Biotransformation and clearance of 3-(Phenylamino)propane-1,2-diol, a compound present in samples related to toxic oil syndrome, in C57BL/6 and A/J mice

In May 1981, a massive food-borne intoxication occurred in Spain. The so-ca lled toxic oil syndrome (TOS) was associated with the consumption of anilin e-denatured and refined rapeseed oil that was illegally sold as edible oliv e oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)pro pane-1,2-diol were detected in oils and implicated as potential toxic agent s and markers of toxic oil batches. Epidemiological evidence points to 3-(p henylamino)propane-1,2-diol derivatives as the putative toxic agents, which were generated during the refining process at the ITH refinery. Here we pr esent the biotransformation and clearance of 3-(phenylamino)propane-1,2-dio l (PAP) administered intraperitoneally to A/J and C57BL/6 mice that have be en proposed as a murine model for the immunological features of TOS. Mice e liminated 6 mu Ci of [U-C-14]PAP during a 24 h period, mostly in urine. Ani mals exhibited urine elimination rates of 70 and 36% in A/J and C57BL/6 str ains, respectively. A/J mice exhibited no increase in the elimination rate when induced with P-naphthoflavone, whereas C57BL/6 did increase the rate o f elimination to 57%. Feces contributed to a lesser extent to the eliminati on rate (0.6 and 3.3% in A/J and C57BL/6 mice, respectively). Radioactivity remaining in organ tissues was lower than 1% (liver, lung, kidney, spleen, heart, and muscle). Metabolic species in urine were identified by HPLC cou pled to UV and radioisotope detectors and further GC/MS analyses. 2-Hydroxy -3-(phenylamino)propanoic acid metabolite was the major chemical species ex creted in urine in both strains, in both control and induced animal groups. This compound was the main urinary metabolite of PAP, and unmetabolized PA P excreted in urine constituted less than 1% of the total administered dose . Two additional highly polar metabolites also detected in urine were ident ified as 3- [(4'-hydroxyphenyl)amino] propane-1,2-diol and 2-hydroxy-3-[(4' -hydroxyphenyl) amino] propanoic acid. These findings are the first reporte d on PAP metabolism and clearance in mice strains and suggest that PAP can be extensively metabolized in vivo and potential reactive species can be ge nerated.