Insecticidal Agents in Pest Control: Sources, Challenges, and Advantages

Abstract

Insect pests are found commonly in two critical areas of human life: the farms and crop storage facilities and the home, where they cause a number of problems, including the destruction of various forms of materials such as clothes and cellulose-based items by ants, as well as nuisances and disease-transmitting activities perpetrated by mosquitoes, flies, cockroaches, and bugs. For ages, man has tried to fight the menace of insects using traditional and scientific methods, including the use of chemicals. In this work, the historical aspect of the use of insecticides for pest control, the challenge of the development of insect resistance, the potential for and incidences of environmental and health hazards, adverse effects on climate change, and the search for new agents, particularly from natural products of plant origin, are discussed. The challenges and the strategic advantages of the use of various classes of insecticides are also presented. The need for the application of lessons learned from human pharmaceutical science, the deployment of emerging technologies in the search for new insecticidal moieties and biopesticides, and the development of new and more efficient insecticide application tools and technologies are also discussed.

1. Introduction

Pests have been defined in various ways by various researchers, but may be summarized as any form of plant or animal or any pathogenic agent that is injurious or has the potential to be injurious to plants, plant products, livestock, and man. They include insects and the other arthropods, vertebrates, nematodes, weeds, and pathogens such as fungi, bacteria, viruses etc. [1, 2]. An estimated 67,000 species of vertebrate and invertebrate pests exist globally, destroying about 40% of agricultural produce annually [3].

Pests have been in existence since the creation of the universe, and the threat of pests such as mosquitoes, cockroaches, rodents, parasitic worms, pathogens, and snails has been well known and challenged by man. Both vertebrates and invertebrate pests cause huge damage to crops annually in the fields, gardens, and homes. Of the invertebrates the arachnids and in particular the insects constitute the most important crop pests. They cause damage by their eating habits, leading to defoliation and damage to the roots of plants by insects and larvae. Insects such as the aphids suck the plant sap and therefore cause physical damage as well as act as vectors for infective agents. The resultant effects are decreased agricultural yields, food quality and quantity, and increased hunger among the population [4]. Ancient man had used his ingenuity to deploy various methods to control their menace, including smoky fire, the spread of mud on the body, prayers, magic spells, cultivation systems, mechanical practice, as well as application of organic and inorganic substances to protect his crops from attack of weeds, diseases, and insect pests [5]. While agricultural yield has greatly improved to 70–100% in the industrialized nations due to better pest management and improved plant species, the challenge of poor yield due primarily to pests persists in the developing countries of Africa [3].

In recent years, the global concern is the impact of the activities of pests on agricultural outputs in terms of quantity and quality of food production by farmers all over the world, and disease transmission [6, 7, 8, 9, 10]. Annual crop losses due to pests is 35–45% which amounts to about $470 billion USA [11]. The world population is rapidly increasing, and as of today it is about 7.95 billion [12]. Thus, population growth pressure and limited options have put an enormous burden on the need to develop measures to meet food demands, which is a serious challenge in developing countries of Asia and Africa [13, 14]. To minimize the devastating impact of pests, particularly on agricultural production, as well as eliminate disease-borne vectors as part of primary healthcare measure, pesticides have been developed. Some reports have it that as of today, the pesticide consumption has reached 4 million tons of which 50% are herbicides, 30% are insecticides, and 18% are fungicides [15]. Also, the world market in 2019 was US$84.5 billion, with the prospect of reaching US$130.7 billion in 2023 [16]. As our knowledge of pests and their activities has expanded, the definition of pesticides has also been expanded in terms of actions on the pests. A version by Maton et al. [1] defines a pesticide as “any natural or synthetic chemical that causes directly the death, impulsion, attraction, deterrence of pests or in other ways influences pests for useful purposes”. However, Lopes et al. [11] while not disagreeing with the above definition defined a pesticide as any compound or mixture of components intended for preventing, destroying, repelling, or mitigating any pest. In any case, they include herbicides, insecticides, fungicides, rodenticides, and nematicides [17].

Among the pests, perhaps one of the most devastating agents are the insects, which destroy plant crops on the farmlands, crops in storage, and home furniture and act as disease vectors in aquatic and terrestrial environments. The chemicals for killing or inhibiting insect pests worldwide are called insecticides and probably were the earliest chemicals to be used by man in agriculture and in the home, to prevent vector-borne diseases, for crop protection and food preservation, and in aquaculture [18].

This work focuses on insecticidal agents in pest control and addresses issues relating only to insects and chemicals in use to control them. Thus, as much as possible chemicals used as antimicrobial (antibacterial and fungicidal), anthelmintic, herbicidal, molluscicidal, or piscicidal agents will not be discussed. However, associated chemicals such as repellents, attractants, and synergistic agents are included. The history and sources of insecticidal agents and their contribution to agricultural productivity and healthcare as well as the challenges and advantages in their applications will be presented.

