VKM Report 2016: 31 Risk assessment of "other substances" – Piperine Opinion of the Panel Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety Report from the Norwegian Scientific Committee for Food Safety (VKM) 2016: 31 Risk assessment of other substances – Piperine Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety 27.06.2016 ISBN: 978-82-8259-221-5 Norwegian Scientific Committee for Food Safety (VKM) Po 4404 Nydalen N – 0403 Oslo Norway Phone: +47 21 62 28 00 Email: [email protected] www.vkm.no www.english.vkm.no Cover photo: iStock Photo Suggested citation: VKM. (2016) Risk assessment of "other substances" – Piperine. Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety, ISBN: 978-82-8259- 221-5, Oslo, Norway. VKM Report 2016: 31 Risk assessment of "other substances" – Piperine Authors preparing the draft opinion Jens Rohloff Assessed and approved The opinion has been assessed and approved by Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics. Members of the panel are: Inger-Lise Steffensen (Chair), Ellen Bruzell, Berit Granum, Ragna Bogen Hetland, Trine Husøy, Jens Rohloff, Trude Wicklund. (Panel members in alphabetical order after chair of the panel) Acknowledgment The Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics has answered the request from the Norwegian Food Safety Authority. Project leader from the VKM secretariat has been Gro Haarklou Mathisen. Jens Rohloff is acknowledged for his valuable work on this opinion. Jan Alexander (the Scientific Steering Committee), Åshild Krogdahl (the Scientific Steering Committee) and Helle Margrete Meltzer (former member of Panel on Nutrition, Dietetic Products, Novel Food and Allergy) constituted a reference group and are acknowledged for their valuable comments and suggestions on this opinion. Competence of VKM experts Persons working for VKM, either as appointed members of the Committee or as external experts, do this by virtue of their scientific expertise, not as representatives for their employers or third party interests. The Civil Services Act instructions on legal competence apply for all work prepared by VKM. VKM Report 2016: 31 Table of Contents Summary ................................................................................................................ 6 Sammendrag på norsk ........................................................................................... 8 Abbreviations and glossary .................................................................................. 10 Background as provided by the Norwegian Food Safety Authority ...................... 11 Terms of reference as provided by the Norwegian Food Safety Authority ........... 12 Assessment .......................................................................................................... 13 1 Introduction ................................................................................................. 13 2 Hazard identification and characterisation .................................................. 15 2.1 Literature ............................................................................................................ 15 2.1.1 Previous risk assessments .......................................................................... 15 2.1.2 Summary of previous risk assessments ....................................................... 17 2.1.3 Literature search ....................................................................................... 17 2.1.3.1 Search strategy ...................................................................................... 17 2.1.3.2 Publication selection ............................................................................... 17 2.2 General information ............................................................................................. 19 2.2.1 Chemistry ................................................................................................. 19 2.2.2 Occurrence ............................................................................................... 19 2.3 Absorption, distribution, metabolism and excretion (ADME) ..................................... 20 2.3.1 In humans ................................................................................................ 20 2.3.2 Animal studies .......................................................................................... 20 2.4 Toxicological data/Adverse effects ......................................................................... 20 2.4.1 Human studies .......................................................................................... 20 2.4.1.1 Interactions ........................................................................................... 21 2.4.1.2 Allergic sensitisation (including adjuvant effects) ....................................... 22 2.4.2 Animal studies .......................................................................................... 22 2.4.2.1 Genotoxicity in vivo ................................................................................ 28 2.4.2.2 Interactions ........................................................................................... 29 2.4.2.3 Allergic sensitisation (including adjuvant effects) ....................................... 29 2.4.3 In vitro studies .......................................................................................... 30 2.4.3.1 Genotoxicity in vitro ................................................................................ 30 2.4.3.2 Interactions ........................................................................................... 30 2.4.4 Vulnerable groups ..................................................................................... 30 VKM Report 2016: 31 2.5 Summary of hazard identification and characterisation ............................................ 30 3 Exposure / Intake ........................................................................................ 32 3.1 Food supplements ................................................................................................ 32 3.2 Other sources ...................................................................................................... 32 4 Risk characterisation.................................................................................... 33 4.1 Food supplements ................................................................................................ 33 5 Uncertainties ................................................................................................ 34 5.1 Hazard identification and characterisation .............................................................. 34 6 Conclusions with answers to the terms of reference ................................... 35 7 Data gaps ..................................................................................................... 37 8 References ................................................................................................... 38 9 Appendix ...................................................................................................... 43 VKM Report 2016: 31 Summary The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet, NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements and other foods. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances", VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of piperine, and it is based on previous risk assessments and articles retrieved from a literature search. According to information from NFSA, piperine, derived from black pepper, is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of the dose 1.5 mg/day of piperine in food supplements. The total exposure to piperine from other sources than food supplements, such as foods or cosmetics, is not included in the risk assessment. Piperine ((E,E)-piperine) is a naturally occurring alkaloid which is the major pungent compound found in spices like black pepper (Piper nigrum L.) and long pepper (Piper longum L.), but it also occurs in Grains of Paradise (Aframomum melegueta K. Schum.). (E,E)- piperine is the isomeric form which is used in food supplements. Several isomers structurally related to (E,E)-piperine are found in pepper with less hot taste, including isopiperine, chavicine and isochavicine. In the European/Western cuisine, black pepper is the major source of piperine in the human diet. Other sources in the diet are piperine (pepper)- flavoured finished food