Ethyl Butylacetylaminopropionate Research Articles

In the arm-in-cage test, topical repellents activate mosquitoes to disengage upon contact instead of repelling them at distance

Topical repellents provide protection against mosquito bites and their efficacy is often assessed using the arm-in-cage test. The arm-in-cage test estimates the repellent’s protection time by exposing a repellent-treated forearm to host-seeking mosquitoes inside a cage at regular intervals until the first confirmed mosquito bite. However, the test does not reveal the repellents’ behavioural mode of action. To understand how mosquitoes interact with topical repellents in the arm-in-cage test, we used a 3D infrared video camera system to track individual Aedes aegypti and Anopheles stephensi females during exposure to either a repellent-treated or an untreated forearm. The repellents tested were 20% (m/m) ethanolic solutions of N, N-diethyl-meta-toluamide, p-menthane-3,8-diol, icaridin and ethyl butylacetylaminopropionate. All four repellents substantially reduced the number of bites compared to an untreated forearm, while the flight trajectories indicate that the repellents do not prevent skin contact as the mosquitoes made multiple brief contacts with the treated forearm. We conclude that, in the context of the arm-in-cage test, topical repellents activate mosquitoes to disengage from the forearm with undirected displacements upon contact rather than being repelled at distance by volatile odorants.

Study of the Repellent Activity of 60 Essential Oils and Their Main Constituents against Aedes albopictus, and Nano-Formulation Development.

Mosquitoes are one of the most important disease vectors from a medical viewpoint in that they transmit several diseases such as malaria, filariasis, yellow and Dengue fever. Mosquito vector control and personal protection from mosquito bites are currently the most efficient ways to prevent these diseases. Several synthetic repellents such as DEET, ethyl butylacetylaminopropionate (IR3535) and 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) (Picaridin), have been widely used to prevent humans from receiving mosquito bites. However, the use of synthetic repellents has raised several environment and health concerns. Therefore, essential oils (EOs) as natural alternatives receive our attention. In order to discover highly effective mosquito repellents from natural sources, the repellent activity of 60 commercial EOs against Ae. albopictus was screened in this study. Eight EOs including cinnamon, marjoram, lemongrass, bay, chamomile, jasmine, peppermint2, and thyme, showed a suitable repellent rate (>40%) at the tested dose of 10 μg/cm2. Then, their main constituents were analyzed by GC-MS, and the active constituents were identified. The most active compounds including cinnamaldehyde, citral and terpinen-4-ol, exhibited an 82%, 65% and 60% repellent rate, respectively. Moreover, the nanoemulsions of the three active compounds were prepared and characterized. In the arm-in-cage assay, the protection times of the nanoemulsions of cinnamaldehyde and citral were significantly extended compared with their normal solutions. This study provides several lead compounds to develop new mosquito repellents, and it suggests that nanoemulsification is an effective method for improving the duration of the activity of natural repellents.

Structure, Properties, and Release Kinetics of the Polymer/Insect Repellent System Poly (l-Lactic Acid)/Ethyl Butylacetylaminopropionate (PLLA/IR3535)

The insect repellent ethyl butylacetylaminopropionate (IR3535) was used as a functional additive for poly (l-lactic acid) (PLLA) to modify its structure and mechanical properties and achieve insect repellency. PLLA/IR3535 mixtures at various compositions were prepared via melt extrusion. In the analyzed composition range of 0 to 23 m% IR3535, PLLA and IR3535 were miscible at the length scale represented by the glass transition temperature. Addition of IR3535 resulted in a significant decrease in the glass transition temperature of PLLA, as well as in the elastic modulus, indicating its efficiency as a plasticizer. All mixtures were amorphous after extrusion, though PLLA/IR3535 extrudates with an IR3535 content between 18 and 23 m% crystallized during long-term storage at ambient temperature, due to their low glass transition temperature. Quantification of the release of IR3535 into the environment by thermogravimetric analysis at different temperatures between 50 and 100 °C allowed the estimation of the evaporation rate at lower temperatures, suggesting an extremely low release rate with a time constant of the order of magnitude of 1-2 years at body temperature.

