Repellent activity of essential oils to the Lone Star tick, Amblyomma americanum.

BACKGROUND: The Lone Star tick, Amblyomma americanum is important to human health because of a variety of pathogenic organisms transmitted to humans during feeding events, which underscores the need to identify novel approaches to prevent tick bites. Thus, the goal of this study was to test natural and synthetic molecules for repellent activity against ticks in spatial, contact and human fingertip bioassays. METHODS: The efficacy of essential oils and naturally derived compounds as repellents to Am. americanum nymphs was compared in three different bioassays: contact, spatial and fingertip repellent bioassays. RESULTS: Concentration response curves after contact exposure to 1R-trans-chrysanthemic acid (TCA) indicated a 5.6 µg/cm2 concentration required to repel 50% of ticks (RC50), which was five- and sevenfold more active than DEET and nootkatone, respectively. For contact repellency, the rank order of repellency at 50 µg/cm2 for natural oils was clove > geranium > oregano > cedarwood > thyme > amyris > patchouli > citronella > juniper berry > peppermint > cassia. For spatial bioassays, TCA was approximately twofold more active than DEET and nootkatone at 50 µg/cm2 but was not significantly different at 10 µg/cm2. In spatial assays, thyme and cassia were the most active compounds tested with 100% and 80% ticks repelled within 15 min of exposure respectively and was approximately twofold more effective than DEET at the same concentration. To translate these non-host assays to efficacy when used on the human host, we quantified repellency using a finger-climbing assay. TCA, nootkatone and DEET were equally effective in the fingertip assay, and patchouli oil was the only natural oil that significantly repelled ticks. CONCLUSIONS: The differences in repellent potency based on the assay type suggests that the ability to discover active tick repellents suitable for development may be more complicated than with other arthropod species; furthermore, the field delivery mechanism must be considered early in development to ensure translation to field efficacy. TCA, which is naturally derived, is a promising candidate for a tick repellent that has comparable repellency to commercialized tick repellents.

A prospective cohort study of exposure to household pesticide with cardiovascular diseases mortality in older adults.

OBJECTIVES: We examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). METHODS: Information on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. RESULTS: The participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. CONCLUSIONS: Exposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.

An updated review on the safety of N, N-diethyl-meta-toluamide insect repellent use in children and the efficacy of natural alternatives.

N, N-diethyl-meta-toluamide (DEET) has been considered the 'gold standard' for insect repellent use since the 1950s and constitutes most insect repellents on the market. However, conflicting data in the scientific literature and confusing information in the media are at the core of debates about the safety of DEET insect repellents for the protection of children against arthropod bites. The few fatal occurrences involving DEET insect repellents and complications of their use in the pediatric population are typically the result of accidental overdoses or misuse of insect repellents that disregard warnings on product labels. With appropriate application, the safety record of DEET insect repellents continues to be excellent with few side effects. The purpose of this review is to provide a summary of the literature on safety outcomes of DEET insect repellent use in children; outline the pediatric recommendations relating to DEET insect repellents; and provide an overview of EPA-approved and naturally derived alternatives to DEET that possess low toxicity while providing a similar level of protection to synthetic insect repellents.

What's Eating You? Rhipicephalus Ticks Revisited.

Rhipicephalus ticks are vectors of disease in humans and animals. Rhipicephalus sanguineus sensu lato (the brown dog tick) is one of the most geographically widespread tick species worldwide, likely due to its ability to colonize human and canine dwellings over a range of habitats. They transmit a variety of diseases to dogs and humans, including canine babesiosis, canine monocytic ehrlichiosis, hepatozoonosis, Mediterranean spotted fever, and Rocky Mountain spotted fever. Tick bites manifest as intensely pruritic, erythematous papules at the site of tick attachment; symptomatic relief usually can be achieved with topical antipruritics. Prevention of tick bites is best achieved through a combination of veterinary and environmental control; protective clothing; repellents, such as N,N-diethyl-meta-toluamide (DEET) and permethrin; and prompt identification and removal of ticks.

