The subchronic toxicity of oral L-tryptophan produced by fermentation with metabolically engineered Corynebacterium glutamicum was evaluated in Sprague-Dawley rats. Doses of 0, 500, 1000, and 2000 mg/kg/day were administered to groups of 10 male and 10 female rats for 90 days. For the groups administered 0 and 2000 mg/kg/day, an additional 5 male and 5 female rats were tested as a recovery group. No adverse effects associated with the test substance were observed in all rats during the 90-day administration of the product, irrespective of dose, and at 4 weeks of recovery at dosages of 0 and 2000 mg/kg/day. Furthermore, histochemical and immunohistochemical analyses for L-tryptophan-associated eosinophilia-myalgia syndrome (EMS) did not reveal significant changes in both sexes of groups administered 0 or 2000 mg/kg/day. Based on these results, it could be concluded that there were no significant adverse effects related to the test substance in all animals; therefore, dried L-tryptophan fermentation product can be used as feed additive material.
Keywords: BUN, blood urea nitrogen; DRF, dose range-finding; Dried L-tryptophan fermentation product; EMS, eosinophilia-myalgia syndrome; Eosinophilia-myalgia syndrome; FFPE, formalin-fixed paraffin-embedded; GHS, globally harmonized system; GLP, good laboratory practice; HED, human equivalent dose; IHC, immunohistochemistry; Metabolically engineered Corynebacterium glutamicum; NOAEL, no observed adverse effect level; OECD, Organization for Economic Cooperation and Development; Oral administration; SD, Sprague-Dawley; Subchronic toxicity; WBC, white blood cell; pAb, polyclonal antibody.
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