The potential long-term, irreversible impacts from the rapidly increasing emissions of TFA from anthropogenic sources should be used as a rationale to start immediately discussing policy, industry and innovation actions towards the phase-out of high-volume substances that lead to increasing TFA accumulation. Obvious places to start would be to limit the direct production of TFA, and more importantly, of TFA-precursors, such as HFOs (like HFO-1234yf) and pesticides such as flufenacet . Other pharmaceuticals, veterinary products and industrial chemicals that release TFA via transformation processes 7 should also be considered for phase-out or substitutions, following the principles of safe-and-sustainable by design 124 and essential use 125 to avoid regrettable substitution 126 to more hazardous substances. As discussions and policy mechanisms to phase out the sources of TFA could take some time, the rational response to the global threat posed by accumulating TFA is to act swiftly before the irreversible impacts are manifested at a global scale to humans and the environment.