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A field study to compare a formulation containing 40% deet (N,N-diethyl-3-methyl benzamide) in ethanol (Bushman™) and a battery-powered fan emanator with a chemical strip containing 31.2% metofluthrin (OFF!® Clip-On™) was conducted at Redcliffe, Queensland, Australia, in February 2016. The 40% deet provided 100% protection against mosquitoes for 5 h until tests ceased, while the OFF! Clip-On device provided only 42.2-60.8% protection against Aedes vigilax during the same period., Competing Interests: Mention of a commercial product does not constitute an endorsement by the Australian Defence Force., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

Background: Prevention of arthropod-borne infections hinges on bite prevention. We aimed to investigate travellers' use of repellents., Methods: We measured the amount of applied repellent with a spray containing 30% DEET and 20% Icaridin versus a lotion with 20% Icaridin alone. We calculated the concentration of active ingredient reached on the skin and evaluated formulation acceptability. The travellers completed a questionnaire evaluating Knowledge, Attitudes and Practice (KAP) to anti-vectorial protective measures (AVPM)., Results: Some 200 volunteers travelling to mosquito borne infection endemic areas were recruited. The mean concentration of active substance achieved on the skin of the left arm was 0.52 mg/cm 2 of DEET/Icaridin spray versus 0.21 mg/cm 2 of Icaridin lotion. These levels are below the recommended protective dose (1 mg/cm 2 ) for each formulation. Women were significantly more likely to apply a higher, protective dose of repellent. Travellers to Africa, women and older participants showed higher projected adherence to AVPM., Conclusions: Only 2.5% of recruited travellers applied the recommended protective dose of repellent. Women and older travellers are the most adherent users of repellents. The pre-travel health consultation should provide more information on the application quantity and correct use of repellents., (Copyright © 2018. Published by Elsevier Ltd.)

Gulf War Illness (GWI) is a chronic multi-symptom disorder experienced by as many as a third of the veterans of the 1991 Gulf War; the constellation of "sickness behavior" symptoms observed in ill veterans is suggestive of a neuroimmune involvement. Various chemical exposures and conditions in theater have been implicated in the etiology of the illness. Previously, we found that GW-related organophosphates (OPs), such as the sarin surrogate, DFP, and chlorpyrifos, cause neuroinflammation. The combination of these exposures with exogenous corticosterone (CORT), mimicking high physiological stress, exacerbates the observed neuroinflammation. The potential relationship between the effects of OPs and CORT on the brain versus inflammation in the periphery has not been explored. Here, using our established GWI mouse model, we investigated the effects of CORT and DFP exposure, with or without a chronic application of pyridostigmine bromide (PB) and N,N-diethyl-meta-toluamide (DEET), on cytokines in the liver and serum. While CORT primed DFP-induced neuroinflammation, this effect was largely absent in the periphery. Moreover, the changes found in the peripheral tissues do not correlate with the previously reported neuroinflammation. These results not only support GWI as a neuroimmune disorder, but also highlight the separation between central and peripheral effects of these exposures., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: 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., Method: Identification and analysis of laboratory and field-based trials published in peer-reviewed journals that compared DEET to picaridin efficacy., Results: 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., Conclusion: 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.

Preventing tick bites using repellents could make a valuable contribution to an integrated tick management programme for dogs. Here, the ability of a range of essential oils or active ingredients of commercially available repellents, to abolish the orientation and taxis of the tick Ixodes ricinus towards sebum extracted from dog hair was examined in laboratory bioassays. Substantial differences between oils were observed, but turmeric oil was both able to prevent a climbing response by ticks and had a longer residual activity than other oils. A blanket-drag field assay was then used to compare the attachment of ticks to blankets impregnated with one of: turmeric oil, DEET (positive control), orange-oil or excipient only (negative controls). In total, 899 ticks were counted, with an average of 23.3 (SD ± 21.3) ticks per blanket drag for excipient-only (n = 16), 26.9 (SD ± 28.6) for orange oil (n = 16), 2.6 (SD ± 2.0) for turmeric oil (n = 16) and 3.4 (SD ± 3.7) for DEET (n = 16). Finally, in a participatory in vivo trial, tick acquisition by 15 untreated control dogs was compared with 24 dogs sprayed with turmeric-oil and 16 dogs sprayed with orange oil (both 2.5% v/v diluted in water with a 1% coco glucoside excipient) before each walk in known tick infested areas. The percentage of dogs with ticks attached to the legs or belly of dogs sprayed with turmeric oil suspension (15% ± 19.4%) was significantly lower than that of ticks attached to the same areas of dogs sprayed with orange oil suspension (85% ± 19.4%) and unsprayed dogs (73% ± 26.2%) (P < 0.05). The data indicate that turmeric-oil may form a valuable component of a tick management programme for domestic dogs., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Competing Interests: Competing interests: None declared.