Mosquito Repellents: Efficacy Tests of Commercial Skin-Applied Products in China.

As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5–3.88 h landing time and/or 1–5.63 h probing time) and lower prices (13.9–21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents.

3D-printing of the polymer/insect-repellent system poly(l-lactic acid)/ethyl butylacetylaminopropionate (PLLA/IR3535)

The polymer/solvent system poly(l-lactic acid)/ethyl butylacetylaminopropionate (PLLA/IR3535) is regarded as an insect-repellent-delivery system, serving, e.g., for fighting mosquito-borne tropical diseases. In such systems the solid polymer hosts the liquid repellent, with the latter slowly released to the environment, expelling mosquitoes. As a new approach, exceeding prior work about application of different technologies to obtain such devices, in this work, samples of the polymer/repellent system PLLA/IR3535 were prepared by 3D-printing. The experiments showed that it is possible to print 3D-parts containing up to 25 m% repellent, with an only minor loss of repellent during the printing process. For samples containing low amount of repellent, crystallization of PLLA was suppressed due to the rather fast cooling step and the low bed temperature of around 25 °C, being lower than the glass transition temperature of the homogeneous polymer/repellent strands. At higher repellent concentration, due to the lowering of the glass transition temperature to near or even below ambient temperature, the crystallinity slowly increased during storage after printing. For all samples, regardless of the initial repellent concentration, the repellent-release rate increases with temperature, and at ambient temperature the release-time constant is in the order of 10 days. The study successfully proved the applicability of the technology of extrusion-based 3D-printing for the preparation of polymer parts with a specific shape/design containing mosquito-repellent at a concentration which raises the expectation to be used as a repellent delivery-device.

Synthesis of polymeric particles with insect repellent for potential application on textile substrates

This paper presents a process for producing particles loaded with the insect repellent ethyl butylacetylaminopropionate (IR3535®). The encapsulated particles were prepared via emulsification using monomers—2-hydroxyethyl methacrylate, methyl methacrylate, and sodium styrene sulfonate—and sodium persulfate—the initiator of the reaction—in an aqueous colloidal silica solution. The emulsion polymerization was carried out at 75 °C for 240 min without surfactants. The encapsulated materials were characterized by dynamic light scattering, electrophoretic mobility, scanning electron microscopy, Raman spectroscopy, and thermogravimetry. The encapsulated particles were in the submicrometric scale with an average diameter of 879 nm, moderate polydispersity index of approximately 0.5, and negative zeta potential. The encapsulation of 12.2% IR3535® was confirmed by high-performance liquid chromatography, demonstrating the efficacy of the encapsulated active material. The emulsion polymerization processes produced insect-repellent-carrying submicroparticles, thereby presenting a promising system for protection against mosquito bites with possible application to textiles.

Crystallization-Induced Polymer Scaffold Formation in the Polymer/Drug Delivery System Poly(l-lactic acid)/Ethyl Butylacetylaminopropionate (PLLA/IR3535)

Polymer/mosquito-repellent scaffolds exhibit increasing importance in long-lasting human skin protection to be used as wearable devices and allowing for controlled release of repellents. In this study, ethyl butylacetylaminopropionate (IR3535) was used as a human and environmental friendly active mosquito-repellent serving as a solvent to form functional poly(l-lactic acid) (PLLA) scaffolds by crystallization-based solid-liquid thermally induced phase separation. Crystallization of PLLA in the presence of IR3535 is faster than melt-crystallization of neat PLLA, and in the investigated concentration range from 5 to 50 mass % PLLA, its maximum crystallization rate increases with the PLLA content, by both, increases of the maximum crystal growth rate and of the nuclei density. By adjusting the polymer concentration and the crystallization temperature, microporous scaffolds of different fine structures are obtained, hosting the mosquito-repellent in intra- and interspherulitic pores for its intended later evaporation.

