Multiple Pyrethroid Research Articles

Unraveling the degradation mechanism of multiple pyrethroid insecticides by Pseudomonas aeruginosa and its environmental bioremediation potential.

Extensive use of pyrethroid insecticides poses significant risks to both ecological ecosystems and human beings. Herein, Pseudomonas aeruginosa PAO1 exhibited exceptional degradation capabilities towards a range of pyrethroid family insecticides including etofenprox, bifenthrin, tetramethrin, D-cypermethrin, allethrin, and permethrin, with a degradation efficiency reaching over 84% within 36h (50mg·L-1). Strain PAO1 demonstrated effective soil bioremediation by removing etofenprox across different concentrations (25-100mg·kg-1), with a degradation efficiency over 77% within 15days. Additionally, 16S rDNA high-throughput sequencing analysis revealed that introduction of strain PAO1 and etofenprox had a notable impact on the soil microbial community. Strain PAO1 displayed a synergistic effect with local degrading bacteria or flora to degrade etofenprox. UPLC-MS/MS analysis identified 2-(4-ethoxyphenyl) propan-2-ol and 3-phenoxybenzoic acid as the major metabolites of etofenprox biodegradation. A new esterase gene (estA) containing conserved motif (GDSL) and catalytic triad (Ser38, Asp310 and His313) was cloned from strain PAO1. Enzyme activity and gene knockout experiments confirmed the pivotal role of estA in pyrethroid biodegradation. The findings from this study shed a new light on elucidating the degradation mechanism of P. aeruginosa PAO1 and present a useful agent for development of effective pyrethroid bioremediation strategies.

Evaluating the agronomic and economic benefit of including spinosad with and without pyrethroid insecticides in bermudagrass stem maggot treatments

AbstractThe bermudagrass stem maggot (BSM; Atherigona reversura Villeneuve) is known to have a detrimental effect on bermudagrass (Cynodon spp.). Currently, two strategically timed pyrethroid applications are recommended for BSM suppression in each harvest cycle. However, producers are interested in applying spinosad because of its residual effects for other insects or reducing the number of pyrethroid applications to cut input costs. Therefore, the objective of this study was to determine the agronomic and economic implications of one or multiple pyrethroid (zeta‐cypermethrin) and/or spinosad applications on ‘Alicia’ and ‘Tifton 85’ bermudagrasses. Generally, zeta‐cypermethrin treatments resulted in a greater herbage accumulation compared to the untreated control in both cultivars. Regardless of cultivar, spinosad only treatments did not improve upon the herbage accumulation observed in the untreated control. Crude protein and total digestible nutrients were not affected by insecticide treatments in either cultivar. Finally, two zeta‐cypermethrin applications resulted in greater net profit compared to other insecticide treatments. These data illustrate that there is not yet an alternative for two pyrethroid applications for BSM suppression. Ongoing research and breeding efforts are focused on BSM tolerance and reduced pyrethroid usage to prevent resistance to the insecticide.

Association between prenatal exposure to indoor residual spraying insecticides and infection rates among South African children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE)

