SYNONYMS

Denatonyumbenzoat; Denatoniumbenzoate; denatonyumbenzoate; denatoniumbenzoat; denatonium benzoat; denatonyum benzoat; Denatoniumbenzoate; denatonyumbenzoate; denatoniumbenzoat; denatonium benzoat; denatonyum benzoat; Denatoniumbenzoate; denatonyumbenzoate; denatoniumbenzoat; denatonium benzoat; denatonyum benzoat; DENATONYUM BENZOATE; DENATONIUM BENZOAT; DENATONIUM BENZOAT; DONATYUM BENZOAT; DENATONYUM; BITREX; BİTREKS; BİTREKS; DONATYUM; bitreks; bıtreks; Bitreks; DENATONYUM; DENATONIUM BENZOATE; DENATONİUM; BENZOATE DE DONATENIUM; denatonyum, denatonyum benzoat, denatonium benzoat, denatonium,benzoate, denature alkol, denatural, alkol acılaştırma, bitter, alcohol bittering, alkol acı,acı, alcohol denature etmek,; alkol acılaştırma, bitrex, denatonium saccharide, denatonyum sakkarit, denatonyum sakarit, sakarid, sakkarit, sakkarid,denatonyum sakkarid, denatonyum sakarid, ; Lidocaine benzyl benzoate; Benzyl diéthyl (2,6-xylyl carbométhyl) benzoate d'ammonium; Bitrex; Aversion; phenylmethyl-[2- [(2,6-dimethylphenyl)amino]- 2-oxoethyl]-diethylammonium benzoate; Lidocaine benzyl benzoate; Benzyl diéthyl (2,6-xylyl carbométhyl) benzoate d'ammonium; Bitrex; Aversion; Saccharinate de dénatonium; Chlorure de dénatonium; DENATONIUM BENZOATE; 3734-33-6; Bitrex; Lidocaine benzyl benzoate; Anispray; Aversion;; denatonyum; donatonyum; donatonıum; denatonıum; benzoate denatonıum; DENATONYUM BENZOATE; DENATONYUM BENZOATE; DENATONYUM BENZOAT; DENATONYUM BENZOATE BİTREX; BİTREKS DENTAONYUM; BİTREKS DENTANYUM; DENATONYUM BİTREKS; BİTREKS DENATONYUM; DENATONYUM BİTREKS; BİTREKS BENZOATE; DENATONIUM BENZOATE; BİTREKS; BITREX; denatonıum; donatonyum; denatonyum; donatonyum; denatonDenatonium (benzoate); Gori; THS-839; Caswell No. 083BB; UNII-M5BA6GAF1O; Denatonium benzoate anhydrous; WIN 16568; Denatonii benzoas [INN-Latin]; EINECS 223-095-2; Benzoate de denatonium [INN-French]; Benzoato de denatonio [INN-Spanish]; M5BA6GAF1O; Denatonium benzoate [USAN:INN:BAN]; EPA Pesticide Chemical Code 009106; NSC 157658; Denatonium benzoate granules; Benzyldiethyl((2,6-xylylcarbamoyl)methyl)ammonium benzoate; Benzyldiethyl[(2,6-xylylcarbamoyl)methyl]ammonium benzoate; NCGC00017043-02; AK161798; CAS-3734-33-6; N-Benzyl-2-((2,6-dimethylphenyl)amino)-N,N-diethyl-2-oxoethanaminium benzoate; Benzenemethanaminium, N-(2-((2,6-dimethylphenyl)amino)-2-oxoethyl)-N,N-diethyl-, benzoate; DSSTox_CID_14376; DSSTox_RID_79149; DSSTox_GSID_34376; W-106547; ((2,6-Xylylcarbamoyl)methyl)diethyl benzyl ammonium benzoate; C28H34N2O3; Ammonium, benzyldiethyl((2,6-xylylcarbamoyl)methyl)-, benzoate; Denatonii benzoas; N-(2-((2,6-Dimethylphenyl)amino)-2-oxoethyl)-N,N-diethylbenzeneme- thanaminium benzoate; Benzoato de denatonio; Benzoate de denatonium; 2-[diethylbenzylamino]-N-(2,6-dimethylphenyl)acetamide, benzoic acid;Bitreks; Benzenemethanaminium, N-(2-((2,6-dimethylphenyl)amino)-Bitreks; 2-oxoethyl)-N,N-diethyl-, benzoate (1:1); Benzenemethanaminium, N-[2-[(2,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate (1:1); SCHEMBL4951; MLS002154073; Denatonium benzoate, >=98%; CHEMBL1371493; Denatonium Benzoate 25% in EG; DTXSID8034376; benzyl-[2-(2,6-dimethylanilino)-2-oxoethyl]-diethylazanium;benzoate; Denatonium benzoate, analytical standard; Ammonium,6-xylylcarbamoyl)methyl]-, benzoate; BENZYLDIETHYL [(2,6-XYLYLCARBAMOYL)-AMMONIUM BENZO; Denatonium benzoate, certified reference material, TraceCERT(R); Benzyldiethyl[(2,6-dimethylphenylcarbamoyl)methyl]ammonium Benzoate; benzyl-[(2,6-dimethylphenyl)carbamoylmethyl]-diethyl-azanium benzoate; Benzyl-[(2,6-dimethylphenylcarbamoyl)methyl]-diethylammonium benzoate; Denatonium benzoate, United States Pharmacopeia (USP) Reference Standard; [2-(2,6-dimethylanilino)-2-oxoethyl]-diethyl-(phenylmethyl)ammonium benzoate; Benzenemethanaminium,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate; Benzenemethanaminium,N-[2-[(2,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate; N-benzyl-2-(2,6-dimethylphenylamino)-N,N-diethyl-2-oxoethanaminium benzoate; [2-[(2,6-dimethylphenyl)amino]-2-oxidanylidene-ethyl]-diethyl-(phenylmethyl)azanium benzoate; N-[2-[(2,6-Dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-benzenemethanaminium benzoate; N,N-Diethyl-N-[(2,6-dimethylphenylcarbamoyl)methyl]benzylammonium benzoate; Benzyldiethyl(2,6-xylylcarbamoylmethyl)ammonium; Denatonyumbenzoat; DENATONYUM BENZOATE; DENATONIUM BENZOAT; DENATONIUM BENZOAT; DONATYUM BENZOAT; DENATONYUM; BITREX; BİTREKS; BİTREKS; DONATYUM; bitreks; bıtreks; Bitreks; DENATONYUM; DENATONIUM BENZOATE; DENATONİUM; BENZOATE DE DONATENIUM; denatonyum, denatonyum benzoat, denatonium benzoat, denatonium,benzoate, denature alkol, denatural, alkol acılaştırma, bitter, alcohol bittering, alkol acı,acı, alcohol denature etmek,; alkol acılaştırma, bitrex, denatonium saccharide, denatonyum sakkarit, denatonyum sakarit, sakarid, sakkarit, sakkarid,denatonyum sakkarid, denatonyum sakarid, ; Lidocaine benzyl benzoate; Benzyl diéthyl (2,6-xylyl carbométhyl) benzoate d'ammonium; Bitrex; Aversion; phenylmethyl-[2- [(2,6-dimethylphenyl)amino]- 2-oxoethyl]-diethylammonium benzoate; Lidocaine benzyl benzoate; Benzyl diéthyl (2,6-xylyl carbométhyl) benzoate d'ammonium; Bitrex; Aversion; Saccharinate de dénatonium; Chlorure de dénatonium; DENATONIUM BENZOATE; 3734-33-6; Bitrex; Lidocaine benzyl benzoate; Anispray; Aversion;; denatonyum; donatonyum; donatonıum; denatonıum; benzoate denatonıum; DENATONYUM BENZOATE; DENATONYUM BENZOATE; DENATONYUM BENZOAT; DENATONYUM BENZOATE BİTREX; BİTREKS DENTAONYUM; BİTREKS DENTANYUM; DENATONYUM BİTREKS; BİTREKS DENATONYUM; DENATONYUM BİTREKS; BİTREKS BENZOATE; DENATONIUM BENZOATE; BİTREKS; BITREX; denatonıum; donatonyum; denatonyum; donatonyum; denatonDenatonium (benzoate); Gori; THS-839; Caswell No. 083BB; UNII-M5BA6GAF1O; Denatonium benzoate anhydrous; WIN 16568; Denatonii benzoas [INN-Latin]; EINECS 223-095-2; Benzoate de denatonium [INN-French]; Benzoato de denatonio [INN-Spanish]; M5BA6GAF1O; Denatonium benzoate [USAN:INN:BAN]; EPA Pesticide Chemical Code 009106; NSC 157658; Denatonium benzoate granules; Benzyldiethyl((2,6-xylylcarbamoyl)methyl)ammonium benzoate; Benzyldiethyl[(2,6-xylylcarbamoyl)methyl]ammonium benzoate; NCGC00017043-02; AK161798; CAS-3734-33-6; N-Benzyl-2-((2,6-dimethylphenyl)amino)-N,N-diethyl-2-oxoethanaminium benzoate; Benzenemethanaminium, N-(2-((2,6-dimethylphenyl)amino)-2-oxoethyl)-N,N-diethyl-, benzoate; DSSTox_CID_14376; DSSTox_RID_79149; DSSTox_GSID_34376; W-106547; ((2,6-Xylylcarbamoyl)methyl)diethyl benzyl ammonium benzoate; C28H34N2O3; Ammonium, benzyldiethyl((2,6-xylylcarbamoyl)methyl)-, benzoate; Denatonii benzoas; N-(2-((2,6-Dimethylphenyl)amino)-2-oxoethyl)-N,N-diethylbenzeneme- thanaminium benzoate; Benzoato de denatonio; Benzoate de denatonium; 2-[diethylbenzylamino]-N-(2,6-dimethylphenyl)acetamide, benzoic acid;Bitreks; Benzenemethanaminium, N-(2-((2,6-dimethylphenyl)amino)-Bitreks; 2-oxoethyl)-N,N-diethyl-, benzoate (1:1); Benzenemethanaminium, N-[2-[(2,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate (1:1); SCHEMBL4951; MLS002154073; Denatonium benzoate, >=98%; CHEMBL1371493; Denatonium Benzoate 25% in EG; DTXSID8034376; benzyl-[2-(2,6-dimethylanilino)-2-oxoethyl]-diethylazanium;benzoate; Denatonium benzoate, analytical standard; Ammonium,6-xylylcarbamoyl)methyl]-, benzoate; BENZYLDIETHYL [(2,6-XYLYLCARBAMOYL)-AMMONIUM BENZO; Denatonium benzoate, certified reference material, TraceCERT(R); Benzyldiethyl[(2,6-dimethylphenylcarbamoyl)methyl]ammonium Benzoate; benzyl-[(2,6-dimethylphenyl)carbamoylmethyl]-diethyl-azanium benzoate; Benzyl-[(2,6-dimethylphenylcarbamoyl)methyl]-diethylammonium benzoate; Denatonium benzoate, United States Pharmacopeia (USP) Reference Standard; [2-(2,6-dimethylanilino)-2-oxoethyl]-diethyl-(phenylmethyl)ammonium benzoate; Benzenemethanaminium,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate; Benzenemethanaminium,N-[2-[(2,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate; N-benzyl-2-(2,6-dimethylphenylamino)-N,N-diethyl-2-oxoethanaminium benzoate; [2-[(2,6-dimethylphenyl)amino]-2-oxidanylidene-ethyl]-diethyl-(phenylmethyl)azanium benzoate; N-[2-[(2,6-Dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-benzenemethanaminium benzoate; N,N-Diethyl-N-[(2,6-dimethylphenylcarbamoyl)methyl]benzylammonium benzoate; Benzyldiethyl(2,6-xylylcarbamoylmethyl)ammonium

