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

• Published in: Chemical research in toxicology Vol. 12; no. 12; pp. 1127 - 1137
• Main Authors: Ladona, Margarita G, Bujons, Jordi, Messeguer, Angel, Ampurdanés, Coral, Morató, Anna, Corbella, Jacint
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-12-1999
• Subjects: 3-phenylamino-1,2-propanediol; Animals; beta-Naphthoflavone - pharmacology; Biotransformation; Enzyme Induction - drug effects; Injections, Intraperitoneal; Mice; Mice, Inbred C57BL; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Plant Oils - poisoning; Poisoning - metabolism; Propylene Glycols - chemistry; Propylene Glycols - pharmacokinetics; Spain; Species Specificity; Syndrome
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx990105j

In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were detected in oils and implicated as potential toxic agents and markers of toxic oil batches. Epidemiological evidence points to 3-(phenylamino)propane-1,2-diol derivatives as the putative toxic agents, which were generated during the refining process at the ITH refinery. Here we present the biotransformation and clearance of 3-(phenylamino)propane-1,2-diol (PAP) administered intraperitoneally to A/J and C57BL/6 mice that have been proposed as a murine model for the immunological features of TOS. Mice eliminated 6 μCi of [U-14C]PAP during a 24 h period, mostly in urine. Animals exhibited urine elimination rates of 70 and 36% in A/J and C57BL/6 strains, respectively. A/J mice exhibited no increase in the elimination rate when induced with β-naphthoflavone, whereas C57BL/6 did increase the rate of elimination to 57%. Feces contributed to a lesser extent to the elimination 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 coupled to UV and radioisotope detectors and further GC/MS analyses. 2-Hydroxy-3-(phenylamino)propanoic acid metabolite was the major chemical species excreted in urine in both strains, in both control and induced animal groups. This compound was the main urinary metabolite of PAP, and unmetabolized PAP excreted in urine constituted less than 1% of the total administered dose. Two additional highly polar metabolites also detected in urine were identified as 3-[(4‘-hydroxyphenyl)amino]propane-1,2-diol and 2-hydroxy-3-[(4‘-hydroxyphenyl)amino]propanoic acid. These findings are the first reported on PAP metabolism and clearance in mice strains and suggest that PAP can be extensively metabolized in vivo and potential reactive species can be generated.