In 2021, 53 countries conducted indoor residual spraying (IRS), the application of insecticides such as dichlorodiphenyl trichloroethane (DDT) or pyrethroids to the walls of homes to control malaria. Animal studies show that these insecticides can increase susceptibility to infections but only one human study was conducted in a population from an area where IRS is applied. The aim of the present study was thus to investigate whether maternal exposure to DDT, its breakdown product dichlorodiphenyl dichloroethylene (DDE) or pyrethroid insecticides is associated with symptoms of infection among children living in a region of South Africa were IRS is conducted annually. As part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) we measured maternal serum concentrations of DDT and DDE, and urinary concentrations of four pyrethroid metabolites in peripartum samples. Poisson regression models with robust variance estimates were used to investigate associations with the rates of infection symptoms between ages 3.5–5 years among 629 children as assessed based on caregiver interviews. Multiple pyrethroid metabolites were associated with infection symptoms. For instance, cis-DBCA was associated with increased rates of ear infection (Incidence Rate Ratio for a 10-fold increase (IRR10) = 1.4; 95 % Confidence Interval (CI) = 1.0, 2.1) and persistent diarrhea (IRR10 = 2.1; 95 % CI = 1.2, 3.9), trans-DCCA was associated with increased rates of colds in children (IRR10 = 1.3; 95 % CI = 1.0, 1.6) and persistent fever (IRS10 = 1.4; 95 % CI = 1.0, 2.0), and 3-PBA was associated with increased rates of persistent fever (IRR10 = 1.8; 95 % CI = 1.0, 3.0). We found limited evidence of association between maternal DDE and DDT serum concentrations and infection symptoms. Results suggest that prenatal exposure to pyrethroid insecticides may be associated with infections among children from an area where IRS is conducted.

Pyrethroid-associated nephrotoxicity in channel catfish, Ictalurus punctatus, and blue catfish, I. furcatus, at a public aquarium.

Over the course of an approximately 11-month period, an outdoor, freshwater, mixed species, recirculating, display system at a public aquarium experienced intermittent mortalities of channel catfish (Ictalurus punctatus) and blue catfish (I. furcatus). Catfish acutely presented for abnormal buoyancy, coelomic distention, and protein-rich coelomic effusion. Gross lesions typically involved massive coelomic distension with protein-rich effusion, generalized edema, and gastric hemorrhage and edema. Microscopically, primary lesions included renal tubular necrosis, gastric edema with mucosal hemorrhages, and generalized edema. Aerobic culture and virus isolation could not recover a consistent infectious agent. Intracoelomic injection of coelomic effusion and aspirated retrobulbar fluid from a catfish into naïve zebrafish (bioassay) produced peracute mortality in 3 of 4 fish and nervous signs in the fourth compared with 2 saline-injected control zebrafish that had - no mortality or clinical signs. Kidney tissue and coelomic effusion were submitted for gas chromatography tandem mass spectrometry by multiple reaction monitoring against laboratory standards, which detected the presence of multiple pyrethroid toxins, including bioallethrin, bifenthrin, trans-permethrin, phenothrin, and deltamethrin. Detection of multiple pyrethroids presumably reflects multiple exposures with several products. As such, the contributions of each pyrethroid toward clinical presentation, lesion development, and disease pathogenesis cannot be determined, but they are suspected to have collectively resulted in disrupted osmoregulation and fluid overload due to renal injury. Pesticide-induced toxicoses involving aquarium fish are rarely reported with this being the first description of pyrethroid-induced lesions and mortality in public aquarium-held fish.

Multiple Pyrethroid Resistance in Urban Male and Female An. gambiae s.l Populations in Ilorin Nigeria: Implications for Swarm Spraying and Toxic Sugar Bait Malaria Vector Control

Background: Male mosquito control through swarm spraying and Attractive Toxic Sugar Baits (ATSB) have been identified as potential strategies to complement the regular but insufficient female mosquito-based insecticide-treated net (ITN) approach. However, the effectiveness of these control strategies relies on under-standing the insecticide susceptibility status of the targeted male and female mosquito populations. Therefore, this study aimed to assess the insecticide susceptibility status of male and female An. gambiae s.l. Popu-lations in urban Ilorin, Nigeria. Methods: Using WHO kits and protocol, adult male and female mosquitoes reared from the same larval col-lections from different sites were exposed separately to permethrin, deltamethrin, and alphacypermethrin insecticides. Joint insecticide susceptibility tests, involving exposures of equal numbers of male and female mosquitoes to each insecticide, were also conducted in anticipation of joint insecticide exposure on the field. Exposed mosquitoes were identified to species level. Results: Higher kdt50s (52.5-641.3mins) and lower mortalities (permethrin 39-62%, deltamethrin 57-68%, alphacypermethrin 44-60%), indicating higher levels of resistance, were observed for the females compared to the male (22.1-42.2 mins, 60-94%) mosquitoes. The percentage mortalities of males (71-94%) were sig-nificantly (P ≤ 0.043) higher than those of the jointly exposed females (39-62%). However, separately ex-posed male mosquito mortalities (60-81%) were not significantly (P ≥ 0.067) higher than the females (55-68%). All the male mosquito populations were resistant to permethrin (75-94% mortality), deltamethrin (60-82%), and alphacypermethrin (74-86%) insecticides after joint and separate exposures. Resistant male and female mosquitoes were identified predominantly as An. arabiensis (74-84%). Conclusion: Multiple pyrethroid insecticide resistance detected in the male and female mosquito populations indicates the potential ineffectiveness of pyrethroid-based swarm spraying, pyrethroid ATSB and ITNs in the study location

