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Review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET).

A review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET) is presented. Workers using repellent containing this compound may be exposed to greater than 442 g in 6 mo. In human studies, variable penetration into the skin of from 9 to 56% of a topically applied dose and absorption into the circulatory system of approximately 17% have been reported. Excretion of DEET by humans was initially rapid but not as complete as in animal models. Only about one-half of the absorbed DEET was excreted by humans over 5 d. Depot storage of DEET in the skin was also documented. Skin irritant effects, including scarring bullous dermatitis in humans, were reported. One animal study that reported embryotoxicity could not be confirmed by other investigators. The limited testing for mutagenicity and carcinogenicity provided negative results. Neurotoxic effects were observed in workers exposed to 4 g or more per week. Six young girls developed encephalopathies after exposure to unspecified amounts of DEET ranging from small to massive doses. Three of these girls later died. The cause of their death has not been resolved. Because of the lack of information, further research into the absorption, carcinogenicity, and neurotoxic effects is needed.

Absorption↗

Severe toxic reactions and death following the ingestion of diethyltoluamide-containing insect repellents.

N,N-diethyl-m-toluamide (DEET) is the most commonly used mosquito repellent. This report describes five cases of toxic reactions after ingestion of insect repellents containing DEET. Each patient ingested large amounts of concentrated (47.5% to 95%) products. Their common symptoms and signs were coma, seizures, and hypotension occurring within one hour of ingestion. Two patients died; three survivors had no sequelae. The two patients who died had serum DEET levels of 0.88 mmol/L (16.8 mg/dL) and 1.25 mmol/L (24 mg/dL). It is concluded that the ingestion of DEET can produce severe toxic reactions of rapid onset that may be fatal in some instances.

Adolescent↗

An appropriate method for extracting the insect repellent citronellol from an indigenous plant (Pelargonium graveolens L'Her) for potential use by resource-limited animal owners.

Veterinary needs appraisals in rural, peri-urban and urban areas have indicated a need for affordable and accessible veterinary health care. It was also found that farmers and animal owners used indigenous plants for treating animals. In Africa, insects such as Culex, Culicoides and Stomoxys may transmit diseases, cause irritation to animals or prevent wound healing. Insect repellents used topically are generally safer and cheaper than insecticides. Using readily available commercial sources of ethanol 43% v/v (brandy and cane spirits), it was shown that citronellol could be extracted from uncrushed leaves of the indigenous shrub Pelargonium graveolens L'Hér. Efficacy of extraction was compared to that using reagent grade absolute ethanol. The peak concentration of citronellol was achieved within 7 days of extraction and thereafter remained constant for 4 months. Extraction methods using tap water and cooking oil were not successful. The extraction was also less successful when the leaves were crushed or macerated before being placed into ethanol. Gas chromatography was used to monitor the concentration of citronellol in the different extracts.

Acyclic Monoterpenes↗

Insect repellents, phenoxyherbicide exposure, and non-Hodgkin's lymphoma.

OBJECTIVE: We sought to test a hypothetical explanation of contradictory results in studies of phenoxyherbicides and NHL, that the exposure of rubber gloves recommended for use by farmers when mixing or applying pesticides simultaneously to 2,4-D (2,4-dichlorophenoxyacetic acid), DEET (N,N-diethyl-m-toluamide), and ultraviolet rays increased their permeability to 2,4-D. METHODS: We conducted a case (NHL n = 513)/control (n = 1506) study among men using age; province of residence; exposure to insect repellents containing DEET, phenoxy-herbicides, or dicamba; and gloves when handling pesticides. RESULTS: Using conditional logistic regression, the stratum with reported exposure to mecoprop, to DEET and the use of rubber gloves had higher odds ratios (3.86; 95% confidence interval = 1.57-9.49) compared with strata with other combinations. CONCLUSIONS: In conclusion, the etiologic complexity of NHL was demonstrated.

2,4-Dichlorophenoxyacetic Acid↗

Novel semi-automated methodology for developing highly predictive QSAR models: application for development of QSAR models for insect repellent amides.

Conventional 3D-QSAR models are built using global minimum conformations or quantum-mechanics based geometry-optimized conformations as bioactive conformers. QSAR models developed using the global minima as bioactive conformers, employing the GFA, PLS and G/PLS methodologies, gave good non-validated r(2) (0.898, 0.868 and 0.922) and performed well on an internal validation test with leave-one-out correlation q(2) (LOO) (0.902, 0.726 and 0.924), leave-10%-out correlation q(2) (L10O) (0.874, 0.728 and 0.883) and leave-20%-out q(2) (L20O) (0.811, 0.716 and 0.907). However, they showed poor predictive ability on an external data set with best predictive r(2) (Pred-r(2)) of 0.349, 0.139 and 0.204 respectively. A novel methodology to mine bioactive conformers, from clusters of conformations with good 3D-spatial representation around pharmacophoric moiety, furnishes highly predictive 3D-QSAR models. The best QSAR model (model A) showed r(2) of 0.989, q(2) (LOO) of 0.989, q(2) (L10O) of 0.980, q(2) (L20O) of 0.963 and Pred-r(2) on eight test compounds of 0.845. The methodology is based on mimicking the multi-way Partial Least Squares (PLS) technique by performing several automated sequential PLS analyses. The poses/shapes of the mined bioactive conformers provide valuable insight into the mechanism of action of the insect repellents. All of the repetitive tasks were automated using Tcl-based Cerius2 scripts.

