piperidines and picaridin

Topics: Administration, Topical; Animals; DEET; Humans; Insect Bites and Stings; Insect Repellents; Piperidines; Plant Oils; Propionates

This review examines the published laboratory and field tests where the repellents DEET and picaridin have been compared for their efficacy as repellents against mosquitoes. The review is limited to an assessment of whether the duration of protection afforded by picaridin is similar to or better than DEET.. Identification and analysis of laboratory and field-based trials published in peer-reviewed journals that compared DEET to picaridin efficacy.. Only eight field studies and three laboratory studies met the review criteria for inclusion and most were considered to be of high risk of bias and of lower quality when judged against evidence-based principles. Overall, the studies showed little potential difference between DEET and picaridin applied at the same dosage, with some evidence pointing to a superior persistence for picaridin.. Applied dosage is one important variable in determining the persistence of a repellent experienced by users but the maximum concentration in current picaridin formulation is <30%w/v. Therefore, where only 30% DEET or lower concentrations are available, then on current evidence, it is reasonable to offer DEET or picaridin as a first choice. Where >50% DEET products are available then the protection time advantage associated with these formulations reasonably can be invoked to consider them as first choice repellents.

Topics: Animals; Culicidae; DEET; Dose-Response Relationship, Drug; Humans; Insect Bites and Stings; Insect Repellents; Piperidines; Travel-Related Illness

Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances.

Topics: Administration, Cutaneous; Animals; DEET; Humans; Insect Repellents; Piperidines; Skin Absorption; Sunscreening Agents

Mosquito-borne disease is an annual problem in Australia, with endemic pathogens such as Ross River virus infecting thousands of people each year. The recent emergence of Zika virus in South America and the Pacific, together with ongoing outbreaks of dengue viruses in Southeast Asia, generated great community interest in the most effective strategies to avoid mosquito bites. Large-scale mosquito control programs are not common in Australia and are limited in New South Wales (NSW). The use of topical insect repellents is a key recommendation by health authorities to prevent mosquito-borne disease. All products sold in Australia purporting to repel mosquitoes must be registered with the Australian Pesticides and Veterinary Medicines Authority. Despite around 100 commercial products registered as repelling mosquitoes, there are relatively few active ingredients used across these formulations. The most common are diethyltoluamide (DEET), picaridin, p-menthane-3,8-diol (PMD) and a range of plant-derived products (e.g. melaleuca, eucalyptus, citronella oils). Research has shown that each of these active ingredients varies in the duration of protection provided against biting mosquitoes. Recommendations by health authorities are informed by this research, but inconsistencies between recommendations and available repellent formulations and their concentration of active ingredients can cause confusion in the community. There are conflicts between the data resulting from scholarly research, marketing promotion by manufacturers and recommendations provided by overseas health authorities. A review was undertaken of NSW Health's current recommendations on choosing and using insect repellents, taking into consideration recent research and currently registered topical repellents.

Topics: Animals; Australia; Culicidae; Cyclohexane Monoterpenes; DEET; Humans; Insect Repellents; Menthol; Piperidines; Practice Guidelines as Topic

Ticks are arthropods and the most important vectors of major human diseases after mosquitoes. Due to their impact on public health, in vitro and in vivo assays have been developed to identify molecules with repellent activities on ticks. Repellents are useful to reduce tick bite exposure and the potential transmission of pathogens; they can be used topically or in impregnated clothing. Presently, mainly synthetic molecules are commercialized as skin repellents, e.g., N,N-diethyl-meta-toluamide (DEET), IR3535, picaridin or KBR 3023, and para-menthanediol. Permethrin is largely used for fabric impregnation. Intensive research has been conducted to identify new molecules with repellent activity and more recently, plant-derived molecules, as an alternative to synthetic molecules.

Topics: Acaricides; Animals; Arthropod Vectors; Biological Assay; DEET; Humans; Oils, Volatile; Permethrin; Piperidines; Plant Extracts; Propionates; Protective Clothing; Tick Bites; Tick-Borne Diseases; Ticks

Arthropod bites remain a major cause of patient morbidity. These bites can cause local or systemic effects that may be infectious or inflammatory in nature. Arthropods, notably insects and arachnids, are vectors of potentially serious ailments including malaria, West Nile virus, dengue, and Lyme disease. Measures to curtail the impact of insect bites are important in the worldwide public health effort to safely protect patients and prevent the spread of disease. The history of insect repellent (IR) lends insight into some of the current scientific strategies behind newer products. Active ingredients of currently available IRs include N,N-diethyl-3-methylbenzamide (DEET), botanicals, citronella, and, the newest agent, picaridin. Currently, the Environmental Protection Agency's registered IR ingredients approved for application to the skin include DEET, picaridin, MGK-326, MGK-264, IR3535, oil of citronella, and oil of lemon eucalyptus. DEET has reigned as the most efficacious and broadly used IR for the last 6 decades, with a strong safety record and excellent protection against ticks, mosquitoes, and other arthropods. Newer agents, like picaridin and natural products such as oil of lemon eucalyptus are becoming increasingly popular because of their low toxicity, comparable efficacy, and customer approval. Various characteristics and individual product advantages may lead physicians to recommend one agent over another.

Topics: Adult; Animals; Child; DEET; Eucalyptus; Garlic; Humans; Insect Bites and Stings; Insect Repellents; Oils, Volatile; Permethrin; Piperidines; Plant Oils; Receptors, Odorant

In many United States households, there are many substances used to control the exposure of our children to mosquitoes, mice and rats. This review provides information on common mosquito repellents and rodenticides used in households and discusses their toxicity, in order to help pediatricians better advise their patients of their proper use.. A recent study has demonstrated that many continue to have practices of applying DEET (N,N-diethyl-3-methylbenzamide) based repellents that may lead to undesirable effects. Picaridin and oil of lemon eucalyptus are two products that have recently been shown to have an efficacy similar to that of DEET-based repellents. Studies within the last five years show that most unintentional superwarfarin ingestions can be managed at home with close outpatient follow-up. There does not appear to be a benefit of prophylactic vitamin K or gastrointestinal decontamination in patients with relatively small ingestions of superwarfarins.. With education and correct usage, mosquito repellents and the superwarfarin rodenticides can help protect children from significant vector-borne diseases. Not all exposures lead to significant morbidity or mortality. With recognition of the current literature, most of these exposures can be managed safely at home or as an outpatient, ultimately saving healthcare costs.

Topics: 4-Hydroxycoumarins; Child; DEET; Eucalyptus; Humans; Insect Repellents; Phytotherapy; Piperidines; Rodenticides

The protection against arthropods especially disease transmitting mosquitoes is becoming more and more important. The problems with drugs used for treatment and prophylactic of malaria are rapidly growing due to emergence of resistant parasites and unwanted side effects. Furthermore the population living in endemic area often can't afford the new expensive drugs. A safe and effective way of preventing insect bites is needed. One can prevent arthropod born diseases by avoiding insect bites through physical and chemical means or a combination of both. Repellents are substances applied to the skin, which effectively prevent insects from biting. The gold standard is still Diethylbenzamine (DEET), which is highly effective, well documented and in use for more than 50 years. The new repellent Bayrepel (hydroxyethyl isobutyl piperidin carboxylate) available to the consumer since 1998, seems to have an efficacy comparable with DEET. Insecticides have a direct toxic effect on the nervous system of arthropods. Mainly synthetic pyrethroids, which produce less ecological problems than the older products, are used. They are supplied in form of sprays, vaporising mats or coils. An important progress is the combination of insecticides with physical means. Insecticide treated bed nets or clothes give an excellent protection. Topical or systemic Vitamin B1, acoustic devices and electrocuters are still sold and widely used although their complete ineffectivity is documented in many studies.

Topics: Animals; beta-Alanine; Culicidae; Humans; Insect Bites and Stings; Insect Control; Insect Repellents; Insect Vectors; Insecticides; Piperidines; Plants; Protective Clothing; Pyrethrins; Travel

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013.. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events.. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use.. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

Topics: Cambodia; Dizziness; Headache; Humans; Insect Repellents; Mosquito Control; Piperidines; Rural Population; Treatment Outcome

Although effective topical repellents provide personal protection against malaria, whether mass use of topical repellents in addition to long-lasting insecticidal nets can contribute to a further decline of malaria is not known, particularly in areas where outdoor transmission occurs. We aimed to assess the epidemiological efficacy of a highly effective topical repellent in addition to long-lasting insecticidal nets in reducing malaria prevalence in this setting.. A cluster randomised controlled trial was done in the 117 most endemic villages in Ratanakiri province, Cambodia, to assess the efficacy of topical repellents in addition to long-lasting insecticidal nets in controlling malaria in a low-endemic setting. We did a pre-trial assessment of village accessibility and excluded four villages because of their inaccessibility during the rainy season. Another 25 villages were grouped because of their proximity to each other, resulting in 98 study clusters (comprising either a single village or multiple neighbouring villages). Clusters were randomly assigned (1:1) to either a control (long-lasting insecticidal nets) or intervention (long-lasting insecticidal nets plus topical repellent) study group after a restricted randomisation. All clusters received one long-lasting insecticidal net per individual, whereas those in the intervention group also received safe and effective topical repellents (picaridin KBR3023, SC Johnson, Racine, WI, USA), along with instruction and promotion of its daily use. Cross-sectional surveys of 65 randomly selected individuals per cluster were done at the beginning and end of the malaria transmission season in 2012 and 2013. The primary outcome was Plasmodium species-specific prevalence in participants obtained by real-time PCR, assessed in the intention-to-treat population. Complete safety analysis data will be published seperately; any ad-hoc adverse events are reported here. This trial is registered with ClinicalTrials.gov, number NCT01663831.. Of the 98 clusters that villages were split into, 49 were assigned to the control group and 49 were assigned to the intervention group. Despite having a successful distribution system, the daily use of repellents was suboptimum. No post-intervention differences in PCR plasmodium prevalence were observed between study groups in 2012 (4·91% in the control group vs 4·86% in the intervention group; adjusted odds ratio [aOR] 1·01 [95% CI 0·60-1·70]; p=0·975) or in 2013 (2·96% in the control group vs 3·85% in the intervention group; aOR 1·31 [0·81-2·11]; p=0·266). Similar results were obtained according to Plasmodium species (1·33% of participants in the intervention group vs 1·10% in the intervention group were infected with Plasmodium falciparum; aOR 0·83 [0·44-1·56]; p=0·561; and 1·85% in the control group vs 2·67% in the intervention group were infected with Plasmodium vivax; aOR 1·51 [0·88-2·57]; p=0·133). 41 adverse event notifications from nine villages were received, of which 33 were classified as adverse reactions (11 of these 33 were cases of repellent abuse through oral ingestion, either accidental or not). All participants with adverse reactions fully recovered and 17 were advised to permanently stop using the repellent.. Mass distribution of highly effective topical repellents in resource-sufficient conditions did not contribute to a further decline in malaria endemicity in a pre-elimination setting in the Greater Mekong subregion. Daily compliance and appropriate use of the repellents remains the main obstacle.. Bill & Melinda Gates Foundation.