Efficient biodegradation of multiple pyrethroid pesticides by Rhodococcus pyridinivorans strain Y6 and its degradation mechanism

Pyrethroids are one of the most widely used insecticides, which have adverse biological effects and poses a serious threat to ecological environments and human health. In this study, a novel pyrethroid-degrading strain Rhodococcus pyridinivorans Y6 was isolated from activated sludge contaminated by multiple pesticides. Within 36 h, the Y6 strain was able to completely metabolize multiple pyrethroid pesticides including prallethrin, allethrin, D-cyphenothrin, fenvalerate, and beta-cypermethrin (50 mg·L−1). The results of the soil remediation indicated that the Y6 strain could effectively remove prallethrin from soil and slurry with indigenous microbes. Moreover, 16S high-throughput sequencing of the soil demonstrated that the strain Y6 had no adverse effects on the soil community structure and diversity of indigenous microbes after it entered the soil. A p-nitrophenyl esterase gene (pnbA1564) containing conserved pentapeptide motif Gly190-X-Ser192-X-Gly194 was cloned from the Y6 genome, in which Ser192 was the active center of the catalytic triad of Ser192-His416-Asp314. RT-PCR and enzyme activity analysis showed that PnbA1564 was involved in the hydrolysis of prallethrin. GC–MS results further confirmed that prallethrin could be hydrolyzed via ester bond by PnbA1564. Taken together, these original findings provide a comprehensive assessment of R. pyridinivorans strain Y6 and contribute to a better understanding of the molecular mechanism responsible for the pyrethroid biodegradation.

Broad-spectrum portable magnetic relaxation switching immunosensor with gold-functionalized magnetic nanoprobes for the sensitive detection of multiple pyrethroids

At present, the most available pyrethroid (PYR) detection methods still suffer from a narrow detection spectrum, low sensitivity, and less portability. Herein, a novel magnetic relaxation switching (MRS) sensor was elaboratively designed to detect multiple PYRs, combining a novel broad-spectrum antibody CL-CN/1D2 and synthesized immune gold-functionalized magnetic nanoparticles, with the inherent response of the sensor. A series of antibodies and the immune gold-functionalized magnetic nanoparticles were designed and synthesized. The broad-spectrum antibody CL-CN/1D2 and high-performance gold-functionalized magnetic nanoprobe were further selected. The target analytes were effectively captured by the gold-functionalized magnetic nanoparticles in 20% (v/v) ethanol, resulting in the number increase of the signaling probes in the supernatant after magnetic separation. This sensor can detect multiple PYRs with a detection limit of 2.72 μg/L for cypermethrin, 3.58 μg/L for β-cypermethrin, 4.07 μg/L for cyfluthrin, 3.66 μg/L for λ-cyhalothrin, 4.42 μg/L for β-cyhalothrin, 3.51 μg/L for fenpropathrin, 4.41 μg/L for fenvalerate, and 4.12 μg/L for deltamethrin in lake water and milk within 35 min. This study not only achieves broad-spectrum PYRs detection at a trace amount but also provides an effective and universal strategy for enhancing the sensitivity and stability of the portable MRS sensor when detecting hydrophobic analytes in the environment.

