Methylated derivatives of pyrene and fluorene: Evaluation of genotoxicity in the hepatocyte/DNA repair test and tumorigenic activity in newborn mice

The genotoxicity of 1‐methylpyrene, 1,6‐dimethylpyrene, 1‐methylfluorene, 9‐methylfluorene, and 1,9‐dimethylfluorene was evaluated in the hepatocyte primary culture/DNA repair test, and the tumorigenic potency of these compounds was tested by bioassay in newborn mice. With the exception of 1‐methylfluorene, all of these methylated polycyclic aromatic hydrocarbons are known mutagens in Salmonella typhi‐murium. Both 1‐methylpyrene and 1,6‐dimethylpyrene induced unscheduled DNA synthesis in rat hepatocytes. However, only 1‐methylpyrene was tumorigenic when administered to newborn male mice. None of the methylated fluorenes assayed in the hepatocyte primary culture/DNA repair test induced unscheduled DNA synthesis. While 1,9‐dimethyfluorene exhibited weak tumorigenic activity when administered by subcutaneous injection to newborn mice, 1‐methylfluorene and 9‐methylfluorene were inactive.