Comparative toxicity of N-hydroxy-2-acetylaminofluorene in several strains of rats

Male Spraque-Dawley rats were 6 or 7 times more susceptible than females to the acute toxic effects of a single i.p. injection of N-hydroxy-2-acetylaminofluorene. The N-hydroxy compound were equally toxic in male and female Fischer rats and about twice as toxic to male as to female Wistar rats. A negative correlation between the 50% lethal dose of N-hydroxy-2-acetylaminofluorene and hepatic N-hydroxy-2-acetylaminofluorene sulfotransferase activity was found. These data substantiate earlier indications that the level of the liver sulfotransferase is an important factor in determining the degree of toxicity of N-hydroxy-2-acetylaminofluorene. It is suggested that the reported sex difference in the hepatocarcinogenicity of N-hydroxy-2-acetylaminofluorene might be peculiar to the Sprague-Dawley rat.