Toxic and genotoxic effects of azaarenes: Isomers and metabolites

Heterocyclic PAH and their metabolites can show toxic, mutagenic, carcinoge nic and teratogenic effects. In this study, a relation between toxic and mu tagenic effects, and chemical structures of nitrogen substituted polycyclic hetero-aromatic hydrocarbons was sought using seven azaarenes and two azaa rene metabolites. Survival of first instar larvae of the midge Chironomus r iparius was determined to measure toxicity. Mortality increased with increa sing number of aromatic rings of the compound, but metabolism of acridine a nd phenanthridine to 9(10H)-acridone and 6(5H)-phenanthridinone, respective ly, strongly decreased toxicity. However, acridone was the most genotoxic o f the azaarenes tested in the Mutatox(TM) test. Although mortality and geno toxic activity are well described by molecular descriptors relevant to bioa ccumulation, in both cases exceptions are found on this general rule, even between isomers. Furthermore, it is shown that metabolism of azaarenes chan ged the impact on different biological end-points, clearly putting severe l imitations on environmental standards solely based on the narcotic effects of parent PAH.