2. History and sources of insecticides

A number of substances were used in pest control between 500 BC and World War II in the 19th century, and were considered as pesticides. A pesticide is “any substance or mixture of substances intended for preventing, destroying, repelling or mitigating any pest”. They included brimstone (sulfur), arsenic, lead, and mercury [13, 19]. Others were cryolite (sodium hexafluoroaluminate), petroleum oil, hydrogen cyanide gas, nicotine, pyrethrum, and rotenone [20]. In 1874 DDT (dichlorodiphenyltrichloroethane) was synthesized, and during the second half of World War II, its insecticidal activity was discovered and effectively used to control malaria and typhus diseases among the troops. It became the first synthetic organic pesticide used after the war for agricultural purposes [21]. However, it was established that synthetic organic pesticides, particularly chlorinated hydrocarbons such as DDT and derivatives, led to serious environmental pollution (water, air, and soil), affecting human health and causing deaths of non-target organisms (animals, plants, and fish). This led to the Stockholm Convention in 2001 and the eventual ban of DDT in 2004 [22]. Before the ban, efforts were already made by researchers for alternative sources of pesticides due to other reasons including (a) non-selectivity/specificity, (b) ineffectiveness, (c) not many of the synthetic compounds having been successfully marketed due to lack of interest by potential users, (d) high cost of synthetic chemicals, and (e) development of resistance [23, 24].

The development of pesticide resistance has led to rising number of insect species, and today there are over 10,000 species of insects. The “green revolution” in the 1960s by a number of countries led to the heavy use of pesticidal agrochemicals, with Argentina, Brazil, China, Russia, Canada, Australia, Columbia, France, and India as top consumers [25].

3. Classification of insecticides

Based on these earlier uses, insecticides were generally classified according to their mode of action as they have very diverse chemical structures. Thus, they included fumigants that were delivered as smokes, aerosol sprays, volatile liquids, and gases and they enter the insects through the breathing pores called spiracles. Other classes included stomach poisons, which were inorganic in nature and need to be eaten, and their organic counterparts are contact poisons, which penetrate the insect cuticle into the nervous system to cause paralysis. More recently, the systemics were introduced and they act by entering the plant tissues and then being absorbed by the insects. Thus, they are similar to stomach poisons [4]. Today, we have broader and sometimes micro-classifications such as contact (with no residual effect), systemic (with long-term activity), repellent and non-repellent, deterrents, and botanicals [1, 26, 27]. The broad classes are presented as follows:

3.1 Chemical insecticides

Chemical insecticides are synthetic compounds designed to target and eliminate specific insect pests. These agents are categorized based on their mode of action, including neurotoxins, growth regulators, and stomach poisons. Widely used in agriculture, chemical insecticides provide rapid and effective control of pests but are also associated with concerns such as resistance development and environmental impacts. As earlier emphasized, sulfur and a number of heavy metals such as arsenic, copper, lead, mercury, etc., were used as insecticides by the ancient man. However, since World War II (1940), which opened the “Modern Era of Chemical Control”, a number of organic chemical insecticides have been developed and used, including naphthalene, carbon tetrachloride, tetrachloroethane, 1,1-dichloro-1-nitroethane, nicotine, azobenzene, sulfotep, fumazone, telone, dazomet, metham sodium, triphenyl phosphine, phenothiazine, DNC (4,4′-dinitrocarbanilide), dinex, DDT, gammexane, carbamates, the cyclodienes such as aldrien, and dieldrin, and the organophosphorus compounds dimefox, TEPP (Tetraethyl pyrophosphate), schraden, malathion, parathion, and dichlorvos as well as the bridged diphenyl compounds, dicofol and tedion (tetradifon) [10, 19, 20]. These chemicals can be further classified as follows.

3.1.1 Organochlorines

This group includes the diphenyl aliphatics such as chlorobenzilate (1), DDT (2), DDD (Dichlorodiphenyldichloroethane, 3), dicofol (4), ethylan (5), and methoxychlor (6). Most of these have been banned because of environmental toxicity [20].

Of the above organochlorides, DDT has been the most widely used from 1940 up till 1973 when its use was prohibited in the United States by the United States Environmental Protection Agency (USEPA), though it is still being widely used in many developing countries for the control of insect-vectored diseases such as malaria and yellow fever. For its high toxicity, DDT was eventually banned in 2004 after the Stockholm Convention in 2001 [20, 22]. The mode of action of DDT is suspected to be by disrupting the balance of Na⁺ and K⁺ ions in the axon of the neurons blocking normal transmission of nerve impulses resulting in spontaneous convulsion and death [20].

Hexachlorohexane, also known as benzene hexachloride (BHC), was discovered in 1940. Of the five isomers, alpha, beta, gamma, delta, and epsilon, only the gamma isomer has insecticidal properties and is sold under the trade name lindane. It was banned in the US in 2002, although it is still used in some developing countries. Like DDT it is a neurotoxicant [20].

The cyclodienes class of organochlorines was developed after World War II between 1945 and 1958. They include chlordane (7), aldrin (8), dieldrin (9), heptachlor, endrin, mirex, endosulfan, and chlordecone. They were mostly used as termiticides and larvicides against soil-borne insects. Cyclodienes are relatively stable to ultraviolet light from the sun, and persistent in the soil. Chlordane, aldrin, and dieldrin are able to protect treated wood for over 60 years. Due to its environmental persistence, bioaccumulation in the wildlife food chain, and causing the development of insect-pest resistance, it was banned in the US in the 1980s. Unlike DDT and BHC, cyclodienes have a positive temperature correlation. Their activities increase as the temperature increases. Cyclodienes are believed to be neuro-active like DDT and BHC, but act by inhibiting GABA (g-aminobutyric acid) receptor [19, 20].

