Late deaths among young women affected by the toxic oil syndrome in Spain.
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Biomedical subjects
Publications and source records attributed to I Abaitua.
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Toxic oil syndrome appeared in epidemic form in Spain in 1981. Epidemiologic studies have demonstrated that illness was caused by consumption of rapeseed oil that had been denatured with aniline. Chemical analyses of oil specimens conducted in conjunction with epidemiologic studies have established that consumption of specific oils containing fatty acid anilide contaminants was associated with increased risk for disease. New chemical analytic methods identified a family of compounds, the di-fatty acid esters of phenylamino propane-diol, and one of these compounds, the 1,2-di-oleyl ester of 3-(N-phenylamino)-1,2-propanediol (DPAP), has been found to be more strongly associated with disease status than the fatty acid anilides. We found the odds ratio for exposure to DPAP (OR = 26.4, 95% CI = 6.4-76.3) is much higher than the odds ratio for exposure to oleyl anilide (OR = 4.1, 95% CI = 2.2-7.8), implying that exposure to DPAP was a more relevant risk factor for development of toxic oil syndrome than exposure to oleyl anilide. In this paper, we review and present analyses of data from multiple studies of the possible etiologic role of DPAP in toxic oil syndrome. The presence of DPAP in oil collected from affected and unaffected households was a more specific correlate of case relatedness than was the presence of fatty acid anilides, and it was equally sensitive. Moreover, DPAP was found in oil from the only refinery whose oil was clearly associated with illness.
The toxic oil syndrome (TOS), a multisystemic disease, that occurred in Spain in 1981, was caused by the ingestion of rapeseed oil denatured with 2% aniline. Due to the clinical course of the disease, immunopathological mechanisms have been suspected but a direct connection was never demonstrated. To analyse this possibility, we determined several immunological parameters in the sera of patients with TOS and without the disease, using a case-control design: total immunoglobulins, IgG and IgE antibodies against different toxic agents (oleylanilide, aniline, linoleyl-anilide, and 3-phenylaminopropane-1-2-diol), autoantibodies, cytokines (IL-4, IL-6, TNF, GM-CSF) and soluble receptors (sCD23 and sIL-2R). We detected high levels of sIL-2R in TOS patients compared to controls (P < 0.0001). A higher levels of sCD23 and IgE were also found. In addition, the response to oleyl-anilide of peripheral blood lymphocytes from TOS patients was studied and a significant proliferative response in 30% of TOS patients versus 5% controls was observed. Our data support the implication of the immune system in the acute phase of TOS, with a possible activation of T-cells and release of cytokines, that could explain some of the clinical findings in this phase of the disease.
The participation of eosinophils in the Spanish toxic oil syndrome (TOS) was investigated. Eosinophil infiltration and degranulation in tissues from 52 patients with the TOS were examined by immunofluorescence staining for the eosinophil granule major basic protein (MBP). Serum MBP levels were determined in sera from 323 patients. Eosinophil infiltration and degranulation were found in several tissues, especially during the acute phase of the TOS, and serum MBP was significantly elevated during all phases of the disease, suggesting that eosinophils play a role in the pathogenesis of the TOS.
Toxic-oil syndrome (TOS), a new disease that occurred in epidemic form in Spain in 1981, has been associated with the ingestion of unlabelled oil bought principally from travelling salesmen. Chemical analysis of oils taken from ill families has shown them to consist of varying proportions of different vegetable oils and animal fats, often showing chemical evidence of prior treatment with aniline. We investigated the unusual circumstances surrounding the reported occurrence of three TOS cases in two families in Sevilla, a city located far away (approximately 300 km) from the group of 14 provinces in central and northwestern Spain where 99% of the TOS cases occurred. Each case we investigated fitted the clinical picture of TOS and was not consistent with any other diagnosis. Illness apparently occurred as a result of ingestion of oil taken from the ITH oil refinery in Sevilla, a plant in which rapeseed and grapeseed oils were refined for the distributing firm through which oil bearing the causative agent of TOS is thought to have entered the market. These data provide further strong support for the hypothesis that food oil was the vehicle by which the aetiological agent of TOS was transmitted. Because ingestion of refined denatured rapeseed oil was most closely associated with the illness in time, the TOS agent was probably contained initially in this type of oil. The agent very probably entered later oil mixtures through such contaminated rapeseed oil.
Two patients with hereditary, clinical, electromyographical and histological data typical of myotonic dystrophy are discussed. In both there was a thyroid disorder. The first patient had primary hypothyroidism, and the second a non-toxic multinodular goiter which necessitated total thyroidectomy. The EMG findings and the muscle histopathology of both patients are commented on and compared with the changes described in hypothyroidism. The disease processes in both patients are also discussed in relation to the muscle and metabolic changes described in myotonic dystrophy. The coexistence of these two diseases is not explicable in the light of present knowledge on the basis of a known genetic predisposition. Only two similar cases of myotonic dystrophy and hypothyroidism have been reported.
This Field Note aims to make known the decisions taken by the Ethics Committee of the Instituto de Salud Carlos III for Toxic Oil Syndrome regarding the secondary use of research specimens in biological research when informed consent is lacking. This is a common concern in the field of biomedical research. After debating the ethical suitability of the secondary use of these samples, our main conclusion is that researchers conducting prospective studies should expressly solicit written informed consent from participants in the study about i) whether there will or could be any secondary use of the samples and, if so, ii) whether such secondary use would be conditional on the type of research.