Gulf War Illness (GWI) is a chronic disease that affects the 1991 Gulf War (GW) veterans for which treatment is lacking. It has been hypothesized that drugs used to protect military personnel from chemical attacks and insects during the war: pyridostigmine bromide (PB),N, N-diethyl-m-toluamide (DEET), and permethrin (PER) together with stress may have contributed collectively and synergistically to generate GWI. There is a need to find markers of pathology to be used in pre-clinical trials. For this purpose we employed a previously validated mouse model of GWI evoked by daily exposure to PB (1.3 mg/kg), DEET (40 mg/kg), PER (0.13 mg/kg), and 5 min of restraint stress for 28 days to analyze behavior, brain pathology and neurochemical outcomes three months later. GWI-model mice were characterized by increased anxiety, decreased hippocampal levels of N-acetyl aspartate, GABA, the GABA-producing enzyme GAD-67 and microglial activation. We also observed that GWI model was sexually dimorphic on some measures: males had increased while females had decreased protein levels of the acetylcholine-synthesizing enzyme, choline acetyltransferase, in the septum and hippocampus and decreased levels of the receptor for brain-derived neurotrophic factor, TrkB140, in the hippocampus. Increased hippocampal levels of nerve growth factor were detected in males only. Together the data show behavioral and neuropathological abnormalities detected at 3 months post-exposure and that some of them are sexually dimorphic. Future preclinical studies for GWI may take advantage of this short latency model and should include both males and females as their response to treatment may differ., (Published by Elsevier B.V.)

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.

Schistosomiasis is a parasitic infection acquired through freshwater exposure in the tropics. It is an infection that can have devastating implications to military personnel if it is not recognized and treated, especially later in life. While there is an abundance of information available about schistosomiasis in endemic populations, the information on nonendemic populations, such as deployers, is insufficient. Definitive studies for this population are lacking, but there are actions that can and should be taken to prevent infection and to treat patients. This literary review presents a case study, reviews basic science, and explores the information available about schistosomiasis in nonendemic populations. Specifically, the authors provide recommendations for the prevention, diagnosis, and postexposure management in military personnel., (2016.)

Objective: We assessed the efficacy of commercial repellents available in Yucatan against Aedes aegypti, vector of dengue, Chikungunya and Zika., Materials and Methods: Protection time was determined based on WHO/CTD/ WHOPES/IC y la NOM-032-SSA2-20I4., Results: Products with DEET (N, N-diethyl-3-methylbenzamide) at 25% met the recommended protection. Efficacy was directly proportional to the concentration of DEET; botanicals repellents resulted no protective., Conclusions: Repellents with DEET provided more protection against Ae. aegypti and botanical repellents, including impregnated wristbands, provided no protection.

The objective of this study was to clarify the efficacy of a currently available N,N-diethyl-m-toluamide (DEET) repellent against tick species in Japan. We performed 2 different field trials: "human trap," and "flag-dragging." In total, 482 ticks were collected from white flannel cloths in the field studies. The collected tick species were Ixodes persulcatus and I. ovatus, which accounted for 5.3% and 94.7% of the ticks in the human trap test and 31.4% and 68.6% in the flag-dragging test, respectively. The repellency levels of DEET-treated flannel cloths in the human trap and flag-dragging tests were 84.0% and 99.7%, respectively. The escape times for I. persulcatus and I. ovatus female adults from DEET-treated flannel cloths were determined. The median escape times for I. persulcatus and I. ovatus on DEET-treated flannel cloths were 48 s (95% confidence interval [CI]: 30-96) and 10 s (95% CI: 5-24), respectively. In contrast, many ticks remained on the untreated flannel cloths for 10 min after mounting. These results indicate that DEET repellents appear to prevent tick bites and that the use of DEET repellents against ticks is an effective personal protection measure.

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.

