Diethyltoluamide

Identification

Name
Diethyltoluamide
Accession Number
DB11282
Type
Small Molecule
Groups
Approved
Description

Diethyltoluamide (DEET) is the common active ingredient in many insect repellent products. It is widely used to repel biting pests such as mosquitoes and ticks. Every year, DEET formulations are used to protect populations from mosquito-borne illnesses like West Nile Virus, the Zika virus, malaria, and/or tick-borne illnesses like Lyme disease and Rocky Mountain spotted fever. And, despite concerns over excessive exposure to the chemical, appropriate usage of the chemical at the recommended dosages and routes of administration have generally proven to be safe - even when most DEET products are largely designed to be applied directly to human skin, where the exact mechanisms of actions in which DEET is capable of repelling insects and causing toxicity to humans is still not fully elucidated.

Structure
Thumb
Synonyms
  • 3-methyl-N,N-diethylbenzamide
  • DEET
  • diethyl toluamide
  • diéthyltoluamide
  • diethyltoluamidum
  • dietiltoluamida
  • N,N-diethyl-m-toluamide
External IDs
ENT-20218 / ENT-22542 / NSC-33840
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Croc Bloc Combinator SPF 15Diethyltoluamide (10 %) + Octinoxate (6.5 %) + Oxybenzone (2 %)LotionTopicalCroc Bloc Products Inc.1999-05-212002-07-11Canada
Sunsect Insect Repellent SunscreenDiethyltoluamide (20 g/100g) + Octinoxate (7.5 g/100g) + Octisalate (5 g/100g) + Oxybenzone (6 g/100g)LotionTopicalIguana Llc2015-06-01Not applicableUs
International/Other Brands
Autan / Detamide / Flypel / m-Delphene / Metadelphene / Muscol / Off! / Repel
Categories
UNII
FB0C1XZV4Y
CAS number
134-62-3
Weight
Average: 191.2695
Monoisotopic: 191.131014171
Chemical Formula
C12H17NO
InChI Key
MMOXZBCLCQITDF-UHFFFAOYSA-N
InChI
InChI=1S/C12H17NO/c1-4-13(5-2)12(14)11-8-6-7-10(3)9-11/h6-9H,4-5H2,1-3H3
IUPAC Name
N,N-diethyl-3-methylbenzamide
SMILES
CCN(CC)C(=O)C1=CC(C)=CC=C1

Pharmacology

Indication

Diethyltoluamide, or DEET, is an active ingredient that is predominantly indicated for as an insect repellant used to repel biting pests like mosquitoes and ticks [5]. Products containing DEET currently are available to the public in a variety of liquids, lotions, sprays, and impregnated materials like towelettes or roll-ons [5].

Associated Conditions
Pharmacodynamics

When used appropriately, diethyltoluamide (DEET) containing products are designed to be applied directly to people's skin as a means to elicit a repelling action to keep insects from targeting human skin [5]. At the amounts and doses recommended for use on human children and adults, noticeable absorption or systemic exposure is not expected [5, 6]. Owing to the proportional difference in size between humans and insects, however, the exposure of insects to the applied DEET (whether topically or via inhalation of DEET) is expected to be enough to interfere with the insects' sensory attraction to human skin [5, 6].

Mechanism of action

The exact mechanism(s) of action by which both (a) insects are repelled by diethyltoluamide (DEET), and (b) humans can be affected deleteriously by exposure to toxic amounts of DEET have not yet been formally elucidated [5, 6, 8].

Research is ongoing regarding the exact mechanism of action by which DEET is capable of repelling insects. However, the most longstanding mechanism proposes that the DEET chemical blocks the olfactory receptors of insects for the volatile 1-octen-3-ol compound that is an element in human sweat and breath [1]. As a consequence, this proposed mechanism suggests that the blockade of insects' senses for this 1-octen-3-ol blinds and prevents the triggering of their biting and/or feeding instinct on humans and other animals that produce that compound [1]. Nevertheless, this theory has not yet been fully elucidated.

Furthermore, recent studies have demonstrated that DEET binds to certain molecular targets like the Anopheles gambiae odorant binding protein 1 (AgamOBP1) with high shape complementarity [2] and the antennae-specific odorant receptor CquiOR136 of the southern house mosquito, Culex quinquefasciatus [9]. In southern house mosquitos with reduced CquiOR136 transcript levels, behavioral tests demonstrated that this phenotype showed demonstrably lower responses/repulsion to DEET [9]. Again, however, such findings require continued research and do not formally elucidate the mechanism of action by which DEET can repel insects.

