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.