Low Mammalian Toxicity Research Articles

Energy-converting biomaterials for cancer therapy: Category, efficiency, and biosafety.

Energy-converting biomaterials (ECBs)-mediated cancer-therapeutic modalities have been extensively explored, which have achieved remarkable benefits to overwhelm the obstacles of traditional cancer-treatment modalities. Energy-driven cancer-therapeutic modalities feature their distinctive merits, including noninvasiveness, low mammalian toxicity, adequate therapeutic outcome, and optimistical synergistic therapeutics. In this advanced review, the prevailing mainstream ECBs can be divided into two sections: Reactive oxygen species (ROS)-associated energy-converting biomaterials (ROS-ECBs) and hyperthermia-related energy-converting biomaterials (H-ECBs). On the one hand, ROS-ECBs can transfer exogenous or endogenous energy (such as light, radiation, ultrasound, or chemical) to generate and release highly toxic ROS for inducing tumor cell apoptosis/necrosis, including photo-driven ROS-ECBs for photodynamic therapy, radiation-driven ROS-ECBs for radiotherapy, ultrasound-driven ROS-ECBs for sonodynamic therapy, and chemical-driven ROS-ECBs for chemodynamic therapy. On the other hand, H-ECBs could translate the external energy (such as light and magnetic) into heat for killing tumor cells, including photo-converted H-ECBs for photothermal therapy and magnetic-converted H-ECBs for magnetic hyperthermia therapy. Additionally, the biosafety issues of ECBs are expounded preliminarily, guaranteeing the ever-stringent requirements of clinical translation. Finally, we discussed the prospects and facing challenges for constructing the new-generation ECBs for establishing intriguing energy-driven cancer-therapeutic modalities. This article is categorized under: Nanotechnology Approaches to Biology >Nanoscale Systems in Biology.

Cloning of a novel topramezone-resistant 4-hydroxyphenylpyruvate dioxygenase gene and improvement of its resistance through pressure acclimation

Topramezone is a new 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicide that is widely used on corn to control annual grass weeds and broadleaf weeds. Due to its broad-spectrum weed control capacity, improved activity, excellent crop selectivity, low mammalian toxicity and high environmental safety, topramezone is considered an ideal target herbicide for transgenic engineering of herbicide tolerance. In this study, a topramezone-resistant strain, Burkholderia sp. BW-1, was screened from soil, and a novel topramezone-resistant HPPD gene (Bkhppd) was cloned from this strain. Purified BkHPPD displayed relatively high HPPD activity and topramezone resistance with a half-maximal inhibitory concentration (IC50) of 572.0 nM. Two BkHPPD mutants designated as BkHPPDt31 and BkHPPDt76 were screened through pressure acclimation. BkHPPDt31 contained three amino acid substitutions (H65D, N160 T and N258S), whereas BkHPPDt76 contained four amino acid substitutions (H65D, N160 T, N258S and N343 T). The topramezone IC50 values of BkHPPDt31 and BkHPPDt76 were 1.1- and 2.3-fold higher, respectively, than that of wild-type BkHPPD. In addition, site-directed mutagenesis indicated that the increased resistance conferred by BkHPPDt31 resulted from the synergistic effects of the three site mutations rather than a single site mutation, and that substitution of asparagine 343 with threonine significantly decreased catalytic efficiency and affinity but increased topramezone resistance. In summary, this study provides a novel topramezone-resistant HPPD gene for the engineering of genetically modified herbicide-resistant crops and facilitates further elucidation of the resistance mechanism of BkHPPD and improvement of resistance through directed evolution.

How Plants Synthesize Pyrethrins: Safe and Biodegradable Insecticides.

Natural pyrethrin insecticides produced by Dalmatian pyrethrum (Tanacetum cinerariifolium) have low mammalian toxicity and short environmental persistence, providing an alternative to widely used synthetic agricultural insecticides that pose a threat to human health and the environment. A recent surge of interest in the use of pyrethrins as agricultural insecticides coincides with the discovery of several new genes in the pyrethrin biosynthetic pathway. Elucidation of this pathway facilitates efforts to breed improved pyrethrum varieties and to engineer plants with improved endogenous defenses or hosts for heterologous pyrethrin production. We describe the current state of knowledge related to global pyrethrum production, the pyrethrin biosynthetic pathway and its regulation, and recent efforts to engineer the pyrethrin pathway in diverse plant hosts.