The polychloroterpenes include the toxaphene (10) and strobane (11), developed in 1947 and 1951, respectively. Toxaphene has been widely used alone or as a synergist with DDT and organophosphorus insecticides such as methyl parathion. Its mode of action is similar to that of the cyclodienes. Its use was discontinued in the US in 1983 by the USEPA due to its high aquatic toxicity [20].

3.1.2 Organophosphates

These are phosphorus-containing organic compounds used as insecticides. Their insecticidal property was first noted during World War II when the extremely toxic organophosphate nerve gases, sarin, soman, and tabun, were studied for their structural similarities and as substitutes for nicotine, which was in short supply as insecticide in Germany. Organophosphates are generally more toxic to vertebrates than other classes of insecticides, and most are chemically unstable or nonpersistent. Their non-persistence made them more environmentally friendly and constituted a suitable substitute for organochlorines. Organophosphates inhibit cholinesterase, an enzyme of the nervous system, resulting in the accumulation of acetylcholine at the neuron/neuron and neuron/muscle (neuromuscular) junctions or synapses. Most organophosphates were discontinued for use in the 1990s for food-safety reasons [19, 20].

All organophosphates are esters of phosphorus having varying combinations of oxygen, carbon, sulfur, and nitrogen attached, resulting in six different subclasses: phosphates, phosphonates, phosphorothioates, phosphorodithioates, phosphorothiolates, and phosphoramidates. Generally, organophosphates are divided into three groups, viz.: aliphatic, phenyl, and heterocyclic derivatives. Tetraethyl pyrophosphate (TEPP, 12), and dichlorvos (13) are aliphatic organophosphate; ethyl parathion (14) and famphur (15) are phenyl derivatives, while diazinon (16) and chlorpyrifos-methyl (17) are heterocyclic derivatives [20].

3.1.3 Organosulfurs

This class has two phenyl rings like DDT but has sulfur in place of carbon as the central atom. They are used as acaricides (miticides) for their low toxicity. Examples include tetradifon (18), propargite (19), and ovex (20) [20].

3.1.4 Carbamates

The carbamates are derivatives of carbamic acid just as organophosphates are from phosphoric acid. They act by inhibiting cholinesterase enzyme. Members of the class are carbaryl (21), methomyl (22), carbofuran, and primicarb (23), etc. [19, 20].

Most carbamates exhibit an irreversible inhibition of cholinesterase, poisoning the insect central nervous system (CNS) [28].

3.1.5 Formamidines

Examples of this group include chlordimeform (24), formetanate (25), and amitraz (26). They are now mainly used in the control of organophosphate and carbamate-resistant pests. Formamidines inhibit monoamine oxidase responsible for degrading the neurotransmitters norepinephrine and serotonin leading to their accumulation. The high concentration of the neurotransmitters causes paralysis and death of the insect [20].

3.1.6 Dinitrophenols

The dinitrophenols have a broad range of uses as insecticides, ovicides, herbicides, and fungicides. They act by inhibiting oxidative phosphorylation, preventing the generation of adenosine triphosphate (ATP). They have all been withdrawn from industrial use due to toxicity. Examples include binapacryl (27) and dinocap (28) [20].

3.1.7 Organotins

These are compounds containing tin (Sn) and used mainly to eliminate ticks and mites, although they are also good fungicides. They also act by preventing oxidative phosphorylation and the production of ATP. Examples are cyhexatin (29) and fenbutatin oxide (30) [20].

3.1.8 Pyrethroids

These are synthetic pyrethrin-like substances created in recent decades to replace natural pyrethrum for agricultural purposes because of their lower cost and better stability in sunlight. Natural pyrethrums are unstable in sunlight and expensive to produce. They are generally effective against several agricultural insect pests at low doses of 0.0045 to 0.045 kg per acre. Pyrethriods act by attacking the sodium channel of the axon of the neurons like DDT, affecting both the peripheral and CNS of the insect. Examples include allethrin, tetramethrin, phonothrin, permethrin, cypermethrin (31), acrinathrin, imiprothrin (32), and gamma-cyhalothrin (33), etc. [19, 20].

3.1.9 Nicotinoids

These are a class of synthetic insecticides that are similar to or analogs of the natural nicotine. They were previously referred to as nitro-quanidines, neonicotinyls, neonicotinoids, chloronicotines, and chloronicotinyls. An example is imidacloprid (34), which has root-systemic profile and notable contact and stomach action. It works by irreversibly blocking the postsynaptic nicotinergic acetylcholine receptors causing the collapse of the CNS and death of the insect. It is used as a soil, seed, or leaf treatment for the elimination and long residual control of sucking insects, soil insects, whiteflies, termites, turf insects, etc. Imidacloprid does not affect mites or nematodes [19, 20, 28, 29, 30]. Other examples include acetamiprid, thiamethoxam (35), thiacloprid, nitenpyram, clothianidin, dinotefuran (36) and clothianidin.

3.1.10 Fiproles (or phenylpyrazoles)

The only example is fipronil (37). It is effective against insects resistant or tolerant to pyrethroid, organophosphate, and carbamate insecticides. It acts by blocking the g-aminobutyric acid (GABA) regulated chloride channel in neurons, thus antagonizing the “calming” effects of GABA, similar to the action of the cyclodienes [20].

