AbstractNaphthalene (NA) is metabolically activated to the reactive intermediates, naphthalene oxide (NO) and naphthoquinones. To investigate the role of circulating reactive metabolites in NA toxicity, the half-life of NO was examined. The in vitro half-life of NO in both whole blood and plasma was 10min. Detectable levels of NO were seen in perfusate leaving the isolated perfused liver of B6C3F1 mice infused with 10mol/h NA. Identification of protein sulfhydryl adducts in NA-exposed mice (50 and 100mg/kg, IP, 24h) revealed a predominance of quinone adducts in liver, lung, kidney, red blood cells and brain. The epoxide adduct predominated in plasma protein. Administration of the sulfate conjugate of 1,4-dihydroxynaphthalene (NHQS) (100mg/kg) resulted in formation of naphthoquinone protein sulfhydryl adducts in lung, liver and kidney. Administration of 1,4-naphthoquinone (NQ) (5mg/kg) produced NQ adducts in liver, lung, kidney, plasma and brain.