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 some sort of low level environmental agent may play a role if such extremely small quantities of contaminants are indeed capable of causing disease. Although the exact identity of the etiologic agent in toxic oil syndrome remains unknown, work on toxic oil syndrome continues. Follow-up clinical studies and long-term mortality studies are under way. Investigation of the mechanisms involved in toxic oil syndrome continues. The identification of suspect chemical compounds, their characterization, and effects will hopefully one day contribute to the prevention of other similar diseases.

中文翻译：

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有毒油综合症：20年后的角度。

1981年5月，西班牙有毒的油综合症爆发，耗尽了新近发展的政治和社会医学体系的资源。致病性毒剂的媒介物被确定为非法油，已从工业用途中转移并精制以去除苯胺变性剂，并且由巡回销售员以无标签的5升容器出售。最终有20,000多人受到影响，受影响人群中有1,200多人因各种原因死亡。毒性油综合症的流行病学调查涉及调查和分析工作的各个方面；从参观工厂和面试工人到复杂的化学和统计分析技术。这项调查可以进一步说明所有类型的数据和信息，为了广泛解决流行病学的奥秘，需要对来自广泛领域的信息进行系统地收集和评估。然而，对患者的敏锐临床观察导致了这样的假说，即有毒油综合症是有毒暴露的结果。在这种和其他病因不明的流行病中，临床观察以及对临床医生的认真观察，对患者病史，体征和症状的严格检查，常常导致可以在流行病学上进行检验的假说。当医学上未知时，精明的临床医生的作用仍然至关重要。如果控制和调节食品供应或其他消费产品的系统发生故障，那么有毒油综合症的流行就是一个例子，说明即使是发达国家也可能受到大规模的环境起源流行的影响。然而，如果大型商业网络在监管边缘运作，并且这些企业缺乏对制造条件变更后果的深入了解，那么此类故障就可能发生。嗜酸性粒细胞-肌痛综合征也是如此，当L-色氨酸生产条件的明显改变导致产品中杂质的增加，这些杂质后来与疾病有关。在控制系统很少或不一致的国家，这些风险甚至更大，这使得食品和药品供应有可能进入严重危害健康的准入门户，海地因合法消费产品引起的小儿肾衰竭的悲剧性事件进一步证明了这一点，对乙酰氨基酚mol剂是使用欺诈性供应的有毒成分制造的，二甘醇（81）。掺假菜籽油中潜在的毒物含量极少。如果脂肪酸酐或相关化合物确实是有毒油综合症的病因，那么这些化合物在所发现的百万分之几的浓度下必须具有极高的毒性。此外，致病因素在诸如硬皮病，嗜酸性筋膜炎，嗜酸性周肌炎和其他类似疾病等疾病发展中的作用尚不清楚，但科学家们可以推测，如果这种极少量的环境因子可能起某种作用的污染物确实能够引起疾病。尽管尚不清楚毒油综合征中病因的确切身份，但有关毒油综合征的工作仍在继续。后续临床研究和长期死亡率研究正在进行中。有关有毒油综合症的机制的研究仍在继续。鉴定可疑化合物，表征和作用有望在一天之内有助于预防其他类似疾病。