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Subchronic toxicity evaluation of 5-hexenyl isothiocyanate, a nature identical flavoring substance from Wasabia japonica, in F344/DuCrj rats

Akagi, Jun-ichi, Cho, Young-Man, Mizuta, Yasuko, Toyoda, Takeshi, Ogawa, Kumiko
Food and chemical toxicology 2018 v.122 pp. 80-86
Eutrema japonica, bladder, body weight changes, cholesterol, females, heart, hyperplasia, intragastric administration, isothiocyanates, liver, males, no observed adverse effect level, rats, subchronic toxicity, toxicology, triacylglycerols
5-Hexenyl isothiocyanate (5-HeITC) is a naturally derived flavoring substance from Wasabia japonica. To clarify the toxicological profile of 5-HeITC, we performed a subchronic toxicity study of 5-HeITC with intragastric administration at daily doses of 0, 3, 12, or 48 mg/kg body weight (BW) to 6-week-old male and female F344/DuCrj rats for 13 weeks. Body weight gain was decreased in the male 48 mg/kg BW group. Decreased triglycerides were observed in the male over 12 mg/kg BW and female 48 mg/kg BW groups. Decreased total cholesterol was observed in the male 48 mg/kg BW group. Increases in relative liver weights were observed in the male 48 mg/kg BW and female over 12 mg/kg BW groups. Increases in absolute and relative heart weights were observed in the female over 12 mg/kg BW groups. Simple hyperplasia in the urinary bladder was found in the male and female 12 mg/kg BW groups, and nodular hyperplasia was found in the female 48 mg/kg BW group. Based on these findings, the target organs of 5-HeITC were determined to be the urinary bladder, heart, and liver. The no-observed-adverse-effect level of 5-HeITC for both sexes was estimated to be 3 mg/kg BW.