Multiscale Effects of Environmentally Relevant Mixtures Containing Two Estrogenic Endocrine Disruptors, Chlordecone and Propylparaben, in Hydra vulgaris Pallas, 1766

ABSTRACT This study investigates the chronic effects of chlordecone (CLD) and propylparaben (PP), two pro‐estrogenic endocrine disruptors, on Hydra vulgaris Pallas, 1766 using a multiscale approach over a 14‐day exposure period. Environmentally relevant concentrations of CLD (0.5, 5, 20 μg L −1 ) and PP (0.01, 0.05, 0.40 μg L −1 ) were tested individually and in mixtures. CLD and PP single exposures reduced the asexual reproductive rate (RHR) by 20% at intermediate CLD and high PP concentrations, whereas mixtures caused stronger declines up to 60.0% at high concentration. Severe morphological damage occurred only under high‐dose mixtures. We analyzed the expression of 17 genes covering detoxification, oxidative stress, endocrine function, regeneration, neurotransmission, proteolysis, and epigenetic regulation. Except for G6pd and Thypedin , single exposures to CLD and PP either increased or decreased gene expression. Only a limited subset of genes ( Cyp17‐like and Cyp1a‐like under CLD; Cyp17‐like , G6pd , and Thypedin under PP) displayed dose‐related tendencies, while most other genes showed non‐monotonic or irregular responses typical of endocrine disruptors. Mixture effects included antagonism, potentiation, and coalition, with non‐monotonic responses such as Cyp17‐like induction showing a 2‐fold increase at low concentration and reversal or neutralization of oxidative‐stress markers. Mixtures also increased ubiquitin in damaged hydras exposed to high‐dose mixtures and reduced global DNA methylation (up to −43%). Together, these results highlight that mixture effects diverge markedly from single‐compound responses, show no additive effects, reinforce the importance of assessing endocrine disruptors in combination, and confirm the relevance of H. vulgaris as a sensitive model at environmental concentrations.