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Regul Toxicol Pharmacol

Title:		"Safety assessment of 2-ethyl-3,(5 or 6) dimethylpyrazine as a food ingredient"
Author(s):		Burdock GA; Carabin IG;
Address:		"Burdock Group, 801 North Orange Ave Suite 710, Orlando, FL 32801, USA. gburdock@burdockgroup.com"
Journal Title:		Regul Toxicol Pharmacol
Year:		2008
Volume:		20080116
Issue:		3
Page Number:		303 - 312
DOI:		10.1016/j.yrtph.2007.12.007
ISSN/ISBN:		0273-2300 (Print) 0273-2300 (Linking)
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"
Keywords:		"Animals Carcinogenicity Tests Eating Female Flavoring Agents/*toxicity Food Industry History, 20th Century Humans Legislation, Food/history Mutagenicity Tests Pheromones/chemistry/pharmacokinetics/*toxicity Pregnancy Pyrazines/chemistry/pharmacokinetics/*;"
Notes:		"MedlineBurdock, George A Carabin, Ioana G eng Historical Article Research Support, Non-U.S. Gov't Netherlands 2008/02/29 Regul Toxicol Pharmacol. 2008 Apr; 50(3):303-12. doi: 10.1016/j.yrtph.2007.12.007. Epub 2008 Jan 16"