BIOTRANSFORMATION OF 3-(PHENYLAMINO)-1,2-PROPANEDIOL TO 3-(PHENYLAMINO)ALANINE - A CHEMICAL LINK BETWEEN TOXIC OIL SYNDROME AND EOSINOPHILIA-MYALGIA-SYNDROME

During late 1989, the eosinophilia-myalgia syndrome (EMS) developed as an epidemic in the United States, with numerous additional cases repo rted in several other countries worldwide. Eight years earlier, a clos ely-related disease, the toxic oil syndrome (TOS), occurred in Spain a s a massive food-borne epidemic. Although EMS was linked to the ingest ion of tainted L-tryptophan, and TOS to aniline-denatured rapeseed oil , the etiologic agent(s) responsible for both diseases remains undeter mined. Contaminants in these foodstuffs are believed to have triggered the diseases. Aniline contaminants, including 3-(phenylamino)-1,2-pro panediol (PAP), have been reported in oil used by patients who develop ed TOS. A related aniline derivative, 3-(phenylamino)-L-alanine (PAA), was recently isolated from L-tryptophan associated with the onset of EMS. Here, we demonstrate the biotransformation of PAP into PAA by bot h rat hepatocytes and human liver tissue. The structural characterizat ion of PAA was unequivocally determined using on-line HPLC coupled wit h atmospheric pressure chemical ionization tandem mass spectrometry (L C-APCI-MS/MS). This finding is the first reported chemical link betwee n TOS and EMS and suggests that these two related diseases share a com mon etiology, namely, PAA.