Potential implication of aniline derivatives in the Toxic Oil Syndrome (TOS).
The Toxic Oil Syndrome (TOS) was an epidemic disease appeared in central Spain in 1981, causing over 400 deaths and affecting more than 20,000 people, mainly women and children. The disease was linked to the consumption of rapeseed oil denatured with aniline, illegally refined at the ITH oil refinery in Seville, mixed with other oils and sold as edible olive oil. Among the aniline derivatives detected in the oil batches generated by an uncontrolled deodorisation procedure during the refining process, fatty acid anilides were first postulated as the causal agents. Nevertheless, compounds identified as 3-(N-phenylamino)propane-1,2-diol (PAP) and its mono-, di-, and triacyl derivatives (mPAP, dPAP and tPAP, respectively), were subsequently considered better biomarkers of toxic oils and the best candidates for causing the intoxication. In this account, we will discuss the results obtained in recent years by our group concerning: (a) The effect of different variables intervening in the deodorisation process that could influence the formation of PAP derivatives. To this end we decided to take the aniline derivatives linked to oleic acid as compound models since this is the fatty acid present in highest amounts in rapeseed oil. The study was focused on the influence of different parameters on the formation of the diester PAP derivative (OOPAP) the monoester derivative (OPAP) and the corresponding amide (oleanilide, OA), and the interactions between any two of these variables. Of particular interest was the interaction observed between OOPAP and OA, due to its potential relevance to the final composition of the toxic oil model. (b) Xenobiochemical aspects of PAP derivatives, specifically: the stereospecific hydrolysis of OPAP and OOPAP by human pancreatic lipase, the in vitro activation of PAP by human and rat liver microsomes as well as by recombinant 450 enzymes, and the formation and stability of GSH and N-acetylcysteine adducts of a highly reactive iminoquinone intermediate generated in the biotransformation of PAP.
Department of Chemical and Biomolecular Nanotechnology, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), J. Girona, 18, 08034 Barcelona, Spain. angel.messeguer@iqac.csic.es
Angel
A
Messeguer
D000814:Aniline Compounds / Q000633:toxicity*; D001711:Biotransformation; D005229:Fatty Acids, Monounsaturated; D006801:Humans; D008049:Lipase / Q000378:metabolism; D010938:Plant Oils / Q000493:pharmacokinetics / Q000506:poisoning*; D000074262:Rapeseed Oil
D000814:Aniline Compounds; D005229:Fatty Acids, Monounsaturated; D010938:Plant Oils; D000074262:Rapeseed Oil; D008049:Lipase; C023650:aniline