Topics: Adolescent; Adult; Animals; Cambodia; Child; Cluster Analysis; Cross-Sectional Studies; Female; Humans; Insect Repellents; Insect Vectors; Insecticide-Treated Bednets; Malaria, Falciparum; Malaria, Vivax; Male; Mosquito Control; Piperidines; Prevalence

The public health value of a vector control tool depends on its epidemiological efficacy, but also on its ease of implementation. This study describes an intensive distribution scheme of a topical repellent implemented in 2012 and 2013 for the purpose of a cluster-randomized trial using the existing public health system. The trial aimed to assess the effectiveness of repellents in addition to long-lasting insecticidal nets (LLIN) and occurred in a province of Cambodia. Determinants for accessibility and consumption of this tool were explored.. 135 individuals were appointed to be repellent distributors in 57 villages. A 2-weekly bottle exchange programme was organized. Distributors recorded information regarding the amount of bottles exchanged, repellent leftover, and reasons for not complying in household data sheets. Distributor-household contact rates and average 2-weekly consumption of repellent were calculated. Household and distributors characteristics were obtained using questionnaires, surveying 50 households per cluster and all distributors. Regression models were used to explore associations between contact and consumption rates and determinants such as socio-economic status. Operational costs for repellent and net distribution were obtained from the MalaResT project and the provincial health department.. A fourfold increase in distributor-household contact rates was observed in 2013 compared to 2012 (median2012 = 20 %, median2013 = 88.9 %). Consumption rate tripled over the 2-year study period (median2012 = 20 %, median2013 = 57.89 %). Contact rates were found to associate with district, commune and knowing the distributor, while consumption was associated with district and household head occupation. The annual operational cost per capita for repellent distribution was 31 times more expensive than LLIN distribution (USD 4.33 versus USD 0.14).. After the existing public health system was reinforced with programmatic and logistic support, an intense 2-weekly distribution scheme of a vector control tool over a 2-year period was operated successfully in the field. Lack of associations with socio-economic status suggested that the free distribution strategy resulted in equitable access to repellents. The operational costs for the repellent distribution and exchange programme were much higher than LLIN distribution. Such effort could only be justified in the context of malaria elimination where these interventions are expected to be limited in time.

Topics: Administration, Topical; Adolescent; Adult; Aged; Cambodia; Family Characteristics; Female; Health Services Accessibility; Humans; Insect Repellents; Insecticide-Treated Bednets; Malaria; Male; Middle Aged; Piperidines; Public Health; Rural Health Services; Surveys and Questionnaires; Young Adult

The efficacies of a 20% 1-methyl-propyl-2- (hydroxyethyl)-1-piperidinecarboxylate (picaridin) spray, 20% 3-(N-acetyl-N-butyl)aminopropionic acid ethyl ester (IR3535) spray, 20% picaridin lotion, 10% IR3535 lotion, and 33% N,N-diethyl-3-methylbenzamide (deet) cream in repelling nymphal lone star ticks, Amblyomma americanum (L.), were determined at 2-h intervals over 12 h using human subjects. A repellent formulation was applied in a 5-cm-wide band encircling a volunteer's lower leg. For each challenge, 70 host-seeking nymphs were released on each volunteer's ankle, and tick locations were recorded 10 min after the ticks were released. Ticks that crawled entirely across the repellent band were considered not repelled. For all formulations and time points, significantly fewer (all P < 0.0001) A. americanum nymphs crossed the treatment bands on the volunteers' ankles than crossed the corresponding area on the untreated control legs. Formulations containing > or = 20% active ingredient were highly effective, with <10% of the ticks crossing through the treatment bands for any challenge during the 12 h. At least 40% of ticks exposed to any formulation for any challenge fell or crawled off the volunteers. There was no difference in effectiveness between the 20% spray and 20% lotion formulations of picaridin. The 10% IR3535 lotion was significantly less effective than the formulations with higher concentrations of repellent. In the formulations tested, deet, picaridin, and IR3535 provided lasting protection against A. americanum.

Topics: Administration, Topical; Animals; DEET; Humans; Insect Repellents; Ixodidae; Piperidines; Propionates; Time Factors

The repellent efficacies of the U.S. military repellent 33% N,N-diethyl-3-methylbenzamide (deet), 10% and 20% (1S, 2'S) 2-methylpiperidinyl-3-cyclohexene-1-carboxamide (SS220) and 10% and 20% 1-methyl-propyl-2-(hydroxyethyl)-1-piperidinecarboxylate (Bayrepel) cream formulations on human volunteers against the lone star tick Amblyomma americanum (L.) were evaluated in a simulated forest floor environment over a 12-h testing period. At 2-h intervals, volunteers, with repellent applied in a 5-cm-wide band around each ankle, stood for 5 min in plastic tubs containing leaf litter and 100 host-seeking A. americanum nymphs. Ticks were allowed to remain on a volunteer's feet and ankles for an additional 5 min after the volunteer exited the tub. All repellent formulations provided high levels of protection for the entire 12 h. No ticks crossed 5-cm-wide bands of 20% SS220 and Bayrepel during any challenge, and thus 100% protection was afforded throughout the test. These formulations showed a long-lasting efficacy hitherto unknown in tick repellents intended for use on human skin.

Topics: Administration, Topical; Adult; Animals; Cross-Over Studies; Cyclohexenes; DEET; Dose-Response Relationship, Drug; Female; Humans; Insect Repellents; Ixodidae; Male; Nymph; Piperidines; Skin; Smell; Time Factors; Treatment Outcome

Leech attachment is a common nuisance to outdoor recreationists and farmers in aquatic environments. Consequences include bleeding, infection, and, rarely, death. Methods to prevent leech attachment are anecdotal and individual; effective repellent formulations with universal applicability are needed. In this study, icaridin is demonstrated to be repellent and toxic to aquatic leech, and formulation of icaridin loading nitrocellulose (Icar-Nitr) is proposed as a new leech repellent. The nitrocellulose provided sustained drug release and waterproof properties. One optimal formulation, 10-Icar-Nitr, proved effective for leech repelling in aquatic environment. Using a rat model, the same formulation also showed removal and killing after leech attachment. The nitrocellulose reduced percutaneous absorption of icaridin, and 10-Icar-Nitr showed good biocompatibility. This study provides a potential new and practicable strategy for prevention and removal against leech attachment and bites.

Topics: Animals; Bites and Stings; Collodion; Insect Repellents; Piperidines; Rats; Rodent Diseases

The most important arboviruses are those that cause dengue, yellow fever, chikungunya, and Zika, for which the main vector is the

Topics: Acyclic Monoterpenes; Aedes; Animals; Arboviruses; Cellulose; Hydrogels; Insect Repellents; Mosquito Vectors; Nanoparticles; Piperidines; Zein; Zika Virus; Zika Virus Infection

After the latest dengue and Zika outbreaks, the fight against mosquito vectors has become an emerging area of research. One tool for this combat is repellents; however, these products are composed of different toxic agents. Botanical compounds with repellent potential are an alternative; however these compounds are highly volatile. Thus, the present study aimed to synthesize zein-based polymeric nanoparticles as an efficient carrier system for the sustained release of the repellents icaridin and geraniol and evaluate the toxicity of these nanorepellents comparing two different cell models. In vitro tests were carried out due to current Brazilian legislation prohibiting animal testing for cosmetics (current classification of repellents). The cytotoxicity and genotoxicity of the nanoparticles were evaluated in 2D and co-culture cell models (A549/lung epithelium, HaCaT/keratinocytes, HT-29/intestinal epithelium, and THP-1/peripheral blood monocytes). Cell viability by mitochondrial activity, cell membrane integrity, damage to genetic material, and expression of genes involved in the allergic/inflammatory system were evaluated. The results of cytotoxicity evaluation showed cell viability above 70% in both cell models. No differences were observed in genotoxicity assessment between cells exposed to nanorepellents and controls. In contrast, gene expression analysis showed increased cytokine expression for the emulsion compounds in 2D cell cultures compared to co-cultures. These findings open perspectives that zein-based nanorepellents have potential applications due to the reduced toxicity observed when the compounds are encapsulated and emerge as an alternative for arbovirus control. In addition, the study demonstrated that depending on the analysis, different results might be observed when comparing 2D and co-culture cell models to evaluate the toxicity of new nanosystems.

Topics: Acyclic Monoterpenes; Animals; Cell Culture Techniques; Coculture Techniques; Insect Repellents; Nanoparticles; Piperidines; Zein; Zika Virus; Zika Virus Infection

The use of repellents is considered an alternative against biting insects, including Lutzomyia longipalpis (Diptera: Psychodidae), the main vector of the protozoan Leishmania infantum, visceral leishmaniasis's (VL) etiologic agent in the Americas. This study aimed to evaluate the repellent efficacy of icaridin nanostructured solution applied on cotton knitting fabric against L. longipalpis. Arm-in-cage tests were performed in eight volunteers at different concentrations (5%, 10%, 25%, and 50%), using L. longipalpis (n = 30). The bioassay was performed in 1, 24, 48, 72, 96, 120, and 144 h after impregnation and one test after washing the fabrics with icaridin. The total repellency rate (%R) > 95% was used as a reference to define a minimum effective concentration (MEC). The results revealed that the insects' landing mean decreased significantly in different icaridin concentrations, compared with the control tests (p < 0.05) and the 25% and 50% concentrations compared to lower concentration (5%) (p < 0.05). The higher concentrations (25% and 50%) provided longer complete protection times (CPTs) with 120 and 144 h of protection, respectively and the %R of 100% for 72 and 96 h after impregnation, respectively. The 25% was the MEC (%R Total = 98.18%). Our results indicate, for the first time, that icaridin nanostructured solution applied on cotton knitting fabric proved to be an efficient repellent against L. longipalpis with the presence of repellent action even after washing. The concentration of 25% showed better efficiency and may become an efficient method for L. longipalpis biting control.

Topics: Animals; Brazil; Humans; Insect Repellents; Insect Vectors; Leishmania infantum; Leishmaniasis, Visceral; Piperidines; Psychodidae

Repellents are among the leading products used against diseases transmitted by the Aedes aegypti mosquito. However, their indiscriminate use or high concentrations can cause severe adverse reactions, particularly in children and pregnant women. To protect them, nanotechnology is a promising tool to encapsulate active compounds against degradation, increase their effectiveness, and decrease their toxicity, as it can promote the modified release of the active compound. This study aimed to develop polymeric nanocapsules containing the repellent actives geraniol and icaridin using low concentrations of the active component, with the objective of promoting effective activity and greater safety against adverse reactions. The nanocapsules were developed by the interfacial deposition method, and the physicochemical properties of the nanocapsules were evaluated using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), zeta potential, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), release kinetics assay, and mathematical modeling. Cell viability was assessed by the MTT assay and genotoxicity analysis using the comet assay. The developed nanocapsules containing geraniol and icaridin showed mean diameters of 260 nm and 314 nm, respectively, with a polydispersity index < 0.2. The nanocapsules showed encapsulation efficiency values of 73.7 ± 0.1% for icaridin and 98.7 ± 0.1% for geraniol. Morphological analysis showed spherical nanocapsules with low polydispersity. The kinetic parameters calculated using the Korsmeyer−Peppas model indicated an anomalous release profile. Cell viability and genotoxicity analyses showed that the nanocapsules did not alter cell viability or damage DNA. The results demonstrate a promising nanostructured system with good physicochemical characteristics and good stability, with repellent activity against Aedes aegypti.

Topics: Acyclic Monoterpenes; Aedes; Animals; Child; Female; Humans; Insect Repellents; Nanocapsules; Piperidines; Polymers; Pregnancy

Picaridin (icaridin), a member of the piperidine chemical family, is a broad-spectrum arthropod repellent. Its actions have been largely thought to be due to its interaction with odorant receptor proteins. However, to our knowledge, to what extent the presence of picaridin can modify the magnitude, gating, and/or the strength of voltage-dependent hysteresis (Hys

Topics: Insect Repellents; Molecular Docking Simulation; Piperidines; Sodium

Hand sanitizers are developed as alcohol-based liquid gel formulations, generally used to decrease the amount of infectious agents on human hands. Verdegen, LLC proposed to prepare an arthropod repellent gel for public use when the recent outbreaks of Zika infection vectored through Aedes mosquitoes in the American continents prompted multi-faceted emergency measures. Four different gel formulations were developed, comprising two of the most efficacious commercial arthropod repellent active ingredients, N,N-diethyl-3-methyl benzamide (deet) and 2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester (picaridin), each at different concentrations (20 and 33% deet, or 20 and 33% picaridin). Compliance with the use of topical arthropod repellents remains an issue among military personnel. One of the most common complaints by Soldiers is that they do not like how the repellents applied on their skin leave behind an oily or greasy residue. These new gel formulations offer a user-friendly alternative for commonly used arthropod repellents formulations for the military and civilian personnel. We tested the efficacy and protection time of these new gel formulations in comparison with the commercially available cream formulations of deet and picaridin at similar concentrations. Our data show that gel formulations have better topical attributes, and offer equal or better biting protection for up to 48 h against host-seeking Aedes aegypti (L.) (Diptera: Culicidae) female mosquitoes.

