Carcinogenesis bioassay of allyl isothiocyanate

Abstract

Allyl isothiocyanate is a food additive present in many foods and a constituent of oil of mustard and mustard, and is generally considered safe for human consumption. This study was undertaken to determine the carcinogenic potential of food grade allyl isothiocyanate. Allyl isothiocyanate was administered at 12 or 25 mg/kg in corn oil five times per week by gavage to groups of 50 Fischer 344 rats and 50 B6C3F 1 mice of each sex for 103 weeks. Groups of 50 rats and 50 mice of each sex received corn oil alone and served as vehicle controls. Transitional-cell papillomas in the urinary bladder occurred in dosed male rats with a statistically significant trend (p<0.05; controls, 0/49, 0%, low-dose, 2/49, 4%; high-dose, 4/49, 8%). This tumor has not been observed among 568 untreated male control F344 rats at this laboratory. The prevalence of transitional-cell papillomas in male vehicle control and untreated control rats in all laboratories in the NCI/NTP Bioassay Program 2 is only 1/994 (0.1%) and 5/3888 (0.1%) respectively. Administration of allyl isothiocyanate also increased the prevalence of epithelial hyperplasia of the urinary bladder in male rats. Leukemia occurred in dosed male rats with a statistically significant positive trend (p<0.05; controls, 2/50, 4%; low-dose, 6/50, 12%; high-dose, 8/50, 16%). However, because the incidence of leukemia in dosed male rats is similar to the mean historical control rate at this laboratory, this increase was not considered to be related to the administration of allyl isothiocyanate. Fibrosarcomas in the subcutaneous tissue occurred in female rats with a statistically significant positive trend (p<0.05; controls, 0/50, 0%; low-dose, 0/50, 0%; high-dose, 3/50, 6%), but the prevalence in the high-dose group was not significant when compared with that in the control group. Thus, the evidence for allyl isothiocyanate causing this tumor was considered equivocal. Evidence of an association between administration of allyl isothiocyanate and increased tumor incidence was not seen in mice. However, an increased prevalence of cytoplasmic vacuolization in the liver of dosed male mice was related to administration of allyl isothiocyanate (controls, 2/49, 4%; low-dose, 8/49, 16%; high-dose, 13/50, 26%). In large doses, food grade allyl isothiocyanate produces a slight but statistically significant increase in benign urinary bladder tumors (a rare neoplasm) in male F344 rats.