The JFFMA assessment of flavoring substances structurally related to menthol and uniquely used in Japan

Abstract

Using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), we performed safety evaluations on four flavoring substances structurally related to menthol (L-menthyl 2-methylbutyrate, DL-menthyl octanoate, DL-menthyl palmitate, and DL-menthyl stearate) uniquely used in Japan. While no genotoxicity study data were available in the literature, all four substances had no chemical structural alerts predictive of genotoxicity. Moreover, they all four are esters consisting of menthol and simple carboxylic acids that were assumed to be immediately hydrolyzed after ingestion and metabolized into innocuous substances for excretion. As menthol and carboxylic acids have no known genotoxicity, it was judged that the JECFA procedure could be applied to these four substances. According to Cramer's classification, these substances were categorized as class I based on their chemical structures. The estimated daily intakes for all four substances were within the range of 1.54-4.71 μg/person/day and 60-1250 μg/person/day, using the methods of Maximized Survey-Derived Intake and Single Portion Exposure Technique, respectively, based on the annual usage data of 2001, 2005, and 2010 in Japan. As the daily intakes of these substances were below the threshold of concern applied to class I substances viz., 1800 μg/person/day, it was concluded that all four substances raise no safety concerns when used for flavoring foods under the currently estimated intake levels.

Keywords: ADI; Cramer’s decision tree; EFSA; European Food Safety Authority; FEMA; Flavor and Extract Manufacturers Association; JASREC; JECFA; JFFMA; Japan Flavor and Fragrance Materials Association; Japanese unique flavoring substances; Joint FAO/WHO Expert Committee on Food Additives; Joint FAO/WHO Expert Committee on Food Additives (JECFA); MSDI; Maximized Survey-Derived Intake; Menthol; NOEL; SAR; SPET; Safety concerns; Single Portion Exposure Technique; Structure Activity Relationship analyses; The JFFMA Safety Re-evaluation Committee; WHO; World Health Organization; acceptable daily intake; no observed effect level.