Yenmesi uygun olmayan maddelerin yenmesini önlemek için kullanılan caydırıcı madde. ticari adı bitrekstir. 10 ppm kadar küçük seyreltmeleri bile çoğu insan için dayanılmaz ölçüde acıdır. denatonyum denatüre alkol, antifiriz, tırnak yeme önleyiciler, solunum maskeleri, hayvan kovucular, sıvı sabunlar ve şampuanlarda kullanılır.

Genellikle denatonyum benzoat (Denatrol, BITTERANT-b, BITTER + PLUS, Bitrex veya Aversion gibi ticari isimler altında) ve denatonyum sakarit (BITTERANT-s) ticari adları altında bulunan ve 0.05 acılık eşikleri ile bilinen en acı kimyasal bileşik olan denatonyum benzoat için ppm ve sakarit için 0.01 ppm. [2] 1958'de Edinburgh, İskoçya'dan MacFarlan Smith tarafından lokal anesteziklerle ilgili araştırmalar sırasında keşfedildi ve Bitrex ticari markası altında tescil edildi. [3]

10 ppm kadar az dilüsyonlar çoğu insan için dayanılmaz derecede acıdır. Denatonium tuzları genellikle renksiz ve kokusuz katılardır, ancak genellikle çözelti olarak işlem görürler. Uygun olmayan yutmayı önlemek için önleyici ajanlar (bitterantlar) olarak kullanılırlar. Denatonium denatüre alkol, [4] antifriz, tırnak ısırma önleme, solunum maskesi uygunluk testi, hayvan kovucular, sıvı sabunlar ve şampuanlarda kullanılır. Uzun süreli sağlık riski oluşturduğu bilinmemektedir. [2]

Denatonium adı, maddenin bir denaturant olarak birincil kullanımını ve katyon olarak kimyasal doğasını, dolayısıyla Yeni Latin son eki -onium'u yansıtan portmanteau bir kelimedir.

Yapı ve fiziksel özellikler

Denatonium bir kuaterner amonyum katyondur. Benzoat veya sakarit gibi inert bir anyonu olan bir tuz bileşiğidir. Denatonyumun yapısı, sadece amino nitrojene bir benzil grubunun ilave edilmesiyle farklılık gösteren lokal anestetik lidokain ile ilgilidir. Diğer benzer bileşikler prokain ve benzokaindir. [5]

Bileşik için kimyasal isimlerden biri lidokain benzilbenzoattır, ancak denatonyum sadece kuaterner amonyum katyon türlerini belirtir ve benzoat karşıtlığını gerektirmez.

biokimya DENATONYUM BENZOATE

İnsanlarda denatonyum sekiz farklı acı tat reseptörü tarafından tanınır: TAS2R4, TAS2R8, TAS2R10, TAS2R39, TAS2R43, TAS2R16, TAS2R46, TAS2R47, TAS2R47 bileşiğe göre en hassas olanıdır. [6] [7]

Denatonium, hava yolu düz kasındaki acı tat reseptörlerini aktive ederek bronkodilatör görevi görebilir. [8]

Uygulamalar

Bileşiğin acısı, denatonyumun birçok uygulamasını yönlendirir. Denatonium benzoat, etanolü denatüre etmek için kullanılır, böylece vergilendirme ve satış kısıtlamaları bakımından alkollü bir içecek olarak muamele görmez. Özellikle bir isim olan SD-40B, etanolün denatonyum benzoat kullanılarak denatüre edildiğini gösterir.

Denatonium, bazı ilaçların acı tadını eşleştirmek için klinik çalışmalarda kullanılan plasebo ilaçlarına yaygın olarak dahil edilir. [2]

Denatonium ayrıca metanol gibi zararlı alkollerin ve etilen glikol gibi katkı maddelerinin tüketimini de önler. Denatonium, aktif olmayan bir madde olarak alkolün ovulmasında kullanılır. Solventler (oje çıkarıcı gibi), boyalar, vernikler, banyo malzemeleri ve diğer kişisel bakım ürünleri, tırnak ısırmasını önlemek için özel oje ve diğer çeşitli ev ürünleri de dahil olmak üzere birçok zararlı sıvıya eklenir. Ayrıca, uçucu buharların uçucu madde kötüye kullanımını engellemek için daha az tehlikeli aerosol ürünlerine (gaz tozları gibi) eklenir.

1995 yılında ABD'nin Oregon eyaletinde, çocukların ve hayvanların zehirlenmesini önlemek için tatlı tadımlı etilen glikol ve antifriz ve ön cam yıkayıcı sıvısı gibi metanol içeren ürünlere denatonium benzoat ilave edilmesi gerekiyordu. [9] Aralık 2012'de ABD üreticileri gönüllü olarak ülke çapında satılan antifrizlere denatonyum benzoat eklemeyi kabul ettiler. [10]

Hayvanların denatonyumun etkilerine karşı farklı hassasiyetleri olduğu bilinmektedir. Bazı hayvan kovucularda (özellikle geyik gibi büyük memelilerde) kullanılır. Sıçan zehirlerini insan tüketiminden korumak için kullanılmıştır, [11] insanlar denatonumu kemirgenlerden çok daha düşük konsantrasyonlarda tespit edebilmektedir. [12]

Video oyun şirketi Nintendo, Nintendo Switch oyun konsolu için oyun kartlarına denatonium benzoat içeren bir kaplama uygulayarak çocukların küçük boyutlarından dolayı onları yutmasını engelliyor. [13]

DENATONYUM BENZOATE

DENATONYUM BENZOATE GENEL BAKIŞ

Denatonium benzoat (de-an-TOE-nee-um BEN-zoh-ate) genellikle bilimle bilinen herhangi bir bileşiğin en acı tadı olarak kabul edilir. Bitrex® ticari adı altında satılmaktadır. Denatonium benzoat güçlü bir tada sahip olmasına rağmen, renksiz ve kokusuzdur. Ancak tadı o kadar güçlü ki, çoğu insan milyonlarca denatonyum benzoat başına 30'dan fazla konsantrasyona tahammül edemez. Alkol veya sudaki denatonyum benzoat çözeltileri çok stabildir ve acı tatlarını yıllarca korur. Işığa maruz kalmak bileşiğin acı tadını azaltmaz.

