WHO Technical Report Series 928 EVALUATION OF CERTAIN FOOD ADDITIVES Sixty-third report of the Joint FAO/WHO Expert Committee on Food Additives World Health Organization Geneva 2005 E i ECF PR 1 30/5/2005, 11:10 AM Black WHO Library Cataloguing-in-Publication Data Joint FAO/WHO Expert Committee on Food Additives (2004 : Geneva, Switzerland) Evaluation of certain food additives : sixty-third report of the Joint FAO/WHO Expert Committee on Food Additives. (WHO technical report series ; 928) 1.Food additives — toxicity 2.Food additives — analysis 3.Flavoring agents — analysis 4.Food contamination 5.Risk assessment I.Title II.Series. ISBN 92 4 120928 3 (NLM classification: WA 712) ISSN 0512-3054 © World Health Organization 2005 All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications — whether for sale or for noncommercial distribution — should be addressed to Marketing and Dissemination, at the above address (fax: +41 22 791 4806; email: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distin- guished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization. Typeset in Hong Kong Printed in Singapore ECF PR 2 30/5/2005, 11:10 AM Black Contents 1. Introduction 1 2. General considerations 1 2.1 Modification of the agenda 2 2.2 Principles governing the toxicological evaluation of compounds on the agenda 2 2.3 The safety evaluation of flavouring agents 2 2.3.1 Estimating intake of flavouring agents 2 2.3.2 Flavour complexes derived from natural sources 3 2.4 Evaluation of dietary nutrients and other ingredients 10 2.5 Principles governing the establishment and revision of specifications 10 2.5.1 Determination of carotenoids 10 2.5.2 Revision of heavy metals and arsenic specifications 10 2.6 Core Standing Committee for JECFA 11 2.7 Provision of scientific advice by FAO and WHO 12 2.8 IPCS Project on Dose–Response Modelling 12 2.9 Joint FAO/WHO Project to Update the Principles and Methods for the Risk Assessment of Chemicals in Food 13 3. Specific food additives (other than flavouring agents) 13 3.1 Safety evaluations 13 3.1.1 Benzoyl peroxide 13 3.1.2 a-Cyclodextrin 16 3.1.3 Hexose oxidase from Chondrus crispus expressed in Hansenula polymorpha 21 3.1.4 Lutein from Tagetes erecta L. 23 3.1.5 Peroxyacid antimicrobial solutions containing 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) 26 3.1.6 Steviol glycosides 34 3.1.7 D-Tagatose 39 3.1.8 Xylanases from Bacillus subtilis expressed in Bacillus subtilis 42 3.1.9 Zeaxanthin 45 3.2 Revision of specifications 48 3.2.1 Aluminium powder, iron oxides and titanium dioxide 48 3.2.2 Aluminium lakes of colouring matters — general specifications 49 3.2.3 Hydroxypropyl cellulose 50 3.2.4 Hydroxypropylmethyl cellulose 50 3.2.5 Magnesium sulfate 50 3.2.6 Polyvinyl alcohol 51 3.3 Revision of metals levels and arsenic specifications 51 4. Flavouring agents 51 4.1 Flavouring agents evaluated by the Procedure for the Safety Evaluation of Flavouring Agents 51 4.1.1 Pyridine, pyrrole and quinoline derivatives 55 ECF PR 3 30/5/2005, 11:10 AM Black 4.1.2 Aliphatic and alicyclic hydrocarbons 64 4.1.3 Aromatic hydrocarbons 73 4.1.4 Aliphatic, linear a,b-unsaturated aldehydes, acids and related alcohols, acetals and esters 77 4.1.5 Monocyclic and bicyclic secondary alcohols, ketones and related esters 86 4.1.6 Amino acids and related substances 98 4.1.7 Tetrahydrofuran and furanone derivatives 106 4.1.8 Phenyl-substituted aliphatic alcohols and related aldehydes and esters 113 5. A natural constituent: glycyrrhizinic acid 121 6. Future work 126 7. Recommendations 126 Acknowledgement 126 References 127 Annex 1 Reports and other documents resulting from previous meetings of the Joint FAO/WHO Expert Committee on Food Additives 128 Annex 2 Acceptable daily intakes, other toxicological information and information on specifications 137 Annex 3 Further information required or desired 146 Annex 4 Summary of the safety evaluation of secondary components of flavouring agents with minimum assay values of less than 95% 147 Corrigenda 157 E iv ECF PR 4 30/5/2005, 11:10 AM Black Sixty-third meeting of the Joint FAO/WHO Expert Committee