Fluazaindolizine mitigates plant-parasitic nematode activity at sublethal dosages

Plant-parasitic nematodes are significant pests for many crops with considerable economic impact worldwide. Alternatives to highly toxic soil fumigants and nematicides are urgently sought after. Fluazaindolizine is a fluorinated nematicide with a novel, unknown mode-of-action and very low mammalian toxicity. The current research investigated the early responses of several plant-parasitic nematode species to the compound by in vitro mortality and parasitism trials with nematode-susceptible host plants. After a 72-h in vitro exposure time, fluazaindolizine exhibited the most potent toxic activity against the second-stage juveniles (J2) of Meloidogyne incognita and Tylenchulus semipenetrans with LC50 values of 177.14 and 355.2 mg L−1, respectively. Pratylenchus brachyurus, J2 of the Heterodera schachtii, and eggs of M. incognita were considerably less sensitive to the nematicide. The fitness of M. incognita J2 was strongly affected when exposed to various concentrations of fluazaindolizine for 12 h before inoculation of cucumber seedlings in soilless seed pouches. The lowest level of 5 mg L−1 reduced root galling, egg mass production, and the number of eggs to about 25% compared to the water control. In another bioassay, H. schachtii J2 were exposed to fluazaindolizine at 100 and 200 mg L−1 for 72 h before used to infest soil with 3-day-old radish seedlings. About 39.8% and 59.6%, respectively, fewer J2 invaded the roots compared to the control. In conclusion, the tested nematode species varied considerably in their in vitro mortality following fluazaindolizine exposure. However, the bioassays demonstrated that parasitism was already severely impacted at non-lethal concentrations and short-term exposure to the nematicide.

Evaluation of three new insecticide formulations based on inert dusts and botanicals against four stored-grain beetles

Three new insecticide formulations were developed that combine diatomaceous earth (Celatom MN 23) with compounds with low mammalian toxicity. Sitophilus oryzae, Sitophilus granarius, Rhyzopertha dominica and Tribolium castaneum were held on wheat (13.5% moisture content) treated with different doses of the formulations at 28 ± 1 °C and 60 ± 5% RH for 2–7 days, and then held for progeny emergence. The three formulations were made up of: dill essential oil, bait, silica gel and DE (Dill-DE); pyrethrin, PBO, dill essential oil, silica gel and DE (Py-Dill-DE); and disodium octaborate tetrahydrate (DOT), pyrethrin, PBO, dill essential oil, silica gel and DE (DOT-PY-Dill-DE). They were applied either as powders or as slurries. Applying the formulations as powders over a range of concentrations showed that pure DE is the least effective insecticide, with 50% mortality ranging from 430 to 1000 ppm depending on the species after 2–3 days. Dill-DE formulation was the next least effective formulation. The Py-Dill-DE and DOT-Py-Dill-DE formulations had similar activity and being the most effective formulations with 50% mortality from 40 to 260 ppm depending on the species. Bioassays were also run at single doses. Dill-DE was applied at 300 ppm, Py-Dill-DE at 150 ppm and DOT-PY-Dill-DE at 200 ppm. After 3 days, Py-Dill-DE and DOT-PY-Dill-DE formulations there was 100% mortality for S. oryzae, S. granarius and R. dominica. After 7 days the mortality of T. castaneum was from 96 to 100%. Both formulations reduced the progeny almost by 100%. There was survival for all insects with Dill-DE formulation. The concentrations of 150 ppm of Py-Dill-DE, 200 ppm of DOT-PY-Dill-DE and 300 ppm of Dill-DE reduced bulk densities by 0.7, 0.8 and 5.7 kg/hL, respectively.