3.1.11 Pyrroles

The only available member of this group is the chlorfenapyr (38). It acts by inhibiting oxidative phosphorylation and the production of ATP, mediated by the mitochondrial electron transport at the NADH-CoQ reductase site. They are effective against aphids, psylla, thrips, and whitefly [19, 20].

3.1.12 Pyrazoles

Examples of this class include tebufenpyrad (39), fenpyroximate (40), ethiprole (41) and tolfenpyrad (42). They have broad activity against a wide range of chewing and sucking insects. They are contact and stomach active. Their mode of action is by inhibiting mitochondrial electron transport at the NADH-CoQ reductase site, leading to the disruption of adenosine triphosphate (ATP) formation [19, 20].

3.1.13 Pyridazinones

Pyridaben (43) is the only member of this class. It is a selective contact insecticide and miticide, effective against thrips, aphids, whiteflies, and leafhoppers. It is a metabolic inhibitor that interrupts mitochondrial electron transport at site 1, similar to the quinazolines [19, 20].

3.1.14 Quinazolines

The only example is fenazaquin (44), which is a contact and stomach active agent. It inhibits mitochondrial electron transport at Site 1, similar to the pyridazinones [20]. Quinazolines also act on the larval stages of most insects by inhibiting or blocking the synthesis of chitin in the exoskeleton. Developing larvae exhibit rupture of the malformed cuticle or death by starvation [19].

3.1.15 Benzoylureas

Benzoylureas are quite a different class of insecticides that act as growth regulators in the insects by regulating the synthesis of chitin, rather than attacking the insect nervous system like the other poisons. They are taken up more by ingestion than by contact. Their greatest value is in the control of caterpillars and beetle larvae. Examples are triflumuron, chlorfluazuron, teflubenzuron, hexaflumuron, flufenoxuron, flucycloxuron, flurazuron, novaluron (45), lufenuron (46), diafenthiuron (47), bistrifluron, noviflumuron, diflubenzuron (48). Though not a benzoylurea, cyromazine (49), a triazine, is also a potent chitin synthesis inhibitor. Chitin synthesis inhibitors are very effective against the larval stages of most insects since chitin is the vital and almost indestructible part of the insect exoskeleton. The developing larvae are eliminated by the rupture of malformed cuticles or death by starvation. Adult female boll weevils exposed to diflubenzuron lay eggs that do not hatch. Thus, mosquito larvae control can be achieved with as little as 1.0 gram of diflubenzuron per acre of surface water [19, 20].

In the last decade, more than 34 insecticides have been launched with a shift from organophosphorus, carbamates, and synthetic pyrethroids to nicotinic and diamide insecticides known as neonicotinoids, which were used in Europe in 2005–2013 to protect wildlife such as pollinators (honey bees), mammals, birds, fish, amphibians, and reptiles [11]. Another advance in the development and use of insecticides to control pests was the introduction of groups of chemicals known as attractants and repellents to minimize the use of highly toxic chemical insecticides [27].

3.2 Biological control agents

Biological control agents encompass a range of living organisms that can regulate pest populations. Beneficial insects, such as parasitoids and predators, nematodes, fungi, and bacteria, are examples of biological control agents that offer a sustainable and eco-friendly approach to pest management. These agents can be integrated into pest control programs to reduce reliance on chemical insecticides and promote natural pest suppression mechanisms. A new class of biological insecticides has recently been discovered, and its use is gradually gaining importance, particularly in developed countries. They are the microbial insecticides, which use microbial metabolites from microorganisms to kill insect larvae. For example, Bacillus thuringiensis produces delta-endotoxin, which is active against lepidopterous and dipterous larvae [29]. Another microbial insecticide is beauvericin, a toxic substance from the fungus, Beauveria bassiana [31].

Also included among the biological insecticides is the spinosad, derived from naturally occurring soil bacteria, Saccharopolyspora spinosa. Spinosad is a mixture of two compounds, spinosyn A (50) and spinosyn D (51) (thus its name, spinosAD), and is used in organic farming. It is obtained as a fermentation metabolite of the soil-inhabiting microorganism Saccharopolyspora spinosa and, thus, can rightly be classified under biological insecticides. It is particularly effective as a broad-spectrum material for most caterpillar pests at the low rate of about 18 to 40 grams per acre. It has both contact and stomach activity against lepidopteran larvae, leaf miners, thrips, and termites, with long residual activity. It acts on the nervous system of insects by disruptively binding acetylcholine in nicotinic acetylcholine receptors at the postsynaptic cell [19, 20, 32].

Of great interest today are the insect growth regulators (IGRs), which have the capacity to disrupt the growth and development of insects by interfering with their hormonal regulation, the molting process, or reproduction. They include juvenile hormone analogs, chitin synthesis inhibitors, and ecdysone receptor agonists. Some natural chemical compounds such as cinnamyl phenols, though not insecticides themselves, possess sterilizing properties against adult mosquitoes and houseflies, and therefore help to control the insect population. In this way, they act remotely as insecticides and do not impact the environment or human health [33, 34, 35].

3.3 Botanicals

Natural insecticides derived from plants or plant products are perhaps the earliest insecticides used by man. Botanical extracts derived from plants contain compounds with insecticidal properties. Neem oil, camphor, pyrethrum, hellebore, quassia, turpentine, tobacco, and citrus extracts are examples of botanical insecticides that can repel or kill pests [20]. Other plant-derived insecticides such as cinnamaldehyde (52), eugenol (53), and limonene (54) are referred to as floral or scented plant chemicals.

