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Scientific Opinion SCIENTIFIC OPINION ADOPTED: DD Month YEAR doi:10.2903/j.efsa.20YY.NNNN 1 Evaluation of the health risks related to the 2 presence of cyanogenic glycosides in foods other than raw 3 apricot kernels 4 5 EFSA Panel on Contaminants in the Food Chain (CONTAM), 6 Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl- 7 Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Carlo 8 Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Dieter 9 Schrenk, Christiane Vleminckx, Heather Wallace, Diane Benford, Leon Brimer, Francesca 10 Romana Mancini, Manfred Metzler, Barbara Viviani, Andrea Altieri, Davide Arcella, Hans 11 Steinkellner and Tanja Schwerdtle 12 Abstract 13 In 2016, the EFSA CONTAM Panel published a scientific opinion on the acute health risks related to 14 the presence of cyanogenic glycosides (CNGs) in raw apricot kernels in which an acute reference dose 15 (ARfD) of 20 µg/kg bw was established for cyanide (CN). In the present opinion, the CONTAM Panel 16 concluded that this ARfD is applicable for acute effects of CN regardless the dietary source. Estimated 17 mean acute dietary exposures to cyanide from foods containing CNGs did not exceed the ARfD in any 18 age group. At the 95th percentile, the ARfD was exceeded up to about 2.5-fold in some surveys for 19 children and adolescent age groups. The main contributors to exposures were biscuits, juice or nectar 20 and pastries and cakes that could potentially contain CNGs. Taking into account the conservatism in 21 the exposure assessment and in derivation of the ARfD, it is unlikely that this estimated exceedance 22 would result in adverse effects. The evidence from animal and human studies does not allow the 23 derivation of a chronic health based guidance value (HBGV) for cyanide and thus chronic risks could 24 not be assessed. 25 © 20YY European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on 26 behalf of European Food Safety Authority. 27 28 Keywords: cyanide, cyanogenic glycosides, health based guidance values, risk assessment 29 30 Requestor: European Commission 31 Question number: EFSA-Q-2016-00802 32 Correspondence: [email protected] Cyanogenic glycosides in food 33 Panel members: Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina 34 Grasl-Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Carlo Stefano 35 Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Dieter Schrenk, Tanja 36 Schwerdtle, Christiane Vleminckx and Heather Wallace. 37 Minority opinion: In case of a minority opinion, please add: [Part of this/This] scientific output is 38 not shared by the following member(s) of the Panel: [add names in the format Name Surname, Name 39 Surname and Name Surname]. 40 Competing interests: In case of identified conflict(s) of interest, please add: In line with EFSA’s 41 policy on declarations of interest, Panel member(s) [add names in the format Name Surname, Name 42 Surname and Name Surname] did not participate in the development and adoption of this scientific 43 output. 44 Acknowledgements: The Panel wishes to thank the hearing expert Klaus Abraham for the support 45 provided to this scientific output. 46 Suggested citation: EFSA Panel on Contaminants in the Food Chain (CONTAM), Bignami M, Bodin L, 47 Chipman JK, del Mazo J, Grasl-Kraupp B, Hogstrand C, Hoogenboom LR, Leblanc J-C, Nebbia CS, 48 Nielsen E, Ntzani E, Petersen A, Sand S, Schrenk D, Vleminckx C, Wallace H, Benford D, Brimer L, 49 Mancini FR, Metzler M, Viviani B, Altieri A, Arcella D, Steinkellner S and Schwerdtle T, 20YY. Scientific 50 opinion on the evaluation of the health risks related to the presence of cyanogenic glycosides in foods 51 other than raw apricot kernels. EFSA Journal 20YY;volume(issue):NNNN, 89 pp. 52 doi:10.2903/j.efsa.20YY.NNNN 53 ISSN: 1831-4732 54 © 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on 55 behalf of European Food Safety Authority. 56 This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, 57 which permits use and distribution in any medium, provided the original work is properly cited and no 58 modifications or adaptations are made. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. 59 Cyanogenic glycosides in food 60 Summary 61 Following a request from the European Commission (EC), the EFSA Panel on Contaminants in the 62 Food Chain (CONTAM Panel) evaluated the risks to human health related to the presence of 63 cyanogenic glycosides (CNGs) in foods other than raw apricot kernels. Previous assessments from the 64 European Food Safety Authority (EFSA), in particular the opinion on acute health risks related to the 65 presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot 66 kernels (2016), and assessments from other international and national scientific bodies, have been 67 used as a starting point for the evaluation together with publications identified in a targeted literature 68 search. EFSA guidance documents and general principles for risk assessment have been applied for 69 hazard and exposure assessment in this opinion. 