N,N,Diethyltoluamide (DEET) is a chemical compound derived from toluic acid. It was given the acronym DEET in 1957 by the Committee on Insecticide Terminology of the Entomological Society of America for brevity.

It appears as an oily yellowish liquid, stable, hydrolyses slowly in water. Incompatible with strong oxidising agents, strong acids, strong bases. Flammable.

What it is used for and where

Insect repellent. There are currently more than 100 products worldwide that contain a concentration of between 4% and 100% DEET. The EU Biocides Directive 528/2012, considers repellents to be biocidal products.

Medical

The most commonly used insect and tick repellents on the market are DEET (N,N,Diethyltoluamide), IR3535 (Ethyl Butylacetylaminopropionate) a derivative of β-alanine and Icaridin (Picaridin). IR3535 has a lower level of toxicity and is as effective as DEET. Icaridin has the same efficacy as DEET, but has a lower level of toxicity and a longer duration of protection. A natural product, clove essential oil has shown good repellency, but requires relatively high dosages to cause high effects.

Diethyltoluamide was developed by the US Army as a repellent for the mosquito vector of yellow fever (Aedes aegypti), malaria (Anopheles gambiae), dengue (Aedes aegypti) and chikungunya (Aedes aegypti, Aedes albopictus), in 1946 and placed on the market in 1957. It was re-registered in 1998 with the US EPA (Health and Environmental Protection Agency set up by President Richard Nixon in 1970 and very strict about product registration requirements). In 1999, insect olfactory receptors were identified and research into the molecular targets of DEET began (1). Insects use odour receptors, ionotropic receptors and gustatory receptors to smell the target. Some gustatory receptors detect carbon dioxide emitted by the body via the respiratory system, others are attracted to a broad spectrum of odourants. However, it is believed that there are many different sensory signals from humans that guide female mosquitoes as they feed on blood, an essential protein source for egg development.

Many scientific studies have used the mosquitoes Culex quinquefasciatus and Drosophila (also known as fruit flies) to understand the mechanism by which DEET disturbs the receptors of these insects, a mechanism that is still not fully elucidated.

Advantages and disadvantages of DEET

DEET repels insects, it is non-toxic, but some precautions must be taken to ensure repellency:

• the concentration of DEET must be above 10%, but if it exceeds 50%, the improvement is insignificant.
• DEET formulations ≥35% are only useful for those working in tick-infested areas or for those exposed to many flies or mosquitoes for many hours.
• DEET should be re-smeared on the skin every 6-8 hours
• some mosquitoes have shown resistance to DEET
• DEET is not recommended for pregnant women and children up to 6 months of age

Alternatives to DEET

Nepeta cataria also called catnip, has shown some efficacy as a spatial repellent but less effective than DEET as a contact repellent (2).

VUAA1, a chemical compound that functions as a co-receptor ion channel agonist of the insect odour receptor (3).

Repellents of natural and plant origin such as Icaridin (picaridin;1-(1-Methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) and cinnamon oil have shown repellency almost equal to DEET, while margosa extract (Azadirachta indica (A.Juss., Sapindales: Meliaceae) has slightly lower efficacy (4). Other repellents: lemon eucalyptus oil, citronella oil, catnip oil and 2-undecanone, para-menthane-3,8-diol (distilled from Eucalyptus citriodora), geraniol.

Other uses

Used in pharmaceutical intermediates, anhydrides and salts. Compounds labelled with isotopes. 

Solvent for dissolving plastics, synthetic fabrics such as rayon, spandex and painted surfaces.

For more information:

Diethyltoluamide studies

Typical commercial product characteristics N,N-Diethyl-m-toluamide/DEET

Appearance	Colorless or light yellow transparent liquid
Boiling Point	297.5±0.0°C at 760 mmHg
Melting Point	-45ºC
Flash Point	141.7±13.3°C
Density	1.0±0.1 g/cm3
PSA	20.31000
Vapor Pressure	0.0±0.6 mmHg at 25°C
Refraction Index	1.517
LogP	1.96
Acidity	0.4ml (0.01NnaOH)/g       0.025mgNaOH/g
Specific Gravity	0.996-1.002
Water	≤0.5%
o-DEET	≤0.30%
p-DEET	≤0.40%
Diethyl amine,PPM	≤10
Diethyl benzamide	≤0.70%
Trimethyl biphenyls	≤1%
N-Ethyl toluamide	≤1.0%
Safety

