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International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 8 Number 12 (2019) Journal homepage: http://www.ijcmas.com

Review Article https://doi.org/10.20546/ijcmas.2019.812.030

Insect Growth Regulators for Insect Control

Sanjay Cyril Masih1* and Bhat Rayees Ahmad2

1Department of Zoology, Ewing Christian Post Graduate College, Allahabad, India 2Department of Zoology, Kurukshetra University, Kurukshetra, India

*Corresponding author

ABSTRACT

Insecticides with growth regulating properties (IGR) may adversely affect insects by regulating or inhibiting specific biochemical pathways or processes essential for insect growth and development. Some insects exposed to such compounds may die due to K e yw or ds

abnormal regulation of hormone-mediated cell or organ development. Other insects Insect growth may die either from a prolonged exposure at the developmental stage to other regulators, mortality factors (susceptibility to natural enemies, environmental conditions etc.) or Carvacrol,

Derivatives insect from an abnormal termination of a developmental stage itself. Insect growth regulators pests, Insect may come from a blend of synthetic chemicals or from other natural sources, such as hormones plants. The chemical composition of hormones indigenous to insects is now being

studied and used as a basis for developing analogs or mimics against insects. The Article Info similarities, however, in certain aspects of biochemistry among vertebrates and

Accepted: invertebrates may result in the limited development of IGRs. Environmental 04 November 2019 contamination also creates a hurdle as well as a challenge for industries to develop Available Online: compounds that provide a more environmentally or ecologically sound insect pest 10 December 2019 control. As part of on-going search for new biologically active molecules prepared from compound of natural origin, we thought of Insect Growth Regulators as

substitute to that are commercially used.

Introduction play a role in growth and development are: 1. Brain hormone: They are also called activation Insect Growth Regulators (IGRs) are hormone (AH). AH is secreted by neuro compounds which interfere with the growth, secretory cells (NSC) which are neurons of development and metamorphosis of insects. central nervous system (CNS). Its role is to IGRs include synthetic analogues of insect activate the corpora allata to produce juvenile hormones such as ecdysoids and juvenoids hormone (JH). 2. (JH): Also and non-hormonal compounds such as called neotinin. It is secreted by corpora allata precocenes (Anti JH) and chitin synthesis which are paired glands present behind insect inhibitors. Natural hormones of insects which brain. Their role is to keep the larva in

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Int.J.Curr.Microbiol.App.Sci (2019) 8(12): 208-218 juvenile condition. JH I, JH II, JH III and JH 1966. They found that the paper towel kept in IV have been identified in different groups of a glass jar used for rearing a Pyrrhocoris bug insects. The concentration of JH decreases as caused the bug to die before reaching adult the larva grows and reaches pupal stage. JH I, stage. They named the factor from the paper II and IV are found in larva while JH III is as „paper factor‟ or „juvabione‟. They found found in adult insects and are important for that the paper was manufactured from the development of ovary in adult females. 3. wood pulp of balsam fir tree (Abies balsamea) Ecdysone: Also called Moulting hormone which contained the JH mimic. Juvenoids (MH). Ecdysone is a steroid and is secreted by have anti-metamorphic effect on immature Prothoracic Glands (PTG) present near stages of insect. They retain status quo in prothoracic spiracles. Moulting in insects is insects (larva remains larva) and extra (super brought about only in the presence of numerary) moultings take place producing ecdysone. Ecdysone level decreases and is super larva, larval-pupal and pupal-adult altogether absent in adult insects. Although, intermediates which cause death of insects. agricultural have prevented pest Juvenoids are larvicidal and ovicidal in action damage of between 5% and 30 % of potential and they disrupt diapause and inhibit production in many crops, however, they have embryogenesis in insects. is a JH posed a number of problems in agriculture, mimic and is useful in the control of larva of including the killing of beneficial insects, hornfly, stored tobacco pests, green house outbreak of secondary pests, and the homopterans, red ants, leaf mining flies of development of resistant pests. Insect vegetables and flowers. Growth Regulators (IGR‟s) disrupt and impede the development of the life cycle of Anti JH or precocenes insects in the larval and egg stage. In short, IGR is a form of “birth control” for pests They act by destroying corpora allata and which helps keep the populations of unwanted preventing JH synthesis. When treated on pests under control by preventing current and immature stages of insect, they skip one or future infestations. two larval instars and turn into tiny precocious adults. They can neither mate, nor oviposit IGRs used in pest management and die soon. e.g. EMD, FMev, and PB (Piperonyl Butoxide). Ecdysoids Chitin synthesis inhibitors These compounds are synthetic analogues of natural ecdysone. When applied in insects, kill Benzoyl phenyl ureas have been found to have them by formation of defective cuticle. The the ability of inhibiting chitin synthesis in vivo development processes are accelerated by blocking the activity of the enzyme chitin bypassing several normal events resulting in synthetase. Two important compounds in this integument lacking scales or wax layer. category are (Dimilin) and Penfluron. The effects they produce on insects Juvenoids (JH mimics) include: Disruption of moulting, Displacement of mandibles and labrum, Adult fails to escape They are synthetic analogues of Juvenile from pupal skin and dies and Ovicidal effect. Hormone (JH). They are most promising as Chitin synthesis inhibitors have been hormonal insecticides. JH mimics were first registered for use in many countries and used identified by Williams and Slama in the year successfully against pests of soybean, cotton,

