Scientific Opinion on Flavouring Group Evaluation 86, Revision 2 (FGE.86Rev2): Consideration of aliphatic and arylalkyl amines and amides evaluated by JECFA (65th meeting)

Abstract

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 30 aliphatic and arylalkyl amines and amides evaluated by JECFA at the 65 th meeting in 2005. This revision is required owing to additional available toxicity data on piperine .003] and deca-(2E,4E)-dienoic acid isobutyl-amide .091]. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological thresholds of concern and available data on metabolism and toxicity. The Panel agrees with JECFA's conclusion "No safety concern at estimated levels of intake as flavouring substances" based on the Maximised Survey-derived Daily Intake (MSDI) approach for all substances considered in this FGE. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered and for all 30 substances, the information is adequate. The previous version of this consideration, FGE.86Rev1, dealt with 34 aliphatic and arylalkyl amines and amides which are in the Register and which were evaluated by JECFA at its 65 th meeting. The Panel concluded that no structurally related substances to support the evaluation in a corresponding Flavouring Group Evaluation (FGE) was available. © European FoodSince the publication of FGE.86Rev1, the Industry has informed that four of the substances, 16.049, 16.093 and 16.094], are no longer used as flavouring substances in Europe and will therefore not be further considered in this FGE. The present consideration therefore only deals with 30 flavouring substances.In FGE.86Rev1, the Panel agreed with the application of the Procedure as performed by JECFA for 27 of the 30 substances. For two substances, piperine .003] and deca-(2E,4E)-dienoic acid isobutyl-amide .091], the Panel did not agree with JECFA that appropriate studies are available for deriving NOAELs and concluded that additional toxicity data are required for these two substances.The present revision of FGE.86Rev1 is due to the submission of the requested toxicity data for [FLno: 14.003 and 16.091]. Based on the results of two 90-day oral toxicity studies received by EFSA the Panel now concludes that these two substances are not of safety concern when used as flavouring substances at the estimated levels of exposure based on the MSDI approach.For N-isopentylidene isopentylamine .017] the Panel concluded that this substance can be metabolised to innocuous products and accordingly evaluated along the A-side of the Procedure (while JECFA evaluated .017] along the B-side). Like JECFA the Panel concluded that ] is of no safety concern at estimated level of intake, ba...

Safety Aspects of the Use of Isolated Piperine Ingested as a Bolus

“…In its assessment of isolated piperine and several aliphatic and arylalkyl amines and amides as flavouring agents, the European Food Safety Authority EFSA (2015) reported an estimated European per capita intake of 6.2 µg piperine/day for the use of isolated piperine as a flavouring substance based on the EU Maximised Survey-derived Daily Intake (MSDI) method (see also below). However, EFSA noted in this assessment that the use levels were needed for some of the abovementioned flavouring substances, including piperine, to calculate the Modified Theoretical Added Maximum Daily Intakes (mTAMDIs) in order to identify those flavouring substances that required a more refined exposure assessment and to finalise the evaluation [32].…”

“…In its evaluations, EFSA (2008;2011;2015) disagreed with a No Observed Effect Level (NOEL) of 20 mg piperine/kg bw/day that had previously been identified by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (2006), due to the shortcomings of the underlying animal study (lack of histopathology, study duration) and in 2015 identified a No Observed Adverse Effect Level (NOAEL) of 5 mg piperine/kg bw/day, based on a newly available 90-day rat feeding study performed according to OECD guideline 408 (endpoint: dose-dependent increase in cholesterol level in male animals) [29,32,[48][49][50] (see (2) in Section 4.2.2). In its final conclusion, EFSA (2015) agreed with the JECFA (2006) conclusion "no safety concern at estimated levels of intake as flavouring substance" based on the MSDI approach (estimated European per capita intake by the MSDI approach: 6.2 µg piperine/day) [32,50]. Currently, isolated piperine is approved as a flavouring agent in the European Union with no restrictions on use or maximum levels set in regulation (EC) No.…”

Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

“…Recently, the European Food Safety Authority (EFSA) identified the NOAEL of piperine, which is 5 mg/kg b.w. per day based on the most comprehensive study available (90-day dietary toxicity study in rats) [147].…”

“…Although the dietary consumption of black pepper varies considerably within the population, EFSA calculated that the estimated exposure to piperine from natural sources when consuming black pepper as a flavoring ingredient is 6.2 µg/day in Europe and 0.07 µg/day in the USA, based on the maximized survey-derived daily intake [147], which are below the TTC threshold level of 1.5 µg/kg b.w./day (90 µg/day) for Cramer Class III compounds.…”

Piperine: Old Spice and New Nutraceutical?

“…Based on these data, and the fact that piperine is more irritant rather than toxic, its intake from regular food raised no safety concern. No observed adverse effect level (NOAEL) of piperine is 5 mg/kg daily [56].…”