Detrimental effects of temephos on male fertility: An in vitro study on a mouse model

The World Health Organization recommends temephos as a nonsystemic organophosphorus pesticide due to its low mammalian toxicity compared with other chemical compounds. Although several studies have reported that temephos may be toxic under certain conditions, little research effort has been made to evaluate its effects on mammalian fertility. Therefore, the present study was designed to evaluate the effect of temephos on sperm functions and male fertility. Initially, cauda epididymis from mouse spermatozoa was incubated with temephos (0, 0.1, 1, 10, and 100 μM). Then, sperm motility and motion kinematics, capacitation status, intracellular adenosine triphosphate level, lactate dehydrogenase level, protein kinase A (PKA) activity, and degree of tyrosine phosphorylation were analyzed. Finally, the rates of fertilization and early embryonic development were evaluated. Sperm motility and motion kinematics were found to be significantly altered in temephos groups. In addition, the acrosome reaction and capacitation significantly increased and decreased in the 100 μM temephos group, respectively. Intracellular adenosine triphosphate levels significantly decreased in the 1, 10, and 100 μM temephos groups compared with that in the control group. Moreover, PKA activity and tyrosine phosphorylation significantly decreased in most temephos groups. Further, the rates of fertilization and early embryonic development significantly decreased in all temephos groups. Taken together, it was determined that temephos had harmful effects on male fertility. Therefore, the reproductive toxicity of temephos should be considered before its use.

Insecticidal activity of ring-fluorinated benzyl acetone analogs in Queensland fruit fly, a softer class of insecticides

Insecticides used to control fruit fly pests have been implicated in negative effects on natural enemies, human health and the environment. As potential ‘softer’ insecticides, natural compounds such as essential oils and their constituents have received increased attention as insecticide candidates. Queensland fruit fly (Q-fly), Bactrocera tryoni (Froggatt), is the most economically damaging fruit fly species in Australia. Cuelure and melolure are plant-based attractants of males in Q-fly and many other dacine fruit flies and are structurally similar to benzyl acetone. We hypothesized that fluorination of benzyl acetone would introduce toxicity that could be exploited for insecticidal applications. Toxicity to Q-fly of nine fluorinated analogs of benzyl acetone as well as the known attractants cuelure and melolure was investigated. LC50 and LC90 values of the compounds were obtained using a surface-film assay method. Fluorination at the meta and/or para-position of benzene ring was found to increase toxicity to both Q-fly sexes. We further examined toxicity and short-range attraction to Q-fly using traps in outdoor cages. The nine fluorinated analogs of benzyl acetone were all highly toxic to male Q-flies, whereas cuelure and melolure were not. Some analogs were attractive to male Q-flies. None of the nine analogs, cuelure or melolure had an inhibitory effect on the proliferation of BEAS-2B human bronchial epithelial cells, suggesting very low or negligible mammalian toxicity. Fluorinated analogs of benzyl acetone have potential as new toxicants for Q-fly, and likely other insects, and some may also have attractive properties for cuelure-responding fruit flies.

Chronology of sodium channel mutations associated with pyrethroid resistance in Aedes aegypti.

Aedes aegypti is the primary mosquito vector of dengue, yellow fever, Zika and chikungunya. Current strategies to control Ae. aegypti rely heavily on insecticide interventions. Pyrethroids are a major class of insecticides used for mosquito control because of their fast acting, highly insecticidal activities and low mammalian toxicity. However, Ae. aegypti populations around the world have begun to develop resistance to pyrethroids. So far, more than a dozen mutations in the sodium channel gene have been reported to be associated with pyrethroid resistance in Ae. aegypti. Co-occurrence of resistance-associated mutations is common in pyrethroid-resistant Ae. aegypti populations. As global use of pyrethroids in mosquito control continues, new pyrethroid-resistant mutations keep emerging. In this microreview, we compile pyrethroid resistance-associated mutations in Ae. aegypti in a chronological order, as they were reported, and summarize findings from functional evaluation of these mutations in an in vitro sodium channel expression system. We hope that the information will be useful for tracing possible evolution of pyrethroid resistance in this important human disease vector, in addition to the development of methods for global monitoring and management of pyrethroid resistance in Ae. aegypti.

