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Toxic Oil Syndrome The WHO Regional OILSYNDROME TOXIC Offi ce for Europe The World Health Organization (WHO) is a specialized agency of the United Nations This is the third book published by WHO on the outbreak created in 1948 with the of the condition that came to be called the toxic oil primary responsibility for international syndrome (TOS), which struck Spain in 1981. It killed health matters and public health. The several hundred people and affected more than 20 000, WHO Regional Offi ce many of whom remain ill today. The two previous books for Europe is one of six regional offi ces described, respectively, early observations and scientifi c throughout the world, each with its own fi ndings gathered throughout the 1980s. programme geared to the particular health conditions of the This volume refl ects the progress made in the last ten countries it serves. years under a carefully planned strategy undertaken on Member States Albania | four main fronts by the WHO/CISAT Scientifi c Committee TENYEARS OF PROGRESS Andorra for the Toxic Oil Syndrome. First, various projects were Armenia supported aiming at the full chemical characterization Austria Azerbaijan of the oil matrix. Second, attempts were made to Belarus reproduce, on both a laboratory and an industrial scale, Belgium Bosnia and Herzegovina the refi ning process to which the suspect oil had been Bulgaria subjected in an attempt to establish the conditions Croatia Cyprus under which the toxin(s) were generated and to provide Czech Republic Denmark suffi cient amounts of reconstituted oils for toxicological Estonia studies. Third, a search was undertaken for an animal Finland France model in which to study the disease. Finally, work on the Georgia possible immune origin of the intoxication was stepped Germany Greece up, with promising results to date. Hungary Iceland Ireland Israel Italy Kazakhstan Kyrgyzstan Latvia Lithuania Luxembourg Malta Monaco Netherlands Norway Poland Portugal Republic of Moldova Romania Russian Federation San Marino World Health Organization Serbia and Montenegro Regional Offi ce for Europe Slovakia Slovenia Scherfi gsvej 8 Spain Sweden DK-2100 Copenhagen Ø Switzerland Denmark Tajikistan The former Yugoslav Tel.: + 45 39 17 17 17 AMS 5046349 Republic of Macedonia Turkey Fax: + 45 39 17 18 18 ISBN 92 890 1063 0 Turkmenistan E-mail: [email protected] E84423 Ukraine United Kingdom Web site: www.euro.who.int Original: English Uzbekistan TToxOilCovEnumber.inddoxOilCovEnumber.indd 1 110-08-20040-08-2004 111:12:091:12:09 Toxic oil syndrome Ten years of progress Edited by: Benedetto Terracini This publication received fi nancial support from the Institute of Health Carlos III, Ministry of Health and Social Affairs of Spain. ABSTRACT This report provides an update on research on the toxic oil syndrome (TOS) since the last WHO review was published in 1992. Although it has been known since the late 1980s that the disease was caused by the consumption of illicitly refi ned rapeseed oil, it has been obvious for many years that a concerted scientifi c effort was needed to precisely identify the agent(s) responsible for the outbreak and to assess the pathogenesis and clinical evolution of the condition. Although many questions remain to be answered and no animal model for TOS has been identifi ed, much knowledge has now been gained on the biological properties of chemicals found in the adulterated oil, on the pathogenesis of the disease and on the conditions by which the illegal refi ning might have produced toxic compounds. These investigations are relevant not only to protecting the health of TOS victims but also to preparedness for similar circumstances in the future. Keywords BRASSICA FOOD POISONING – ETIOLOGY PLANT OILS – TOXICITY SPAIN ISBN 92 890 1063 0 Address requests about publications of the WHO Regional Office to: • by e-mail [email protected] (for copies of publications) [email protected] (for permission to reproduce them) [email protected] (for permission to translate them) • by post Publications WHO Regional Office for Europe Scherfigsvej 8 DK-2100 Copenhagen Ø, Denmark © World Health Organization 2004 All rights reserved. The Regional Offi ce for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. 