Denatonium

Denatonium, usually available as denatonium benzoate (under trade names such as Denatrol, BITTERANT-b, BITTER+PLUS, Bitrex or Aversion) and as denatonium saccharide (BITTERANT-s), is the most bitter chemical compound known, with bitterness thresholds of 0.05 ppm for the benzoate and 0.01 ppm for the saccharide.[2] It was discovered in 1958 during research on local anesthetics by MacFarlan Smith of Edinburgh, Scotland, and registered under the trademark Bitrex.[3]

Denatonium benzoate
Names
Preferred IUPAC name
N-Benzyl-2-(2,6-dimethylanilino)-N,N-diethyl-2-oxoethan-1-aminium benzoate
Other names
N-Benzyl-2-[(2,6-dimethylphenyl)amino]-N,N-diethyl-2-oxoethan-1-aminium benzoate
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.020.996
PubChem CID
UNII
Properties
Chemical formula
 C28H34N2O3
Molar mass 446.581
Appearance white crystalline
Melting point 163 to 170 °C (325 to 338 °F; 436 to 443 K)
Hazards
R-phrases (outdated) R22 R36 R37 R38
S-phrases (outdated) S26 S36[1]
NFPA 704 (fire diamond)
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilHealth code 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

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. Denatonium is used in denatured alcohol,[4] antifreeze, nail biting preventions, respirator mask fit-testing, animal repellents, liquid soaps, and shampoos. It is not known to pose any long-term health risks.[2]

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.[5]

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.[6][7]

Denatonium can act as a bronchodilator by activating bitter taste receptors in the airway smooth muscle.[8]

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.[2]

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 (such as nail polish remover), 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 (such as gas dusters) 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.[9] In December 2012, U.S. manufacturers voluntarily agreed to add denatonium benzoate to antifreeze sold nationwide.[10]

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). It has been used to safeguard rat poisons from human consumption,[11] as humans are able to detect denatonium at much lower concentrations than rodents.[12]

The video game company Nintendo applies a coating containing denatonium benzoate to the game cards for their Nintendo Switch gaming console to deter children from ingesting them due to their small size.[13]

See also
  • Amarogentin

References
  1. "Safety & Documentation". D5765 Aldrich: Denatonium benzoate ≥98%. Sigma-Aldrich Co. LLC. Retrieved 10 September 2014.
  2. Final Report Study of Aversive Agents (PDF). Consumer Product Safety Commission United States of America. 18 November 1992. Archived from the original (PDF) on 16 June 2011. Retrieved 15 November 2010.
  3. "Bitrex(R) — Branded Denatonium Benzoate". Macfarlan Smith. Retrieved 2010-05-09.
  4. "Ethanol Denaturants". The Online Distillery Network. 1993-11-22.
  5. Holvoet, Jean-Patrick. "Denatonium". Sentinalco. Retrieved 2 October 2015.
  6. Meyerhof, W.; Batram, C.; Kuhn, C.; Brockhoff, A.; Chudoba, E.; Bufe, B.; Appendino, G.; Behrens, M. (2009). "The Molecular Receptive Ranges of Human TAS2R Bitter Taste Receptors". Chemical Senses. 35 (2): 157–170. doi:10.1093/chemse/bjp092. PMID 20022913.
  7. "BitterDB - Denatonium benzoate". Hebrew University of Jerusalem. Retrieved 11 June 2013.
  8. Deshpande, D. A.; Wang, W. C. H.; McIlmoyle, E. L.; Robinett, K. S.; Schillinger, R. M.; An, S. S.; Sham, J. S. K.; Liggett, S. B. (2010). "Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction". Nature Medicine. 16 (11): 1299–1304. doi:10.1038/nm.2237. PMC 3066567. PMID 20972434.
  9. Mullins ME, Zane Horowitz B (June 2004). "Was it necessary to add Bitrex (denatonium benzoate) to automotive products?". Veterinary and human toxicology. 46 (3): 150–2. ISSN 0145-6296. PMID 15171494.
  10. "Antifreeze and Engine Coolant Being Bittered Nationwide". Consumer Specialty Products Association. 13 December 2012. Archived from the original on 28 December 2012. Retrieved 30 June 2016.
  11. "Rats - Rat Poison & Rat Bait Stations". Pestcontrolshop.co.uk. Archived from the original on 2011-01-06. Retrieved 2011-01-17.
  12. Frank ME, Bouverat BP, MacKinnon BI, Hettinger TP. The distinctiveness of ionic and nonionic bitter stimuli. Physiol Behav. 2004 Jan;80(4):421-31. doi:10.1016/j.physbeh.2003.09.009
  13. Kwame Opam (1 March 2017). "Yes, Nintendo Switch cartridges taste terrible". theverge.com.
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