Background: Long-lasting insecticidal nets (LLINs) have limited effect on malaria transmitted outside of sleeping hours. Topical repellents have demonstrated reduction in the incidence of malaria transmitted in the early evening. This study assessed whether 15% DEET topical repellent used in combination with LLINs can prevent greater malaria transmission than placebo and LLINs, in rural Tanzania., Methods: A cluster-randomized, placebo-controlled trial was conducted between July 2009 and August 2010 in a rural Tanzanian village. Sample size calculation determined that 10 clusters of 47 households with five people/household were needed to observe a 24% treatment effect at the two-tailed 5% significance level, with 90% power, assuming a baseline malaria incidence of one case/person/year. Ten clusters each were randomly assigned to repellent and control groups by lottery. A total of 4,426 individuals older than six months were enrolled. All households in the village were provided with an LLIN per sleeping space. Repellent and placebo lotion was replaced monthly. The main outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive case detection (PCD). Incidence rate ratios were estimated from a Poisson model, with adjustment for potential confounders, determined a priori. According-to-protocol approach was used for all primary analyses., Results: The placebo group comprised 1972.3 person-years with 68.29 (95% C.I 37.05-99.53) malaria cases/1,000 person-years. The repellent group comprised 1,952.8 person-years with 60.45 (95% C.I 48.30-72.60) cases/1,000 person-years, demonstrating a non-significant 11.44% reduction in malaria incidence rate in this group, (Wilcoxon rank sum z=0.529, p=0.596). Principal components analysis (PCA) of the socio-economic status (SES) of the two groups demonstrated that the control group had a higher SES (Pearson's chi square=13.38, p=0.004)., Conclusions: Lack of an intervention effect was likely a result of lack of statistical power, poor capture of malaria events or bias caused by imbalance in the SES of the two groups. Low malaria transmission during the study period could have masked the intervention effect and a larger study size was needed to increase discriminatory power. Alternatively, topical repellents may have no impact on malaria transmission in this scenario. Design and implementation of repellent intervention studies is discussed., Trial Registration: The trial was registered ISRCTN92202008--http://www.controlled-trials.com/ISRCTN92202008.

N,N-diethyl-m-toluamide (DEET) has been registered for commercial use as an insect repellent for over five decades, and is used widely across the world. Concerns over the safety of DEET first emerged during the 1980s after reports of encephalopathy following DEET exposure, particularly in children. However, the role of DEET in either the illness or deaths was and remains purely speculative. In response to these cases a number of reviews and investigations of DEET safety were carried out. Here we examine the methods used and information available to determine the safety of DEET in humans. Animal testing, observational studies and intervention trials have found no evidence of severe adverse events associated with recommended DEET use. Minor adverse effects noted in animal trials were associated with very large doses and were not replicated between different test species. The safety surveillance from extensive humans use reveals no association with severe adverse events. This review compares the toxicity assessment using three different models to define the risk assessment and safety threshold for DEET use in humans and discusses the clinical consequences of the thresholds derived from the models.The theoretical risks associated with wearing an insect repellent should be weighed against the reduction or prevention of the risk of fatal or debilitating diseases including malaria, dengue, yellow fever and filariasis. With over 48 million European residents travelling to regions where vector borne diseases are a threat in 2009, restricting the concentration of DEET containing repellents to 15% or less, as modelled in the 2010 EU directive, is likely to result in extensive sub-therapeutic activity where repellents are infrequently applied. Future European travellers, as a consequence of inadequate personal protection, could potentially be at increased risk of vector borne diseases. Risk assessments of repellents should take these factors into account when setting safe limits.

DEET (N,N-diethyl-m-toluamide) is the most common active ingredient in the insect repellents commonly detected in European groundwater. The aim of this study was to investigate the effect of subchronic DEET exposure on biochemical and haematological parameters, antioxidant enzymes, including catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and the amount of thiobarbituric acid reactive substances (TBARS) in common carp (Cyprinus carpio L.). Two specific proinflammatory and anti-inflammatory cytokine genes were selected to assess an immunological status of the fish. Fish were exposed for 28 days to three concentrations of DEET (1.0 µg/L, 0.1 mg/L, and 1.0 mg/L) where 1 µg/L is corresponding to the concentration found in the environment. DEET had a significant (P < 0.05) effect on increased RBC, decreased mean corpuscular volume (MCV), and mean corpuscular haemoglobin value (MCH) compared to control groups in the concentration of 1 mg/L. A significant decline (P < 0.05) in triacylglycerols (TAG) in plasma was found in the concentration of 1 mg/L compared to the control groups. The parameters of oxidative stress in tissues of common carp were weekly affected and immunological parameters were not affected.

Urinary metabolites of DEET of 17 children (5-7 years of age) and 9 adults (23-25 years of age) were examined in the study described in this article. Urine samples were collected from each subject within eight hours after a single dermal application of 10 mL 12% DEET-containing insect repellent. Two metabolites, m-diethylaminocarbonyl benzoic acid (R3N0) and N-ethyl-m-toluamide (RON1), with unchanged DEET, were identified in the urine. The major metabolite was R3NO, which was 78.2% and 46.1% of the total DEET metabolites from children and adults, respectively, indicating that the pathway of ring methyl oxidation predominated. The recovered DEET metabolites were observed significantly more from children (1,116 pg) than from adults (446.2 pg) (p < .001). The difference in dermal absorption, albeit primarily attributed to DEET loading, was found to be related to height by regression analysis. The inverse association between height and dermal absorption of DEET suggests that shorter individuals (i.e., children) are subjected to dermal uptake of DEET. To avoid unnecessary exposure, parents need to be cautious when applying DEET-containing insect repellent on children.