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Int.J.Curr.Microbiol.App.Sci (2019) 8(12): 208-218 apple, fruits, vegetables, forest trees and fractions. In the 1970, Benzoyl phenyl ureas, mosquitoes and pests of stored grain compounds with high degree of selectivity and low mammalian toxicity were discovered by A new approach to insect is the scientists at Philips-Duphar, Netherlands. use of substances that adversely affect insect Actually it was a attempt for development of growth and development. These substances weed control agent but the product was found are classified as “insect hormone mimics‟‟ or to be more effective as an showing “insect growth regulators‟ (IGRs) owing to delay in toxicity when the insect next molted. their effects on certain physiological regulatory processes essential to the normal Because CSIs interfere with the development of insects or their progeny. They polymerization of chitin, this mode of action are quite selective in their mode of action and has been targeted for control of several potentially act only on target species. The different insect pests. CSIs cause abnormal action of IGRs, however, should not be deposits of endocuticle that accumulate during confused with other synthetic insecticides, molting, specifically uridine diphospho-N- such as and carbamates, acetylglucosamine monomers thereby since these chemicals interfere with other preventing chitin synthesis. This produce a physiological processes but do not regulate the weakened cuticle and causes mortality when development of normal insects. An IGR, the pro-cuticle is subjected to the stresses of therefore, does not necessarily have to be toxic ecdysis and cuticular expansion. to its target, but may lead instead to various Consequences of CSI toxicity also include abnormalities that impair insect survival mortality in the absence of metamorphosis and (Siddall, 1976). Interestingly, most of the include swollen appendages, decrease in IGRs that have shown effectiveness against locomotion, inability to eat due to dislocation insect pests cause the rapid death of the insect of mandibles, malformed or absent peritrophic through failure of a key regulatory process to matrix, as well as suppressed fecundity and operate or function. IGRs generally control egg viability. insects either through regulation of metamorphosis or interference with Benzoyl Phenyl Ureas (BPU) reproduction (Riddiford and Truman, 1978). Compounds developed to disrupt Benzoyl phenyl urea, an important type of metamorphosis ensure that no reproductive insect growth regulators, acting on the larval adults are formed. Those that specifically stages of the Lepidoptera insects by inhibiting interfere with reproduction may include the chitin synthesis have been rapidly developed development of adults with certain after the introduction of the first benzoyl morphogenetic abnormalities that reduce their phenyl urea diflubenzuron in 1972. Besides reproductive potential. Adults may be sterile diflubenzuron, hexaflumuron, lufenuron, or possess abnormally developed genitalia, penflzuron, noveluron, tefluenzuron and which hinders the mating process or the chlorfluazuron were some of other widely capacity to produce fertile offspring. Chitin used IGRs. Benzoyl phenyl urea have a unique synthesis inhibitors, the insect cuticle serves mode of action coupled with a high degree of as an interface between the living animal and activity on target pests and low toxicity to its environment; and forms the exoskeleton, non-target organisms, that is why they have supporting the linings of the gut, respiratory attracted considerable attention for decades systems, reproductive ducts, and some gland and have become a new tool for integrated ducts. It consists of protein and chitin pest management.

