methoprene and fenoxycarb

Synthetic compounds that mimic the action of juvenile hormones (JHs) are founding members of a class of insecticides called insect growth regulators (IGRs). Like JHs, these juvenoids block metamorphosis of insect larvae to reproductive adults. Many biologically active juvenoids deviate in their chemical structure considerably from the sesquiterpenoid JHs, raising questions about the mode of action of such JH mimics. Despite the early deployment of juvenoid IGRs in the mid-1970s, their molecular effect could not be understood until recent discoveries of JH signaling through an intracellular JH receptor, namely the ligand-binding transcription factor Methoprene-tolerant (Met). Here, we briefly overview evidence defining three widely employed and chemically distinct juvenoid IGRs (methoprene, pyriproxyfen, and fenoxycarb), as agonist ligands of the JH receptor. We stress that knowledge of the target molecule is critical for using these compounds both as insecticides and as research tools.

Topics: Animals; Gene Expression Regulation, Developmental; Insecticide Resistance; Insecticides; Juvenile Hormones; Ligands; Metamorphosis, Biological; Methoprene; Phenylcarbamates; Pyridines; Structure-Activity Relationship

The frequent use of insecticides in vector control causes the development of insecticide resistance. Insect growth regulators (IGRs), which effect insect development, are used as a promising alternative to control resistant insect vectors. This study aimed to develop novel effective tools for Aedes aegypti control by evaluating the efficacy of different IGRs on larval development, blood feeding capacity, fecundity, and fertility in females and sperm productivity in males across geographical regions of Thailand.. The efficacy of 16 technical grade IGRs were evaluated against laboratory strain Ae. aegypti larvae in order to determine their emergence inhibition (EI) at 50% and 95% under laboratory conditions. Six IGRs were selected for fecundity, fertility, and sperm productivity studies using feed-through treatments at EI95 concentration levels against adult Ae. aegypti field strains.. The results from larval bioassay tests indicate that juvenile hormone mimics (EI50 = 0.010-0.229 ppb; EI95 = 0.066-1.118 ppb) and chitin synthesis inhibitors affecting CHS1 (EI50 = 0.240-2.412 ppb; EI95 = 0.444-4.040 ppb) groups effectively inhibited adult Ae. aegypti emergence. Methoprene and fenoxycarb significantly reduced blood feeding capacity. Egg production was comparable among strains while methoprene, pyriproxyfen and diflubenzuron induced egg production. Egg retention was detected in females fed on diflubenzuron. Methoprene, fenoxycarb, diflubenzuron, and teflubenzuron reduced egg hatching rates in mosquito field strains compared to laboratory strain. Male mosquitoes fed on fenoxycarb showed significantly lower sperm production compared to other treatments.. Juvenile hormone analogues and chitin synthesis inhibitors affecting CHS1 groups showed excellent results in adult emergence inhibition in this study. They also disrupted reproductive systems in both adult males and females. This study suggested that they can be used as an alternative larvicide in mosquito control programs.

Topics: Aedes; Animals; Chitin; Diflubenzuron; Female; Insecticides; Juvenile Hormones; Larva; Male; Methoprene; Mosquito Control; Mosquito Vectors; Phenylcarbamates; Semen; Thailand

Topics: Animals; Cladocera; Endocrine Disruptors; Humans; Insecticides; Juvenile Hormones; Methoprene; Phenylcarbamates; Reproduction; Survival Analysis; Water Pollutants, Chemical

Juvenile hormone analogue (JHA) insecticides are endocrine disrupters that interfere with hormonal action in insects by mimicking their juvenile hormones (JH). As the structure and functions of methyl farnesoate in crustaceans are similar to those of JH in insects, exogenous JHA insecticides could have adverse effects on the development and reproduction of crustaceans. This study examined the toxic effects of two JHA insecticides, fenoxycarb and methoprene, on a freshwater shrimp model of cherry shrimp, Neocaridina davidi. Both insecticides had detrimental effects on cherry shrimp, but fenoxycarb was more toxic than methoprene. Chronic exposure to these insecticides reduced the shrimp's body length and molting frequency. Based on transcriptome annotations for N. davidi, we identified important gene homologues that were active in both insect JH biosynthetic and degradative pathways as well as JH and ecdysteroid signaling pathways. Chronic treatments with JHAs had significant effects on these genes in N. davidi. Our transcriptomic analysis showed that genes involved in the pathways related to cuticle development, serine protease activity, and carbohydrate, peptide and lipid metabolic processes were differentially expressed in shrimp exposed to JHAs. These results demonstrate the toxicity of fenoxycarb and methoprene to freshwater crustaceans and indicate the need to monitor the use of JHA insecticides.