İsimler

Tercih edilen IUPAC adı

N-Benzil-2- (2,6-dimetilanilino) -N, N-dietil-2-oksoetan-1-aminyum benzoat

Diğer isimler

N-Benzil-2 - [(2,6-dimetilfenil) amino] -N, N-dietil-2-oksoetan-1-aminyum benzoat

Tanımlayıcılar

CAS numarası

3734-33-6 ☑

ChEMBL

ChEMBL1371493 ☒

ChemSpider

18392 ☑

ECHA Bilgi Kartı 100.020.996

PubChem CID

19518

DENATONYUM BENZOATE DENATONYUM BENZOATE Denatonium benzoat (Bitrex®) Amerika Birleşik Devletleri'nde 20 yılı aşkın bir süredir alkol denaturan olarak kullanılmaktadır. Son yıllarda, çocukların yanlışlıkla yutulmasını önlemek için ev ürünlerine, bahçe ürünlerine ve kozmetik ürünlerine dahil edilmeleri için yoğun bir şekilde teşvik edilmiştir. ABD'de ev ürünlerine ek olarak doğrudan halka satılacak konsantre bir denatonyum benzoat çözeltisi mevcuttur. Denatonyum benzoat üzerindeki etkinlik ve güvenlik çalışmaları sınırlıdır ve potansiyel bir zehirlenme durumu bağlamında bakıldığında değişik yorumlara tabi olabilir. Güvenlik verileri düşük toksisite profilini gösterir. Bununla birlikte, özellikle insanlarda kronik toksisite, teratojenisite ve insan aşırı duyarlılık potansiyeli ile ilgili bilgi konusunda önemli boşluklar vardır [59]. 33 yaşında erkek hasta, bir böcek ilacı spreyi ile denatonyum benzoata maruz kalmaktan astım ve ürtiker geliştirdi. Daha önce alkol bazlı bir cilt dezenfektanına ve denatonyum benzoat ile denatüre edilmiş diğer ürünlere maruz kaldıktan sonra aynı semptomları geliştirmişti. Bu nedenle semptomlarının nedeninin, acil aşırı duyarlılık tipinin immünolojik bir mekanizması olması muhtemeldir. Şu anda mevcut olan kuşkusuz sınırlı veriler, denatonyum benzoatın aslında düşük bir toksisite profiline sahip olabileceğini göstermektedir. Alkol için bir denaturan olarak geniş kullanılabilirliği göz önüne alındığında, insan toksisitesinin sadece bir kez bildirilmesi şaşırtıcıdır. Bununla birlikte, denatonyum toksisitesi, ürünün toplam kimyasal yapısının küçük bir yüzdesini temsil ettiği için genellikle ürün bileşen listelerine dahil edilmediğinden tanınmamış olabilir. İnsanlarda akut oküler veya inhalasyon maruziyeti, insanlarda veya hayvanlarda kronik deri maruziyeti veya insanlarda veya hayvanlarda kronik soluma maruziyeti hakkında veri yoktur. Kırık veya aşınmış cilt üzerindeki güvenliği araştırılmamıştır. Teratojenisite çalışması yoktur.

Temmuz 1991'de Amerikan Veteriner ve Karşılaştırmalı Toksikoloji Akademisi, eşlik eden hayvanlar tarafından tehlikeli maddelerin alımını sınırlamak için acı bir ajan kullanımını teşvik etmek için bir karar aldı [60]. Rodgers [61], aşındırıcı maddelerin eklenebileceği kostikler ve hidrokarbonlar gibi bazı ürünlerin tek bir yutma ile toksisite üretebileceğini ve olumsuz bir ajanın eklenmesinin üzerinde faydalı bir etkisi olmayacağı görüşünü ifade etmişlerdir. bu tür yutmaların sonucu. Denatonyum benzoat ilavesinin, bu tür yutulmaların toksisite potansiyelini gerçekten artırabileceğini önerdi, çünkü kusma aspirasyon riskini artırabilir. Bu nedenle, etilen glikol, metanol ve toksik pestisitler içerenler dahil sınırlı sayıda üründe denatonyum benzoat kullanılmasını önerdi.

Özetle, denatonyum benzoat düşük bir konsantrasyonda aversif bir ajan olarak kullanıldığında güvenli gibi görünmektedir. Bununla birlikte, önleyici ajanların pediatrik yutmanın sayısı veya şiddeti üzerinde bir etkisi olup olmadığı hakkında sınırlı veri vardır ve kullanımı, çocuğa dirençli kapaklar gibi diğer önleyici tedbirlerin yerine geçmemelidir.

Denatonium, fenilmetil- [2- [(2,6-dimetilfenil) amino] -2-oksoetil] -dietilamonyumdan daha uygun bir isimdir. İki etil kollu, bir benzil ve bir büyük amid olan iki kuaterner amonyum katyondur ve genellikle bir benzoat - bir benzoik asit tuzu olarak gelir. Şöhret iddiası basit, nahoş ama değerli - denatonium benzoat henüz keşfedilen en acı maddedir.

Bu reaktif olmayan, renksiz, kokusuz bileşik ilk olarak 1958'de İskoç ilaç üreticisi T & H Smith, daha sonra Macfarlan Smith tarafından üretildi ve burada araştırmacılar lignokain adı verilen diş hekimleri için bir anestezik varyantları deniyorlardı. Kısa süre sonra, bu agresif tatsız bileşiğin insanlar için tatsız bir madde haline getirmesi için milyonda denatonyum benzoatın sadece birkaç kısmının yeterli olduğu keşfedildi. denatonyum benzoatın ne kadar güçlü olduğunu göstermede yardımcı olur. İnsan dili kübinin acı vuruşunu metreküp başına yaklaşık 0.008 mol konsantrasyonda alabilir. Buna karşılık, denatonium benzoat, bu konsantrasyonun binde birinin saptanmasını gerektirir.

Denatonyum benzoata karşı olağanüstü reaksiyonumuzun, dil üzerindeki TAS2R tat reseptörlerinin bu özel bileşiğe tepki verme biçiminin kazara bir işlevi olması muhtemeldir. Ancak bu, bol miktarda kullanım bulmuş bir kazadır, çünkü denatonyum benzoat, Bitrex, BITTER + PLUS ve Aversion gibi tüm bitterant çeşitleri veya aversif ajanlar olarak pazarlanmaktadır.

DENATONYUM BENZOATE Fikir basit - tüketilebilecek bir şey varsa, ancak olmaması gerekiyorsa, biraz denatonyum benzoat eklersiniz ve hatta küçük miktarları bile insanları erteleyecektir. Kaçınılmaz olarak, yapmamaları gereken maddeleri tüketme olasılığı en yüksek olan çocuklar, yılda 30.000 kişi hastaneye kaldırılıyor.Sadece İngiltere'de zehirlenme şüphesi var, denatonyumun acı saldırısına karşı özellikle hassas görünüyor, bu da onu iş için ideal yapıyor.

Bazı uygulamalar basittir - aksi takdirde tatlı tatma, ancak zehirli antifriz etilen glikol ve sıçan zehiri (şanslı sıçan dilleri bileşiğe çok daha az duyarlıdır). Daha sinsice, etanol denatonyum eklenerek 'denatüre edilebilir' ve bu da içilemez hale getirilebilir. Bu, alkolün temizlik için veya yakıt olarak kullanılması gerektiğinde, genellikle alkollü bir içeceğe eşlik eden büyük vergi yükü olmadan satılabileceği anlamına gelir - biyoetanolün artan kullanımı ile özellikle yaygın bir uygulama.

Denatonium benzoat bir takımın üyesi olsaydı, kimsenin üzerinde durmadığı, ancak herkesin hatırladığı dikenli olurdu. Tat alma duyumuz daha zayıf duyulardan biri olabilir, ancak hala yapmamamız gereken şeyleri yemememizi sağlamada temel bir yardımcı olmaya devam ediyor. Ünlü şefler hayatlarını gastronomi zevklerini takip ederek, en son tat hissini takip ederek geçirebilirler, ancak denatonium benzoat, kötü tadın lezzetli ikramlar kadar yararlı olabileceğini hatırlatmak için her zaman oradadır. Ve bu bir doz kriptonitten çok daha yararlı.

