Scientists Create Bug Spray that is Safer, Better than DEET

A blood-engorged female Aedes albopictus mosquito feeding on a human host. Credit: James Gathany/CDC

In the summer months, the fight against mosquitoes can feel like a losing battle. DEET has proven mostly effective at keeping the disease transmitters away, but the chemical also comes with its challenges. It has a distinct smell and feel when sprayed on the body and protection is short-lived. And while it has been tested and approved for children, some experts say not to use DEET with more than 30 percent concentration on the youngsters, and to only apply it once per day as irritation is a common side effect.

In recent years, Icaridin, or picaridin, has emerged as an alternative to DEET since it lasts longer and it doesn’t have an odor, but it’s not as strong/effective as DEET. Additionally, both DEET and Icaridin have to be reapplied after swimming or sweating.

Now, Italian researchers from the University of Firenze have designed safe alternatives that have advantages over both DEET, including a pleasant smell and a much longer protection timeframe.

In prior work, Francesca Dani and her colleagues used two plant-based natural repellents as starting materials, which offered only short-term protection from mosquitos. So, the researchers converted the terpenoids into cyclic acetals and hydroxyacetals, thereby extending their protective timespan beyond that of DEET.

Still, Dani and team sought to further improve these new products, including verifying toxicity and safety levels.

In the current work, published in ACS’ Journal of Agricultural and Food Chemistry, the research team synthesized additional cyclic hydroxyacetals from inexpensive, commercially available carbonyls. This time, they expanded their choice of chemicals to include other carbonyl compounds—including those that have never been reported as mosquito repellents.

According to the study results, all 11 of the hydroxyacetals tested had a protection time of at least 7 hours—5 hours longer than DEET—with some lasting up to 8 hours, comparable with Icaridin. Additionally, all but one repellent was stronger than Icaridin, with six showing the same or higher protection efficacy as DEET. In fact, two of the team’s tested repellants demonstrated protection efficacy twice that of DEET—16.7 ug/cm² compared with 8.3 ug/cm^2.

Overall, when testing was performed on human volunteers against Aedes albopictus, which have spread widely in the U.S. and carry diseases such as encephalitis, dengue and dog heartworm, seven compounds kept a repellence above 95% for at least 8 hours.

Since there was no biological data available for the class of acetals tested, Dani and team said they felt a preliminary evaluation of safety was necessary. Thus, they evaluated the toxicity of the most promising repellents in terms of cell toxicity, immunogenicity, and epithelial permeability. DEET and Icaridin were also included in the study as reference standards.

According to the study data, some of the best repellents showed little cell toxicity—all equal to or less than DEET and Icaridin. The team showed that two hydroxyacetals were also less likely to cause immune reactions or penetrate cell layers when compared with Icaridin.

“These compounds could provide effective nitrogen-free alternatives to the most powerful active repellents present on the market. These data might be useful in providing a wider base for a better understanding of the relationship between the structure and repellent activity,” conclude the researchers.