Combined Effect of Methanol Extracts and Essential Oils of Callistemon rigidus (Myrtaceae) and Eucalyptus camaldulensis (Myrtaceae) against Anopheles gambiae Giles larvae (Diptera: Culicidae)

Biopesticides from botanicals are nowadays actively encouraged in the mosquito control program because of their low mammalian toxicity, biodegradability, and target specificity. However, leaf methanolic extracts and essential oils of Callistemon rigidus and Eucalyptus camaldulensis were evaluated individually and in combination on third- and fourth-instar larvae of Anopheles gambiae. The extracts were tested individually and in combination at doses of 125, 250, 500, and 1000 ppm while essential oils were applied at 25, 50, 100, and 200 according to the standard protocol of WHO. The commercial insecticide Bi-one tested at the recommended dose of 1000 ppm was used as positive control while the solution of tap water containing 0.5 ml of methanol was used as negative control. The mortality of the larvae was recorded after 24 h postexposure. In the results, 100% mortality of the larvae was recorded with the extracts of C. rigidus and the combinations E50% : C50% and E25% : C75% of the plants as well as positive control (1000 ppm). Similarly, essential oils of the two plants and their combinations caused 100% mortality of the larvae. Among the various combinations of the extracts and essential oils, only the combination E75% : C25% of essential oils presented a synergistic effect. Therefore, the essential oil combination (E75% : C25%) of the plants E. camaldulensis and C. rigidus is recommended in order to promote the its use in the form of natural biocide in the implementation of effective insect controls against the mosquito larvae, vector of malaria.

Etoxazole induces testicular malfunction in mice by dysregulating mitochondrial function and calcium homeostasis

Epidemiological relationships between pesticide use and male infertility have been suggested for a long time. Etoxazole (ETX), an oxazoline pesticide, has been extensively used for pest eradication. It is considered relatively safe and has low mammalian toxicity because it specifically inhibits chitin synthesis. However, ETX may have toxic effects on the reproductive system. In this study, we examined the effects of ETX on the reproductive system using mouse testis cell lines (TM3 for Leydig cells and TM4 for Sertoli cells) and C57BL/6 male mice. We confirmed that ETX has anti-proliferative effects on the TM3 and TM4 cell lines. Moreover, ETX induced mitochondrial dysfunction and hampers calcium homeostasis. Western blot analysis of MAPK and Akt signaling cascades was performed to demonstrate the mode of action of ETX at a molecular level. Moreover, ETX induced misregulation of genes related to testicular function. Upon oral administration of ETX in C57BL/6 male mice, testis weight was reduced and transcriptional expression related to testis function was altered. These results indicate that ETX induces testicular toxicity by inducing mitochondrial dysfunction and calcium imbalance and regulating gene expression.

Chinese star anise (Illicium verum) and pyrethrum (Chrysanthemum cinerariifolium) as natural alternatives for organic farming and health care- A review

Botanical insecticides keep attracting more attention from environmental and small farmers worldwide as they are considered as a suitable alternative to synthetic insecticides. The outstanding properties of pyrethrum include rapid action, low mammalian toxicity, broad spectrum of activity, lack of insect immunity, lack of persistence and of course effective insect repellent. Pyrethrum is a natural insecticide which has many properties, but the most important are rapid action, very low toxicity for mammalian, lack of insect immunity, broad of activity, lack of persistence and quick degradation by UV-sunlight and very effective insect repellent. Using natural pesticide may lead to organic farming, and advantage of organic farming is more beneficial to biodiversity and the environment, which reduces dietary exposure to pesticides. Chinese star anise has anti-bacterial and anti-fungal characters. It is useful in treatment of diseases like asthma, bronchitis and dry cough. One of its most compounds is Shikimic acid which is used as a drug in curing influenza and flu virus. It also consists of Linalool which is good for overall health because of its anti-oxidants characters. Its seeds are good source of minerals like calcium, iron, copper, potassium, manganese, zinc, and magnesium. The seeds are a great source of essential B-complex vitamins such as pyridoxine, niacin, riboflavin and thiamin. Chinese star anise is also a good source of anti-oxidant vitamins such as vitamin-C and vitamin-A. The essential oil of Star anise contains anethole which has shown several functional properties including antimicrobial, antioxidant, hypoglycemic, hypolipidemic and oestrogenic properties. Star anise primarily contains anethole and fatty oil. Its essential oil has a sweetish, burning flavor and a highly aromatic odor. Organic farmers may use these two ancient Chinese herbs which can lead to industrial sustainability.

