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Agaricus Bisporus) Phenylhydrazines in the Cultivated Mushroom (Agaricus bisporus) - occurrence, biological properties, risk assessment and recommendations Phenylhydrazines in the Cultivated Mushroom (Agaricus bisporus) - occurrence, biological properties, risk assessment and recommendations By Andersson, H.C. and Gry, J. TemaNord 2004:558 Phenylhydraz ines in the Cultivated Mushroom (Agaricus bisporus) - occurrence, biological properties, risk assessment and recommendations TemaNord 2004:558 © Nordic Council of Ministers, Copenhagen 2004 ISBN 92-893-1080-4 ISSN 0908-6692 Print: Ekspressen Tryk & Kopicenter Copies: 300 Printed on paper approved by the Nordic Environmental Labelling. This publication may be purchased from any of the sales agents listed on the last page. 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 The Nordic Food Policy Co-operation The Nordic Committee of Senior Officials for Food Issues is concerned with basic Food Policy issues relating to food and nutrition, food toxicology and food microbiology, risk evaluation, food control and food legislation. The co-operation aims at protection of the health of the consumer, common utilisation of professional and administrative resources and at Nordic and international developments in this field. The Nordic Council of Ministers was established in 1971. It submits proposals on co-operation between the governments of the five Nordic countries to the Nordic Council, implements the Council's recommendations and reports on results, while directing the work carried out in the targeted areas. The Prime Ministers of the five Nordic countries assume overall responsibility for the co-operation measures, which are co-ordinated by the ministers for co-operation and the Nordic Co-operation committee. The composition of the Council of Ministers varies, depending on the nature of the issue to be treated. The Nordic Council was formed in 1952 to promote co-operation between the parliaments and governments of Denmark, Iceland, Norway and Sweden. Finland joined in 1955. At the sessions held by the Council, representatives from the Faroe Islands and Greenland form part of the Danish delegation, while Åland is represented on the Finnish delegation. The Council consists of 87 elected members - all of whom are members of parliament. The Nordic Council takes initiatives, acts in a consultative capacity and monitors co-operation measures. The Council operates via its institutions: the Plenary Assembly, the Presidium and standing committees. Table of contents Table of contents...............................................................................................................5 Preface............................................................................................................................... 7 1. Sammanfattning............................................................................................................ 9 1. Summary .................................................................................................................... 13 2. Introduction ................................................................................................................ 17 3. Identity, physical and chemical properties, and analytical methods.......................... 19 3.1. Identity .............................................................................................................. 19 3.2. Physical and chemical properties...................................................................... 21 3.3. Chemical synthesis............................................................................................ 26 3.4. Analytical methods ........................................................................................... 26 4. Biosynthesis ............................................................................................................... 27 5. Occurrence.................................................................................................................. 31 5.1. The content of agaritine and related compounds in fresh mushrooms ............ 31 5.2. Influence of storage and processing.................................................................. 36 5.2.1. Refrigerating ........................................................................................... 36 5.2.2. Freezing and thawing.............................................................................. 39 5.2.3. Freeze-drying. ......................................................................................... 39 5.2.4. Drying. .................................................................................................... 41 5.2.5. Dry baking. ............................................................................................. 41 5.2.6. Boiling..................................................................................................... 41 5.2.7. Canning................................................................................................... 42 5.2.8. Pan-frying ............................................................................................... 43 5.2.9. Deep-frying............................................................................................. 44 5.2.10. Microwave heating ............................................................................... 44 5.3. Other products containing the cultivated mushroom........................................ 44 5.4. Influence of cultivation, including genetic modification.................................. 45 5.5. Conclusion on occurrence................................................................................. 47 6. Production and consumption...................................................................................... 49 6.1. Production......................................................................................................... 49 6.2. Consumption..................................................................................................... 49 6.3. Conclusion on production and consumption .................................................... 49 7. Toxicokinetics ............................................................................................................ 53 7.1. Absorption, distribution and excretion ............................................................. 53 7.2. Biotransformation ............................................................................................. 55 7.3. Conclusion on toxicokinetics............................................................................ 57 8. Effects in short-term tests........................................................................................... 59 8.1. In vitro studies on phenylhydrazine metabolism in the mushroom................. 59 8.2. Studies on DNA binding................................................................................... 59 8.3. Tests in microorganisms ................................................................................... 63 8.4. Tests in cultured mammalian cells.................................................................... 70 8.5. In vivo tests....................................................................................................... 71 8.6. Antimutagenic effects of A. bisporus ............................................................... 73 5 8.7. Conclusions on effects in short-term tests ........................................................ 73 9. Effects on experimental animals ................................................................................ 75 9.1. Acute and subchronic toxicity of mushroom hydrazines and HMBD............. 75 9.2. Long-term carcinogenicity studies. .................................................................. 77 9.2.1. Studies on the cultivated mushroom (Agaricus bisporus). ..................... 78 9.2.2. Studies on phenylhydrazines in the mushroom and related compounds 84 9.3. Non-conventional carcinogenicity studies........................................................ 92 9.4. Antineoplastic effects of phenylhydrazines...................................................... 93 9.5. Reproduction, embryotoxicity and teratogenicity ............................................ 93 9.6. Biological effects of A. bisporus ...................................................................... 94 9.7. Conclusion on effects on experimental animals ............................................... 95 10. Human implications .................................................................................................. 97 11. Previous estimations of risk...................................................................................... 99 12. Present nordic risk assessment................................................................................ 101 12.1. Hazard identification....................................................................................... 101 12.2. Hazard characterization................................................................................... 102 12.3. Exposure characterization. .............................................................................. 103 12.4. Risk characterization....................................................................................... 104 13. Recommendations..................................................................................................
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