Degradation of ethyl butylacetylaminopropionate (IR3535) during chlorination: Tentative identification and toxicity prediction of its disinfection by-products

Studies have reported the presence of ethyl butylacetylaminopropionate (IR3535) in waters, and the content of this repellent is expected to rise significantly in the future. There are extremely scarce data in the literature regarding the behavior of IR3535 and its derivatives in water. The present work reports the results obtained from experiments conducted under controlled conditions aiming at investigating the transformation of IR3535 in chlorinated water, in addition to an attempt to identify its disinfection by-products (DBPs). The work also reports the findings of analyses conducted in swimming pool water samples which sought to investigate the presence and content of IR3535 and its targeted DBPs in these samples. The results obtained in the controlled experiments show that IR3535 is not completely degraded under the chlorinated conditions evaluated and 9 DBPs were tentatively identified. The presence of IR3535 was detected in both adults and children’s pool water samples at concentrations ranging from 62 ng L−1 to 114 ng L−1. Some of the DBPs identified in the controlled experiments were also detected in the pool water samples. The toxicity of the 9 DBPs identified was evaluated using the QSAR model, where some by-products presented mutagenic and carcinogenic properties.

Риск применения репеллентных средств для детей раннего возраста

Flying blood-sucking insects widely distributed on the territory of the Russian Federation. Mosquitoes pose a high epidemiological hazard being vectors of many infectious diseases, for example, West Nile fever. Children are one the most vulnerable category of population when attacked by flying blood-sucking insects. Toxicity and hazard of repellent products in different formulations based on 10 % ethyl butylacetylaminopropionate were studied. In connection with the need of the population to protect their children from mosquito bites, it is relevant to evaluate repellent products intended for use on children under one year old. The harmful effects were revealed in the study of the skin-resorptive action of repellent products in doses exceeding the consumption rate by 30 and 50 times, manifested by a change in the state of the nervous system, liver function and a decrease in red blood parameters.

Full-composition-range glass transition behavior of the polymer/solvent system poly (lactic acid) / ethyl butylacetylaminopropionate (PLA/IR3535®)

The polymer/solvent system poly (lactic acid)/ethyl butylacetylaminopropionate (PLA/IR3535®) is considered as a drug-delivery system, in which a polymer hosts a liquid with a functionality as insect repellent. Such devices require solubility of the components at high temperature and observation of crystallization-induced solid-liquid phase separation on cooling. Precise knowledge of the thermodynamic solubility of the components is then difficult to obtain due to possible superposition of liquid-liquid phase separation with polymer crystallization. Therefore, in the present study the miscibility of the polymer/solvent system PLA/IR3535® was explored by employing non-crystallizable PLA, by analysis of the glass transition behavior in the full composition range. The data revealed that the two components are miscible regardless the system composition, with the glass transition temperature of solutions showing a negative deviation from the linear mixing rule, suggesting rather weak enthalpic interactions of the system components. The study included application of conventional and fast scanning chip calorimetry, which allowed for controlled and stepwise evaporation of solvent by repeated exposing the system to elevated temperature and evaluation of the glass transition temperature during in-between cooling and reheating. This novel approach permits an efficient analysis of the glass transition temperature as function of the system composition in a single experiment in a wide range of solvent concentrations.

Mosquito repellent thermal stability, permeability and air volatility

The effectiveness of mosquito repellents, whether applied topically on the skin or released from a wearable device, is determined by the evaporation rate. This is because a repellent has to be present in the form of a vapour in the vicinity of the exposed skin that needs protection. Therefore, gravimetric techniques were used to investigate the direct evaporation of selected liquid repellents, their permeation through polymer films, and their release from a microporous polyethylene matrix. Evaporation of a repellent into quiescent air is determined by its air permeability. This is a product of the vapour pressure and the diffusion coefficient, i.e. . It was found that repellents could be ranked in terms of decreasing volatility as: ethyl anthranilate > citriodiol > dimethyl phthalate > N,N-diethyl-meta-toluamide (DEET) > decanoic acid > ethyl butylacetylaminopropionate > Icaridin. Experimental SA values, at 50 °C, ranged from 0.015± 0.008 mPa m2 s-1 for the least volatile repellent (Icaridin) to 0.838± 0.077mPam2 s-1 for the most volatile (ethyl anthranilate). The release rate from microporous polyethylene strands, produced by extrusion-compounding into ice water baths followed a similar ranking. These strands featured an integral skin-like membrane that covered the extruded strands and controlled the release of the repellent at a low effective rate. The high thermal and thermo-oxidative stability together with the low volatility of the mosquito repellents ethyl butylacetylaminopropionate and Icaridin make them attractive candidates for long-lasting wearable mosquito-repellent devices. Such anklets/bracelets may have utility for outdoor protection against infective mosquito bites in malaria-endemic regions. © 2019 Society of Chemical Industry.

