Binary combined toxicity of neonicotinoids and co-existing pollutants to non-target invertebrates: A meta-analysis

Mixture exposures dominate real-world environmental settings, yet the toxic impacts of neonicotinoid insecticides (NEOs), one of the most widely used pesticide classes, when combined with co-occurring pollutants on non-target invertebrates remain poorly synthesized. This extensive global analysis integrated data from 47 studies retrieved via Web of Science, PubMed, and CNKI, covering 1706 toxicity endpoint records standardized by toxicological parameters (e.g., survival rate, mortality, enzyme activity), pollutant types, exposure conditions, and species taxonomy, and used Hedges'g as the effect size statistic with a three-level model to assess the impact of NEOs and coexisting pollutant mixtures on non-target invertebrate toxicity. The results revealed that the presence of coexisting pollutants changed NEO toxicity, exacerbating growth and development (Hedges' g = -2.61 ± 0.26), accumulation (Hedges' g = 0.98 ± 0.19), and oxidative damage (Hedges' g = -0.59 ± 0.08), while lowering endocrine disruption and neurotoxic effects (Hedges' g = 0.19 ± 0.12) in specific contexts. Variations in toxicity were found to be influenced by the invertebrate species, NEO type, and pollutant category. Specifically, NEO co-toxicity variations affected by co-existing pollutants were recorded in the higher sensitivity of pollinators (e.g., Hymenoptera bees) and aquatic invertebrates, stronger toxicity of thiacloprid/thiamethoxam, amplified NEO toxicity by fungicides, heavy metals, microplastics and inorganic pollutants, the more severe effects of oral compared contact exposure, and the higher vulnerability of juvenile and early life stages. Meta-regression analysis revealed correlations with biological type, pollutant concentrations, types, and exposure durations, with a slight negative correlation observed between NEO levels, exposure time, and impact severity in co-exposure scenarios, as well as no significant associations with logK_ow. The limitations and prospects of the study highlighted challenges in extrapolating laboratory findings to natural settings, underscoring the need for research focusing on multiple pollutants, prolonged exposure periods, and realistic conditions to enhance ecological risk assessments. This investigation advanced our understanding of combined NEO toxicity mechanisms, providing valuable insights for evidence-based environmental mixture risk management.