On the Generation and Outcome of 3-(N-Phenylamino)propane-1,2-diol Derivatives in Deodorized Model Oils Related to Toxic Oil Syndrome

Abstract

Toxic Oil Syndrome (TOS) was a massive food-born intoxication that occurred in Spain in 1981 and affected more than 20,000 people. TOS was attributed to the ingestion of rapeseed oil that had been adulterated with aniline, illegally refined, and delivered for human consumption. Two chemical species derived from aniline have been identified in oil batches: fatty acid anilides, qualified as biomarkers of the adulterated oil, and fatty acid esters of 3-(N-phenylamino)propane-1,2-diol (PAP), considered toxic oil biomarkers. These esters were generated by chemical processes during oil refining, specifically in the deodorization step, which involves treatment of the oil at high temperatures under vacuum to remove volatile contaminants. Since PAP derivatives are strongly associated with TOS, their formation and putative interconversion in a toxic oil model has been studied. The main results obtained are (i) only triglycerides and aniline are required to produce PAP esters, thus eliminating the possibility that unknown activators present in the deodorization tank were required for toxification of the oil; (ii) PAP and PAP mono- and diesters are chemically interrelated, as are anilides and PAP esters to an even higher degree. In addition to the reaction of aniline with triglycerides, anilides can be also formed via attack of PAP esters by aniline. However, the most important source of anilides during deodorization seems to be the thermal decomposition of PAP esters. Overall, these results suggest that the generation and outcome of PAP derivatives during deodorization is a complex scenario whereby PAP esters are not only generated from different reactions but decompose to produce anilides, among other compounds. In addition to providing a rapeseed oil model that reproduces the composition of case oils with respect to anilides and PAP derivatives, the results presented herein further support the hypothesis imputing PAP diesters or their metabolites for the intoxication episode.

LC‐MS ion maps for the characterization of aniline derivatives of fatty acids and triglycerides in laboratory‐denatured rapeseed oil

“…1), such as the mPAPs, d(1,2)PAPs, d(N)PAP, t(1,2,N)PAPs, m(2)bis(1,3)PAPs, m(N)bis(1,3)PAPs, d(N,2)bis(1,3)PAPs and t(N,2,N′)bis(1,3)PAPs. Some of these anilides, mPAPs, (1,2)PAPs and t(1,2,N)PAPs had been identified earlier12, 14, 16 as chemical markers of toxic oils, but the rest, including monoacylated and diacylated compounds with a bis(1,3)PAP core such as the m(2)bis(1,3)PAPs and d(N,2)bis(1,3)PAPs, are described and characterized here for the first time. These compounds, plus a new class of aniline derivatives (t(N,2,N)bis(1,3)PAPs), and four more compounds associated to the t(1,2,N)PAPs, first tentatively described by Shurz et al ,16 are characterized also for the first time.…”

“…A vacuum source (20–30 Torr) was introduced and the system was maintained for 2 h under these conditions. In addition to the synthetic TOS oil that remained in the distillation flask, samples from the volatile material collected in the cold traps were also obtained 12…”

“…Now, in an effort to expand the search for possible causative agents in TOS‐associated oils and to look for new aniline‐related compounds, we carried out an exhaustive characterization of laboratory‐processed oils. These oils, in the presence of aniline doped with 14 C labeled aniline, were submitted to the conditions required for the generation of PAPs and FAA 3, 12, 13. The aim of this study was to account for all possible combinations of triglyceride‐ and fatty‐acid‐related aniline by‐products through selective separation and identification procedures.…”

Food Contamination

“…47 In experimental studies, the yield of 3 -( N -phenylamino) -1,2 -propanediol (PAP) esters in toxic oil syndrome is highest at 250 -300 ° C ( ∼ 480-570 ° F), similar to those temperatures achieved during the deodorizing step of oil refi ning. All other illicit refi ners of denatured rapeseed oil in Catalonia mixed the denatured and edible oils before refi ning the adulterated oils.…”

Synthesis and Stability Studies of the Glutathione and N-Acetylcysteine Adducts of an Iminoquinone Reactive Intermediate Generated in the Biotransformation of 3-(N-Phenylamino)propane-1,2-diol: Implications for Toxic Oil Syndrome

“…In the absence of thiol reagent, this quinoneimine establishes an equilibrium mixture with the corresponding Schiff base, which upon hydrolysis gives rise to the thiol adduct formally derived from p-aminophenol. All of these adducts have been characterized and can be used as standards for the putative identification of these conjugates in biological samples obtained from the treatment of sensitive animal species with deodorized rapeseed model oils (17). These experiments have been planned by the WHO Management Committee and are in due course.…”