I-NAPHTHYL ISOCYANATE AND 1-NAPHTHYLAMINE AS METABOLITES OF 1-NAPHTHYLISOTHIOCYANATE

The importance of the bioactivation of 1-naphthylisothiocyanate was st udied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excis ed and homogenized. 1-naphthylisothiocyanate and its metabolites in bi le and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in a ll 1-naphthylisothiocyanate-treated animals. They were identified as 1 -naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-napht hylisothiocyanate. When rats were given cycloheximide, which attenuate s 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocy anate (300 mg/kg), 1-naphthyl isocyanate concentration was significant ly lower than in rats receiving only 1-naphthylisothiocyanate. The app earance of 1-naphthylamine was also inhibited by cycloheximide, althou gh not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxic ity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highl y reactive sulfur released from 1-naphthylisothiocyanate might be invo lved in the hepatotoxic effect of 1-naphthylisothiocyanate.