Exposure to and Biomarker Responses From Legacy and Emerging Contaminants Along Three Drainages in the Milwaukee Estuary, Wisconsin, USA.

Legacy contaminants and contaminants of emerging concern (CECs) were assessed in tree swallow (Tachycineta bicolor) tissue and diet samples from three drainages in the Milwaukee estuary, Wisconsin, USA, to understand exposures and possible biomarker responses. Two remote Wisconsin lakes were assessed for comparative purposes. Bioaccumulative classes of contaminants, such as polybrominated diphenyl ethers and per- and polyfluoroalkyl substances, while at higher concentrations than the reference lakes, did not vary significantly among sites or among the three drainages. Polycyclic aromatic hydrocarbons were assessed in diet and sediment and were from primarily pyrogenic sources. Ten biomarkers were assessed relative to contaminant exposure. Polychlorinated biphenyls (PCBs) were elevated above reference conditions at all Milwaukee sites but did not correlate with any measured biomarker responses. Only one site, Cedarburg, just downstream from a Superfund site, had elevated PCBs compared to other sites in the Milwaukee estuary. Few non-organochlorine insecticides or herbicides were detected in tree swallow liver tissue, except for the atrazine metabolite desethylatrazine. Few pharmaceuticals and personal care products were detected in liver tissue except for N,N-diethyl-meta-toluamide, iopamidol, and two antibiotics. The present study is one of the most comprehensive assessments to date, along with the previously published Maumee River data, on the exposure and effects of a wide variety of CECs in birds. Environ Toxicol Chem 2024;43:856-877. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Recent advances in degradation of N,N-diethyl-3-toluamide (DEET)-an emerging environmental contaminant: a review.

N,N-Diethyl-3-toluamide (DEET) is a commonly used insect repellent, which acts as an organic chemical contaminant in water and considered as an emerging contaminant which has been observed worldwide. It gets discharged into the environment through sewage waste. The various methods have been used to degrade DEET, such as UV based, ozonation, photocatalytic degradation, and biodegradation (based on the metabolic activity of fungi and bacteria). However, less research has been done on the degradation of DEET by deploying nanoparticles. Therefore, biodegradation and nanotechnology-based methods can be the potential solution to remediate DEET from the environment. This review is an attempt to analyze the routes of entry of DEET into the atmosphere and its environmental health consequences and to explore physical, chemical, and biological methods of degradation. Furthermore, it focuses on the various methods used for the biodegradation of the DEET, including their environmental consequences. Future research is needed with the application of biological methods for the degradation of DEET. Metabolic pathway for biodegradation was explored for the new potent microbial strains by the application of physical, chemical, and microbial genomics; molecular biology; genetic engineering; and genome sequencing methods.

Efficacy of unregulated minimum risk tick repellent products evaluated with Ixodes scapularis nymphs in a human skin bioassay.