Meera Senthilingam

Bu yüzden ağzınızdaki ekşi tadı unutmayın. Bilim yazarı Brian Clegg, denatonyum benzoatın kimyasıyla gününüze biraz acı getiriyor. Gelecek hafta, ünlü bir Fransız'ın tıbbi rahatsızlıkları.

enatonium benzoate başka birçok uygulamaya sahiptir. Örneğin, kompülsif tırnak ucu olan kişilerin tırnaklarını fırçalamak için seyreltik bir solüsyonda kullanılabilir. Bazı ebeveynler, başparmaklarını olması gerekenden daha fazla emen çocukların başparmaklarında benzer bir çözüm kullanırlar. Denatonium benzoat ayrıca hayvan kovucu olarak da kullanılır. Denatonyum benzoat içeren ürünler, geyiklerin bu ürünler üzerinde otlamasını önlemek için ağaçlara, fırçalara, ekinlere ve diğer malzemelere püskürtülebilir. Ürünün ilk uygulamalarından biri, domuzların birbirlerini ısırmasını önlemek için domuz kuyruklarında bir işlemdi. Elektrik kabloları üzerindeki kaplamalar bazen sıçanların üzerlerinde çiğnemesini engellemek için bir denatonyum benzoat çözeltisi ile emprenye edilir.

Denatonyum benzoatın kullanıldığı diğer uygulamalardan bazıları şunlardır:

DENATONYUM BENZOATE Sıvı çamaşır deterjanlarında;

DENATONYUM BENZOATE umaş şartlandırıcılarında;

DENATONYUM BENZOATE Tuvalet temizleyicilerinde;

DENATONYUM BENZOATE Dezenfektanlarda;

DENATONYUM BENZOATE Ev tipi antiseptiklerde;

DENATONYUM BENZOATE Denatonium Benzoat

Jean-Patrick Holvoet, Elektro Makine Mühendisliği Yüksek Lisansı. © 2014

Denatonium Benzoate acı bir ajandır. Temizleyicilerin, otomotiv malzemelerinin yanı sıra sağlık ve güzellik ürünlerinin imalatında çeşitli kullanımlara sahip en acı kimyasal bileşik olarak kabul edilir. Ticari olarak, bu bileşik beyaz bir kristal toz olarak mevcuttur, ancak denatonyum benzoat granülleri veya çözeltileri de mevcuttur.

Kimya Dünyasına göre, denatonium benzoat, Macfarlan Smith Ltd'nin öncüsü olan bir İskoç ilaç firması olan T & H Smith'teki araştırmacılar tarafından tesadüfi bir formülasyondu. 1958'de, laboratuvar personeli bir diş hekimi olan lignokain ile çalışıyordu anestezik, toz halinde denatonyum benzoatın aşırı acısını keşfettiklerinde. Aşırı tadı nedeniyle, denatonyum benzoat önleyici bir ajan olarak kullanılmıştır. Kral için acı ve rex kelimelerinin bir portmanı olan Bitrex® ticari markası altında mevcuttur. Bitrex® için bilinen ilk uygulama, kendi kuyruklarını ya da diğer domuzların yamyamlığını artıran domuzlar için bir yardımcıydı.

Biyokimyasal Yapı

Kimyasal formül: C21H29N20. Kimyasal veri tabanı PubChem, denatonium'a bir kimyasal kimlik numarası veya 19518 CID'si atadı. 446.58116 g / mol kimyasal ağırlığa ve C28H3 4N203'ün moleküler formülüne sahiptir. Denatonyum benzoat, benzoat veya sakarit gibi inert bir anyonu olan bir tuz bileşiğidir. Yapısı lidokaine benzer ve Novocain ve benzokain ile yakından ilişkilidir. Kokusuz, renksiz ve reaktif değildir, bu da onu baz bileşiğin birincil amacına müdahale etmeyen uygun bir katkı maddesi yapar.

Nasıl Çalışır? İnsanlar genellikle tatlı, ekşi, tuzlu, tuzlu ve acı tadım şeyleri hissedebilirler. Bu tatlar arasında acı tadım kimyasalları en çok tepkiyi verir. Acı aromalara duyarlılık genetiğe bağlıdır: TAS2R38 geni, bir kişinin tonik suda bir bileşen olan kinin gibi maddelerle ilişkili acıları tespit etme yeteneğini belirler. Aynı zamanda bu tip acı aromaların standardıdır. Metreküp başına 0.008 mol'lük bir konsantrasyonda, insan dili kinin varlığını tespit edebilir. Denatonyum benzoat için, metreküp başına 0.000008 mol konsantrasyon insanlar tarafından fark edilebilir.

Uygulamalar

Denatonyum benzoat gibi bitterantlar, tehlikeli otomotiv bileşiklerinin yanlışlıkla yutulmasını önlemek için aşırı katkı maddeleri olarak yararlıdır. Avrupa ve bazı ABD eyaletlerinde, etilen glikol veya antifriz ve ön cam yıkayıcı sıvılarında denatonyum benzoat ilavesi gereklidir. Pencere temizleyicileri, dezenfektanlar, çamaşır deterjanı ve böcek ilacı gibi yaygın ev ürünleri, ağızdan tüketimi caydırmak için belirli miktarda denatonyum benzoat içerir.

Tehlikeli maddelerin önemli ölçüde tüketimini önlemek için oyuncak yüzeylerine acı bir ajan olarak uygulanır. Ayrıca dış mekan kabloları ve telleri üzerinde, kemirgenlerin parça ve ekipman üzerinde çiğnemesini önlemek için uygulanır. Denatonium benzoat, özellikle küçük çocuklar bu zehirli maddelerle temas ettiğinde yutmayı bastırmak için çeşitli pestisitlere, bitki besin çubuklarına ve rodentisitlere eklenen önleyici bir ajandır.

Şimdiye kadar, denatonyum benzoatın en yaygın kullanımı, alkolü denatüre etmek, onu insan tüketimine uygun hale getirmektir ve normalde alkole uygulanan tarifelerden muaftır.

Hayvancılıkta, denatonium benzoat domuzlarda yamyamlığı ve sığırlarda aspirasyon mastitini önlemek için kullanılır. Genç sürgünlere, dallara ve diğer yüzeylere uygulandığında, hayvanların nibbling'ini caydırmak ve böylece maddi hasarı önlemek için bir itici görevi görür.

Bunu sorabileceğini düşündük. İşte bu soruya çok doğru cevaplar.

DENATONYUM BENZOATE Bitrex ...

Denatonium Benzoate - tam, teknik adını vermek için. İronik olarak, bu biraz ağız dolusu. Biz buna Bitrex® diyoruz.

Erkek, kadın veya çocuk tarafından bilinen en acı maddedir. Guinness Dünya Rekorlarına göre.

Bir çocuk veya hayvan yutmaya çalışırsa, zehirlenmeden önce tüküreceklerinden emin olmak için ev, bahçe ve otomotiv ürünlerine konan bir madde.

Tükendiğinde tamamen zararsızdır. Sadece tadı gerçekten çok korkunç.

Bir cankurtaran. Kelimenin tam anlamıyla.

Mutlu bir kazanın ürünü. Bitrex, 1958'de yeni bir lokal anestezi üzerinde çalışan bir Macfarlan Smith bilim adamı ekibi tarafından keşfedildi. Kimyagerlerimiz, dünyanın en acı malzemesi olan dikkate değer bir madde bulduğunu hemen fark ettiler ve çabucak iyi bir şekilde kullandılar ... Yanlışlıkla zehirlenmeyi geçmişte bırakmaya yardımcı olmak.

Kimyasalları çocuğun ulaşamayacağı bir yerde tutmak, güvenlik kapaklarını doğru kullanmak ve etiketleri dikkatlice okumak gibi zehirlenmeleri önlemek için diğer yaygın önlemlerin yerine kullanılır.