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The in vivo or in situ (isolated integument this question, which bears on the incubated in a tissue culture medium) studies environmental impact of JH analogs, new showed that chitin synthetase catalyzing the research would have to involve chemical incorporation of UDPN-acetylglucosamine identification rather than rely on bioassay, (UDP NAGA) to chitin was clearly inhibited which formed the basis of reports Granett by BPUs. However, all of the subsequent (1975) JH activity in mammalian tissues in the studies trying to prove some action of BPUs late 1950's. On phylogenetic grounds it could on any part of the chitin synthesis pathway in be anticipated that JH might occur in other insects in cell free systems (rather than in vivo classes of the phylum arthropoda, such as the and in situ) failed. In addition, BPUs showed crustaceans, which definitely contain the same no inhibitory actions on fungal chitin molting hormones as insects Gilbert (1961). synthetase in vivo as well as in cell free Even this is doubtful, because a large body of systems, which have roughly equivalent chitin toxicological testing of IGRs on various synthesis pathways as insects. Therefore, the crustacean species at several developmental action mechanism of BPUs remained stages has shown no effects which were even unanswered. vaguely hormonal in nature. More extensive tests of the natural JH and several hundreds of Juvenile hormone their analogs revealed no hormonal activity on spider mites belonging to the class Acarina of Although numerous natural substances the arthropod phylum, even though these regulate the growth and development of phytophagous mites which are serious insects, the juvenile hormones (JH) have been agricultural pests exhibit a complex singled out for refinement of their biological metamorphosis comparable with that of and chemical properties by synthesis of insects (Staal, 1975). Although it is chemical analogs which are insect growth conceivable that crustacean and non-insect regulators. Historically, the major reasons for metamorphosis is regulated by known JH, the selection of JH as a rational lead for perhaps so tightly protein-bound as to elude pesticide design were the beliefs Williams detection, it is more reasonable to presume (1967) that this hormone occurred in insects, that molecules other than the known JH may that it had a specific function in insects, and be responsible for the regulation of that it did not occur in higher animals. The metamorphosis of arthropods other than implication was that juvenile hormone would insects. Though several workers have searched therefore be selectively active in insects. for effects of insect JH on nematodes, no Although current knowledge strongly supports clearly hormonal effects have been the beliefs, we have no formal proof that JH demonstrated Hatakoshi (1998). The does not occur outside the class of insects. It widespread distribution of substances identical may be philosophically impossible to obtain with insect molting hormones has been well proof since we are only able to say that JH has documented and reviewed Gelman (1995), but not yet been identified in other organisms, in contrast the insect JH appear to be quite within the detection limits of our restricted to the insects. instrumentation. The real problems are that very few species have been extracted and Diacylhydrazines examined in chemical detail, and that numerous plants and animals are already Dibenzoylhydrazine (DBH) (Diacylhydrazine) known to contain sesquiterpene like molecules compounds are nonecdysteroidal activators of which possess weak JH activity. To pursue the ecdysone receptor complex [heterodimer

