title: Assessment of methods used to determine the safety of the topical insect repellent N,N-diethyl-m-toluamide (DEET).
abstract: 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.
authors.affiliation: Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Vanessa.Chen-Hussey@lshtm.ac.uk.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Chen-Hussey
authors.forename: Ron
authors.initials: R
authors.lastname: Behrens
authors.forename: James G
authors.initials: JG
authors.lastname: Logan
mesh_terms: D000818:Animals; D003671:DEET / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004357:Drug Synergism; D006801:Humans; D007302:Insect Repellents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D007306:Insecticides / Q000009:adverse effects / Q000493:pharmacokinetics; D018675:Toxicity Tests
chemical_list: D007302:Insect Repellents; D007306:Insecticides; D003671:DEET