Symposium 1. Toxicologists versus Toxicological Disasters: Toxic Oil Syndrome (TOS) I Symposia S1. Norman Aldridge Memorial Symposium (Opening symposium). Toxicologists versus Toxicological Disasters: Toxic Oil Syndrome (TOS) ~-1 TOXICOLOGISTS VERSUS TOXICOLOGICAL DISASTERS: TOXIC OIL SYNDROME. CLINICAL ASPECTS Agustfn G6m de la C:4mara *. Madrid, Spain In spring 1981, an epidemic of a new multisystemic disease occurred in Spain. Physicians initially diagnosed the condition as atypical pneumonia on the basis of pulmonary symptoms accompanied by interstitial infiltrates seen on chest roentgenograms. However, pa- tients' failure to respond to antibiotic therapy; the failure to identify a pathogenic microbial agent; the tendency of cases to cluster within families; the lack of cases among groups typically at high risk for infectious diseases, such as students and military personnel; the lack of cases among infants; and the different clinical presentation in chil- dren (eg, higher rate of cutaneous symptoms) led to the hypothesis that exposure to a toxic agent, perhaps through food, had occurred. Three clinical phases have been identified. The acute phase, lasting two months, was characterized by mild fever, rash, myalgia, dyspnea and cough. Chest Roentgenograms showed and interstitial or alveolar infiltrate with or without pleural effusion. Laboratory test demon- strated high count of eosinophils which in many cases exceeds 3,000 cell/ml. Severe myalgias and muscle cramps identify the beginning of the intermediate phase which was characterized by skin infil- trates, pulmonary hypertension, hepatic cholestasis, marked weight loss, alopecia, sicca syndrome, dysphagia, thromboembolism, and paresthesiae. The laboratory data show hypertrigliceridemia, hyper- cholesterolemia, thrombocytosis, thrombocytopenia and persistent eosinophilia. Intermediate phase: It took place the third and fourth months after the onset of the disease and these clinical estage was characterize by pulmonary hypertension and thromboembolic phe- nomena, skin oedema with progressing to thickening and loss of flexibility. Alopecia and severe myalgia was experienced, together with muscular weakness, hyporeflexia, alterations in superficial and deep sensibility, dysphagia, severe weight loss. The chronic phase appeared imperceptibly from In the chronic phase, the patients expe- rience scleroderma, hepatopathy, pulmonary hypertension, persisting paresthesiae and other neurological manifestations. Corficoids, im- munosuppressors, free-radical scavengers and relating agents were ineffective therapies. Current Status. Currently the clinical picture is mainly charac- terized by the resolution of clinical manifestations, although there still remains some percentage of patients with severe sequelae. On the other hand patients claim to have still and in a permanent way severe physical, psychological and social problems derived from their disease. Recent studies showed that there are an 18% of subjects with mod- erate sclerodermiform changes of the skin, 4.5% had dear changes and a 2.9% had atrophic skin. There were found in these studies an 18% of patients with clear polineuropathy, and contractures of the joints were found in 14.6% of the examined patients. The patients's perceived health status was measured by the Not- tingham Health Profile, It was obtained a mean score of 38.8 points. Those with clinical chronic impairment have higher scores and sta- tisticaily significant differences compared with those without current clinical affectation as well as according to the level of clinical severity. It has been observed in sclerodermiform changes of the skin, neuropathy and joint contractures. TOS patients have one of the highest NHP overall score found in the medical literature. The TOS "average" patient has a perceived health status very distressed. Further studies will be needed to adjust the results with another social and anthropological variables. •] TOXIC OIL SYNDROME: UNIQUE CHALLENGES IN TOXICOLOGY R.M. Philen, M. Posada, R.H. Hill, H. Schurz, I. Abaitua, A. Gomez, E.M. Kilbourne. Centersfor Disease Control and Prevention, Centerfor Environmental Health, 4770 Buford Highway, Atlanta, GA 30341 USA In the spring of 1981 the epidemic that came to be known as toxic oil syndrome (TOS) was first identified in Spain. Ultimately, more than 20,000 people were affected. Several early epidemiologic studies were aimed at identifying the causative agent of TOS, including studies in Navas del Marques, Avila. The pivotal study was done in a pediatric hospital in Madrid, and identified the causative agent as an aniline denatured oil which was sold for human consumption in unlabeled 5 liter containers. Further epidemiologic studies showed that this illicit oil had been diverted from industrial use, refined in order to remove the aniline denaturant, and sold by traveling salesmen, often in mercadillos. The epidemiologic investigation of TOS involved all facets of investigative and analytic work, from visits to factories and interviews of workers, to the use of sophis- ticated chemical and statistical analytic techniques. Although initial chemical studies excluded a wide variety of potential toxicants, the causative agent of TOS has yet to be identified. Two studies, which we called "toxico-epidemiologic" studies, because they combine chemical analytic data with statistical methods, have pointed to several chemical compounds as good markers of oils which should be further investigated. Some of the chemical compounds found in the oils studied have been further identified through work which employs recent advances in chemical technology, making possible the continued study of case-related toxic oils and their contaminants. The identification and characterization of these suspect chemical compounds and the elucidation of their effects in in-vivo or in-vitro systems may one day contribute to the prevention of similar diseases, in particular connective tissue syndromes such as systemic lupus erythematosus and scleroderma. [ S • - • TOXICOLOGISTSVERSUS TOXICOLOGICAL DISASTERS:TOXIC OIL SYNDROME (TOS). ANALYTICAL CHEMISTRY/ANALYTICAL TOXICOLOGY Helen H. Schurz *, Robert H. Hill, Manuel Posada de la Paz, Rossanne Philen, Ignacio Abaitua Borda, Edwin M. Kilbourne. Centers for Disease Control and Prevention, Center for Environmental Health, 4770 Buford Highway, Atlanta, GA 30341 USA Toxic oil syndrome was an unprecedented disease that broke out in 1981 centered mostly in Madrid, Spain. Since the outbreak, many laboratories throughout the world have searched for the cause of this disease, and at the Centers for Disease Control and Prevention, we have been fortunate to have participated in this effort. The medium associated with the cause of TOS was a rapeseed oil that had been purchased in France, denatured with aniline, refined in Spain to remove the aniline, and finally mixed with various other oils before being sold to the public. The focus of this talk will be to discuss the results of our laboratory investigations into the contamination of the oils, that is, compounds that were formed by the chemical reac- tion of aniline with tfiglycerides [1]. We used atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) in our analyses, which is a new technique that was not available at the