DENATONYUM BENZOATE Ancak bu çocuk güvenliği katkısına tam olarak öncülük ettik, çünkü ebeveyn olmanın nasıl bir şey olduğunu biliyoruz. Ebeveynlerin taciz edildiğini, yorulduğunu ve gözlerine geldiğini anlıyoruz. İşte bu yüzden Bitrex orada. Çoğu kaza olduğunda dikkatsizlik anları için.

natonyum benzoat

Denatonium'un kimyasal yapısıBenzoatın kimyasal yapısı

Sistematik isim N-benzil-2- (2,6-dimetilfenilamino) -

N, N-dietil-2-oksoetanaminyum benzoat

Kimyasal formül C21H29N2OÂ · C7H5O2

Molekül kütlesi 446.58 g / mol

Yoğunluk x.xxx g / cm³

Erime noktası 166-170 ° C

Kaynama noktası xx.x ° C

CAS numarası [3734-33-6]

Smiles S = CC1 = C = C (C) = C1NC (C [N +] (CC) (CC)

CC2 = C = C = C2) = o.o = C ([O -]) C3 = C = C = C3-

Sorumluluk reddi ve referanslar

Genellikle denatonyum benzoat (veya Bitrex veya Aversion gibi ticari isimler altında) ve denatonyum sakarit olarak mevcut olan denatonyum bilinen en acı bileşiktir. 1958 yılında, Edinburgh, İskoçya'dan Macfarlan Smith tarafından lokal anesteziklerle ilgili araştırma sırasında keşfedildi. 10 ppm kadar az dilüsyonlar çoğu insan için dayanılmaz derecede acıdır. Denatonium tuzları genellikle renksiz ve kokusuz katılardır, ancak genellikle çözelti olarak işlem görürler. Yanlışlıkla yutulmasını önlemek için önleyici ajanlar olarak kullanılırlar. Denatonium, denatüre alkol, antifriz, tırnak ısırma önlemeleri, hayvan iticiler, sıvı sabunlar ve şampuanlarda kullanılır. Maruziyet rahatsız edici ve rahatsız edici olsa da, uzun süreli sağlık riskleri oluşturduğu bilinmemektedir.

Yapı ve fiziksel özellikler

Denatonium bir kuaterner amonyum katyondur. Benzoat veya sakarit gibi inert bir anyonu olan bir tuz bileşiğidir. Denatonyumun yapısı, sadece amino nitrojene bir benzil grubunun ilave edilmesiyle farklılık gösteren lokal anestetik lidokain ile ilgilidir.

Bileşiğin acısı, denatonyumun birçok uygulamasını yönlendirir. Denatonium etanolü denatüre etmek için kullanılır, böylece alkollü bir içecek olarak vergilendirilmez. Özellikle bir adlandırma olan SD-40, etanolün denatonyum kullanılarak denatüre edildiğini gösterir. Aslında, bu kimyasalın ortak adı olan denatonium, bu uygulamayı ifade eder.

Denatonium ayrıca metil alkol ve etilen glikol gibi zararlı alkollerin tüketimini de caydırır. Bu nedenle Denatonium, aktif olmayan bir bileşen olarak alkolün ovulmasında sıklıkla kullanılır. Ayrıca solventler, boyalar, vernikler, banyo malzemeleri ve diğer ev ürünleri de dahil olmak üzere her türlü zararlı sıvıya eklenir.

Oregon Eyaleti, antifriz ve ön cam silecek sıvısına eklenmesini istediğinde 1995'ten beri, bileşik bu maddelerde dünya çapında giderek daha fazla bulunmuştur. Denatonyum ilavesi, tatlı antifriz veya silecek sıvısı içebilen ve sırasıyla etilen glikol veya metanol zehirlenmesi alabilen çocukların ve hayvanların kurtarılmasıyla bilinir. Diğer kullanımlar arasında tırnak ısırmasını önlemek için oje ve hayvan kovucu olarak (özellikle geyik gibi büyük oyunlarda) bulunur.

DENATONYUM BENZOATE Hayvanların denatonyumun etkilerine karşı farklı hassasiyetlere sahip oldukları bilinmelidir. Sıçan zehirlerini insan tüketiminden korumak için kullanılmıştır, bu nedenle sıçanların küçük bir yüzdesinin bu tür yemlerden kaçındığına dair kanıtlar olmasına rağmen, muhtemelen sıçanlar tarafından caydırılmamaktadır. Bazı kedilerin onlar tarafından cazip olduğu bilinmektedir, kediler için insanlar için olduğu kadar etkili bir caydırıcı olmayabilir veya belki de bazı kediler, feniltiyokarbamid tadı algılarını etkileyen genetik bir faktör nedeniyle caydırılmamaktadır.

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]

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]

OVERVIEW

DENATONYUM BENZOATE Denatonium benzoate (de-an-TOE-nee-um BEN-zoh-ate) is generally regarded as having the most bitter taste of any compound known to science. It is sold under the trade name of Bitrex®. Although denatonium benzoate has a powerful taste, it is colorless and odorless. The taste is so strong, however, that most people cannot tolerate a concentration of more than 30 parts per million of denatonium benzoate. Solutions of denatonium benzoate in alcohol or water are very stable and retain their bitter taste for many years. Exposure to light does not lessen the compound's bitter taste.

Names

DENATONYUM BENZOATE 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

3734-33-6 ☑

ChEMBL 

ChEMBL1371493 ☒

ChemSpider 

18392 ☑

ECHA InfoCard 100.020.996

PubChem CID

19518

UNII 

M5BA6GAF1O ☑

CompTox Dashboard (EPA)

DTXSID8034376 Edit this at Wikidata

InChI[show]

SMILES[show]

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

STE AVERSIVE AGENTS

Denatonium benzoate (Bitrex®) has been used in the United States for over 20 years as an alcohol denaturant. In recent years, it has been heavily promoted for inclusion in household products, gardening products, and cosmetics to prevent accidental ingestions by children. A concentrated solution of denatonium benzoate which would be sold directly to the public for addition to household products is available in USA. The efficacy and safety studies on denatonium benzoate are limited and may be subject to varying interpretations when viewed in the context of a potential poisoning situation. Safety data indicate a low toxicity profile. However, there are significant gaps in knowledge, especially relating to chronic toxicity in humans, teratogenicity, and human hypersensitivity potential [59]. A 33-year-old man developed asthma and urticaria from exposure to denatonium benzoate in an insecticidal spray. He had previously developed the same symptoms following exposure to an alcohol-based skin disinfectant and other products denatured with denatonium benzoate. The cause of his symptoms was thus likely to be an immunologic mechanism of the immediate hypersensitivity-type. Currently available, admittedly limited data indicate that denatonium benzoate may actually have a low toxicity profile. Considering its wide availability as a denaturant for alcohol, it is surprising that human toxicity has been reported only once. However, denatonium toxicity may have been unrecognized because it is usually not included on product-ingredient lists since it represents a small percentage of the total chemical make-up of the product. No data exist on acute ocular or inhalation exposure in humans, chronic skin exposure in humans or animals, or chronic inhalation exposure in humans or animals. Its safety on broken or abraded skin has not been investigated. There are no teratogenicity studies.

In July 1991, The American Academy of Veterinary and Comparative Toxicology passed a resolution to encourage the use of a bittering agent to limit the ingestion of hazardous materials by companion animals [60]. Rodgers [61] expressed the view that some of the products, such as caustics and hydrocarbons, to which aversive agents might be added may produce toxicity with a single swallowing and it is unlikely that the addition of an adversive agent would have a beneficial effect on the outcome of such ingestions. He suggested that addition of denatonium benzoate might actually increase the potential for toxicity of such ingestions because vomiting might increase the risk of aspiration. He therefore recommended the use of denatonium benzoate in a limited number of products including those containing ethylene glycol, methanol and toxic pesticides.

In summary, denatonium benzoate appears to be safe when used at low concentrations as an aversive agent. However, there are limited data about whether aversive agents have an impact on either the number or the severity of pediatric ingestions, and its use should not be a substitute for other preventive measures such as child-resistant closures.

Denatonium is a rather more convenient name than phenylmethyl-[2- [(2,6-dimethylphenyl)amino]-2-oxoethyl]-diethylammonium. It is a quaternary ammonium cation, with two ethyl arms, one benzyl and one larger amide one, and usually comes as a benzoate - a salt of benzoic acid. Its claim to fame is simple, unpleasant but valuable - denatonium benzoate is the most bitter substance yet discovered.

This unreactive, colourless, odourless compound was first produced accidentally in 1958 by Scottish pharmaceutical manufacturer T & H Smith, later Macfarlan Smith, where researchers were experimenting with variants of an anaesthetic for dentists called lignocaine. It was soon discovered that just a few parts per million of denatonium benzoate were enough for this aggressively unpleasant compound to render a substance distasteful to humans.Quinine, the archetypal bitter substance associated with this gene, is used as the benchmark for bitterness, and is helpful in demonstrating just how strong denatonium benzoate is. The human tongue can pick up the bitter kick of quinine at a concentration of around 0.008 moles per cubic metre. By contrast, denatonium benzoate requires a thousandth of that concentration to be detected.

Our outstanding reaction to denatonium benzoate is likely to be an accidental function of the way the TAS2R taste receptors on the tongue react to this particular compound. But this is an accident that has found plenty of use, as denatonium benzoate is marketed under names like Bitrex, BITTER+PLUS and Aversion, which are all varieties of bitterants or aversive agents.

The idea is simple - if you have something that may be consumed but shouldn't be, you add some denatonium benzoate and even small quantities of it will put people off. Children, who inevitably are the most likely to try to consume substances they shouldn't, with as many as 30,000 a year taken to hospital in the UK alone with suspected poisoning, seem particularly sensitive to the bitter attack of denatonium, making it ideal for the job.

