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

Food Chem Toxicol. 2018 Dec;122:80-86. doi: 10.1016/j.fct.2018.09.060. Epub 2018 Sep 25.


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.

Keywords: 5-hexenyl isothiocyanate; F344/DuCrj rats; Food additives; Subchronic toxicity study; Urinary bladder hyperplasia.

MeSH terms

  • Administration, Oral
  • Animals
  • Body Weight / drug effects
  • Clinical Chemistry Tests
  • Dose-Response Relationship, Drug
  • Female
  • Flavoring Agents / administration & dosage
  • Flavoring Agents / toxicity*
  • Heart / drug effects
  • Hematologic Tests
  • Hyperplasia / chemically induced
  • Isothiocyanates / administration & dosage
  • Isothiocyanates / toxicity*
  • Liver / drug effects
  • Male
  • No-Observed-Adverse-Effect Level
  • Organ Size / drug effects
  • Rats, Inbred F344
  • Toxicity Tests, Subchronic
  • Urinary Bladder / pathology
  • Wasabia / chemistry*


  • Flavoring Agents
  • Isothiocyanates
  • 5-hexenyl isothiocyanate