Challenges and Prospects in the Application of Experimental, Analytical, and Predictive Models in Combined Toxicity Assessment
Naima Hamid, Qiang Yue, Jun Wang, Muhammad Junaid · 2025
One of the most effective ways to assess the potential health hazards of chemical interactions is through an in-depth and integrated toxicological evaluation. This chapter particularly emphasizes the mechanistic combined toxicity of the legacy and emerging environmental pollutants, both in vivo and in vitro models. Moreover, the existing challenges and future perspectives of applying experimental, analytical, and predictive models in mixture toxicity evaluation were discussed. The majority of the chemical mixtures affected the normal estrogen, thyroid, and metabolism functions, leading to oxidative stress, reproductive organ deformities, disturbed estrogen cycle, and hepatotoxicity. Furthermore, multigenerational epigenetic effects in the form of DNA methylation were found in the F 3 and F 4 generations after mixture exposure. Moreover, analytical techniques are also being applied to investigate the interactions between chemical and biological systems; however, they can be limited by the complexity of the data and require more precision. Predictive models are becoming increasingly popular for their ability to quickly and accurately forecast the toxicity of different chemical mixtures; however, these models require validation. Despite these challenges, the future prospects for mixture toxicology are promising, as researchers continue to refine their methods and develop new techniques, particularly machine learning–based in silico methods for evaluating the safety of different chemical combinations.