Determination of antimicrobial and antiviral properties of IR3535.

Insect repellent is a substance directly applied to skin or clothing in order to repel flies, mosquitoes, ticks etc. IR3535 or Ethyl butylacetylaminopropionate (EBAAP) is a relatively new repellent which is classified as a biopesticide due to exceptional skin tolerance and overall safety. The repellency against various insect and ticks, and the low toxicity of IR3535 are well acknowledged. However, there has been no attempt to investigate the effects on microorganisms or viruses up to now. In the present study, antimicrobial activity was investigated based on disc diffusion and micro-well dilution assays. Disc diffusion assays revealed IR3535 displayed remarkable antimicrobial activity on the microorganisms tested. MIC results showed that the antifungal efficiency of IR3535 is higher with respect to its antibacterial and anticandidal efficiency. Moreover, antiviral test results revealed that IR3535 showed antiviral effects against Poliovirus and Adenovirus. This is the first study that reveals IR3535's antimicrobial and antiviral properties against a broad range of microorganisms and viruses. In consideration of the antimicrobial and antiviral properties, IR3535 is a promising agent that could be used to develop novel therapeutic approaches, new application areas and formulations in the future.

Which insect repellents should we choose? Implications from results of local market survey and review of current guidelines

Mosquito-borne diseases are global problems. The use of topical insect repellents is a key measure recommended by health authorities to prevent mosquito-borne diseases. Despite more than a hundred commercial products available in the market, there are relatively few active ingredients used across these formulations. The most common active components are diethyltoluamide, picaridin, p-menthane-3,8-diol, ethyl butylacetylaminopropionate (IR3535) and a range of plant-derived products. Research has shown that each of these active ingredients vary in the duration of protection provided against biting mosquitoes. However, the wide spectrum of commercial preparations and various recommendations from different health authorities make it a challenge to pick an effective product for end users as well as healthcare personnel. A local market survey was conducted to assess the mosquito repellent formulae in available products in Hong Kong, and a review of the current recommendations issued by local and overseas authorities on choosing the suitable insect repellents is performed with consideration of recent research and currently available topical repellents in the market.

A promising azeotrope-like mosquito repellent blend

Topical repellents play a key role in reducing the outdoor transmission of mosquito-borne diseases by reducing human-vector contact. Excellent repellents are available, but there is always room for improvement. This article reports on a particularly effective binary repellent blend of ethyl butylacetylaminopropionate and nonanoic acid. A composition containing 25 mol% of the acid exhibits negative pseudo-azeotrope behaviour at 50 °C, meaning that the liquid vapour pressure is lower than that of the parent compounds and evaporation occurs without a change in the liquid composition. In tests performed using the South African Medical Research Council’s cup-on-arm procedure, this mixture provided better protection for a longer time than the “gold standard of mosquito repellents”, namely N,N-diethyl-m-toluamide, commonly known as DEET.

Development and validation of an analytical method using High Performance Liquid Chromatography (HPLC) to determine ethyl butylacetylaminopropionate in topical repellent formulations

ABSTRACT Diseases caused by insects are frequent in poor countries, leading to epidemic scenarios in urban areas; e.g., Dengue, Zika and Chikungunya. For this reason, the development of a safe and efficient topical formulation is essential. Ethyl butylacetylaminopropionate (EB) is a mosquito repellent developed by Merck, which is used in products for adults, children and especially babies, due to its low allergenic potential. The aim of this work was to validate an analytical methodology to quantify EB in a new poloxamer-based formulation by high-performance liquid chromatography (HPLC). The quantification methodology was performed at 40 oC using a Kromasil reverse-phase column (C18), with the dimensions of 250 x 4.6 mm. The mobile phase was acetonitrile:water (1:1) at a 1.0 mL/min flow-rate. The detector wavelength was set at 218 nm to detect EB. The methodology was considered validated since the results indicated linearity (R2>0.99), specificity, selectivity, precision and accuracy (active recovery between 98% and 102%). It also presented limits of detection and quantification of 0.255 µg/mL and 0.849 µg/mL, respectively. The present study demonstrated the EB vehiculated in poloxamer gel is promising as a new insect repellent formulation, since it could be quantified and quality control evaluated.

