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Alkaloids in edible lupin seeds A toxicological review and recommendations Kirsten Pilegaard and Jørn Gry TemaNord 2008:605 Alkaloids in edible lupin seeds A toxicological review and recommendations TemaNord 2008:605 © Nordic Council of Ministers, Copenhagen 2008 ISBN 978-92-893-1802-0 Print: Ekspressen Tryk & Kopicenter Cover: www.colourbox.com Copies: 200 Printed on environmentally friendly paper This publication can be ordered on www.norden.org/order. Other Nordic publications are available at www.norden.org/publications Printed in Denmark Nordic Council of Ministers Nordic Council Store Strandstræde 18 Store Strandstræde 18 DK-1255 Copenhagen K DK-1255 Copenhagen K Phone (+45) 3396 0200 Phone (+45) 3396 0400 Fax (+45) 3396 0202 Fax (+45) 3311 1870 www.norden.org Nordic co-operation Nordic cooperation is one of the world’s most extensive forms of regional collaboration, involving Denmark, Finland, Iceland, Norway, Sweden, and three autonomous areas: the Faroe Islands, Green- land, and Åland. Nordic cooperation has firm traditions in politics, the economy, and culture. It plays an important role in European and international collaboration, and aims at creating a strong Nordic community in a strong Europe. Nordic cooperation seeks to safeguard Nordic and regional interests and principles in the global community. Common Nordic values help the region solidify its position as one of the world’s most innovative and competitive. Table of contents Preface................................................................................................................................7 Summary ............................................................................................................................9 Sammendrag..................................................................................................................... 11 1. Introduction .................................................................................................................. 13 2. Chemical characterization ............................................................................................ 19 3. Occurrence.................................................................................................................... 31 3.1 Lupin species........................................................................................................ 31 3.1.1. Edible lupin species............................................................................... 31 3.1.2 Non-edible lupin species ........................................................................ 32 3.2 Alkaloids in lupin species..................................................................................... 33 3.2.1. Lupinus albus (white lupin)................................................................... 33 3.2.2 Lupinus angustifolius (narrow-leaved lupin).......................................... 36 3.2.3 Wild lupin species.................................................................................. 37 3.3 Other constituents in edible lupins ....................................................................... 39 3.3.1 Macronutrients ....................................................................................... 39 3.3.2 Bioactive constituents with putative adverse effects .............................. 40 3.3.3 Mycotoxins............................................................................................. 40 3.3.4 Allergens................................................................................................ 41 4. Exposure....................................................................................................................... 43 4.1 Use of flour .......................................................................................................... 43 4.2 Other uses............................................................................................................. 44 4.3 Debittering of ‘bitter’ lupin seed .......................................................................... 44 4.4 Exposure estimation ............................................................................................. 45 5. Toxicity and feeding studies......................................................................................... 47 5.1 Metabolism........................................................................................................... 47 5.1.1 Lupinus albus and Lupinus angustifolius ............................................... 47 5.1.2 Other lupins............................................................................................ 47 5.2 Acute toxicity studies ........................................................................................... 47 5.3 Subacute/subchronic studies................................................................................. 48 5.4 Chronic/carcinogenicity studies ........................................................................... 52 5.5 Genotoxicity......................................................................................................... 52 5.6 Reproduction/developmental toxicity................................................................... 52 5.7 Feeding studies..................................................................................................... 53 5.7.1 Feeding studies in rats............................................................................ 53 5.7.2 Feeding studies in chickens.................................................................... 56 5.7.3 Feeding studies in sheep and lambs........................................................ 57 5.7.4 Observations in pigs............................................................................... 57 5.8 Summary of toxicity and feeding studies ............................................................. 58 6. Human data................................................................................................................... 61 6.1 Metabolism........................................................................................................... 61 6.2 Acute toxicity ....................................................................................................... 61 6.3 Developmental toxicity ........................................................................................ 62 7. Discussion and conclusions .......................................................................................... 63 8. Recommendations ........................................................................................................ 65 References ........................................................................................................................ 67 Preface The present report was prepared by t he Nordic Pr oject Group on Ris k Assessment of Inherent Natural T oxicants in Food Plants and Mush- rooms. The Project group referred to the Nordic Working Group on Food Toxi- cology and Risk Evaluation (NNT) within Nordic Council of Ministers. Assessment of health risks connect ed with exposure to naturally oc- curring toxicants in foodstuffs has become an important area for NNT in the recent years. A series of Nordic reports based on the work performed by the Nordic Project Group has been published: Gry, J. and Pilegaard, K. (1991) Hydrazines in the Cultivated Mushroom (Agaricus bis- porus). Vår Föda 43;Supplement 1. Uggla, A. and Busk, L. (1992) Ethyl carbamate (urethane) in alcoholic beverages and foodstuffs – a Nordic view. Nordiske Seminar- og Arbejdsrapporter 1992:570. Størmer, F.C., Reistad, R. and Alexander, J. (1993) Adverse health effects of glycyrrhizic acid in licorice. A risk assessment. Nordiske Seminar- og Arbejdsrapporter 1993:526. Andersson, H.C., Slanina, P. and Koponen, A. (1995) Hydrazones in the false morel. TemaNord 1995:561. Søborg, I., Andersson, H.C. and Gry, J. (1996) Furocoumarins in plant food – exposure, biological properties, risk assessment and recommendations. TemaNord 1996:600. Gry, J. and Andersson, H.C. (1998) Nordic seminar on phenylhydrazines in the Cultivated Mushroom (Agaricus bisporus). TemaNord 1998:539. Andersson, H.C. (1999) Glycoalkaloids in tomatoes, eggplants, pepper and two Solanum species growing wild in the Nordic countries. TemaNord 1999:599. Andersson, H.C. (2002) Calystegine alkaloids in Solanaceous food plants. TemaNord 2002:513. Andersson, H.C., Wennström, P. and Gry, J. (2003) Nicotine in Solanaceous food plants. TemaNord 2003:531. Andersson, H.C. and Gry, J. (2004) Phenylhydrazines in the cultivated mushroom (Agari- cus bisporus) – occurrence, biological properties, risk assessment and recommenda- tions. TemaNord 2004:558. Gry, J., Søborg, I. and Andersson, H.C. (2006) Cucurbitacins in plant food. TemaNord 2006: 556. Beckman Sundh, U., Rosén, J. and Andersson, H.C. (2007) Analysis, occurrence and toxicity of ß-methylaminoalanine (BMAA). TemaNord 2007:561. Andersson, H.C., Kristinsson, J. and Gry, J. (2008) Occurrence and use of hallucinogenic mushrooms containing psilocybin alkaloids. TemaNord 2008 (In press). Lupin seeds have no history of use for human consumption in the Nordic countries. In Southern Europe seeds from white lupin (Lupinus albus L.) with high quinolizidine alkaloid content have been eaten as a snack food but only after most of the alkaloids has been re moved. The use of seeds from unsuitable lupus species or cultivars or the use of unprocessed seeds may cause acute intoxicati on in h umans. Low alkaloid containi ng lupin seeds from white