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From Extrapolation to Precision Chemical Hazard Assessment: The Ecdysone Receptor Case Study.

ABSTRACT: Hazard assessment strategies are often supported by extrapolation of damage probabilities, regarding chemical action and species susceptibilities. Yet, growing evidence suggests that an adequate sampling of physiological responses across a representative taxonomic scope is of paramount importance. This is particularly relevant for Nuclear Receptors (NR), a family of transcription factors, often triggered by ligands and thus, commonly exploited by environmental chemicals. Within NRs, the ligand-induced Ecdysone Receptor (EcR) provides a remarkable example. Long regarded as arthropod specific, this receptor has been extensively targeted by pesticides, seemingly innocuous to non-target organisms. Yet, current evidence clearly suggests a wider presence of EcR orthologues across metazoan lineages, with unknown physiological consequences. Here, we address the state-of-the-art regarding the phylogenetic distribution and functional characterization of metazoan EcRs and provide a critical analysis of the potential disruption of such EcRs by environmental chemical exposure. Using EcR as a case study, hazard assessment strategies are also discussed in view of the development of a novel "precision hazard assessment paradigm.

SUBMITTER: Ruivo R

PROVIDER: S-EPMC8778615 | biostudies-literature |

REPOSITORIES: biostudies-literature

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