Some of the applications are straightforward - in the otherwise sweet-tasting but poisonous antifreeze ethylene glycol, for instance, and in rat poison (luckily rat tongues are a lot less sensitive to the compound). Rather more sneakily, ethanol can be ‘denatured' by adding denatonium, making it undrinkable. This means it can be sold without the large tax burden that usually accompanies an alcoholic drink, when the alcohol is to be used for cleaning or as fuel - a particularly common application with the increasing use of bioethanol.

If denatonium benzoate were a member of a team it would be the prickly one that no one else gets on with, but that everyone remembers. Our sense of taste may be one of the weaker senses, but it still remains a fundamental helper in ensuring we don't eat things we shouldn't. Celebrity chefs may spend their lives pursuing gastronomic pleasures, tracking down the latest taste sensation, but denatonium benzoate is always there to remind us that bad taste can be just as useful as tasty treats. And that's so much more useful than a dose of kryptonite.

Meera Senthilingam

So remember that sour taste in your mouth. Science writer Brian Clegg there bringing some bitterness to your day, with the chemistry of denatonium benzoate. Next week, the medical ailments of a famous Frenchman.

enatonium benzoate has many other applications. For example, it can be used in a dilute solution to brush on the fingernails of people who are compulsive fingernail-biters. Some parents use a similar solution on the thumbs of children who suck their thumbs more than they should. Denatonium benzoate is also used as an animal repellent. Products containing denatonium benzoate can be sprayed on trees, brushes, crops, and other material to prevent deer from grazing on those products. One of the product's first applications was as a treatment on pig's tails to prevent pigs from biting each other. The coatings on electric cables are sometimes impregnated with a denatonium benzoate solution to discourage rats from chewing on them.

Some of the other applications in which denatonium benzoate has been used include the following:

In liquid laundry detergents;

In fabric conditioners;

In toilet cleaners;

In disinfectants;

In household antiseptics;

Denatonium Benzoate

by Jean-Patrick Holvoet, Master in Electro Mechanical Engineering. ©2014

Denatonium Benzoate is a bittering agent. It is considered the bitterest chemical compound with a range of uses in the manufacture of cleaners, automotive supplies as well as health and beauty items. Commercially, this compound is available as a white crystalline powder, but denatonium benzoate granules or solutions are also available.

HistoryBitrex (r)According to Chemistry World, denatonium benzoate was an accidental formulation by researchers at T & H Smith, a Scottish pharmaceutical firm that was the precursor for Macfarlan Smith Ltd. In 1958, staff at the laboratory was working with lignocaine, a dental anesthetic, when they discovered the extreme bitterness of denatonium benzoate in powder form. Due to the extreme taste, denatonium benzoate was used as an aversive agent. It is available under the trade name Bitrex®, which is a portmanteau of the words bitter and rex for king. The first known application for Bitrex® was as an aversant for pigs that were cannibalizing their own tails or those of other pigs.

Biochemical Structure

Chemical formula: C21H29N2O . C7H5O2The chemical database PubChem assigned a chemical identification number or CID of 19518 to denatonium. It has a chemical weight of 446.58116 g/mol and a molecular formula of C28 H3 4N 2O3. Denatonium benzoate is a compound of salt with an inert anion such as benzoate or saccharide. Its structure is similar to lidocaine and is closely related to Novocain and benzocaine. It is odorless, colorless and non-reactive, making it a suitable additive that does not interfere with the primary purpose of the base compound.

How it WorksHumans can typically sense sweet, sour, salty, savory and bitter-tasting stuff. Of these flavors, bitter-tasting chemicals elicit the most reaction. Sensitivity to bitter flavors depends on genetics: The TAS2R38 gene determines a person's ability to detect the bitterness associated with substances such as quinine, which is an ingredient in tonic water. It is also the standard for this type of bitter flavor. At a concentration of 0.008 moles per cubic meter, the human tongue can detect the presence of quinine. For denatonium benzoate, a concentration of 0.000008 moles per cubic meter is discernible to humans.

Applications

Bitterants such as denatonium benzoate are useful as aversive additives to prevent accidental ingestion of hazardous automotive compounds. In Europe and in some U.S. states, addition of denatonium benzoate is required in ethylene glycol or anti-freeze and windshield washer fluids. Common household products such as window cleaners, disinfectants, laundry detergent and insecticide include a certain amount of denatonium benzoate to discourage consumption by mouth.

It is applied on surfaces of toys as a bittering agent to prevent substantial consumption of hazardous materials. It is also applied on outdoor cables and wires to discourage rodents from chewing on parts and equipment. Denatonium benzoate is an aversive agent added to various pesticides, plant food sticks and rodenticides to suppress swallowing especially when young children come in contact with these poisonous substances.

By far, the most common use of denatonium benzoate is to denature alcohol, making it unfit for human consumption and exempt from tariffs that normally apply to alcohol.

In livestock farming, denatonium benzoate is used to prevent cannibalism in pigs and aspiration mastitis in cattle. It acts as a repellant when applied to young shoots, branches and other surfaces to discourage nibbling by animals, thereby preventing damage to property.

We thought you might ask that. So here are lots of perfectly correct answers to that question.

Bitrex is...

Denatonium Benzoate - to give it its full, technical name. Ironically, that's a bit of a mouthful. So we call it Bitrex®.

The bitterest substance known to man, woman or child. That's according to The Guinness World Records.

A substance that's put into household, garden and automotive products to ensure that if a child or animal ever tried to swallow it, they would spit it straight out before they could be poisoned.

Completely harmless if consumed. It just tastes really, really horrible.

A lifesaver. Literally.

The product of a happy accident. Bitrex was discovered in 1958 by a team of Macfarlan Smith scientists who were working on a new local anaesthetic. Our chemists realised immediately that they had found a remarkable substance - the world's most bitter material - and quickly put it to good use...Helping to make accidental poisoning a thing of the past.Bitrex is not...

A substitute for other common sense precautions for preventing poisoning, such as keeping chemicals out of a child's reach, using safety closures properly and reading labels carefully.

But we pioneered this child safety additive precisely because we know what it's like to be a parent. We understand that parents get harassed, tired, and up to their eyes. And that is why Bitrex is there. For the moments of inattention when most accidents happen.

natonium benzoate

Chemical structure of DenatoniumChemical structure of benzoate

Systematic name N-benzyl-2-(2,6-dimethylphenylamino)-

N,N-diethyl-2-oxoethanaminium benzoate

Chemical formula C21H29N2O·C7H5O2

Molecular mass 446.58 g/mol

Density x.xxx g/cm³

Melting point 166-170 °C

Boiling point xx.x °C

CAS number [3734-33-6]

SMILES S=CC1=CC=CC(C)=C1NC(C[N+](CC)(CC)

CC2=CC=CC=C2)=O.O=C([O-])C3=CC=CC=C3

Disclaimer and references

Denatonium, usually available as denatonium benzoate (or under trade names such as Bitrex or Aversion) and as denatonium saccharide, is the most bitter compound known. It was discovered in 1958 during research on local anesthetics by Macfarlan Smith of Edinburgh, Scotland. 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 accidental ingestion. Denatonium is used in denatured alcohol, antifreeze, nail biting preventions, animal repellents, liquid soaps, and shampoos. It is not known to pose any long-term health risks although exposure may be irritating and unpleasant.

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.

ApplicationsThe bitterness of the compound guides most applications of denatonium. Denatonium is used to denature ethanol so that it is not taxed as an alcoholic beverage. One designation in particular, SD-40, indicates that ethanol has been denatured using denatonium. In fact, the common name for this chemical, denatonium alludes to this application. 

Denatonium also discourages consumption of harmful alcohols like methyl alcohol and ethylene glycol. Denatonium is therefore often used in rubbing alcohol as an inactive ingredient. It is also added to all kinds of harmful liquids including solvents, paints, varnishes, toiletries, and other household products. 

Since 1995, when the State of Oregon required that it be added to antifreeze and windshield wiper fluid, the compound has been increasingly found in these substances throughout the world. The addition of denatonium is credited with saving children and animals who might otherwise drink sweet antifreeze or wiper fluid and get ethylene glycol or methanol poisoning respectively. Other uses include nail polish for preventing nail biting, and as animal repellent (especially for big game like deer). 

It should be noted that animals are known to have different sensitivities to the effects of denatonium. It has been used to safeguard rat poisons from human consumption, so presumably rats are not deterred by it, although there is evidence that a small percentage of rodents do avoid such baits. Some cats have been known to be tempted by them it may not be as effective a deterrent for cats as it is for humans, or perhaps some cats are not deterred due to a genetic factor similar to that affecting human perceptions of the taste of phenylthiocarbamide.