BACKGROUND: The majority of vector-borne disease cases in the USA are caused by pathogens spread by ticks, most commonly the blacklegged tick, Ixodes scapularis. Personal protection against tick bites, including use of repellents, is the primary defense against tick-borne diseases. Tick repellents registered by the Environmental Protection Agency (EPA) are well documented to be safe as well as effective against ticks. Another group of tick repellent products, 25(b) exempt or minimum risk products, use alternative, mostly botanically derived, active ingredients. These are considered to pose minimal risk to human health and therefore are exempt from EPA registration; efficacy testing is not mandated for these products. METHODS: We used a finger bioassay to evaluate the repellency against I. scapularis nymphs for 11 formulated 25(b) exempt products together with two positive control DEET-based EPA registered products. Repellency was assessed hourly from 0.5 to 6.5 h after product application. RESULTS: The DEET-based products showed ≥ 97% repellency for all examined timepoints. By contrast, an average of 63% of ticks were repelled in the first 1.5 h after application across the 11 25(b) exempt products, and the average fell to 3% repelled between 2.5 and 6.5 h. Ten of the 11 25(b) exempt products showed statistically similar efficacy to DEET-based products at 30 min after application (repellency of 79-97%). However, only four 25(b) exempt products maintained a level of repellency similar to DEET-based products (> 72%) at the 1.5-h mark, and none of these products were effective in repelling ticks at the timepoints from 2.5 to 6.5 h after application. CONCLUSIONS: Neither the claims on the labels nor specific active ingredients and their concentrations appeared to predict the duration of efficacy we observed for the 25(b) exempt products. These products are not registered with the EPA, so the methods used to determine the application guidelines on their labels are unclear. Consumers should be aware that both the level of efficacy and the duration of repellency may differ among unregulated 25(b) exempt repellent products labeled for use against ticks. We encourage more research on these products and the 25(b) exempt active ingredients they contain to help determine and improve their efficacy as repellents under different conditions.

Development of terpenoid repellents against Aedes albopictus: a combined study of biological activity evaluation and computational modelling.

To explore novel terpenoid repellents, 22 candidate terpenoid derivatives were synthesized and tested for their electroantennogram (EAG) responses and repellent activities against Aedes albopictus. The results from the EAG experiments revealed that 5-(2-hydroxypropan-2-yl)-2-methylcyclohex-2-en-1-yl formate (compound 1) induced distinct EAG responses in female Aedes albopictus. At concentrations of 0.1, 1, 10, 100, and 1000 mg/L, the EAG response values for compound 1 were 179.59, 183.99, 190.38, 193.80, and 196.66 mV, demonstrating comparable or superior effectiveness to DEET. Repellent activity analysis indicated significant repellent activity for compound 1, closest to the positive control DEET. The in silico assessment of the ADMET profile of compound 1 indicates that it successfully passed the ADMET evaluation. Molecular docking studies exhibited favourable binding of compound 1 to the active site of the odorant binding protein (OBP) of Aedes albopictus, involving hydrophobic forces and hydrogen bond interactions with residues in the OBP pocket. The QSAR model highlighted the influential role of hydrogen-bonding receptors, positively charged surface area of weighted atoms, polarity parameters of molecules, and maximum nuclear-nuclear repulsion force of carbon-carbon bonds on the relative EAG response values of the tested compounds. This study holds substantial significance for the advancement of new terpenoid repellents.

A tumor-targeted and enzyme-responsive gold nanorod-based nanoplatform with facilitated endo-lysosomal escape for synergetic photothermal therapy and protein therapy.

To tackle the obstacles related to tumor targeting and overcome the limitations of single treatment models, we have developed a nanoplatform that is both tumor-targeted and enzyme-responsive. This nanoplatform integrates photothermal gold nanorods (AuNRs) and protein drugs into a single system. This nanosystem, known as AuNRs@HA-mPEG-Deta-LA, was fabricated by modifying gold nanorods (AuNRs) with a polymeric ligand called hyaluronic acid-grafted-(mPEG/diethylenetriamine-conjugated-lipoic acid). The purpose of this fabrication was to load cytochrome c (CC) and utilize it for the synergetic protein-photothermal therapy of cancer. The resulting nanoplatform exhibited a high efficiency in loading proteins and demonstrated excellent stability in different biological environments. Additionally, CC-loaded AuNRs@HA-mPEG-Deta-LA not only enabled localized hyperthermia for photothermal therapy (PTT) with laser irradiation but also facilitated the release of CC under the action of hyaluronidase, an enzyme known to be overexpressed in tumor cells. The confocal imaging results demonstrated that the presence of a specific polymeric ligand on this nanoparticle enhances the internalization of CD44-positive cancer cells, accelerates endo/lysosomal escape, and facilitates the controlled release of CC within the cells. Furthermore, the results of the MTT assay also showed that AuNRs@HA-mPEG-Deta-LA as a protein nanocarrier demonstrated excellent biocompatibility. Importantly, this synergistic therapeutic strategy effectively induced apoptosis in A549 cancer cells by increasing the intracellular concentration of CC and utilizing the photothermal conversion of AuNRs, which was observed to be more effective compared to using only protein therapy or PTT. Therefore, this study showcased a nanoplatform based on AuNRs that has great potential for tumor-targeted protein delivery in combination with PTT in cancer treatment.

