[Remarks on insect repellents].
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Insect Repellents↗
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The effect of sunscreen on the efficacy of insect repellent: a clinical trial.
Sunscreen loses efficacy when used with the insect repellent N,N -diethyl-3-methylbenzamide (diethyltoluamide; deet). A previous study demonstrated a 33.3% decrease in sun protection factor when insect repellent and sunscreen were applied sequentially to the skin. The purpose of this study was to determine whether the efficacy of insect repellent is affected by two different formulations of sunscreen. The combination of sunscreen and insect repellent was tested in 8 groups: a control group (no sunscreen or insect repellent), sunscreen alone (two groups [gel and cream]), insect repellent alone, insect repellent applied before sunscreen (two groups), and insect repellent applied after sunscreen (two groups). The results of this study showed that insect repellent has the same efficacy even when sunscreen is applied with it. This indicates that in the formulations tested, sunscreen does not reduce the efficacy of insect repellent.
Drug Combinations↗
Perception and use of insect repellent among soldiers in the Singapore Armed Forces.
The Singapore Armed Forces currently uses the 75% DEET formulation insect repellent. To study the perception, use, and acceptability of this insect repellent, a survey was carried out on servicemen who had participated in field exercises. Although over 80% of the servicemen knew the proper use of the insect repellent and brought along the army-issued repellent in the field, less than half used this repellent frequently while on exercise. Eighty-three percent felt that the army repellent was only effective sometimes and that it lasted for 4 hours or less. Skin irritation was a common side effect when using the repellent. About 70.4% had used commercial insect repellents and perceived them to be more long lasting and with fewer side effects. The results from our study indicate that the army-issued insect repellent currently used is not totally acceptable to our servicemen. Thus, there is a pressing need to develop or acquire a better insect repellent that is more or just as effective, has fewer side effects in terms of smell and skin irritation, and with an improved mode of delivery, such as aerosol or pump spray.
Adolescent↗
Evaluation of commercial insect repellents on human skin against Aedes aegypti (Diptera: Culicidae).
An olfactometer was used to evaluate the efficacy of selected commercial insect repellent products against Aedes aegypti (L.). A comparison of 12 commercial repellent products was made on human skin. The products tested included 2 natural oil insect repellent formulations (Buzz Away and Green Ban) containing plant extracts, 2 proprietary products (Skin-So-Soft lotion and bath oil), and 8 commercial deet preparations in various concentrations and forms of spray, aerosol, stick, cream, and lotion. Behavioral responses and time to probe were determined in triplicate using 10 female mosquito challenges per replicate for each product. Generally, products with higher concentrations of deet were found to have longer repellence times. OFF spray and Muskol lotion offered the longest repellence times. However, there was no significant difference in time for mosquitoes to probe among the formulations. Skin-So-Soft lotion and bath oil were not as effective as deet in repelling Ae. aegypti. Natural oil insect repellent formulations offered essentially no repellency against Ae. aegypti. This is a simple and reproducible method to evaluate the efficacy of insect repellents and is recommended for preliminary screening of new insect repellents or formulations.
Aedes↗
Reduced transdermal absorption of N,N-diethyl-m-toluamide from a new topical insect repellent formulation.
Extensive absorption of the topical insect repellent N, N-diethyl-m-toluamide (DEET) causes systemic and local toxicities. This report describes the preparation and characterization of a new insect repellent formulation (FA), a PEG-polyacrylic acid polymer system, for its DEET release, in vitro skin permeation, and in vivo transdermal absorption properties; and for its relative repellency against Aedes aegypti mosquitoes. DEET release and skin permeation were studied in Franz diffusion cells. DEET transdermal absorption and relative repellency of FA were assessed in beagle dogs. A commercial DEET lotion (FB) and technical DEET (FC) were used as references. FA exhibited 19.5% and 61.7% decrease in DEET steady-state skin flux compared with FB and FC, respectively. At 15 mg DEET/kg, the absolute DEET transdermal bioavailability and Cmax were 13.4% and 154.3 ng/ml, respectively, for FA; and were 17.5% and 196.5 ng/ml, respectively, for FB. DEET half-lives (t1/2) for FA (2.52 hr) and FB (2.73 hr) were similar, while MRT for FA (4.99 hr) was significantly greater (p < 0.05) than that for FB (4.38 hr). FA showed lower mosquito biting rates at 1, 2, 3, 4, 5, and 6 hr postdose at 0.5 mg DEET/cm2. FA exhibited reduced in vitro skin permeation and in vivo transdermal absorption of DEET as well as superior repellency compared with FB. The PEG-polyacrylic acid polymer system is of value in the formulation of DEET lotions.