Of particular economic importance among the plants in common use today are the pyrethrum and the tropical plant, Azadirachta indica A. Juss., popularly known as the neem tree. The neem oil is known to control over 25 species of insect pests, and the activity has been linked to the natural compound, azadirachtin (55), a tetranortriterpenoid found in the kernel. Azadirachtin is used on ornaments and in greenhouses. Azadirachtin is a powerful antifeedant that acts by disrupting insect growth regulators. It causes growth malformation and mortality in insect larvae. It disturbs insect development apparently by interfering with the biosynthesis, and release or action of juvenile and ecdysteroids such as the prothoracicotropic hormone (PTTH), allatotropins, and other growth regulators of insect molt [35, 36].

Natural nicotine (56) is an alkaloid derived from the leaves of Nicotiana spp., especially Nicotiana tabacum, the tobacco plant [20]. Nicotine is an autonomic blocking agent acting like acetylcholine at the ganglia and neuromuscular junctions. Like the carbamates, nicotine acts by inhibiting cholinesterase activity responsible for the breakdown of acetylcholine resulting in acute cholinergic toxicity, and CNS disruption [28].

Rotenone (57) naturally occurs in Derris, Lonchocarpus, Tephrosia, and Mundulea species, particularly in the roots of Lonchocarpus species. Rotenone is a colorless and odorless crystalline isoflavonoid that is highly toxic to insects and fish, but moderately hazardous to humans and other mammals [37, 38]. Rotenone is used to eliminate ticks and lice on cats, dogs, and horses and mites on poultry. Rotenone acts by inhibiting the activity of mitochondrial respiratory complex I, generating excess free radicals resulting in cell death by apoptosis [39, 40].

Pyrethrins are a mixture of 6 compounds (pyrethrin I & II (58 & 59), cinerin I & II (60 & 61), and jasmolin I & II (62 & 63)) and are found in over 2000 commercial pesticides, as the active ingredient along with synergists, commonly used against many insect pests including ants, fleas, flies, moths, and mosquitoes. It excites the nervous system of the insects that feed on it causing paralysis and death [41, 42].

These natural alternatives are favored for their lower environmental impact and reduced toxicity to non-target organisms, making them suitable for organic farming and integrated pest management practices. The number of plants that have been investigated for their efficacy and constituents has continued to increase in the past decade [43]. Also, the effectiveness of nine Chinese plant species has been compared with synthetic insecticides against 40 species of insects [43, 44, 45, 46].

Some Nigerian plants such as Piper guineense, certain Dalbergia spp., such as Dalbergia saxatilis and Dalbergia lactea, and essential oils from Eucalyptus spp., like E. citriodora and E. globulus, and Cymbopogon spp (lemon grass) have been studied in some detail and found to exhibit attractant, repellent, and/or insecticidal activities and are worthy of exploitation for commercial purposes. Of particular interest is guineensine (64) which was isolated from the fruit of Piper guineense and has been synthesized [45, 46, 47, 48, 49, 50]. The piperamide, guineensine, is an N-isobutylamide alkaloid that is insecticidal to many insects such as bean weevil, and mosquitoes (Culex pipiens pallens and Aedes aegypti) and thus often used as an insect repellant and antifeedant [51, 52]. Piperamides act as neurotoxins to insects through a pathway that does not interfere with the neurotransmitter system but through the inactivation of voltage-gated sodium ion channels that regulate neuronal intracellular calcium ion release creating Ca²⁺ toxicity. Piperamides also inhibit cytochrome P-450 dependent polysubstrate monooxygenase (PSMO) in insects preventing the detoxification of toxicants, and enhancing the effect of the toxic insecticide(s) [19, 52]. Piperamides are good synergists with additive effects to insecticides like pyrethrum. Similar insecticidal piperamides from Piper nigrum include pipercide, pellitorine, and piperine [52]. Most piperamides are easily degraded under sunlight. Evidence has shown that they possess a half-life of about 40–50 minutes under ultraviolet light [52].

Citronella oil from Cymbopogun citratus (D.C.) Stapf, and eucalyptus oil are strong repellants of some species of Anopheles mosquitoes, especially An. Stephensi. Citronellal (65) and eucalyptol (or 1,8-cineole) (66) are the major constituents of citronella oil and eucalyptus oil, respectively [49, 53, 54]. Linalool, a monoterpenoid and constituent of many essential oils, influences the ion transport and acetylcholine esterase release in insects. Some other insecticidal constituents of essential oils have been demonstrated to act through octopamine-mediated modification of insect physiology by activating the octopaminergic receptor [55, 56, 57]. Limonene affects the sensory nerves of the peripheral nervous system [19].

The list of some commercial botanical insecticides, the constituents, mode of action, and targets is shown in Table 1.

