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Emilio Gelpí,¹ Manuel Posada de la Paz,² Benedetto Terracini,³ Ignacio Abaitua,² Agustín Gómez de la Cámara,⁴ Edwin M. Kilbourne,⁵ Carlos Lahoz,⁶ Bénoit Nemery,⁷ Rossanne M. Philen,⁸ Luis Soldevilla,² and Stanislaw Tarkowski⁹ (WHO/CISAT Scientific Committee for the Toxic Oil Syndrome)

¹Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain; ²Centro de Investigacion para el Sídrome del aceite Tóxico y Enfermedades Raras, Instituto Carlos III, Madrid, Spain; ³Centro per la Prevenzione Oncologica, Dipartimento di Scienze Biomediche e Oncologia Umana, Università, Torino, Italy; ⁴Unidad de Investigación de Epidemiologia Clínica, Hospital 12 de Octubre, Madrid, Spain; ⁵Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁶Departamento de Immunologia, Clinica de la Concepción, Fundación Jimenez Diaz, Madrid, Spain; ⁷Laboratorium voor Pneumologia, Katholieke Universiteit, Leuven, Belgium; ⁸National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁹Department of Environmental Health Hazards, Nofer Institute of Occupational Medicina, Lodz, Poland

Abstract

In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused an outbreak of a previously unrecorded condition, later known as toxic oil syndrome (TOS) , clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization's Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s) , to assess toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientific literature. Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with chemical analyses of case-related oils have shown that the disease is strongly associated with the consumption of oils containing fatty acid esters of 3-(N-phenylamino) -1,2-propanediol (PAP) . These chemicals have also been found in oils synthesized under conditions simulating those hypothesized to have occurred when the toxic oil was produced in 1981. Whether PAP esters are simply markers of toxicity of oils or have the capability to induce the disease remains to be elucidated. Key words: autoimmunity, foodborne intoxication, oleyl anilide, 3-phenylamino-1, 2-propanediol esters, rapeseed oil, toxic oil syndrome. Environ Health Perspect 110:457-464 (2002) . [Online 29 March 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p457-464gelpi/ abstract.html

Address correspondence to B. Terracini, Centro per la Prevenzione Oncologica, Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Via Santena 7, 10126 Torino, Italy. Telephone: 39 011 670-6526. Fax: 39 011 670-6692. E-mail terracini@etabeta.it

The WHO/CISAT Scientific Committee for the Toxic Oil Syndrome includes E. Gelpí (Chairman) , M. Posada de la Paz (General Coordinator) , B. Terracini (Rapporteur for the present paper) , I. Abaitua, A. Gómez de la Cámara, E.M. Kilbourne, C. Lahoz, B. Nemery, R.M. Philen, L. Soldevilla, and S. Tarkowski.

We are grateful to R. Goulding for his chairmanship of the committee until 1992. A vital and thoughtful input to the activity of the committee was given by the late N. Aldridge.

We gratefully acknowledge the support and secretarial and technical help of the World Health Organization Regional Office for Europe and of the Toxic Oil Syndrome Research Center (CISAT) of the Institute of Health Carlos III.

Received 13 July 2001 ; accepted 4 December 2001.