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. Where the designation “country or area” appears in the headings of tables, it covers countries, territories, cities, or areas. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specifi c 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 distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. The views expressed by authors or editors do not necessarily represent the decisions or the stated policy of the World Health Organization. Contents Contributors ................................................................................................v Joint WHO/CISAT Scientifi c Committee for the Toxic Oil Syndrome .......ix Foreword......................................................................................................xi Preface – Emilio Gelpí and Manuel Posada de la Paz....................................xiii Introduction – Benedetto Terracini ................................................................1 1. Epidemiology of toxic oil syndrome: advances since 1992 – Rossanne M. Philen, Manuel Posada de la Paz, Benedetto Terracini and Edwin Kilbourne..............................................................................5 2. Sample repositories – Ignacio Abaitua, Concepción Martín-Arribas, Victoria del Pozo and Manuel Posada de la Paz.......................................17 3. Clinical aspects – Agustín Gómez de la Cámara, Manuel Posada de laPaz, María del Mar Plaza Cano, Eva Estirado de Cabo, María Luisa García de Aguinaga, Maravillas Izquierdo Martínez, Concepción Martín-Arribas and Francisco Pozo Rodríguez.......................25 4. Chemistry – Emilio Gelpí and Manuel Posada de la Paz ........................37 5. Experimental toxicology – Stanislaw Tarkowski and Benoit Nemery.......43 6. Immunology – Soledad Gallardo, Blanca Cárdaba, Victoria del Pozo and Carlos Lahoz ...................................................................................69 7. Ethical and social aspects – Benedetto Terracini and Concepción Martín-Arribas ...................................................................85 iii 8. Future research strategies – Manuel Posada de la Paz and Emilio Gelpí .........................................................................................95 Annex 1. The etiology of the Spanish toxic syndrome: interpretation of the epidemiological evidence – Sir Richard Doll.......................................................................... 99 Annex 2. Guidelines for the use of aniline derivatives related to toxic oil syndrome in biological and toxicological assays – Jordi Gibergans, Anna Morató and Angel Messeguer.................... 131 Annex 3. Proposal for the updating and rationalization of the nomenclature on abbreviations of PAP compounds – Joaquin Abian, Emilio Gelpí and Angel Messeguer ...................... 141 Annex 4. Part 1. Chemical analyses of TOS oils – Rosa Elena Calaf, Juana Peña, Montserrat Carrascal, Sonia Paytubi, Natalia Reig, Rosario Prieto, Yolanda Castaño, Benjamin C. Blount, Manuel Posada de la Paz, Emilio Gelpí and Joaquin Abian ................................................................... 145 Part 2. Identifi cation of new PAP derivatives – Natalia Reig, Yolanda Castaño, Rosario Prieto, Rosa Elena Calaf, Angel Messeguer, Anna Morató and Joaquin Abian...................... 161 Part 3. Synthesis of PAP derivatives – Anna Morató and Angel Messeguer ............................................ 175 Part 4. Reproducing the refi ning process – Victoria Ruiz Méndez and Manuel Posada de la Paz .................. 181 iv Contributors Dr Ignacio Abaitua Centro de Investigación sobre el Síndrome del Aceite Tóxico y Enferme- dades Raras (CISATER), Instituto de Salud Carlos III, Madrid, Spain Dr Joaquin Abian Structural and Biological Mass Spectrometry Unit, Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona (IIBB), Consejo Superior de Investigaciones Científi cas (CSIC), Barcelona, Spain Dr Benjamin C. Blount Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA Dr Rosa Elena Calaf Structural and Biological Mass Spectrometry Unit, Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona (IIBB), Consejo Superior de Investigaciones Científi cas (CSIC), Barcelona, Spain Dr Blanca Cárdaba Department of Immunology, Clínica de la Concepción, Fundación Jiménez Díaz, Madrid, Spain
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