The Phytochemical Composition of Melia volkensii and Its Potential for Insect Pest Management.

Due to potential health and environmental risks of synthetic pesticides, coupled with their non-selectivity and pest resistance, there has been increasing demand for safer and biodegradable alternatives for insect pest management. Botanical pesticides have emerged as a promising alternative due to their non-persistence, high selectivity, and low mammalian toxicity. Six Meliaceae plant species, Azadirachta indica, Azadirachta excelsa, Azadirachta siamens, Melia azedarach, Melia toosendan, and Melia volkensii, have been subject to botanical pesticide evaluation. This review focuses on Melia volkensii, which has not been intensively studied. M. volkensii, a dryland tree species native to East Africa, has shown activity towards a broad range of insect orders, including dipterans, lepidopterans and coleopterans. Its extracts have been reported to have growth inhibiting and antifeedant properties against Schistocerca gregaria, Trichoplusia ni, Pseudaletia unipuncta, Epilachna varivestis, Nezara viridula, several Spodoptera species and other insect pests. Mortality in mosquitoes has also been reported. Several limonoids with a wide range of biological activities have been isolated from the plant, including volkensin, salannin, toosendanin, trichilin-class limonoids, volkendousin, kulactone among others. This paper presents a concise review of published information on the phytochemical composition and potential of M. volkensii for application in insect pest management.

Evaluation of Resmethrin Toxicity to Neonatal Testes in Organ Culture.

Resmethrin is a widely used pyrethroid insecticide, which causes low toxicity in mammals. However, its toxicity in testes has not been fully investigated. Therefore, we evaluated the toxicity of resmethrin in mouse testes using an in vitro organ culture. Mouse testicular fragments (MTFs) derived from neonates were cultured in medium containing resmethrin for 30 days. Effects on spermatogenesis in the cultured testes were investigated as functions of both time and dose. Resmethrin significantly downregulated the transcription levels of marker genes for spermatogonia and the number of spermatogenic germ cells relative to those of the controls, according to quantitative PCR and immunostaining. In addition, spermatocyte was observed in the control, but not in 50 μM resmethrin-exposed cultures. Levels of the SYCP3 meiotic marker and phosphorylated H2AX decreased by resmethrin treatment, as observed by Western blotting. Toxic or apoptotic effects of resmethrin in Sertoli and Leydig cells from MTFs were not observed by immunostaining and Tunnel assay. No changes in the expression of steroidogenic enzymes were noted. Apoptosis was only detected in the germ cells of resmethrin-treated MTFs. Thus, the highest dose of resmethrin tested (50 μM) completely inhibited spermatogenesis, because of apoptosis of germ cells and spermatocytes. Although the in vivo toxicity of resmethrin has not yet been studied in detail, significant evidence for cytotoxicity was observed in our organ cultures. This methodological approach is useful for the study of reproductive toxicity before proceeding to animal models, as it greatly reduces the use of laboratory animals.

Synergistic enhancement of beta-lactam antibiotics by modified tunicamycin analogs TunR1 and TunR2.

The β-lactams are the most widely used group of antibiotics in human health and agriculture, but this is under threat due to the persistent rise of pathogenic resistance. Several compounds, including tunicamycin (TUN), can enhance the antibacterial activity of the β-lactams to the extent of overcoming resistance, but the mammalian toxicity of TUN has precluded its use in this role. Selective hydrogenation of TUN produces modified compounds (TunR1 and TunR2), which retain the enhancement of β-lactams while having much lower mammalian toxicity. Here we show that TunR1 and TunR2 enhance the antibacterial activity of multiple β-lactam family members, including penems, cephems, and third-generation penicillins, to a similar extent as does the native TUN. Eleven of the β-lactams tested were enhanced from 2 to >256-fold against Bacillus subtilis, with comparable results against a penicillin G-resistant strain. The most significant enhancements were obtained with third-generation aminothiazolidyl cephems, including cefotaxime, ceftazidime, and cefquinome. These results support the potential of low toxicity tunicamycin analogs (TunR1 and TunR2) as clinically valid, synergistic enhancers for a broad group of β-lactam antibiotics.