Sensitive determination of pyrethroid insecticide residues in tea using a molecularly imprinted fiber array based on homemade solid-phase microextraction coatings

In this study, we proposed a homemade solid-phase microextraction fiber array based on molecularly imprinted polymer coatings. This sample pretreatment technique was used prior to high-performance liquid chromatography (HPLC) to identify pyrethroids, of a class of high-efficiency insecticides for controlling plant pests and diseases in agriculture. Findings revealed that the molecularly imprinted three-fiber array for solid-phase microextraction significantly increased the extraction capacity by 2.1 to 3.5 times compared with a single molecularly imprinted fiber, and it also increased the extraction capacity by 2.0 to 3.4 times compared with two different commercial fiber arrays. The imprinted fiber array extraction coupled with the HPLC analytical method was effective and sensitive in an aqueous solution. In addition, this combined method improved the extraction and screening capacities of pyrethroid insecticides. The detection limits of pyrethroid insecticides in tea samples were 0.16–0.33 μg/L with linear correlation coefficients of 0.9900–0.9994. The spiked recoveries were 72.74–119.66 %, with RSD (n = 3) below 14.53 %. Thus, this work provides an effective, sensitive, and practical method with good enrichment effects for analyzing and determining of multiple pyrethroids in tea samples.

Exposure to multiple pyrethroid insecticides affects ovarian follicular development via modifying microRNA expression

Pyrethroids, a class of insecticides widely used in agriculture and residential pest control, have been considered as endocrine-disrupting chemicals (EDCs). Our previous epidemiological study reported a positive association of urinary levels of pyrethroid metabolites with the risk of primary ovarian insufficiency in women, suggesting that pyrethroid exposure may be a potential risk factor for female ovarian health. In this study, female mice at gestational, lactational or peripubertal stages were exposed to eight most commonly used pyrethroids at the doses of acceptable daily intake (ADI) recommended by the World Health Organization (WHO). Gestational exposure to eight pyrethroids at ADI doses led to a significant decrease in the number of primary follicles in female offspring on postnatal day (PND) 3, and an increase in the number of atretic follicles and granulosa cell apoptosis, as well as lower estrogen and higher follicle-stimulating hormone (FSH) levels in adult female offspring. Lactational and peripubertal exposure to pyrethroid mixture had no significant effects on follicular development and ovarian functions. The data of high-throughput microRNA (miRNA) sequencing showed that 23 miRNAs were differentially expressed in the ovaries of female offspring mice on PND 1 after gestational exposure to pyrethroid mixture. The results of qPCR confirmed that miR-152-3p, miR-450b-3p and miR-196a-5p were significantly upregulated in the neonatal ovaries in the exposed group. The bioinformatic analysis indicates that the modification of the expression of ovarian miRNAs by pyrethroid exposure may disrupt the key biological processes (such as mRNA processing) and major signaling pathways (such as PI3K/Akt pathway, adipocytokine pathway and GnRH pathway) governing follicular development and ovarian functions. This study first reported that gestational exposure of female mice to multiple pyrethroids at the recommended human safe doses had irreversible adverse effects on the ovaries in female offspring in adulthood through regulating the expression of miRNAs during early developmental stages.

Characteristics of Pyrethroid Pesticide Residues in Soil of Shenyang, China

Pyrethroid residues in the surface soils and among different soil layers of the open fields and greenhouse soils of Shenyang, China, were analyzed. In addition, the relationship between the soil properties and the pesticide residues was also assessed. Results showed that the detection rates of the pyrethroids were high and multiple pyrethroid pesticides were detected and the average level of trans–cypermethrin was 73.05 μg/kg, which was the highest among the concentration of all test pyrethroids. The detection rate and the residual amount of the same pyrethroid residues were at the low levels in different regions around Shenyang. Comparing the pyrethroid concentrations in greenhouse and the open fields, the residues in greenhouse were higher than those in the open fields. In different soil layers, the pesticide residues were found mainly in the 0-20cm soil layer, and there were no significant differences among the soil depths of 20 cm, 40 cm, 60 cm, 80 cm and 100 cm. Statistical analysis results showed that the residues of fenvalerate were more with the increase of pH value. Organic matter contents were positively correlated with the residues of α-cypermethrin and cypermethrin, and negatively correlated with the residues of lambdacyhalothrin.

