A Comparative Study Of Tissue Distribution And Excretion Among Three Substances Implicated In Eosinophilia-Myalgia Syndrome

Epidemiological studies have suggested that L-tryptophan(L-TRP) produced by a specific manufacturer may be implicated in eosinophilia-myalgia syndrome(EMS) in the United States and other countries(Belongia et al., 1990). The implicated L-TRP has been shown to contain more than 60 impurities(Hill et al., 1993), some of which might contribute to EMS(Centers for Disease Control, 1990; Crofford et al., 1990). Of these, the first impurity statistically associated with EMS was identified as l,l’-ethylidenbis [tryptophan] (EBT) (Mayeno et al., 1990). EBT was vulnerable to acid and readily decomposed to 1-methyltetrahydro-β-carboline(MTCA) in artificial gastric fluid(CDC 1990). In addition MTCA was detected in blood and urine of rats treated with EBT(Adachi et al., 1993). A second impurity has now been isolated(Toyo’oka et al., 1991), and its chemical structures has been determined to be 3-(phenylamino)alanine(PAA) (Goda et al., 1992). We administered EBT, MTCA and PAA to rats to compare their distributions and excretions. We then investigated the effect of chronic treatment of PAA on the tissue concentration and the retention of PAA in their tissues following the animals’ return to a standard control diet. Finally, we investigated its metabolites in rat urine.