title: Possible etiologic agents for toxic oil syndrome: fatty acid esters of 3-(N-phenylamino)-1,2-propanediol.
abstract: 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.
authors.affiliation: National Center for Environmental Health, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia 30341-3724.
authors.forename: R H
authors.initials: RH
authors.lastname: Hill
authors.forename: H H
authors.initials: HH
authors.lastname: Schurz
authors.forename: M
authors.initials: M
authors.lastname: Posada de la Paz
authors.forename: I
authors.initials: I
authors.lastname: Abaitua Borda
authors.forename: R M
authors.initials: RM
authors.lastname: Philen
authors.forename: E M
authors.initials: EM
authors.lastname: Kilbourne
authors.forename: S L
authors.initials: SL
authors.lastname: Head
authors.forename: S L
authors.initials: SL
authors.lastname: Bailey
authors.forename: W J
authors.initials: WJ
authors.lastname: Driskell
authors.forename: J R
authors.initials: JR
authors.lastname: Barr
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism / Q000506:poisoning*; D001937:Brassica; D004952:Esters; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated; D010938:Plant Oils / Q000506:poisoning*; D011041:Poisoning / Q000209:etiology; D011409:Propylene Glycols / Q000032:analysis* / Q000633:toxicity; D000074262:Rapeseed Oil; D013030:Spain; D013577:Syndrome
chemical_list: D000814:Aniline Compounds; D004952:Esters; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D010938:Plant Oils; D011409:Propylene Glycols; D000074262:Rapeseed Oil; C092834:3-(N-phenylamino)-1,2-propanediol 1-oleoyl ester; C077151:3-phenylamino-1,2-propanediol; C092835:3-(N-phenylamino)-1,2-propanediol 1,2-dioleoyl ester