Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2,3-Dimethoxyphenyl)-1H-1,2,4-triazol-5-yl)thio)methyl)pyridine

• Published in: Toxicology reports Vol. 3; pp. 501 - 512
• Main Authors: Karanewsky, Donald S, Arthur, Amy J, Liu, Hanghui, Chi, Bert, Ida, Lily, Markison, Stacy
• Format: Journal Article
• Language: English
• Published: Elsevier 01.01.2016
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2016.05.002

A toxicological evaluation of a umami flavour compound, 2-(((3-(2,3-dimethoxyphenyl)-1 H -1,2,4-triazol-5-yl)thio)methyl)pyridine (S3643; CAS 902136-79-2), was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism in vitro with rat microsomes producing the S3643-sulfoxide and 4′-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the O -demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites. In pharmacokinetic studies in rats, the S3643-sulfoxide represents the dominant biotransformation product. S3643 was not found to be mutagenic or clastogenic in vitro , and did not induce micronuclei in CHO-WB L cells. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL) for S3643 was 100 mg/kg bw/day (highest dose tested) when administered in the diet for 90 consecutive days.