Topics: Animals; Decapoda; Endocrine Disruptors; Insecticides; Juvenile Hormones; Methoprene; Molting; Phenylcarbamates; Reproduction; Transcriptome

Daphnia magna has been used extensively to evaluate organism- and population-level responses to pollutants in acute toxicity and reproductive toxicity tests. We have previously reported that exposure to juvenile hormone (JH) agonists results in a reduction of reproductive function and production of male offspring in a cyclic parthenogenesis, D. magna. Recent advances in molecular techniques have provided tools to understand better the responses to pollutants in aquatic organisms, including D. magna. DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to JH agonists: methoprene (125, 250 and 500 ppb), fenoxycarb (0.5, 1 and 2 ppb) and epofenonane (50, 100 and 200 ppb). Exposure to these JH analogs resulted in chemical-specific patterns of gene expression. The heat map analyses based on hierarchical clustering revealed a similar pattern between treatments with a high dose of methoprene and with epofenonane. In contrast, treatment with low to middle doses of methoprene resulted in similar profiles to fenoxycarb treatments. Hemoglobin and JH epoxide hydrolase genes were clustered as JH-responsive genes. These data suggest that fenoxycarb has high activity as a JH agonist, methoprene shows high toxicity and epofenonane works through a different mechanism compared with other JH analogs, agreeing with data of previously reported toxicity tests. In conclusion, D. magna DNA microarray is useful for the classification of JH analogs and identification of JH-responsive genes.

Topics: Animals; Animals, Newborn; Daphnia; Dose-Response Relationship, Drug; Down-Regulation; Female; Gene Expression Regulation, Developmental; Gene Ontology; Juvenile Hormones; Male; Methoprene; Oligonucleotide Array Sequence Analysis; Phenylcarbamates; Reproduction; Terpenes; Toxicity Tests, Acute; Toxicity Tests, Chronic; Transcriptome; Up-Regulation

Use of Juvenile Hormone Analogues (JHA) in sericulture practices has been shown to boost good cocoon yield; their effect has been determined to be dose-dependent. We studied the impact of low doses of JHA compounds such as methoprene and fenoxycarb on selected key enzymatic activities of the silkworm Bombyx mori. Methoprene and fenoxycarb at doses of 1.0 microg and 3.0 fg/larvae/48 hours showed enhancement of the 5th instar B. mori larval muscle and silkgland protease, aspartate aminotransaminase (AAT) and alanine aminotransaminase (ALAT), adenosine triphosphate synthase (ATPase) and cytochrome-c-oxidase (CCO) activity levels, indicating an upsurge in the overall oxidative metabolism of the B.mori larval tissues.

Topics: Adenosine Triphosphatases; Alanine Transaminase; Animals; Aspartate Aminotransferases; Bombyx; Dose-Response Relationship, Drug; Electron Transport Complex IV; Energy Metabolism; Gene Expression Regulation, Developmental; Juvenile Hormones; Larva; Metamorphosis, Biological; Methoprene; Phenylcarbamates

During insect development, ecdysteroids and juvenile hormones (JHs) interact to regulate larval growth, metamorphosis and reproduction but the molecular mechanisms by which both hormones influence each other's activity remain unknown. Because of their ease of use and straightforward genetic manipulation, insect cell lines often have been used to clarify the actions and interactions of hormones at the molecular level. Here we report on the use of two insect culture cell lines, Drosophila melanogaster S2 and Bombyx mori Bm5 cells, to investigate two molecular processes in which ecdysteroids and JH have been shown to interact: (1) direct modulation of the activity of the ecdysteroid receptor transcription complex and (2) interference at the level of induction of the primary gene E75. Our data do not support JH analogs (JHAs) acting through the above processes: 'antagonism' of ecdysteroid receptor activity by JHAs correlated with cytotoxicity and induction of E75 expression by JHAs was not demonstrated. However, we confirm previous studies in which it was observed that methoprene can partially reverse the growth inhibition by 20E in S2 cells (but not Bm5 cells). Therefore, the molecular mechanism by which both hormones influence each other's activity to regulate cell growth in S2 cells remains unknown.

Topics: Animals; Bombyx; Cell Line; DNA-Binding Proteins; Dose-Response Relationship, Drug; Drosophila melanogaster; Drosophila Proteins; Humans; Insecticides; Juvenile Hormones; Methoprene; Phenylcarbamates; Protein Isoforms; Receptors, Steroid; Transcription Factors

Analogues of insect juvenile hormones (juvenoids) have been tested for settling inhibition of cyprids from three species of barnacle, Balanus balanoides (L.), Balanus improvisus Darwin and Balanus amphitrite Darwin. Some 3-alkoxypyridine derivatives exhibited strong activity at mg litre(-1) concentrations; 3,7-dimethyloctyl 2-methyl-5-pyridyl ether (8) gave an EC(50) of 0.006 mg litre(-1) when tested on B. balanoides. When compound 8 and similar juvenoids were incorporated into paints, test panels kept in seawater for 8 months were free of barnacles.

