Drawing a Line: Where Might the Cohort of Concern End?

The definitions of the chemical classes in Cohort Concern (CoC) by Kroes and co-workers are based on broad structural alerts, particular for N-nitroso compounds?for which alert consists essentially N–N?O substructure without further refinement. Recent pharmaceutical recalls have focused presence dialkyl N-nitrosamine impurities, some exceptionally potent carcinogens?2 orders magnitude more than Threshold Toxicological (TTC), 1.5 ?g/day. However, class “N-nitroso compounds” is potentially significantly broader. This Perspective looks at compounds that edges cohort, where changes mechanism, metabolic activation potential, stability, or indeed toxicity data lead to questions about whether these should be classed as CoC. critical mechanism action, ?-hydroxylation leading a diazonium ion, presented, along with pathways not N-nitrosamines can comparable DNA adducts.