Le benzoate de dénatonium est un sel benzoïque de dénatonium au goût très amer. Il a été découvert en 1958 lors de recherche sur les anesthésiques locaux. Il est utilisé comme répulsif pour prévenir l'ingestion des produits ménagers et des antigels, en vernis à ongles dans la lutte contre l'onychophagie et sert à dénaturer l'éthanol. Ce composé artificiel est aussi amer que la quassine, le composé naturel connu le plus amer.

Le benzoate de dénatonium a été découvert fortuitement en 1958 par un laboratoire pharmaceutique écossais du nom de MacFarlan Smith à Édinbourg5. Cette découverte est intervenue lors de recherches en vue d'améliorer les propriétés anesthésiques de la lidocaïne.

Le laboratoire extrayait déjà la brucine (composé amer) afin de dénaturer les alcools, mais le benzoate de dénatonium étant plus amer et dépourvu de toxicité, ce dernier est vite devenu le dénaturant idéal. C'est d'ailleurs du nom de son utilisation de dénaturant que ce composé tire son nom, le nom commercial étant lié lui au mot anglais bitter signifiant amer 5. Une autre des premières applications du Bitrex comme agent d'aversion était une crème conçue pour éviter que les porcs ne mangent la queue de leur voisin5.

Législation[

Dès 1960, le benzoate de dénatonium, sous la marque Bitrex, est autorisé aux États-Unis et au Royaume-Uni dans les parfums, la parfumerie, les cosmétiques et autres usages industriels. Depuis il est reconnu comme un agent dénaturant et agent d'aversion dans plus de 40 pays5.

En 1993, il est autorisé dans l'Union Européenne comme dénaturant de l'alcool en vue de l'exonération du droit d'accise6.

En 1995, la loi française a, par décret, rendu obligatoire l'adjonction par les industriels de benzoate de dénatonium ou d'un autre agent répulsif dans les antigels et fluides caloporteurs contenant du monoéthylèneglycol7.

Depuis 1999, il est obligatoire de l'utiliser dans certains pesticides5.

Structure et propriétés[

Structure[

Le benzoate de dénatonium est un sel de synthèse comprenant un anion (le benzoate) associé à un cation (un ammonium quaternaire). Le cation a une structure similaire à l'anesthésique local, la lidocaïne, dont il ne diffère que par l'addition d'un groupe benzyle sur l'amine tertiaire.

Le dénatonium peut être associé avec d'autres anions sous forme de sel tels que l'ion saccharinate pour former le saccharinate de dénatonium8 ou l'ion chlorure pour former le chlorure de dénatonium9.

Propriétés physico-chimiques[

Le benzoate de dénatonium est soluble dans l'eau1, l'éthanol, le méthanol, le butanol, l'isopropanol et le chloroforme4.

La température de fusion du benzoate de dénatonium est de 168 °C3.

Propriété sensorielle[

Le benzoate de dénatonium a un seuil de détection à 10 ppb et un seuil de reconnaissance de l'amertume de 0,05 ppm, ce qui le rend aussi amer que la quassine, le composé naturel connu le plus amer avec un seuil de reconnaissance de l'amertume de 0,06 ppm10.

La nature de l'anion avec lequel le sel de dénatonium est associé modifie la concentration du seuil de reconnaissance de l'amertume. Ainsi, pour le saccharinate de dénatonium et le chlorure de dénatonium, celui-ci est de 0,01 ppm et 0,1 ppm respectivement9.

Le benzoate de dénatonium est vraiment très amer vers 10 ppm11.

Dermatologie[

Le benzoate de dénatonium est considéré comme inoffensif pour la peau dans les produits cosmétiques aux doses utilisées (0,0006 %)11.

Utilisation

Le benzoate de dénatonium est principalement utilisé pour son goût amer comme dénaturant, agent répulsif, agent d'aversion ou amérisant.

Dans l'Union européenne, le benzoate de dénatonium est utilisé comme dénaturant dans les alcools, principalement pour l'exonération du droit d'accise6.

Il est aussi utilisé pour décourager la consommation des alcools toxiques tels que le méthanol et l'éthylène glycol. En France les industriels ajoutent un minimum de 20 ppm de benzoate de dénatonium dans les produits contenant de l'éthylène glycol, cela concerne les antigels, les fluides caloporteurs et produits lave-glace7.

Le benzoate de dénatonium est recommandé dans la lutte pour la protection des enfants et la diminution des accidents ménagers dus à l'absorption de produits ménagers (détergents, produits de lessive, adoucissants), cosmétiques, parfums et produits de bain (shampoing). L'amertume intense du benzoate de dénatonium oblige l'enfant à recracher le produit aussitôt après l'avoir mis en bouche12.

Le benzoate de dénatonium est utilisé comme additif dans les produits de lutte contre les rongeurs (campagnol, ragondin, rat, souris) et cervidés13.

Le benzoate de dénatonium est également utilisé dans un vernis à ongles amer pour lutter contre la manie de se ronger les ongles (onychophagie).

Les cartouches de la console Nintendo Switch en sont enduites, de façon que les enfants ne les avalent pas14 ; elles sont en effet très petites.

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]

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.

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

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]

Denatonium, usually available as denatonium benzoate (or under trade names such as Bitrex or Aversion) and as denatonium saccharide, is the most bitter compound known. It was discovered in 1958 during research on local anesthetics by Macfarlan Smith of Edinburgh, Scotland. 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 accidental ingestion. Denatonium is used in denatured alcohol, antifreeze, nail biting preventions, animal repellents, liquid soaps, and shampoos. It is not known to pose any long-term health risks although exposure may be irritating and unpleasant.

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.

Applications

The bitterness of the compound guides most applications of denatonium. Denatonium is used to denature ethanol so that it is not taxed as an alcoholic beverage. One designation in particular, SD-40, indicates that ethanol has been denatured using denatonium. In fact, the common name for this chemical, denatonium alludes to this application. 

Denatonium also discourages consumption of harmful alcohols like methyl alcohol and ethylene glycol. Denatonium is therefore often used in rubbing alcohol as an inactive ingredient. It is also added to all kinds of harmful liquids including solvents, paints, varnishes, toiletries, and other household products. 

Since 1995, when the State of Oregon required that it be added to antifreeze and windshield wiper fluid, the compound has been increasingly found in these substances throughout the world. The addition of denatonium is credited with saving children and animals who might otherwise drink sweet antifreeze or wiper fluid and get ethylene glycol or methanol poisoning respectively. 

Other uses include nail polish for preventing nail biting, and as animal repellent (especially for big game like deer). 

It should be noted that animals are known to have different sensitivities to the effects of denatonium. It has been used to safeguard rat poisons from human consumption, so presumably rats are not deterred by it, although there is evidence that a small percentage of rodents do avoid such baits. Some cats have been known to be tempted by them it may not be as effective a deterrent for cats as it is for humans, or perhaps some cats are not deterred due to a genetic factor similar to that affecting human perceptions of the taste of phenylthiocarbamide.

DENATONIUM BENZOATE

3734-33-6

Bitrex

Lidocaine benzyl benzoate

Anispray

Aversion

Denatonium (benzoate)

Gori

THS-839

Caswell No. 083BB

UNII-M5BA6GAF1O

Denatonium benzoate anhydrous

WIN 16568

Denatonii benzoas [INN-Latin]

EINECS 223-095-2

Benzoate de denatonium [INN-French]

Benzoato de denatonio [INN-Spanish]

M5BA6GAF1O

Denatonium benzoate [USAN:INN:BAN]

EPA Pesticide Chemical Code 009106

NSC 157658

Denatonium benzoate granules

Benzyldiethyl((2,6-xylylcarbamoyl)methyl)ammonium benzoate

Benzyldiethyl[(2,6-xylylcarbamoyl)methyl]ammonium benzoate

NCGC00017043-02

AK161798

CAS-3734-33-6

N-Benzyl-2-((2,6-dimethylphenyl)amino)-N,N-diethyl-2-oxoethanaminium benzoate

Benzenemethanaminium, N-(2-((2,6-dimethylphenyl)amino)-2-oxoethyl)-N,N-diethyl-, benzoate

DSSTox_CID_14376

enatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable.

Patient concerns: 

A 34-year-old female nurse rapidly developed shortness of breath, cough, and agitation after denatonium benzoate fit testing. She had a history of allergy to shrimp, crab, mite, and disinfecting products (containing quaternary ammonium).

Diagnoses: 

Due to typical symptoms of asthma after exposure to denatonium benzoate aerosol without any other apparent cause, serial pulmonary function tests indicating obstructive lung function and a higher concentration of immunoglobulin antibody E, she was diagnosed with allergic asthma.

Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable.

Patient concerns: 

A 34-year-old female nurse rapidly developed shortness of breath, cough, and agitation after denatonium benzoate fit testing. She had a history of allergy to shrimp, crab, mite, and disinfecting products (containing quaternary ammonium).