Pyrethrin-resembling pyrethroids are metabolized more readily than heavily modified ones by CYP9As from Helicoverpa armigera

The cotton bollworm, Helicoverpa armigera, is a polyphagous pest threatening many economically important crops worldwide. Until recently, synthetic pyrethroids remain in wide use for controlling pest insects including the cotton bollworm. Understanding the metabolic mechanism of pyrethroids in a given pest can provide significant implication for a smart choice of insecticides, and such information is useful for the development of novel selective and safe insecticides. In this study, we used complexes of recombinant H. armigera cytochrome P450 CYP9A and NADPH-dependent cytochrome P450 reductase to investigate the capacity of three CYP9A paralogs in the transformation of seven structurally different pyrethroids by metabolism assays. The results showed that the three paralogous CYP9As were able to metabolize multiple pyrethroids. Interestingly, all the three CYP9As transformed pyrethrin-resembling pyrethroids (e.g. bioallethrin) more efficiently than the heavily modified ones (e.g. bifenthrin). These findings suggest that herbivorous insects can cope with synthetic insecticides using their physiological systems that initially evolved to survive exposure to the defensive chemicals in their host plants, adding support to the pre-adaptation hypothesis.

IR-TEx: An Open Source Data Integration Tool for Big Data Transcriptomics Designed for the Malaria Vector Anopheles gambiae.

IR-TEx is an application written in Shiny (an R package) that allows exploration of the expression of (as well as assigning functions to) transcripts whose expression is associated with insecticide resistance phenotypes in Anopheles gambiae mosquitoes. The application can be used online or downloaded and used locally by anyone. The local application can be modified to add new insecticide resistance datasets generated from multiple -omics platforms. This guide demonstrates how to add new datasets and handle missing data. Furthermore, IR-TEx can be completely and easily recoded to use-omics datasets from any experimental data, making it a valuable resource to many researchers. The protocol illustrates the utility of IR-TEx in identifying new insecticide resistance candidates using the the microsomal glutathione transferase, GSTMS1, as an example. This transcript is upregulated in multiple pyrethroid resistant populations from Côte D'Ivoire and Burkina Faso. The identification of co-correlated transcripts provides further insight into the putative roles of this gene.

In vitro assessment of pyrethroid bioaccessibility via particle ingestion

Due to their intensive use in agricultural and residential pest control, human exposure to residues of multiple pyrethroids frequently occurs. Pyrethroids have exceptionally high affinity for solid particles, highlighting the need to understand human exposure through oral ingestion of contaminated soil or dust particles. In this study, we used artificial gastrointestinal fluids to measure the desorption or bioaccessibility of eight current-use pyrethroids in soil and dust samples. Tenax was further included as a sink in parallel treatments to simulate the effect of removal due to transfer of pyrethroids to lipid membranes. The use of 0.4 g of Tenax in 20 mL digestive fluids resulted in rapid and efficient trapping of pyrethroids, and further, greatly increased bioaccessibility. In the artificial digestive fluids without Tenax, 6.0–48.0% of pyrethroids were desorbed over 21 h, and the fractions increased by 1.6–4.1 folds to 21.5–79.3% with the Tenax sink. Therefore, 6.0–79.3% of soil or dust-borne pyrethroids may be considered bioavailable upon ingestion. While protein and sucrose increased the estimated bioaccessibility, co-presence of lipid (vegetable oil) decreased the bioaccessibility of pyrethroids, likely due to competitive phase partition. Pyrethroids were also found to be unstable in the artificial intestinal fluid containing pancreatin, further decreasing the potential bioaccessibility of pyrethroids on soil or dust particles. The limited bioaccessibility should be considered to refine the prediction of human exposure and risk through oral ingestion of pyrethroid residues.

