Insecticides with novel modes of action: Mechanism, selectivity and cross-resistance

Efforts have been made during the past two decades to develop insecticides with selective properties that act specifically on biochemical sites present in particular insect groups, but whose properties differ from other insecticides. This approach has led to the discovery of compounds that affect the hormonal regulation of molting and developmental processes in insects; for example, ecdysone agonists, juvenile hormone mimics and chitin synthesis inhibitors. In addition, compounds that selectively interact with the insect nicotinic acetylcholine receptor, such as imidacloprid, acetamiprid and thiamethoxam, have been introduced for the control of aphids, whiteflies and other insect species. Natural products acting selectively on insect pests, such as avermectins, spinosad and azadirachtin, have been introduced for controlling selected groups of insect pests. Compounds acting on the nervous site that controls the sucking pump of aphids and whiteflies, such as pymetrozine, or respiration, such as diafenthiuron, have been introduced for controlling sucking pests. All the above compounds are important components in pest and resistance management programs.     

Evaluation of juvenile hormone analogues as rodent feed-through insecticides for control of immature phlebotomine sandflies

The juvenile hormone analogues methoprene and pyriproxyfen were evaluated as rodent feed-through insecticides for control of immature stages of the sandfly Phlebotomus papatasi Scopoli (Diptera: Psychodidae). The development and survival of P. papatasi second-instar larvae fed faeces from Syrian hamsters, Mesocricetus auratus, that had been fed a diet containing methoprene (0, 9.788, 97.88 or 978.8 p.p.m.) or pyriproxyfen (0, 9.82, 98.2 or 982 p.p.m.) were evaluated. The faeces of methoprene-treated hamsters greatly reduced the percentage of larvae that pupated at all concentrations tested and prevented adult emergence at all but the lowest concentration (9.788 p.p.m.). Pyriproxyfen prevented both pupation and adult emergence at all concentrations tested. The results of this study suggest that a control strategy using rodent baits containing juvenile hormone analogues to control phlebotomine sandflies that live in rodent burrows and feed on rodent faeces may be possible. As rodent reservoirs and vectors of Leishmania major live in close association in many parts of the Middle East, control of the transmission of the agent of zoonotic cutaneous leishmaniasis may also be possible.     

Enantiomeric Separations of Pyriproxyfen and its Six Chiral Metabolites by High‐Performance Liquid Chromatography

Pyriproxyfen is a chiral insecticide, and over 10 metabolites have been identified in the environment. In this work the separations of the enantiomers of pyriproxyfen and its six chiral metabolites were studied by high‐performance liquid chromatography (HPLC). Both normal phase and reverse phase were applied using the chiral columns Chiralpak IA, Chiralpak IB, Chiralpak IC, Chiralcel OD, Chiralcel OD‐RH, Chiralpak AY‐H, Chiralpak AD‐H, Chiracel OJ‐H, (R,R)‐Whelk‐O 1, and Lux Cellulose‐3. The effects of the chromatographic parameters such as mobile phase composition and temperature on the separations were investigated and the enantiomers were identified with an optical rotation detector. The enantiomers of these targets could obtain complete separations (resolution factor Rs > 1.5) on Chiralpak IA, Chiralpak IB, Chiralcel OD, Chiralpak AY‐H, or Chiracel OJ‐H under normal conditions. Chiralcel OJ‐H showed the best chiral separation results with n‐hexane as mobile phase and isopropanol (IPA) as modifier. The simultaneous enantiomeric separation of pyriproxyfen and four chiral metabolites was achieved on Chiralcel OJ‐H under optimized condition: n‐hexane/isopropanol = 80/20, 15°C, flow rate of 0.8 ml/min, and UV detection at 230 nm. The enantiomers of pyriproxyfen and the metabolites A , C , and D obtained complete separations on Chiralpak IA, Chiralpak IC, and Lux Cellulose‐3 under reverse phase using acetonitrile/water as the mobile phase. The retention factors (k) and selectivity factors (α) decreased with increasing temperature, and the separations were better under low temperature in most cases. The work is of significance for the investigation of the environmental behaviors of pyriproxyfen on an enantiomeric level. Chirality 28:245–252, 2016. © 2016 Wiley Periodicals, Inc.     

