POSSIBLE ETIOLOGIC AGENTS FOR TOXIC OIL SYNDROME - FATTY-ACID ESTERS OF 3-(N-PHENYLAMINO)-1,2-PROPANEDIOL

The etiologic agent(s) that was responsible for the 1981 toxic oil syn drome [TOS] epidemic in Spain has not been identified. Liquid chromato graphy combined with atmospheric pressure ionization tandem mass spect rometry was used for the analysis of oils associated with TOS. Analyse s 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 concentratio ns in TOS case-associated oils than in control oils with odds ratios o f 13.7 (95% CI 5.0-38) and 21.9 (95% 6.1-78), respectively. Other fatt y acid esters of PAP are also likely to be present in the TOS case-ass ociated oils. More significantly, DEPAP and MEPAP were found in anilin e-denatured rapeseed oil refined at ITH, the oil refining company with the dearest link to TOS cases, yet these PAP esters were not detected in unrefined aniline-denatured samples of rapeseed oil delivered to I TH. These results show that the esters of PAP were products of the ITH refining process and were not formed spontaneously during storage. PA P esters were not detected in samples of other aniline-denatured rape seed oils that were refined elsewhere, and which were not associated w ith illness. These findings provide strong support for the hypothesis that one or more of the fatty acid esters of PAP were the etiologic ag ents for TOS.