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The call for a new toxicology is mainly a call for cellular approaches and their computational integration. This article reflects on cell models, which are necessary to facilitate the transition. A mechanistic perspective has prompted the characterization of toxicity pathways and toxicity networks in order to develop robust cell-based assays for toxicity testing. Differing use scenarios for cell systems require higher degrees of sophistication, e.g., human-on-a-chip approaches are based on complex organotypic cultures to approximate the repertoire of human physiological reactions and high-throughput tests require simplicity and robustness. The new paradigm emerging under the branding of Toxicology for the 21st Century needs complex models for pathway of toxicity identification and simpler assays for testing the perturbation of any given pathway. With increasing knowledge about underlying mechanisms, the needs for complexity and test specificity will change. Selective cell-based assays are desirable, especially for the detection of novel toxicants and biothreats. Examples from endocrine disruption, pyrogenicity, and especially shellfish toxin testing are used to illustrate such developments.
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