Safety Evaluation of 6-(Methylsulfinyl) Hexyl Isothiocyanate (6-MSITC) and Wasabi Sulfinyl, a 6-MSITC-containing Supplement

The safety of 6-(methylsulfinyl) hexyl isothiocyanate (6-MSITC) and Wasabi sulfinyl (WS), a 6-MSITC-containing supplement from Wasabi rhizome, was evaluated by a toxicity test and human clinical trial. Synthetic 6-MSITC (SS) and WS were used in the Ames test to clarify their mutagenic activity, and then used in acute and sub-acute toxicity tests via oral administration in five-week-old Sprague-Dawley rats. WS was further estimated by a human clinical trial. Eleven healthy subjects, aged 20–64 years, were enrolled in the clinical trial; they ingested five WS capsules daily for four weeks. The incidence and severity of WS ingestion-related adverse events were estimated by physical examination, weight and vital sign measurements (resting systolic and diastolic blood pressures, and heart rate), blood analysis, and urinalysis. In the Ames test, no mutagenicity of SS was observed in the range of 20–1 250 µg/plate. Lethal dose 50 (LD50) values of SS were estimated to be 451.2 mg/kg in male rats and 400.7 mg/kg in female rats. No sub-acute toxicity was observed in Sprague-Dawley rats administrated WS at 2 500 mg/kg/day (containing 2.5 mg 6-MSITC/kg/day). In the human clinical trial, three adverse events occurred in 2 of 11 (18.2%) subjects, which were classified not to be side effects from WS ingestion by clinical physicians. Although some fluctuations were observed in clinical laboratory values and physical measurement values, these fluctuations were within the reference ranges without clinical significance. Thus, ingestion of 500 mg/day of WS was demonstrated for the first time to be safe at the least. Taken together, our data on the safety evaluation of 6-MSITC and WS, a 6-MSITC-containing supplement, provide the first standard references for Wasabi supplement application.