Reye-like syndrome associated with use of insect repellent in a presumed heterozygote for ornithine carbamoyl transferase deficiency

Lietman, Paul S.; Heick, H. M. C.; Shipman, R.T.; Norman, Margaret G.; James, W. P. T.

doi:10.1016/s0022-3476(80)80209-5

Cited by 67 publications

(1 citation statement)

References 9 publications

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“…The first case involved a 3 and a half year old girl who developed seizures, and it was reported that for the two weeks prior to the illness DEET had been applied to her clothes, bedding and skin resulting in an estimated exposure of 0.14 ml per kg body weight per day [14]. One of the fatal cases involved a six year old girl [15] who had applied DEET ‘extensively’. However, in this case a history of similar episodes without DEET exposure led to the hypothesis that the girl may have had undiagnosed ornithine carbamyl transferase deficiency.…”

Section: Introductionmentioning

confidence: 99%

Assessment of methods used to determine the safety of the topical insect repellent N,N-diethyl-m-toluamide (DEET)

Chen-Hussey

Behrens

Logan

2014

Parasites & Vectors

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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.

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Section: Introductionmentioning

confidence: 99%

Assessment of methods used to determine the safety of the topical insect repellent N,N-diethyl-m-toluamide (DEET)

Chen-Hussey

Behrens

Logan

2014

Parasites & Vectors

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Severe Toxic Reactions and Death Following the Ingestion of Diethyltoluamide-Containing Insect Repellents

Tenenbein¹

1987

JAMA

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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.

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Acylated 1,3-Aminopropanols as Repellents against Bloodsucking Arthropods

et al. 1996

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Starting from a set of known repellent compounds, a general structural framework with high probability for repellent activity was developed by molecular modelling techniques. Synthesis, structure-biological activity relationships of acylated 1,3-aminopropanols on the yellow fever mosquito Aedes aegypti and the properties and activity of the new development candidate compound KBR 3023 on Ae. aegypti, the malaria mosquito Anopheles stephensi, the common house mosquito Culex quinquefasciatus and the stable fly Stomoxys calcitrans are described. The sensory effect of KBR 3023 and deet has been studied in behavioural and neurophysiological investigations on Ae. aegypti and the American cockroach Periplaneta americana.The compounds clearly reduce or even eliminate the approach behaviour towards attractants like host odours or sexual pheromones. Electrophysiological studies on the insects' olfactory receptor organs reveal that certain cell types, which are not involved in perception of the attractive odorants, respond to deet and/or KBR 3023. As soon as one of the compounds is presented together with an attractant, a new input is active in the brain, which adds to the input from other receptors activated by the attractant. This new overall pattern clearly differs from that elicited by the attractant, so that the insect is no longer able to detect the latter.The specificity and mode of action of KBR 3023 was investigated by experiments exploring second-messenger responses elicited in antenna1 preparations of male P. americana. KBR 3023 induced a rapid increase in the concentration of inositol triphosphate in a dose-dependent and tissue-specific manner; other second-messenger systems were not affected. These observations suggest that KBR 3023 may act via subsets of G-protein-coupled receptors in sensory neurones.

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Reye-like syndrome associated with use of insect repellent in a presumed heterozygote for ornithine carbamoyl transferase deficiency

Cited by 67 publications

References 9 publications

Assessment of methods used to determine the safety of the topical insect repellent N,N-diethyl-m-toluamide (DEET)

Assessment of methods used to determine the safety of the topical insect repellent N,N-diethyl-m-toluamide (DEET)

Severe Toxic Reactions and Death Following the Ingestion of Diethyltoluamide-Containing Insect Repellents

Acylated 1,3-Aminopropanols as Repellents against Bloodsucking Arthropods

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