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E assumes that pollution impacts start at lower (molecular) levels of biological hierarchy and later cascade to ecologically more relevant levels. Another major assumption is of monotonic toxicity (i.e., equal or greater effects as contaminant exposure increases). These dogmas fostered an analytical reductionism that tackled traditional chemical pollution. Contemporary society requires a broader sense of sustainability, however. In this context, planetary boundaries are of direct concern to ecotoxicology as the boundary “novel entities” refer to the new forms of chemical, particulate, energy, or microbiological contaminants. Reductionist ecotoxicology may fail to protect ecosystems whenever the effects of novel entities interact with the complexity of the biosphere. Incremental improvements in current ecotoxicology are unlikely to provide timely solutions for the many pressing sustainability challenges. Thus, there are four vital updates required to prepare ecotoxicology for the Anthropocene. Update 1: Single vs Mixture. Toxicity risk assessments are based on single compounds, whereas the environmental exposure occurs as complex contaminant mixtures. This deep-rooted problem has particularly acute consequences now. There are ∼8 000 000 commercial chemicals, but ecotoxicological data are available for less than ∼100 000. Testing individual contaminants is a challenge and testing all relevant mixtures and environmental conditions is virtually impossible. Despite achievements made on nontarget screening for environmental contaminants and toxicity, such piecemeal advances might provide only obsolete solutions. A new way to monitor homeostasis in multistressed biological systems focusing on biological resilience is required. Update 2: Lethal vs Sublethal. The increasing diversity of contaminants is accompanied by a decrease of the lethal toxicity of new contaminants. Meant to be safer, novel entities entail individually lower lethality than their predecessors. Nevertheless, the perspective of a progressively diverse sublethal mixture of stressors threatens the central assumption of monotonicity. Acute mortality is a drastic outcome and it may be mostly monotonic to single chemicals. However, the sustainability of life forms (e.g., nourishing, reproduction, behavior) requires machinery that may be adversely affected in multiple nonmonotonic ways. From gene expression to endocrine systems, or from proper display of phenological traits in trees to the mating songs of animals, successful survival of populations is replete with responses highly dependent on physiological modulation (referred as mediation in statistics). Mediated processes often exhibit nonlinearity (i.e., one endpoint influences the dose−response of other endpoints), and hence lack of monotonicity. Low doses of pollutants could interact with vital processes other than lethal toxicity targets, thus modulating significant sublethal effects. Numerous critical environmental transitions are attributed to the interaction of sublethal stressors. Sublethal contaminants, albeit individually accounting for negligible lethality, in combination may trigger more severe effects at population levels indirectly by adverse effects on reproduction (behavior, gamete production, etc.) or on the immune system as shown for endocrine disruptors and light pollution. Ecotoxicology should go beyond lethality and focus on the resilience of biological systems. Update 3: Chemical vs Novel Entity. Contaminants are chemicals, materials, particles, or energy. Current ecotoxicological principles apply predominantly to chemicals, however. Moreover, the combination of chemical and nonchemical stressors frequently yields more-than-additive effects. Novel entities with potential to impact the biosphere such as microbiological contaminants, nanoparticles, polymer-based materials, and light pollution interact with biota differently from chemicals. Traditional assumptions might simply not hold true because these stressors differ in their inherent energetic, temporal, and spatial patterns. We reported clear nonmonotonicity for a microbial-based biopesticide used

Novel Concepts for Novel Entities: Updating Ecotoxicology for a Sustainable Anthropocene