Topics: Aedes; Animals; DEET; Dose-Response Relationship, Drug; Female; Gels; Insect Repellents; Piperidines

In addition to its primary function as an insect repellent, DEET has many "off-label" properties, including a deterrent effect on the attraction of gravid female mosquitoes. DEET negatively affects oviposition sites. While deorphanizing odorant receptors (ORs) using the Xenopus oocyte recording system, we have previously observed that DEET generated outward (inhibitory) currents on ORs sensitive to oviposition attractants. Here, we systematically investigated these inhibitory currents. We recorded dose-dependent outward currents elicited by DEET and other repellents on ORs from Culex quinquefasciatus, Aedes aegypti, and Anopheles gambiae. Similar responses were observed with other plant-derived and plant-inspired compounds, including methyl jasmonate and methyl dihydrojasmolate. Inward (regular) currents elicited by skatole upon activation of CquiOR21 were modulated when this oviposition attractant was coapplied with a repellent. Compounds that generate outward currents in ORs sensitive to oviposition attractants elicited inward currents in a DEET-sensitive receptor, CquiOR136. The best ligand for this receptor, methyl dihydrojasmolate, showed repellency activity but was not as strong as DEET in our test protocol.

Topics: Aedes; Animals; Anopheles; Chemotaxis; Culex; Cyclohexane Monoterpenes; DEET; Insect Proteins; Insect Repellents; Menthol; Oviposition; Piperidines; Propionates; Receptors, Odorant

The mode of action for most mosquito repellents is unknown. This is primarily due to the difficulty in monitoring how the mosquito olfactory system responds to repellent odors. Here, we used the Q-system of binary expression to enable activity-dependent Ca

Topics: Animals; Anopheles; DEET; Female; Humans; Insect Repellents; Odorants; Olfactory Perception; Piperidines; Propionates; Receptors, Odorant; Smell

Antibiotic and insecticidal bioactivities of the extracellular secondary metabolites produced by entomopathogenic bacteria belonging to genus

Topics: Aedes; Animals; Anopheles; Culex; DEET; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Feeding Behavior; Female; Insect Repellents; Oligopeptides; Piperidines; Polyamines; Xenorhabdus

Ticks are vectors of human and animal diseases.. The aim of this study was to investigate the efficacy of four different formulations containing DEET, Icaridin, IR3535 and mix of three compounds: DEET, IR3535 and geraniol, against Dermacentor reticulatus ticks.. The repellent effectiveness of these products to adult ticks was different. At 90 minutes after application the repellent A (DEET 30%), repellent D (DEET 30%, IR3535 20%, geraniol 0.1%) and repellent G (IR3535 12%) exhibited a 100% effectiveness in protection against ticks, but the efficacy of repellent C (Icaridin 20%) dropped to 95%.. DEET is considered by many authors to be the ‘gold’ standard of insect repellents, and we have also confirmed this in our studies with Dermacentor reticulatus. DEET expressed the higher repellency after 7 hours of application (90%) comparing to other formulation - repellent D containing DEET 30%, IR3535 20% and geraniol 0.1%, whose effectiveness dropped to 60%. Repellents C (Icaridin 20%) and G (IR3535 12%) were effective only up to four hours after application (the efficacy was 85% and 40%, respectively).. DEET has proven to be the most effective repellent against Dermacentor reticulatus ticks.

Topics: Adult; Animals; DEET; Dermacentor; Female; Humans; Male; Piperidines; Propionates

In the face of mosquito-borne disease outbreaks, effective mosquito control is a primary goal for public health. Insect repellents, containing active compounds such as DEET and picaridin, are a first defence against biting insects. Owing to widespread use and incomplete sewage treatment, these compounds are frequently detected in surface waters, but their effects on aquatic taxa such as mosquito larvae or their naturally occurring aquatic predators are poorly understood. We investigated the effects of environmentally realistic concentrations of commercial products containing DEET and picaridin on survivorship of mosquito larvae, and their potential indirect effects on survival of larval salamanders, a major predator of mosquito larvae. Larval mosquitos were not affected by exposure to repellents containing DEET or picaridin. We found no larval salamander mortality in control and DEET treatments, but mortality rates in picaridin treatments ranged from 45 to 65% after 25 days of exposure. Salamander larvae exposed to repellents containing picaridin began to display tail deformities and impaired development four days after the experiment began. Our findings suggest the possibility that environmentally realistic concentrations of picaridin-containing repellents in surface waters may increase the abundance of adult mosquitos owing to decreased predation pressure.

Topics: Ambystoma; Animals; Culicidae; DEET; Food Chain; Insect Repellents; Larva; Piperidines; Tail; Water Pollutants, Chemical

Escape responses, knockdown (KD), and toxicity of laboratory strains of Anopheles minimus Theobald and Culex quinquefasciatus Say to three synthetic mosquito repellents, DEET (N, N-diethyl-3-methylbenzamide), IR3535, or picaridin, at 5% v/v concentrations, were evaluated using repellent-treated papers in standard WHO tube assays and an excito-repellency (ER) test chamber system. The tube assays recorded knockdown effects of each repellent immediately after 30-min exposure and the final morality following a 24-h holding period. DEET showed 100% KD at 30 min and complete toxicity at 24 h against both species. Both actions were either minimal or absent for IR3535 and picaridin, respectively. Culex quinquefasciatus showed significantly greater escape with DEET compared with the other compounds in both contact irritancy (excitation) and noncontact spatial repellency trials. Anopheles minimus showed much more pronounced irritancy and repellency flight escape to IR3535 than picaridin. DEET was the most active irritant and repellent compound against Cx. quinquefasciatus. When adjusting contact test responses based on paired noncontact repellency assays, DEET and IR3535 showed much stronger spatial repellent properties than irritancy with An. minimus. Picaridin performed poorly as an irritant or repellent against both species. We conclude that DEET, followed by IR3535, act as strong spatial repellents at 5% concentration. DEET also performs as a strong toxicant. Our findings show that different mosquitoes can respond contrastingly to repellents, thus the importance to test a wider range of species and populations to assess the full range of chemical action.

Topics: Animals; Anopheles; Culex; DEET; Female; Insect Repellents; Piperidines; Propionates

Insect repellents are widely applied to various materials and to both human and animal skin to deter mosquitoes and ticks. The most common deterrent compounds applied are DEET, EBAAP and icaridin (picaridin, Bayrepel). Due to their extensive application, these repellents are frequently detected in surface waters in considerable concentrations. As these compounds are designed to alter invertebrates' behaviour rather than to intoxicate them, we hypothesised that insect repellents have the potential to modify the natural behaviour of non-target invertebrates in natural freshwater bodies. To test this, we used a well-established laboratory assay designed to quantify the odour-mediated foraging behaviour of freshwater gastropods and the great pond snail Lymnaea stagnalis (Linnaeus, 1758) as a model organism to test for potential deterrent effects of insect repellents on aquatic snails. Using a wide concentration range from the picogramme per litre to microgramme per litre range (and by far exceeding the range of concentrations reported from natural waters), we found no evidence for a deterrent effect of either of the three repellents on foraging L. stagnalis. Our data and other recent studies give no indication for undesirable behavioural alterations by common insect repellents in surface waters.

Topics: Animals; Behavior, Animal; beta-Alanine; DEET; Insect Repellents; Lymnaea; Models, Animal; Piperidines

Topics: Animals; Anopheles; Calorimetry; Crystallography, X-Ray; DEET; Fluorescence; Hydrogen Bonding; Insect Repellents; Models, Molecular; Piperidines; Protein Binding; Protein Multimerization; Proton Magnetic Resonance Spectroscopy; Receptors, Odorant; Solutions; Static Electricity; Stereoisomerism

One essential oil (clove oil), one skin repellent (icaridin), and one insecticide (transfluthrin) were tested for spatial repellent effects against non-blood-fed female Aedes aegypti (L.) mosquitoes. The compounds were tested in acetone dilution series using a Y-olfactometer, a double cage system, and a double room system. All compounds exhibited spatial repellent effects at certain concentrations. Clove oil required relative high dosages to cause high effects (Y-olfactometer 6 mg, double cage 60 mg, and double room 1,200 mg). The dosages to achieve comparable results with icaridin were lower (Y-olfactometer and double cage 1 mg, and double room 150 mg). For transfluthrin, the equivalent dosages were lower again (Y-olfactometer 0.003 mg, double cage 0.03 mg, and double room 0.1 mg). Furthermore, these results reveal a correlation between the size of the test system and the effective dosage. Averaged for the three compounds, the quantity for the double room was 21-fold higher than for the double cage, which required again a 9-fold higher dosage than the Y-olfactometer. An establishment of a screening cascade is discussed starting with the Y-olfactometer (high throughput rate), followed by the double cage system and ending with the double room system as the most nearest to practical conditions. Furthermore, the testing of existing repellent products to validate the double room test, the role of sublethal dosages concerning insecticides including possible upcoming of resistance after exposure, the delayed action and impact on blood feeding and oviposition are exemplified.

Topics: Aedes; Animals; Clove Oil; Cyclopropanes; Dose-Response Relationship, Drug; Female; Fluorobenzenes; Insect Repellents; Insecticides; Piperidines

The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject's arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays.

Topics: Aedes; Animals; Culex; Culicidae; DEET; Dose-Response Relationship, Drug; Female; Humans; Insect Repellents; Models, Theoretical; Mosquito Control; Mosquito Vectors; Piperidines; Zika Virus Infection

Commercial insect repellents like DEET (N,N-diethyl-m-toluamide), EBAAP (IR3535(®), (3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester)) or Icaridine (picaridin, Bayrepel, 1-piperidinecarboxylic acid, 2-(2-hydroxyethyl), 1-methylpropyl ester) are used worldwide to protect against biting insects and ticks. The detection of these repellents in surface waters in concentrations up to several μg/L levels has caused concern that these substances might affect non-target organisms in freshwaters. Daphnia sp., a keystone organism in lakes and ponds, is known for diel vertical migration (DVM) and life-history changes (LHCs) as inducible defenses against predation by fish. Here we test whether (i) environmentally relevant concentrations of DEET, EBAPP or Icaridine have repellent effects on Daphnia magna and (ii) if these repellents are infodisruptors for DVM and LHCs. Using concentrations of up to 44 μg/L, the repellents neither had effects on juvenile somatic growth nor on clutch size. In thermally stratified water columns with a repellent-free hypolimnion, no repellent effects of the test compounds on D. magna were observed. The presence of fish-born infochemicals induced LHCs, which are characterized by a reduced size at first reproduction, and DVM in D. magna. These effects were not affected by the presence of either repellent. Hence no evidences for infodisruption of the chemical communication of fish and Daphnia by DEET, EBAAP or Icaridine were found.

Topics: Animals; beta-Alanine; Daphnia; DEET; Insect Repellents; Piperidines; Propionates

While low toxicity is reported, there are sparse data on the safety of acute picaridin (icaridin) exposures in humans.. The purpose of this study was to review National Poison Data System (NPDS) data regarding ingestion of insect repellents containing picaridin and compare those to insect repellents containing DEET and other insect repellents not containing DEET.. NPDS was queried for single agent human insect repellent ingestions reported between 1 January 2000 and 31 May 2015 using the American Association of Poison Control Center generic categories 201048 (Insect Repellents with DEET) and 201049 (Insect Repellents without DEET). Picaridin-containing product exposures were assessed using Poisindex(®) product ID 6744589. Insect repellents of unknown type were not included.. 68,429 exposures occurred; 24% were non-DEET-containing products, of which 2% were picaridin-containing products. Among picaridin exposures, 92.9% were managed outside of a health-care facility; there were no reported cases of major effect or death, and only one case of moderate effect. Primary symptoms across all insect repellent exposures included ocular irritation/pain, vomiting, red eye/conjunctivitis, and oral irritation. Treatment primarily included dilution/irrigation/wash.. Unintentional ingestion of picaridin-containing and other insect repellents was associated only with minor toxicity and was generally managed outside of a health-care facility.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Insect Repellents; Male; Middle Aged; Piperidines; Poison Control Centers; United States; Young Adult

A new approach employing a combination of pyrethroid and repellent is proposed to improve the protective efficacy of conventional pyrethroid-treated fabrics against mosquito vectors. In this context, the insecticidal and repellent efficacies of commonly used pyrethroids and repellents were evaluated by cone tests and arm-in-cage tests against Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae). At concentrations of LD50 (estimated for pyrethroid) or ED50 (estimated for repellent), respectively, the knock-down effects of the pyrethroids or repellents were further compared. The results obtained indicated that deltamethrin and DEET were relatively more effective and thus these were selected for further study. Synergistic interaction was observed between deltamethrin and DEET at the ratios of 5 : 1, 2 : 1, 1 : 1 and 1 : 2 (but not 1 : 5). An optimal mixing ratio of 7 : 5 was then microencapsulated and adhered to fabrics using a fixing agent. Fabrics impregnated by microencapsulated mixtures gained extended washing durability compared with those treated with a conventional dipping method. Results indicated that this approach represents a promising method for the future impregnation of bednet, curtain and combat uniform materials.

