Deltamethrin Contact Exposure Mediated Toxicity and Histopathological Aberrations in Tissue Systems of Public Health Importance Cockroach Species Periplaneta americana and Blattella germanica.

Cockroach species Periplaneta americana and Blattella germanica potentially survive in locations close to human activity. Besides spoiling food material, cockroaches also transfer pathogens of different diseases among human beings. Since the insecticides have been used extensively to control cockroaches, information on their insecticide susceptibility and toxicity at the cellular level may be crucial. In the study, deltamethrin toxicity as well as the deltamethrin-mediated cytomorphological changes in the brain, ovary and midgut of the two important cockroach species have been assessed. Different concentrations [0.00025% (0.0025 mg/ml), 0.0025% (0.025 mg/ml), 0.025% (0.25 mg/ml), 0.25% (2.5 mg/ml), 0.5% (5 mg/ml), 1% (10 mg/ml)] of deltamethrin in acetone were used to expose test species in WHO bottle assay. Knockdown was recorded after 5 min interval while delayed mortality was observed after 24 h. Brain, ovary and gut were dissected post 1 h exposure and 24 h holding (for 0.25, 0.5 and 1% concentration), and tissues were processed for microscopic analysis. Deltamethrin exposed cockroaches and dissected tissues were used to estimate deltamethrin using HPLC. At 0.00025% (lowest concentration), the percentage knock-down observed was 66.7% for P. americana and 80% B. germanica respectively (R 2 = 0.78; p = 0.0001) in 1 h. KDT50 value was found to be 8.7 min (95% CI: 7.3-10.2), while KDT99 was 20.7 min (95% CI: 16.0-35.7) in P. americana at 1% concentration. Whereas, the KDT50 and KDT99 values for B. germanica were 7.4 min (95% CI: 5.4-9.1) and 27.4 min (95% CI: 18.2-80.0) at a similar concentration. LD50 and LD95 values (for 60 min standard exposure) were 0.0006% (95% CI: 0.00-0.001) and 0.034% (95% CI: 0.013-0.49) respectively for P. americana, while these values were 0.0005 (95% CI: 0.00-0.001) and 0.04 (95% CI: 0.01-0.23) for B. germanica. Exposure to 1% deltamethrin induced a considerable toxic effect in the epithelial cells in the midgut. HPLC estimated 0.21 ± 0.05 mg (95% CI: 0.18-0.25; CoV 23.9%) deltamethrin in P. americana post 1% exposure. Even short term exposure to a low concentration of synthetic pyrethroid deltamethrin displayed immediate knockdown and delayed mortality in both the test species. Considerable histological damage was observed in both the insects at 1% exposure. In India, resistance to deltamethrin may have been reported among different insects due to its extensive use. However, the formulations such as insecticide paints, attractant baits etc. developed using deltamethrin as an active ingredient could be useful in cockroach control operations.

Deltamethrin Microencapsulation in Emulsion Paint Binder and Its Long-Term Efficacy Against Dengue Vector Aedes aegypti.

Various control interventions have been effective in the control of arthropod vectors to a certain extent; still, sustained vector control is an existing problem globally. Insecticide-based formulations have been found to be useful, however the proper delivery of active molecules to target vectors is important. Currently, synthetic pyrethroid deltamethrin (DM) has been microencapsulated in the emulsion paint binder and evaluated for long-term effectiveness against dengue vector Aedes aegypti. Different compositions of emulsion binder were prepared by varying the content of monomer and DM. A selection was made for the composition yielding the best combination of properties like solid content, intrinsic viscosity, and DM content. Developed formulation was tested against laboratory-reared and pathogen-free Ae. aegypti mosquitoes. Encapsulation of DM in emulsion binder during polymerization showed a uniform distribution. The optimized formulation was stable and did not have a considerable plasticizing effect. Scanning electron microscopy revealed that grain-like micro crystals of DM and surfactant sodium lauryl sulfate (SDS) were uniformly distributed on the formulation surface. The best optimized formulation was highly effective against dengue vector Ae. aegypti and found to provide efficacy for up to 18 months of application. The knockdown time (KDT) values KDT10 and KDT50 were 7.4 min (95% CI: 5.6-9.1) and 22.1 min (95% CI: 19.7-24.3) respectively, whereas 24 h corrected mortality was 90% (95% CI: 82.5-97.5) after 18 months of application (T18). The probit model used to determine knockdown values did not deviate from the linearity and displayed normal distribution of knockdown % with time for different formulations (p ≥ 0.1). Presently developed DM microencapsulated emulsion binder was stable, smooth, and uniform. The binder displayed excellent anti-insect property and was capable of providing long-term effectiveness against dengue vectors Ae. aegypti. Such a formulation after field-scale evaluation could be very useful in attaining long-term protection from arthropod vectors.

