Denatonium


Denatonium, usually available as denatonium benzoate and as denatonium saccharide, is the most bitter chemical compound known, with bitterness thresholds of 0.05 ppm for the benzoate and 0.01 ppm for the saccharide.
It was discovered in 1958 during research on local anesthetics by MacFarlan Smith of Edinburgh, Scotland, and registered under the trademark Bitrex.
Dilutions of as little as 10 ppm are unbearably bitter to most humans. Denatonium salts are usually colorless and odorless solids but are often traded as solutions. They are used as aversive agents to prevent inappropriate ingestion. Denatonium is used in denatured alcohol, antifreeze, preventive nail biting preparations, respirator mask fit-testing, animal repellents, liquid soaps, Nintendo Switch game cards, and shampoos. It is not known to pose any long-term health risks.
The name denatonium is a portmanteau word reflecting the substance's primary use as a denaturant and its chemical nature as a cation, whence the New Latin suffix -onium.

Structure and physical properties

Denatonium is a quaternary ammonium cation. It is a compound of a salt with an inert anion like benzoate or saccharide. The structure of denatonium is related to the local anesthetic lidocaine, differing only by the addition of a benzyl group to the amino nitrogen. Other similar compounds are procaine and benzocaine.
One of the chemical names for the compound is lidocaine benzylbenzoate, although denatonium only denotes the quaternary ammonium cation species itself, and does not necessitate the benzoate counterion.

Biochemistry

Denatonium in humans is recognized by eight distinct bitter taste receptors: TAS2R4, TAS2R8, TAS2R10, TAS2R39, TAS2R43, TAS2R16, TAS2R46, TAS2R47, with TAS2R47 being by far the most sensitive to the compound.
Denatonium can act as a bronchodilator by activating bitter taste receptors in the airway smooth muscle.

Applications

The bitterness of the compound guides most applications of denatonium. Denatonium benzoate is used to denature ethanol so that it is not treated as an alcoholic beverage with respect to taxation and sales restrictions. One designation in particular, SD-40B, indicates that ethanol has been denatured using denatonium benzoate.
Denatonium is commonly included in placebo medications used in clinical trials to match the bitter taste of certain medications.
Denatonium also discourages consumption of harmful alcohols like methanol, and additives like ethylene glycol. Denatonium is used in rubbing alcohol as an inactive ingredient. It is also added to many kinds of harmful liquids including solvents, paints, varnishes, toiletries and other personal care items, special nail polish for preventing nail biting, and various other household products. It is also added to less hazardous aerosol products to discourage inhalant abuse of the volatile vapors.
In 1995, the U.S. state of Oregon required that denatonium benzoate be added to products containing sweet-tasting ethylene glycol and methanol such as antifreeze and windshield washer fluid to prevent poisonings of children and animals. In December 2012, U.S. manufacturers voluntarily agreed to add denatonium benzoate to antifreeze sold nationwide.
Animals are known to have different sensitivities to the effects of denatonium. It is used in some animal repellents. It has been used to safeguard rat poisons from human consumption, as humans are able to detect denatonium at much lower concentrations than rodents.