The disposition of allyl isothiocyanate in the rat and mouse

Abstract

The urine was the major route of excretion of radioactivity (50–80% of dose) following the oral administration (2.5 and 25 mg/kg body weight) of allyl[ 14isothiocyanate (AITC) to male and female Fischer 344 rats and B6C3F 1 mice. Smaller amounts were found in the faeces (6–12%) and expired air (3–7%). The major difference between the two species was the greater retention of radioactivity after 4 days within rats (18–24% of dose) when compared with mice (2–5% of dose). Thre radioactive components were found in the urine of mice and two in rats. The three components were inorganic thiocyanate, allylthiocarbamoylmercapturic acid and allylthiocarbamoylcysteine in mice, but no cysteine conjugate was found in rat urine. In the mouse, approximately 80% of the 14C was present in the urine as the thiocyanate ion whereas in the rat some 75% was as the mercapturate. This indicates that in the mouse, hydrolysis of AITC was the major metabolic pathway whereas in the rat glutathione conjugation was the major route. A species difference was seen in the amount of [ 14C]AITC-derived radioactivity present in the whole blood of rats and mice; measurable levels of radioactivity remained within rat blood for a longer time period (up to 240 hr) when compared with mice (96 hr). Examination of the urinary bladders of male and female rats following oral dosing with [ 14C]AITC showed a sex difference with greater amounts of [ 14C]AITC and/or its metabolites within the bladder tissue of male rats. This data is discussed in terms of the known species- and sex-specificity of the urinary bladder tumours, which occurred after long-term administration to male rats, but not to female rats or mice of either sex, in a carcinogenicity study conducted by the National Toxicology Program in the USA.