Topics: Aedes; Animals; Chromatography, High Pressure Liquid; Clothing; Culicidae; DEET; Drug Compounding; Insect Repellents; Insecticides; Laundering; Mosquito Control; Nitriles; Permethrin; Piperidines; Propionates; Pyrethrins

Topics: Animals; Attitude to Health; Consumer Health Information; Culicidae; Cyclohexane Monoterpenes; DEET; Eucalyptus; Health Behavior; Health Education; Humans; Insect Bites and Stings; Insect Repellents; Menthol; Mosquito Control; Phytotherapy; Piperidines; Plant Extracts; Time Factors

Topics: Animals; Culicidae; Cyclohexane Monoterpenes; DEET; Humans; Insect Bites and Stings; Insect Repellents; Malaria; Menthol; Piperidines; Travel

The present study had the aim to test the repellent potential of the compound icaridin = Saltidin® against the tick species Ixodes ricinus and Ixodes persulcatus using different formulations of the compound. Tests were done on backs of impregnated human hands, on impregnated linen cloth and versus impregnated dog hair. It was found that 1. Ixodes persulcatus-the common Eastern European, Russian Ixodes species is significantly sensitive to icaridin = Saltidin® as I. ricinus protecting for the test period of 5 h. This is an important finding, since I. persulcatus is the vector of agents of the severe Eastern meningoencephalitis; 2. that this repellent compound acts similarly on both I. ricinus and I. persulcatus, when sprayed either on naked skin or on cloths; 3. that there are only slight differences in duration of the repellency when using different formulations containing icaridin = Saltidin®; 4. that icaridin = Saltidin® sprayed on dog hair has identical repellent effects like those seen on human skin and cloths; thus, this compound can also be used to protect animals such as dogs, cats, horses; and 5. that the icaridin = Saltidin® did not induce a bad sensation on skin, nor bad smells; furthermore, it was not sticky and did not leave residuals neither on clothes nor on dog's hair.

Topics: Animals; Clothing; Dogs; Hair; Hand; Humans; Insect Repellents; Ixodes; Piperidines

Topics: Animals; Bites and Stings; Culicidae; Cyclohexane Monoterpenes; Cymbopogon; DEET; Humans; Insect Repellents; Menthol; Piperidines; Propionates; Ticks

Insect repellents are known since many decades ago and constitute a major tool for personal protection against the biting of mosquitoes. Despite their wide use, the understanding of why and how repellents repel is relatively recent. In particular, the question about to what extent insects other than mosquitoes are repulsed by repellents remains open. We developed a series of bioassays aimed to test the performance of well established as well as potential repellent molecules on the Chagas disease vector Rhodnius prolixus. Besides testing their ability to prevent biting, we tested the way in which they act, i.e., by obstructing the detection of attractive odours or by themselves. By using three different experimental protocols (host-biting, open-loop orientation to odours and heat-triggered proboscis extension response) we show that DEET repels bugs both in the presence and in the absence of host-associated odours but only at the highest quantities tested. Piperidine was effective with or without a host and icaridine only repelled in the absence of a living host. Three other molecules recently proposed as potential repellents due to their affinity to the Ir40a(+) receptor (which is also activated by DEET) did not evoke significant repellency. Our work provides novel experimental tools and sheds light on the mechanism behind repellency in haematophagous bugs.

Topics: Animals; Behavior, Animal; Chagas Disease; DEET; Disease Vectors; Feeding Behavior; Humans; Insect Repellents; Nymph; Odorants; Piperidines; Rhodnius; Smell

The High Throughput Screening System (HITSS) has been applied in insecticide behavioral response studies with various mosquito species. In general, chemical or natural compounds can produce a range of insect responses: contact irritancy, spatial repellency, knock-down, and toxicity. This study characterized these actions in essential oils derived from citronella, hairy basil, catnip, and vetiver in comparison to DEET and picaridin against Aedes aegypti and Anopheles minimus mosquito populations. Results indicated the two mosquito species exhibited significantly different (P<0.05) contact irritant escape responses between treatment and control for all tested compound concentrations, except with the minimum dose of picaridin (P>0.05) against Ae. aegypti. Spatial repellency responses were elicited in both mosquito species when exposed to all compounds, but the strength of the repellent response was dependent on compound and concentration. Data show that higher test concentrations had greatest toxic effects on both mosquito populations, but vetiver had no toxic effect on Ae. aegypti and picaridin did not elicit toxicity in either Ae. aegypti or An. minimus at any test concentration. Ultimately, this study demonstrates the ability of the HITSS assay to guide selection of effective plant essential oils for repelling, irritating, and killing mosquitoes.

Topics: Aedes; Animals; Anopheles; Chrysopogon; Cymbopogon; DEET; Female; High-Throughput Screening Assays; Insect Repellents; Insecticides; Mortality; Nepeta; Oils, Volatile; Piperidines; Plant Oils

To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA and ICA II in rat plasma. The quantification was performed by using multiple reaction monitoring of the transitions m/z 677.1/531.1 for ICA, 515.1/369.1 for ICA II and 463.1/301.1 for diosmetin-7-O-β-d-glucopyranoside (IS). The assay showed linearity over the concentration range of 1.03-1032 ng/mL, with correlation coefficients of 0.9983 and 0.9977. Intra- and inter-day precision and accuracy were within 15%. The lower limit of quantification for both ICA and ICA II was 1.03 ng/mL, respectively. The recovery of ICA and ICA II was more than 86.2%. The LC-MS/MS method has been successfully used in the pharmacokinetic studies of ICA and ICA II in rats. The results indicated that 91.2% of ICA was transformed into ICA II after oral administration by rats, whereas only 0.4% of ICA was transformed into ICA II after intravenous administration. A comparison of the pharmacokinetics of ICA and ICA II after oral administration revealed that the Cmax and AUC0-t of ICA II were 3.8 and 13.0 times higher, respectively, than those of ICA. However, after intravenous administration, the Cmax and AUC0-t of ICA II were about only 12.1% and 4.2% of those of ICA. These results suggest that ICA and ICA II have distinct pharmacokinetic properties, and the insights obtained facilitate future pharmacological action studies.

Topics: Administration, Oral; Animals; Biological Availability; Chromatography, Liquid; Drugs, Chinese Herbal; Flavonoids; Insect Repellents; Male; Piperidines; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Tissue Distribution

Insect repellents are topically applied to the skin and clothing of human and pet to keep flies, mosquitoes, and ticks away. Two important repellents, N,N-diethyl-meta-toluamide (DEET) and Picaridin, have been widely used since their discovery. Although repellency and toxicological effects of DEET and Picaridin on human being and insects are well documented without understanding molecular mechanisms, there have been no attempts to study their effects on microorganisms up to now. In the current study, DEET and Picaridin have been investigated for their antimicrobial characteristics against a broad range of microorganisms including bacteria, yeast, and fungi for the first time. They exhibited considerable antibacterial, anticandidal and antifungal properties. Even though bacteria was found to be more sensitive to Picaridin, yeast and fungi were more susceptible to DEET. Antimicrobial properties of these two repellents will increase the usage and application areas of the products containing DEET and Picaridin.

Topics: Anti-Infective Agents; Bacteria; DEET; Fungi; Insect Repellents; Microbial Sensitivity Tests; Microbial Viability; Piperidines

Behavioral bioassays remain a standard tool in the discovery, development, and registration of arthropod repellents. Tick repellent bioassays are generally uncomplicated, but their results can be affected by basic variables (e.g., dimensions of testing materials, substrate, timing, temperature) of the assay. Using lone star tick, Amblyomma americanum (L.), nymphs in climbing bioassays, we tested for the effects of substrate, solvent, and drying time on tick responses. In dose-response tests, the widely used repellents N,N-diethyl-3-methyl benzamide (deet) and 1-methyl-propyl-2-(hydroxyethyl)-1-piperidinecarboxylate (picaridin) were applied to filter paper strips and challenged by ticks at 10, 20, 30, 40, and 120 min after application. At 10-min drying time, repellency at the intermediate concentration 500 nmol repellent/cm2 filter paper was significantly lower for ethanol solutions of deet and picaridin (0 and 10% ticks repelled, respectively) than for solutions of deet and picaridin in acetone (96.7 and 76.7% ticks repelled, respectively). Repellency was greatest for both the acetone and ethanol solutions of deet and picaridin when challenged 120 min after application, and at shorter drying times at the highest concentration tested (2,000 nmol compound/ cm2). The repellency of picaridin relative to deet differed at some combinations of solvent and drying time but not others. In dose-response tests using different paper substrates and a drying time of 10 min, both ethanol and acetone solutions of deet differed in repellency, depending on both the paper substrate and the solvent. However, there were no differences in repellency between ethanol and acetone solutions of deet applied to nylon organdy in an in vitro and in an in vivo (fingertip) bioassay. When deet in solution with various proportions of ethanol:water was applied at 2,000 nmol deet/cm2 filter paper, the proportion of ticks repelled decreased as the proportion of water in the test solutions increased. Somewhat similar results were seen for solutions of deet in an acetone solvent. Water absorbed from the atmosphere may affect the efficacy of repellents in solution with anhydrous ethanol. Overall, results obtained from bioassays that differ in seemingly minor ways can be surprisingly different, diminishing the value of comparing studies that used similar, but not identical, methods. Nylon organdy or another similar thin cloth may be preferable to filter papers and copier paper for minimizing solv

Topics: Acaricides; Acetone; Animals; Biological Assay; DEET; Desiccation; Dose-Response Relationship, Drug; Ethanol; Ixodidae; Nymph; Piperidines; Solvents

The interactions between insect repellents and the olfactory system have been widely studied, however relatively little is known about the effects of repellents on the gustatory system of insects. In this study, we show that the gustatory receptor neuron (GRN) located in the medial styloconic sensilla on the maxillary palps of gypsy moth larvae, and known to be sensitive to feeding deterrents, also responds to the insect repellents DEET, IR3535, and picaridin. These repellents did not elicit responses in the lateral styloconic sensilla. Moreover, behavioral studies demonstrated that each repellent deterred feeding. This is the first study to show perception of insect repellents by the gustatory system of a lepidopteran larva and suggests that detection of a range of bitter or aversive compounds may be a broadly conserved feature among insects.

Topics: Animals; Behavior, Animal; DEET; Insect Repellents; Larva; Moths; Piperidines; Propionates

Commercial formulations of 3 repellents: OFF Active (active ingredient [AI] 15% N,N-diethyl-meta-toluamide [deet]), OFF Family Care (AI 5% picaridin), and CVS Pharmacy Fresh Insect Repellent (AI 10% citronella, 2% lauryl sulfate, and 0.2% potassium sorbate) were evaluated to determine the mean protection time provided against the large floodwater mosquitoes, Psorophora ciliata and Ps. howardii. Each of these products contained different active ingredients and displayed different protection times, but repellency was in accordance with each product's label reapplication times/repellency durations. The CVS Pharmacy Fresh Insect Repellent provided the least protection (2 h and 26 min), followed by OFF Family Care (3 h and 46 min). OFF Active afforded the longest protection (5 h and 41 min), which was significantly higher than the other treatments (P < 0.001).