Hydraulic retention time governed the micro/nanostructures of titanium-incorporated diatoms and their photocatalytic activity.

Titanium-incorporated diatoms are promising biomaterials to photodegrade micropollutants such as pharmaceuticals and personal care products (PPCPs). Hydraulic retention time (HRT) is a key parameter for diatom cultivation and the incorporation of titanium into diatom frustules. This study assessed how HRT governs the micro/nanostructures, titania (TiO2) content and distribution, and the photocatalytic activity of titanium-incorporated diatom frustules. We cultivated a diatom strain Stephanodiscus hantzschii using a feed solution containing titanium(IV) in membrane bioreactors (MBRs) at a solids retention time (SRT) of 10 d and staged HRTs from 24 to 12 and to 6 h. The decrease in HRT reduced the porosity of diatom frustules but increased their silicon and titania contents. When the HRT decreased from 24 to 12 and to 6 h, the specific surface areas of the diatom decreased from 37.65 ± 3.19 to 31.53 ± 3.71 and to 18.43 ± 2.69 m2·g-1 frustules, while the titanium (Ti) contents increased from 53 ± 14 to 71 ± 9 and to 85 ± 13 mg Ti·g-1 frustules. The increase in the influent flow rates of the MBRs with decreasing HRTs likely enhanced nutrient diffusion inside the diatom valve pores, facilitating the uptake and incorporation of silicon and titanium. The titanium-incorporated frustules were effective in removing two representative PPCPs, bisphenol A (BPA) and N,N-diethyl-meta-toluamide (DEET), from water. As photocatalytic activity depends on the amount of titanium, decreasing the HRT substantially increased the photocatalytic activity of the titanium-incorporated frustules. In batch tests under ultraviolet light, frustules from the diatom cultivated at HRTs of 24, 12, and 6 h had the pseudo-first-order removal (mainly through photodegradation) rate constants of BPA of 0.376, 0.456, and 0.683 h-1, respectively. Under the same experimental condition, the pseudo-first-order removal rate constants of DEET by the frustules cultivated at HRTs of 24, 12, and 6 h increased from 0.270 to 0.330 and to 0.480 h-1.

Association between N, N-diethyl-m-toluamide exposure and the odds of kidney stones in US adults: a population-based study.

Background: Currently, there is limited research on the specific relationship between N, N-diethyl-m-toluamide (DEET) exposure and the odds of kidney stones. We aimed to investigate the relationship between DEET exposure and the prevalence of kidney stones. Methods: We included 7,567 qualified participants in our research from the 2007-2016 NHANES survey. We carried out three logistic regression models to explore the potential association between DEET exposure and the odds of kidney stones. Spline smoothing with generalized additive models (GAM) was utilized to assess the non-linear relationship and restricted cubic spline (RCS) curves was to determine the dose-response association. Multivariate regression models were used to conduct stratified analysis and sensitivity analysis. Results: Baseline characteristics of study participants presented the distribution of covariables. Regression analysis revealed that the odds of kidney stones were positively associated with the main metabolites of 3-diethyl-carbamoyl benzoic acid (DCBA) (log2) (OR = 1.05, 95% CI 1.02 to 1.08). The fourth quartile of urine DCBA showed a greater risk of kidney stones in the fully adjusted model (OR = 1.36, 95% CI 1.08 to 1.72). Another DEET metabolite of N, N-diethyl-3-hydroxymethylbenzamide (DHMB) was used to confirm the accuracy and stability of the results. The spline smoothing curve represented two main DEET metabolites had similar no-linear relationships and a positive trend with kidney stones proportion. RCS implied that the incidence of kidney stones rose with increasing levels of DEET exposure. High-risk groups on kidney stones were exhibited by stratified analysis under DEET exposure. Conclusion: Our study suggests that DEET exposure is positively associated with odds of kidney stones. Further investigation into the underlying processes of this association is required to guide the prevention and treatment of kidney stones.