And finally, the mechanism of toxicity in which DEET is capable of eliciting effects of neurotoxicity in humans who have been exposed to toxic levels of the agent is also poorly understood [6, 3]. A recent study proposes that DEET is capable of blocking Na+ and K+ channels in the rat animal model [3]. This ion channel blocking activity of DEET in neurons may subsequently contribute to the kind of neuro-sensory adverse effects like numbness experienced after inadvertent application to the lips or mouth of humans [3].

Absorption

Most diethyltoluamide (DEET) formulations employ the agent as a liquid to be applied onto human skin in an effort to repel mosquitoes from feeding on the skin. Topical application and absorption is consequently the most common route of absorption. When used appropriately, DEET formulations are generally not indicated for too many other routes of absorption or administration, like parenterally or orally.

DEET is absorbed quickly through intact skin; 48% of the applied dose is totally absorbed within 6 hours [6]. Topical absorption is the usual route of entry as DEET is normally applied to the skin as a mosquito repellent [6]. DEET applied to the skin has also been shown to accumulate in the dermis [6]. DEET is rapidly absorbed after oral ingestion [6]. Additionally, animal experiments demonstrate that DEET can cross the placenta [6].

DEET is efficiently absorbed across the skin and by the gut [10]. Blood concentrations of about 3 mg/L have been reported several hours after dermal application in the prescribed fashion [10].

Between 9% and 56% of dermally applied DEET is absorbed through the skin with peak blood levels being attained within 1 hour [6]. Absorption through the skin varies according to the site exposed to the DEET [6]. In animal model surfaces corresponding to the human palmar surface (an area that is typically heavily exposed during the application of liquid DEET), 68% of administered topical DEET was absorbed [6]. As a consequence, small children are at increased risk of excessive absorption of DEET applied to the skin because of their relatively higher surface to volume ratio compared to adults [6].

Volume of distribution

After dermal application, about 17% of the absorbed diethyltoluamide (DEET) dose enters the bloodstream [6]. DEET accumulates in the skin, contributing to local irritation and possibly even bullous dermatitis [6]. Accumulation within the body, however, has not been reported and experimentally there have been no cumulative effects of subtoxic doses of DEET; but various case reports of toxicity in man suggests that accumulation of the repellent could occur, and with deleterious effects [6].

Protein binding

Readily accessible data regarding the protein binding of diethyltoluamide (DEET) is not available.

Metabolism

Diethyltoluamide (DEET) is metabolized in humans by cytochrome P450 enzymes into the primary metabolites N,N-diethyl-m-hydroxymethylbenzamide (BALC) and Nethyl-m-toluamide (ET) [7]. Although several P450 isoenzymes have elicited activity in DEET metabolism, it appears that the CYP2B6 and CYP2C19 enzymes are the principal P450s responsible for the transformation of DEET to BALC and ET, respectively [7]. Most of the body load is metabolized by such hepatic P450 enzymes, with only 10%–14% recovered unchanged in the urine [4].

Route of elimination

Diethyltoluamide (DEET) is principally excreted via the kidneys, where the initial phase is initially rapid but not more than 50% of the absorbed dose is excreted during the first 5 days [6]. In a study with a human volunteer weighing 65.8 kg and having been treated with 15 g of 95% DEET, urinary levels of DEET and a metabolite were measurable 4 hours after the initial exposure and persisted 48 hours later [6]. Maximum urinary levels of DEET observed were 207 mg/L at 8 hours [6].

Half life

The elimination half-life of diethyltoluamide (DEET) is observed to be about 2.5 hours [4].

Clearance

Readily accessible data regarding the clearance of diethyltoluamide (DEET) is not available.

