Toxic oil syndrome: Traceback of the toxic, oil and evidence for a point source epidemic

Paz, Manuel Posada de la; Philen, Rossanne M.; Borda, Ignacio Abaitua; Socias, J.M. Sicilia; Cámara, Agustı́n Gómez de la; Kilbourne, Edwin M.

doi:10.1016/0278-6915(95)00111-5

Cited by 34 publications

(18 citation statements)

References 10 publications

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“…The epidemic curve shown in figure 2 is compatible with a shortterm point source exposure (15). Interestingly, the curve begins to fall about 1 week before the announcement of the oil-disease relation on June 10, 1981.…”

Section: Descriptive Epidemiologymentioning

confidence: 81%

Toxic Oil Syndrome: The Perspective after 20 Years

Паз

Philen

Borda

2001

Epidemiologic Reviews

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Toxic oil syndrome burst upon the scene in Spain in May of 1981, draining the resources of a newly evolving political and social medicine system. The vehicle of the causative toxic agent was identified as an illicit oil that had been diverted from industrial use and refined in order to remove the aniline denaturant, and that was sold in unlabeled 5-liter containers by itinerant salesmen. Over 20,000 people were ultimately affected, and over 1,200 deaths from all causes have been recorded in the affected cohort. The epidemiologic investigation of toxic oil syndrome involved all facets of investigative and analytical work; from visits to factories and interviewing workers, to sophisticated chemical and statistical analytical techniques. This investigation serves as a further illustration that data and information of all types, and from a wide range of fields, need to be systematically collected and evaluated in order to best resolve an epidemiologic mystery. Astute clinical observation of the patients, however, led to the hypothesis that toxic oil syndrome was a result of a toxic exposure. In this and other epidemics of unknown etiology, clinical observation and the intense scrutiny of patients' histories, signs, and symptoms by treating clinicians have often led to hypotheses that could be tested epidemiologically. When there are medical unknowns, the role of the astute clinician continues to be crucial. The toxic oil syndrome epidemic is an example of how even a developed country can be affected by a massive epidemic of environmental origin if failures occur in the systems that control and regulate the food supply or other consumer products. However, such failures could occur anywhere that large commercial networks operate on the regulatory edge, and if these business lack an in depth knowledge of the consequences of alterations in manufacturing conditions. Such was the case with eosinophilia-myalgia syndrome as well, when apparently minor alterations in manufacturing conditions of L-tryptophan led to an increase in impurities in the product that were later associated with the illness. These risks are even greater in countries with few or inconsistent control systems, making the food and drug supply potential portals of entry for serious health hazards, as is further exemplified by the tragic episode of pediatric renal failure in Haiti associated with a legitimate consumer product, paracetamol elixir, that had been manufactured using a fraudulently supplied toxic ingredient, diethylene glycol (81). The potential toxicants in the adulterated rapeseed oil were present in extremely small amounts. If fatty acid anilides or related compounds are indeed the etiologic agents in toxic oil syndrome, then these compounds must be extremely toxic at the parts per million concentrations at which they were found. Further, the roles of causative agents in the development of disorders such as scleroderma, eosinophilic fasciitis, eosinophilic perimyositis, and other similar diseases are unknown, but scientists can speculate that ...

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Section: Descriptive Epidemiologymentioning

confidence: 81%

Toxic Oil Syndrome: The Perspective after 20 Years

Паз

Philen

Borda

2001

Epidemiologic Reviews

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“…The initial chemical analysis identified OA as the primary contaminant and marker for case-associated oils, but the number of anilides and unidentified contaminants suggested that other compounds might also be involved in the mechanism of TOS (Aldridge, 1992;Posada de la Paz et al, 1996). A review of 70 chemical entities associated with mineral oil and the oil refinery process stream indicated that none of the common refinery products, additives or contaminants induced symptoms and pathology consistent with those of TOS (Hard, Journal of Immunotoxicology Downloaded from informahealthcare.com by CDL-UC Davis on 11/17/14…”

Section: Chemistry Of Toxic Oil Syndromementioning

confidence: 98%

“…The relationship between disease symptoms and consumption of the oil, and the subsequent readmission of many patients who had been treated and discharged in good condition yet continued to use the same oil, led to an official oil recall by the Spanish 52 PATTERSON AND GERMOLEC Ministry of Health and Consumer Affairs two months after the onset of the epidemic (Tabuenca, 1981;Posada de la Paz et al, 1996;Philen et al, 1997).…”

Section: Introductionmentioning

confidence: 97%

“…Chemical analysis of the case-associated oil identified brassicasterol, a marker for rapeseed oil, trace amounts of aniline, oleyl anilide (OA), and other fatty acid anilides and contaminants (Posada de la Paz et al, 1996). The toxin(s) appear to be stable since consumption of toxic oil one year after the main epidemic led to development of the disease (Posada de la Paz et al, 1989).…”

Section: Introductionmentioning

confidence: 98%

“…To protect a major domestic export product, the Spanish government limited imported edible oils to those denatured for industrial use. However, evidence suggests that a number of companies imported rapeseed oil denatured with 2% aniline from France, refined the oil, mixed it with other oils, and fraudulently sold the product as pure olive oil through itinerant vendors (Posada de la Paz et al, 1996;Philen et al, 1997). Anilide-contaminated oils returned in the recall by a household in which at least one family member had developed the disease were classified "case" oils for future studies.…”

Section: Introductionmentioning

confidence: 98%

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Review Article Toxic Oil Syndrome: Review of Immune Aspects of the Disease

Patterson

Germolec

2005

Journal of Immunotoxicology

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In 1981-1982, individuals in fourteen central and northwest provinces in Spain were affected by an illness that was eventually labeled toxic oil syndrome (TOS) by the World Health Organization. Thousands of individuals were diagnosed with, and 356 people eventually died from, the disease. The disease shares striking similarities with several autoimmune diseases, particularly eosinophilia-myalgia syndrome (EMS) and diffuse fasciitis with eosinophilia (DFE). As with many other autoimmune diseases, women were more severely affected than men and made up a significant portion of TOS-related deaths. While a number of etiologic agents were investigated, disease occurrence was found to be significantly associated with consumption of contaminated rapeseed oil produced by a particular refinery. Two compounds, 1,2-di-oleyl ester (DEPAP) and oleic anilide are considered to be biologically relevant contaminants that may contribute to disease development. Toxic oil syndrome was a three-phase disease with an initial non-necrotizing vasculitis in multiple organs. Suspected immune mechanisms in TOS include activation of T-cells, altered cytokine production, and several studies have associated disease severity with HLA-DR2 and polymorphisms in metabolism and immune response genes. While a number of animal models have been used to investigate the underlying immune mechanisms in TOS, only a few studies in rodents have demonstrated the classical symptoms of TOS. Biotransformation and oxidation of the parent compound(s) to reactive intermediates prior to induction of autoreactive pathways appears to be an important component of the disease process. These reactive intermediates could haptenate self-proteins and activate autoreactive T-cells, disrupt signal transduction, or induce apoptosis and necrosis to release abnormal forms of self-antigens. Although the TOS epidemic was limited to a discrete period of time, the origin of the contamination determined, and the spread of the disease halted by government intervention, the underlying immune mechanisms have yet to be elucidated.

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