Behavioural response of mosquito vectors Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus to synthetic pyrethroid and organophosphorus-based slow-release insecticidal paint.

BACKGROUND: The direct toxicological impact of insecticides on vector mosquitoes has been well emphasized; however, behavioural responses such as excito-repellency and physical avoidance as a result of insecticide exposure have not been much studied. We have demonstrated the excito-repellency and behavioural avoidance in certain vector mosquito species on exposure to a slow-release insecticidal paint (SRIP) formulation in addition to direct toxicity. METHODS: A SRIP formulation developed by the Defence Research and Development Establishment, Gwalior, contains chlorpyriphos, deltamethrin and pyriproxyfen as active insecticides. Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti mosquitoes were used to study the excito-repellency response of the formulation. The experiments were performed in a specially designed dual-choice exposure and escape chamber made of transparent polymethyl methacrylate. For the experiments, the SRIP formulation was applied undiluted at a rate of 8 m2 per kg on 15 cm2 metallic surfaces. Mosquitoes were introduced into the exposure chamber, and observations of the movement of mosquitoes into the escape chamber through the exit portal were taken at 1-min intervals for up to 30 min. RESULTS: The evaluated formulation displayed strong excito-repellency against all three tested vector mosquito species. Results showed that the ET50 (escape time 50%) for Ae. aegypti, An. stephensi and Cx. quinquefasciatus was 20.9 min, 14.5 min and 17.9 min for contact exposure (CE) respectively. Altogether in CE, the escape rates were stronger in An. stephensi mosquitoes at different time intervals compared to Ae. aegypti and Cx. quinquefasciatus mosquitoes. The probit analysis revealed that the determined ET did not deviate from linearity for both non-contact exposure (NCE) and placebo exposure (PE) (χ2 ≤ 7.9; p = 1.0) for Ae. aegypti mosquitoes and for NCE (χ2 = 8.3; p = 1.0) and PE (χ2 = 1.7; p = 1.0) treatments in Cx. quinquefasciatus. Mortality (24 h) was found to be statistically higher (F = 6.4; p = 0.02) in An. stephensi for CE but did not vary for NCE (p ≥ 0.3) and PE (p = 0.6) treatments among the tested mosquito species. Survival probability response suggested that all the three tested species displayed similar survival responses for similar exposures (χ2 ≤ 2.3; p ≥ 0.1). CONCLUSION: The study demonstrates the toxicity and strong behavioural avoidance in known vector mosquito species on exposure to an insecticide-based paint formulation. The combination of insecticides in the present formulation will broaden the overall impact spectrum for protecting users from mosquito bites. The efficacy data generated in the study provide crucial information on the effectiveness of the tested formulation and could be useful in reducing the transmission intensity and disease risk in endemic countries.

Pyriproxyfen treated surface exposure exhibits reproductive disruption in dengue vector Aedes aegypti.