Variability of pyrethroid concentrations on hard surface kitchen flooring in occupied housing.

Pyrethroids are a class of neurotoxic insecticides, and some studies have used single-time wiping of hard surface flooring to estimate indoor pyrethroid concentrations. Considering that human activities may affect concentrations, knowledge of temporal variability is needed to reduce the uncertainty of exposure estimates that are calculated using wipe sampling of pyrethroids in occupied housing. During weeks one, two, and six of a 6-week study, two wipe samples of hard surface kitchen flooring were collected in each of 50 occupied residences and used to estimate the temporal variability of eight pyrethroids and six pyrethroid degradation products. Beginning 1month prior to sample collection, the participants kept pesticide use diaries. All pyrethroids were widely distributed among the houses, and co-occurrence of multiple pyrethroids was common structured. Application diaries and detection frequencies appeared unconnected, but the applications were correlated with measurable changes in pyrethroid concentrations. In general, degradation products were detected less frequently and at lower concentrations than their parent pyrethroids. Estimates of the intraclass correlation coefficient (ICC) for individual pyrethroids ranged from 0.55 (bifenthrin) to 0.80 (deltamethrin), and two sampling events at each residence would have been sufficient to estimate the mean concentration of most pyrethroids with an ICC of 0.80.

Environmentally relevant pyrethroid mixtures: A study on the correlation of blood and brain concentrations of a mixture of pyrethroid insecticides to motor activity in the rat.

Human exposure to multiple pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to pyrethroids, it is important to understand their disposition and toxicity in target organs such as the brain, and surrogates such as the blood when administered as a mixture. The objective of this study was to assess the correlation between blood and brain concentrations of pyrethroids and neurobehavioral effects in the rat following an acute oral administration of the pyrethroids as a mixture. Male Long-Evans rats were administered a mixture of β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate and cis- and trans-permethrin in corn oil at seven dose levels. The pyrethroid with the highest percentage in the dosing solution was trans-permethrin (31% of total mixture dose) while deltamethrin and esfenvalerate had the lowest percentage (3%). Motor activity of the rats was then monitored for 1h. At 3.5h post-dosing, the animals were euthanized and blood and brain were collected. These tissues were extracted and analyzed for parent pyrethroid using HPLC-tandem mass spectrometry. Cypermethrin and cis-permethrin were the predominate pyrethroids detected in blood and brain, respectively, at all dosage levels. The relationship of total pyrethroid concentration between blood and brain was linear (r=0.93). The pyrethroids with the lowest fraction in blood were trans-permethrin and β-cyfluthrin and in brain were deltamethrin and esfenvalerate. The relationship between motor activity of the treated rats and summed pyrethroid blood and brain concentration was described using a sigmoidal Emax model with the Effective Concentration50 being more sensitive for brain than blood. The data suggests summed pyrethroid rat blood concentration could be used as a surrogate for brain concentration as an aid to study the neurotoxic effects of pyrethroids administered as a mixture under the conditions used in this study.