Topics: Animals; Fatty Acids, Unsaturated; Juvenile Hormones; Methoprene; Paint; Phenylcarbamates; Pyridines; Thoracica

A diverse set of reference compounds suspected of having an endocrine-disrupting mode of action (i.e., testosterone, flutamide, ethinylestradiol, precocene, nonylphenol, fenoxycarb, and methoprene) were tested for acute toxicity to the estuarine mysid Neomysis integer (Crustacea: Mysidacea). Neomysis integer was very sensitive to all tested compounds, with 96-h median lethal concentrations in a narrow range between 0.32 and 1.95 mg/L. The pesticides methoprene and fenoxycarb, both synthetic insect juvenile hormone analogs, were most toxic to N. integer. In addition, the short-term sublethal effects of methoprene and nonylphenol (an estrogen agonist) on the energy and steroid metabolism of N. integer were evaluated. Both compounds significantly affected energy and testosterone metabolism of N. integer at concentrations below acute toxicity levels. Energy consumption in methoprene- and nonylphenol-exposed mysids was significantly induced at 100 microg/L, resulting in a lower cellular energy allocation in these animals. Testosterone phase I metabolism was affected at 10 microg/L, whereas glycosylation was the most important phase II pathway affected in mysids exposed to 100 microg/L of both compounds. Methoprene exposure resulted in a concentration-dependent increase in the metabolic androgenization ratio. Mysids exposed to nonylphenol at 10 microg/L had a significantly higher metabolic androgenization ratio. The present study indicates that energy and testosterone metabolism of mysids, as endpoints, are able to detect endocrine-disruptive activity of chemicals after short-term exposure to environmentally realistic levels of endocrine disruptors.

Topics: Animals; Carbamates; Crustacea; Endocrine System; Energy Metabolism; Glycosylation; Lethal Dose 50; Methoprene; Multivariate Analysis; Pesticides; Phenols; Phenylcarbamates; Testosterone; Time Factors; Toxicity Tests, Acute; Water Pollutants, Chemical

Cat flea, Ctenocephalides felis felis (Bouché), adults exposed to sprays of methoprene, pyriproxyfen, or fenoxycarb as cocooned pupae emerged approximately 1 d earlier than adults from water-treated control pupae. Mortality of adult fleas, after exposure to juvenile hormone mimics as pupae, was increased over that of controls. Females had higher mortality than males within the first 48 h of feeding. Fecundity of females exposed as pupae to juvenile hormone mimics was not different from that of controls. Early emergence of preemerged adults from treated cocoons is discussed along with reasons for higher female susceptibility to juvenile hormone mimics.

Topics: Animals; Carbamates; Cats; Female; Fertility; Juvenile Hormones; Male; Methoprene; Phenylcarbamates; Pupa; Pyridines; Sex Characteristics; Siphonaptera

Sperm transfer into the epididymis was completed without a blood meal, when newly emerged male cat fleas. Ctenocephalides felis (Bouché), were exposed to filter papers treated with juvenile hormone III or the juvenile hormone mimics fenoxycarb, methoprene, or pyriproxyfen. As the concentration of juvenile hormone or the time of flea exposure to juvenile hormone or the juvenile hormone mimics increased, the percentage of fleas that transferred sperm also increased. The percentage of pyriproxyfen-treated males that transferred sperm reached 100% after 3 d: whereas, 7 d exposure to juvenile hormone, fenoxycarb and methoprene was required for 100% of the males to transfer sperm. Although sperm were present in the epididymis of treated fleas, insemination of females did not take place off the host either on juvenile hormone-treated filter paper or on juvenile hormone-treated dog hair.

Topics: Animals; Carbamates; Cats; Dogs; Eating; Epididymis; Female; Genitalia, Male; Insecticides; Insemination; Juvenile Hormones; Male; Methoprene; Molecular Mimicry; Phenylcarbamates; Pyridines; Sesquiterpenes; Siphonaptera; Spermatozoa; Testis

Applying the proinsecticide principle developed earlier for neurotoxic carbamate insecticides, a series of new N-sulfenylated, N-sulfinylated, and N-sulfonylated derivatives of fenoxycarb were synthesized and evaluated for juvenile hormone mimicking activity. Laboratory evaluations of the compounds using Pieris brassicae and Sitophilus oryzae, as well as field experiments using Bemisia tabaci, showed that several symmetrical biscarbamates with either a sulfenyl or sulfinyl bridge possessed higher activity than the parent carbamate. From the unsymmetrical compounds containing biologically inert derivatizing moieties, one of the sulfenylated biscarbamates also showed improved activity against P. brassicae. The changes in the biological activity of the sulfur-containing derivatives compared to that of the parent compound are attributed to the modified physicochemical characteristics, i.e., increased lipophilicity facilitating penetration, transport, as well as protection of the compound from metabolism.

