Denatonium Benzoate

Basic Information

Name: Denatonium Benzoate

CAS No: Benzyldiethyl[(2,6-xylylcarbamolyl)methyl]ammonium benzoate anhydrous [3734-33-6], Benzyldiethyl[(2,6-xylylcarbamolyl)methyl]ammonium benzoate monohydrate [86398-53-0]

Functional Categories

Alcohol denaturant Flavoring agent

1. Nonproprietary Names

USP-NF: Denatonium Benzoate

2. Synonyms

Bitrex; Bitterguard; N-[2-(2,6-dimethylphenyl)amino]-2-oxoethyl]- N,N-diethylbenzenemethanaminium benzoate monohydrate; lignocaine benzyl benzoate.

3. Chemical Name & CAS Registry

Benzyldiethyl[(2,6-xylylcarbamolyl)methyl]ammonium benzoate anhydrous [3734-33-6], Benzyldiethyl[(2,6-xylylcarbamolyl)methyl]ammonium benzoate monohydrate [86398-53-0]

4. Empirical Formula & Molecular Weight

C28H34N2O3 446.59 (for anhydrous) C28H34N2O3H2O 464.60 (for monohydrate)

5. Structural Formula

6. Applications

Denatonium benzoate is among the most bitter of substances known and is detectable at concentrations of approximately 10 ppb. In pharmaceutical and other industrial applications it is added to some products as a deterrent to accidental ingestion.(1–4) It is most commonly used at levels of 5–500 ppm. Denatonium benzoate may also be used to replace brucine or quassin as a denaturant for ethanol. In pharmaceutical formulations, denatonium benzoate has been used as a flavoring agent in placebo tablets, and in a topical formulation it has been used in an anti-nailbiting preparation.(5)

7. Description

Denatonium benzoate occurs as an odorless, very bitter tasting, white crystalline powder or granules.

8. Pharmacopeial Specifications

See Table I.

9. Typical Properties

Density (bulk) 0.3–0.6 g/cm3 Density (tapped) 0.4–0.7 g/cm3 Solubility Very soluble in chloroform, and methanol; soluble in ethanol (95%), and water; sparingly soluble in acetone; practically insoluble in ether.

10. Stability & Storage

Denatonium benzoate is stable up to 1408C and over a wide pH range. It should be stored in a well-closed container (such as polythene-lined steel) in a cool, dry place. Aqueous or alcoholic solutions retain their bitterness for several years even when exposed to light.

11. Incompatibilities

Denatonium benzoate is incompatible with strong oxidizing agents.

12. Method of Manufacture

Denatonium benzoate was first synthesized in the 1950s and is usually prepared by reacting denatonium chloride with benzyl benzoate.

13. Safety

Denatonium benzoate is generally regarded as a nonirritant and nonmutagenic substance. However, there has been a single report of contact urticaria attributed to denatonium benzoate occurring in a 30-year-old man who developed asthma and pruritus after using an insecticidal spray denatured with denatonium benzoate.(6) LD50 (rabbit, oral): 0.508 g/kg(7) LD50 (rat, oral): 0.584 g/kg

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Containers should be kept tightly closed and handled in areas with good ventilation. Eye protection, gloves, and a dust mask are recommended. Denatonium benzoate is moderately toxic by ingestion and when heated to decomposition emits toxic vapors of NOx. Denatonium benzoate may also cause hypersensitization.

15. Regulatory Status

Denatonium benzoate is used worldwide as a denaturant for alcohol. It is included in the FDA Inactive Ingredients Database (topical gel and solution).

16. Related Substances

17. Comments

Several HPLC methods of analysis for denatonium benzoate have been reported.(8–10) The EINECS number for denatonium benzoate is 223-095-2. The PubChem Compound ID (CID) for denatonium benzoate is 19518.