Plant Name	Product/trade name	Active compound	Group/mode of action	Targets
Adenium obesum (Forssk.) Roem. & Schult.	Water extract of Chacals Baobab (Senegal)	Chacal; Baobab; extract	Insecticidal	Cotton pests, particularly the larvae of ballworm (Heliotis spp.), spiny ballworm (Earias sp.), and Sudan ballworm (Diparopsis watersi)
Azadirachta indica L.	Neem oil,; Neem cake,; Neem powder,; Bionimbecidine; (GreenGold)	Azadirachtin	Repellent; Antifeedant; Nematicide; Sterilant; Anti-fungal	Dandruff, Eczema, Nematodes, Sucking and chewing insects (caterpillars, aphids, thrips and maize weevils)
Chrysanthemum; cinerariaefolium (Trevir.) Vis.	Pyrethrum	Pyrethrins	Insecticidal	Crawling and flying insects such as cockroaches, ants, mosquitoes, termites, bees
Citrus trees	Essential oil	δ-Limonene; Linalool	Contact poison	Fleas, aphids, mites, paper wasps, house crickets, dips for pets, bugs, blister beetles
Derris elliptica (Wall.) Benth.	Rotenone	Rotenone	Insecticidal	Aphids, bean leaf beetle, cucumber beetles, leafhopper, red spider mite
Lonchocarpus spp	Rotenone	Rotenone
Nicotiana tabacum L.	Tobacco	Nicotine	Insecticidal Antifungal	Aphids, thrips, mites, bugs, fungi, gnats, leafhoppers
Ryania speciose	Ryania	Ryanodine	Insecticidal	Caterpillars, thrips, beetles, bugs, aphids
Schoenocaulon officinale (Schltdl. & Cham.) A.Gray	Sabadilla dust from the seed	Veratran D and Cevadine	Insecticidal	Flies, caterpillars, potato leafhopper

Table 1.

List of some commercial botanical insecticides (From: Okwute [43]).

4. Challenges of insecticidal agents in pest control

There is no doubt that the use of insecticidal agents has contributed enormously to agricultural productivity and global healthcare, but it is evident that over time because of intensive use of insecticides the environment has been saturated with toxic chemicals and some of these have impacted negatively on non-intended targets. Thus, indiscriminate use of insecticidal agents has the potential to upset the ecosystem [58]. One of the primary challenges associated with insecticidal agents is the development of resistance in pest populations. Prolonged exposure to the same insecticide can lead to genetic adaptations in pests, rendering the agent less effective over time. To combat resistance, integrated pest management strategies that combine multiple control methods have been recommended [59].

Environmental impacts are another significant concern related to insecticidal agents, as shown in Figure 1. Chemical insecticides can persist in the environment, contaminating soil, water sources, and non-target organisms. This can disrupt ecosystem dynamics, harm beneficial insects, and pose risk to human health. For example, some common household insecticides used in Nigeria have been shown to induce oxidative stress in Wistar rats [60]. Also, insecticide poisoning fatalities in children have been reported in some countries including South Korea, South Africa, Canada, Turkey, India, and Tanzania [3, 9, 18, 19]. Carbamate and organophosphate insecticides are very toxic to humans. The potential hazards of insecticides from environmental pollution, ozone depletion, persistence, and bioaccumulation, have made the search for new and environmentally friendly insecticides an imperative. This has led to a renewed desire to develop new and environmentally friendly biological and botanical insecticides for agricultural and healthcare purposes [3, 19, 55, 61, 62]. However, the short half-life of many biological and botanical insecticides is also a concern. Many natural insecticides are degraded under sunlight and in the soil within 48 and 240 hours, respectively, requiring frequent and repeated application for optimum desired effect [52].

Figure 1.

Environmental pollution pathway for insecticides’ use [19].

5. Remedial approaches to the challenges

The desire to improve agricultural yield and eliminate insect-vector diseases has led to the increasing use of insecticides over the decades, despite growing health and environmental hazards, and the destruction of global biodiversity. The global use of pesticidal agents, particularly insecticides, increased between 1990 and 2017 by about 80% leading to increased yields in agricultural products and sharp drops in their market prices [63]. Safety concerns surrounding insecticidal agents therefore highlight the importance of responsible application and handling. Improper use of chemical insecticides can result in human exposure, pesticide residues in food products, and toxicity to wildlife [63]. Sustainable pest control practices aim to minimize environmental impacts by promoting the judicious use of insecticidal agents and exploring alternative solutions. Some of the steps that need to be taken to remediate these challenges include the following:

5.1 Responsible handling of insecticidal agents and regulatory oversight

In the home, to combat disease-vector insects there has been extremely careless application of very toxic insecticides usually as sprays in very high concentrations. For most African dwellers, in most cases personal protective equipment (PPE) are not worn when spraying farms, and homes (especially bedrooms and living rooms), and perhaps not much gap is given between spraying time and cultivation or sleeping time. This practice, which is a gross display of ignorance of the hazardous effects of chemical insecticides, is very dangerous to human, animal, and environmental health. It is perhaps the most hazardous aspect of our effort to eradicate the destructive effect of insect invasion in agricultural practices, and the spread of insect-vectored diseases like malaria and trypanosomiasis transmitted by mosquitoes and tsetse flies. For instance, non-adherence to safety precautions in the use of long-lasting insecticidal nets (LLINs), and failure to use PPE in indoor residual sprayings (IRS), could be potential sources of insecticide hazards [59]. The use of facemask, chemical-resistant gloves, goggles, and respirators is recommended during spraying of farms, homes, and environment to minimize chemical hazards. Care should also be taken to avoid contact with non-targeted animals and plants. For highly toxic chemical insecticides, a number of countries, particularly the United States, have enacted laws to ban some insecticides. For example, the United States banned the use of insecticides of the group chlorpyrifos in 2021, while Brazil, China, and Europe have planned to do the same [18, 64, 65]. Some researchers have also established a list of about 18 insecticides considered safe to comparatively natural enemies [14]. This is expected to limit the indiscriminate use of very toxic chemical insecticides in the environment and target specific crops and pests.