Topics: Animals; Culicidae; Cymbopogon; DEET; Female; Humans; Insect Bites and Stings; Insect Repellents; Male; Middle Aged; Phytotherapy; Piperidines; Plant Preparations; Young Adult

Recently, vector-borne diseases have been resurging in endemic areas and expanding their geographic range into nonendemic areas. Such changes have refocused attention to the potential for major public health events, as naive populations are exposed to these pathogens. Personal topical repellents, recommended by the United States Centers for Disease Control and Prevention and World Health Organization, remain a first line of protection against infection. The current study evaluated the repellent efficacy of four new U.S. Environmental Protection Agency-registered topical repellent products, two with picaridin as the active ingredient and two with IR3535, against a standard DEET (N,N-diethyl-3-methylbenzamide)-based product. All products were evaluated against a wide range of vector species under field conditions across the Americas. Human volunteers were used to evaluate product efficacy as compared with a well-known DEET-based formulation and determine suitability for use by the U.S. military. Findings demonstrated the new formulations performed as well as the standard U.S. military repellent and could be recommended for use.

Topics: Administration, Topical; Americas; Humans; Insect Bites and Stings; Insect Repellents; Piperidines; Propionates

Insect repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET (N,N-diethyl-3-methylbenzamide) is a 6-decade-old synthetic repellent, which is still considered the gold standard of mosquito repellents. Mosquitoes use their sense of smell to detect DEET, but there are currently two hypotheses regarding its mode of action: activation of ionotropic receptor IR40a vs. odorant receptor(s). Here, we demonstrate that DEET, picaridin, insect repellent 3535, and p-menthan-3,8-diol activate the odorant receptor CquiOR136 of the southern house mosquito, Culex quinquefasciatus. Electrophysiological and behavioral assays showed that CquiIR40a knockdown had no significant effect on DEET detection and repellency. By contrast, reduction of CquiOR136 transcript levels led to a significant decrease in electroantennographic responses to DEET and a complete lack of repellency. Thus, direct activation of an odorant receptor, not an ionotropic receptor, is necessary for DEET reception and repellency in Culex mosquitoes. Interestingly, methyl jasmonate, a repellent derived from the nonvolatile jasmonic acid in the signaling pathway of plant defenses, elicited robust responses in CquiOR136•CquiOrco-expressing Xenopus oocytes, thus suggesting a possible link between natural products with long insect-plant evolutionary history and synthetic repellents.

Topics: Acetates; Aldehydes; Animals; Arthropod Antennae; Avoidance Learning; beta-Alanine; Cloning, Molecular; Culex; Cyclohexane Monoterpenes; Cyclopentanes; DEET; Electrophysiology; Feeding Behavior; Female; Insect Repellents; Menthol; Models, Neurological; Molecular Sequence Data; Oocytes; Oxylipins; Piperidines; Receptors, Ionotropic Glutamate; Receptors, Odorant; Recombinant Fusion Proteins; RNA Interference; Smell; Transcription, Genetic; Xenopus laevis

Scaling up of insecticide treated nets has contributed to a substantial malaria decline. However, some malaria vectors, and most arbovirus vectors, bite outdoors and in the early evening. Therefore, topically applied insect repellents may provide crucial additional protection against mosquito-borne pathogens. Among topical repellents, DEET is the most commonly used, followed by others such as picaridin. The protective efficacy of two formulated picaridin repellents against mosquito bites, including arbovirus and malaria vectors, was evaluated in a field study in Cambodia. Over a period of two years, human landing collections were performed on repellent treated persons, with rotation to account for the effect of collection place, time and individual collector. Based on a total of 4996 mosquitoes collected on negative control persons, the overall five hour protection rate was 97.4% [95%CI: 97.1-97.8%], not decreasing over time. Picaridin 20% performed equally well as DEET 20% and better than picaridin 10%. Repellents performed better against Mansonia and Culex spp. as compared to aedines and anophelines. A lower performance was observed against Aedes albopictus as compared to Aedes aegypti, and against Anopheles barbirostris as compared to several vector species. Parity rates were higher in vectors collected on repellent treated person as compared to control persons. As such, field evaluation shows that repellents can provide additional personal protection against early and outdoor biting malaria and arbovirus vectors, with excellent protection up to five hours after application. The heterogeneity in repellent sensitivity between mosquito genera and vector species could however impact the efficacy of repellents in public health programs. Considering its excellent performance and potential to protect against early and outdoor biting vectors, as well as its higher acceptability as compared to DEET, picaridin is an appropriate product to evaluate the epidemiological impact of large scale use of topical repellents on arthropod borne diseases.

Topics: Animals; Arbovirus Infections; Cambodia; Culicidae; Insect Repellents; Insect Vectors; Insecticide Resistance; Malaria; Piperidines

The kissing bug, Triatoma rubida (Uhler) is a common hematophagous bug in Tucson, AZ, and is responsible for causing severe allergic reactions in some bitten individuals. DEET, picaridin, tea tree oil, peppermint oil, and citronella oil were tested for repellency to T. rubida and its ability to probe and feed on a small restrained rat. No long range repellency was observed with any of the test materials. The lowest repellent concentrations observed were: 10% DEET, 7% picaridin; 30% tea tree oil, 3.3% peppermint oil, and 0.165% citronella oil. Only citronella oil was able to stop all probing and feeding by T. rubida. Citronella oil appears to be a promising potential repellent to prevent sleeping people from being bitten by kissing bugs.

Topics: Animals; DEET; Dose-Response Relationship, Drug; Insect Repellents; Mentha piperita; Oils, Volatile; Piperidines; Plant Oils; Tea Tree Oil; Triatoma

Topical insect repellent is commonly used throughout the world. Active ingredients typically include N,N-diethyl-meta-toluamide (DEET) or picaridin. Reactions to topical repellents have ranged from contact dermatitis to urticaria. Exposure to DEET can produce contact urticaria; however, it is unknown if patients with a sensitivity to DEET can tolerate picaridin. We report the case of a 22-year-old man who presented for evaluation of contact urticaria that had developed immediately after the application of insect repellent and contact with individuals who had used DEET-containing repellents. No systemic manifestations were noted. Commercially available products containing DEET or picaridin were used for open patch testing. The patient showed immediate urticarial responses to 7% DEET and 7% DEET in ethanol, but patch tests for 5% picaridin and 5% picaridin in ethanol were negative. Based on these results, we conclude that insect repellents containing picaridin may be acceptable alternatives in patients who demonstrate sensitivity to products containing DEET.

Topics: Adult; DEET; Humans; Insect Repellents; Male; Patch Tests; Piperidines; Urticaria; Young Adult

In recent years, the common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), became a major public health concern in urban communities. Bed bugs are notoriously difficult to control, and their bites are not tolerated by most people. The public has an urgent need for materials and methods to reduce bed bug introduction and bites during work, travel, or sleep. A repellent product will help achieve these goals by discouraging and preventing bed bugs from moving to a protected area. We evaluated the repellency of three commercially available insect repellent or control materials and five nonregistered materials with the goal of identifying safe and effective bed bug repellents. The two commercial repellent products that contained 7% picaridin or 0.5% permethrin had little repellency against bed bugs. N,N-diethyl-m-toluamide (DEET), the most commonly used insect repellent, provided a high level of repellency against bed bugs. When a host cue (carbon dioxide) was present, the minimum DEET concentration to repel > or = 94% of the bed bugs for a9-h period was 10%. The longevity of repellency of DEET was concentration dependent. At 25% concentration, DEET-treated fabric surface remained highly repellent to bed bugs for a 14-d period. However, DEET has a strong smell and dissolves certain plastic materials. Therefore, we evaluated several odorless, noncorrosive, and potentially effective repellents. Isolongifolenone and isolongifolanone, two natural products and recently reported insect repellents, exhibited strong repellent property against bed bugs but at significantly lower levels than DEET. Three novel potential repellent compounds discovered by Bedoukian Research Inc. (Danbury, CT) exhibited similar level of repellency and longevity as DEET for repelling bed bugs. These nonirritant and odorless compounds are promising candidates as alternatives to DEET for reducing the spread of bed bugs and bed bug bites.

Topics: Animals; Bedbugs; DEET; Insect Repellents; Male; Nymph; Permethrin; Piperidines

Changes in the time to first bite (TFB) and the bloodfeeding behavior of adult female Aedes aegypti (L.) mosquitoes following dissemination of Sindbis virus (SINV) were observed after exposure to repellents with the active ingredients (AI) DEET, picaridin, 2-undecanone (2-U), and oil of lemon eucalyptus. Dissemination of SINV significantly decreased (P<0.0001) the TFB of DEET (15%) and picaridin (15%) by 46% and 37%, respectively. Significant (P<0.0001) changes in activation, probing, and engorgement times were observed in SINV infected mosquitoes after exposure to the four repellents compared to uninfected mosquitoes. Taken together, a decrease in TFB and time to complete the four bloodfeeding stages will lessen the prey-status, and enhance both the chances of mosquito survival and arbovirus transmission.

Topics: Aedes; Animals; Behavior, Animal; DEET; Female; Insect Bites and Stings; Insect Repellents; Ketones; Piperidines; Sindbis Virus; Time Factors

Insect repellents are prophylactic tools against a number of vector-borne diseases. There is growing demand for repellents outperforming DEET in cost and safety, but with the current technologies R&D of a new product takes almost 10 years, with a prohibitive cost of $30 million dollar in part due to the demand for large-scale synthesis of thousands of test compounds of which only 1 may reach the market. R&D could be expedited and cost dramatically reduced with a molecular/physiological target to streamline putative repellents for final efficacy and toxicological tests.. Using olfactory-based choice assay we show here that the fruit fly is repelled by not only DEET, but also IR3535 and picaridin thus suggesting they might have "generic repellent detector(s)," which may be of practical applications in new repellent screenings. We performed single unit recordings from all olfactory sensilla in the antennae and maxillary palps. Although the ab3A neuron in the wild type flies responded to picaridin, it was unresponsive to DEET and IR3535. By contrast, a neuron housed in the palp basiconic sensilla pb1 responded to DEET, IR3535, and picaridin, with apparent sensitivity higher than that of the DEET detectors in the mosquitoes Culex quinquefasciatus and Aedes aegypti. DmOr42a was transplanted from pb1 to the "empty neuron" and showed to be sensitive to the three insect repellents.. For the first time we have demonstrated that the fruit fly avoids not only DEET but also IR3535 and picaridin, and identified an olfactory receptor neuron (ORN), which is sensitive to these three major insect repellents. We have also identified the insect repellent-sensitive receptor, DmOr42a. This generic detector fulfils the requirements for a simplified bioassay for early screening of test insect repellents.

Topics: Action Potentials; Animals; Animals, Genetically Modified; Arthropod Antennae; DEET; Drosophila melanogaster; Extracellular Space; Insect Repellents; Olfactory Receptor Neurons; Piperidines; Propionates; Stereoisomerism

Concurrent application of insect repellent picaridin or DEET with sunscreens has become prevalent due to concerns on West Nile virus and skin cancer. The objectives of this study were to characterize the percutaneous permeation of picaridin and sunscreen oxybenzone from commercially available preparations and to compare the differences in permeability between picaridin and DEET in association with oxybenzone. In vitro diffusion studies were carried out to measure transdermal permeation of picaridin and oxybenzone from four different products, using various application concentrations and sequences. Results were then compared to those of repellent DEET and sunscreen oxybenzone under identical conditions. Transdermal permeation of picaridin across human epidermis was significantly lower than that of DEET, both alone and in combination with oxybenzone. Concurrent use resulted in either no changes or suppression of transdermal permeation of picaridin and oxybenzone. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed. In addition, permeation of picaridin, DEET and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type. It was concluded from this comparative study that picaridin would be a better candidate for concurrent use with sunscreen preparations in terms of minimizing percutaneous permeation of the chemicals.

