Denatonium, usually available as denatonium benzoate (under

trade name A trade name, trading name, or business name, is a pseudonym used by companies that do not operate under their registered company name. The term for this type of alternative name is a "fictitious" business name. Registering the fictitious name ...

s such as Denatrol, BITTERANT-b, BITTER+PLUS, ''Bitrex'', and ''Aversion'') and as denatonium saccharide (BITTERANT-s), is the most

bitter Bitter may refer to: Common uses * Resentment, negative emotion or attitude, similar to being jaded, cynical or otherwise negatively affected by experience * Bitter (taste), one of the five basic tastes Books * ''Bitter (novel)'', a 2022 novel ...

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one ele ...

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 anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...

s by MacFarlan Smith of

Edinburgh Edinburgh ( ; gd, Dùn Èideann ) is the capital city of Scotland and one of its 32 Council areas of Scotland, council areas. Historically part of the county of Midlothian (interchangeably Edinburghshire before 1921), it is located in Lothian ...

, 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 ( bitterants) to prevent inappropriate

ingestion Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in a substance through the mouth into the gastrointestinal tract, such as through eating or drinking. In single-celled organisms ingest ...

. Denatonium is used in

denatured alcohol Denatured alcohol (also called methylated spirits in Australia, Canada, Ireland, New Zealand, South Africa, and the United Kingdom; wood spirit; and denatured rectified spirit) is ethanol that has additives to make it poisonous, bad-tasting, foul ...

antifreeze An antifreeze is an additive which lowers the freezing point of a water-based liquid. An antifreeze mixture is used to achieve freezing-point depression for cold environments. Common antifreezes also increase the boiling point of the liquid, al ...

, preventive nail biting preparations,

respirator A respirator is a device designed to protect the wearer from inhaling hazardous atmospheres including fumes, vapours, gases and particulate matter such as dusts and airborne pathogens such as viruses. There are two main categories of resp ...

mask fit-testing, animal repellents,

liquid soaps A liquid is a nearly Compressibility, incompressible fluid that conforms to the shape of its container but retains a (nearly) constant volume independent of pressure. As such, it is one of State of matter#Four fundamental states, the four fund ...

shampoo Shampoo () is a hair care product, typically in the form of a viscous liquid, that is used for cleaning hair. Less commonly, shampoo is available in solid bar format. Shampoo is used by applying it to wet hair, massaging the product into th ...

s, and Nintendo Switch game cards to prevent accidental swallowing or choking by children. It is not known to pose any long-term health risks. The name ''denatonium'' reflects the substance's primary use as a denaturant and its chemical nature as a

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

, hence the

New Latin New Latin (also called Neo-Latin or Modern Latin) is the revival of Literary Latin used in original, scholarly, and scientific works since about 1500. Modern scholarly and technical nomenclature, such as in zoological and botanical taxonomy ...

suffix ''-onium''.

Structure, synthesis and physical properties

Denatonium is a

quaternary ammonium cation In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium cat ...

. It is a compound of a

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quanti ...

with an

inert Inert may refer to: * Chemically inert, not chemically reactive ** Inert gas ** Noble gas, historically called inert gas * Inert knowledge, information which one can express but not use * Inert waste, waste which is neither chemically nor biol ...

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

benzoate Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoi ...

or saccharinate. It can be obtained by the quaternization of lidocaine, a popular anesthetic, with benzyl halides. It was synthesized for the first time in 1963 by reacting benzyl chloride with lidocaine. This reaction required heating the substrates to for 35 hours. Now, reaction time can be reduced to two hours at by using acetonitrile as solvent and potassium iodide as catalyst. In order to obtain other salts, like the benzoate, the formed denatonium chloride is subjected to an anion exchange reaction with sodium benzoate in ethanol or to sodium hydroxide, and the resulting denatonium hydroxide is neutralized with benzoic acid. Other similar compounds are

procaine Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity o ...

and

benzocaine Benzocaine, sold under the brand name Orajel amongst others, is an ester local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as produ ...

. One of the chemical names for the compound is ''

lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, li ...

'' benzylbenzoate, although denatonium only denotes the

species itself, and does not necessitate the benzoate

counterion 160px, cation-exchange_resin.html" ;"title="Polystyrene sulfonate, a cation-exchange resin">Polystyrene sulfonate, a cation-exchange resin, is typically supplied with as the counterion. In chemistry, a counterion (sometimes written as "counter ...

Biochemistry

Denatonium in humans is recognized by eight distinct bitter taste receptors:

TAS2R4 Taste receptor type 2 member 4 is a protein that in humans is encoded by the ''TAS2R4'' gene. Function This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that ...

, TAS2R8, TAS2R10,

TAS2R39 Taste receptor type 2 member 39 is a protein that in humans is encoded by the ''TAS2R39'' gene. See also * Taste receptor A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other s ...

TAS2R43 Taste receptor type 2 member 43 is a protein that in humans is encoded by the ''TAS2R43'' gene. See also * Taste receptor A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other ...

, TAS2R16, TAS2R46, and TAS2R47, being by far the most sensitive to the compound. Denatonium can act as a

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the l ...

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 An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The c ...

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 placebos used in clinical trials to mimic the bitter taste of certain medications. Denatonium also discourages consumption of poisonous

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

s such as methanol and additives such as

ethylene glycol Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...

. It is also added to many kinds of harmful liquids including

solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

s (such as

nail polish remover Nail polish (also known as nail varnish or nail enamel) is a lacquer that can be applied to the human fingernail or toenails to decorate and protect the nail plates. The formula has been revised repeatedly to enhance its decorative properties ...

paint Paint is any pigmented liquid, liquefiable, or solid mastic composition that, after application to a substrate in a thin layer, converts to a solid film. It is most commonly used to protect, color, or provide texture. Paint can be made in many ...

varnish Varnish is a clear transparent hard protective coating or film. It is not a stain. It usually has a yellowish shade from the manufacturing process and materials used, but it may also be pigmented as desired, and is sold commercially in vario ...

es, 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 (such as gas dusters) to discourage inhalant abuse of the volatile vapors. In 1995, the U.S. state of

Oregon Oregon () is a state in the Pacific Northwest region of the Western United States. The Columbia River delineates much of Oregon's northern boundary with Washington, while the Snake River delineates much of its eastern boundary with Idah ...

required that denatonium benzoate be added to products containing sweet-tasting ethylene glycol and methanol such as

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 (especially for such large mammals as

deer Deer or true deer are hoofed ruminant mammals forming the family Cervidae. The two main groups of deer are the Cervinae, including the muntjac, the elk (wapiti), the red deer, and the fallow deer; and the Capreolinae, including the ...

). It has been used to safeguard

rat poison Rodenticides are chemicals made and sold for the purpose of killing rodents. While commonly referred to as "rat poison", rodenticides are also used to kill mice, squirrels, woodchucks, chipmunks, porcupines, nutria, beavers, and voles. Despite ...

s from human consumption, as humans are able to detect denatonium at much lower concentrations than rodents.Frank ME, Bouverat BP, MacKinnon BI, Hettinger TP. The distinctiveness of ionic and nonionic bitter stimuli. ''Physiol Behav''. 2004 Jan;80(4):421-31.

Nintendo Switch The is a hybrid video game console developed by Nintendo and released worldwide in most regions on March 3, 2017. The console itself is a tablet that can either be docked for use as a home console or used as a portable device, making it a ...

game cards are coated in denatonium benzoate to prevent young children from consuming them.

References

{{reflist Benzoates Benzyl compounds Quaternary ammonium compounds Bitter compounds Safety *