Early-life exposure to low levels of permethrin exerts impairments in learning and memory with the effects on neuronal and glial population in adult male mice.

Permethrin, a pyrethroid chemical, is widely used as a pesticide because of its rapid insecticidal activity. Although permethrin is considered to exert very low toxicity in mammals, the effects of early, low-level, chronic exposure on the adult central nervous system are unclear. In this study, we investigated the effects of low-level, chronic permethrin exposure in early life on the brain functions of adult mice, using environmentally relevant concentrations. We exposed mice to the acceptable daily intake level of permethrin (0.3ppm) in drinking water during the prenatal and postnatal periods. We then examined the effects on the central nervous system in adult male offspring. In the permethrin group, we detected behavior that displayed incomplete adaptation to a novel environment, as well as an impairment in learning and memory. In addition, immunohistochemical analysis revealed an increase in doublecortin- (an immature neuron marker) positive cells in the hippocampal dentate gyrus in the permethrin exposure group compared with the control group. Additionally, in the permethrin exposure group there was a decrease in astrocyte number in the hilus of the dentate gyrus, and remaining astrocytes were often irregularly shaped. These results suggest that exposure to permethrin at low levels in early life affects the formation of the neural circuit base and behavior after maturation. Therefore, in the central nervous system of male mice, low-level, chronic permethrin exposure during the prenatal and postnatal periods has effects that were not expected based on the known effects of permethrin exposure in mature animals.

Entomotoxic efficacy of aluminium oxide, titanium dioxide and zinc oxide nanoparticles against Sitophilus oryzae (L.): A comparative analysis

The development of resistance in both stored grain and field insect pests to conventional insecticides, coupled with increased consumer awareness of the consequences of their residual toxicity in food crops and environmental contamination have led agro-chemical researchers to reappraise the use of inert dusts as alternative insecticide. Diatomaceous Earth or DE became popular as an alternative insecticide in last two decades for its low mammalian toxicity and physical mode of action. But due to several limitations of DE many researchers are trying to explore the possibility of using nanoparticles as potential insecticide. In this study, a comparison on entomotoxic efficacy of different oxide nanoparticles like aluminium oxide, titanium dioxide and zinc oxide was evaluated on Sitophilus oryzae. Though more than 90% S. oryzae died after 4 days of nano aluminium oxide treatment at 1 g kg−1 dosage, nano zinc oxide and titanium dioxide treatment could attain this efficacy at 2 g kg−1 after 14 days. Even then use of nano zinc oxide and titanium dioxide in agriculture sector is preferred to nano aluminium oxide as the latter nanoparticle has adverse effects on plant growth. Moreover due to the antimicrobial property of nano zinc oxide and titanium dioxide have antimicrobial property, they will not only protect the agricultural produce from insect pests, but also from microbial infection.

Analytical performance for determination of synthetic pyrethroids residue in Indonesian fermented cocoa using GC-ECD

Pyrethroid insecticides are causing problems for the environment because they are toxic at such small concentrations and very difficult to determine. Characteristics of pyrethroids insecticides include high efficiency, wide spectrum, low biodegradability, and low mammalian and avian toxicity. They also demonstrate strong selectivity for insects and invertebrates. This study presents the results of the analysis conducted on four synthetic pyrethroids in fermented cocoa samples from Indonesia. The pesticides were extracted using acetonitrile and the analysis was carried out by Gas Chromatography with Electron Capture Detector (GC-ECD). Column programming temperature was conducted to get a complete separation. The total operation took less than 10 minutes to separate four standards of synthetic pyrethroids. The synthetic pyrethroids were identified by their retention times and quantified using an external calibration method. The linearity test was carried out for four standard synthetic pyrethroids, namely: lambda-cyhalothrin, permethrin, cypermethrin, and fenvalerate, from 1 μg/kg to 10 μg/kg. The coefficient of correlation (r) was found to be 0.9999; 0.9998; 0.9944; and 0.9999 for lambda-cyhalothrin, permethrin, cypermethrin, and fenvalerate, respectively. The detection limit for synthetic pyrethroids residue was found to be below the EU and Japan regulations, and the method can be applied for the determination of synthetic pyrethroids residues in fermented cocoa.

