THE DISPOSITION OF ALLYL ISOTHIOCYANATE IN THE RAT AND MOUSE

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[C-14]isothiocyanate (AITC) to male and female Fischer 344 r ats 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). Three radioact ive components were found in the urine of mice and two in rats. The th ree components were inorganic thiocyanate, allylthiocarbamoylmercaptur ic acid and allylthiocarbamoylcysteine in mice, but no cysteine conjug ate was found in rat urine. In the mouse, approximately 80% of the C-1 4 was present in the urine as the thiocyanate ion whereas in the rat s ome 75% was as the mercapturate. This indicates that in the mouse, hyd rolysis of AITC was the major metabolic pathway whereas in the rat glu tathione conjugation was the major route. A species difference was see n in the amount of [C-14]AITC-derived radioactivity present in the who le blood of rats and mice; measurable levels of radioactivity remained within rat blood for a longer time period (up to 240 hr) when compare d with mice (96 hr). Examination of the urinary bladders of male and f emale rats following oral dosing with [C-14]AITC showed a sex differen ce with greater amounts of [C-14]AITC and/or its metabolites within th e bladder tissue of male rats. This data is discussed in terms of the known species-and sex-specificity of the urinary bladder tumours, whic h occurred after long-term administration to male rats, but not to fem ale rats or mice of either sex, in a carcinogenicity study conducted b y the National Toxicology Program in the USA. (C) 1997 Elsevier Scienc e Ltd. All rights reserved.