Background: Mosquito vectors of malaria in Southeast Asia readily feed outdoors making malaria control through indoor insecticides such as long-lasting insecticidal nets (LLINs) and indoor residual spraying more difficult. Topical insect repellents may be able to protect users from outdoor biting, thereby providing additional protection above the current best practice of LLINs., Methods and Findings: A double blind, household randomised, placebo-controlled trial of insect repellent to reduce malaria was carried out in southern Lao PDR to determine whether the use of repellent and long-lasting insecticidal nets (LLINs) could reduce malaria more than LLINs alone. A total of 1,597 households, including 7,979 participants, were recruited in June 2009 and April 2010. Equal group allocation, stratified by village, was used to randomise 795 households to a 15% DEET lotion and the remainder were given a placebo lotion. Participants, field staff and data analysts were blinded to the group assignment until data analysis had been completed. All households received new LLINs. Participants were asked to apply their lotion to exposed skin every evening and sleep under the LLINs each night. Plasmodium falciparum and P. vivax cases were actively identified by monthly rapid diagnostic tests. Intention to treat analysis found no effect from the use of repellent on malaria incidence (hazard ratio: 1.00, 95% CI: 0.99-1.01, p = 0.868). A higher socio-economic score was found to significantly decrease malaria risk (hazard ratio: 0.72, 95% CI: 0.58-0.90, p = 0.004). Women were also found to have a reduced risk of infection (hazard ratio: 0.59, 95% CI: 0.37-0.92, p = 0.020). According to protocol analysis which excluded participants using the lotions less than 90% of the time found similar results with no effect from the use of repellent., Conclusions: This randomised controlled trial suggests that topical repellents are not a suitable intervention in addition to LLINs against malaria amongst agricultural populations in southern Lao PDR. These results are also likely to be applicable to much of the Greater Mekong Sub-region., Trial Registration: This trial is registered with number NCT00938379.

Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.

Coping strategies including smoke screens are used against nuisance bites of Simulium damnosum Theobald (Diptera:Simuliidae) in onchocerciasis endemic communities. To find more effective alternatives, the efficacy of commercially available N,N-diethyl-3-methylbenzamide (DEET) products with active concentrations of 9.5, 13, 25, 50 and 98.1-100% and 'NO MAS,' (active component: para-menthane-3,8-diol and lemon grass oil) were tested at Bui-Agblekame, Ghana. A Latin square study design was implemented using eight groups of two vector collectors each, who used repellents (treatment), mineral oil or nothing each day until the end of the study. Flies were caught and their numbers each hour recorded using the standard methods for onchocerciasis transmission studies. T-tests were used to compare the mean duration of protection and a one-way analysis of variance controlling for catchers and repellents was performed. Tukey's test was used to compare protection by repellents and mineral oil. The highest percentage protection was 80.8% by NO MAS and the least 42.5% by the 13% DEET product. The period of absolute protection was 5 h by NO MAS and 1 h by 50% DEET product. No significant increase in protection was offered beyond 25% active DEET products and no significance was observed in terms of catcher × repellent effect (F = 1.731, d.f. = 48, P = 0.209)., (© 2012 The Royal Entomological Society.)

Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Two newly designed formulations of stick camouflage face paint, one with 30% N,N-diethyl-3-methylbenzamide (DEET) and the other without DEET, were evaluated for acceptability among soldiers upon completion of normal military field training exercises. A total of 156 soldiers participated and completed a self-administered survey answering questions about product acceptability, packaging, and ease of use. Results of the study indicated that soldiers found stick formulations, with and without DEET, to be acceptable for use (62.9% and 83.7%, respectively). This data will be used by the Program Management Office at the U.S. Army Medical Materiel Development Activity to support a request to the Armed Forces Pest Management Board to assign a National Stock Number.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.