BACKGROUND: Reduced susceptibility of mosquito vectors to currently used insecticides hampers control interventions. Recently pyriproxyfen, an insect growth regulator has been demonstrated to effectively reduce the reproductive potential in vector mosquitoes. METHODS: Pyriproxyfen (PPF), in different concentrations (0.75%, 0.075%, 0.0075%, and 0.00075%) was applied on papers and Indian wild type Aedes aegypti female mosquitoes (N ≥ 20 for each treatment) were exposed onto it as per WHO guidelines, to study the reproductive disruption. PPF concentration on treated papers was quantitatively cross-determined using HPLC method. Reduction in fecundity, fertility and adult emergence in exposed female Ae. aegypti was determined. Abnormal development in ovary and eggs of exposed females was studied microscopically after different time intervals. RESULTS: Eggs laid, eggs hatched, pupae formed and adults emerged per female exposed in both before blood meal and after blood meal groups declined significantly from lowest to highest concentration of PPF (F ≥ 5.2; p < 0.02). Adult emergence inhibition in females exposed to PPF before and after blood meal groups ranged from 58.8% [OR = 0.18 (95% CI = 0.09-0.36)] to 79.2% [OR = 0.04 (95% CI = 0.02-0.10)] and 64.4% [OR = 0.12 (95% CI = 0.05-0.28)] to 77.1% [OR = 0.05 (95% CI = 0.02-0.14)] respectively in different concentrations. The probit model used suggested that FI50 (50% fertility inhibition) and EI50 (50% emergence inhibition) were 0.002% (p = 0.82) and 0.0001% (p = 0.99) for females exposed before blood meal, while 0.01% (p = 0.63) and <0.0001% (p = 0.98) for the females exposed after blood meal, respectively. The eggs laid by the females exposed to PPF-treated surface showed altered body organization, desegmentation and disoriented abdominal and cervical regions in the developing embryo. Quantification of PPF on impregnated papers showed that it was uniformly distributed throughout the matrix. CONCLUSIONS: The present study has shown that tarsal contact to PPF-treated surface for a small time drastically influenced the fecundity, fertility and adult emergence in Indian wild Ae. aegypti mosquitoes. Results suggest that a certain minimum concentration of PPF through contact exposure can reduce the abundance of vector mosquitoes to a considerable level. The formulations based on combination of PPF and other compatible insecticides may be an impactful approach where susceptible mosquitoes are killed by the insecticide component while resistant mosquitoes are sterilised by PPF.

Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE).

Previously (Karade et al., 2014), we have reported the synthesis and in vitro evaluation of bis-pyridinium derivatives of pyridine-3-yl-(2-hydroxyimino acetamide), as reactivators of sarin and VX inhibited hAChE. Few of the molecules showed superior in vivo protection efficacy (mice model) (Kumar et al., 2014; Swami et al., 2016) in comparison to 2-PAM against DFP and sarin poisoning. Encouraged by these results, herein we report the synthesis and in vitro evaluation of isonicotinamide derivatives of pyridine-3-yl-(2-hydroxyimino acetamide) (4a-4d) against sarin and VX inhibited erythrocyte ghost hAChE. Reactivation kinetics of these compounds was studied and the determined kinetic parameters were compared with that of commercial reactivators viz. 2-PAM and obidoxime. In comparison to 2-PAM and obidoxime, oxime 4a and 4b exhibited enhanced reactivation efficacy toward sarin inhibited hAChE while oxime 4c showed far greater reactivation efficacy toward VX inhibited hAChE. The acid dissociation constant and IC50 values of these oximes were determined and correlated with the observed reactivation potential.

Chemospecific and ligand free CuI catalysed heterogeneous N-arylation of amines with diheteroaryl halides at room temperature.

A ligand free, copper-catalyzed N-arylation reaction of amines with diheteroaryl halides in heterogeneous medium at room temperature has been developed. The protocol is very effective for low boiling amines and useful for amines available in aqueous solution. The reaction gives chemospecific arylation of amines with diheteroaryl halides in the mixture monoheteroaryl halides, diheteroaryl halides and carbocyclic aryl halides. The reaction is also chemospecific with respect to arylation of aliphatic amines. Monoarylated piperazines were also synthesized at room temperature following this protocol.

Imidazole-catalyzed monoacylation of symmetrical diamines.

An imidazole-catalyzed protocol for monoacylation of symmetrical diamines has been developed. The protocol gave selective monoacylation of aliphatic (cyclic and acyclic) primary and secondary diamines. In the reaction, imidazole acts as both catalyst and a leaving group. Different monoacylated piperazines and other diamines were synthesized at room temperature in an ethanol/water solvent system.