Life after endosulfan, the Australian macadamia experience

As of October 2012 the use of endosulfan was prohibited in Australian Horticulture. Within the macadamia pest management system endosulfan had been a mainstay of production for NSW growers in particular since the mid-1980s. It offered a compromise between a residual flower spray with miticide properties and a low bee toxicity not found in other pesticides of that generation. Some pesticide free crops had been grown prior to 2012 but recent changes to pest distributions in these areas have put pressure on the feasibility and profitability of that approach. Outbreak populations of pests like macadamia lace bugs (especially Ulonemia decoris Drake), and macadamia seed weevils (Sigastus sp.) have developed in many macadamia crops in the NSW growing districts since late 2008 (50% of Australian production area). These threaten production even in areas with good spray coverage and monitoring. These pests are migrating freely from abandoned orchards causing almost total crop loss in some instances. The APVMA needs to realise how reliant the Australian macadamia industry (30% of world production) is on access to effective chemistry. Without endosulfan, new chemistry for managing Scirtothrips albomaculatus and Polyphagotarsonemus sp. (broad mites) on the expanding macadamia buds in autumn is required because multiple pyrethroid and organophosphate applications will generate more activity. Abamectin appears to be the most effective short term solution.

Detection of 3-phenoxybenzoic acid in river water with a colloidal gold-based lateral flow immunoassay

3-Phenoxybenzoic acid (3-PBA) is a general metabolite of synthetic pyrethroids. It could be used as a generic biomarker for multiple pyrethroids exposure for human or pyrethroid residues in the environment. In this study, monoclonal antibodies (mAbs) against 3-PBA were developed by using PBA–bovine serum albumin (BSA) as an immunogen. In the competitive enzyme-linked immunosorbent assay (ELISA) format, the I50 and I10 values of purified mAbs were 0.63 and 0.13μg/ml, respectively, with a dynamic range between 0.19 and 2.04μg/ml. Then, the colloidal gold (CG)-based lateral flow immunoassay was established based on the mAbs. The working concentration of coating antigen and CG-labeled antibodies and the blocking effects were investigated to get optimal assay performance. The cutoff value for the assay was 1μg/ml 3-PBA, and the detection time was within 10min. A total of 40 river water samples were spiked with 3-PBA at different levels and determined by the lateral flow immunoassay without any sample pretreatments. The negative false rate was 2.5%, and no positive false results were observed at these levels. This lateral flow immunoassay has the potential to be an on-site screening method for monitoring 3-PBA or pyrethroid residues in environmental samples.

The recent escalation in strength of pyrethroid resistance in Anopheles coluzzi in West Africa is linked to increased expression of multiple gene families.

BackgroundSince 2011, the level of pyrethroid resistance in the major malaria mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that none of the long lasting insecticide treated nets (LLINs) currently in use throughout the country kill the local mosquito vectors. We investigated whether this observed increase was associated with transcriptional changes in field-caught Anopheles coluzzi using two independent whole-genome microarray studies, performed in 2011 and 2012.ResultsMosquitoes were collected from south-west Burkina Faso in 2011 and 2012 and insecticide exposed or non-exposed insects were compared to laboratory susceptible colonies using whole-genome microarrays. Using a stringent filtering process we identified 136 genes, including the well-studied detoxification enzymes (p450 monoxygenases and esterases) and non-detoxification genes (e.g. cell transporters and cuticular components), associated with pyrethroid resistance, whose basal expression level increased during the timeframe of the study. A subset of these were validated by qPCR using samples from two study sites, collected over 3 years and marked increases in expression were observed each year. We hypothesise that these genes are contributing to this rapidly increasing resistance phenotype in An. coluzzi. A comprehensive analysis of the knockdown resistance (kdr) mutations (L1014S, L1014F and N1575Y) revealed that the majority of the resistance phenotype is not explained by target-site modifications.ConclusionsOur data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here. Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d’Ivoire. This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1342-6) contains supplementary material, which is available to authorized users.