Topics: Benzophenones; Chromatography, High Pressure Liquid; DEET; Diffusion; Diffusion Chambers, Culture; Drug Combinations; Drug Synergism; Humans; In Vitro Techniques; Insect Repellents; Piperidines; Skin Absorption; Sunscreening Agents

Picaridin and oxybenzone are two active ingredients found in repellent and sunscreen preparations, respectively. We performed a series of in vitro diffusion studies to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Permeation of picaridin (PCR) and oxybenzone (OBZ) across human epidermis was suppressed when both active ingredients were used concurrently; increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. The findings were different from concurrent use of repellent DEET and sunscreen oxybenzone in which a synergistic permeation enhancement was observed. Further comparative studies are therefore needed to understand permeation mechanisms and interactions between picaridin and oxybenzone.

Topics: Benzophenones; Diffusion; Dimethylpolysiloxanes; Epidermis; Humans; Insect Repellents; Membranes, Artificial; Permeability; Piperidines; Skin Absorption; Sunscreening Agents

The spread of resistance to pyrethroids in the major Afrotropical malaria vectors Anopheles gambiae s.s. necessitates the development of new strategies to control resistant mosquito populations. To test the efficacy of nets treated with repellent and insecticide against susceptible and insecticide-resistant An. gambiae mosquito populations, we impregnated mosquito bed nets with an insect repellent mixed with a low dose of organophosphorous insecticide and tested them in a rice-growing area near Bobo-Dioulasso, Burkina Faso. During the first 2 weeks posttreatment, the mixture was as effective as deltamethrin alone and was more effective at killing An. gambiae that carried knockdown resistance (kdr) or insensitive acetylcholinesterase resistance (Ace1R) genes. The mixture seemed to not kill more susceptible genotypes for the kdr or Ace1R alleles. Mixing repellents and organophosphates on bed nets could be used to control insecticide-resistant malaria vectors if residual activity of the mixture is extended and safety is verified.

Topics: Acetylcholinesterase; Alleles; Animals; Anopheles; Burkina Faso; Cholinesterase Inhibitors; DEET; Female; Genes, Insect; Humans; Insect Repellents; Insect Vectors; Insecticide Resistance; Insecticides; Malaria; Male; Mosquito Control; Nitriles; Organothiophosphorus Compounds; Piperidines; Pyrethrins

For the use of topical insect repellents, DEET and picaridin, human health risk assessments were conducted for various population subgroups. Acute, subchronic, and chronic dermal exposures were examined. No-observed-effect-levels (NOELs) of 200, 300, and 100mg/kg body weight (BW) were used as endpoints for DEET for acute, subchronic, and chronic exposures, respectively. For picaridin, a NOEL of 2000 mg/kg BW/day for acute exposure and a NOEL of 200 mg/kg BW/day for subchronic and chronic exposures were used. Daily exposures to several population subgroups were estimated. Risks were characterized using the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100. Estimates of daily exposures ranged from 2 to 59 mg/kg BW/day for DEET and 2 to 22 mg/kg BW/day for picaridin. Children had the lowest MOEs. However, none of the estimated exposures exceeded NOELs for either repellent. At 40% DEET for acute exposure, children < or = 12 years had MOEs below 100. For subchronic and chronic exposures children at > or = 25% DEET and at 15% picaridin had MOEs below 100. Therefore, we found no significant toxicological risks from typical usage of these topical insect repellents.

Topics: Administration, Cutaneous; Adolescent; Animals; Child; DEET; Dose-Response Relationship, Drug; Environmental Exposure; Female; Humans; Insect Repellents; Male; No-Observed-Adverse-Effect Level; Piperidines; Risk Assessment; Toxicity Tests

Seven proprietary repellent formulations (3 hydro-alcoholic spray solutions and 4 skin lotions) with active ingredient IR3,535 (ethyl butylacetylaminopropionate, EBAAP) or Picaridin (hydroxyethyl isobutyl piperidine carboxylate, KBR 3,023, Bayrepel) were tested in a field study on 10 test persons over a period of 10 h for their efficacy at preventing bites. The tests were conducted in Belo Horizonte, Brazil on field populations of the yellow fever mosquito Aedes aegypti. The concentration of the active substances ranged from 10% to 20%. All the tested samples provided lasting protection (time to first bite) over several hours: ranging from 5 h 20 min to 6 h 50 min with a mean of approximately 6 h. The longest protection until the second bite (=first confirmation bite) was approximately 7 h 40 min, whereas the shortest protection was 6 h 50 min. The longest protection until the third bite (=second confirmation bite) was 8 h 35 min, whereas the shortest protection was 7 h 40 min. In the control tests in which none of the samples were applied, the mean times until the first, second and third bites were 26, 46 and 59 min, respectively. The basis for this field study was provided by two American guidelines, which have the greatest international acceptance. The first is a draft guideline from the Environmental Protection Agency (EPA (United States Environmental Protection Agency), Product performance test guidelines. OPPTS 810.3700. Insect repellents for human skin and outdoor premises. Public Draft, 1999) and the second is a standard from the American Society for Testing and Materials (ASTM (American Society for Testing and Materials International), E 939-94 (reapproved 2,000): standard test method of field testing topical applications of compounds as repellents for medically important and pest arthropods (including insects, ticks, and mites): I. Mosquitoes, 2,000). Both guidelines recommend measuring the duration of protection until the first and second bites and also determining the relative protection efficacy in terms of a 95% protection level. The ASTM standard permits different repellents to be applied, whereas the EPA guidelines only permit the use of a single repellent (in different concentrations) on the extremities (forearms or lower leg). In the study presented here, to exclude any possibility of different repellents or concentrations of a single repellent having a reciprocal effect on each other, each test person had repellent samples applied to on

Topics: Aedes; Animals; Dosage Forms; Insect Repellents; Piperidines; Propionates; Time Factors

Dermatitis caused by penetrating bird schistosome cercariae is an emerging global public health problem. Infections may be prevented by the use of topical formulations that inhibit cercarial skin penetration. We evaluated nine water resistant formulations by exposing treated arms of volunteers to Trichobilharzia szidati cercariae. Six formulations protected from cercarial invasion. However, after immersion of the treated skin in water (2 x 20 min), only two formulations offered full protection: (1) Safe Sea, a cream protecting against jelly fish, (2) niclosamide in water resistant sun protecting cream formulations at concentrations as low as 0.05%. In an in vitro system Safe Sea and a 0.1% niclosamide formulation caused a high damage rate in T. szidati (92% and 99% after 5 min; only niclosamide with lethal effect) but not in Schistosoma mansoni (1% and 72%; both formulations with lethal effect). However, a 1% niclosamide formulation damaged S. mansoni sufficiently (100% after 5 min) and might offer full penetration protection.

Topics: Adult; Animals; Anthelmintics; DEET; Dermatitis; Dimethylpolysiloxanes; Dosage Forms; Humans; Lauric Acids; Middle Aged; Niclosamide; Piperidines; Propionates; Schistosomatidae; Time Factors; Trematode Infections

To manage the kdr pyrethroid-resistance in Anopheline malaria vectors, new compounds or new strategies are urgently needed. Recently, mixing repellents (DEET) and a non-pyrethroid insecticide (propoxur) was shown to be as effective as deltamethrin, a standard pyrethroid, under laboratory conditions, because of a strong synergy between the two compounds. In the present study, the interactions between two repellents (DEET and KBR 3023) and a non-pyrethroid insecticide (pyrimiphos methyl or PM) on netting were investigated. The residual efficacy and the inhibition of blood feeding conferred by these mixtures were assessed against Anopheles gambiae mosquitoes.. DEET and KBR 3023 were mixed with pyrimiphos methyl (PM), a organophosphate (OP) insecticide. The performance of mono- and bi-impregnated nets against adult mosquitoes was assessed using a miniaturized, experimental hut system (laboratory tunnel tests) that allows expression of behavioural responses to insecticide, particularly the mortality and blood feeding effects.. Both mixtures (PM+DEET and PM+KBR3023) induced 95% mortality for more than two months compared with less than one week for each compound used alone, then reflecting a strong synergy between the repellents and PM. A similar trend was observed with the blood feeding rates, which were significantly lower for the mixtures than for each component alone.. Synergistic interactions between organophosphates and repellents may be of great interest for vector control as they may contribute to increase the residual life of impregnated materials and improve the control of pyrethroid-resistance mosquitoes. These results prompt the need to evaluate the efficacy of repellent/non-pyrethroid insecticide mixtures against field populations of An. gambiae showing high level of resistance to Ops and pyrethroids.

Topics: Animals; Anopheles; Bedding and Linens; DEET; Drug Synergism; Feeding Behavior; Female; Guinea Pigs; Insect Repellents; Insect Vectors; Insecticides; Mosquito Control; Organophosphates; Organothiophosphorus Compounds; Piperidines; Pyrethrins

A series of behavioral tests with Aedes aegypti (L.), Anopheles stephensi Liston, mosquitoes, and the sand fly Phlebotomus papatasi Scopoli in the presence of Deet, SS220, and Picaridin topically applied to the skin of human volunteers showed that the insects were deterred from feeding on and repelled from surfaces emanating the compounds. When offered a 12- or 24-cm2 area of skin, one-half treated with compound and one-half untreated, the insects fed almost exclusively on untreated skin. The sand flies and mosquitoes did not at any time physically contact chemically treated surfaces. When treated and untreated skin areas were covered with cloth, insects contacted, landed, and bit only through cloth covering untreated skin. These observations provided evidence that the compounds deterred feeding and repelled insects from treated surfaces primarily as a result of olfactory sensing. When cloth, one-half untreated and one-half treated with chemical, was placed over untreated skin, insects only touched and specifically bit through the untreated cloth. This showed that the activity of the chemicals does not involve a chemical x skin interaction. In the presence of any of the three chemicals, no matter how they were presented to the insects, overall population biting activity was reduced by about one-half relative to controls. This reduction showed a true repellent effect for the compounds. Results clearly showed that Deet, SS220, and Picaridin exert repellent and deterrent effects upon the behavior of mosquitoes and sand flies. Heretofore, the combined behavioral effects of these compounds upon mosquito and sand fly behavior were unknown. Moreover, protection afforded by Deet, SS220, and Picaridin against the feeding of these three disease vectors on humans is mechanistically a consequence of the two chemical effects.

Topics: Aedes; Animals; Anopheles; Biological Assay; Cyclohexenes; DEET; Feeding Behavior; Female; Humans; Insect Bites and Stings; Insect Repellents; Male; Phlebotomus; Piperidines; Smell

The aim of this study was to detect the role of some mosquito organs in their sensation of repellent materials. A total of 250 females (15 days old) of the target species Aedes aegypti and Anopheles stephensi were prepared and divided into five groups: group 1, without antenna; group 2, without maxillary bulbs; group 3, without proboscis; group 4, without frontal tarsus; and group 5, normal females as control. A mixture of five oils containing Litsea cubeba 1%, Melaleuca leucadendron 1%, Melaleuca quinquenervia 1%, Viola odorata 1%, and Nepeta cataria 1% was included in a complex solvent containing 20% genapol, 10% polyethylene glycol, 20% ethanol, and 50% water. Furthermore, Bayrepel was used in this experiment at a 20% concentration in the same solvent. Pure water was used as control in this study. The test was carried out by spreading 100 microl of the repellent material or water on a 30-cm2 exposure area of a human volunteer's arm. In A. aegypti, the biting and landing percentages increased significantly in those mosquito groups that lacked some organs (especially maxillary bulbs), while in A. stephensi, it became not clear which organ is responsible for perception of repellents.

