Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2, 3-Dimethoxyphenyl)-1H-1, 2, 4-triazol-5-yl)thio)methyl)pyridine. (2016)

• Record Type: Journal Article
• Authors: Karanewsky, Donald S.; Arthur, Amy J.; Liu, Hanghui; Chi, Bert; Ida, Lily; Markison, Stacy
• Is Part Of: Toxicology reports. Volume 3(2016)
• Page Start: 501
• Page End: 512
• Publication Date: 2016
• Subjects: amu atomic mass unit -- AUC area under the curve -- CL plasma clearance -- Cmax peak plasma concentration -- CYP cytochrome P450 -- FDA Food and Drug Administration -- FEMA Flavour and Extract Manufacturers Association of the United States -- FL-no FLAVIS number -- GLP Good Laboratory Practices -- GMP Good Manufacturing Practices -- GPCR G-protein-coupled receptor -- GRAS generally recognized as safe -- HPBL human peripheral blood lymphocytes -- LC/MS liquid chromatography with mass spectrometry -- MC methylcellulose -- MSG monosodium glutamate -- NOAEL no-observed-adverse-effect-level -- NOEL no-observed-effect-level -- OECD Organization for Economic Cooperation and Development -- PK pharmacokinetics -- RCG Relative Cell Growth -- RMI Relative Mitotic Index -- t1/2 half-life -- Tmax time to reach Cmax -- TK toxicokinetics -- Vss volume of distribution at steady-state; Umami flavour -- S3643 -- FEMA GRAS -- Subchronic toxicological evaluation -- Genetic toxicological evaluation; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2016.05.002
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: 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-WBL 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.