70 CNGs contain chemically bound cyanide and are present in foods such as almonds, linseed, or 71 cassava. When the plant cells are damaged, by for example grinding or chewing, CNGs and their 72 degrading enzymes are brought into contact and cyanide is released. Cyanide is readily absorbed from 73 the gastrointestinal tract and rapidly distributed to all organs. Peak concentrations of cyanide in blood 74 and tissue depend on the amount of CNGs in the food consumed and the rate of release of cyanide 75 which in turn depends on the presence and activity of the degrading enzymes. Peak blood cyanide 76 concentration can be used as a reliable biomarker for acute cyanide exposure. In a human 77 bioavailability study, mean peak concentrations of cyanide in blood were different after consumption 78 cassava root, linseed and persipan, indicating a fast and practically complete release of cyanide after 79 chewing of bitter almonds and cassava roots but not with linseed and persipan. 80 In experimental animals, acute toxicity of cyanide and CNGs is characterised by dyspnea, ataxia, 81 arrhythmia, convulsions, loss of consciousness, decreased respiration and death. Upon repeated dose 82 exposure to cyanide, histopathological alterations in the thyroid, kidney, liver and CNS, and changes in 83 epididymis cauda weights, sometimes paralleled with clinical signs have been reported, but the 84 findings are not consistent between different studies. With the CNGs linamarin and amygdalin, 85 alterations in haematology and clinical chemistry parameters and histopathological alterations were 86 seen. With gari (a cassava product for direct human consumption) and cassava, behavioural changes 87 have been observed. There are indications of developmental effects in hamsters exposed to CNGs or 88 cassava and in rats exposed to potassium cyanide (KCN), which were often observed in the presence 89 of maternal toxicity. Cyanide is not genotoxic. No information is available on the genotoxicity of CNGs. 90 The acute lethal oral dose of cyanide in humans is reported to be between 0.5 and 3.5 mg/kg body 91 weight (bw). The toxic threshold value for cyanide in blood is considered to be between 0.5 (ca. 20 92 µM) and 1.0 mg/L (ca. 40 µM), the lethal threshold value ranges between 2.5 (ca. 100 µM) and 3.0 93 mg/L (ca. 120 µM). Signs of acute cyanide poisoning in humans include headache, vertigo, agitation, 94 respiratory depression, metabolic acidosis, confusion, coma, convulsions, and death. Poisoning cases, 95 some fatal, have resulted from ingestion of amygdalin preparations, bitter almonds and cassava. 96 Several neurological disorders and other diseases have been associated with chronic exposure to 97 cyanide in populations where cassava constitutes the main source of calories. 98 The primary mode of action for acute toxicity of cyanide is the inhibition of oxidative phosphorylation 99 leading to anaerobic energy production. Due to the high oxygen and energy demand, brain and heart 100 are particularly sensitive to cyanide which can result in hypoxia, metabolic acidosis and impairment of 101 vital functions. The role of cyanide in neurological impairment upon long-term consumption of foods 102 containing CNGs has not been elucidated. 103 The CONTAM Panel concluded that there are no data indicating that the acute reference dose (ARfD) 104 for cyanide of 20 µg/kg bw, established in 2016, should be revised and that it is applicable for acute 105 effects of cyanide regardless of the dietary source. For foods other than raw apricot kernels, bitter 106 almonds and cassava roots, this ARfD is likely to be over-conservative but establishment of different 107 ARfDs for different types of food is not appropriate. The evidence from animal and human studies 108 does not allow the derivation of a chronic health-based guidance value (HBGV) for cyanide (CN). 109 A total of 2,586 analytical results on total cyanide in foods were available in the EFSA database (of 110 which about 89% came from Germany and of which 46% were left-censored) to estimate acute and 111 chronic dietary exposure. Highest occurrence values were reported in bitter almonds (mean www.efsa.europa.eu/efsajournal 3 EFSA Journal 20YY;volume(issue):NNNN Cyanogenic glycosides in food 112 concentration 1,437 mg/kg) and in linseed (mean concentration 192.1 mg/kg). No occurrence data 113 were available in the database for cassava and products derived thereof. 114 To account for differences in cyanide bioavailability after ingestion of certain food items, for cassava 115 and cassava derived products and for almonds a factor of 1, for linseed a factor of 3 and for 116 marzipan/persipan a factor of 12 was calculated based on results from a human bioavailability study.
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