Ecotoxicology in the Context of Biodiversity Loss: Lessons from Seven Decades of Chemical Impacts and Paths Forward.

Chemical pollution is a major anthropogenic driver of biodiversity loss, yet its relative contribution compared to other stressors remains difficult to quantify. Ecotoxicology emerged as a discipline in response to evidence that chemicals in the environment can harm wildlife, but anticipating and preventing ecological damage remains challenging. This Review examines how ecotoxicology research has informed environmental protection, drawing on case studies spanning over 70 years, including pesticides and birds, tributyltin and mollusks, diclofenac and vultures, and 6PPD-quinone and salmon. These examples highlight recurring challenges─such as unpredicted species-specific sensitivities, unanticipated exposure pathways, and modes of action overlooked by standard testing frameworks─that have typically resulted in reactive rather than preventive regulatory responses. In light of the thousands of chemicals in use and widespread environmental mixtures, the Review evaluates strengths and limitations of current ecotoxicological testing and regulatory practices. It proposes pragmatic principles for enhanced protection, emphasizing prevention, prioritization under uncertainty, improved predictive capacity, and cross-sector collaboration, while acknowledging inevitable trade-offs between environmental safeguards and essential societal uses of chemicals. The Review argues that ecotoxicology must evolve rapidly by embracing predictive non-animal and data-driven approaches to more effectively reduce the risk of severe, widespread, or irreversible ecological harm.