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Int.J.Curr.Microbiol.App.Sci (2019) 8(12): 208-218 of ecdysone receptor (EcR) and ultraspiracle/ assays. Firstly, halofenozide was used retinoid-X-receptor (USP/RXR)] in insects. successfully against soil-dwelling Their use as insecticides is based on their coleopterans, such as scarabid beetles, in spite capacity to induce a premature and incomplete of their rather low activity in binding assays moult during which susceptible insects die using in vitro produced coleopteran EcR/USP from desiccation and starvation. DBH (RXR) protein or reporter assays using compounds can be applied to the field because coleopteran cell lines. of their favourable physicochemical and biological properties, such as high Secondly, it was observed that, while activities hydrophobicity, which allows the penetration of DBH compounds in reporter assays were of the cuticle and the midgut of the insects, nearly identical using cell lines derived from and their slow clearance from the insect‟s the silkmoth Bombyxmori (Bm5 cells) and the body, resulting in persistence of action. In cotton leafworm Spodopteralittoralis(Sl2 addition, DBHs have a high safety profile, cells), great differences were observed in which is compatible with their use in toxicity assays between larvae of these integrated pest management (IPM) lepidopteran species. programmes. Various studies revealed that the prototype All commercial ecdysone agonists used in ecdysteroid against RH-5849 presented high IPM are DBH analogues, such as activity in species of Lepidoptera and (RH-5992), methoxyfenozide (RH-2485), Coleoptera, but were superseded later by RH- halofenozide (RH-0345) and chromafenozide 5992, RH-2485 and RH-0345, which have (ANS-118). The ecdysteroid agonist RH-0345 enhanced activity against lepidopteran and (halofenozide) represents a new class of IGRs, coleopteran pest insects. The ecdysteroid which has been developed to provide safe against compounds exert their toxicity by insecticides with high activity in Coleoptera. binding to the nuclear ecdysteroid receptor Agrochemical research has resulted in the EcR as does the natural insect moulting discovery of novel insecticides that act on hormone, 20-hydroxyecdysone (20E). selective biochemical sites present in specific insect groups. Good examples are the insect Moulting hormones growth regulators (IGRs), ecdysteroid agonists, which affect the hormonal regulation The brain/molting hormone ecdysone initiates of moulting and development processes. the molting process and induces metamorphosis. DBH compounds are considered to be highly specific to lepidopteran insects, although Precocenes halofenozide is also marketed for control of coleopteran pests. According to in vitro The compounds which would antagonize the reporter assays for activation of EcR/USP insect hormone activity and derange the (RXR) in insect cell lines, activities of DBH insect‟s development are called as compounds differ by orders of magnitude “Precocenes” because of their ability to induce between lepidopteran versus coleopteran and precocious metamorphosis of the immature dipteran insects. However, recent observations insects. The mode of action of precocenes have indicated that in vivo parameters can seems to be the prevention of JH biosynthesis play a large role in determining the efficacy of corpora allata, since application of exogenous a compound, which cannot be predicted by the JH can reverse their action. activity of the compounds in vitro reporter 212

