N,N-Diethyl-m-toluamide

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 . Topical absorption is the usual route of entry as DEET is normally applied to the skin as a mosquito repellent . DEET applied to the skin has also been shown to accumulate in the dermis . DEET is rapidly absorbed after oral ingestion . Additionally, animal experiments demonstrate that DEET can cross the placenta .
DEET is efficiently absorbed across the skin and by the gut . Blood concentrations of about 3 mg/L have been reported several hours after dermal application in the prescribed fashion .
Between 9% and 56% of dermally applied DEET is absorbed through the skin with peak blood levels being attained within 1 hour . Absorption through the skin varies according to the site exposed to the DEET . 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 . 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 .

Toxicity

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

Description

DEET was first developed and patented by the US Army in 1946. It was approved for general public use by the US Environmental Protection Agency (EPA) in 1957 and was reregistered in 1998. It has been estimated that more than 1.8 million kg (～4 million pounds) of DEET are used in the United States every year in more than 225 registered products. DEET is often sold and used in lotions or sprays with concentrations up to 100%. However, the Center for Disease Control recommends only 30–50% DEET to reduce the incidence of vector-borne disease transmission. Registered products must contain at least 95% of the meta-isomer, but small amounts of the more toxic ortho-isomer and the less toxic para-isomer are permitted.

Description

N,N-Diethyl-m-toluamide, known familiarly as DEET, has been the most widely used active ingredient in insect repellents since 1957. The compound was mentioned in the literature under the name “Autan” in connection with disinfection processes as early as 1907, but its first reported synthesis was in 1929 by N. N. Maxim in a Romanian journal.
Maxim’s article did not mention DEET’s use as an insect repellent; but in 1954, E. T. McCabe and colleagues at the US Department of Agriculture (Beltsville, MD) reported the preparation of 33 diethylamides of aromatic acids and concluded: “The most promising mosquito repellents of this series were derived from the ring-substituted benzoic acids.”—including DEET. Samuel Gertler, one of McCabe’s coauthors, had developed the compound 10 years earlier for use by the US Army as a result of soldiers’ experiences in jungle combat during World War II.
DEET has been used effectively and, for the most part, safely for more than 60 years. But, as the hazard information table shows, it can cause some skin problems and has environmental concerns. Only rare cases of DEET toxicity or severe skin reactions have been reported.
As successful as DEET is , an improved product may be on its way to market. See this week’s Molecule of the Future below.
Originally the Molecule of the Week for September 22, 2008

The Uses of N,N-Diethyl-m-toluamide

Insect repellent

Background

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.

Indications

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 . Products containing DEET currently are available to the public in a variety of liquids, lotions, sprays, and impregnated materials like towelettes or roll-ons .

What are the applications of Application

Deet is an active ingredient in insect repellants

Pharmacokinetics

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 . At the amounts and doses recommended for use on human children and adults, noticeable absorption or systemic exposure is not expected . 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 .

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) . 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 . Most of the body load is metabolized by such hepatic P450 enzymes, with only 10%–14% recovered unchanged in the urine .