Development and characterization of repellent formulations based on nanostructured hydrogels

Diseases caused by insects could lead to epidemic scenarios in urban areas and insect repellents are a shield against a wide range of insects, but they need to be safe without compromising efficacy. Ethyl butylacetylaminopropionate (EB) is a synthetic mosquito repellent, which could be used in products for adults and children due to its low-allergenic potential. The aim of this study was to develop and characterize EB and Poloxamer 407 nanoemulsions regarding their droplets mean size, pH, rheological properties, cytotoxicity and in vitro permeation profile. The developed formulations (F1 with 12.5% of EB and F2 with 25% of EB) were compared with a commercial formulation containing 12.5% of EB. Droplets mean size was determined by DLS, and for both nanoemulsions they were around 200 nm; however, the commercial formulation presented a droplets mean size of 10 nm, which could contribute to its high permeation. F1 and F2 presented a gel-like behavior, however F2 presented lower viscosity due to the presence of more EB between the polymer chains preventing them to interact with each other. Also, F2 was less retained by the epidermis when compared to F1 probably due to its lower viscosity. For the cytotoxicity assay only F2, which presented the highest concentration of EB was tested, and it was not toxic to the cells. This result could be also extended to F1 which presented half the EB concentration. The present study demonstrated that EB and Poloxamer 407 nanoemulsions are promising as new insect-repellent formulations.

Coticotropine-Releasing Hormone receptor 1 (CRHR1) signalling interferes with steroid biosynthesis of ovarian granulosa cells

Repellency activity of Thai essential oils derived from ylang ylang (Cananga odorata (Lamk.) Hook.f. & Thomson: Annonaceae) and lemongrass (Cymbopogon citratus (DC.) Stapf: Poaceae) were tested against two mosquito vectors, Aedes aegypti (L.) and Culex quinquefasciatus (Say). There were compared with two chemical repellents (DEET 20% w/w; Sketolene Shield® and IR3535, ethyl butylacetylaminopropionate 12.5% w/w; Johnson's Baby Clear Lotion Anti-Mosquito®). Each herbal repellent was applied in three diluents; coconut oil, soybean oil and olive oil at 0.33 μl/cm2 on the forearm of volunteers. All herbal repellent exhibited higher repellent activity than IR3535 12.5% w/w, but lower repellent activity than DEET 20% w/w. The C. odorata oil in coconut oil exhibited excellent activity with 98.9% protection from bites of A. aegypti for 88.7 ± 10.4 min. In addition, C. citratus in olive oil showed excellent activity with 98.8% protection from bites of C. quinquefasciatus for 170.0 ± 9.0 min. While, DEET 20% w/w gave protection for 155.0 ± 7.1–182.0 ± 12.2 min and 98.5% protection from bites of two mosquito species. However, all herbal repellent provided lower repellency activity (97.4–98.9% protection for 10.5–88.7 min) against A. aegypti than C. quinquefasciatus (98.3–99.2% protection for 60–170 min). Our data exhibited that C. odorata oil and C. citratus oil are suitable to be used as green repellents for mosquito control, which are safe for humans, domestic animals and environmental friendly.