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Some of the agricultural pests used for the Maharashtra, Gujarat, Karnataka, Madhya insects growth regulator activity Pradesh, Punjab, Rajasthan, Haryana, Tamil Nadu and Uttar Pradesh. This crop is severely Spodopteralitura attacked by number of pests. Red cotton bug or cotton stainer or red seed bug is a colourful Spodopteralitura is also known as the Oriental bug in the family pyrrhocoridae. Seriously leafworm moth, Cluster caterpillar, Cotton affects the crop yield and quality of fruits leafworm, Tobacco cutworm, Tropical thereby reducing the market value of cotton. armyworm, Taro caterpillar, Tobacco Besides cotton, it feeds on variety of plants. budworm, Rice cutworm, and Cotton Female (20 mm) is longer than male (18 mm). Cutworm. This moth is found in Asia, with some specific problematic pest population Scientific classification reports occurring in Cambodia, Hong Kong, India, the Pacific islands, Guam, American Phylum: Arthropoda Samoa, and Hawaii. In Australia, it is found in Subphylum: Uniramia northern two thirds of the country. It is not Class: Insecta established in the United States; however, it is Order: Heteroptera a pest of national, regulatory concern. Based Family: Pyrrhocoridae on the available geographic records of this Subfamily: Pyrrhocorinae moth, it is predicted that 48 Per cent of the Genus: Dysdercus U.S. will be suitable for survival of this moth. Species: Dysdercuskoenigii This pest is considered to be of concern from a regulatory perspective. It is believed to have IGRS from neem potentially high economic impact in terms of its direct pest damage, trade implications, high Leaf and seed extracts of neem which contains outbreaks or problems on new hosts. azadirachtin as the active ingredient, when applied topically causes growth inhibition, Scientific classification malformation, mortality and reduced fecundity in insects. Kingdom: Animalia Phylum: Arthropoda Hormone mimics from other living Class: Insecta organisms Order: Lepidoptera Family: Noctuidae Ecdysoids from plants (Phytoecdysones) have Genus: Spodoptera been reported from plants like mulberry, ferns Species: Spodopteralitura and conifers. Juvenoids have been reported from yeast, fungi, bacteria, protozoans, higher Cotton bug (Dysdercuskoenigii) animals and plants.

It is serious pest of cotton which infests cotton Carvacrol in all the cotton growing regions of India. The red cotton bug, Dysdercusis a most important Recent studies have indicated that Carvacrol damaging pest of okra also in North Eastern has anti-hapatocarcinojenic activities; Hep G2 Hill region. Both the adults and nymphs feed cell growth by inducing apoptosis as shown by on developing fruits of Cotton Gossypium Hoechst 33258 strain and flow cytometric hirsutum Linn. (Malvaceae), the major crop of (FCM) analysis. Apoptosis by direct activation India and grown on large scale in of mitochondrial pathway and the mitogen 213

Int.J.Curr.Microbiol.App.Sci (2019) 8(12): 208-218 activated protein kinase pathway has been have broad insecticidal and acaricidal activity suggested to play important role in antitumor against agricultural, stored-product, and effect of Carvacrol. The first report on medical arthropod pests. identification of the antiproliferal effects of Carvacrol in prostate cancer cells has stated Carvacrol derivatives in pest management that the carvacrol may be valuable as the potential the therapeutic agents for prostate Series of Carvacryl ethers and esters have cancer. These are the importance of Carvacrol been synthesized and evaluated as in Pest Management. Monoterpenoids can antibacterial agents. Modifications into some induce several types of biological activates in of these derivatives exhibited potential for pests. They are relatively safer group of developing as antifungal and antibacterial natural products. Monoterpenoids are ten agents. Synthetic derivatives of carbon hydrocarbons or related compounds monoterpenoids have been reported as leads having hydroxyl, carbonyl, carboxylic for new insect-control agents by Roller functional groups which can be relatively (1988). The results obtained through easily modified to various derivatives. They systematic bioassay and structure-activity are naturally occurring and exists abundantly relationships indicated that the in plants, marine algae and insects. More than monoterpenoids and their synthetic derivatives 1000 Monoterpenoids have been identified so have a relatively wide spectrum of activity far and many possess interesting chemical against agricultural and public health insect ecological properties. They are typically rather pests, the acyl derivatives of the more lipophillic compounds and thus may monoterpenoids, has been reported to have interfere with basic metabolic, biochemical, significantly improved the acute, fumigant, physiological & behavioral functions of larvicidal and ovicidal activities against insects. They have shown toxicity to insects insects. The ether derivatives exhibited but most of them are less toxic to mammals. enhanced insecticidal activity. Some of them Several monoterpenoids are included on the exhibited insect growth and development generally recognized as safe (GRAS) list in activity against mosquito larvae. Our research U.S.A. and they are used as artificial group has emphasized mainly on the flavouring agents in food, as fragrances in preparation characterization and biological cosmetics and as pharmaceuticals. activities of derivatives of the two phenolic monoterpenoids, Thymol and Carvacrol. As part of search for natural insecticides useful for fruit and vegetable plant protection, A piece of research work on Carvacrol is on insecticidal activities of 23 water-distilled ether and ester derivatives and includes essential oils and their principal compounds antifungal, antibacterial activities on plant including carvacrol have been reported by pathogenic microorganisms as well as Sampson et al., From the outcome it has been insecticidal activities against stored grain suggested that aphids such as Turnip aphids pests. Carvacryl esters were found to be most that are resistant to conventional active against plant pathogenic bacteria. insecticides and Lipaphis Carvacryl acetate and carvacryl allyl ether and pseudobrassicae which is also vectors ca 10 thymyl 4-methoxybenzylideneaniline non-persistent crucifer viruses can be exhibited comparable antibacterial activity controlled easily with them and essential oils with standard streptocyclin against and further noted with their novel, highly A.radiobacter and P.solanacearum (Fig. 1–6). bioactive compounds can be developed as insecticides. Carvacrol had also been shown to 214