Administration, Topical↗
Field efficacy of four insect repellent products against vector mosquitoes in a tropical environment.
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.
Aedes↗
Percutaneous absorption of carbon 14 labeled insect repellents in hairless dogs.
The percutaneous penetration of three insect repellents was determined in hairless dogs. Each compound was administered intravenously and topically to three dogs. Urine, feces and blood samples were assayed for radioactivity by scintillation counting. The percent penetration for N,N-diethyl-m-toluamide (m-deet, the most widely used insect repellent), its isomer N,N-diethyl-p-toluamide and 2-ethyl-1,3-hexanediol were 7.9%, 7.6%, and 10.3% respectively. The results for m-deet penetration in the hairless dog are comparable to those in man.
Administration, Topical↗
Molecular similarity analysis between insect juvenile hormone and N, N-diethyl-m-toluamide (DEET) analogs may aid design of novel insect repellents.
Molecular similarity analysis of stereoelectronic properties between natural insect juvenile hormone (JH), -a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and N, N-diethyl-m-toluamide (DEET) and its analogs reveals similarities that may aid the design of more efficacious insect repellents and give a better insight into the mechanism of repellent action. The study involves quantum chemical calculations using the AM1 semi-empirical computational method enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds, followed by complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic and the DEET compounds. The similarity of stereoelectronic attributes of the amide/ester moiety, the negative electrostatic potential regions beyond the van der Waals surface, and the large distribution of hydrophobic regions in the compounds appear to be the three important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the van der Waals surface is likely to play a crucial role in molecular recognition interaction with the JH receptor from a distance. This also suggests electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor. The insect repellent property of the DEET analogs may thus be attributed to a conflict of complementarity for the JH receptor binding sites.
Algorithms↗
Development & evaluation of controlled release formulations of DEPA, an insect repellent.
Three controlled release formulations of the insect repellent DEPA (N, N-Diethyl phenylacetamide), Depa-A, Depa-B and Depa-C have been developed and tested on human subjects against Aedes aegypti adult mosquitoes for repellency and the results were compared to those of a solution of DEPA (Depa-0). The increase in the protection time of the formulations, as compared to Depa-0 was compared. Depa-B was found to be effective with a protection time of 7.13 and 6.15 h and percentage increase in protection time of 44.5 and 38.2 at the two application rates of 0.5 and 0.25 mg/cm2 of the repellent. This observation agreed with the studies carried out on the evaporation of the repellent formulations on two models, on adsorbing and nonadsorbing surfaces for the relative adsorption and evaporation by analysing the repellent concentrations, using an infrared spectrophotometer.
Acetamides↗
[Study of the preparations attracting and repelling insects].
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Animals↗
Insect repellents: an overview.
The optimal management of arthropod bites is prevention, and many over-the-counter insect repellents are available. Since first marketed in 1956, deet has remained the most effective repellent against mosquitoes, biting fleas, gnats, and chiggers. Permethrin is applied to clothing rather than to skin, and it is a better repellent against ticks than deet. The risk of serious side effects with the use of deet is slight; nevertheless, the lowest effective concentration should be used. The current, popular repellent agents (for adults and children) and their active ingredients are discussed. In addition, the Environmental Protection Agency guidelines for the safe use of insect repellents are supplied.
Adult↗
Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985-1989.
This study analyzed 9,086 human exposures involving N,N-diethyl-m-toluamide--containing insect repellents that were reported to Poison Control Centers from 1985-1989. Nearly two-thirds of those exposed had no adverse effects or only experienced minor symptoms that resolved rapidly. Symptoms were more likely to occur after ocular or inhalation exposures and least likely to occur if the product was ingested. The only reported death occurred in a patient who suicidally ingested 8 oz of an insect repellent containing N,N-diethyl-m-toluamide. Five patients may have experienced a serious or potentially life-threatening effect but the poison center record did not provide unequivocal substantiation of the effect or clearly establish N,N-diethyl-m-toluamide as the causative agent. From the analysis of those patients calling Poison Control Centers, it appears the risk of serious medical effects with the labeled use of N,N-diethyl-m-toluamide-containing insect repellents is low in comparison with its reported annual use by about 30% of Americans. For patients contacting Poison Control Centers, the occurrence of adverse effects appears to be related to the route of exposure rather than age or gender of the patient or the concentration of N,N-diethyl-m-toluamide in the product.
Adolescent↗
Acute and subacute inhalation toxicity studies of a new broad spectrum insect repellent, N,N-diethylphenylacetamide.