on Food Additives Geneva, 8–17 June 2004 Members Professor J.R. Bend, Professor and Chair, Department of Pharmacology & Toxicol- ogy, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada Dr D.G. Hattan, Senior Toxicologist, Office of Food Additives Safety, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, USA Dr Y. Kawamura, National Institute of Health Sciences, Setagaya, Tokyo, Japan Dr A.G.A.C. Knaap, Center for Substances and Risk Assessment, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands Dr P.M. Kuznesof, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, USA Dr J.C. Larsen, Senior Consultant, Division of Toxicology and Risk Assessment, Danish Institute of Food and Veterinary Research, Søborg, Denmark Mrs I. Meyland, Danish Food and Veterinary Research, Mørkhøj, Søborg, Denmark Dr M. Veerabhadra Rao, Director, Central Laboratories Unit, United Arab Emirates University, Al Ain, United Arab Emirates Dr J. Schlatter, Food Toxicology Section, Swiss Federal Office of Public Health, Zurich, Switzerland Dr M.C. de Figueiredo Toledo, Professor of Food Toxicology, State University of Campinas, Faculty of Food Engineering — Unicamp, Campinas SP, Brazil Mrs E. Vavasour, Food Directorate, Health Canada, Ottawa, Ontario, Canada (Rapporteur) Dr P. Verger, Unit Director INRA 1204, Méthodologie d’analyse des Risques Alimentaires, Paris, France Professor R. Walker, Emeritus Professor of Food Science, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, England Secretariat Dr P.J. Abbott, Food Standards Australia New Zealand (FSANZ), Canberra, ACT, Australia (WHO Temporary Adviser) Dr M.C. Archer, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada (WHO Temporary Adviser) Dr Ma. P.V. Azanza, Department of Food Science and Nutrition, College of Home Economics, UP Diliman, Quezon City, Philippines (FAO Consultant) Dr D. Benford, Food Standards Agency, London, England (WHO Temporary Adviser) E v ECF PR 5 30/5/2005, 11:10 AM Black Dr R. Cantrill, American Oil Chemists’ Society (AOCS), Champaign, IL, USA (FAO Consultant) Ms M. de Lourdes Costarrica, Senior Officer, Food Quality Liaison Group, Food Quality and Standards Service, Food and Nutrition Division, Food and Agricul- ture Organization of the United Nations (FAO), Rome, Italy (FAO Staff Member) Dr M. Das, Deputy Director and Head, Food Toxicology Laboratory, Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow, India (WHO Temporary Adviser) Dr M. DiNovi, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, USA (WHO Tempo- rary Adviser) Professor Y. El-Samragy, Food Science Department, Ain Shams University, Heliopoils West, Cairo, Egypt (FAO Consultant) Dr A.B. Hanley, Leatherhead Food International, Leatherhead, Surrey, England (FAO Consultant) Professor H. Ishiwata, Seitoku University, Chiba, Japan (FAO Consultant) Professor Fujio Kayama, Division of Environmental Medicine, Center for Community Medicine, Jichi Medical School, Tochigi, Japan (WHO Temporary Adviser) Professor R. Kroes, Institute for Risk Assessment Sciences, Utrecht University, Soest, Netherlands (WHO Temporary Adviser) Dr S. Lawrie, Food Standards Agency, London, England (FAO Consultant) Dr C. Leclercq, Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN), Rome, Italy (FAO Consultant) Dr M. Lützow, Food and Agriculture Organization of the United Nations, Rome, Italy (FAO Joint Secretary) Dr A. Mattia, Division of Biotechnology and GRAS Notice Review, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, USA (WHO Temporary Adviser) Dr G. Moy, Food Safety Programme, World Health Organization, Geneva, Switzer- land (WHO Staff Member) Dr I.C. Munro, CanTox Health Sciences International, Mississauga, Ontario, Canada (WHO Temporary Adviser) Dr A. Nishikawa, Section Chief, Division of Pathology, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, Japan (WHO Temporary Adviser) Dr Z. Olempska-Beer, Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, College Park, MD, USA (FAO Consultant) Dr S. Page, International Programme on Chemical Safety, World Health Organiza- tion, Geneva, Switzerland (WHO Staff Member) Mrs I.M.E.J.