Toxicity

Ingestion of diethyltoluamide (DEET) in adults may lead to hypotension, seizures, and/or coma within as little as an hour [4]. Deaths have been associated with serum concentrations of 1 mmol/L [4]. Psychosis was described in an adult who had applied a product containing 70% DEET to the skin [4].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Ditzen M, Pellegrino M, Vosshall LB: Insect odorant receptors are molecular targets of the insect repellent DEET. Science. 2008 Mar 28;319(5871):1838-42. doi: 10.1126/science.1153121. Epub 2008 Mar 13. [PubMed:18339904]
  2. Tsitsanou KE, Thireou T, Drakou CE, Koussis K, Keramioti MV, Leonidas DD, Eliopoulos E, Iatrou K, Zographos SE: Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents. Cell Mol Life Sci. 2012 Jan;69(2):283-97. doi: 10.1007/s00018-011-0745-z. Epub 2011 Jun 14. [PubMed:21671117]
  3. Swale DR, Sun B, Tong F, Bloomquist JR: Neurotoxicity and mode of action of N, N-diethyl-meta-toluamide (DEET). PLoS One. 2014 Aug 7;9(8):e103713. doi: 10.1371/journal.pone.0103713. eCollection 2014. [PubMed:25101788]
  4. Koren G, Matsui D, Bailey B: DEET-based insect repellents: safety implications for children and pregnant and lactating women. CMAJ. 2003 Aug 5;169(3):209-12. [PubMed:12900480]
  5. United States Environmental Protection Agency: DEET Profile [Link]
  6. IPCS INCHEM: DEET Profile [Link]
  7. In Vitro Human Metabolism and Interactions of Repellent N,N-Diethyl-m-Toluamide [Link]
  8. National Pesticide Information Centre: DEET Technical Fact Sheet [Link]
  9. "Mosquito odorant receptor for DEET and methyl jasmonate." Proceedings of the National Academy of Sciences. [Link]
  10. NIH Toxnet: Diethyltoluamide Profile [Link]
External Links
KEGG Drug
D02379
KEGG Compound
C10935
ChemSpider
4133
ChEBI
7071
ChEMBL
CHEMBL1453317
HET
DE3
Wikipedia
DEET
ATC Codes
P03BX01 — Diethyltoluamide
PDB Entries
3n7h

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LotionTopical
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.68 mg/mLALOGPS
logP2.1ALOGPS
logP2.5ChemAxon
logS-2.1ALOGPS
pKa (Strongest Basic)-0.95ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area20.31 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity59.47 m3·mol-1ChemAxon
Polarizability22.16 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Mass Spectrum (Electron Ionization)MSsplash10-014l-4900000000-c13868bc7a5900810817
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-995982de47cfbcedff66
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014l-0900000000-49b97cb5b12bcd0757bb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-5c845107ddf24f631344
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-4e7d4be8f6085796f370
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-281ad1f50c96e62d93dc
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-6f014def377ae48a45e8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-3ec7134a184c674a70e2
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014l-0900000000-be3e4ba15c24f2ff7ae3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-1900000000-c118ef147fc9025ced44
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-3900000000-53c7c6316dce45b27287
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00kf-9800000000-2b501045198b5f22a55e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-3c12af86f43b00cea820
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-84ab99b187682ae43e94
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014l-0900000000-604acf0d90339752c932
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-1900000000-31f8aee182e7dcf3c1f3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-3900000000-6482109d03926fb851ea
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00kf-9800000000-03e78de19a2c02564209
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-c8cb356261079f7901ce
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00kf-0900000000-016ad5fd459430fed4da
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-3900000000-a4d39e5affdbed2f78fb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-9000000000-e8dff62fa5b19c34156d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-4a90a4f4e3dc17b85d26
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014l-5900000000-edcb7cd1a4cce35b37dd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-222df5ae0e8c01a39ffd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-49d22bd0be7bf40c6c93
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014l-9711100000-6efb069e880ace92d4cb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-0900000000-1791a943d7aa4656d861
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-0900000000-c6c359aa759070510456
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-9300000000-ec022d393b15c42c949c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-9300000000-b62698e906473f56b941
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-9100000000-f9c402802da1e83e8391
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-9100000000-635d2983114317ed6801
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as n,n-dialkyl-m-toluamides. These are aromatic that contain a m-toluamide, where the carboxamide group is N- substituted with two alkyl chains.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Toluenes
Direct Parent
N,N-dialkyl-m-toluamides
Alternative Parents
Benzamides / Benzoyl derivatives / Tertiary carboxylic acid amides / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
N,n-dialkyl-m-toluamide / Benzoic acid or derivatives / Benzamide / Benzoyl / Tertiary carboxylic acid amide / Carboxamide group / Carboxylic acid derivative / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid amide, benzamides (CHEBI:7071) / Insect repellents (C10935)

Drug created on December 03, 2015 09:52 / Updated on November 02, 2018 07:08