N,N-Diethylphenylacetamide (DEPA) is an inexpensive, long-acting and broad spectrum insect repellent. The acute LC50 for a 4-h exposure of DEPA aerosol was found to be 1.451 mg l-1 (1.290-1.633) in male and 1.375 mg l-1 (1.307-1.447) in female rats. DEPA did not cause delayed deaths. Acute exposure to 0.9 LC50 revealed that liver might be a target organ for DEPA toxicity. On subacute exposures to 0.2, 0.6 and 0.8 LC50 for 6 h per day, 5 days a week for 2 weeks, there was no significant change in the 0.2 LC50 group, as evaluated by the body weight gain and organ body weight ratio. The minimal changes observed in the 0.6 LC50 group were of reversible type as the animals recovered on cessation of exposure. A massive concentration of 0.8 LC50 produced lethal effects. The study shows that DEPA has a low mammalian toxicity by inhalation as was found earlier with cutaneous application of the insect repellent.
Acetamides↗
Compatibility of army face paint and insect repellent formulation.
The compatibility studies of a new controlled-release repellent formulation (NSN 6840-01-284-3982, insect repellent personal application) and a new camouflage face paint (NSN 6850-01-262-0635) indicated that the repellent did not interfere with the use of face paints when repellent was applied first, and the face paints did not reduce the effectiveness of the repellent against mosquitoes.
Aedes↗
Dermal penetration of three topical insect repellents in dogs and rabbits.
Three (14)C-labeled candidate insect repellents, cyclohexamethylene carbamide, n-butylsufonimidocyclohexamethylene and 2-hydroxyethylcyclohexane carboxylate were evaluated for skin penetration in dogs and rabbits. Absorption of the repellents was determined by monitoring excreted urine daily for seven days following topical application. Significant percutaneous absorption of all three repellents occurred within 24 hours. (14)C-cyclohexamethylene carbamide showed the greatest absorption. Measurable amounts of radioactivity persisted at the application site for both species after seven days.
Administration, Topical↗
In vivo experimental model to evaluate the insect repellent N-N, diethylphenylacetamide in Periplaneta americana Linn.
The responsiveness of insect antennae to bornyl acetate (BA), a sex pheromone mimic and N,N-diethyl phenylacetamide (DEPA), a multi-insect repellent has been studied. Electrical activity from the antennal lobe was quantified to observe the alterations in power and frequency spectrum in P. americana Linn. following exposure to these chemicals. Two distinct patterns of responses were exhibited on exposure to BA and DEPA, the former producing a marked excitation and the latter inhibition of electrical discharge during the exposure to these compounds at a concentration of 200 micrograms.
Acetamides↗
Study on dermal toxicity and urinary metabolites of the new insect repellent N,N-diethylphenylacetamide in rabbits.
Dermal toxicity of the new multi-insect repellent N,N-diethylphenylacetamide (DEPA) was studied in female rabbits. LD50 of DEPA was estimated to be 3505 mg/kg b.w. On daily topical application for 21 d at a dose of 50 mg/kg b.w., dermal irritancy score and blood chemistry changes indicated that the compound is non-irritant and non-toxic. N-Ethylphenylacetamide and conjugated phenylacetic acid were identified as the urinary metabolites of DEPA by gas-liquid chromatography.
Acetamides↗
The conduct of a two-generation reproductive toxicity study via dermal exposure in the Sprague-Dawley rat--a case study with KBR 3023 (a prospective insect repellent).
KBR 3023, 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine, a prospective insect repellent being developed by the Bayer Corporation, was evaluated for reproductive toxicity in the Sprague-Dawley rat. As the intended human use of the test compound is topical, the test system was also exposed to the compound via the dermal route. Specifically, the adult rats (P generation) were fitted with Elizabethan collars, to reduce the likelihood of oral ingestion, and dermally administered either 0, 50, 100, or 200 mg KBR 3023/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Clinical signs and changes in body weight and food consumption were assessed throughout the study. All adults and neonates underwent a gross necropsy examination. Tissues retained for microscopic examination from all adult animals included the kidney, liver, pituitary, reproductive organs, and samples of skin from the shaved dose site. In addition to the parameters noted above, the animals were evaluated for the effect of the test compound on estrous cycling, mating, fertility, gestation length, litter size, pup sex ratio, and pup viability. There were no test compound-related clinical signs or effects on body weight or food consumption observed in either the adults or the pups during any phase of the study. There were no compound-related effects on any reproductive or litter parameters. Dermal findings at the dose site (acanthosis and hyperkeratosis) were noted in both generations. Other than the dermal findings, no compound-related necropsy findings were seen in either the adults or the pups. No compound-related histopathologic findings were noted in the reproductive tissues of either the males or females. Based on these results, KBR 3023, administered as described in this study at dose levels as high as 200 mg/kg body weight (the physical limit of dermal application for this compound), did not demonstrate any reproductive toxicity.
Administration, Topical↗