Regulatory oversights and education programs are also essential to ensure insecticidal agents’ safe and effective use while minimizing risks to human health and the environment. Such policies should control the indiscriminate sale, purchase, and use of chemical insecticides that have become common tools for committing murder and suicide by food and drink poisoning, particularly in the developing countries where insecticidal products are displayed in the open markets. Thus, in many Sub-Saharan African and South Asian countries, while there may be registration of agrochemical businesses, the pesticides are unlabeled and sold in the open markets [17]. Thus, treaties such as the Stockholm Convention, and local national regulatory agencies should be strengthened or empowered to perform their oversight functions [65].

5.2 Use of combined intervention methods

Another approach to the reduction of insecticide concentration in the environment is perhaps to use a combination of small quantities of insecticides in combination with non-toxic pesticides such as insect attractants or sex pheromones, which have the capability of bringing insects in mass to a location where the insecticide is applied. During the mating season, the male insects are attracted by the pheromones produced and released by their female counterparts. Hence, the use of pheromones as additives helps attract the insects for insecticidal action of applied insecticide(s), and also to disrupt their natural mating cycle. Undesired biodiversity destruction can be avoided by the use of selective pesticidal natural biomolecules, also called biorational products. Biorationals exhibit selective toxicity and have relatively low or no direct toxicity to non-targeted organisms [66]. Some secondary metabolites of plants act as allelochemicals stimulating antixenotic intrinsic and extrinsic defense against herbivorous insects. Thus, allelochemicals can act as kairomones (defensive stimulus for adaptive benefit toward another species), allomones (defensive stimulus for adaptive benefit toward the same species), or synomones (defensive stimulus for adaptive benefit toward same species and other species) depending on the effect they have on the specific insect [66]. The use of pheromones (or allelochemicals) can reduce the quantity and the applicable space for the application of the insecticide, especially in cases involving sprays, promoting environmental safety and cost-effectiveness in insect pest control. On the other hand, use of insect repellents, antifeedants, and deterrents that do not primarily aim to kill the insects ensures that no real toxic chemical insecticide will be applied, as toxic and staining repellents are not suitable for human use, especially against mosquitoes and flies [67, 68].

5.3 Use of botanicals

In the face of insect resistance to synthetic insecticides, their high toxicity to non-target organisms, and environmental persistence, attention has been shifted to plant-based pesticidal plants in the past few decades. The folkloric use of higher terrestrial plants by the natives of various parts of the world as pesticidal materials has been well known [69, 70]. Perhaps, one of the early plants so recorded as pesticidal material was tobacco (Nicotiana tabacum). The use of tobacco leaf infusion to kill aphids led to the isolation of the alkaloid, nicotine, while the chemical investigation of the Japanese plant, Roh-ten (Rhododendron hortense) in 1902 showed rotenone as the active constituent [4]. In this class of age-old pesticidal plants are species belonging to the genus Chrysanthemum found in Kenya and other highlands in Africa, which are the sources of the all-purpose and very successful insecticidal extract, pyrethrum, and the active constituents, the pyrethrins [71]. The relative success of these early botanical insecticides gives impetus to the current search for new and eco-friendly insecticides from plant sources.

The search for insecticidal plants, including repellents, antifeedants, and deterrents, has been extensive and successful particularly in Africa and Asia, including some Nigerian plants (Table 2) [45, 78, 79].

Family	Species	Parts screened	Form	Activity	Organisms	Compounds
Annonaceae	Dennettia tripetala	Leaf	Extract	Protectant	Weevils	β-phenyl-nitroethane; Terpenes
Fabaceae	Dalbergia saxatilis	Stem bark & leaf	Extract &; Powder	Insecticidal	Mosquitoes; Housefly	Unidentified
Melliceae	Azadirachta indica	Seeds	Powder	Protectant	25 species of plant pests	Limonoids
Mimosoidae	Tetrapleura tetraptera	Root & stem bark; LeafFruit	Extracts; Seed oil	Insect repellant; Insecticidal; Larvaticidal	Callosobruchus maculatus (cowpea weevil); Anopheles Gambiae	Aridanin (70); transgeranylgeraniol; Scopoletin (71); [72, 73, 74]
Amaranthaceae	Alternanthera sessilis L.	Leaf	Extracts	Larvaticidal	Culex quinquefasciatus (mosquito larvae)	Phytosterols, flavonoids, and terpenes; [75, 76, 77]
Piperaceae	Piper guineense	Fruits	Powder Extract	Insecticidal	Weevils; Grasshoppers	Alkaloids
Rutaceae	Clausena anisata	Leaf; Root	Extract	Insecticidal; Antifeedant	Grasshopper Armyworm	Alkaloids; Coumarins

Table 2.

Biological and phytochemical screening results on some Nigerian pesticidal plants (Source: [45]).

Prominent among the plants in common use today is the tropical plant Azadirachta indica, popularly known as the neem tree. In India as well as in Nigeria the plant is effectively used to control over 25 different species of insect pests. The activity has been associated with the presence of azadirachtin, which is said to be eco-friendly and safe and the concentration is highest in the kernel than in the leaves and other tissues of the plant [5, 44].

