Research Article| Volume 56, ISSUE 7, P701-708, July 2003

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Toxic oil syndrome: Survival in the whole cohort between 1981 and 1995


      Background and Objective: In 1981, toxic oil syndrome (TOS) appeared in Spain, affecting more than 20,000 persons and causing over 2500 deaths to date. Previous studies have addressed mortality only by gender and age. We analyzed possible prognostic factors in the survival of the cohort.
      Methods: The study period was 1 May 1981 to 31 December 1995 (31 December 1995 was the cut-off date for survivors). The study population consisted of the entire cohort. Overall mortality and TOS-related deaths were studied. Kaplan-Meier method and Cox regression were used in the analyses.
      Results: Among the 20,084 subjects in the cohort, 12,164 (60.6%) were women, and 7917 (39.4%) were men. Of the 1799 deaths, 958 (53.3%) were women, and 841 (46.71%) were men; of the 356 TOS-related deaths, 234 (65.7%) were women, and 122 (34.3%) were men. TOS was the leading cause of death among subjects <40 years of age. Among the TOS-related deaths, the shortest survival times were for women and subjects <40 years of age. The major disease manifestations had the highest relative risks (RR) (liver disease, RR 3.83; pulmonary infection, RR 1.54; motor neuropathy, RR 2.24; pulmonary hypertension, RR 3.19; and eosinophilia, RR 1.14.).
      Conclusions: The major clinical manifestations showed worse prognosis for overall and TOS-related mortality. Application of these results to the survivors will help clarify the validity of these conclusions.


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        • Tabuenca J.M
        Toxic allergic syndrome caused by ingestion of rapeseed oil denatured with aniline.
        Lancet. 1981; 2: 567-568
        • Posada de la Paz M
        • Philen R.M
        • Abaitua Borda I
        Toxic oil syndrome: the perspective after 20 years.
        Epidemiol Rev. 2001; 23: 231-247
        • Calaf R.E
        • Pena J
        • Paytubi S
        • et al.
        Determination of aniline derivatives in oils related to the toxic oil syndrome by atmospheric pressure ionization-tandem mass spectrometry.
        Anal Chem. 2001; 73: 3828-3837
        • Posada M
        • Philen R.M
        • Abaitua I
        • et al.
        Manufacturing processes at two French rapeseed oil companies: possible relationships to toxic oil syndrome in Spain.
        Food Chem Toxicol. 1991; 29: 797-803
      1. Toxic oil syndrome: mass food poisoning in Spain.
        in: Grandjean P Tarkowski S Report of a WHO meeting: Madrid 21 March 1983. World Health Organization Regional Office for Europe, Copenhagen1984: 3-9
        • Ministerio de Sanidad y Consumo
        Sı́ndrome Tóxico X. Epidemiologı́a: distribución espacial.
        Boletı́n Epidemiológico Semanal. 1981; 1491: 201-203
        • Abaitua Borda I
        • Posada de la Paz M
        Clinical findings.
        in: World Health Organization. Regional Office for Europe. Toxic oil syndrome: current knowledge and future perspectives. World Health Organization Regional Office for Europe, Copenhagen1992: 25-35
        • Kilbourne E.M
        • Perez-Rigau J.G
        • Heath C.W
        • et al.
        Clinical epidemiology of toxic oil syndrome: manifestations of a new illness.
        N Engl J Med. 1983; 309: 1408-1414
        • Philen R.M
        • Posada M
        Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8–10, 1991, World Health Organization Meeting Report.
        Sem Arthrit Rheum. 1993; 23: 104-124
        • Abaitua Borda I
        • Philen R.M
        • Posada de la Paz M
        • et al.
        Toxic oil syndrome: thirteen-year mortality study.
        Int J Epidemiol. 1998; 27: 1057-1063
        • Posada de la Paz M
        • Abaitua I
        • Terracini B
        • et al.
        Late deaths among young women affected by the toxic oil syndrome in Spain.
        Epidemiology. 1999; 10 ([letter]): 345
      2. Abaitua Borda I. Study on mortality. 7th revision. WP02A21. Presented at the 31st Scientific Committee for the Toxic Oil Syndrome Meeting. Copenhagen, May 14–15, 2002.

        • Ministerio de Sanidad y Consumo
        Clasificación internacional de enfermedades. 9a revisión. Modificación clinica. vol. 1. Ministerio de Sanidad y Consumo, Madrid1994
        • Harris E.K
        • Albert A
        Survivorship analysis for clinical studies.
        in: Owen D.B Cornel R.G Kenedy W.J Kshirsagar A.M Schilling E.G Statistics, textbooks and monographs. vol. 114. Marcel Dekker, New York1991
        • Wang M.-C
        Nonparametric estimation from cross-sectional survival data.
        J Am Stat Assoc. 1991; 86: 130-143
        • Miller Jr., R.G
        Survival analysis. John Willey & Sons, New York1981
        • Belsey D.A
        Conditioning diagnostics: collinearity and weak data in regression.
        John Wiley & Sons, New York1991
        • Christensen E
        Multivariate survival analysis using Cox's regression.
        Hepatology. 1987; 7: 1346-1358
        • Gómez de la Cámara A
        • Posada de la Paz M
        • Abaitua Borda I
        • et al.
        Health status measurement in toxic oil syndrome.
        J Clin Epidemiol. 1998; 51: 867-873
        • Toxic Epidemiology Study Group 1981
        Toxic epidemic syndrome Spain.
        Lancet. 1982; 2: 697-702
        • Posada de la Paz M
        • Owen D.B
        • Cornel R.G
        • Kenedy W.J
        • Kshirsagar A.M
        • Schiuing E.G
        Late cases of toxic oil syndrome: evidence that the aetiologic agent persisted in oil stored for up to one year.
        Food Chem Toxicol. 1989; 27: 517-521
        • Ladona M.G
        • Izquierdo-Martinez M
        • Posada de la Paz M
        • et al.
        Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the Spanish toxic oil syndrome.
        Environ Health Perspect. 2001; 109: 369-375
      3. Posada de la Paz M, Abaitua Borda I, Sánchez-Porro P, et al. A case series analysis of deaths in the TOS cohort: studies of risks factors and the validity of the cause of death certificates. Presented at the World Health Organization 26th meeting. Leuven, October 20–21, 1999.

        • Wohlfart J
        • Andersen P.K
        • Melbye M
        Multivariate competing risks.
        Stat Med. 1999; 18: 1023-1030
        • Lung M
        • Mc Neil D
        Applying Cox regression to competing risks.
        Biometrics. 1995; 51: 524-532
        • Gelpi E
        • Posada de la Paz M
        • Terracini B
        • et al.
        (WHO/CISAT Scientific Committee for the Toxic Oil Syndrome). The Spanish Toxic Oil Syndrome: epidemiological, immunological and toxicological knowledge twenty years after its occurrence.
        Environ Health Perspect. 2002; 110: 457-464