Diagnoses: Due to typical symptoms of asthma after exposure to denatonium benzoate aerosol without any other apparent cause, serial pulmonary function tests indicating obstructive lung function and a higher concentration of immunoglobulin antibody E, she was diagnosed with allergic asthma.

More

RESEARCH ARTICLE: CLINICAL CASE REPORT

Asthma associated with denatonium benzoate in a healthcare worker in Taiwan

A case report

Chen, Kou-Huang PhDa; Chung, Kuo-Mou MDb,c; Chung, Ju-Hui RNd; Chen, Kow-Tong MD, PhDe,f,*Section Editor(s): NA., Author Information

Medicine: May 2019 - Volume 98 - Issue 21 - p e15818

doi: 10.1097/MD.0000000000015818

OPEN

Metrics

Abstract

Rationale: 

Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable.

Patient concerns: 

A 34-year-old female nurse rapidly developed shortness of breath, cough, and agitation after denatonium benzoate fit testing. She had a history of allergy to shrimp, crab, mite, and disinfecting products (containing quaternary ammonium).

Diagnoses: 

Due to typical symptoms of asthma after exposure to denatonium benzoate aerosol without any other apparent cause, serial pulmonary function tests indicating obstructive lung function and a higher concentration of immunoglobulin antibody E, she was diagnosed with allergic asthma.

Interventions: 

This patient was treated with omalizumab (Xolair), corticosteroid, β2 agonist, montelukast, and Symbicort turbuhaler.

Outcomes: 

The patient showed quick responses after treatment with diphenhydramine (intramuscularly), fenoterol HBr (inhalation), and prednisolone (oral). Approximately 2 weeks later, she suffered from difficulty breathing and asthmatic symptoms again when she was exposed to polished wax and disinfectant. She was treated with omalizumab (Xolair), corticosteroid, β2 agonist, montelukast, and Symbicort turbuhaler. The patient was in stable condition with improvement in symptoms during follow-up.

Lessons: 

There may be potentially important health risks when healthcare workers are exposed to denatonium benzoate. Individuals who have a history of allergy to disinfecting products (containing quaternary ammonium) should avoid exposure of denatonium benzoate. More advanced research is needed in the future.

1 Introduction

Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure.[1] During the coronavirus severe acute respiratory syndrome (SARS) outbreak in Taiwan in 2003,[2] a significant number of the infected subjects were healthcare workers (HCWs) who contracted the SARS infection from their patients. For the prevention of airborne infections, many HCWs in hospitals have been fit tested for respirator use as a part of respiratory protection programs since 2003.[2,3] The main purpose of fit testing is to ensure that the respirator being used by the individual forms a tight enough seal to adequately protect the person from unwanted airborne hazard exposures. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable.[3] Under these circumstances, the health consequences for individuals given denatonium benzoate become an important issue. We report a case that required hospitalization for a severe asthmatic reaction related to denatonium benzoate fit testing.

2 Case report

A 34-year-old female nurse worked at a regional hospital for 3 years before hospitalization with severe asthma. She was healthy prior to the assignment to join the respirator fit testing program at 5 PM on October 13, 2017. She had a history of allergy to shrimp, crab, mite, and disinfecting products (contain quaternary ammonium). Skin rash and itching were noted when she contacted disinfectants (containing quaternary ammonium). She had no family history of asthma. She denied previous major illness or abuse of alcohol and drugs, including over-the-counter medications. She rapidly developed shortness of breath, cough, and agitation after the 1st part of the respirator fit test. Respirator fit testing was performed using the 3M Fit Test Kit FT-31 (3M Canada Company, Ontario, Canada) (denatonium benzoate solution).[4] In the procedure for the respirator fit testing program,[5] the 1st part of the test is to screen the ability of the examinee to detect (taste) aerosolized droplets of a dilute solution of denatonium benzoate; then the examinee wears the respirator for the 2nd part of the test, and a more concentrated solution of the denatonium benzoate is sprayed into the hood while the individual performs a set of actions. The test criterion of the respirator fit test is the failure to taste the denatonium benzoate by the examinee.[4,6]

More

RESEARCH ARTICLE: CLINICAL CASE REPORT

Asthma associated with denatonium benzoate in a healthcare worker in Taiwan

A case report

Chen, Kou-Huang PhDa; Chung, Kuo-Mou MDb,c; Chung, Ju-Hui RNd; Chen, Kow-Tong MD, PhDe,f,*Section Editor(s): NA., Author Information

Medicine: May 2019 - Volume 98 - Issue 21 - p e15818

doi: 10.1097/MD.0000000000015818

OPEN

Metrics

Abstract

Rationale: 

Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable.

Patient concerns: 

A 34-year-old female nurse rapidly developed shortness of breath, cough, and agitation after denatonium benzoate fit testing. She had a history of allergy to shrimp, crab, mite, and disinfecting products (containing quaternary ammonium).

Diagnoses: 

Due to typical symptoms of asthma after exposure to denatonium benzoate aerosol without any other apparent cause, serial pulmonary function tests indicating obstructive lung function and a higher concentration of immunoglobulin antibody E, she was diagnosed with allergic asthma.

Interventions: 

This patient was treated with omalizumab (Xolair), corticosteroid, β2 agonist, montelukast, and Symbicort turbuhaler.

Outcomes: 

The patient showed quick responses after treatment with diphenhydramine (intramuscularly), fenoterol HBr (inhalation), and prednisolone (oral). Approximately 2 weeks later, she suffered from difficulty breathing and asthmatic symptoms again when she was exposed to polished wax and disinfectant. She was treated with omalizumab (Xolair), corticosteroid, β2 agonist, montelukast, and Symbicort turbuhaler. The patient was in stable condition with improvement in symptoms during follow-up.

Lessons: There may be potentially important health risks when healthcare workers are exposed to denatonium benzoate. Individuals who have a history of allergy to disinfecting products (containing quaternary ammonium) should avoid exposure of denatonium benzoate. More advanced research is needed in the future.

1 Introduction

Denatonium benzoate is a useful indicator to ensure that the respirator being used by an individual forms a tight enough seal to adequately protect against unwanted airborne exposure.[1] During the coronavirus severe acute respiratory syndrome (SARS) outbreak in Taiwan in 2003,[2] a significant number of the infected subjects were healthcare workers (HCWs) who contracted the SARS infection from their patients. For the prevention of airborne infections, many HCWs in hospitals have been fit tested for respirator use as a part of respiratory protection programs since 2003.[2,3] The main purpose of fit testing is to ensure that the respirator being used by the individual forms a tight enough seal to adequately protect the person from unwanted airborne hazard exposures. Although the relative risk for adverse effects of fit testing using denatonium benzoate is low, the absolute number of workers with adverse reactions may nevertheless be sizeable.[3] Under these circumstances, the health consequences for individuas given denatonium benzoate become an important issue. We report a case that required hospitalization for a severe asthmatic reaction related to denatonium benzoate fit testing.

2 Case report

A 34-year-old female nurse worked at a regional hospital for 3 years before hospitalization with severe asthma. She was healthy prior to the assignment to join the respirator fit testing program at 5 PM on October 13, 2017. She had a history of allergy to shrimp, crab, mite, and disinfecting products (contain quaternary ammonium). Skin rash and itching were noted when she contacted disinfectants (containing quaternary ammonium). She had no family history of asthma. She denied previous major illness or abuse of alcohol and drugs, including over-the-counter medications. She rapidly developed shortness of breath, cough, and agitation after the 1st part of the respirator fit test. Respirator fit testing was performed using the 3M Fit Test Kit FT-31 (3M Canada Company, Ontario, Canada) (denatonium benzoate solution).[4] In the procedure for the respirator fit testing program,[5] the 1st part of the test is to screen the ability of the examinee to detect (taste) aerosolized droplets of a dilute solution of denatonium benzoate; then the examinee wears the respirator for the 2nd part of the test, and a more concentrated solution of the denatonium benzoate is sprayed into the hood while the individual performs a set of actions. The test criterion of the respirator fit test is the failure to taste the denatonium benzoate by the examinee.[4,6]

((2,6-Xylylcarbamoyl)methyl)diethyl benzyl ammonium benzoate

Ammonium, benzyldiethyl((2,6-xylylcarbamoyl)methyl)-, benzoateDenatonii benzoas

N-(2-((2,6-Dimethylphenyl)amino)-2-oxoethyl)-N,N-diethylbenzeneme- thanaminium benzoate

Denatonium Benzoate 25% in EG

Pharmakon1600-01505987

benzyl-[2-(2,6-dimethylanilino)-2-oxoethyl]-diethylazanium;benzoate

Denatonium benzoate, analytical standard

AC-14888

Ammonium,6-xylylcarbamoyl)methyl]-, benzoate