate's nervous system than the vertebrate ones, making them more specific. As a mode of toxicity, neonicotinoids are neurotoxins, which target insect nicotinic acetylcholine receptors (nAChRs). By 2018, neonicotinoids made up ∼30% of insecticide sales worldwide [36, 37]. However, due to their adverse impact on pollinators such as honey bees and bumble bees, as well as aquatic invertebrates, some neonicotinoids are being banned by the EU, and other countries may also follow suit in future [36]. Neonicotinoids have become popular in Kenya and are already widely used in the horticultural sectors [4]; as many are registered by the PCPB.

#### **2.6 Insect growth regulators (IGRs)**

IGRs are chemical substances that disrupt insect growth and development, resulting eventually in death. They are pesticides that affect insects' ability to grow and mature normally, rather than killing them outright as 'conventional' insecticides do. Currently, there are 5 IGRs, namely *juvenoids, benzoylphenylureas, diacylhydrazines, triazines and thiadiazines*, respectively. The IGRs have low mammalian toxicity, and there are many of their formulations in the market, including the Kenyan market [3, 11]. They are very useful in controlling disease vectors such as mosquitoes, specifically mosquito larvae [3, 31]. Many IGR products can also be mixed with other insecticides that kill adult insects. Several features of IGR make them attractive as alternatives to broadspectrum insecticides; i.e. they are more selective, less harmful to the environment and more compatible with integrated pest management. Because IGRs act on systems unique to insects, they are less likely to affect other organisms. Some of the modes of action include acting as antijuvenile hormone agents by blocking juvenile hormone production, mimicking hormones and therefore interfering with stages of growth or life cycle, from eggs to larvae, to pupae, and to adults; and inhibiting chitin synthesis by preventing development of exoskeleton, respectively [31]. Examples of known juvenoid active ingredients are *methoprene, hydropene, fenoxycarb, pyriproxyfen* and *diflubenzuron (a benzoylphenylurea). Benzoylphenylureas* (e.g. *diflubenzuron*) and *diacylhydrazines* are known to prevent chitin synthesis by inhibiting chitin synthetase. Thiadiazines (e.g. *buprofezin*), diacylhydrazines (e.g. *halofenozide*, *methoxyfenozide* and *tebufenozide*) and benzoylureas (e.g. *novaluron*) disrupt or mimick insect growth hormones, inhibit chitin synthesis, prevent molting and metamorphosis, respectively [6].

*Methoprene* (LD50: 34,600 mg/kg oral rats) is a larvicide juvenoid, which mimicks juvenile insect hormones, since it is similar in chemical structure to them. It has been used to control mosquitoes (in flood waters, effective at 2–4 instars stage), cigarette beetles and fleas. It is not toxic to the pupal or adult stages, with treated larvae able to pupate but adults do not hatch from the pupal stage [38]. The optically active juvenile hormone analogue, S-(+)-methoprene is synthesized by a chemical procedure [3, 39]. *Hydropene* is also a juvenoid, which is registered for use against cockroaches and mosquito larvae, with an LD50 > 34,000 mg/kg (oral, rats). It disrupts normal development and emergence of insects by mimicking juvenile hormones [3, 6]. It may also cause adult sterility, physical abnormalities, desiccation, and premature death [6]. Its products are used in a variety of sectors, with commercial formulations including aerosols, liquids and impregnated materials (i.e. bait stations) [6]. *Fenoxycarb* is a carbamate insect growth regulator, with low toxicity to bees, birds and humans, but is toxic to fish [6]. The oral LD50 for rats is greater than 16,800 mg/kg and is used in fire ant flea baits, and for control of mosquitoes and cockroaches, as well as butterflies, moths, beetles, and scale and sucking insects on olives, vines, cotton and fruit, where it is often formulated as a grit or corncob bait. Fenoxycarb blocks metamorphosis into adults and larval molting. *Pyriproxyfen* affects a target if touched or eaten, but it is rarely toxic to adult insects. It disturbs egg-laying, egg-hatch and keeps young insects from growing into adult form, and has been used against fleas, cockroaches, ticks, ants and mosquitoes [6]. *Diflubenzuron* is a synthesized active compound, an acaricide/insecticide and IGR used to control many leaf-eating insect larvae in agricultural, forest and ornamental plants, as well as mosquito larvae in standing water, using various formulations such as emulsifiable and solution concentrates, flowable concentrates, wettable powders and pellets. Some of its benefits include being relatively non-toxic to avian species, small mammals, freshwater fish, marine/estuarine fish and bees on an acute oral dietary basis [3, 6].