Topics: Animal Structures; Animals; Culicidae; Drug Combinations; Female; Humans; Insect Repellents; Piperidines; Plant Oils; Sense Organs

Topics: Animals; Culicidae; DEET; Humans; Insect Bites and Stings; Insect Repellents; Patient Compliance; Piperidines

The knock-down, mortality and 'irritancy' effects of three synthetic repellents (DEET, IR3535 and KBR 3023) on Aedes aegypti (L) (Diptera: Culicidae) were evaluated in the laboratory in the absence of animal bait. Filter paper tests were carried out to assess the knock-down effect (KDt(50) and KDt(95)) and mortality (LC(50) and LC(95)) induced by each repellent. 'Irritancy' tests were carried out to compare the flight response (time to first take-off, or FT) to increasing concentrations of repellents (2-7%) and at five distances from the treated surface (0-40 mm). DEET had an insecticidal effect (KDt(50) = 9.7 min at 7%; CL(50)= 1165 mg/m(2)), whereas IR3535 and KBR 3023 did not. Relative to an untreated control, IR3535 was an irritant (relative irritancy or RI > 1) at doses of 5% and 7% (RI = 17.7 and 9.9, respectively), whereas DEET was an irritant at lower concentrations (RI = 12.3 at 2% DEET). KBR 3023 was the weakest irritant over the same range of concentrations (RI(max) = 3.6 at 6%). DEET was more of an irritant (RI(20) = 9.4) than IR3535 (RI(20) = 2.9) over a range of distances (0-20 mm), and KBR 3023 was not an irritant unless mosquitoes made contact with the treated surface. All three repellents had a significant effect on mosquitoes, but DEET exhibited a more complex mode of action than the others due to its insecticidal properties. The repellents do not behave as a single class of compounds with a common mode of action, but most probably affect different physiological systems in insects. The physiological and molecular mechanisms of repellents, especially DEET, should be investigated to ensure a better use of these molecules for skin applications and/or for treating materials against mosquitoes.

Topics: Aedes; Animals; Behavior, Animal; DEET; Insect Repellents; Lethal Dose 50; Piperidines; Propionates

A Klun & Debboun (K&D) test module, previously developed and used for quantitative measurement of the efficacy of mosquito repellents on human volunteers, was adapted for in vitro evaluation of repellents by coupling the module with a membrane-blood reservoir. Performance of Deet, Bayrepel, and SS-220 insect repellents in the new in vitro system was compared with their performance on humans against mosquitoes using our standard in vivo system. For each compound, in vitro dose-response assays were conducted with compounds applied to cloth positioned over blood reservoirs covered with Baudruche membrane against Aedes aegypti. The repellents were also tested in vitro against Anopheles stephensi and Ae. aegypti at a fixed dose of 24 nmol compound/cm2 cloth over the Baudruche and Edicol collagen membranes. Concurrently, the repellents were tested at the fixed dose using the K&D module on human volunteers. The observed proportions of both mosquito species deterred from biting in the fixed doses in the in vitro assays were similar to those obtained using humans, being clearly able to distinguish controls from repellents, and differing only in the ranking of the effectiveness of some of the repellents. Dose-response relationships of the in vitro and in vivo systems were also very similar, although not directly comparable because the data were not collected concurrently. This new in vitro assay system can be used in high throughput screening of compounds to identify new repellents having potential for use as topical mosquito repellents on humans.

Topics: Aedes; Animals; Anopheles; Biological Assay; Culicidae; DEET; Humans; In Vitro Techniques; Insect Repellents; Piperidines

Topics: DEET; Eucalyptus; Humans; Insect Repellents; Piperidines; Plant Oils; West Nile Fever

An alternative to DEET for protection against mosquitoes.

Topics: Animals; Costs and Cost Analysis; DEET; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Insect Repellents; Mosquito Control; Piperidines

Topics: Adult; Allergens; Dermatitis, Allergic Contact; Diagnosis, Differential; Emulsifying Agents; Extremities; Humans; Insect Repellents; Male; Patch Tests; Piperidines

Both 1-methylisopropyl 2-(2-hydroxyethyl)piperidine-1-carboxylate, (Picaridin((R))) and cyclohex-3-enyl 2-methylpiperidin-1-yl ketone (AI3-37220; 220) have two asymmetric centers, and the four diastereoisomers of each compound are known to have differing degrees of mosquito-repellent activity according to quantitative behavioral assays conducted at the United States Department of Agriculture. Computational chemistry was used to identify the structural and configurational basis for repellent activity. Molecular overlay of the optimized geometries of the lowest energy conformers of the diastereoisomers was investigated to elucidate the role of chiral centers in 220 and Picaridin. It was found that the presence of a chiral carbon alpha to the nitrogen with the S configuration in the piperidine ring is essential to the three-dimensional arrangement of the atoms of the pharmacophore for effective repellent activity.

Topics: Animals; Biological Assay; Culicidae; DEET; Insect Repellents; Piperidines; Stereoisomerism; Structure-Activity Relationship

Topics: DEET; Eucalyptus; Humans; Insect Repellents; Leisure Activities; Piperidines; Plant Oils

Field trials comparing commercially available repellent formulations containing picaridin (1-piperidinecarboxylate acid, 2-(2-hydroxyethyl)-1-methylpropylester) and deet (N,N-diethyl-3-methylbenzamide) against mosquitoes in Northern Territory, Australia, were conducted. Three repellents were compared: Autan Repel containing 9.3% picaridin, RID containing 10% deet, and Bushman Ultra containing 80% deet in a gel. The predominant mosquito species collected were Culex annulirostris Skuse (63.2%), Ochlerotatus normanensis (Taylor) (19.6%), and Anopheles meraukensis Venhuis (8.6%). Autan Repel provided >95% protection against all mosquitoes for 2 h, RID for 7 h, and Bushman for >8 h. Against Cx. annulirostris, Autan Repel provided >95% protection for 5 h, RID for 7 h, and Bushman for >8 h. The study showed that both deet formulations provided significantly better protection against mosquitoes than picaridin (Autan Repel). All 3 repellents provided good protection against Cx. annulirostris, an important vector of arboviruses in Australia.

Topics: Animals; Anopheles; Culex; Culicidae; DEET; Insect Repellents; Northern Territory; Ochlerotatus; Piperidines

We conducted laboratory tests to assess the sensitivity to the insect repellent 1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-, 1-methylpropylester (known as KBR 3023 or Picaridin, trade name Bayrepel) of West African strains of the yellow fever mosquito Aedes aegypti and of malaria vectors of the Anopheles gambiae complex, in comparison with the standard repellent N,N-diethyl-3-methyl-benzamide (DEET). Test mosquitoes were exposed according to a 'separate arms' protocol to logarithmic dose increments applied on one arm of human subjects to evaluate the relative potency, and the median effective dosages (ED50 and ED90). According to a logistic regression model fitted to the experimental data, the dose-response relationship for the two repellents was the same within each species, thus pooled ED values were assessed for each mosquito separately. The median ED of KBR 3023 and DEET was estimated at 0.78 (95% confidence limits (CI): 0.57-1.04) and at 0.018 microg/cm2 (0.004-0.052) for mosquitoes of the An. gambiae complex and Ae. aegypti, respectively. ED90 values were 125.6 (81.4-201.3) and 24.0 microg/cm2 (5.7-208.5) for An. gambiae s.l. and Ae. aegypti, respectively. The relative potency of KBR 3023 was not significantly different from that of DEET for An. gambiae s.l. (95% confidence limits 0.7-1.0), whereas in the case of Ae. aegypti it was with 95% probability 1.1-2.0 times more potent than DEET. On the basis of available evidence, KBR 3023 represents a promising alternative to DEET for personal protection against bites of these important vectors of disease in the Afrotropical region.

Topics: Aedes; Animals; DEET; Dose-Response Relationship, Drug; Humans; Insect Repellents; Insect Vectors; Piperidines; Regression Analysis

Field efficacy of repellent formulations containing picaridin (1-methyl-propyl 2-(2-hydroxyethyl)-1-piperidinecarboxylate) or deet (N,N,-diethyl-3-methylbenzamide) against mosquitoes in Northern Territory, Australia, was evaluated. The following repellent treatments were evaluated: 19.2% picaridin (Autan Repel Army 20), a solution of 20% deet in ethanol, and 35% deet in a gel (Australian Defense Force [ADF]). The predominant mosquito species were Culex annulirostris Skuse (57.8%), Anopheles merankensis Venhuis (15.4%), and Anopheles bancroftii Giles (13.2%). The protection provided by repellents against Anopheles spp. was relatively poor, with 19.2% picaridin and ADF deet providing >95% protection for only 1 h, whereas 20% deet provided <95% protection at 1 h after repellent application. In contrast, the repellents provided good protection against Cx. annulirostris, with 19.2% picaridin providing >95% protection for 5 h and both deet formulations providing >95% protection for 7 h when collections ceased. This study provides additional field data showing tolerance of Anopheles spp. for repellents. The response of field populations of Cx. annulirostris, an important vector of arboviruses in Australia, to repellents containing deet and picaridin is reported for the first time.

Topics: Animals; Culex; Culicidae; DEET; Insect Repellents; Northern Territory; Piperidines; Species Specificity

Synthetic insect repellents, IR3535 and KBR 3023 (also known as picaridin, or by the trade name Bayrepel, were tested in Burkina Faso against mosquito vectors of disease to compare their relative efficacy and persistence profiles to those of the 'gold standard' DEET. Collection of >49000 mosquitoes (approximately 95% belonging to the Anopheles gambiae complex) showed that after an exposure of 10h, KBR 3023 produced the highest protection against anophelines, followed by DEET, then IR3535. The response of aedines was more variable. By fitting a logistic plane model we estimated 95% effective dosages (ED95) for An. gambiae s.l., as well as a decay constant characterizing the exponential loss of repellent from the skin, with time. The ED95 values for DEET, IR3535, and KBR 3023 were 94.3, 212.4, and 81.8 microg/cm2 respectively. The decay constants were estimated at -0.241, -0.240, and -0.170 h(-1) respectively. The corresponding estimates of half-life were 2.9, 2.9, and 4.1h. Immunoenzymatic detection of the circumsporozoite protein (CSP) of Plasmodium falciparum in 842 An. gambiae s.l. showed that CSP-positive mosquitoes were equally frequent in treated and control subjects, indicating that the repellents could produce a reduction in the number of malaria infectious bites.

Topics: Administration, Topical; Adult; Aedes; Animals; Anopheles; Burkina Faso; DEET; Dose-Response Relationship, Drug; Female; Humans; Insect Repellents; Insect Vectors; Malaria; Male; Piperidines; Propionates; Rural Health; Time Factors; Treatment Outcome

Insect repellents such as N,N-diethyl-m-toluamide (DEET) which are used as protection against mosquitoes or ticks were detected in all wastewater and anthropogenically influenced surface waters analyzed. In Germany, the concentrations of DEET have constantly decreased since 1999, when DEET was substituted by Bayrepel (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl), 1-methylpropyl ester; KBR 3023) in commercial insect repellent formulations. A sensitive quantitative method was developed in order to study the occurrence and fate of Bayrepel in the aquatic environment. It was thus determined that Bayrepel undergoes rapid primary aerobic biodegradation, yielding a more stable metabolite, Bayrepel-acid (1-piperidinecarboxylic acid, 1-methylpropyl ester, 2-acetic acid). In order to study the biodegradation and investigate the fate of this metabolite, Bayrepel-acid was synthesized and characterized. Various chromatographic and mass spectrometric techniques, such as gas chromatography-mass spectrometry (MS) after derivatization, liquid chromatography (LC)-electrospray ionization (ESI) MS and LC-ESI time-of-flight MS were applied.

Topics: Chromatography, High Pressure Liquid; Insect Repellents; Mass Spectrometry; Piperidines; Structure-Activity Relationship

During summer months the insect repellent N,N-diethyl-m-toluamide (DEET) could always be detected in influents and effluents of wastewater treatment plants (WWTP) and anthropogenically influenced surface waters. In Germany the concentrations have decreased constantly since 1999, when DEET was substituted by Bayrepel. DEET can be degraded in WWTP, but only after an adaptation period and values in the influent above the threshold value. Since the year 2000 Bayrepel could also be detected during the summer months in the influents of WWTP, whereas in the effluents Bayrepel was not present.