5.4 Use of synergists

Another approach to avoiding the application of high concentrations of highly toxic chemical insecticides is the use of synergists along with moderately toxic insecticides. Synergists have the capability to potentiate moderately active insecticides. For example, piperine (72) has been shown to act synergistically with guineensine in its activity to control the garden insect, Zonocerus variegatus [45]. Table 3 shows the comparative activities of the crude petroleum and chloroform extracts of Piper guineense and the insecticidal activities of its constituents, guineensine and piperine. The presence of a synergist provides for use of a limited quantity of the toxic insecticide though the exact mechanism is not quite understood.

Sample	% of insects (dead or moribund)	Effective concentration (ppm)
Piperine	50.0	5000
Guineensine	35.0	500
Chloroform extract	30.0	1000
Petroleum ether extract	20.0	1000

Table 3.

Percentage of insects dead or moribund in 1 hour of treatment with extracts and extractives from Piper guineense (Source: [45]).

6. Advantages of insecticidal agents in pest control

Despite the associated challenges, insecticidal agents offer several advantages in pest control. These agents provide efficient and targeted control of pest populations, helping to protect crops, reduce economic losses, and safeguard public health. By selectively targeting pests, insecticidal agents can minimize damage while preserving beneficial organisms in the ecosystem. Thus, they have contributed to increased food production, profits for farmers, and prevention of diseases. Globally, pesticide use has increased since the 1940s just as the average life expectancy. Data in the United States showed that the life span increased from 68 years in 1950 to 70.5 years in 1970 and was projected to increase to 75 in 1990 [13]. It has been estimated that between 1945 and 2018, the use of pesticides has prevented the death of about seven million people by killing pests that transmit diseases such as malaria caused by mosquitoes, bubonic plague carried by rat fleas, and typhus carried by body lice [80]. It has been reported that 17% of human infections are vector-borne, causing about 700,000 deaths annually, with 400,000 deaths attributable to malaria, of which Sub-Saharan Africa accounts for over 90%. However, a substantial achievement has been recorded in malaria control between 2000 and 2015 using a combination of interventions involving long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), and prompt management with ACTS therapies [81]. In Nigeria, a plant disease sarcastically labeled tomato ebola, which was quickly stopped from spreading in 2016 by the use of insecticides, is a strong demonstration of the importance of pesticides in modern agriculture. For the period it lasted, there was a serious scarcity of tomatoes leading to the collapse of some tomato paste–producing companies, and thus affecting the national economy [9].

Also, an FAO report has suggested that to meet the demands of the increasing global population, agriculture will need to produce almost 50% more food, feed, and biofuel in 2030 than it did in 2012, when the world population may reach 9.73 billion. This is particularly very important in Sub-Saharan Africa and South Asia where agricultural output will need to be doubled. This target can only be achieved with heavy and intensive application of insecticides and new technological innovations [82].

7. Search for new insecticidal agents and future research

In solving the challenges of insect resistance, health and environmental toxicity, climate change, and corrosion of household and agricultural tools/utensils associated with the use of existing synthetic insecticidal agents, current research initiatives must focus on natural products as sources of new insecticidal molecules. While natural products may be the source of structural guides to new molecules, structural modifications may be necessary to improve (i) stability, (ii) specificity, (iii) effectiveness, (iv) environmental tolerance, and (v) commercial viability. Evidence has shown that the mode of action of acaricidal agents is diverse with some agents modulating several pathways in exterminating the insect pest. However, structurally related substances employ similar pathways for their mode of action [83, 84]. Exploration of existing promising botanical insecticidal agents through chemical and/or biological modification to create new moieties that address existing challenges of resistance management, health and environmental toxicity, and depletion of the ozone layer is a necessary approach [85]. There must be renewed search for new natural chemical moieties from plants, animals, and microbes, and future research should cover the deployment of emerging technologies such as nanotechnology, co-crystallization techniques, computational chemistry, and genetic engineering such as mRNA technology to create nucleopolyhedroviruses [86], for the development of new insecticides to control environmental releases and effectiveness, safety in humans, and specificity. New researches must adopt lessons learned from human pharmaceutical research and development to unravel new insecticide targets and increase target diversity [87].

8. Conclusion

In conclusion, insecticidal agents play a critical role in pest control by providing efficient, targeted, and versatile solutions for managing pest populations. While challenges such as resistance, environmental impacts, and safety concerns must be addressed, the advantages of insecticidal agents in pest control are significant. One important approach to addressing the hazardous environmental impact of current commercially available insecticides is focusing on botanical pesticides to guide the development of new generation of insecticides for industrial, agricultural, and healthcare use. In addition, future researches must employ emerging technologies such as nanotechnology, co-crystallization, computational chemistry, genomic, and lessons learned from human pharmaceutical science to provide feasible solutions to existing and potential threats and challenges. By harnessing the strengths of diverse insecticidal agents and integrating them into sustainable pest management practices, we can mitigate the impact of pests on agriculture, promote environmental stewardship, and ensure food security and quality healthcare for future generations.

Acknowledgments

The authors wish to acknowledge the support of the management of their institutions during the development of the manuscript.

Conflict of interest

The authors declare no conflict of interest. There was no specific funding for the development of this work.