Monitoring of serum 25-(OH)D level in infants and its correlation with bone density and development.

Serum 25-hydroxyvitamin D (25(OH)D) is an indicator of nutritional status in the body. Vitamin D (VD) is important for promoting calcium and phosphorus absorption and bone health. This work investigated the correlation between 25(OH)D level and bone density and bone development in infants. the bone density in 150 infants aged 0 to 3 years was measured by ultrasound. Based on the values of bone density, the infants were grouped into a normal (N) group (n = 95) and an abnormal (ABN) group (n = 55). At the same time, serum 25(OH)D, calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH) levels were detected to analyze their correlations. 25(OH)D, calcium, and phosphorus levels in the ABN group were greatly decreased, while ALP and PTH levels were increased obviously, all presenting remarkable differences with those in the N group (P<0.05). 25(OH)D was positively linked with bone density (r=0.918, P<0.01), calcium level (r=0.316, P<0.05) and phosphorus level (r=0.209, P<0.05) but showed negative associations with ALP level (r=-0.428, P<0.01) and PTH level (r=-0.327, P<0.05). elevating 25(OH)D was crucial in reducing the incidence of abnormal bone density, bettering bone metabolism, and improving the bone health of infants.

Green Production of a High-value Mosquito Insecticide of Nootkatone from Seaweed Hydrolysates.

Nootkatone is a type of valuable sesquiterpene that is widely used in food, cosmetics, fragrance, and other fields. The industry is faced with a major challenge due to the high expenses associated with plant-extracted nootkatone. We have developed a fermentation process for valencene production using seaweed hydrolysate as a carbon source via engineered Saccharomyces cerevisiae. Reduced-pressure distillation purified valencene was used as a substrate, and a yeast strain carrying HPO/AtCPR1 and ADH genes was constructed for whole-cell catalysis. After biotransformation at 25 °C for 3 h, a high yield of 73% for nootkatone production was obtained. Further, simple rotary evaporation was used to obtain nootkatone with a high purity of 97.4%. Mosquito-repellent testing showed that 1% nootkatone has a mosquito-repellent effect lasting up to 6 h, which is comparable to the 20% N,N-diethyl-meta-toluamide (DEET) effect. This study provided practical experience for developing third-generation biomass resources, generating new ideas for green manufacturing of valuable chemical products, and serving as a reference for creating efficient and eco-friendly mosquito repellents.

Diverse mechanisms of taste coding in Drosophila.

Taste systems encode chemical cues that drive vital behaviors. We have elucidated noncanonical features of taste coding using an unconventional kind of electrophysiological analysis. We find that taste neurons of Drosophila are much more sensitive than previously thought. They have a low spontaneous firing frequency that depends on taste receptors. Taste neurons have a dual function as olfactory neurons: They are activated by most tested odorants, including N,N-diethyl-meta-toluamide (DEET), at a distance. DEET can also inhibit certain taste neurons, revealing that there are two modes of taste response: activation and inhibition. We characterize electrophysiological OFF responses and find that the tastants that elicit them are related in structure. OFF responses link tastant identity to behavior: the magnitude of the OFF response elicited by a tastant correlated with the egg laying behavior it elicited. In summary, the sensitivity and coding capacity of the taste system are much greater than previously known.

Fabrication of amine-functionalized and multi-layered PAN-(TiO2)-gelatin nanofibrous wound dressing: In-vitro evaluation.

