title: Safety assessment of 2-ethyl-3,(5 or 6) dimethylpyrazine as a food ingredient.
abstract: 2-Ethyl-3,(5 or 6)-dimethylpyrazine (CAS No. 27043-05-6), a heterocyclic, nitrogen-containing compound, is used in the food industry as a flavor ingredient for its characteristic roasted odor and flavor, reminiscent of roasted cocoa or nuts. Pyrazines, including 2-ethyl-3,(5 or 6)-dimethylpyrazine, are widely distributed in foods and because of their natural unavoidable occurrence in cooked food; therefore, pyrazine compounds, including 2-ethyl-3,(5 or 6)-dimethylpyrazine, are commonly consumed in the daily diet. 2-Ethyl-3,(5 or 6)-dimethylpyrazine is oxidized in rats almost exclusively via its aliphatic side-chain to carboxylic acid derivatives. The LD(50) of 2-ethyl-3,(5 or 6)-dimethylpyrazine in rats was reported as 460 mg/kg and it is reported to be irritating to the skin, eyes and the upper respiratory tract. Two 90-day rat feeding studies have been conducted on 2-ethyl-3,(5 or 6)-dimethylpyrazine, with the one reporting a no effect level of 12.5mg/kg/day (both sexes) and a second study reporting a NOAEL of 2-ethyl-3,(5 or 6)-dimethylpyrazine 17 and 18 mg/kg/day for male and female rats, respectively. Although no genotoxicity studies were found on 2-ethyl-3,(5 or 6)-dimethylpyrazine, structurally similar pyrazine derivatives were reported as clastogenic in mammalian cells and non-mutagenic in bacterial assays. The relevance of the positive results in assays with Saccharomyces cerevisiae and Chinese hamster ovary cells in vitro is unclear. The data and information available, including a prolonged history of safe use, indicate that at the current level of intake, the food flavoring use of 2-ethyl-3,(5 or 6)-dimethylpyrazine is safe.
authors.affiliation: Burdock Group, 801 North Orange Ave Suite 710, Orlando, FL 32801, USA. gburdock@burdockgroup.com
authors.forename: George A
authors.initials: GA
authors.lastname: Burdock
authors.forename: Ioana G
authors.initials: IG
authors.lastname: Carabin
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D004435:Eating; D005260:Female; D005421:Flavoring Agents / Q000633:toxicity*; D019649:Food Industry; D049673:History, 20th Century; D006801:Humans; D007881:Legislation, Food / Q000266:history; D009152:Mutagenicity Tests; D010675:Pheromones / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011719:Pyrazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity
chemical_list: D005421:Flavoring Agents; D010675:Pheromones; D011719:Pyrazines; D013723:Teratogens; C504321:2-ethyl-3,6-dimethylpyrazine; C522035:2-ethyl-3,5-dimethylpyrazine