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Zebrafish are widely used not only as a model in ecotoxicology but also to study the potential impact of chemicals on human health. Typically, zebrafish are exposed to chemicals dissolved in egg water or other defined media, which is the standard routine for ecotoxicology testing. This straightforward exposure method is usually also employed to monitor adverse effects in zebrafish to predict potential hazards and modes of action in humans. Here, we compared different exposure media and studied the impact of salinity and solvents relevant to ecotoxicity testing. For comparison, toxicants also were directly injected into the bloodstream of zebrafish embryos, as this method better simulates the exposure scenario for assessing the adverse effects of drugs administered intravenously to patients. As model compounds we studied platinum-based anticancer drugs, which are known micropollutants, but also lead to severe side effects in humans. Striking differences in sensitivity and phenotypes, i.e. adverse outcomes, were observed dependent on the exposure route and media. The bioavailability of the platinum compounds was significantly altered in the different media and by the commonly used solvent DMSO. These findings highlight the relevance of the exposure route and media as well as of solvents to be considered when interpreting zebrafish studies in the field of ecotoxicology or in cross-species comparisons to predict effects on human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)