Topics: Animals; DEET; Fresh Water; Gas Chromatography-Mass Spectrometry; Germany; Insect Repellents; Piperidines; Poison Control Centers; Seasons; Time Factors; Waste Disposal, Fluid

The bont tick, Amblyomma hebraeum Koch, is the principal vector of Rickettsia africae, the agent of African tick bite fever, in southern Africa. In contrast to most other hard ticks, members of the genus Amblyomma exhibit a characteristic attack host-seeking behavior. The efficacy of topically applied 20% lotions of DEET (diethyl-3-methylbenzamide), the currently considered reference repellent substance, and KBR 3023, a recently developed piperidine compound, was evaluated against laboratory-reared A. hebraeum nymphs on treated fingers. Both substances repelled >85% of nymph attacks at 0 and 1 h postapplication. At 2, 3, and 4 h, the repellent efficacies of DEET were 84%, 68% and 71%, whereas those of KBR 3023 were 56, 55, and 54%. The observed differences between the two test substances were statistically significant only at 2 h postapplication. This first study of topical repellents against A. hebraeum suggests that 20% lotions of DEET and KBR 3023 are effective for 2 and 1 h, respectively, but that the repellent efficacies decrease thereafter.

Topics: Administration, Topical; Adult; Animals; DEET; Humans; Insect Repellents; Ixodidae; Piperidines; Tick Infestations; Time Factors; White People

Optically active (1S,2'S)-2-methylpiperidinyl-3-cyclohexen-1-carboxamide (SS220) is a new synthetic arthropod repellent. A three-step synthesis based on a chiral Diels-Alder reaction and diastereomeric resolution of 2-methylpiperidine was developed to prepare the compound. Quantitative laboratory assays using human volunteers compared the effectiveness of SS220 with the commonly used repellents Deet and Bayrepel against Aedes aegypti (Linnaeus) and Anopheles stephensi Liston mosquitoes. In two experiments using Aedes aegypti, one using a single identical dose and one with varying doses used to develop a dose-response curve, SS220 was as effective as Deet and both compounds were more effective than Bayrepel. The three compounds were equally effective against An. stephensi. Based on the ease of its synthetic preparation and its repellent efficacy, we surmise that SS220 is a candidate to serve as a new and effective alternate repellent for protection against arthropod disease vectors.

Topics: Aedes; Animals; Anopheles; DEET; Dose-Response Relationship, Drug; Human Experimentation; Humans; Insect Repellents; Piperidines; Stereoisomerism

Topics: Animals; Culicidae; DEET; Humans; Insect Bites and Stings; Insect Repellents; Piperidines

IR3535, KBR3023, para-Menthane-3,8-diol (PMD), and deet were evaluated in controlled studies with human subjects (n = 5) for repellency to black salt marsh mosquitoes (Ochlerotatus taeniorhynchus Wiedemann), in the Everglades National Park, FL. In tests of 6-h duration, with an average mosquito biting pressure on exposed forearm skin of 19.5 (+/- 13.7) bites per minute, the mean percent repellencies (SE) for IR3535, KBR3023, PDM, and deet was 88.6 (3.2), 97.5 (1.7), 89.2 (2.9), and 94.8 (2.5), respectively. Mean complete protection times (SE) for IR3535, KBR3023, PMD), mean deet were 3.0 (1.0), 5.4 (0.6), 3.8 (1.4), and 5.6 (0.5) h, respectively. Untreated (ethanol) controls provided 0% repellency. When mosquito biting rates on the untreated forearm skin of repellent-treated subjects were compared with biting rates on the forearm skin of control subjects, the former were 23%-40% lower early in tests and as much as 22% higher late in tests. These differences cast doubt on the technical merit of test designs comprising evaluation of more than one repellent at a time on the same human subject while underscoring the importance of untreated subjects as negative controls in field repellent bioassays.

Topics: Activity Cycles; Animals; Culicidae; Cyclohexane Monoterpenes; Florida; Humans; Insect Bites and Stings; Insect Repellents; Insecticides; Menthol; Piperidines; Propionates; Terpenes

Field trials to compare repellent formulations containing either picaridin or deet against rainforest mosquitoes in northern Queensland, Australia, were conducted. Three repellents were compared at night: 9.3% picaridin and 19.2% picaridin (Autan Repel and Autan Repel Army 20, respectively, Bayer, Sydney, Australia) and 35% deet in a gel (Australian Defense Force [ADF]). During the day, the following three repellents were compared: 19.2% picaridin, 20% deet in a controlled release formulation (Sawyer Controlled Release Deet), and 33% deet in a polymer formulation (U.S. Army Extended Duration Topical Insect and Arthropod Repellent [EDTIAR]). The predominant mosquito species collected was Verrallina lineata (Taylor), with smaller numbers of Ochlerotatus kochi (Donitz), Anopheles farauti s.s. Laveran, Ochlerotatus notoscriptus (Skuse), and Coquilletidia xanthogaster (Edwards). In nighttime tests, 19.2% picaridin provided >94.7% protection for at least 9 h, and ADF deet provided >95% protection for 7 h. The 9.3% picaridin formulation provided >95% protection for only 2 h, and provided 60% protection at 9 h. In daytime tests, Sawyer 20% deet provided >95% protection for 6 h, and both 19.2% picaridin and U.S. Army EDTIAR provided >95% protection for 8 h. In both nighttime and daytime tests 19.2% picaridin provided similar or better protection than deet formulations.

Topics: Animals; Australia; Culicidae; DEET; Female; Humans; Insect Bites and Stings; Insect Repellents; Male; Mosquito Control; Piperidines; Trees; Tropical Climate

The relative efficacy of commercially available formulations of the new repellent KBR 3023 (Bayrepel, Bayer, Germany) was compared against Phlebotomus duboscqi. The results provided laboratory evidence of phlebotomine sandfly sensitivity.

Topics: Animals; Drug Evaluation, Preclinical; Insecticides; Phlebotomus; Piperidines; Reproducibility of Results

KBR 3023, 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)piperidine, a prospective insect repellent being developed by Bayer Corporation, was evaluated for developmental toxicity in the Sprague-Dawley rat and Himalayan rabbit. As the intended human usage of the test compound is topical, the test systems were exposed to the compound via the dermal route. Specifically, the animals were fitted with Elizabethan collars, to reduce the likelihood of oral ingestion, and dermally administered either 0, 50, 200, or 400 mg KBR 3023/kg (rat), and 0, 50, 100, or 200 mg KBR 3023/kg (rabbit) on gestation days 0-19 (rat) and 0-28 (rabbit). Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain and food consumption during gestation, was characterized. Animals were sacrificed on gestation day 20 (rat) and 29 (rabbit), at which time fetuses were removed by cesarean section and a gross maternal necropsy was performed. All fetuses were evaluated for external anomalies. With rats, approximately half of each litter was examined for visceral effects; the other half underwent a skeletal examination. With rabbits, all fetuses underwent both visceral and skeletal examinations. No effects were observed on maternal body weight gain or food consumption in either the rat or rabbit. In the rat, dermal effects (scaling/sloughing), were observed at the dose site of all test substance-treated groups from approximately gestation day 7 until termination of the study. Also noted were an increase in both absolute and relative liver weights in rats in the 400-mg/kg dose group. In the rabbit, dermal effects (slight erythema, squamous and cracked skin) were noted at the dose site of virtually all does administered the test compound, from approximately gestation day 7 until termination. Also observed in the rabbits was a potentially compound-related increase in soft stool, particularly at the highest dose level. In both species, there were no statistically significant effects on any reproductive parameters, or any embryonic endpoints, including pre/post-implantation loss and resorptions. There were no statistically significant effects on litter size or fetal or placental weights. No test compound-related external, visceral, or skeletal findings were observed. No effect on the individual fetal or litter incidence of total malformations or variations was observed and there was no difference in the incidence of malformations between males and females. KBR 3023 Technical

Topics: Administration, Cutaneous; Analysis of Variance; Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Embryo Implantation; Female; Fetus; Gestational Age; Insect Repellents; Male; Piperidines; Pregnancy; Rabbits; Rats; Rats, Sprague-Dawley; Reproduction; Toxicity Tests

Four insect repellent products (RPs) (RP 1, Experimental Repellent Lotion [Bayrepel 12%]; RP 2, Experimental Repellent Cream [Bayrepel 5%]; RP 3, Off! Insect Repellent II Aerosol [deet 15%]; and RP 4, Off! Skintastic II Cream [deet 7.5%]) were evaluated simultaneously for their efficacy against vector and nuisance mosquitoes. The aim of this study was to compare the relative efficacy of RPs based on a new repellent compound, Bayrepel (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-1-methylpropylester), with deet (N,N-diethyl-m-toluamide)-based RPs. An 8-h field efficacy of above repellents was evaluated against the day-biting mosquito (Aedes albopictus) and night-biting mosquitoes (Culex quinquefasciatus and Anopheles spp.). Evaluation was carried out by exposing humans with repellent-treated bare limbs to mosquitoes landing and to mosquitoes landing and biting. Repellent product 1 or 2 was applied on the left arm and leg, whereas RP 3 or 4 was applied on the right arm and leg, respectively. Application of these 4 RPs significantly reduced (P < 0.05) the landing and the landing and biting of day-biting and night-biting mosquitoes. All 4 RPs were found to be equally effective (P < 0.05) against Ae. albopictus and Cx. quinquefasciatus. However, for protection against Anopheles spp., RPs 1 and 3 exhibited significantly (P < 0.05) better repellency effect than RPs 2 and 4.

Topics: Aedes; Animals; Anopheles; Culex; Culicidae; DEET; Humans; Insect Repellents; Malaysia; Piperidines; Tropical Climate

The carcinogenic potential of 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine (KBR 3023), a prospective new insect repellent intended for human use, was studied in mice using the dermal route of application. Relying upon the toxicology profile that emerged in the subchronic rat bioassay that was conducted using dermally applied dosages of 0, 80, 200, 500, and 1000 mg KBR 3023/kg body weight per day, it was determined, in concert with the EPA, that dermally applied dosages of 0, 50, 100, or 200 mg KBR 3023/kg body weight per day would be used in the conduct of all definitive forms of subchronic, chronic, and lifetime descriptive testing performed with the chemical. Using this testing approach, the specific results of this 18-month study are as follows. All in-life parameters, which included body weight, food consumption, clinical observations, survival, and hematology were unaffected by exposure to KBR 3023. Similarly, postmortem analyses, which included organ weights and gross pathology, and histopathology were also unchanged following exposure to KBR 3023. No evidence of a compound-induced neoplasia was suggested in this bioassay.

Topics: Administration, Cutaneous; Animals; Biological Assay; Body Weight; Carcinogenicity Tests; Dose-Response Relationship, Drug; Eating; Eye; Female; Insect Repellents; Male; Mice; Mice, Inbred ICR; Organ Size; Piperidines; Skin

The chronic toxicology and carcinogenic potential of 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine (KBR 3023), a prospective new insect repellent intended for human use, was studied in rats using the dermal route of application. Relying upon the toxicology profile that emerged in the subchronic rat bioassay that was conducted using dermally applied dosages of 0, 80, 200, 500 and 1000 mg KBR 3023/kg body wt/day, it was determined, in concert with the Environmental Protection Agency (EPA), that dermally applied dosages of 0, 50, 100 or 200 mg KBR 3023/kg body wt/day would be used in the conduction of all definitive forms of subchronic, chronic, and lifetime descriptive testing performed with the chemical. Using this testing approach, the specific results of this 2-year study are as follows. All in-life parameters, which included body weight, food consumption, clinical observations, survival, ophthalmology, clinical chemistry, hematology, and urinalysis, were unaffected by exposure to KBR 3023. Similarly, postmortem analyses, which included organ weights and gross pathology, were also unchanged following exposure to KBR 3023. Histopathology at the dose site/skin was characterized by a pattern of acanthosis and/or hyperkeratosis across all doses in 1- and 2-year rats. Beyond the dosing site, cystic degeneration of the liver was described in 2-year 200-mg KBR 3023/kg body wt/day males. No other compound-related non-dosing site lesion was identified at any dose tested. No evidence of a compound-induced neoplasia was suggested in this bioassay.

Topics: Administration, Cutaneous; Animals; Biological Assay; Body Weight; Carcinogenicity Tests; Dose-Response Relationship, Drug; Drug Administration Schedule; Eating; Eye; Female; Insect Repellents; Liver; Male; Organ Size; Piperidines; Rats; Rats, Sprague-Dawley; Skin