Effects of pyriproxyfen on ovarian development and fecundity ofRhagoletis pomonella flies

Three-day old female apple maggot flies,Rhagoletis pomonella (Walsh), were topically exposed to different doses (0.1, 1, 10, and 100 μg per fly) of a juvenile hormone mimic, pyriproxyfen, in the laboratory. Pyriproxyfen had little lethal effect on females except at the extremely high dose of 100 μg. It also had no significant effect on egg viability of treated females. A non-lethal dose of 1 μg per fly did, however, enhance significantly the fecundity (egg production) as well as the ovarian development (number of eggs in ovaries and length of egg folicles) of treated flies. We conclude that pyriproxyfen could be a useful aid in exploring endocrine regulation of feeding and reproductive physiology behavior inR. pomonella, about which current knowledge is scant.     

Effects of the juvenile hormone analog pyriproxyfen on German cockroach, Blattella germanica (L.), tergal gland development and production of tergal gland secretion proteins

Male German cockroaches possess secretory glands that secrete fluid into a pair of transverse depressions on the seventh and eighth abdominal tergites. We investigated the effects of altered juvenoid titer during the first part of the last instar on tergal gland secretory tissue development and the production of tergal gland secretion proteins. Male fifth (last) instar nymphs (1-3 days post-emergent) were topically treated with the JH analog pyriproxyfen. Light and transmission electron microscopy demonstrated that treatment with pyriproxyfen produced a visible decrease in the amount of tergal gland tissue present, a deformation of the overall shape of the gland located on tergite seven, and a less orderly arrangement of the secretory cells in the tissue. The protein fraction of tergal gland secretion was examined in pyriproxyfen-treated and control insects 1, 5, and 15 days after the insects molted to the adult stage. Amounts of all tergal secretion proteins were reduced in treated insects.     

Mispatterning in the ommatidia of Apis mellifera pupae treated with a juvenile hormone analogue

To further understand the function of morphogenetic hormones in honeybee eye differentiation, the alterations in ommatidial patterning induced by pyriproxyfen, a juvenile hormone (JH) analogue, were studied by scanning and transmission electron microscopy. Prepupae of prospective honeybee workers were treated with pyriproxyfen and the effects on ommatidial differentiation were described at the end of the pupal development. The results show that the entire ommatidia, i.e., the dioptric as well as the receptor systems, were affected by the JH analogue. The wave of ommatidial differentiation, which progresses from the posterior to the anterior region of the pupal eyes, was arrested. In treated pupae, the rhabdomeres only differentiated at the apical axis of the retinula, the secondary and tertiary pigment cells did not develop their cytoplasm protrusions, and the cone cell quartet did not pattern correctly. Simultaneously, an intense vacuolization was observed in cells forming ommatidia. In a previous study we showed that pyriproxyfen exerts an inhibition on pupal ecdysteroid secretion. In this sense, the arrested ommatidial differentiation in pyriproxyfen-treated pupae could be due to a secondary effect resulting from an alteration in pupal ecdysteroid titers.     

Effects of a juvenile hormone analog, pyriproxyfen, on the apterous form of Lipaphis erysimi

Effects of a juvenile hormone analog, pyriproxyfen, on various developmental stadia of the apterous form of the turnip aphid, Lipaphis erysimi (Kaltenbach), were bioassayed at three concentrations (50, 100, and 150 mg [AI]/l) in the laboratory. Supernumerary-molted nymphs with 1-3 extra molts were found when the first three nymphal instars were treated, and all these nymphs died prematurely. In contrast, all treated fourth instar nymphs molted normally to adults. The longevity of all pyriproxyfen-treated L. erysimi nymphs and adults and the fecundity of treated adults were reduced by 50%. Higher concentrations of pyriproxyfen (100 and 150 mg [AI]/l) caused sterility in adults from treated fourth instars; whereas the lowest concentration (50 mg [AI]/l) did not cause any adult sterility. A majority of adults from treated fourth instars and treated adults produced normal nymphs, and some adults produced dead nymphs with normal appendages or dead and deformed nymphs without any appendages. Normal nymphs produced by the adults from treated adults or treated at fourth instars developed more slowly from first instar to adult than the water-treated nymphs, and all adults in the new generation apparently reproduced normally. The potential role of pyriproxyfen in a vegetable aphid IPM program was discussed.     