N,N-diethyl-3-methylbenzamide (DEET) is popular insect repellent which is considered safe and effective, yet is subject to considerable skin absorption. Skin absorption decreases effective repellency since less DEET is available for evaporation. We have investigated the extent to which DEET skin absorption can be reduced and evaporation sustained through encapsulation. DEET permeation through human skin in vitro was measured for an ethanolic solution standard and for two novel topical controlled-release formulations in which the DEET active material was temporarily sequestered within a permeable, charged-film microcapsule. Evaporation measurements were gathered using Tenax TA cartridges and a sampling pump drawing air over the skin. Three formulations were studied: a previously reported microcapsule formulation (Formulation A); a newly-developed microcapsule formulation (Formulation B); and a non-encapsulated ethanol control solution. Formulation B led to a 30% reduction in DEET permeation versus control. The two microcapsule DEET formulations exhibited 36-40% higher cumulative evaporation from the skin than did the control. The vapor trapping measurements in vitro show that Formulation B provided more than 48h of effective evaporation rate for repellency, while Formulation A provided less than 35h and the ethanol control less than 15h. This establishes a technical advantage for the controlled-release approach., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Unlabelled: BACKGROUND. Mosquitoes are blood-sucking insects, nuisance to humans and animals. Their bites cause itching and allergic reactions. These insects are also vectors of several viruses, bacteria and parasites. Protection against mosquitoes is therefore justified and desirable. This can give repellents and products for protection small outdoor areas such as terraces, home gardens. OBJECTIVE. The aim of this study was to evaluate the effectiveness of eight selected products with different formulations used against mosquitoes including: 5 preparations for use on the body or clothing (repellents A, B, C, D, E and 3 products for use in small outdoor spaces (I, J, K)., Material and Methods: [corrected] Repellents were tested in laboratory trials, when volunteers were exposed to Aedes aegypti females breeding in the laboratory. Products I, J, K were tested in field trials; volunteers were exposed to female mosquitoes at various ages from the environment (Aedes sp, Culex sp)., Results: The results showed that all tested repellents were efficient during 4 hrs. After this time their effectiveness decreased--fast in the case of repellent B (10% DEET), not very fast, but significant--in the case of repellent C (15% DEET). Three products for small area protection gave (each of them) 3-hour protection against mosquito bites. Product K (21,97% allethrin) was 100% effective (no bites at all)., Conclusions: Both kinds of product can give effective protection against mosquito bites. Their use is most effective, cheaper and more safe for the environment method of protection against mosquitoes than chemical spraying of large areas.

Insect repellents (e.g. N,N-diethyl-m-toluamide or DEET) applied to the skin can potentially interfere with sweat production and evaporation, thus increasing physiological strain during exercise-heat stress. The purpose was to determine the impact of 33% DEET lotion on sweating responses, whole body thermoregulation and thermal sensation during walking exercise in the heat. Nine volunteers (2 females, 7 males; 22.1 ± 4.9 years; 176.4 ± 10.0 cm; 79.9 ± 12.9 kg) completed 5 days of heat acclimation (45°C, 20% rh; 545 watts; 100 min/day) and performed three trials: control (CON); DEET applied to forearm (DEET(LOC), 12 cm(2)); and DEET applied to ~13% body surface area (DEET(WB),). Trials consisted of 30 min walking (645 watts) in 40°C, 20% rh environment. Local sweat rate (SR), onset and skin wettedness were measured in DEET(LOC), and heart rate (HR), rectal temperature (T (re)), skin temperature (T (sk)), RPE, and thermal sensations (TS) were measured during DEET(WB). No differences (p > 0.05) were observed between DEET(LOC) versus CON, respectively, for steady state SR (1.89 ± 0.44 vs. 2.09 ± 0.84 mg/cm(2)/min), SR area under the curve (46.9 ± 11.7 vs. 55.0 ± 20.8 mg/cm(2)), sweating onset, or skin wettedness. There were no differences (p > 0.05) in HR, T (re), T (sk), Physiological Strain Index, RPE or TS between DEET(WB) versus CON. DEET did not impact measures of local forearm sweating and when applied according to military doctrine, did not adversely impact physiological responses during exercise-heat stress. DEET can be safely worn during military, occupational and recreational activities in hot, insect infested environments.

The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: This review aims to examine the effectiveness of citronella preparation used as a mosquito repellent., Methods: Multiple computerized databases such as MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, and AMED, were searched for controlled laboratory experiments that compared the effectiveness of citronella products to control in repelling Aedes, Anopheles and Culex mosquitoes using the cage or room methods. Outcomes measures were protection time and percentage repellency. The weighted mean difference and 95% confidence interval were calculated comparing the outcomes in the citronella and control groups. Meta-analysis was performed using the DerSimonian and Laird method under a random-effects model., Results: Eleven studies met inclusion criteria. Based on a meta-analysis of studies using the cage method, protection time of the citronella oil for preventing Aedes mosquitoes was less than that in the DEET (N,N-diethyl-m-toluamide) group, with a difference in protection time of 253 min (95% confidence interval: 169-336). The combination of citronella oil and vanillin is likely to have a longer protection time compared with citronella oil alone. In studies using the room method, citronella oil and/or the combination of citronella oil and vanillin provided complete repellency at least 3 h. In Anopheles and Culex mosquitoes, a combination of citronella oil and vanillin product demonstrated a comparable protection time against DEET; however, it remained inconclusive due to a limited number of studies., Conclusions: Citronella products are less effective than DEET products in terms of duration of protection. Adding vanillin to citronella oil products could prolong the protection time., (© 2011 Blackwell Publishing Ltd.)

