The etiologic agent(s) that was responsible for the 1981 toxic oil syndrome [TOS] epidemic in Spain has not been identified. Liquid chromatography combined with atmospheric pressure ionization tandem mass spectrometry was used for the analysis of oils associated with TOS. Analyses focused on measuring 3-(N-phenylamino)-1,2-propanediol [PAP], the 3-oleyl ester of PAP [MEPAP], and the 1,2-di-oleyl ester of PAP [DEPAP]. DEPAP and MEPAP were found more frequently and at higher concentrations in TOS case-associated oils than in control oils with odds ratios of 13.7 (95% CI 5.0-38) and 21.9 (95% 6.1-78), respectively. Other fatty acid esters of PAP are also likely to be present in the TOS case-associated oils. More significantly, DEPAP and MEPAP were found in aniline-denatured rapeseed oil refined at ITH, the oil refining company with the clearest link to TOS cases, yet these PAP esters were not detected in unrefined aniline-denatured samples of rapeseed oil delivered to ITH. These results show that the esters of PAP were products of the ITH refining process and were not formed spontaneously during storage. PAP esters were not detected in samples of other aniline-denatured rapeseed oils that were refined elsewhere, and which were not associated with illness. These findings provide strong support for the hypothesis that one or more of the fatty acid esters of PAP were the etiologic agents for TOS.

TS translated the surveys into their native languages and disseminated them in their respective countries. All authors have read and approved the final manuscript.

In rare disease (RD) research there is a huge need to systematically collect biomaterials, phenotypic and genomic data in a standardized way and to make them Findable, Accessible, Interoperable and Reusable (FAIR). RD-Connect is a 6 years global infrastructure project initiated in November 2012 that links genomic data with patient registries, biobanks, and clinical bioinformatics tools to create a central research resource for RDs. Here we present RD-Connect Registry & Biobank Finder, a tool that helps RD researchers to find RD biobanks and registries and provide information on the availability and accessibility of content in each database. The Finder concentrates information that is currently sparse on different repositories (inventories, websites, scientific journals, technical reports, etc.), including aggregated data and metadata from participating databases. Aggregated data provided by the Finder, if appropriately checked, can be used by researchers who are trying to estimate the prevalence of a RD, to organize a clinical trial on a RD, or to estimate the volume of patients seen by different clinical centers. The Finder is also a portal to other RD-Connect tools, providing a link to the RD-Connect Sample Catalogue, a large inventory of RD biological samples available in participating biobanks for RD research. There are several kinds of users and potential uses for the RD-Connect Registry & Biobank Finder, including researchers collaborating with academia and the industry, dealing with the questions of basic, translational and/or clinical research. As of November 2017 the Finder is populated with aggregated data for 222 registries and 21 biobanks.