The development of advanced multifunctional wound dressings remains a major challenge. Herein, a novel multilayer (ML) electrospun nanofibers (NFs) wound dressing based on diethylenetriamine (DETA) functionalized polyacrylonitrile (PAN), TiO2 nanoparticles (NPs) coating (Ct), and bioderived gelatin (Gel) was developed for potential applications in wound healing. The ML PAN-DETA-Ct-Gel membrane was developed by combining electrospinning, chemical functionalization, synthesis, and electrospray techniques, using a layer-by-layer method. The ML PAN-DETA-Ct-Gel membrane is comprised of an outer layer of PAN-DETA as a barrier to external microorganisms and structural support, an interlayer TiO2 NPs (Ct) as antibacterial function, and a contact layer (Gel) to improve biocompatibility and cell viability. The NFs membranes were characterized by scanning electron microscopy (SEM), surface profilometry, BET analysis, and water contact angle techniques to investigate their morphology, surface roughness, porosity, and wettability. The ML PAN-DETA-Ct-Gel wound dressing exhibited good surface roughness, porosity, and better wettability. Cell morphology, proliferation, and viability were determined using fibroblasts (3T3), and antibacterial assays were performed against six pathogens. The ML PAN-DETA-Ct-Gel NFs membrane showed good cell morphology, proliferation, viability, and antibacterial activity compared with other membranes. This new class of ML NFs membranes offers a multifunctional architecture with adequate biocompatibility, cell viability, and antibacterial activity.

Poly(oxyethylene)/Poly(oxypropylene) butyl ether prolongs the repellent effect of N,N-diethyl-3-toluamide on the skin.

N,N-diethyl-meta-toluamide (DEET) is a widely used insect repellent, with minimal skin permeation and sustained repellent activity in the superficial layers of the skin. In this study, we prepared a 10% DEET formulation consisting of 40% ethanol with or without 2% poly(oxyethylene)/poly(oxypropylene) butyl ether (POE-POP), an amphiphilic random copolymer. Further, we demonstrated the effects of POE-POP on tensile stress (stickiness), hydrophobicity, skin retention, permeation, and repellent activity of DEET. Stickiness was measured in male ICR mice (7-week old), and skin retention and permeation were evaluated in male Wistar rats (7-week old). In addition, female Aedes albopictus were used to measure the repellent action of DEET. The addition of POE-POP did not affect stickiness, volatility, and degradability but decreased logP and increased viscosity of DEET. Next, we demonstrated the behavior of DEET formulations in the rat skin. POE-POP prolonged the retention of DEET in the superficial layers of the rat skin (skin surface and stratum corneum) and decreased the penetration of DEET into rat skin tissues (epithelium and dermis). The repellent effect of DEET was also enhanced by the addition of POE-POP. However, severe skin damage was not observed after repetitive treatment with DEET formulations containing POE-POP for one month (twice a day). In conclusion, we demonstrated that a 10% DEET formulation consisting of 40% ethanol and 2% POE-POP attenuated the skin penetration and prolonged the repellent action of DEET without causing stickiness and skin damage. We conclude that the combination of ethanol and POE-POP is useful as a safe and effective delivery system for the development of insect repellent formulations containing DEET.

Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort.

BACKGROUND: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. METHODS: We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17ß-estradiol, and testosterone was assessed using structural equation modeling. RESULTS: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration (ß)=-0.19 95% confidence interval (CI): -0.31, -0.07], language [ß=-0.12 (95% CI: -0.23, -0.01)], and memory/learning [ß=-0.11 (95% CI: -0.22, 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ß=-0.08 (95% CI: -0.14, -0.01)]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. CONCLUSION: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

Repellent efficacy of the nanogel containing Acroptilon repens essential oil in comparison with DEET against Anopheles stephensi.

