GRASr2 Evaluation of Aliphatic Acyclic and Alicyclic Terpenoid Tertiary Alcohols and Structurally Related Substances Used as Flavoring Ingredients

Abstract

This publication is the 1st in a series of publications by the Expert Panel of the Flavor and Extract Manufacturers Assoc. summarizing the Panel's 3rd re-evaluation of Generally Recognized as Safe (GRAS) status referred to as the GRASr2 program. In 2011, the Panel initiated a comprehensive program to re-evaluate the safety of more than 2700 flavor ingredients that have previously met the criteria for GRAS status under conditions of intended use as flavor ingredients. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics, and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances as flavoring ingredients are evaluated. The group of aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances was reaffirmed as GRAS (GRASr2) based, in part, on their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic studies and the lack of significant genotoxic and mutagenic potential.

Production, Properties, and Applications of α-Terpineol

“…In 2011, a panel of experts from the Flavor and Extract Manufacturers Association (FEMA) initiated the safety reassessment of 2700 flavor ingredients so far labeled as "generally recognized as safe" (GRAS). The study supported the conclusion that consumption of αterpineol as part of the food supply is not associated with any significant risk to human health (Marnett et al 2014). Moreover, according to the Joint FAO/WHO Expert Committee on Food Additives (JECFA), α-terpineol intake…”

“…Furthermore, new α-terpineol derivatives could be produced (by condensation with different anhydrides or acyl chlorides; condensation with bromoacetyl bromide, followed by nucleophilic substitution at the αposition of the ester carbonyl functionality of the intermediate Not associated with any significant risk to human health. Marnett et al (2014) No safety concern at current levels of intake when used as a flavoring agent. JECFA (1998) Volume of dermal systemic exposure: 0.07 mg kg −1 day −1 ; maximum daily use level 5.7% of skin surface.…”

FEMA GRAS assessment of natural flavor complexes: Origanum oil, thyme oil and related phenol derivative-containing flavoring ingredients

“…The use of metabolic data in the safety evaluation of flavoring compounds and a summary of the expected metabolism of flavoring compounds by congeneric group is described in a FEMA Expert Panel publication (Smith et al, 2018). In addition, the Panel has also published evaluations of metabolic data for Group 19 (Aliphatic and aromatic hydrocarbons), Group 12 (Aliphatic and aromatic tertiary alcohols and related esters constituents) and Group 10 (Alicyclic ketones, secondary alcohols and related esters flavoring compounds (Adams et al, 1996;Adams et al, 2011;Marnett et al, 2014) and assessments of other groups or individual constituents (Adams et al, 2004;Adams et al, 2005a, b, c;Adams et al, 2002;Adams et al, 1997;Adams et al, 2008;Adams et al, 1998;Adams et al, 2007;Newberne et al, 1999;Smith et al, 2002).…”

The safety evaluation of food flavoring substances: the role of genotoxicity studies

“…The following section examines the genotoxicity data and determinations available for flavorings as published by the FEMA Expert Panel (Adams et al 1996(Adams et al , 1997(Adams et al , 1998Newberne et al 1999;Smith et al 2002;Adams et al 2004Adams et al , 2005aAdams et al , 2005bAdams et al , 2005cAdams et al , 2007Adams et al , 2008Adams et al , 2011Marnett et al 2014;Cohen et al 2017a;Cohen et al 2019) or by JECFA in a series of published monographs as referenced previously (Food Additive Series No. 40-73).…”