Toxic effects of trace metal(loid) mixtures on aquatic organisms.

The co-occurrence of metal (loid)s in realistic aquatic environments necessitates the evaluation of their combined effects. However, the generality of the additive effect hypothesis is contentious, particularly due to metal(loid)-metal(loid) interactions. The absence of systematic evaluation approaches restricts our ability to draw overall conclusions and make reliable predictions. In this study, we reviewed 1473 effect sizes from 38 publications, and classified all responses into seven main categories (from molecular to individual levels) according to their toxicological significance. Our meta-analysis revealed that metal(loid) mixtures had significant effects on aquatic organisms (33 %, 95 % CI 28 %-39 %, P < 0.05), along with significant response heterogeneity (Qt = 690,319.62, P < 0.0001; I = 99.95 %). Concurrently, we developed a Random Forest machine learning model to predict adverse effects and identify key variables. These two methods demonstrated that the toxicity of metal(loid) mixtures is primarily linked to the choice of toxicity endpoints, and the characteristics of metal(loid) mixtures. Our findings underscore the potential of combining meta-analysis with machine learning, a more systematic approach, to enhance the understanding and prediction of the adverse effects of metal(loid) mixtures, and they offer guidance for risk assessment and policy-making in complex environmental scenarios.