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The rapid development of nanomaterials (NMs) and the emergence of new multicomponent NMs will inevitably lead to simultaneous exposure of organisms to multiple engineered nanoparticles (ENPs) at varying exposure levels. Understanding the joint impacts of multiple ENPs and predicting the toxicity of mixtures of ENPs are therefore evidently of importance. We reviewed the toxicity of mixtures of ENPs to a variety of different species, covering algae, bacteria, daphnia, fish, fungi, insects, and plants. Most studies used the independent-action (IA)-based model to assess the type of joint effects. Using co-occurrence networks, it was revealed that 53% of the cases with specific joint response showed antagonistic, 25% synergistic, and 22% additive effects. The combination of nCuO and nZnO exhibited the strongest interactions in each type of joint interaction. Compared with other species, plants exposed to multiple ENPs were more likely to experience antagonistic effects. The main factors influencing the joint response type of the mixtures were (1) the chemical composition of individual components in mixtures, (2) the stability of suspensions of mixed ENPs, (3) the type and trophic level of the individual organisms tested, (4) the biological level of organization (population, communities, ecosystems), (5) the exposure concentrations and time, (6) the endpoint of toxicity, and (7) the abiotic field conditions (e.g., pH, ionic strength, natural organic matter). This knowledge is critical in developing efficient strategies for the assessment of the hazards induced by combined exposure to multiple ENPs in complex environments. In addition, this knowledge of the joint effects of multiple ENPs assists in the effective prediction of hybrid NMs.

This is the first study to explore synergistic effects of mixtures of carbon-based NMs associated with metal NPs. Exposure to GNPs and/or RGO induced enhanced cytotoxicity of nZrO 2 to algae. Cellular oxidative stress and membrane functional changes led to toxicity increase. Mitochondria-generated ROS regulated treatment-induced cellular response. RGO induced more cytotoxic responses from algal cells than GNPs.

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