Sublethal effects of pyriproxyfen,a juvenile hormone analogue,on Plutella xylostella (Lepidoptera: Plutellidae): life table study

The sublethal effects of pyriproxyfen (PYR, a juvenile hormone analogue) were investigated for two consecutive generations on life-history parameters, such as developmental time, pupal weight, fecundity, fertility and longevity of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae). After topical application bioassay of third instar larvae, the LC₂₅ and LC₅₀ values (as sublethal doses) were determined to be 1.49 and 2.01 μg/μl, respectively. The results showed that the egg incubation period, larval and pupal duration times and oviposition period were increased in treated groups compared with the control (treated with distilled water). Pupal weight, adult longevity, fecundity and fertility were significantly reduced in the treatment groups compared with the control. Using the age-stage, two-sex life table analysis, we found that the intrinsic rate of increase (r), finite rate of increase (λ), gross reproduction rate (GRR) and net reproductive rate (R ₀) significantly decreased while the mean generation time (T) and doubling time (DT) increased in two treatment groups compared with the control. In addition, administration of PYR induced morphogenetic abnormalities including untanned pupae, larval–pupal intermediates and various defective adults. The LC₅₀ value was more effective on all of the above biological characteristics than the LC₂₅ for both generations, although parents were more affected than the offspring. In general, our results revealed that PYR was highly effective against P. xylostella in the laboratory both directly (causing mortality) and indirectly (disruption of normal growth and development). We conclude that PYR is an excellent candidate for suppressing populations of P. xylostella through its sublethal effects.     

Growth of the male accessory gland in adult locusts: Roles of juvenile hormone,JH esterase,and JH binding proteins

The participation of juvenile hormone (JH) in the regulation of growth and protein synthesis in the accessory reproductive gland of male Locusta migratoria has been investigated. After elimination of endogenous JH with ethoxyprecocene, the accessory gland failed to grow, but growth was restored by a single application of the JH analog, pyriproxyfen. Pyriproxyfen appeared to stimulate total protein synthesis by 3 h, with a significant effect by 12 h, in contrast to 24 h observed in fat body. The dose curve for stimulation of protein synthesis 12 h after applying pyriproxyfen gave an ED₅₀ of 0.1 μg; the dose curve for gland growth at 72 h was biphasic, with steps at about 0.01 μg and 10 μg, suggesting two phases in JH action. SDS-PAGE analysis showed several components that were stimulated by pyriproxyfen, the effect being strongest in an 11 kDa band. A 5 kDa component was enhanced in the soluble and reduced in the particulate fraction after precocene treatment. The accessory gland contained JH esterase activity at levels about 100 times those in fat body or hemolymph, and was higher in precocene treated locusts. Binding activity for [³H]10R -JH III was high in cytosolic and nuclear fractions, and was identified immunologically as due to the previously described hemolymph JH binding protein. The results indicate that the mode of action of JH in the accessory gland may differ from that in the fat body. The presence of intracellular JH binding protein suggests a direct action of JH within the gland, that may be modulated by JH esterase. © 1995 Wiley-Liss, Inc.     

Laboratory Evaluation of the Lethal Efficacy of an Insect Growth Regulator, Pyriproxyfen against Anopheles sinensis (Diptera, Culicidae) Larvae

The granular formulation of 0.5% pyriproxyfen is a mosquito insect growth regulator larvicide. It was evaluated for residual activity for killing and/or emergence inhibition against 3rd stage larvae of Anopheles sinensis in the laboratory. Mortality rates ranged from 60.9% to 79.7% at 0.01, 0.05 and 0.1 mg/L of water during the first seven days. Except for the lowest concentration (0.01 mg/L) mortality rates were greater than 80% from day 8 through 28. Mortality rates for 0.01 mg/L concentrations were 70.4% from days 8‐14, and thereafter exceeded 80% through day 28. The residual activity gradually increased post‐treatment since the granular formulation of pyriproxyfen has a gradual solubility and increases concentration of active ingredient over time. The mortality rates of An. sinensis larvae and pupae eventually reached 100% for the three (0.01, 0.05, 0.1 mg/L) concentrations.