Persistent Non-Metabolizable Selective Agents (PeNSAs) as a New Framework for Evolutionary Toxicology in the Anthropocene

Persistent anthropogenic contaminants increasingly shape evolutionary processes across natural populations. While many pollutants can be metabolized, degraded, or eliminated, a subset of highly persistent compounds remains in ecosystems and organisms over ecologically and evolutionarily relevant timescales. Here, we propose the concept of Persistent Non-metabolizable Selective Agents (PeNSAs) to describe contaminants that exert chronic selective pressures while resisting biological degradation and effective elimination. Using per- and polyfluoroalkyl substances (PFASs) as a model case, we argue that exposure to PeNSAs creates a distinctive evolutionary regime in which adaptation is more likely to proceed through tolerance, physiological compensation, and damage mitigation than through contaminant removal. This dynamic generates a decoupling between adaptation and remediation, whereby populations may evolve increased fitness under exposure while contaminant burdens remain unchanged. We develop a conceptual framework describing the ecological and evolutionary consequences of PeNSA exposure, including energetic trade-offs, incomplete evolutionary resolution, maintenance of genetic variation, and heterogeneous adaptive outcomes among populations. We further derive testable predictions that distinguish PeNSA-driven evolution from classical models of resistance and detoxification. By integrating evolutionary biology, ecotoxicology, and environmental science, the PeNSA framework provides a foundation for investigating adaptation to persistent contaminants and highlights implications for environmental monitoring, risk assessment, and ecosystem management in the Anthropocene.