Background & Objectives: Repellents are commonly used personal protection measures to avoid mosquito bites. In the present study, Advanced Odomos cream (12% N, N-diethyl-benzamide) was tested for its efficacy against mosquitoes in comparison to DEET (N,N-diethyl-3-methyl benzamide)., Methods: Bioassays were conducted to assess the repellency of Advanced Odomos and DEET creams against Anopheles stephensi and Aedes aegypti. Their efficacy was tested on human volunteers applied with different concentrations of test creams ranging from 1 to 12 mg/cm 2 and by exposing them to mosquitoes at hourly intervals. Field evaluation was also carried out to test the duration of protection of the test creams against Anopheles and Aedes mosquitoes during whole night and day time collections, respectively on human volunteers. Mosquito collections were done using torch light and aspirator., Results: Complete (100%) protection was achieved at 10 mg/cm 2 cream formulation of Advanced Odomos (1.2 mg a.i/cm 2 ) dose against An. stephensi and 12 mg/cm 2 (1.44 mg a.i./cm 2 ) against Ae. aegypti on human baits. There was no statistically significant differences in per cent protection against mosquito bites between Advanced Odomos and DEET cream (P>0.05) in respective doses. Complete protection up to 11 h was observed against Anopheles mosquitoes during whole night collections and up to 6 h against Ae. aegypti in day time collections. No adverse reactions such as itching, irritation, vomiting, nausea, etc. were reported by the volunteers., Interpretation & Conclusions: Advanced Odomos cream applied at 10 mg/cm 2 concentration provided 100% protection from Anopheles mosquitoes up to 11 h whereas about 6 h protection was recorded against Ae. aegypti. The laboratory and field trials indicate that for longer protection against Anopheles mosquitoes 10 mg/cm 2 will be appropriate and in case of Ae. aegypti more than 10 mg/cm 2 application is required for complete protection. In conclusion, the Advanced Odomos cream was comparable to the known repellent cream DEET for prolonged protection against malaria and dengue vectors.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both., (© The Author(s) 2010)

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.

DEET is the most widely used insect repellent worldwide. In Drosophila olfactory receptor neurons (ORNs), DEET is detected through a mechanism employing the olfactory receptor, OR83b. However, it is controversial as to whether ORNs respond directly to DEET or whether DEET blocks the response to attractive odors. Here, we showed that DEET suppressed feeding behavior in Drosophila, and this effect was mediated by gustatory receptor neurons (GRNs). DEET was potent in suppressing feeding as <0.1% DEET elicited aversive behavior. Inhibition of feeding required multiple gustatory receptors (GRs) expressed in inhibitory GRNs. DEET stimulated action potentials in GRNs that respond to aversive compounds, and this response was lost in the Gr32a, Gr33a, and Gr66a mutants. Since 0.02% DEET elicited action potentials, we conclude that DEET directly activates of GRNs. We suggest that the effectiveness of DEET in pest control owes to its dual action in inducing avoidance simultaneously via GRNs and ORNs., (2010 Elsevier Inc. All rights reserved.)

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.

On the military training facility of Tekong Island, Singapore, a comprehensive vector-borne disease control program was started in end-2006 to reduce mosquito populations and negate the need for anti-malaria chemoprophylaxis. The program was based on 1) preventing importation of malaria through screening of visitors, 2) preventing human-to-mosquito transmission through early case detection and mosquito control, 3) preventing mosquito-to-human transmission through personal protection, and 4) contingency plans. Systematic environmental works were performed to reduce breeding sites, and insecticide use targeted both adult mosquitoes and larvae. Mosquito populations declined from 103 mosquitoes per sampling site in January 2007 to 6 per site by March 2007 (P < 0.001). The proportion of positive ovitraps declined from 93% in January 2007-2% in March 2007 (P < 0.001). There were no malaria cases on the island despite chemoprophylaxis termination, showing that comprehensive combination vector-control strategies were effective in reducing the risk of malaria.