EPA's SHEDS-multimedia model: Children's cumulative pyrethroid exposure estimates and evaluation against NHANES biomarker data

The U.S. EPA's SHEDS-Multimedia model was applied to enhance the understanding of children's exposures and doses to multiple pyrethroid pesticides, including major contributing chemicals and pathways. This paper presents combined dietary and residential exposure estimates and cumulative doses for seven commonly used pyrethroids, and comparisons of model evaluation results with NHANES biomarker data for 3-PBA and DCCA metabolites. Model input distributions were fit to publicly available pesticide usage survey data, NHANES, and other studies, then SHEDS-Multimedia was applied to estimate total pyrethroid exposures and doses for 3–5year olds for one year variability simulations. For dose estimations we used a pharmacokinetic model and two approaches for simulating dermal absorption. SHEDS-Multimedia predictions compared well to NHANES biomarker data: ratios of 3-PBA observed data to SHEDS-Multimedia modeled results were 0.88, 0.51, 0.54 and 1.02 for mean, median, 95th, and 99th percentiles, respectively; for DCCA, the ratios were 0.82, 0.53, 0.56, and 0.94. Modeled time-averaged cumulative absorbed dose of the seven pyrethroids was 3.1nmol/day (versus 8.4nmol/day for adults) in the general population (residential pyrethroid use and non-use homes) and 6.7nmol/day (versus 10.5nmol/day for adults) in the simulated residential pyrethroid use population. For the general population, contributions to modeled cumulative dose by chemical were permethrin (60%), cypermethrin (22%), and cyfluthrin (16%); for residential use homes, contributions were cypermethrin (49%), permethrin (29%), and cyfluthrin (17%). The primary exposure route for 3–5year olds in the simulated residential use population was non-dietary ingestion exposure; whereas for the simulated general population, dietary exposure was the primary exposure route. Below the 95th percentile, the major exposure pathway was dietary for the general population; non-dietary ingestion was the major pathway starting below the 70th percentile for the residential use population. The new dermal absorption methodology considering surface loading had some impact, but did not change the order of key pathways.

Environmentally relevant mixing ratios in cumulative assessments: A study of the kinetics of pyrethroids and their ester cleavage metabolites in blood and brain; and the effect of a pyrethroid mixture on the motor activity of rats

National surveys of United States households and child care centers have demonstrated that pyrethroids are widely distributed in indoor habited dwellings and this suggests that co-exposure to multiple pyrethroids occurs in nonoccupational settings. The purpose of this research was to use an environmentally relevant mixture of pyrethroids to assess their cumulative effect on motor activity and develop kinetic profiles for these pyrethroids and their hydrolytic metabolites in brain and blood of rats. Rats were dosed orally at one of two levels (1.5× or 5.0× the calculated dose that decreases rat motor activity by 30%) with a mixture of cypermethrin, deltamethrin, esfenvalerate, cis-/trans-permethrin, and β-cyfluthrin in corn oil. At 1, 2, 4, 8, or 24h after dosing, the motor activity of each animal was assessed and the animals sacrificed. Concentrations of pyrethroids in brain and blood, and the following metabolites: cis-/trans-dichlorovinyl-dimethylcyclopropane-carboxylic acid, 3-phenoxybenzoic acid, 3-phenoxybenzyl alcohol, 4-fluoro-3-phenoxybenzoic acid, and cis-dibromovinyl-dimethylcyclopropane-carboxylic acid were determined using liquid chromatography tandem mass spectrometry (LC–MS/MS). Using this pyrethroid mixture in rats, the results suggest there is greater metabolism of trans-permethrin prior to entering the systemic circulatory system. All pyrethroids had tissue half-lives (t1/2) of less than 5h, excepting esfenvalerate in brain. At early time points, relative pyrethroid brain concentrations approximated their dose mixture proportions and a sigmoidal Emax model described the relationship between motor activity decrease and total pyrethroid brain concentration. In blood, the t1/2's of the cyclopropane metabolites were longer than the phenoxybenzoic metabolites. However, relative to their respective precursors, concentrations of the phenoxybenzoic acids were much higher than concentrations of the cyclopropane metabolites. Brain concentrations of all metabolites were low relative to blood concentrations. This implies limited metabolite penetration of the blood-brain barrier and little metabolite formation within the brain. In conclusion: toxicokinetic differences between the pyrethroids did not appear to be important determinants of their relative potency and their effect on motor activity was consistent with a pyrethroid dose additive model.