Topics: Animals; Biological Assay; Butterflies; Carbamates; Coleoptera; Insecta; Insecticides; Juvenile Hormones; Molecular Mimicry; Molecular Structure; Phenylcarbamates; Prodrugs; Sulfur

The effects of juvenile hormone-III (JH-III) and the juvenile hormone analogues (JHA) methoprene and fenoxycarb on the growth and macromolecular biosynthesis in Trypanosoma cruzi were studied in vitro. It was observed that JH-III and JHA blocked growth and 3H-thymidine incorporation without killing the cells within certain concentrations (< or = 1 x 10(-4) M), but they caused cellular death at concentrations over 1 x 10(-3) M. The inhibitory effect on growth was partially reversible. On the other hand, the inhibitory action of JH-III, methoprene and fenoxycarb was an unspecific effect according to the results obtained with Leishmania mexicana mexicana (promastigotes) and human peripheral blood lymphocytes. The JHA have a good possibility of being used in the control of trypanosomiasis.

Topics: Animals; Carbamates; DNA, Protozoan; Humans; Insecticides; Juvenile Hormones; Leishmania mexicana; Lymphocytes; Methoprene; Phenylcarbamates; Protein Biosynthesis; Protein Precursors; Proteins; RNA Precursors; RNA, Protozoan; Thymidine; Trypanosoma cruzi

Three insect growth regulators, fenoxycarb, methoprene, and pyriproxyfen, formulated as total release aerosols, were tested for their residual effectiveness on carpet in bioassays with cat flea, Ctenocephalides felis (Bouché), larvae. All treatments except methoprene produced significant mortality for the 7-mo duration of the test. In general, fenoxycarb and the higher rates of pyriproxyfen reduced adult flea emergence by > 80%.

Topics: Animals; Carbamates; Cats; Floors and Floorcoverings; Insect Control; Insecticides; Juvenile Hormones; Larva; Lethal Dose 50; Methoprene; Pesticide Residues; Phenylcarbamates; Pyridines; Siphonaptera

The potential of insect growth regulators (methoprene, hydroprene, fenoxycarb, diflubenzuron and triflumuron) to control populations of the North American house-dust mite Dermatophagoides farinae (Hughes) was assessed in laboratory bioassays. Methoprene was most effective at suppressing population growth, especially at concentrations of 1.0% (10,000 ppm) and 5.0% (5000 ppm) active ingredient. Hydroprene, structurally related to methoprene, also suppressed house-dust mite populations but not as consistently as methoprene. Fenoxycarb may be effective at controlling house-dust mites but at greater concentrations than were tested. Diflubenzuron and triflumuron, two chitin-synthesis inhibitors, failed to suppress mite numbers and may, in fact, stimulate reproduction in some cases. Almost all concentration of the insect growth regulators were shown to be ineffective when assayed 90 days after treatment.

Topics: Animals; Benzamides; Biological Assay; Carbamates; Diflubenzuron; Dust; Fatty Acids, Unsaturated; Female; Insecticides; Juvenile Hormones; Male; Methoprene; Mites; Molecular Structure; North America; Phenylcarbamates

Topics: Animals; Bacillus thuringiensis; Bacterial Proteins; Carbamates; Cyprinodontiformes; Diflubenzuron; Insecticides; Killifishes; Lethal Dose 50; Methoprene; Mosquito Control; Phenylcarbamates; Temefos; Water Pollutants; Water Pollutants, Chemical

Four new insect growth regulators (IGRs) and a slow-release formulation of a currently-used IGR were evaluated for the control of Culex peus and Cx. quinquefasciatus in dairy wastewater lagoons. The IGR AC-291898 (CME 13406) proved highly efficacious, producing 100% control for one week and about 98% control for two weeks at the rate of 0.05 lb AI/acre (0.056 kg/ha). The IGR XRD-473 produced similar results at this rate. The effective rate of these two compounds seems to be in the range of 0.05 to 0.1 lb AI/acre (0.056-0.11 kg/ha). A granular formulation of S-31183 (0.5 G) applied at 0.05 lb AI/acre (0.056 kg/ha) yielded mediocre reduction whereas fenoxycarb EC 1 at up to 0.25 lb AI/acre (0.28 kg/ha) and methoprene 4% slow release pellets at up to 1.0 lb AI/acre (1.12 kg/ha) produced little or no control of Culex in the dairy wastewater lagoons. These compounds need to be applied at higher rates or suitable formulations will have to be developed to achieve satisfactory control.

Topics: Animals; Benzamides; California; Carbamates; Culex; Dairying; Dose-Response Relationship, Drug; Juvenile Hormones; Larva; Methoprene; Phenylcarbamates; Phenylurea Compounds; Sewage