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

Rapeseed oil denatured with aniline was the vehicle of the causal agent of the toxic oil syndrome (TOS) epidemic that occurred in Spain in 1981. Although the precise aetiologic agent remains unknown, researchers established that increasing concentrations of oleyl anilide and other fatty acid anilides were associated with an increased risk for disease. To examine the hypothesis that 5-litre plastic containers of rapeseed oil associated with TOS, and which contained oleyl anilide had a characteristic shape, we measured fatty acid, sterol and fatty acid anilide levels in oil from containers of different shapes. We identified 1673 bottles of oil that had been collected during the Spanish Government's oil exchange programme and linked these bottles to people with TOS as reported in the official government census of patients with TOS. Although rapeseed oil (identified by the presence of brassicasterol) was found in 798 (47.7%) of the 1673 bottles examined, contamination with fatty acid anilide occurred in only 329 (19.6%) of the 1673 bottles and 319 (97%) of the 329 were oil containers of the shape sold by RAELCA, an oil company in Madrid. The first aniline-denatured oil that RAELCA had purchased to be refined specifically for distribution was refined at the ITH refinery of Seville, and this oil has been most directly associated with the epidemic. Previous work has shown that the only toxic oil linked to a specific refinery was that associated with rapeseed oil from the ITH refinery in Seville, and the epidemic began shortly after this oil was delivered to RAELCA for retail sale. On the basis of these findings, we conclude that oil refined by ITH and distributed by RAELCA was the principal, and probably the only, oil responsible for the TOS epidemic. Information about the history and treatment of this oil may yield important clues towards identifying the aetiologic agent of TOS.