Carcinogenesis Bioassay of Allyl Isothiocyanate (CAS No. 57-06-7) in F344/N Rats and B6C3F1 Mice (Gavage Study)
Chemical Formula: C4H5NS
A 2-year carcinogenesis bioassay of food-grade allyl isothiocyanate (greater than 93% purity), a flavoring agent, was conducted by administering 12 or 25 mg/kg allyl isothiocyanate in corn oil five times per week by gavage to groups of 50 F344/N rats and 50 B6C3F1 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.
A single-dose study, a 14-day study, and a 13-week study were performed before the chronic study was conducted. Pathologic findings seen in the 14-day study at 50 mg/kg included a thickened mucosal surface of the stomach in rats and mice and a thickened urinary bladder wall in male mice. No gross or microscopic lesions were seen at the highest dose level (25 mg/kg) in the 13-week study.
In the chronic study, survival of the dosed and control rats of each sex was comparable. Throughout the study, the mean body weights of high-dose male rats were lower than those of the controls, while during the last half of the study the mean body weights of the low-dose and high-dose female rats were higher than the mean body weights of the control animals. Final body weights in control and dosed groups were comparable.
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/N rats at this laboratory. The incidence of transitional papillomas in male vehicle control rats in all laboratories in the NCI/NTP Bioassay Program is 1/994 (0.1%). Epithelial hyperplasia in the urinary bladder was also observed at increased incidences in dosed male rats (0/49, 1/49, 6/49). The hyperplasia did not occur in the same animals that had papillomas.
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 incidence in the high-dose group was not significant when compared with that in the control group. The historical incidence of this lesion is 1/591 (0.2%) in untreated control female F344/N rats at this laboratory and 9/999 (0.9%) in female gavage control rats in all laboratories in the Bioassay Program.
Survival of control and dosed female mice, although comparable, was unusually low. Mean body weights of high-dose mice of each sex were higher than those of the controls throughout most of the study. Final body weights in the control and dosed groups were comparable. The mice probably did not receive the maximum tolerated dose of allyl isothiocyanate.
The increased incidence 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%).
Under the conditions of this bioassay, allyl isothiocyanate was carcinogenic for male F344/N rats, causing transitional-cell papillomas in the urinary bladder. Evidence for associating allyl isothiocyanate with subcutaneous fibrosarcomas in female F344/N rats was equivocal. Allyl isothiocyanate was not carcinogenic for B6C3F1 mice of either sex.
Report Date: October 1982