The enhancement/retardation of percutaneous permeation of diethyl-m-toluamide (DEET) in the presence of five percutaneous penetration modifiers (laurocapram, 3-dodecanoyloxazolidin-2-one (N-0915), S,S-dimethyl-N-(4-bromobenzoyl) iminosulfurane (DMBIS), S,S-dimethyl-N-(2-methoxycarbonylbenzenesulfonyl) iminosulfurane (DMMCBI) and tert-butyl 1-dodecyl-2-oxoazepan-3-yl-carbamate (TBDOC)) was investigated. These permeation modifiers were formulated in either water, propylene glycol (PG), ethanol or polyethylene glycol 400 (PEG 400). The permeation studies indicated that laurocapram enhanced DEET permeation in PG, but retarded in PEG 400. Likewise, N-0915 acted as a retardant with ethanol and PEG 400, but not with water. DMBIS decreased the permeation with ethanol as compared to permeation with water, PEG 400 or PG. Similarly, DMMCB acted as a retardant with ethanol and PEG 400, but not with water or PG. TBDOC formulations revealed its activity as a retardant with ethanol, but behaved as enhancer with water, PG and PEG 400. In addition, penetration modifier interactions with stratum corneum ceramide were investigated using chemical modeling. This investigation is significant since it confirms the role of pharmaceutical formulations and shows for the first time that an enhancer can become a retardant or vice versa depending upon the vehicle in which it is applied to the skin. Hence, we should be using the term "penetration modifiers" for all such compounds., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids., Methodology/principal Findings: We present here the results of two trials run against free-flying Anopheles gambiae populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures., Conclusion: These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors.

The synergic in vitro skin permeation enhancing-effect of N,N-diethyl-m-toluamide (DEET) and dodecylamine was investigated in order to develop a novel non-scrotal matrix-type transdermal delivery system of testosterone (TS). When DEET was loaded in DuroTak 87-2510 together with 2% TS and 3% dodecylamine, the in vitro rat skin permeation rate of TS synergistically increased as DEET concentration increased up to 0.5%. No further increase in permeation was observed thereafter and a plateau was observed up to 3.8% DEET. Moreover, compared to 0.5% DEET concentration, the addition of 3.8% of DEET in combination with 3% dodecylamine and 6% TS further increased the permeation rate of TS, and the maximum permeation rate of 11.21 microg/cm(2)/h was achieved. The in vitro skin permeation rates of TS from a transdermal delivery system of DuroTak 87-2510 containing 6% TS, 3% dodecyamine, and 3.8% DEET were in the following order: hairless mouse skin > rat skin > human cadaver skin. Assuming that a system with a surface area of 60 cm(2) is applied, the human cadaver skin permeation rate of 5.74 microg/cm(2)/h achieved in this study can be interpreted as being equivalent to delivering approximately 8. 27 mg of TS per day. Considering that the commercially available product (Testoderm TTS) for non-scrotal skin of the same surface area is designed to administer 5 mg of TS per day, the new formulation could maintain therapeutic plasma concentration of TS at a smaller surface area of 40 cm(2).

Mite infestations are important in dermatology because these may cause dermatologic diseases that range from papulosquamous eruptions to urticarial lesions to bullous eruptions and may spread infectious diseases. These clinical manifestations are important to recognize because mite-associated diseases may have systemic complications and may be confused with other dermatologic conditions. In treating mite infestations, oral antibiotics may be necessary. Prevention of infestation may be accomplished by pre-treating clothing with permethrin, using insect repellent N,N-Diethyl-meta-toluamide on clothing and skin, and treating animals infected with mites. This article will review etiology, clinical manifestation, and treatment of mite infestations.

N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4-/CD8- and CD4+/CD8- lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses.

Celery-based products were investigated for chemical composition, skin irritation, and mosquito repellency in comparison to commercial repellents and the standard chemical, N,N-diethyl-3-methylbenzamide (DEET), with a goal to develop a natural alternative to synthetic repellents for protection against mosquitoes. Chemical identification by gas chromatography coupled with mass spectrometry discovered that the major constituents of Apium graveolens hexane extract (AHE) were 3-n-butyl-tetrahydrophthalide (92.48%), followed by 5.10% beta-selinene and 0.68% gamma-selinene. Evaluation of skin irritation in 27 human volunteers revealed no irritant potential from 25% ethanolic AHE solution. Laboratory investigated repellent against female Aedes aegypti mosquitoes demonstrated that G10 formula, the best AHE-developed product, provided remarkable repellency with a median protection time of 4.5 h (4.5-5 h), which was greater than that of ethanolic DEET solution (25% DEET, 3.5 h) and comparable to that of the best commercial repellent, Insect Block 28 (28.5% DEET, 4.5 h). According to significantly promising results, including highly effective repellency and no potential skin irritation or other side effects, the G10 formula is a worthwhile product that has the promise of being developed for commercialized registration. This developed AHE product could be an acceptable and affordable alternative to conventional synthetic chemicals in preventing mosquito bites, and in turn, helping to interrupt mosquito-borne disease transmission.