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Fig.1 Classification of insect growth regulators

Fig.2 Market available chitin synthesis inhibitor / benzoyl phenyl urea compounds

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Fig.3 Juvenile Hormone I, II and III Compounds

Fig.4 Diacylhydrazines as moulting hormone

Fig.5 Moulting hormones α-ecdysone and ecdysterone

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Fig.6 Precocenes I, II and III

These are the advantages of using IGRs; References effective in minute quantities and so are economical Target specific and so safe to Ascher, K.R. 1993. Nonconventional natural enemies Bio-degradable, non- insecticidal effects of pesticides persistent and non-polluting Non-toxic to available from the neem tree, humans, animals and plants. Most synthetic Azadirachta indica. Arch. Insect insecticides are toxic to all animals including Biochem. Physiol. 22: 433-449. human beings. Although many insecticides Asai, T.A., M. Kajihara, F. Fukada and S. can be used safely, a few are persistent in the Makekawa. 1985. Studies on the mode environment and a small number have of action of II. Effects on multigenic, carcinogenic and teratogenic reproduction of the brown planthopper, effects on human beings and domestic NivaparvatalugensStal (Homoptera: animals. Furthermore, their magnification in Delphacidae). Appl. Entomol. Zool. 20: the food chain sometimes threatens non-target 111-117. organisms. These facts have become of deep Awad, T.I., F. Önder and fi. Kısmalı. 1998. concern to agricultural and health scientists, Azadirachtaindica A. Juss (Meliaceae) producers and consumers alike. Based on the a¤acındaneldeedilendo¤alpestisitlerüze previous discussion, IGRs represent the rindebirinceleme. Türk. Entomol. newest of all approaches to operational and Derg. 22: 225-240. commercial insect control. Their species or Bull, D.L. and R.W. Meola. 1993. Effect and stage-specificities that were higher than those fate of the insect growth regulator of conventional insecticides offer a good after application to the alternative for a selective insect pest control horn fly (Diptera: Muscidae). J. Econ. that is in harmony with existing IPM Entomol. 86: 1754-1760. programs. IGRs generally have a good margin Carton, B., G. Smagghe and L. Tirry. 2003. of safety for most non-target biota including Toxicity of two ecdysone agonists, invertebrates, fish, birds, and other wildlife. halofenozide and metoxyfenozide, They are relatively safe for human beings and against the multicolored Asian lady domestic animals. beetle, Harmonia axyridis, (Col.,

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How to cite this article:

Sanjay Cyril Masih and Bhat Rayees Ahmad. 2019. Insect Growth Regulators for Insect Pest Control. Int.J.Curr.Microbiol.App.Sci. 8(12): 208-218. doi: https://doi.org/10.20546/ijcmas.2019.812.030

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