[Remarks on insect repellents].
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Insect Repellents↗
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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↗
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↗
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↗
Some corrections to the record on insect repellents and attractants.
Fifteen apparent errors of observation, reporting, interpretation, or attribution occurring in the insect repellent and attractant literature were examined. Topics discussed are the boiling point effect, solvents and solutions, repellent-treated netting, terpineol and diphenyl oxide, lactic acid, the smell and feel of deet (diethylmethylbenzamide), effective half-life, protection time, protection time of deet for men and women, McGuire's formula, "plussing out", King's classification, exorbitant doses, extrapolated doses, and extreme observations. The decay constant (1.36 hr-1) and half-life (0.51 hr) of a mosquito-repellent bath oil (Skin-So-Soft) are reported for the first time.
Animals↗
Toxic encephalopathy in a child after brief exposure to insect repellents.
Seizures and acute behaviour change developed in an 8-year-old girl following exposure to Muskol and Off insect repellents. She recovered within 3 days with supportive treatment, including anticonvulsant medication. The assumed toxic agent was N,N-diethyltoluamide.
Acute Disease↗
Distribution and metabolism of insect repellant N,N-diethylphenylacetamide on oral exposure in rats.
Oral toxicity, distribution and metabolism of a new multi-insect repellant, N,N-diethylphenylacetamide (DEPA) was studied in rats. On administration of DEPA (851 mg/kg body wt.) labelled with 14C blood, liver, stomach and stomach contents had 2.65, 3.97, 12.07 and greater than 50.66% radioactivity, respectively, after 20 min. Gas chromatographic analysis showed presence of both DEPA and its metabolite N-ethylphenylacetamide (EPA) in blood, liver, kidneys and lungs while only DEPA was present in stomach and stomach contents. EPA, phenylacetamide and conjugated phenylacetic acid were excreted along with unmetabolized parent compound in urine of rats when a low oral dose of DEPA (70 mg/kg body wt.) was administered. Activities of erythrocyte cholinesterase and carbonic anhydrase did not change significantly upon acute oral exposure to DEPA.
Acetamides↗
Insect repellent N,N-diethylphenylacetamide: an update.
N,N-diethylphenylacetamide (DEPA) has repellent activity against hematophagous insects including mosquitoes, black flies, horse flies, muscoid flies, rat fleas, and ticks, as well as land leeches and cockroaches. The efficacy of DEPA is comparable to that of N,N-diethyl-3-methylbenzamide (DEET) in both laboratory and field tests. Toxicological studies indicate that DEPA is safe for human use. Different formulations as well as fabrics impregnated with DEPA are effective for personal protection from insect bites.
Acetamides↗
Toxicity and metabolism of a new insect repellent N,N-diethylphenylacetamide in mice, rats and guinea pigs on cutaneous application.
Cutaneous LD50 of N,N-diethylphenylacetamide (DEPA), a new multi insect repellent was 2200, 3200 and 7100 mg/kg body weight in female mice, rats and guinea pigs; and 1600 and 4000 mg/kg in male mice and rats indicating a high degree of safety on skin contact. Dermal application of DEPA to young growing rats for 21 days at a dose of 50 mg/kg did not exert any adverse effects while massive doses of 500 and 1000 mg/kg caused marked reduction of body weight gain and lowering of activities of serum alanine aminotransferase, aspartate aminotransferase and cholinesterase. Along with DEPA, N-ethylphenylacetamide, phenylacetamide and phenylacetic acid were detected in the urine of DEPA treated mice, rats and guinea pigs.
Acetamides↗
N,N-diethylphenylacetamide, an insect repellent: absence of mutagenic response in the in vitro Ames test and in vivo mouse micronucleus test.
N,N-diethylphenylacetamide (DEPA), a promising new insect repellent, was tested for mutagenicity in the in vitro Ames Salmonella/microsome mutagenicity test and the in vivo mouse micronucleus test. For the Ames test, DEPA was assayed both in the presence and absence of Aroclor 1254-induced rat-liver S-9 mix (5 and 20% S-9 fraction), using five tester strains of Salmonella typhimurium--TA97a, TA98, TA100, TA102 and TA104. For the micronucleus test, mice were exposed to DEPA through ip injection for 2 and 5 days in separate experiments, and bone marrow and peripheral blood were sampled 6 and 48 hr after the final injection, respectively. DEPA did not induce a mutagenic response in the Ames test, and mouse bone marrow and peripheral blood micronucleus tests. DEPA was not considered cytotoxic, as a depression of the percentage PCE was not observed at any dose in the range of 1 to 100 mg/kg body weight with either treatment protocol of the micronucleus test.
Acetamides↗
Some cardiovascular effects of the insect repellent N,N-diethyl-m-toluamide (DEET).
Initial toxicological safety evaluations of the insect repellent N,N-diethyl-m-toluamide (DEET) indicated a potential hypotensive effect. The current study was initiated in order to pursue this aspect of DEET toxicity and to elucidate potential mechanisms for this response. Sublethal intraperitoneal injections of DEET in anesthetized rats were found to decrease mean blood pressure and heart rate in a dose-related fashion. Doses ranged from 56 to 225 mg/kg. Dogs treated with 225 mg/kg of DEET exhibited a similar hypotension and bradycardia. Cardiac output was also significantly reduced but stroke volume and total peripheral resistance were not altered. Lead II ECG changes included small increases in P-R and Q-T intervals. In a series of pharmacological studies in rats, DEET was found to decrease the hypotension and bradycardia associated with acetylcholine injection; epinephrine, norepinephrine, and histamine responses were not altered. Atropine pretreatment reduced but did not eliminate the hypotensive effects of DEET.
Acetylcholine↗
Carbon dioxide released from human skin: effect of temperature and insect repellents.
Measurement with an infrared analyzer of CO2 given off by the hands of human volunteers under laboratory conditions showed that they continuously produced CO2 at the rate of 1.0-1.8 ml/h. Increased production of CO2 was observed with increase in temperature for all subjects. Treatment of subjects with three insect repellents or ethanol resulted in a short-term drop in CO2 production, after which it returned to pretreatment levels. Olfactometer studies showed no correlation between the amount of CO2 produced by hands and the attractancy of the subjects to host-seeking female Ae. aegypti (L.). The supplemental addition of five times the amount of CO2 given off by the hands did not affect attractancy of subjects to mosquitoes. The amount of CO2 released by hands is negligible compared to ambient levels of 300 ppm, and it is unlikely to be attractive at this level of release by itself.
Animals↗
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↗
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↗