Price

250 mg          €45.50

• Molecular Formula     C₁₂H₁₇NO
• Molecular Weight    191.27
• Exact Mass     191.131012
• CAS  134-62-3
• UNII    FB0C1XZV4Y
• EC Number   205-149-7
• DSSTox Substance ID  DTXSID2021995
• IUPAC  N,N-diethyl-3-methylbenzamide
• InChI=1S/C12H17NO/c1-4-13(5-2)12(14)11-8-6-7-10(3)9-11/h6-9H,4-5H2,1-3H3 
• InChl Key      MMOXZBCLCQITDF-UHFFFAOYSA-N
• SMILES   CCN(CC)C(=O)C1=CC=CC(=C1)C
• MDL number    MFCD00009046
• PubChem Substance ID    329755385
• ChEBI  7071   
• NSC   759564     33840
• RTECS   XS3675000
• Beilstein        2046711

Synonyms

• DEET
• N,N-diethyl-3-methylbenzamide 
• N,N-diethyl-m-toluamide

References______________________________________________________________________

(1) Vosshall LB, Amrein H, Morozov PS, Rzhetsky A, Axel R. A spatial map of olfactory receptor expression in the Drosophila antenna. Cell. 1999 Mar 5;96(5):725-36. doi: 10.1016/s0092-8674(00)80582-6.

Abstract. Insects provide an attractive system for the study of olfactory sensory perception. We have identified a novel family of seven transmembrane domain proteins, encoded by 100 to 200 genes, that is likely to represent the family of Drosophila odorant receptors. Members of this gene family are expressed in topographically defined subpopulations of olfactory sensory neurons in either the antenna or the maxillary palp. Sensory neurons express different complements of receptor genes, such that individual neurons are functionally distinct. The isolation of candidate odorant receptor genes along with a genetic analysis of olfactory-driven behavior in insects may ultimately afford a system to understand the mechanistic link between odor recognition and behavior.

(2) Bernier UR, Furman KD, Kline DL, Allan SA, Barnard DR. Comparison of contact and spatial repellency of catnip oil and N,N-diethyl-3-methylbenzamide (deet) against mosquitoes. J Med Entomol. 2005 May;42(3):306-11. doi: 10.1603/0022-2585(2005)042[0306:cocasr]2.0.co;2.

Abstract. Nepetalactone, the primary component of catnip oil, was compared with the repellent N,N-diethyl-3-methylbenzamide (deet) for its ability to affect the host-seeking ability of Aedes aegypti (L.). A triple cage olfactometer was used to bioassay each substance and to assess its attraction inhibition (spatial repellent) attributes when combined with the following attractants: carbon dioxide, acetone, a blend of L-lactic acid and acetone, and human odors. Repellent tests were conducted with each substance against female Ae. aegypti, Anopheles albimanus Weidemann, and Anopheles quadrimaculatus Say. Catnip oil and deet were both weakly attractive to Ae. aegypti, catnip oil was the better spatial repellent, whereas deet was a more effective contact repellent in tests with all three species of mosquitoes.

(3) Rinker, D. C., Jones, P. L., Pitts, R. J., Rutzler, M., Camp, G., Sun, L., ... & Zwiebel, L. J. (2012). Novel high‐throughput screens of Anopheles gambiae odorant receptors reveal candidate behaviour‐modifying chemicals for mosquitoes. Physiological Entomology, 37(1), 33-41.

Abstract. Despite many decades of multilateral global efforts, a significant portion of the world population continues to be plagued with one or more mosquito-vectored diseases. These include malaria and filariasis as well as numerous arboviral-associated illnesses including Dengue and Yellow fevers. The dynamics of disease transmission by mosquitoes is complex, and involves both vector competence and vectorial capacity. One area of intensive effort is the study of chemosensory-driven behaviours in the malaria vector mosquito Anopheles gambiae Giles, the modulation of which are likely to provide opportunities for disease reduction. In this context recent studies have characterized a large divergent family of An. gambiae odorant receptors (AgORs) that play critical roles in olfactory signal transduction. This work has facilitated high-throughput, cell-based calcium mobilization screens of AgOR-expressing HEK cells that have identified a large number of conventional AgOR ligands, as well as the first non-conventional Orco (olfactory receptor co-receptor) family agonist. As such, ligand-mediated modulation serves as a proof-of-concept demonstration that AgORs represent viable targets for high-throughput screening and for the eventual development of behaviour-modifying olfactory compounds. Such attractants or repellents could foster malaria reduction programmes.

(4) Krüger A, Schmolz E, Vander Pan A. Methods for Testing Repellents Against Bed Bugs (Hemiptera: Cimicidae). J Econ Entomol. 2021 Feb 9;114(1):265-273. doi: 10.1093/jee/toaa304.