Subchronic toxicity of 3-phenylamino alanine, an impurity in L-tryptophan reported to be associated with eosinophilia-myalgia syndrome.
Consumption of certain product lots of L-tryptophan (LT) has been reported to be epidemiologically associated with an outbreak of eosinophilia-myalgia syndrome (EMS) in the United States. Since the production lots were found to contain 3-phenylamino alanine (PAA) as an impurity, its effects were studied by administering the substance orally by gavage to 5-week-old Sprague-Dawley rats. Groups of animals were given PAA for 13 consecutive weeks at dose levels of 1, 10 and 100 mg/kg per day. The animals were killed at 4 or 8 weeks. Hematological and blood biochemical tests were performed and detailed histopathological observations were made. No significant abnormalities were observed in the test animals and in particular no EMS-like conditions. A brief summary of other animal studies using several species of rats and mice performed in our laboratory since 1989 on various LT related substances is also presented. No EMS-like effects were observed in these studies.
Safety Evaluation Center, Central Research Laboratory, Chiba, Japan.
F
F
Sato
Y
Y
Hagiwara
Y
Y
Kawase
D000284:Administration, Oral; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001774:Blood Chemical Analysis; D001921:Brain / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects; D014018:Tissue Distribution; D014364:Tryptophan / Q000737:chemistry* / Q000378:metabolism
C078798:3-(phenylamino)alanine; D014364:Tryptophan; D000409:Alanine