Here I report the first findings of consistently high, long-duration efficacy of IR3535 (ethyl butyl acetyl aminopropionate) formulations in the United States. I tested novel, controlled-release formulations of IR3535, at 10% in lotion and at 20% in pump spray and aerosol, against mosquitoes in the field and blacklegged ticks in the laboratory. These were also the first studies to be conducted under the authority of the U.S. Environmental Protection Agency's Human Studies Rule of 2006, and the protocols underwent science and ethics reviews by five entities. IR3535 is better known in Europe than in North America, having been marketed in the United States only more recently, and there are comparatively few publications on its efficacy. I began with pretrial studies of dosing behavior to compute formula-specific mean dosing rates for the subsequent efficacy trials. Dosing rates were lower than the 1 ml/600 cm rate commonly used to quantify efficacy. Complete protection times ranged from 7.1 to 10.3 h for mosquitoes and from 9.1 to 12.2 h for blacklegged ticks. Long protection duration resulted in many cases being truncated by darkness or eventual subject withdrawal, which suggests that actual protection times were probably greater.

The insect repellent N,N-diethyl-3-methylbenzamide (DEET) is widely used and is generally regarded as safe when used according to label instructions. Yet many studies have shown it to be absorbed through the skin. The objective of this study was to determine whether the skin absorption rate of DEET could be decreased while maintaining an evaporation rate consistent with effective repellency. To this end, an aqueous suspension containing 14C-DEET (15%w/w) entrapped in walled polysaccharide microcapsules was prepared and tested for skin absorption in vitro using modified Franz cells maintained in a fume hood. The control formulation was 15%w/w DEET in ethanol. Two doses (3 microL and 5 microL per 0.79 cm2 cell) of each formulation were applied to split-thickness human cadaver skin (n=8/dose), and permeation was monitored for 24h. The microencapsulated DEET formulation lead to a 25-35% reduction of radiolabel permeation compared to the ethanolic DEET formulation. Skin levels of radioactivity at 24h were comparable, indicating that DEET evaporation from the microencapsulated formulation was comparable to or greater than that from ethanol. Hence microencapsulation increased the ratio of DEET evaporation rate to skin penetration rate relative to unencapsulated control in this in vitro study.

This study evaluated the repellency effect of 3 topical repellents (permethrin, DEET and neem tree extract) against 3-5 day old females of laboratory and field strains of Anopheles stephensi. Probing/biting rates on the shaved belly of white rabbits were counted. Effective dose (ED) 50 and ED95 values were calculated by probit statistic software. The results revealed ED50 values of 0.007, 0.005 and 0.191 mg/cm2 for permethrin, DEET and neem, respectively, against the field strain. The figures for the laboratory strain were 0.006, 0.007, 0.156 mg/cm2. Major heterogeneity of response was observed using DEET. Although neem was the least effective agent, extracts of locally produced neem oil offer a promising repellent against mosquito biting.

Textile materials treated with synthetic repellents have the potential to provide protection against insect disease vectors but lack the residual activity necessary to achieve a prolonged effect or to be cost-effective. DEET MC is a formulation of DEET (N,N diethyl-m-toluamide) in which the repellent is gradually released from a capsule that binds the repellent. An experiment carried out on DEET-treated mosquito netting showed that the formulation repels, inhibits blood-feeding and kills mosquitoes for a period of at least 6 months under laboratory conditions. Such formulations may have the potential for use on nets against pyrethroid-resistant mosquitoes or on clothing or bedding materials distributed in disasters, emergencies or refugee camp situations.

The synergistic percutaneous enhancement between insect repellent DEET and sunscreen oxybenzone has been proven in our laboratory using a series of in vitro diffusion studies. In this study, we carried out an in vivo study to characterize skin permeation profiles from topical skin application of three commercially available repellent and sunscreen preparations. The correlation between skin disposition and drug metabolism was attempted by using data collected. Both DEET and oxybenzone permeated across the skin after the application and achieved substantial systemic absorption. Combined use of DEET and oxybenzone significantly enhanced the percutaneous penetration percentages (ranging 36-108%) due to mutual enhancement effects. Skin disposition indicated that DEET produced a faster transdermal permeation rate and higher systemic absorption extent, but oxybenzone formed a concentrated depot within the skin and delivered the content slowly over the time. In vivo AUCP/MRT of DEET and oxybenzone was increased by 37%/17% and 63%/10% when the two compounds were used together. No DEET was detected from the urine samples 48 h after the application. Tape stripping seemed to be a satisfactory approach for quantitative assessment of DEET and oxybenzone penetration into the stratum corneum. It was also concluded that pharmacological and toxicological perspectives from concurrent application of insect repellent and sunscreen products require further evaluation to ensure use efficacy and safety of these common consumer healthcare products.