Vol. 23, No. 2 Printed in U.S.A.
Toxic Oil Syndrome: The Perspective after 20 Years
Manuel Posada de la Paz,1 Rossanne M. Philen,2 and Ignacio Abaitua Borda1
In 1981, a progressive multisystem disease, later called toxic oil syndrome, abruptlybroke out in epidemic proportions in central and northwestern Spain (1). This previously unknown syndrome affected thousands of people, and several hundred deaths were attributed to toxic oil syndrome. As a result of this epidemic, the Spanish national health system was faced with one of the most critical public health problems of this century. Although certain clinical characteristics of toxic oilsyndrome resembled those of other diseases such as scleroderma and graft-versus-host disease, a similar disease had never before been seen, and its effects on the public and the medical community were dramatic. Twenty years later many questions about this epidemic remain unresolved (2). Toxic oil syndrome resulted from the consumption of rapeseed oil that had been denatured with 2 percent anilinefor industrial use, subsequently refined, and then illicitly sold as pure olive oil (3). To date, the causal toxic agent remains unknown, as many substances which could potentially be the causative compound have been found in the implicated oils (4, 5). Adulterated oils have contributed to serious epidemics in the past, such as one in Morocco in 1959 due to ortho-cresyl phosphate contamination ofjet aircraft oil, which was fraudulently sold as food oil (6), and the one that occurred in Japan in 1968 from the accidental contamination of rice oil with polychlorinated biphenyls (6, 7). The toxic oil syndrome epidemic represents a unique episode of intoxication, however, since in this case the oil was known to be unfit for human consumption because of denaturation with aniline. The appearanceof an epidemic that affected the population in terms of a large number of illnesses and deaths, the
Received for publication August 29, 2000, and accepted for publication July 20, 2001. Abbreviations: CISAT, Centra de Investigacibn sobre el Si'ndrome del Aceite T6xico; DEPAP, 3-(A/-phenylamino)-1,2-propanediol; WHO, World Health Organization. 1 Centra de Investigaci6n sobre el Sindrome delAceite T6xico, Instituto de Salud Carlos III, Madrid, Spain. 2 Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, GA. Reprint requests to Dr. Rossanne M. Philen, Division of Environmental Hazards and Health Effects (E-23), National Center for Environmental Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta,GA 30333 (e-mail: email@example.com).
discovery of a specific food as the vehicle of the toxic exposure, the elucidation of the nature of a disease unknown in humans or animals, the response of the scientific community facing an unknown, acute phenomenon, and the attitude of the affected people and the society as a whole present issues and responses that are widely applicable to othersituations. Epidemiologic research and the collaboration of epidemiologists with basic scientists have been fundamental to our present understanding of toxic oil syndrome. Twenty years after toxic oil syndrome first appeared in Spain, we propose to review and update the knowledge, potential causes, and past and present studies of toxic oil syndrome.
EARLY EVENTS Hypothesis generation
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On May 1, 1981, the index case of toxic oil syndrome, a boy aged 8 years, was pronounced dead on arrival at a Madrid hospital (8). Shortly afterward and over the next few days, five other members of his family were examined at the same hospital with signs and symptoms that included interstitial pulmonary infiltrate, headache,...