Pinene-rich essential oils from Haplophyllum dauricum (L.) G. Don display anti-insect activity on two stored-product insects

Continuous use of synthetic insecticides increases environmental contamination and resistance in many species. Botanical insecticides, such as essential oil, were considered to be suitable alternatives due to multiple modes of action and low mammalian toxicity. Haplophyllum dauricum is a overlooked plant for the control of stored-product insects. Five essential oils (EOs) from Haplophyllum dauricum collected in October and November, rich in pinene, were extracted and evaluated on anti-insect activity against two stored-product insects, Tribolium castaneum (Coleoptera: Tenebrionidae) and Lasioderma serricorne (Coleoptera: Anobiidae). The lethal doses (LD50 and LD90), lethal concentrations (LC50 and LC90) and percentage repellency (PR) were evaluated. The GC-MS analysis showed that pinene (α-pinene and β-pinene) were major constituent of the EOs (54.61% and 57.33% in fruits, 46.80% in stems + leaves, and 30.57% in leaves), followed by β-phellandrene (14.49% and 21.34% in fruits and leaves), 3-carene (26.84% in leaves) and limonene (15.77%, 11.09%, 12.40%, 7.59%, and 6.24% in five EOs, respectively). Five EOs and selected major compounds provided promising fumigant, contact and repellent activity against T. castaneum and L. serricorne. The EO of stems + leaves collected in October showed the strongest contact toxicity on T. castaneum (LD50 = 20.21μg/adult), as well as fumigant and contact toxicity on L. serricorne (LC50 = 17.17 mg/L air, LD50 = 25.46 μg/adult). All the five EOs exhibited effective repellent activity (PR>80%) against T. castaneum. The results highlight that the EOs from H. dauricum have a promising potential as eco-friendly botanical insecticides.

Biological activities associated with the volatile compound 2,5-bis(1-methylethyl)-pyrazine.

Pyrazines are 1,4-diazabenzene-based volatile organic compounds and known for their broad-spectrum antimicrobial activity. In the present study, we assessed the antimicrobial activity of 2,5-bis(1-methylethyl)-pyrazine, produced by Paenibacillus sp. AD87 during co-culture with Burkholderia sp. AD24. In addition, we were using transcriptional reporter assays in E. coli and mammalian cells to decipher the possible mode of action. Bacterial and mammalian luciferase reporter strains were deployed to elucidate antimicrobial and toxicological effects of 2,5-bis(1-methylethyl)-pyrazine. At high levels of exposure, 2,5-bis(1-methylethyl)-pyrazine exerted strong DNA damage response. At lower concentrations, cell-wall damage response was observed. The activity was corroborated by a general toxicity reporter assay in E. coli ΔampD, defective in peptidoglycan turnover. The maximum E. coli cell-wall stress activity was measured at a concentration close to the onset of the mammalian cytotoxicity, while other adverse outcome pathways, such as the activation of aryl hydrocarbon and estrogenic receptor, the p53 tumour suppressor and the oxidative stress-related Nrf2 transcription factor, were induced at elevated concentrations compared to the response of mammalian cells. Because of its broad-spectrum antimicrobial activity at lower concentrations and the relatively low mammalian toxicity, 2,5-bis(1-methylethyl)-pyrazine is a potential bio-based fumigant with possible applications in food industry, agriculture or logistics.

An Approach to Identify New Insecticides Against Myzus Persicae. In silico Study Based on Linear and Non‐linear Regression Techniques

Neonicotinoids are known to have high insecticidal potency, low mammalian toxicity and relatively tough activity for the development of resistance against aphids. A series of guadipyr insecticides, active against Myzus persicae was engaged in silico studies, based on Multiple Linear Regression (MLR), Partial Least Squares regression (PLS), Artificial Neural Networks (ANN), Support Vector Machine (SVM) and Pharmacophore modeling. Robust and predictive models were built using correlations between the insecticidal profile, expressed by experimental pLC50 values, and molecular descriptors, calculated from the energy optimized structures. Four new potential insecticides active against Myzus persicae and their predicted pLC50 toxicity values were reported for the first time. The models presented here can be used as an approach in the screening and prioritization of chemicals in a scientific and regulatory frame and for toxicity prediction.