Algorithms↗

Insect repellants in urban settings.

Why kill bugs when you can just make them go away? Used primarily for biting-insect control, repellants may control household pests as well, once their potential is fully realized. Repellents may provide low-dose, specific and low-toxicity augmentations to conventional pesticides applied around the home and workplace.

Animals↗

Seizure following brief exposure to the insect repellent N,N-diethyl-m-toluamide.

A 5-year-old boy with a history of mild developmental delay experienced a major motor seizure at day camp after topical application that morning of the insect repellent Muskol and a later application of OFF [both contain N,N-Diethyl-m-toluamide (DEET)]. The patient continued convulsing in the emergency department and was treated with diazepam. Laboratory tests were unremarkable, as were lumbar puncture, computed tomography scan, and blood cultures. Skin decontamination was performed. DEET levels in the urine were 0.003 micrograms/mL. Although seizures and encephalopathic syndrome have been described with DEET in previous case reports involving topical exposure of pediatric patients, atypical aspects with regard to this case include that this patient was a male (most other case reports involve females), exposure was relatively brief compared with other reports, and the patient developed seizures without a prodrome described in previous reports. Avoidance of high-concentration DEET formulations in pediatric patients should be considered.

Administration, Topical↗

Efficacy of three insect repellents against the malaria vector Anopheles arabiensis.

Three commercial repellents marketed in South Africa: Bio-Skincare (BSC, oils of coconut, jojoba, rapeseed and vitamin E), Mosiguard towelletes with 0.574 g quwenling (p-menthane-3,8-diol, PMD) and the standard deet (15% diethyl-3-methylbenzamide, Tabard lotion), were compared against a laboratory colony of the mosquito Anopheles arabiensis Patton (Diptera: Culicidae), the predominant malaria vector in South Africa. Human forearms were treated with 1.2 g BSC, 0.8 g PMD towelette or 0.5 g deet and exposed to 200 hungry An. arabiensis females for 1 min, at intervals of 1-6 h post-treatment. Tests were conducted by three adult male volunteers (aged 30-45 years, crossover controlled test design for 3 consecutive days), using their left arm for treatment and right arm for untreated control. Biting rates averaged 39-52 bites/min on untreated arms. All three repellents provided complete protection against An. arabiensis for up to 3-4 h post-application; deet and PMD gave 90-100% protection up to 5-6h, but BSC declined to only 52% protection 6h post-treatment. These results are interpreted to show that all three repellent products give satisfactory levels of personal protection against An. arabiensis for 4-5 h, justifying further evaluation in the field.

Adult↗

Field evaluation of three plant-based insect repellents against malaria vectors in Vaca Diez Province, the Bolivian Amazon.

The efficacy of repellents against Anopheles darlingi, the main malaria vector in Bolivia, was evaluated. This mosquito has a peak in biting activity early in the evening. Three natural repellents (1 eucalyptus based, 1 neem based, and 1 containing several repellent essential oils) were tested in comparison with 15% deet in human landing catches in Bolivia. The eucalyptus-based repellent containing 30% p-menthane-diol applied at a dose similar to those used in practice gave 96.89% protection for 4 h. Deet gave 84.81% protection. The other 2 products did not provide significant protection from mosquito bites.

Animals↗

Insect repellents. What really works?

DEET remains one of the most effective repellents against a wide variety of insects. Although adverse reactions have been reported in the medical literature and magnified in the press, the compound is remarkably safe and has been used by hundreds of millions of people over the past 40 years. Permethrin is a better deterrent of ticks and, like DEET, is remarkably safe. Concomitant use of these two agents provides superior protection. Citronella and a bath oil, Avon Skin-So-Soft, also provide limited protection against some types of flying insects. The promise of new agents or protective strategies is on the horizon. Recently it was shown that retroviral vectors could be used to integrate and express foreign genes in the malaria mosquito, Anopheles gambiae. Conceivably, a genetically engineered mosquito that is resistant to malaria and other transmissible diseases may one day be developed, obviating some of the need for repellents. Almost certainly, future research will yield additional agents to further protect against mosquitoes.

DEET↗