The current environmental risk assessment framework for pesticides remains anchored to inadequate metrics and approaches. Although regulatory bodies incorporated chronic toxicity studies and developed advanced guidance, critical gaps in implementation undermine their effectiveness. Among these gaps are 1) continued primacy of the acute median lethal dose as a trigger for higher-tier assessments, 2) lack of standardized sublethal endpoints, 3) inadequate consideration of chemical mixtures, and 4) near-exclusive reliance on Apis mellifera as a surrogate for pollinator communities. Further, interactions between pesticides and other environmental stressors are not systematically assessed. This review critically examines the limitations of the current paradigm and proposes a structured, ecologically integrated framework for modernizing pollinator risk assessment. This review outlines 7 pillars: 1) taxonomic diversification of test species, 2) mandatory inclusion of chronic and sublethal endpoints at Tier 1, 3) standardization of sublethal behavioral assays, 4) tiered assessment of pesticide mixtures incorporating increasingly realistic ecological scenarios, 5) incorporation of landscape-scale exposure modeling, 6) explicit integration of multi-stressor interactions, and 7) in silico models to link individual-level effects to colony and population outcomes. While acknowledging the significant investment required, it is postulated that a phased transition is scientifically necessary and economically prudent, given the indispensable value of pollination services to global agriculture and ecosystem stability.
F. Castagna, S. Ruga, Roberto Bava et al.· Journal of Toxicology and En...· 0 citations
Background/Objectives: Antimicrobial resistance among ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens has become a major global health threat, significantly reducing the effectiveness of conventional antibiotics. Plant-derived compounds have emerged as promising antibiotic adjuvants capable of restoring antibiotic activity through multiple resistance-modulating mechanisms. This review aims to critically evaluate the current evidence regarding phytochemicals that enhance antibiotic efficacy against drug-resistant ESKAPE pathogens. Methods: Relevant studies investigating plant-derived compounds with antibiotic adjuvant activity against ESKAPE pathogens were identified and critically analyzed. Particular attention was given to mechanisms of action, synergistic interactions with conventional antibiotics, structure–activity relationships, and translational evidence from in vivo studies. Results: Numerous phytochemicals have demonstrated the ability to potentiate antibiotic activity through efflux pump inhibition, biofilm disruption, membrane permeabilization, and quorum sensing interference. For instance, the flavonoid quercetin inhibits the NorA efflux pump in Staphylococcus aureus, restoring ciprofloxacin susceptibility, while the sulfur-containing compound ajoene from garlic disrupts quorum sensing in Pseudomonas aeruginosa, sensitizing biofilms to tobramycin. Although several compounds exhibit promising synergistic effects in vitro, significant barriers remain regarding bioavailability, standardization, pharmacokinetics, and clinical translation. Conclusions: Plant-derived antibiotic adjuvants represent a promising strategy to combat multidrug-resistant ESKAPE pathogens. However, greater emphasis on translational research, standardized methodologies, and clinically relevant experimental models is required to facilitate their development toward therapeutic applications.
S. Ruga, Elisa Matarese, F. Castagna et al.· Antibiotics· 0 citations
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