OBJECTIVE: Malaria is a vector-borne disease that causes many deaths worldwide; repellents are a practical approach to malaria prevention, especially in endemic regions. RESULTS: Gas chromatography-mass spectrometry analysis was used to identify compounds in Acroptilon repens essential oil (EO). Alpha-copaene (15.67%), α-cubenen (3.76%), caryophyllene oxide (14.00%), 1-heptadecane (5.61%), and δ-cadinene (2.84) were five major compounds. After that, the nanoemulsion containing the EO with a particle size of 46 ± 4 nm, SPAN 0.85, PDI 0.4, and zeta potential - 5.7 ± 0.4 mV was prepared. Then, it was gellified by adding CMC (carboxymethyl cellulose) to the nanoemulsion. Besides, ATR-FTIR analysis (Attenuated Total Reflection-Fourier Transform InfraRed) was used to confirm the EO's successful loading in the nanogel. Finally, the protection time and repellent activity of nanogel compared to DEET (N, N-diethyl-meta-toluamide) were investigated against Anopheles stephensi. Interestingly, the nanogel with a protection time of 310 ± 45 min was significantly more potent than DEET (160 ± 17 min). It could thus be considered for future investigation against other mosquitoes.

Biomonitoring Equivalents for N,N-Diethyl-meta-toluamide (DEET).

N,N-Diethyl-meta-toluamide (DEET) is widely used as an effective mosquito and tick repellent. DEET is absorbed systemically after applications to skin. Once absorbed, DEET is rapidly metabolized with the predominant metabolite being m-dimethylaminocarbonyl benzoic acid (DBA). DEET and metabolites are predominantly excreted in urine after being absorbed systemically. Exposures to DEET are typically biomonitored via measures of DEET and DBA in urine. In this evaluation, we review available health-based risk assessments and toxicological reference values (TRVs) for DEET and derive Biomonitoring Equivalent (BE) values for interpretation of population biomonitoring data. BEs were derived based on existing TRVs derived by Health Canada, yielding 38 and 23 mg/L DBA in urine for adults and 57 and 34 mg/L DBA in urine in children for the acute oral and intermediate dermal TRVs, respectively. The BEs for unchanged DEET in urine are 21 and 12 mg/L in adults and 4.5 and 2.7 mg/L in children for the acute oral and intermediate dermal TRVs. The BE values derived in this manuscript can serve as a guide to help public health officials and regulators interpret population based DEET biomonitoring data in a public health risk context.

Challenges encountered by natural repellents: Since obtaining until the final product.

Vector-borne diseases, particularly the arboviruses dengue, Zika, chikungunya, and yellow fever caused by the Aedes aegypti mosquito, have been driving the use of repellents worldwide. The most representative synthetic repellent, DEET stands out as the market's oldest and most efficient repellent. It is considered a reference standard but presents considerable toxicity, not recommended for children up to 6 months old and pregnant women. For this reason, alternatives have been sought, and natural repellents derived mainly from essential oils have been studied, highlighting the essential oils of lemon (Corymbia citriodora), citronella (Cympobogon sp.), Andiroba (Carapa guianensis). However, the development and commercialization of products containing natural repellents are significantly lower when compared to DEET and other synthetic repellents. In order to understand the reasons, aspects related to safety, mechanism of action, efficacy as well development and complexity of the products were evaluated. It is concluded that, as for safety, there is lacking information in the literature regarding the effects on non-target organisms and robust toxicity data. The mechanism of action is based on theories, with less information on the exact mode of action, molecular targets, and interaction with the olfactory and taste receptors of insects. Despite being a current trend to search for actives from natural sources highly present in essential oils, however they reduced action time because due to rapid evaporation after application to the skin, thus requiring repellent vehicles. The development and complexity related to these products bring challenging aspects, beginning on the plant cultivation and extraction processes to produce essential oils with a more homogeneous chemical composition towards the formulation stabilization processes due to fast evaporation and short action time, with the use of pharmaceutical technology such as encapsulation techniques.