Efficacy of Thai herbal essential oils as green repellent against mosquito vectors

Repellency activity of Thai essential oils derived from ylang ylang (Cananga odorata (Lamk.) Hook.f. & Thomson: Annonaceae) and lemongrass (Cymbopogon citratus (DC.) Stapf: Poaceae) were tested against two mosquito vectors, Aedes aegypti (L.) and Culex quinquefasciatus (Say). There were compared with two chemical repellents (DEET 20% w/w; Sketolene Shield® and IR3535, ethyl butylacetylaminopropionate 12.5% w/w; Johnson's Baby Clear Lotion Anti-Mosquito®). Each herbal repellent was applied in three diluents; coconut oil, soybean oil and olive oil at 0.33μl/cm2 on the forearm of volunteers. All herbal repellent exhibited higher repellent activity than IR3535 12.5% w/w, but lower repellent activity than DEET 20% w/w. The C. odorata oil in coconut oil exhibited excellent activity with 98.9% protection from bites of A. aegypti for 88.7±10.4min. In addition, C. citratus in olive oil showed excellent activity with 98.8% protection from bites of C. quinquefasciatus for 170.0±9.0min. While, DEET 20% w/w gave protection for 155.0±7.1–182.0±12.2min and 98.5% protection from bites of two mosquito species. However, all herbal repellent provided lower repellency activity (97.4–98.9% protection for 10.5–88.7min) against A. aegypti than C. quinquefasciatus (98.3–99.2% protection for 60–170min). Our data exhibited that C. odorata oil and C. citratus oil are suitable to be used as green repellents for mosquito control, which are safe for humans, domestic animals and environmental friendly.

English

Repellent activity of Thai essential oils derived from ylang-ylang (Cananga odorata), lemon grass (Cymbopogon citratus) and citronella grass (Cymbopogon nardus) were evaluated against female Aedes aegypti (L.) and Culex quinquefasciatus (Say) and compared a commercially available repellents (IR3535, ethyl butylacetylamino propionate 12.5% w/w; Johnson’s Baby Clear Lotion Anti-Mosquito®). Each test repellent was applied at 0.17 and 0.33 µl/cm2 on the forearm of volunteers. All essential oils at 0.17 µl/cm2 showed lower protection time and percentage of protection against two mosquito species than at 0.33 µl/cm2. All essential oils exhibited higher repellent activity than chemical repellent. The essential oil of C. citratus at 0.33µl/cm2 exhibited excellent repellent activity with 98.67% protection from bites of A. aegypti for 116.67±55.75 min and 99.75% protection from bites of C. quinquefasciatus for 128.33±12.89 min. However, repellent activity in order of protection time and percentage of protection against two mosquito species in three essential oils was C. citratus oil >C. odorata oil >C. nardus oil. Our data showed that C. citratus oil is an effected green repellent for mosquitoes that is safe for humans and environmentally friendly.   Key words: Repellent, Aedes aegypti, Culex quinquefasciatus, Thai essential oil.

Expert Review of the Evidence Base for Arthropod Bite Avoidance

Bite avoidance measures are commonly recommended to international travelers to help reduce the risk of various arthropod‐borne diseases. A key strategy is the use of repellents applied topically to skin or clothing which are considered in the first part of this review. Also advised are a variety of methods that employ the use of insecticides and physical barriers such as mosquito nets or oil preparations applied to the skin. In the following document, the authors considered some of the most widely used bite avoidance methods and identified the strength and quality of evidence that determined efficacy. The overall purpose of the review is to provide the available evidence, in a graded format, upon which to base recommendations for the selection of appropriate repellents and other methods of bite avoidance in those traveling overseas. The authors were asked to consider the effectiveness of the most commonly used active ingredients (AIs) in repellent formulations and methods of bite avoidance. The evidence base considered protection against nuisance biting insects, reduction in the incidence of arthropod‐borne diseases, and safety profile. Effectiveness of the repellent related to spectrum of activity against various mosquito species and other arthropods was examined as well as longevity of applied dose. Where possible, efficacy was compared to deet as being the accepted gold standard. All sections employed MEDLINE via PubMed in literature searches augmented by others depending on the subject area investigated. Details of the review process can be found at http://www.istm.org; click on “ISTM Committees” and then “Publications.” ### Major Findings N , N ‐diethyl‐3‐methylbenzamide (deet), (2‐(2‐hydroxyethyl)‐piperidinecarboxylic acid 1‐methyl ester (icaridin), p ‐methane 3, 8‐diol (PMD), and ethyl butylacetylaminopropionate (IR3535)‐based repellents all provide protection against biting arthropods, but volatile oils and other natural products are less reliable. On the strength of available evidence, the first‐line choice for those visiting areas where …